To

Gill, Emma and Abigail

to
Alison, Jonathan and Sophie
and to
Pat, Ethan and Molly
Content Strategist: Jeremy Bowes
Content Development Specialist: Sheila Black
Project Manager: Luca Prez
Designer: Christian Bilbow
Illustration Manager: Jennifer Rose
Anaesthesia
and Intensive
Care AZ
An Encyclopaedia of Principles
and Practice
FIFTH EDITION

Steve M Yentis BSc MBBS MD MA FRCA

Consultant Anaesthetist, Chelsea and Westminster Hospital;
Honorary Reader, Imperial College London, UK

Nicholas P Hirsch MBBS FRCA FRCP FFICM

Consultant Anaesthetist, The National Hospital for Neurology and Neurosurgery;
Honorary Senior Lecturer, The Institute of Neurology, London, UK

James K Ip BSc MBBS FRCA

Specialty Registrar, Imperial School of Anaesthesia, London, UK

Original contributions by Gary B Smith BM FRCA FRCP

EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2013
 2013 Elsevier Ltd. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publishers permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).

First edition 1993

Second edition 2000
Third edition 2004
Fourth edition 2009
Fifth edition 2013

ISBN 978-0-7020-4420-5

1 British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library

2 Library of Congress Cataloging in Publication Data

A catalog record for this book is available from the Library of Congress

Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our understanding, changes in research methods, professional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using
any information, methods, compounds, or experiments described herein. In using such information or methods
they should be mindful of their own safety and the safety of others, including parties for whom they have a
professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most
current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be
administered, to verify the recommended dose or formula, the method and duration of administration, and
contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of
their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient,
and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any
liability for any injury and/or damage to persons or property as a matter of products liability, negligence or
otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the
material herein.

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Preface

In the 20 years since the publication of the first edition of activities performed by our anaesthetic, intensive care,
of our textbook, we have been delighted to find that nursing and other colleagues, and also reflects the ever-
the AZ has been adopted by both trainees and estab- changing field in which we work.
lished practitioners alike. Whilst our original idea was to
produce a readily accessible source of information for The publication of a textbook requires the support of
those sitting the Royal College of Anaesthetists Fellow- a multitude of people. We are indebted to our colleagues,
ship examinations, it is now obvious that the book both junior and senior, who have gently criticised previ-
appeals to a far wider readership. We hope that the AZ ous editions; their suggestions have been invaluable and
will continue to be useful to all staff who help us care have directly resulted in changes found in each new
for patients on a daily basis, as well as to anaesthetists edition over the years. We also thank the staff of Elsevier
and intensivists of all grades. and their predecessors for their support during the life
of this project. Finally, this is the first edition of the AZ
As with previous new editions, each entry has been on which two of the original authors, SMY and NPH,
reviewed and, where appropriate, revised, and new ones have worked without the third, Gary Smith, though his
inserted. For the first time, we have compiled a struc- contributions exist throughout the book in both the
tured checklist of entries, at the back of the book, that format and content of entries from previous editions. We
we hope will be useful to those planning their revision shall both miss Garys expertise, input and good humour,
for exams. but are delighted to welcome James Ip to the team.

The difference between the list of entries in the first

edition and those in the current one continues to increase, SMY
with a huge expansion of new entries and revision of NPH
existing ones. This change acknowledges the enormous JKI
breadth of information needed to satisfy the vast range

v
Explanatory notes

Arrangement of text Recommended International

Entries are arranged alphabetically, with some related Non-proprietary Names (rINNs)
subjects grouped together to make coverage of one Following work undertaken by the World Health Organ-
subject easier. For example, entries relating to tracheal ization, recent European law requires the replacement
intubation may be found under I as in Intubation, awake; of existing national drug nomenclature with rINNs. For
Intubation, blind nasal, etc. most drugs, rINNS are identical to the British Approved
Name (BAN). The Medicines Control Agency (UK) has
Cross-referencing proposed a two-stage process for the introduction of
Bold type indicates a cross-reference. An abbreviation rINNs. For substances where the change is substantial,
highlighted in bold type refers to an entry in its fully both names will appear on manufacturers labels and
spelled form. For example, ARDS may occur . . . refers leaflets for a number of years, with the rINN preceding
to the entry Acute respiratory distress syndrome. Further the BAN on the drug label. For drugs where the change
instructions appear in italics. presents little hazard, the change will be immediate.
For some drugs which do not appear in either of the
References
above two categories, the British (or USP) name may
Reference to a suitable article is provided at the foot of
still be used.
the entry where appropriate.
There are over 200 affected drugs, many of them no
Proper names
longer available. Affected drugs that are mentioned in
Where possible, a short biographical note is provided
this book (though not all of them have their own entries)
at the foot of the entry when a person is mentioned.
are listed below though please note that, in common
Dates of birth and death are given, or the date of descrip-
with the British Pharmacopoeia, the terms adrenaline
tion if these dates are unknown. No dates are given
and noradrenaline will be used throughout the text in
for contemporary names. Where more than one epony-
preference to epinephrine and norepinephrine respec-
mous entry occurs, e.g. Haldane apparatus and
tively, because of their status as natural hormones.
Haldane effect, details are given under the first entry.
Thus (with the exception of adrenaline and noradrena-
The term anaesthetist is used in the English sense,
line), the format for affected drugs is rINN (BAN), e.g.
i.e. a medical practitioner who practises anaesthesia;
Tetracaine hydrochloride (Amethocaine). Non-BAN,
the terms anesthesiologist and anaesthesiologist are
non-rINN names are also provided for certain other
not used.
drugs (for example, Isoproterenol, see Isoprenaline) to
Drugs help direct non-UK readers or those unfamiliar with UK
Individual drugs have entries where they have especial terminology.
relevance to, or may by given by, the anaesthetist or
intensivist. Where many different drugs exist within the Examination revision checklist
same group, for example -adrenergic receptor antago- At the back of the book is a checklist based on entries
nists, those which may be given intravenously have their of particular relevance to examination candidates, that
own entry, whilst the others are described under the have been classified and listed alphabetically in order to
group description. The reader is referred back to entries support systematic study of examination topics accord-
describing drug groups and classes where appropriate. ing to the subject area.

continued over page

vii
 Explanatory notes

continued

BAN rINN
Adrenaline Epinephrine
Amethocaine Tetracaine
Amoxycillin Amoxicillin
Amphetamine Amfetamine
Amylobarbitone Amobarbital
Beclomethasone Beclometasone
Benzhexol Trihexyphenidyl
Benztropine Benzatropine
Busulphan Busulfan
Cephazolin Cefazolin
Cephradine Cefradine
Cephramandole Ceframandole
Chlormethiazole Clomethiazole
Chlorpheniramine Chlorphenamine
Corticotrophin Corticotropin
Cyclosporin Ciclosporin
Dicyclomine Dicycloverine
Dothiepin Dosulepin
Ethamsylate Etamsylate
Ethacrynic acid Etacrynic acid
Frusemide Furosemide
Indomethacin Indometacin
Lignocaine Lidocaine
Methohexitone Methohexital
Methylene blue Methylthioninium chloride
Noradrenaline Norepinephrine
Oxpentifylline Pentoxifylline
Phenobarbitone Phenobarbital
Sodium cromoglycate Sodium cromoglicate
Sulphadiazine Sulfadiazine
Sulphasalazine Sulfasalazine
Tetracosactrin Tetracosactide
Thiopentone Thiopental
Tribavarin Ribavarin
Trimeprazine Alimemazine

viii


Abbreviations

ACE inhibitors angiotensin converting enzyme GFR glomerular filtration rate

inhibitors GIT gastrointestinal tract
ACTH adrenocorticotrophic hormone GTN glyceryl trinitrate
ADP adenosine diphosphate HCO3 bicarbonate
AF atrial fibrillation HDU high dependency unit
AIDS acquired immune deficiency syndrome HIV human immunodeficiency virus
cAMP cyclic adenosine monophosphate HLA human leucocyte antigen
APACHE acute physiology and chronic health 5-HT 5-hydroxytryptamine
evaluation
ICP intracranial pressure
ARDS acute respiratory distress syndrome
ICU intensive care unit
ASA American Society of Anesthesiologists
IgA, IgG, etc., immunoglobulin A, G, etc.
ASD atrial septal defect
im intramuscular
ATP adenosine triphosphate
IMV intermittent mandatory ventilation
AV atrioventricular
IPPV intermittent positive pressure ventilation
bd twice daily
iv intravenous
BP blood pressure
IVRA intravenous regional anaesthesia
CMRO2 cerebral metabolic rate for oxygen
JVP jugular venous pressure
CNS central nervous system
LMA laryngeal mask airway
CO2 carbon dioxide
MAC minimal alveolar concentration
COPD chronic obstructive pulmonary disease
MAP mean arterial pressure
CPAP continuous positive airway pressure
MH malignant hyperthermia
CPR cardiopulmonary resuscitation
MI myocardial infarction
CSE combined spinalextradural
MODS multiple organ dysfunction syndrome
CSF cerebrospinal fluid
MRI magnetic resonance imaging
CT computed tomography
mw molecular weight
CVA cerebrovascular accident
NAD(P) nicotinamide adenine dinucleotide
CVP central venous pressure (phosphate)
CVS cardiovascular system NHS National Health Service
CXR chest X-ray NICE National Institute for Health and Clinical
DIC disseminated intravascular coagulation Excellence
DNA deoxyribonucleic acid NMDA N-methyl-D-aspartate
2,3-DPG 2,3-diphosphoglycerate N2O nitrous oxide
DVT deep vein thrombosis NSAID non-steroidal anti-inflammatory drug
ECF extracellular fluid O2 oxygen
ECG electrocardiography od once daily
EDTA ethylenediaminetetraacetate ODA/P operating department assistant/practitioner
EEG electroencephalography PCO2 partial pressure of carbon dioxide
EMG electromyography PE pulmonary embolus
ENT ear, nose and throat PEEP positive end-expiratory pressure
FEV1 forced expiratory volume in 1 s PO2 partial pressure of oxygen
FIO2 fractional inspired concentration of oxygen PONV postoperative nausea and vomiting
FRC functional residual capacity pr per rectum
FVC forced vital capacity qds four times daily
G gauge RNA ribonucleic acid
GABA -aminobutyric acid RS respiratory system

ix
 Abbreviations

sc subcutaneous TIVA total intravenous anaesthesia

SIRS systemic inflammatory response syndrome TPN total parenteral nutrition
SLE systemic lupus erythematosus TURP transurethral resection of prostate
SVP saturated vapour pressure UK United Kingdom
SVR systemic vascular resistance US(A) United States (of America)
SVT supraventricular tachycardia VF ventricular fibrillation
TB tuberculosis V / Q ventilation/perfusion
tds three times daily VSD ventricular septal defect
TENS transcutaneous electrical nerve stimulation VT ventricular tachycardia

x
 A
A severity characterisation of trauma (ASCOT). impair ventilation and be associated with reduced
Trauma scale derived from the Glasgow coma scale, sys- venous return, cardiac output, renal blood flow and urine
tolic BP, revised trauma score, abbreviated injury scale output. Increased CVP may lead to raised ICP. Diag-
and age. A logistic regression equation provides a prob- nosed by clinical features and intra-abdominal pressure
ability of mortality. Excludes patients with very poor or measurement (performed via a bladder catheter or
very good prognoses. Has been claimed to be superior nasogastric tube, in combination with a water column
to the trauma revised injury severity score system, manometer).
although is more complex. Management includes laparotomy silastic material
Champion HR, Copes WS, Sacco WJ, etal (1996). J to cover the abdominal contents. Paracentesis may be
Trauma; 40: 428 effective if raised intra-abdominal pressure is due to
accumulation of fluid, e.g. ascites. Full resuscitation must
AadO2, see Alveolararterial oxygen difference be performed before decompression as rapid release of
pressure may result in sudden washout of inflammatory
ABA, see American Board of Anesthesiology mediators from ischaemic tissues, causing acidosis and
hypotension. Mortality of the syndrome is 2570%.
Abbott, Edward Gilbert, see Morton, William Malbrain ML, Cheatham ML, Kirkpatrick A etal (2006).
Intensive Care Med; 32: 172232, and Cheatham ML,
Abbreviated injury scale (AIS). Trauma scale first Malbrain ML, Kirkpatrick A (2007). Intensive Care
described in 1971 and updated many times since. Com- Med; 33: 95162
prises a classification of injuries with each given a six- See also, Compartment syndromes
digit code (the last indicating severity, with 1 = minor
and 6 = fatal). The codes are linked to International Abdominal field block. Technique using 100200ml
Classification of Diseases codes, thus aiding standardisa- local anaesthetic agent, involving infiltration of the skin,
tion of records. The anatomical profile is a refinement subcutaneous tissues, abdominal muscles and fascia. Pro-
in which the locations of injuries are divided into four vides analgesia of the abdominal wall and anterior peri-
categories; the AIS scores are added and the square toneum, but not of the viscera. Now rarely used. Rectus
root taken to minimise the contribution of less severe sheath block, transversus abdominis plane block, iliac
injuries. crest block and inguinal hernia field block are more
Copes WS, Lawnick M, Champion HR, Sacco WJ (1988). specific blocks.
J Trauma; 28: 7886
Abdominal sepsis, see Intra-abdominal sepsis
Abciximab. Monoclonal antibody used as an antiplate-
let drug and adjunct to aspirin and heparin in high-risk Abdominal trauma. May be blunt (e.g. road traffic acci-
patients undergoing percutaneous coronary interven- dents) or penetrating (e.g. stabbing, bullet wounds).
tion. Consists of Fab fragments of immunoglobulin Often carries a high morbidity and mortality because
directed against the glycoprotein IIb/IIIa receptor on injuries may go undetected. Massive intra-abdominal
the platelet surface. Inhibits platelet aggregation and blood loss or abdominal compartment syndrome may
thrombus formation; effects last 2448h after infusion. follow. The abdomen can be divided into three areas:
Careful consideration of risks and benefits should intrathoracic: protected by the bony thoracic cage.
precede use since risk of bleeding is increased. Licensed Contains the spleen, liver, stomach and diaphragm.
for single use only. Injury may be associated with rib fractures. The dia-
Dosage: initial loading of 250g/kg over 1min iv, phragm may also be injured by blows to the lower
followed by iv infusion of 125ng/kg/min (max 10g/ abdomen (which impart pressure waves to the dia-
min) 1060min (up to 24h in unstable angina) before phragm) or by penetrating injuries of the chest.
angioplasty with 125g/kg/min (up to 10g/min for true abdomen: contains the small and large bowel,
12h afterwards). bladder and, in the female, uterus, fallopian tubes
Side effects: bleeding, hypotension, nausea, bradycar- and ovaries.
dia. Thrombocytopenia occurs rarely. retroperitoneal: contains the kidneys, ureters, pan-
creas and duodenum. May result in massive blood
Abdominal compartment syndrome. Combination of loss from retroperitoneal venous injury.
increased intra-abdominal pressure and organ dysfunc- Management:
tion (e.g. following abdominal trauma or extensive basic resuscitation as for trauma generally.
surgery) resulting from haemorrhage or expansion of initial assessment: examination of the anterior
the third space fluid compartment. May also follow liver abdominal wall, both flanks, back, buttocks,
transplantation, sepsis, burns and acute pancreatitis. perineum (and in men, the urethral meatus) for
Intra-abdominal pressures above 2025 cmH2O may bruises, lacerations, entry and exit wounds. Signs

1
2 ABO blood groups

may be masked by unconsciousness, spinal cord reduction in incidence of events from a% to b%, it
injury or the effects of alcohol or drugs. Abdominal equals (a b)%.
swelling usually indicates intra-abdominal haemor- See also, Meta-analysis; Odds ratio; Relative risk
rhage; abdominal guarding or rigidity usually indi- reduction
cates visceral injury. Absence of bowel sounds may
indicate intraperitoneal haemorrhage or peritoneal Abuse of anaesthetic agents. May occur because of
soiling with bowel contents. Colonic or rectal inju- easy access to potent drugs by operating theatre or ICU
ries may cause blood pr. A high index of suspicion staff. Opioid analgesic drugs are the most commonly
is required for retroperitoneal injuries since exami- abused agents, but others include benzodiazepines and
nation is difficult. inhalational anaesthetic agents. Abuse may be suggested
imaging: abdominal X-ray may reveal free gas by behavioural or mood changes, or excessive and inap-
under the diaphragm (erect or semi-erect; may propriate requests for opioids. Main considerations
also be visible on CXR) or laterally (lateral decu include the safety of patients, counselling and psychiatric
bitus X-ray); other investigations include pelvic therapy for the abuser and legal aspects of drug abuse.
X-ray and urological radiology if indicated (e.g. iv May be associated with alcoholism.
urogram), CT and MRI scanning and ultrasound. Bryson EO, Silverstein JH (2008). Anesthesiology; 109:
peritoneal lavage is indicated in blunt abdominal 90517
trauma associated with: See also, Misuse of Drugs Act; Sick doctor scheme; Sub-
- altered pain response (head injury, spinal cord stance abuse
injury, drugs, etc.).
- unexplained hypovolaemia following multiple Acarbose. Inhibitor of intestinal alpha glucosidases and
trauma. pancreatic amylase; used in the treatment of diabetes
- equivocal diagnostic findings. mellitus, usually in combination with a biguanide or sul-
insertion of a nasogastric tube and urinary catheter phonylurea. Delays digestion and absorption of starch
(provided no urethral injury; a suprapubic catheter and sucrose and has a small blood glucose-lowering
may be necessary). effect.
indications for laparotomy include penetrating inju- See also, Meglitinides; Thiazolidinediones
ries, obvious intra-abdominal haemorrhage, signs of
bowel perforation or a positive peritoneal lavage. Accessory nerve block. Performed for spasm of trape-
See also, Pelvic trauma zius and sternomastoid muscles (there is no sensory
component to the nerve). 510ml local anaesthetic
ABO blood groups. Discovered in 1900 by Landsteiner agent is injected 2cm below the mastoid process into the
in Vienna. Antigens may be present on red blood cells, sternomastoid muscle, through which the nerve runs.
with antibodies in the plasma (Table 1). The antibodies,
mostly type-M immunoglobulins, develop within the first Accident, major, see Incident, major
few months of life, presumably in response to naturally
occurring antigens of similar structure to the blood anti- ACD, Acidcitratedextrose solution, see Blood storage
gens. Infusion of blood containing an ABO antigen into
ACD-CPR, Active compression decompression CPR,
a patient who already has the corresponding antibody
see Cardiac massage; Cardiopulmonary resuscitation
may lead to an adverse reaction; hence the description
of group O individuals as universal donors, and of group ACE, Angiotensin converting enzyme, see Renin/
AB individuals as universal recipients. angiotensin system
[Karl Landsteiner (18681943), Austrian-born US
pathologist] ACE anaesthetic mixture. Mixture of alcohol, chloro-
See also, Blood compatibility testing; Blood groups; form and diethyl ether, in a ratio of 1:2:3 parts, sug-
Blood transfusion gested in 1860 as an alternative to chloroform alone.
Popular into the 1900s as a means of reducing total dose
ABPI, see Ankle Brachial Pressure Index and side effects of any one of the three drugs.
Abruption, see Antepartum haemorrhage ACE inhibitors, see Angiotensin converting enzyme
inhibitors
Absolute risk reduction. Indicator of treatment effect
in clinical trials, representing the decrease in risk of a Acetaminophen, see Paracetamol
given treatment compared with a control treatment, i.e.
the inverse of the number needed to treat. For a Acetazolamide. Carbonic anhydrase inhibitor. Reduces
renal bicarbonate formation and hydrogen ion excretion
at the proximal convoluted tubule, thereby inducing a
metabolic acidosis. A weak diuretic, but rarely used as
Table 1 Antigens and antibodies in ABO blood groups such. Also used to treat glaucoma, metabolic alkalosis,
altitude sickness and childhood epilepsy. Useful in the
Group Incidence in UK (%) Red cell antigen Plasma antibody treatment of severe hyperphosphataemia as it promotes
urinary excretion of phosphate. May be used to lower
A 42 A Anti-B ICP (e.g. in benign intracranial hypertension) by reduc-
B 8 B Anti-A ing CSF production. Has been used to alkalinise the
AB 3 A and B None urine in tumour lysis syndrome or to enhance excretion
O 47 None Anti-A and anti-B in drug intoxications, e.g. with salicylates.
Dosage: 0.250.5g orally/iv od/bd.
 Acetylcholinesterase 3

CH3 O (a)

CH3 N+ CH2 CH2 O C CH3 Nicotinic

Somatic muscle

CH3 Nicotinic Muscarinic

Parasympathetic
Fig. 1 Structure of acetylcholine
Nicotinic Adrenergic
Most nerves

Acetylcholine (ACh). Neurotransmitter, the acetyl

To sweat Nicotinic Muscarinic
ester of choline (Fig. 1). Synthesised from acetylcoen- Sympathetic
glands
zyme A and choline in nerve ending cytoplasm; the reac-
tion is catalysed by choline acetyltransferase. Choline is To adrenal Nicotinic
actively transported into the nerve and acetylcoenzyme medulla
A is formed in mitochondria. ACh is stored in vesicles.
ACh is the transmitter at: (b)
autonomic ganglia.
parasympathetic postganglionic nerve endings.
sympathetic postganglionic nerve endings at sweat
glands and some muscle blood vessels.
the neuromuscular junction. 10 nm
many parts of the CNS, where it has a prominent
role in learning.
Actions may be broadly divided into either muscarinic
or nicotinic, depending on the acetylcholine receptors
involved. ACh is hydrolysed to choline and acetate by
acetylcholinesterase on the postsynaptic membrane. Lipids
Other esterases also exist, e.g. plasma cholinesterase.
See also, Acetylcholine receptors; Neuromuscular trans-
mission; Parasympathetic nervous system; Sympathetic Cytoskeleton
nervous system; Synaptic transmission
Fig. 2 (a) Types of acetylcholine receptors. (b) Structure of nicotinic
Acetylcholine receptors. Transmembrane receptors
acetylcholine receptor
activated by acetylcholine (ACh). Classified according
to their relative sensitivity to nicotine or muscarine
(Fig. 2a).
Nicotinic receptors: ligand-gated ion channels present
at numerous sites within the nervous system; notable M3: Gq-coupled; smooth muscle (increased tone,
examples include the neuromuscular junction (NMJ) e.g. bronchiolar, intestinal), exocrine glands (stimu-
and autonomic ganglia. Each receptor consists of five latory), brain (stimulatory at vomiting centre).
glycosylated protein subunits that project into the M4/5: brain and adrenal medulla.
synaptic cleft. The adult receptor consists of 2 , , Muscarinic receptor agonists include bethanechol,
and units. The subunit is replaced by a subunit carbachol and pilocarpine (in the eye); antagonists
in the neonate. The subunits span the postsynaptic include hyoscine, atropine and ipratropium bromide.
membrane, forming a cylinder around a central ion The activation threshold of muscarinic receptors is lower
channel (Fig. 2b). The two subunits of each receptor than that of nicotinic receptors. Injection of ACh or poi-
carry the binding sites for ACh. Occupation of these soning with anticholinesterases thus causes parasympa-
sites opens the ion channel, allowing cations (mainly thetic stimulation and sweating at lower doses, before
sodium, potassium and calcium) to flow into the cell having effects at autonomic ganglia and the NMJ at
down their concentration gradients; this produces an higher doses.
excitatory postsynaptic potential. If these summate See also, Neuromuscular transmission; Parasympathetic
and exceed the threshold potential, an action poten- nervous system; Sympathetic nervous system; Synaptic
tial is generated. Non-depolarising neuromuscular transmission
blocking drugs are reversible competitive antagonists
of these receptors at the NMJ. Acetylcholinesterase. Enzyme present at the synaptic
Muscarinic receptors: G protein-coupled receptors, membranes of cholinergic synapses and neuromuscular
largely coupled to either adenylate cyclase or phos- junctions. Also found in red blood cells and the placenta.
pholipase C, via Gi and Gq proteins respectively. Metabolises acetylcholine (ACh) to acetate and choline,
Mediate postganglionic neurotransmission via para- thus terminating its action. The N(CH3)3+ moeity of ACh
sympathetic neurones, as well as sympathetic out- binds to the anionic site of the enzyme, and the acetate
flow to sweat glands (Fig. 2a). Classified according to end of ACh forms an intermediate bond at the esteratic
structural subtype, distribution and function: site. Choline is liberated, and the intermediate substrate/
M1: Gq-coupled; stomach (stimulates acid secre- enzyme complex is then hydrolysed to release acetate
tion) and brain (memory formation). (Fig. 3).
M2: Gi-coupled; heart; decreases heart rate, con- See also, Acetylcholinesterase inhibitors; Neuromuscular
tractility and atrioventricular nodal conduction. transmission; Synaptic transmission
4 Acetylcholinesterase inhibitors

Centrally acting acetylcholinesterase inhibitors (e.g.

Acetylcholine donepezil, rivastigmine, galantamine) are used for symp-
O tomatic treatment of Alzheimers dementia. Of anaes-
+ thetic relevance because of their side effects (including
(CH3)3 N CH2 CH2 O C CH3 nausea, vomiting, fatigue, muscle cramps, increased
H creatine kinase, convulsions, bradycardia, confusion),
O
enhancement of the actions of suxamethonium, and pos-
sible antagonism of non-depolarising neuromuscular
Anionic site Esteratic site blocking drugs.
[Alois Alzheimer (18641915), German neurologist and
pathologist]
Choline O Acetylated See also, Neuromuscular transmission; Organophospho-
+ enzyme rus poisoning
(CH3)3 N CH2 CH2 OH C CH3
O N-Acetylcysteine. Derivative of the naturally occurring
amino acid, L-cysteine. A free radical scavenger, licensed
as an antidote to paracetamol poisoning. Acts by restor-
ing depleted hepatic stores of glutathione and providing
O an alternative substrate for a toxic metabolite of
Acetate paracetamol. Also used as an ocular lubricant and to
C CH3 prevent nephropathy due to radiological contrast media
in patients with reduced renal function.
O
H Has been investigated for the treatment of fulminant
O hepatic failure, MODS, acute lung injury and neuropsy-
chiatric complications of carbon monoxide poisoning,
as well as a possible role in protection against myo
cardial reperfusion injury. Also used as a mucolytic
Fig. 3 Action of acetylcholinesterase
because of its ability to split disulphide bonds in mucus
glycoprotein.
Dosage:
Acetylcholinesterase inhibitors. Substances that paracetamol poisoning: 150mg/kg (to a maximum
increase acetylcholine (ACh) concentrations by inhibit- of 12g) in 200ml 5% dextrose iv over 1h, followed
ing acetylcholinesterase (AChE). Used clinically for by 50mg/kg in 500ml dextrose over 4h, then
their action at the neuromuscular junction in myasthenia 100mg/kg in 1 litre dextrose over 16h.
gravis and in the reversal of non-depolarising neuro to reduce viscosity of airway secretions: 200mg 8
muscular blockade. Concurrent administration of an hourly, orally. May be delivered by nebuliser.
antimuscarinic agent, e.g. atropine or glycopyrronium, Side effects: rashes, anaphylaxis. Has been associated
reduces unwanted effects of increased ACh concentra- with bronchospasm in asthmatics.
tions at muscarinic receptors. Effects at ganglia are
minimal at normal doses. Central effects may occur if the
drug readily crosses the bloodbrain barrier, e.g. physo- Achalasia. Disorder of oesophageal motility caused by
stigmine (used to treat the central anticholinergic idiopathic degeneration of nerve cells in the myenteric
syndrome). plexus or vagal nuclei. Results in dysphagia and oesoph-
Have also been used to treat tachyarrhythmias. ageal dilatation. A similar condition may result from
Classified according to mechanism of action: American trypanosomal infection (Chagas disease).
reversible competitive inhibitors: competitive inhi-
Aspiration pneumonitis or repeated chest infections
bition at the anionic site of AChE prevents binding may occur. Treated by mechanical distension of the
of ACh, e.g. edrophonium, tetrahydroaminocrine. lower oesophagus or by surgery. Hellers cardiomyot-
oxydiaphoretic (or acid-transferring) inhibitors:
omy (longitudinal myotomy leaving the mucosa intact)
act as an alternative substrate for AChE, producing may be undertaken via abdominal or thoracic approaches.
a more stable carbamylated enzyme complex. Sub- Preoperative respiratory assessment is essential. Patients
sequent hydrolysis of the complex and thus reacti- are at high risk of aspirating oesophageal contents, and
vation of the enzyme is slow. Examples: rapid sequence induction is indicated.
- neostigmine, physostigmine (few hours). [Carlos Chagas (18791934), Brazilian physician; Ernst
- pyridostigmine (several hours). Heller (18771964), German surgeon]
- distigmine (up to a day). See also, Aspiration of gastric contents; Induction, rapid
organophosphorus compounds: act by irreversibly
sequence
phosphorylating the esteratic site of AChE; inhibi-
tion can last for weeks until new enzyme is synthe- Achondroplasia. Skeletal disorder, inherited as an auto-
sised. Examples include: ecothiopate (used for the somal dominant gene, although most cases arise by spon-
treatment of glaucoma); parathion (an insecticide); taneous mutation. Results in dwarfism, with a normal
sarin nerve gas (a chemical weapon). size trunk and shortened limbs. Flat face, bulging skull
Acetylcholinesterase inhibitors augment depolarising vault and spinal deformity may make tracheal intubation
neuromuscular blockade and may cause depolarising difficult, and the larynx may be smaller than normal.
blockade in overdose. They may also cause bradycardia, Obstructive sleep apnoea may occur. Foramen magnum
hypotension, agitation, miosis, increased GIT activity, and spinal canal stenoses may be present, the former
sweating and salivation. resulting in cord compression on neck extension, the
 Acidosis, metabolic 5

latter making neuraxial blockade difficult and reducing - filtered HCO3 and excreted H+ form carbonic
volume requirements for epidural anaesthesia. acid.
- carbonic acid is converted to CO2 and water by
Aciclovir. Antiviral drug; an analogue of nucleoside carbonic anhydrase on the cell membrane.
2-deoxyguanosine. Inhibits viral DNA polymerase; - CO2 and water diffuse into the cell and reform
active against herpes viruses and used in the treatment carbonic acid (catalysed again by carbonic
of encephalitis, varicella zoster (chickenpox/shingles) anhydrase).
and postherpetic neuralgia, and for prophylaxis and - carbonic acid dissociates into HCO3 and H+.
treatment of herpes infections in immunocompromised - HCO3 passes into the blood; H+ is exchanged for
patients. Treatment should start at onset of infection; the Na+, etc.
by forming dihydrogen phosphate from monohy-
drug does not eradicate the virus but may markedly
attenuate the clinical infection. drogen phosphate in the distal tubule (HPO4 +H+
Dosage: H2PO4). The H+ is supplied from carbonic acid,
as topical cream, 5 times daily.
leaving HCO3, which passes into the blood.
by combination of ammonia, passing out of the cells,
200800mg orally, 25 times daily in adults.
10mg/kg iv tds, infused over 1h.
with H+, supplied as above. Resultant ammonium
Side effects: rashes, GIT disturbances, hepatic and ions cannot pass back into the cells and are excreted.
renal impairment, blood dyscrasias, headache, dizzi- In acidbase disorders, the primary change determines
ness, severe local inflammation after iv use, confusion, whether a disturbance is respiratory or metabolic. The
convulsions, coma. direction of change in H+ concentration determines aci-
dosis or alkalosis. Renal and respiratory compensation
act to restore normal pH, not reverse the primary change.
Acid. Species that acts as a proton (H+) donor when in For example, in the HendersonHasselbalch equation:
solution (BrnstedLowry definition).
[Johannes N Brnsted (18791947), Danish chemist; [HCO3 ]
pH = pKa + log
Thomas M Lowry (18741936), English chemist] [CO2 ]
See also, Acidbase balance; Acidosis adjustment of the HCO3/CO2 concentration ratio
restores pH towards its normal value, e.g.:
Acidaemia. Arterial pH < 7.35 or hydrogen ion concen- primary change: increased CO2; leads to decreased
tration > 45nmol/l. pH (respiratory acidosis).
See also, Acidbase balance; Acidosis compensation: HCO3 retention by kidneys;
increased ammonium secretion, etc.
Acidbase balance. Maintenance of stable pH in body An alternative approach, suggested by Stewart in 1983,
fluids is necessary for normal enzyme activity, ion distri- focuses on the strong ion difference to explain the
bution and protein structure. Blood pH is normally underlying processes rather than the above traditional
maintained at 7.357.45 (hydrogen ion [H+] concentra- approach, which concentrates more on interpretation of
tion 3545nmol/l); intracellular pH changes with extra- measurements. It is based on the degree of dissociation
cellular pH. During normal metabolism of neutral of ions in solution, in particular the effects of strong ions
substances, organic acids are produced that generate and weak acids, and the role of bicarbonate as a marker
hydrogen ions. of acidbase imbalance rather than a cause.
Maintenance of pH depends on: [Peter Stewart (19211993), Canadian physiologist]
buffers in tissues and blood, which minimise changes See also, Acid; Base; Blood gas interpretation; Breathing,
in H+ concentration. control of; Davenport diagram; Siggaard-Andersen
regulation by kidneys and lungs; the kidneys excrete nomogram
about 6080mmol and the lungs about 15000
20000mmol H+ per day. Acidcitratedextrose solution, see Blood storage
Because of the relationship between CO2, carbonic acid,
bicarbonate (HCO3) and H+, and the ability to excrete Acidosis. A process in which arterial pH < 7.35 (or
CO2 rapidly from the lungs, respiratory function is hydrogen ion > 45mmol/l), or would be < 7.35 if there
important in acidbase balance: were no compensatory mechanisms of acidbase balance.
See also, Acidosis, metabolic; Acidosis, respiratory
H 2O + CO2 H 2CO3 HCO3 + H +
Thus hyper- and hypoventilation cause alkalosis and aci- Acidosis, metabolic. Acidosis due to metabolic causes,
dosis respectively. Similarly, hyper- or hypoventilation resulting in an inappropriately low pH for the measured
may compensate for non-respiratory acidosis or alkalo- arterial PCO2.
sis respectively, by returning pH towards normal. Caused by:
Sources of H+ excreted via the kidneys include lactic increased acid production:
acid from blood cells, muscle and brain, sulphuric acid - ketone bodies, e.g. in diabetes mellitus.
from metabolism of sulphur-containing proteins, and - lactate, e.g. in shock, exercise.
acetoacetic acid from fatty acid metabolism. acid ingestion: e.g. salicylate poisoning.
The kidney can compensate for acidbase distur- +
failure to excrete hydrogen ions (H ):
bances in three ways: - renal failure.

by regulating the reabsorption of filtered HCO3 - distal renal tubular acidosis.
at the proximal convoluted tubule (normally - carbonic anhydrase inhibitors.
8090%): excessive loss of bicarbonate:
- filtered Na+ is exchanged for H+ across the tubule - diarrhoea.
cell membrane. - gastrointestinal fistulae.
6 Acidosis, respiratory

- proximal renal tubular acidosis. Acromegaly. Disease caused by excessive growth

- ureteroenterostomy. hormone secretion after puberty; usually caused by a
May be differentiated by the presence or absence of pituitary adenoma but ectopic secretion may also occur.
an anion gap: Incidence is 68 per million per year.
anion gap metabolic acidosis occurs in renal failure, Features:
lactic acidosis, ketoacidosis, rhabdomyolysis and enlarged jaw, tongue and larynx; widespread
following ingestion of certain toxins (e.g. salicylates, increase in soft tissue mass; enlarged feet and hands.
methanol, ethylene glycol). Nerve entrapment may occur, e.g. carpal tunnel
non-anion gap (hyperchloraemic) metabolic acido- syndrome.
sis is caused by the administration of chloride- respiratory obstruction, including sleep apnoea.
containing solutions (e.g. saline) in large volumes, tendency towards diabetes mellitus, hypertension
amino acid solutions, diarrhoea, pancreatic fistulae, and cardiac failure (may be due to cardiomyopa-
ileal loop procedures, after rapid correction of a thy). Thyroid and adrenal impairment may occur.
chronically compensated respiratory alkalosis or Apart from the above diseases, acromegaly may present
renal tubular acidosis. difficulties with tracheal intubation and maintenance of
Primary change: increased H+/decreased the airway.
bicarbonate. Treatment is primarily pituitary surgery with or
Compensation: without subsequent radiotherapy. Some patients respond
hyperventilation: plasma bicarbonate falls by about to bromocriptine or somatostatin analogues.
1.3mmol/l for every 1 kPa acute decrease in arterial Nemergut EC, Dumont AS, Barry UT, Laws ER (2007).
PCO2, which usually does not fall below 1.31.9 kPa Anesth Analg; 101: 117081
(1015mmHg).
+
increased renal H secretion. ACS, see Acute coronary syndromes
Effects:
hyperventilation (Kussmaul breathing). ACT, Activated clotting time, see Coagulation studies
confusion, weakness, coma.
cardiac depression.
Activated protein C, see Protein C
hyperkalaemia.
Acta Anaesthesiologica Scandinavica. Official journal of
Treatment: the Scandinavian Society of Anaesthesiology and Inten-
of underlying cause.
sive Care Medicine, first published in 1957.
bicarbonate therapy is reserved for treatment of
severe acidaemia (e.g. pH under 7.1) because of ACTH, see Adrenocorticotrophic hormone
problems associated with its use. If bicarbonate is
required, a formula for iv infusion is: Actin. One of the protein components of muscle (mw
base excess body weight (kg) 43000). In muscle, arranged into a double strand of thin
mmol filaments (F-actin) with globular beads (G-actin), to
3
which myosin binds, along their length. Present in all
Half this amount is given initially. cells as microfilaments.
other agents under investigation include sodium See also, Muscle contraction
dichloroacetate, Carbicarb (sodium bicarbonate and
carbonate in equimolar concentrations) and THAM Action potential. Sequential changes in membrane
(2-amino-2-hydroxymethyl-1,3-propanediol). potential that result in the propagation of electrical
Morris CG, Low J (2008). Anaesthesia; 63: 294301 and impulses in excitable cells. Neuronal, myocardial and
396411 cardiac nodal action potentials have distinct character-
See also, Acidaemia; Acidbase balance istics, determined by their underlying ionic fluxes (Fig. 4).
Neuronal action potential (Fig. 4a):
A: depolarisation of the membrane by 15 mV
Acidosis, respiratory. Acidosis due to increased arterial (threshold level).
PCO2. Caused by alveolar hypoventilation. B: rapid depolarisation to +40 mV.
Primary change: increased arterial PCO2.
C: repolarisation, rapid at first then slow.
Compensation:
D: hyperpolarisation.
initial rise in plasma bicarbonate due to increased
E: return to the resting membrane potential.
carbonic acid formation and dissociation. Slow initial depolarisation causes opening of voltage-
increased acid secretion/bicarbonate retention by
gated sodium channels (VGSCs) and influx of Na+ into
the kidneys. In acute hypercapnia, bicarbonate con- the cell, which causes further rapid depolarisation. Na+
centration increases by about 0.7mmol/l per 1 kPa conductance then falls as the VGSCs enter an inactivated
rise in arterial PCO2. In chronic hypercapnia it state. K+ efflux via voltage-gated potassium channels
increases by 2.6mmol/l per 1 kPa. occurs more slowly and helps bring about repolarisation.
Effects: those of hypercapnia.
Normal ion distribution (and hence the resting mem-
Treatment: of underlying cause.
brane potential) is restored by the action of the sodium/
See also, Acidaemia; Acidbase balance potassium pump. The action potential is followed by a
refractory period.
Myocardial action potential (Fig. 4b):
ACLS, see Advanced Cardiac Life Support +
phase 0: fast depolarisation and Na influx via
VGSCs.
Acquired immune deficiency syndrome (AIDS), see phase 1: onset of repolarisation due to sodium
Human immunodeficiency viral infection channel closure.
 Acupuncture 7

phase 0: depolarisation caused by opening of L-type

(a)
VGCCs and Ca2+ influx.
+
phase 3: repolarisation caused by K efflux.
+40 Notably, there is no contribution by Na+ flux to the
action potential in pacemaker cells.
Cardiac excitability is modulated by autonomic inputs
0 and antiarrythmic drugs via their effects on Na+, K+ and
Ca2+ conductance.
mV

C
B See also, Nernst equation; Nerve conduction

55 Activated charcoal, see Charcoal, activated

70 D
A
E
Activated clotting time, see Coagulation studies

Activated protein C, see Protein C

0 1 2 3
Time (ms) Activation energy. Energy required to initiate a chemi-
cal reaction. For ignition of explosive mixtures of anaes-
(b) thetic agents the energy may be provided by sparks, e.g.
from electrical equipment or build-up of static electric-
+20 1 ity. Combustion of cyclopropane requires less activation
2
energy than that of diethyl ether. Activation energy is
0 less for mixtures with O2 than with air, and least for
stoichiometric mixtures of reactants.
See also, Explosions and fires
3
mV

0 Active compression/decompression cardiopulmo-

nary resuscitation, see Cardiac massage; Cardiopulmo-
nary resuscitation

4 Active transport. Energy-requiring transport of parti-

90
cles across cell membranes. Protein pumps within the
membranes utilise energy which is usually supplied by
0 100 200 ATP metabolism, in order to move ions and molecules,
Time (ms) often against concentration gradients. A typical example
is the sodium/potassium pump.
(c)
+30 Acupuncture. Use of fine needles (usually 3033 G) to
produce healing and pain relief. Originated in China
thousands of years ago, and closely linked with the phi-
losophy and practice of traditional Chinese medicine.
0 Thus abnormalities in the flow of Qi (Chi: the life energy
that circulates around the body along meridians, nour-
ishing the internal organs) result in imbalance between
mV

0 3
Yin and Yang, the two polar opposites present in all
30 aspects of the universe. Internal abnormalities may be
diagnosed by pulse diagnosis (palpation of the radial
arteries at different positions and depths). The appropri-
4 4 ate organ is then treated by acupuncture at specific
60 points on the skin, often along the meridian named after,
and related to, that organ. Yin and Yang, and flow of Qi,
0 100 200 are thus restored.
Time (ms) Modern Western acupuncture involves needle inser-
tion at sites chosen for more scientific reasons; e.g.
Fig. 4 (a) Nerve action potential (solid) showing changes in sodium around an affected area, at trigger points found nearby,
(dotted) and potassium (dashed) conductance. (b) Cardiac action or more proximally but within the appropriate derma-
potential (see text). (c) Sinoatrial nodal action potential tome. These may be combined with distant or local tra-
ditional points, although conclusive evidence for the
phase 2: plateau due to Ca2+ influx via voltage-gated existence of acupuncture points and meridians has never
calcium channels (VGCCs). been shown. The needles may be left inserted and stimu-
+
phase 3: repolarisation and K efflux. lated manually, electrically or thermally to increase
phase 4: resting membrane potential. intensity of stimulation. Pressure at acupuncture points
The long plateau of phase 2 prolongs the refractory (acupressure) may produce similar but less intense
period, preventing tetanisation. stimulation.
Cardiac nodal action potential (Fig. 4c): Possible mechanisms:
phase 4: slow spontaneous depolarisation (pace- local reflex pathways at spinal level.
maker potential) caused by a fall in K+ efflux and closure of the gate in the gate control theory of
slow Ca2+ influx via T-type VGCCs. pain.
8 Acute coronary syndromes

central release of endorphins/enkephalins, and pos- ECG pattern). Bundle branch block may be evident.
sibly involvement of other neurotransmitters. NSTEACS may coexist with a normal ECG or:
modulation of the memory of pain. S-T segment depression; S-T segment elevation
Still used widely in China. Increasingly used in the West insufficient to meet reperfusion therapy criteria (see
for chronic pain, musculoskeletal disorders, headache below); T wave flattening or inversion; or biphasic
and migraine, and other disorders in which modern T waves.
Western medicine has had little success. Claims that acu- cardiac biomarkers:
puncture may be employed alone to provide analgesia - cardiac enzymes: largely replaced by troponins.
for surgery are now viewed with scepticism, although it - cardiac troponins:
has been used to provide analgesia and reduce PONV, - regulatory proteins involved in cardiac and
e.g. 5min stimulation at the point P6 (pericardium 6: skeletal muscle contraction.
12 inches [2.55cm] proximal to the distal wrist - composed of three subunits: C, T and I; plasma
crease, between flexor carpi radialis and palmaris longus levels of the latter two are both specific and
tendons). sensitive markers for myocardial damage.
Wang SM, Kain ZN, White P (2008). Anesth Analg; 106: - levels may not rise until 68h after onset of
60210 and 61121 symptoms; samples are therefore routinely
taken at 12h in order to establish a negative
Acute coronary syndromes (ACS). Group of clinical result.
conditions characterised by acute myocardial ischaemia; - levels peak at around 24h, correlating with the
usually caused by acute thrombus formation within a extent of infarction, and may remain elevated
coronary artery upon the exposed surface of a ruptured for 710 days.
or eroded atheromatous plaque. May also occur due - may be elevated in myocardial damage due to
to coronary artery spasm, arteritis or sudden severe other causes, e.g. myocarditis, contusion and
hypo- or hypertension. also other non-cardiac critical illness (e.g. sepsis,
Classification: renal failure, PE), probably reflecting myocar-
S-T segment elevation myocardial infarction dial injury but in most cases not related to coro-
(STEMI): ACS with ST segment elevation on nary artery disease. Likely benefit of NSTEMI
12-lead ECG. Suggestive of total coronary artery treatment in these cases should be assessed on
occlusion. Consistently associated with elevated an individual patient basis.
plasma biomarkers of myocardial damage. Immedi- echocardiography: may be used to assess regional
ate reperfusion therapy (see below) significantly and global ventricular function; regional wall
improves outcomes. ACS with new-onset left bundle motion abnormalities and loss of thickness suggest
branch block (LBBB) or evidence of posterior acute infarction. Also useful in diagnosing compli-
infarction is included in this category for treatment cations of MI (e.g. ventricular aneurysm, mitral
purposes. regurgitation, mural thrombus).
non S-T segment elevation acute coronary syn- Immediate management of suspected ACS:
dromes (NSTEACS): suggestive of sub-total arte- O2 via facemask (if evidence of hypoxia, pulmonary
rial occlusion. Immediate reperfusion therapy is not oedema or ongoing ischaemia), cardiac monitoring,
indicated, although early (within 24h) percutane- 12-lead ECG, iv access.
ous transluminal coronary angioplasty (PTCA) may aspirin 300mg orally.
be considered in high-risk patients. Further subdi- analgesia (e.g. iv morphine in 2mg increments).
vided into: sublingual GTN.
- non S-T segment elevation myocardial infarction associated pulmonary oedema and arrhythmias
(NSTEMI); normal or non-specific changes on should be treated in the usual way.
ECG, with elevated cardiac biomarkers. consideration for immediate reperfusion therapy if:
- unstable angina: ACS without elevated cardiac - presentation < 12h after symptom onset, unre-
biomarkers. lieved by GTN.
Clinical features: - S-T segment elevation > 0.1 mV in two or
pain as for myocardial ischaemia. more contiguous chest leads or two adjacent
arrhythmias; cardiac arrest may occur. limb leads.
anxiety, sweating, pallor, dyspnoea. - new-onset LBBB.
hypertension or hypotension. - posterior infarction (dominant R wave and S-T
cardiac failure and cardiogenic shock. depression in V1V2 chest leads).
Severe infarction is usually associated with more Reperfusion strategies include:
severe symptoms and signs than unstable angina, pharmacological thrombolytic therapy: agents
although painless/silent infarction is also common. include streptokinase, alteplase, tenecteplase
Differential diagnosis: pain and ECG changes may and reteplase. Survival benefit is reduced with
occur with lesions of: increasing delay, and is negligible from 12 h after
heart/great vessels, e.g. aortic dissection, onset of symptoms. Administration of thrombolysis
pericarditis. within 1 h of the patient calling for professional
lung, e.g. PE, chest infection. help is a national audit standard. Contraindications
oesophagus, e.g. spasm, inflammation, rupture. include active bleeding, recent trauma (including
abdominal organs, e.g. peptic ulcer disease, pancre- surgery and CPR), previous haemorrhagic stroke
atitis, cholecystitis. or recent CVA, uncontrolled hypertension and
Investigations: pregnancy.
12-lead ECG (see Myocardial infarction for charac- primary PTCA.
teristic features of STEMI and their localisation by emergency coronary artery bypass surgery.
 Acute kidney injury 9

Thrombolysis is generally only preferred if primary Acute kidney injury (AKI). Previously referred to as
PTCA is unavailable or there would be delay of > 90min acute renal failure, describing a rapid deterioration
in delivering it and the presentation is within 3h of (within 48h) from baseline renal function; classified
symptom onset. Primary PTCA is particularly superior according to severity by the RIFLE criteria. An indepen-
if: there is cardiogenic shock; there are contraindications dent risk factor for in-hospital morbidity and mortality
to thrombolysis; or the patient is at high risk of death and a major cause of death in ICU, especially as part of
(e.g. age > 75, previous MI, extensive anterior infarct). MODS. May develop with or without pre-existing renal
Emergency surgery is generally reserved for those impairment. May follow any severe acute illness, dehy-
known to have disease uncorrectable by PTCA or in dration, trauma or major surgery (especially involving
whom primary PTCA fails. the heart and great vessels), hepatic failure, obstetric
Patients not meeting criteria for immediate reperfu- emergencies, and any condition involving sustained
sion (i.e. those with NSTEACS) are managed either hypotension.
invasively (PTCA within 24h plus abciximab iv) or con- May be classified as:
servatively (pharmacological management only). High- prerenal: caused by renal hypoperfusion, e.g. shock,
risk patients are most likely to benefit from invasive hypovolaemia, cardiac failure, renal artery stenosis.
therapy. renal: caused by renal disease:
Pharmacological adjuncts include: - glomerular, e.g.:
clopidogrel and low-molecular weight heparin (e.g. - glomerulonephritis.
enoxaparin): should be given to all patients (in - diabetes mellitus.
the absence of contraindications) with definite or - amyloid.
strongly suspected ACS, in addition to aspirin. Pra- - tubulointerstitial, e.g.:
sugrel and ticagrelor are newer alternatives to clopi- - acute tubular necrosis (ATN): accounts for
dogrel for certain patients. 75% of hospital AKI. Caused by renal hypoper-
GTN sublingually or by iv infusion if pain persists. fusion or ischaemia and/or chemical toxicity,
glycoprotein IIB/IIIa inhibitors (e.g. abciximab and trauma or sepsis. Nephrotoxins include analge-
tirofiban): beneficial in patients undergoing PTCA, sics (e.g. chronic aspirin and paracetamol
those at high risk of death, or both. therapy), NSAIDs, aminoglycosides, immuno-
-adrenergic receptor antagonists: reduce the rate suppressive drugs, radiological contrast media
of reinfarction and VF and should be commenced and heavy metals. Usually (but not always)
within 24h if there are no contraindications, e.g. associated with oliguria (caused by tubular cell
heart block, pulmonary oedema, hypotension. necrosis, tubular obstruction and cortical arte-
Those unable to receive -blockers should receive riolar vasoconstriction).
one of the non-dihydropyridine calcium channel - acute cortical necrosis: typically associated
blocking drugs (e.g. verapamil). with placental abruption, pre-eclampsia and
ACE inhibitors: improve long-term survival after septic abortion, but also with factors causing
MI and should be commenced within 24h, assum- ATN. Confirmed by renal biopsy. Usually
ing no contraindications. irreversible.
magnesium and potassium supplementation to - tubulointerstitial nephritis/pyelonephritis.
maintain normal levels reduces the indidence of - polycystic renal disease.
arrhythmias. Prophylactic administration of antiar- - tubular obstruction, e.g. in myeloma,
rhythmic drugs is no longer recommended. myoglobinuria.
Kumar A, Cannon CP (2009). Mayo Clin Proc; 84: 917 - vascular, e.g. hypertension, connective tissue
38, 102136 disease.
postrenal: caused by obstruction in the urinary tract,
Acute cortical necrosis, see Renal failure e.g. bladder tumour, prostatic hypertrophy.
Distinction between renal and pre- or postrenal
Acute crisis resource management, see Crisis resource failure is important since diagnosis guides treatment,
management and early intervention can prevent irreversible
injury.
Acute demyelinating encephalomyelopathy, see Features:
Demyelinating diseases oliguria/anuria.
uraemia and accumulation of other substances
Acute life-threatening events recognition and (e.g. drugs): nausea, vomiting, malaise, increased
treatment (ALERT). Multiprofessional course aimed bleeding and susceptibility to infection, decreased
at reducing the incidence of potentially avoidable cardiac healing.
arrests and admissions to ICU. Targeted especially at reduced sodium and water excretion and oedema,
junior doctors and ward nurses. Sharing principles hypertension, hyperkalaemia, acidosis.
of many life-support training programmes (e.g. ALS, The following may aid diagnosis:
ATLS, APLS, CCrISP), its development embraces both analysis of urine: e.g. tubular casts may be seen in
clinical governance and multiprofessional education. ATN, myoglobinuria may be present.
Uses a structured and prioritised system of patient plasma and urine indices (Table 2).
assessment and management to recognise and treat seri- flushing of the urinary catheter using aseptic
ously ill patients or those at risk of deterioration. technique.
Smith GB, Osgood VM, Crane S (2002). Resuscitation; assessment of cardiac and volume status to exclude
52: 2816 hypovolaemia.
See also, Early warning scores; Medical emergency team; a fluid challenge of, e.g. 200300ml: increased urine
Outreach team output may occur in incipient prerenal failure.
10 Acute lung injury

pulmonary wedge pressure 18mmHg or absence

Table 2 Investigations used to differentiate between prerenal
of clinical evidence of left atrial hypertension.
oliguria and acute kidney injury
arterial hypoxaemia resistant to oxygen therapy

Investigation Prerenal oliguria Renal failure alone (PaO2/FIO2 < 39.9 kPa [300mmHg] for defini-
tion of ALI; < 26.6 kPa [200mmHg] for definition
Specific gravity >1.020 <1.010 of ARDS), regardless of the level of ventilatory
Urine osmolality (mosmol/kg) >500 <350 support.
Urine sodium (mmol/l) <20 >40 Other features:
Urine/plasma osmolality ratio >2 <1.1 reduced respiratory compliance, lung volumes and
Urine/plasma urea ratio >20 <10 increased work of breathing.
Urine/plasma creatinine ratio >40 <20 V/Q mismatch with increased shunt.
Fractional sodium excretion (%) <1 >1 pulmonary vascular resistance may be raised.
Renal failure index <1 >1 in uncomplicated ALI, plasma oncotic pressure is

Fractional sodium excretion =

urine/plasma sodium ratio
100% normal.
urea/plasma creatinine ratio MODS may occur and is a common cause of death.
Pathophysiology: ALI results from damage to either
urine sodium
and renal failure index = the lung epithelium or endothelium. Two pathways of
urine/plasma creatinine ratio
injury exist:
direct insult to lung, e.g. aspiration, smoke
inhalation.
indirect result of an acute systemic inflammatory
diuretic administration, e.g. furosemide or mannitol: response involving both humoral (activation
increased urine output may occur in incipient ATN of complement, coagulation and kinin systems;
but there is no evidence of a prophylactic or thera- release of mediators including cytokines, oxidants,
peutic effect; however reduction in renal O2 demand nitric oxide) and cellular (neutrophils, macro-
(furosemide) and scavenging of free radicals (man- phages and lymphocytes) components. Pulmonary
nitol) have been suggested as being theoretically infiltration by neutrophils leads to interstitial fibro-
beneficial. sis, possibly as a result of damage caused by free
renal ultrasound or biopsy. radicals. Examples include sepsis, pancreatitis and
Management: fat embolism.
directed at the primary cause with optimisation of Histopathological findings can be divided into three
renal blood flow. phases: exudative (oedema and haemorrhage), pro
monitoring of weight, cardiovascular status, includ- liferative (organisation and repair) and fibrotic.
ing JVP/CVP/pulmonary capillary wedge pressure Management involves prompt treatment of the
as appropriate, urea and electrolytes, and acidbase underlying cause and supportive therapy:
status. Accurate recording of fluid balance is vital. general support: nutrition, DVT prophylaxis, pre-
fluid restriction if appropriate, e.g. previous hours vention of infection.
urine output + 30ml/h whilst oliguric. O2 therapy, accepting SpO2 > 90%. CPAP is often
H2 receptor antagonists are commonly adminis- helpful as it improves FRC.
tered to reduce GIT haemorrhage. ventilatory support: IPPV may be necessary if
treatment of hyperkalaemia. CPAP is ineffective. Lung protection strategies
monitoring of drug levels, as clearance may be improve survival in ARDS and consist of using low
reduced considerably. tidal volumes/inspiratory pressures (e.g. 46ml/kg
various dialysis therapies. and PPlateau < 30 cmH2O) with moderate PEEP, tol-
adequate nutrition. erating a degree of respiratory acidosis (permissive
Bellomo R, Kellum JA, Ronco C (2012). Lancet; 380: hypercapnia). High-pressure recruitment manoeu-
75666 vres and high PEEP are often beneficial in
life-threatening hypoxaemia, but increase the risk
Acute lung injury (ALI). Syndrome of pulmonary of barotrauma and impaired cardiac output.
inflammation and increased pulmonary capillary perme- Additional ventilatory strategies include inverse
ability associated with a variety of clinical, radiological ratio ventilation (at I:E ratios of up to 4:1), airway
and physiological abnormalities that cannot be explained pressure release ventilation and high-frequency
by, but may coexist with, left atrial or pulmonary capil- ventilation. Extracorporeal membrane oxygenation
lary hypertension. Associated with sepsis, major trauma, has been used with varying success. Extracorporeal
aspiration pneumonitis, blood transfusion, pancreatitis, CO2 removal may be useful in life-threatening
cardiopulmonary bypass and fat embolism. Onset is hypercapnia.
usually within 23 days of the precipitating illness or prone ventilation improves oxygenation in some
injury, although direct lung insults usually have a shorter patients, although overall mortality is not signifi-
latency. Acute respiratory distress syndrome (ARDS) is cantly improved.
now regarded to be the most severe form of ALI, with diuresis and fluid restriction are often instituted to
a mortality of 4060%. The definitions of ALI and reduce lung water, although avoidance of initial
ARDS are increasingly being challenged and diagnostic fluid overload is thought to be more important.
criteria vary, but the most commonly used are those inhaled vasodilator drugs (e.g. prostacyclin, nitric
defined by the 1994 American-European Consensus oxide) have been used to decrease pulmonary vas-
Committee: cular resistance in aerated areas of lung, thereby
acute onset. reducing V /Q mismatch and improving oxygenation,
bilateral diffuse infiltrates seen on the CXR. but with no demonstrable improved survival.
 Adenosine monophosphate, cyclic 11

corticosteroid therapy is controversial. There potassium conductance and reduced calcium conduc-
appears to be no benefit to their prophylactic tance). Also an inhibitory CNS neurotransmitter.
administration, or in high-dose, short-term therapy The drug of choice for treatment of SVT (including
at the onset of ALI/ARDS. However, corticoste- that associated with WolffParkinsonWhite syndrome),
roids may have a role in refractory ARDS. and diagnosis of other tachyarrhythmias by slowing
free radical scavengers, antiprostaglandins and anti- atrioventricular conduction. Its short half-life (810s)
proteases have been investigated. and lack of negative inotropism make it an attractive
Diaz JV, Brower R, Calfee CS, Matthay MA (2010). Crit alternative to verapamil. Not included in the Vaughan
Care Med; 38: 164450 Williams classification of antiarrhythmic drugs.
Has also been used as a directly acting vasodilator
Acute-phase response. A reaction of the haemopoietic drug in hypotensive anaesthesia. Increases cardiac
and hepatic systems to inflammation or tissue injury, output, with stable heart rate. Its effects are rapidly
assumed to be of benefit to the host. There is a rise in reversible on stopping the infusion.
the number/activity of certain cells (neutrophils, plate- Dosage:
lets) and plasma proteins (e.g. fibrinogen, complement, SVT: 6mg by rapid iv injection into a central or
C-reactive protein, plasminogen, haptoglobin) involved large peripheral vein; if unsuccessful after 12min,
in host defence, whilst there is a reduction in proteins may be followed by up to two further boluses of
with transport and binding functions (e.g. albumin, hae- 12mg.
moglobin, transferrin). Initiated by actions of cytokine hypotensive anaesthesia: 50300g/kg/min. ATP
mediators such as interleukins (IL-1, IL-1, IL-6 and has also been used.
IL-11), tumour necrosis factors ( and ) and leukaemia Side effects are usually mild and include flushing,
inhibitory factor. dyspnoea and nausea. Bronchoconstriction may occur
Serum levels of acute-phase proteins (e.g. C-reactive in asthmatics. Bradycardia is resistant to atropine.
protein) can be helpful in diagnosis, monitoring and Adenosines action is prolonged in dipyridamole
prognosis of certain diseases. The rise in fibrinogen levels therapy (because uptake of adenosine is inhibited)
causes an elevation in ESR. The fall in albumin is due to and reduced by theophylline and other xanthines
redistribution and decreased hepatic synthesis. (because of competitive antagonism). Transplanted
hearts are particularly sensitive to adenosines effects.
Acute physiology, age, chronic health evaluation, see [EM Vaughan Williams, English pharmacologist]
APACHE III scoring system
Adenosine monophosphate, cyclic (cAMP). Cyclic
Acute physiology and chronic health evaluation, see adenosine 3,5-monophosphate, formed from ATP by the
APACHE/APACHE II scoring systems enzyme adenylate cyclase. Activation of surface receptors
may cause a guanine nucleotide regulatory protein (G
Acute physiology score (APS). Physiological compo- protein) to interact with adenylate cyclase with resultant
nent of severity of illness scoring systems, such as changes in intracellular cAMP levels (Fig. 5). Many sub-
APACHE II/III and Simplified APS. Weighted values stances act on surface receptors in this way, including
(e.g. 04 in APACHE II) are assigned to each of a range catecholamines, vasopressin, ACTH, histamine, gluca-
of physiological variables (e.g. temperature, mean arte- gon, parathyroid hormone and calcitonin.
rial blood pressure, serum creatinine) on the basis of its Some substances inhibit adenylate cyclase via an
derangement from an established normal range, as inhibitory regulatory protein, e.g. noradrenaline at 2-
measured either upon ICU admission or within 24h of adrenergic receptors (Fig. 5).
entry. The sum of all assigned weighted values for the cAMP is termed a second messenger as it causes
physiological variables that comprise a given scoring phosphorylation of proteins, particularly enzymes, by
system constitutes the acute physiological score. The activating protein kinases. Phosphorylation changes
higher the acute physiology score, the sicker the patient. enzyme and thus cellular activity. cAMP is inactivated
See also, Mortality/survival prediction on intensive care
unit; Simplified acute physiology score
-Receptor 2-Receptor
Acute respiratory distress syndrome (ARDS), see
Acute lung injury
Cell membrane
Acute tubular necrosis, see Renal failure
Gs Gi
Adenylate
Acyclovir, see Aciclovir cyclase
Phosphodiesterase
Addiction, see Alcoholism; Substance abuse
ATP cAMP 5'-AMP
Addisons disease, see Adrenocortical insufficiency
Phosphorylation
ADEM, Acute demyelinating encephalomyelopathy, see Protein kinase of enzymes +
Demyelinating diseases other proteins

Adenosine. Nucleoside, of importance in energy homeo- Gs, stimulatory guanine nucleotide regulatory protein
stasis at the cellular level. Reduces O2 consumption, Gi, inhibitory guanine nucleotide regulatory protein
increases coronary blood flow, causes vasodilatation and
slows atrioventricular conduction (possibly via increased Fig. 5 cAMP involvement in transmembrane signalling
12 Adenosine triphosphate and diphosphate

by phosphodiesterase to 5-AMP. Phosphodiesterase Ideally the opening pressure should be as low as possible
inhibitors, e.g. aminophylline and enoximone, increase to reduce resistance to expiration, but not so low as to
cAMP levels. allow the reservoir bag to empty through it. Most contain
a thin disc held against its seating by a spring, as in the
Adenosine triphosphate and diphosphate (ATP and original Heidbrink valve. Adjusting the tension in the
ADP). ATP is the most important high-energy phos- spring, usually by screwing the valve top, alters the pres-
phate compound. When hydrolysed to form ADP, it sure at which the valve opens. The valve must be vertical
releases energy that may be utilised in many cellular in order to function correctly.
processes, e.g. active transport, muscle contraction. Its Modern valves, even when screwed fully down, will
phosphate bonds are formed using energy from catabo- open at high pressures (60 cmH2O). Most are now
lism; aerobic respiration generates 38 moles of ATP per encased in a hood for scavenging of waste gases.
mole of glucose, while anaerobic respiration (i.e. simple [Jay A Heidbrink (18751957), US anaesthetist]
glycolysis) yields 2 moles of ATP. See also, Anaesthetic breathing systems; Non-rebreathing
Other high-energy phosphate compounds include valves
phosphocreatine (in muscle), ADP itself, and other
nucleotides. ADP, see Adenosine triphosphate and diphosphate
See also, Cytochrome oxidase system; Metabolism; Tri-
carboxylic acid cycle Adrenal gland. Situated on the upper pole of the kidney,
each gland is composed of an outer cortex and an inner
Adenylate cyclase, see Adenosine monophosphate, medulla. The cortex consists of the outer zona glomeru-
cyclic losa (secreting aldosterone), the middle zona fasciculata
(secreting glucocorticoids) and inner zona reticularis
ADH, Antidiuretic hormone, see Vasopressin (secreting sex hormones). Hypersecretion may result
in hyperaldosteronism, Cushings syndrome and
Adhesion molecules. Molecules normally sited on virilisation/feminisation respectively. Hyposecretion
cell surfaces, involved in embryogenesis, cell growth and causes adrenocortical insufficiency.
differentiation, and wound repair. Also mediate endo- The adrenal medulla is thought to be derived from a
thelial cell/leucocyte adhesion, transendothelial migra- sympathetic ganglion in which the postganglionic neu-
tion and cytotoxic T-cell-induced lysis. Four major rones have lost their axons, and secrete catecholamines
families exist: integrins, cadherins, selectins (named after into the bloodstream. Hypersecretion results in phaeo-
the tissues in which they were discovered: L-selectin chromocytoma. See also, Sympathetic nervous system
[leucocytes], E-selectin [endothelial cells], P-selectin
[platelets]) and members of the immunoglobulin Adrenaline (Epinephrine). Catecholamine, acting as a
superfamily. hormone and neurotransmitter in the sympathetic
In general, contact between an adhesion receptor and nervous system and brainstem pathways. Synthesised
the extracellular milieu results in the transmission of and released from the adrenal gland medulla and
information allowing the cell to interact with its environ- central adrenergic neurones (for structure, synthesis and
ment. Defective interactions involving adhesion mole- metabolism, see Catecholamines). Called epinephrine in
cules are implicated in disease (e.g. certain skin diseases, the USA because the name adrenaline, used in other
metastasis of cancer cells). Many pathogens use adhe- countries, was too similar to the US-registered trade
sion receptors to penetrate tissue cells. Overexpression name Adrenalin that referred to a specific product
of intravascular adhesion molecules or receptors has (both adrenaline (Latin) and epinephrine (Greek)
been implicated in rheumatoid arthritis and rejection of referring to the location of the adrenal gland on the
transplanted organs. Control of vascular integrity and kidney).
defence against invasive pathogens require regulation of Stimulates both - and -adrenergic receptors; dis-
adhesive interactions among blood cells and between plays predominantly -effects at low doses, - at higher
blood cells and the vessel walls. Circulating leucocytes doses. Low-dose infusion may lower BP by causing vaso-
bind to the selectins of activated endothelial cells, dilatation in muscle via 2-receptors, despite increased
become activated by chemoattractants and migrate cardiac output via 1-receptors. Higher doses cause 1-
through intracellular gaps to the site of inflammation. mediated vasoconstriction and increased systolic BP,
Thus adhesion molecules play a part in the inflammatory although diastolic pressure may still decrease.
response in sepsis. Clinical uses:
with local anaesthetic agents, as a vasoconstrictor.
Adiabatic change. Volume change of a gas in which in anaphylaxis, cardiac arrest, bronchospasm.
there is no transfer of heat to or from the system. Sudden as an inotropic drug.
compression of a gas without removal of resultant in glaucoma (reduces aqueous humour
heat causes a rise in temperature. This may occur in the production).
gas already present in the valves and pipes of an anaes- in croup.
thetic machine when a cylinder is turned on (hence the Adrenaline may cause cardiac arrhythmias, especially in
danger of explosion if oil or grease is present). Sudden the presence of hypercapnia, hypoxia and certain drugs,
adiabatic expansion of a gas results in cooling, as in the e.g. halothane, cyclopropane and cocaine. During halo-
cryoprobe. thane anaesthesia, suggested maximal dosage of adrena-
See also, Isothermal change line is 10ml 1:100000 solution (100g) in 10min, or
30ml (300g) in 1h. More dilute solutions should be
Adjustable pressure-limiting valves. Valves that open used if possible. Adrenaline should not be used for ring
to allow passage of expired and surplus fresh gas from a blocks of digits or for penile nerve blocks, because of
breathing system, but close to prevent in-drawing of air. possible ischaemia to distal tissues.
 -Adrenergic receptor antagonists 13

Dosage: Used to lower BP and reduce afterload by causing

with local anaesthetic agents, 1:200000 concentra- vasodilatation. Compensatory tachycardia may occur.
tion is usual Side effects: postural hypotension, dizziness, tachycar-
anaphylaxis: 50g iv (0.5ml 1:10000 solution), dia (less so with the selective 1-antagonists, possibly
repeated as required. The recommended initial because the negative feedback of noradrenaline at
route in general medical guidelines is usually im 2-receptors is unaffected). Tachyphylaxis may occur.
(0.51.0ml 1:1000 solution), reflecting the risks of
iv administration without appropriate monitoring. -Adrenergic receptor antagonists (-Blockers).
cardiac arrest: 1mg (10ml 1:10000) iv. Competitive antagonists at -adrenergic receptors.
by infusion: 0.010.15g/kg/min initially, increasing Actions:
as required. reduce heart rate, myocardial contractility and O2
croup: 0.5ml/kg (1:1000 solution) nebulised, up to consumption.
5ml maximum, repeated after 30min if required. increase coronary blood flow by increasing diastolic
Subcutaneous injection in shocked patients results in filling time.
unreliable absorption. Tracheal administration in the antiarrhythmic action results from -receptor
absence of iv access is no longer recommended; the antagonism and possibly a membrane-stabilising
intraosseous route is now the suggested alternative. effect at high doses.
See also, Tracheal administration of drugs antihypertensive action (not fully understood but
may involve reductions in cardiac output, central
-Adrenergic receptor agonists. Naturally occurring sympathetic activity and renin levels).
some have partial agonist activity (intrinsic sym
agonists include adrenaline and noradrenaline, which
stimulate both 1- and 2-adrenergic receptors. pathomimetic activity), e.g. pindolol, acebutolol,
Methoxamine and phenylephrine are synthetic 1- celiprolol and oxprenolol.
practolol, atenolol, metoprolol, betaxolol, bisopro-
receptor agonists, used to cause vasoconstriction, e.g. to
correct hypotension in spinal anaesthesia. lol, nebivolol and acebutolol are relatively cardio
Clonidine acts on central 2-receptors. Clonidine and selective, but all will block 2-receptors at high
other 2-receptor agonists (e.g. dexmedetomidine) have doses. Celiprolol has 1-receptor antagonist and 2-
been shown to reduce pain and anaesthetic require- receptor agonist properties, thus causing peripheral
ments, and have also been used for sedation in ICU. vasodilatation in addition to cardiac effects.
labetalol and carvedilol have - and -receptor
Other 2-receptor agonists (e.g. xylazine, detomidine
and medetomidine) have been used in veterinary prac- blocking properties. The former is available for iv
tice as anaesthetic agents for many years. administration and is widely used for acute reduc-
tion in BP.
Half-lives:
-Adrenergic receptor agonists. Include adrenaline, esmolol: a few minutes; hydrolysed by red cell
dobutamine and isoprenaline, which stimulate both esterases.
1- and 2-adrenergic receptors to varying degrees. metoprolol, oxprenolol, pindolol, propranolol,
Dopamine acts mainly at 1-receptors. timolol: 24h.
Salbutamol and terbutaline predominantly affect 2- atenolol, practolol, sotalol: 612h.
receptors, and are used clinically to cause bronchodilata- nadolol: 24h.
tion in asthma, and as tocolytic drugs in labour. Most are readily absorbed enterally, and undergo exten-
Formoterol and salmeterol are longer-acting agents sive first-pass metabolism. Practolol, atenolol, celiprolol,
given by inhalation for chronic asthma. Ritodrine is also nadolol and sotalol are water-soluble and largely
used as a tocolytic drug. Some 1-receptor effects are excreted unchanged in the urine; propranolol and meto-
seen at high doses, e.g. tachycardia. They have been used prolol are lipid-soluble and almost completely metabo-
in the treatment of cardiac failure and cardiogenic shock; lised in the liver.
stimulation of vascular 2-receptors causes vasodilata- Uses:
tion and reduces afterload. hypertension, ischaemic heart disease, MI,
arrhythmias, hyperthyroidism, anxiety, migraine
-Adrenergic receptor antagonists (-Blockers). prophylaxis. Have been shown to improve outcome
Usually refer to antagonists that act exclusively at in cardiac failure when added to ACE inhibitor
-adrenergic receptors. therapy. Acute perioperative withdrawal of -
Drugs may be: blockers from patients already receiving them is
selective: known to worsen outcomes; they should therefore
- 1-receptors, e.g. prazosin, doxazosin, terazosin, be continued.
indoramin, phenoxybenzamine. Tamsulosin acts perioperatively: to reduce the hypertensive response
specifically at 1A-receptors and is used in benign to laryngoscopy; to treat perioperative hyperten-
prostatic hypertrophy. sion, tachycardias and myocardial ischaemia; in
- 2-receptors: yohimbine. hypotensive anaesthesia. The use of perioperative
non-selective, e.g. phentolamine. -blockade to reduce perioperative cardiovascular
Labetalol and carvedilol (a drug with similar effects) are morbidity and mortality in high-risk patients under-
antagonists at both - and -receptors. Other drugs may going non-cardiac surgery is no longer advocated as
also act at -receptors as part of a range of effects, e.g. the cardiovascular benefits are outweighed by the
chlorpromazine, droperidol. increased incidence of cerebrovascular accidents.
Antagonism may be competitive, e.g. phentolamine, Side effects:
or non-competitive and therefore longer-lasting, e.g. cardiac failure, especially in combination with other
phenoxybenzamine. negative inotropes.
14 -Adrenergic receptor antagonist poisoning

bronchospasm and peripheral arterial insufficiency,

Table 3 Classification and actions of adrenergic receptors
via blockade of 2-receptors.
increased risk of diabetes when used to treat
Receptor
hypertension and reduced cardiovascular (1) type Site Effect of stimulation
and metabolic (2) response to hypoglycaemia in
diabetics. 1 Vascular smooth muscle Contraction
depression and sleep disturbance: less likely with Bladder smooth muscle Contraction
water-soluble drugs. (sphincter)
oral practolol was withdrawn because of the oculo- Radial muscle of iris Contraction
mucocutaneous syndrome following its use. The iv Intestinal smooth muscle Relaxation, but contraction
preparation has been withdrawn for commercial of sphincters
Uterus Variable
reasons.
Salivary glands Viscous secretion
Liver Glycogenolysis
-Adrenergic receptor antagonist poisoning. Uncom- Pancreas Decreased secretion
mon, but overdose is hazardous because of these drugs of enzymes, insulin
low therapeutic ratio. General features include cardiac and glucagon
failure, bradycardia, cardiac conduction defects, hypo- 2 Presynaptic membranes of Reduced release of
tension, bronchospasm, coma and convulsions, the latter adrenergic synapses noradrenaline
two especially with propranolol. Sotalol may cause ven- Postsynaptic membranes Smooth muscle contraction
tricular tachyarrhythmias. Hypoglycaemia is rare. Platelets Aggregation
Treatment: 1 Heart Increased rate and force
of contraction
as for poisoning and overdoses generally.
Adipose tissue Breakdown of stored
CVS effects may require CPR, glucagon (220mg
triglycerides to fatty acids
[50150g/kg in children] iv followed by 50g/ Juxtaglomerular apparatus Increased renin secretion
kg/h) or iv infusion of isoprenaline. Atropine is 2 Vascular smooth muscle Relaxation
often ineffective but should be tried in vagal- (muscle beds)
blocking doses (3mg iv [40g/kg in children]). Bronchial smooth muscle Relaxation
Cardiac pacing may be required. Intestinal smooth muscle Relaxation
Bladder sphincter Relaxation
Adrenergic receptors. G protein-coupled receptors, Uterus Variable; relaxes the
pregnant uterus
activated by adrenaline and other catecholamines, and
Salivary glands Watery secretion
divided into - and -receptors. Further subdivided into Liver Glycogenolysis
1/2/3 and 1/2 receptors (Table 3). Pancreas Increased insulin and
Their effects are mediated by second messengers: glucagon secretion
1-receptor effects by increases in intracellular calcium 3 Adipose tissue Lipolysis
ion concentration, 2-receptor effects by reducing intra-
cellular cAMP, and 1- and 2-receptor effects by
increasing cAMP. There is evidence for mixed receptor
populations at both pre- and postsynaptic membranes.
2-receptors have been further subdivided into 2A
(responsible for central regulation of BP, sympathetic Features:
activity, pain processing and alertness), 2B (causes vaso- acute: hypotension and electrolyte abnormalities
constriction) and 2C (thought to be involved in behav- (hyponatraemia, hyperkalaemia, hypochloraemia,
ioural responses). hypercalcaemia and hypoglycaemia), muscle weak-
See also, -Adrenergic receptor agonists; -Adrenergic ness. In critically ill patients, treatment of occult
receptor agonists; -Adrenergic receptor antagonists; adrenocortical insufficiency may be necessary for
-Adrenergic receptor antagonists; Sympathetic nervous reversal of hypotension that is resistant to vasopres-
system sor drugs.
chronic: weight loss, vomiting, diarrhoea, malaise,
Adrenocortical insufficiency. May be due to: postural hypotension, increased risk of infection,
primary adrenal failure (Addisons disease, high muscle weakness. Dark pigmentation in scars and
ACTH) due to: skin creases occurs in primary disease. Acute insuf-
- autoimmune disease: the most common cause; ficiency (crises) may develop following stress, e.g.
may be associated with other autoimmune disease, infection, surgery, or any critical illness.
e.g. diabetes, thyroid disease, pernicious anaemia, Diagnosed by measurement of plasma cortisol and
vitiligo. ACTH levels, including demonstration of a failed Syn-
- TB, amyloidosis, metastatic infiltration, haemor- acthen test (an impaired cortisol response following
rhage, drugs or infarction, e.g. in shock. Water- administration of tetracosactide, a synthetic analogue of
houseFriderichsen syndrome comprises bilateral ACTH).
adrenal cortical haemorrhage associated with Treatment:
severe meningococcal disease. acute: iv saline, hydrocortisone 100mg iv qds (pref-
secondary adrenal failure (low ACTH) due to: erably as the sodium succinate).
- corticosteroid therapy withdrawal. chronic: hydrocortisone 2030mg/day, fludrocorti-
- ACTH deficiency, e.g. due to surgery, head injury, sone 50300g/day, both orally. Typically, both are
disease of the pituitary or hypothalamus. required in primary insufficiency but only hydrocor-
The term Addisonian describes features of adrenal tisone in secondary insufficiency, although this may
insufficiency irrespective of the cause. not always hold true.
 Advanced life support, adult 15

[Thomas Addison (17931860) and Rupert Waterhouse Advanced life support, adult. Component of CPR
(18731958), English physicians; Carl Friderichsen involving specialised equipment, techniques (e.g.
(18861979), Danish paediatrician] tracheal intubation), drugs, monitoring and 100%
oxygen. Airway management may include use of
Adrenocorticotrophic hormone (ACTH). Polypep- tracheal intubation, LMA, Combitube or, rarely,
tide hormone (39 amino acids; mw 4500) secreted by tracheostomy.
corticotropic cells of the anterior pituitary gland in Recommendations of the European Resuscitation
response to corticotropin releasing factor secreted by Council (2010):
the hypothalamus. Release of ACTH is highest in the attention to ABC of basic life support advanced
early morning and is increased by emotional and physi- airway management, if there is a delay in getting
cal stress, including surgery. It increases corticosteroid a defibrillator. Defibrillation should take place
synthesis in the adrenal glands, particularly glucocorti- without delay for a witnessed or in-hospital cardiac
coids but also aldosterone. ACTH production is inhib- arrest. A precordial thump should be considered for
ited by glucocorticoids (i.e. negative feedback). ACTH witnessed, monitored collapse when a defibrillator
or its synthetic analogue tetracosactide (Synacthen) has is not immediately available.
been used in place of corticosteroid therapy in an actions then depend on the initial rhythm:
attempt to reduce adrenocortical suppression, and is - shockable, i.e. VF/pulseless VT:
used for diagnostic tests in endocrinology. They have - defibrillation: a single shock of 150200 J
also been given to treat or prevent post-dural puncture (biphasic) or 360 J (monophasic) followed by
headache. immediate resumption of CPR without reas-
See also, Stress response to surgery sessing the rhythm or feeling for a pulse. After
2min of CPR, reassess and, if indicated, subse-
Adult respiratory distress syndrome, see Acute respi- quent shocks of 150360 J (biphasic) or 360 J
ratory distress syndrome (monophasic). If it is unclear whether the
rhythm is asystole or fine VF, continue basic life
Advance decision (Advance directive; Living will). support and do not attempt defibrillation.
Statement, usually written, that provides for a mentally - adrenaline 1mg iv if VF/VT persists after the
competent person to refuse certain future medical third shock, then 1mg every 35min if it still
treatments, usually involving life-saving therapies, if he/ persists.
she were subsequently to become mentally or physi- - consider and correct potentially reversible
cally incompetent. The directive may be triggered by causes (see below); if not already done, secure
certain background conditions such as dementia, per- the airway, administer oxygen, get iv access.
sistent vegetative state and terminal disease, or acute Cardiac massage and ventilation at 30:2; com-
events including cardiorespiratory arrest, pneumonia, pressions should be uninterrupted once the
acute kidney injury, major CVA or spinal cord injury. airway has been secured.
Legal and ethical issues relate to competence (capacity) - in refractory VF despite three shocks, consider
of the individual, the possibility of changing ones mind, amiodarone 300mg as an iv bolus; 150mg as a
advances in medicine or techniques since the directive second bolus followed by 900mg/24h. Lido-
was written, the refusal of what might be considered caine 1mg/kg is an alternative if amiodarone
basic care (e.g. feeding), difficulties anticipating the is unavailable, but should not be used in addi-
specific circumstances that may arise and therefore tion (maximum 3mg/kg in the first hour). Con-
be covered, and the objections of doctors, other health- sider use of different pad positions/contacts,
care staff and relatives. Previously commonly referred different defibrillator, buffers, if refractory.
to as advance directives, they were renamed advance Magnesium sulphate 8mmol may be indicated
decisions in the Mental Capacity Act 2005, which in hypomagnesaemia, torsades de pointes or
enshrined them into statute for the first time. From digoxin toxicity.
April 2007, in order to be legally valid, an advance deci- - non-shockable, i.e. asystole or pulseless electri-
sion must: cal activity (PEA):
be made by a person 18 years old, with the capac- - adrenaline 1mg as soon as venous access
ity to make it. obtained, repeated every 35min. CPR for
specify the treatment to be refused (can be in lay 2min. Consider and correct potentially revers-
terms) and the circumstances in which this refusal ible causes; cardiac massage and ventilation as
would apply. for VF (see above).
be made freely without the influence of anyone else. - reassess after 2min and repeat if necessary.
be unaltered from when it was made. potentially reversible causes (4 Hs and 4 Ts):
White SM, Baldwin TJ (2006). Anaesthesia; 61: 3819 hypoxaemia, hypovolaemia, electrolyte and meta-
bolic disorders (especially hyper-/hypokalaemia),
Advanced (Cardiac) Life Support (ACLS/ALS). hypothermia, tension pneumothorax, cardiac
System of advanced management of cardiac arrest and tamponade, toxic/therapeutic disturbances (poison-
its training to paramedics, doctors, nurses and other ing and overdoses), thromboembolic/mechanical
healthcare professionals. Also encompasses the recogni- obstruction (PE). A fifth H (hydrogen ions, i.e.
tion and management of periarrest arrhythmias and acidosis) and a fifth T (coronary thrombosis) have
postresuscitation care. In the UK, ALS courses are run also been suggested.
by the Resuscitation Council (UK). In the USA, the drugs are usually given iv, preferably via a central
American Heart Association runs ACLS courses. vein. Peripheral lines should be flushed with 20ml
See also, Advanced life support, adult; Basic life support, saline after each drug. Tracheal administration of
adult; Cardiopulmonary resuscitation drugs is no longer recommended; the intraosseous
16 Advanced Life Support Group

route is now the suggested alternative in the absence in life-saving techniques. Develops and administers
of iv access. several courses such as APLS, MOET, STaR.
consider buffers, e.g. bicarbonate 50ml 8.4% solu-
tion in severe acidosis (pH < 7.1 or base excess Advanced Life Support in Obstetrics (ALSO). Train-
exceeding 10), or specific conditions, e.g. tricyclic ing system developed in the USA and administered by
antidepressant drug poisoning, hyperkalaemia. the American Association of Family Physicians; intro-
if unsuccessful, CPR is generally discontinued after duced in the UK as part of the Maternal and Neonatal
3060min depending on the circumstances (longer Emergency Training (MANET) project. Aimed at
in treatable conditions and in children). training medical and midwifery staff in the practical
post-arrest care: management of maternal and neonatal emergencies and
- checking of arterial blood gases, electrolytes and provision of life support for the mother and child. Similar
CXR. to other CPR training systems (e.g. ACLS, ATLS) in its
- transfer to ICU and cardiorespiratory support as approach and structure.
required. MODS may occur. See also, Cardiopulmonary resuscitation, neonatal
- therapeutic hypothermia to 3234C for 1224h
improves outcome in unconscious adult patients Advanced Paediatric Life Support (APLS). System of
with spontaneous circulation after out-of-hospital management of the sick or injured child, devised by
cardiac arrest due to VF, and possibly for other specialists in paediatrics, accident and emergency medi-
out-of-hospital arrest rhythms or in-hospital cine, anaesthesia and paediatric surgery in the UK and
arrest. administered by the Advanced Life Support Group. The
special situations: system integrates basic and advanced resuscitation tech-
- trauma, choking, near-drowning, electrocution, niques, similar to those employed in ALS/ACLS and
anaphylaxis. ATLS, to permit the assessment and treatment of
- paediatric and neonatal CPR (see Cardiopulmo- paediatric emergencies (e.g. airway obstruction, cardiac
nary resuscitation, paediatric; Cardiopulmonary arrest, hypothermia, convulsions, poisoning and trauma).
resuscitation, neonatal). Incorporates assessment of the airway, breathing and
Recent changes/controversies: circulation with special emphasis on determining if the
importance of effective chest compressions with child has failure of respiration or circulation. Stresses the
minimal interruption is emphasised, to a depth of anatomical and physiological differences between adults
56cm and at a rate of 100120/min; compressions and children whilst emphasising paediatric normal
to continue during defibrillator charging. ranges (e.g. for weight, cardiorespiratory parameters).
atropine is no longer recommended for PEA/ Underlines the usefulness of specific interventions (e.g.
asystole. insertion of an intraosseous needle).
calcium is not recommended routinely because it See also, Cardiopulmonary resuscitation, paediatric
reduces coronary and cerebral blood flow.
hyperglycaemia is thought to worsen the effects of Advanced Trauma Life Support (ATLS). System
cerebral hypoxia. Avoidance of glucose solutions of trauma management devised by physicians in
during CPR has been suggested. Nebraska, USA in 1978 and adopted by the American
the decision to stop CPR may be difficult in certain College of Surgeons in 1979. Based on the concept of
circumstances, as may the decision not to start, reducing morbidity and mortality in the first (golden)
e.g. terminally ill, elderly patients. Routine regular hour following trauma during which patients may die
consideration of do not resuscitate orders has been from potentially survivable injuries (airway obstruction,
suggested. Advance decisions may specify condi- hypovolaemia, pneumothorax, cardiac tamponade), by
tions under which patients do or do not wish to be teaching all members of the trauma team the same
resuscitated. algorithms and procedures which are then carried out
there has been recent controversy over whether by rote on every patient. Has been criticised (mainly by
relatives of cardiac arrest victims should witness senior doctors) because of its very didactic nature,
resuscitation attempts; discomfort of staff and pos- although this is one of its strengths since those most
sible hindrance of CPR may be offset by the benefi- likely to be in the front line of trauma care are tradi-
cial effects of relatives seeing that adequate efforts tionally junior doctors who lack the expertise and
have been expended and their being able to be judgement of their seniors.
present if the patient dies. Consists of the following phases:
manipulation of intrathoracic pressure has been preparation.
suggested in order to improve cardiac output (see triage.
Cardiac massage). primary survey: incorporates assessment of the
Complications include trauma to abdominal organs and integrity and function of the airway, cervical spine,
ribs and those associated with tracheal intubation/ breathing, circulation and neurological status. The
attempted intubation and vascular access. patient is fully exposed to detect all life-threatening
European Resuscitation Council (2010). Resuscitation; injuries, with resuscitation taking place in tandem
81: 121976 with the primary survey. The need for radiographs
See also, Acute Cardiac Life Support; Brainstem death; of the chest, lateral cervical spine and pelvis should
Cough-CPR; Resuscitation Council (UK) be considered during the primary survey but should
not delay resuscitation (the cervical spine is assumed
to require immobilisation for any injury above the
Advanced Life Support Group. UK charity established clavicles until proven otherwise). This takes place
in 1993, aiming to promote and provide both the public simultaneously with the primary survey.
and healthcare professionals with training and education resuscitation of life-threatening conditions.
 Afterload 17

secondary survey: the patient is fully examined from and 24h after the reaction if anaphylaxis is sus-
head to toe to exclude injuries to scalp, cranium, pected (99% of plasma tryptase arises from mast
face, neck, shoulders, chest, abdomen, perineum, cells; normal plasma levels < 1ng/ml). A signifi-
long bones, spine and spinal cord. Special pro cant rise is suggestive of anaphylaxis, but its
cedures (e.g. abdominal ultrasound, diagnostic peri- absence does not exclude it; conversely it can
toneal lavage, iv pyelogram, CT of brain) may be occur in non-allergic reactions, albeit to a lesser
undertaken during this phase, before planning of extent. Tryptase is stable in solution and its half-
definitive care. life is 2.5h, so back-calculation to the time of the
continued post-resuscitation monitoring and reaction should still be possible if the samples
re-evaluation. actual times are accurately recorded. Histamine,
definitive care: e.g. surgery, ICU admission or trans- complement and immunoglobulin levels may also
fer to a specialist centre. be useful.
ATLS courses are administered in the USA by the - skin testing is the gold standard for the detection
American College of Surgeons and by the Royal College of IgE-mediated reactions and includes:
of Surgeons of England in the UK. - prick testing (placement of a drop of solution
Carmont MR (2005). Postgrad Med J; 81: 8791 on to the skin of the forearm and gently lifting
the underlying skin with a needle): has been
Adverse drug reactions. Undesired drug effects, usually suggested as the most useful investigation for
divided into: specific agents. Since neat solutions may cause
predictable (type A) dose-related side effects, e.g. flares in normal subjects, 1:10 dilutions or lower
hypotension following thiopental. should also be used. Results are read after 15
unpredictable (type B; idiosyncratic) usually less 20min. A wide range of drugs should be tested.
common reactions. These are unrelated to known Waiting for ~6 months after the reaction has
pharmacological properties of a drug (i.e. not due been suggested in order to allow recovery of the
to common side effects or overdose), usually involv- immune system.
ing the immune system in some way (but not always, - intradermal testing (injection of 0.020.05ml
e.g. MH). dilute solution into the skin of the forearm or
Suspected adverse reactions are voluntarily reported to back) has a higher sensitivity but lower speci
the Medicines and Healthcare products Regulatory ficity and is more likely to trigger a systemic
Agency on yellow cards, introduced in 1964 and updated reaction. Results are read after 2030min.
in 2000. The yellow card system was extended to nurse - patch testing: not useful in suspected periopera-
reporters in 2002. Specific yellow cards for reporting tive anaphylaxis, though useful for contact
anaesthetic drug reactions were introduced in 1988, allergic reactions.
to encourage reporting of serious reactions to estab- - specific IgE antibodies may be assayed using fluo-
lished drugs and any reaction to new drugs. Anaesthe- rescence or (less commonly) radioactive detec-
tists give many different drugs iv to large numbers of tion systems and may be useful in reactions to
patients, and therefore reactions are often seen. Reac- suxamethonium, antibacterial drugs and latex;
tions may be more likely if drugs are given quickly and testing for other anaesthetic drugs is no longer
in combination. considered specific enough. Less sensitive than
Mechanisms: skin testing.
on first exposure: - the role of other tests, e.g. in vitro basophil studies,
- direct histamine release, e.g. tubocurarine, atracu- is controversial.
rium, thiopental, Althesin. It is the anaesthetists responsibility to arrange referral
- alternative pathway complement activation, e.g. to an appropriate centre for further testing after a sus-
Althesin. pected severe reaction, and even after unexplained peri-
apparently on first exposure: prior sensitisation by operative collapse/cardiac arrest.
other (e.g. environmental) antigens may cause Dewachter P, Mouton-Faivre C, Emala CW (2009).
crossover sensitivity to subsequently administered Anesthesiology; 111: 114150
drugs; e.g. reactions to dextrans may involve prior See also, Latex allergy
exposure to bacterial antigens.
requiring prior exposure:
AF, see Atrial fibrillation
- anaphylaxis, e.g. to thiopental.
- classical pathway complement activation, e.g.
Althesin. Other drugs dissolved in Cremophor Affinity. Extent to which a drug binds to a receptor. A
EL may crossreact. drug with high affinity binds more avidly than one with
Features range from mild skin rash to anaphylaxis. First lower affinity, whatever its intrinsic activity.
exposure reactions tend to be milder and more frequent
than those requiring prior exposure. Afterload. Ventricular wall tension required to eject
Reported incidence varies between countries and stroke volume during systole. For the left ventricle, after-
according to definitions but severe allergic reactions are load is increased by:
thought to occur in about 1:10000 to 1:20000 cases. an anatomical obstruction, e.g. aortic stenosis.
Management: raised SVR.
immediate medical management as for decreased elasticity of the aorta and large blood
anaphylaxis. vessels.
testing: increased ventricular wall thickness (greater tension
- a blood sample for mast cell tryptase levels should is needed to produce the necessary pressure
be taken as soon as possible and again at 12h [Laplaces law]).
18 Agonist

Increased afterload results in increased myocardial pass to the systemic circulation via the pulmonary vas-
work/O2 consumption, increased end-systolic ventricular cular bed or cardiac septal defects (a probe-patent
volume and decreased stroke volume. Reduction of foramen ovale exists in 2030% of patients at autopsy).
afterload may be achieved with vasodilator drugs. The bubbles may obstruct the coronary or cerebral
See also, Preload vessels.
Clinical features:
Agonist. Substance that binds to a receptor to cause a reduced cardiac output.
response within the cell. It has high affinity for the recep- tachycardia.
tor and high intrinsic activity. cyanosis.
A partial agonist binds to the receptor, but causes less bronchospasm and pulmonary oedema may occur.
response; it may have high affinity, but it has less intrinsic Dyspnoea, coughing and chest pain are common in
activity. It may therefore act as a competitive antagonist the awake patient.
in the presence of a pure agonist. tinkling sounds on auscultation, e.g. with an oesoph-
An agonistantagonist causes agonism at certain ageal/precordial stethoscope; large amounts of air
receptors and antagonism at others. may cause a mill-wheel murmur. May be detected
See also, Doseresponse curves; Receptor theory by a precordial Doppler probe or transoesophageal
echocardiography, although the extreme sensitivity
Agranulocytosis, see Leucocytes of these techniques may reveal many tiny bubbles
of disputed clinical significance.
AGSS, Anaesthetic gas scavenging system, see sudden reduction of end-tidal CO2 due to increased
Scavenging dead space and decreased cardiac output. End-tidal
nitrogen monitoring has also been used to monitor
AIDS, Acquired immunodeficiency syndrome, see air embolism.
Human immunodeficiency viral infection raised pulmonary artery resistance and pressure.
signs of right ventricular strain on the ECG; ven-
Air. Air contains mostly nitrogen and oxygen, with tricular ectopics or fibrillation may occur.
various other constituents (Table 4). Density is approxi- Treatment:
mately 1.2kg/m3 (1.2g/l). to prevent further embolism:
Medical air may be supplied by a compressor or - seal veins.
in cylinders. The latter (containing air at 137 bar) are - flood the wound with fluid.
grey with black and white shoulders. Piped air is nor- - increase venous pressure using head-down tilt, iv
mally at 4 bar. fluids, jugular venous compression, PEEP. The
See also, individual gases latter and the antigravity suit have been advo-
cated for prevention of air embolism in neurosur-
Air embolism. Introduction of air bubbles into the cir- gery in the traditional sitting position. The use of
culation, usually into veins (although arterial air embo- the modified sitting position with the legs placed
lism has been caused by prolonged flushing of arterial horizontally may decrease the incidence.
lines in neonates). A potential risk when venous pres- once air has entered the circulation:
sure is lower than atmospheric pressure. It may occur - CPR if required.
during any surgery when an open vein is raised above - stop N2O.
the heart; it is particularly likely in neurosurgery with - the head-down, left lateral position is said to
the patient in the sitting position since the dural sinuses increase the likelihood of air remaining in the
do not collapse. May also occur during insertion or right atrium.
removal of a CVP line (minimised by tilting the patient - remove air from the right atrium or ventricle via
head-down during the former and using occlusive dress- a central line. Special wide-bore, multi-holed
ings as opposed to gauze in the latter). Procedures catheters are available for this purpose, although
involving insufflation or injection of gas, e.g. laparo whether these are necessary is controversial.
scopy, epidural anaesthesia using loss of resistance to air, - hyperbaric O2 has been used to reduce the size of
laser surgery with gas-cooled probes, may also lead to the embolism and improve oxygenation.
embolism. N2O diffuses into bubbles, increasing their Mirski MA, Lele AJ, Fitzsimmons L, Toung TJK (2007).
volume and exacerbating their effects. Morbidity and Anesthesiology; 106: 16477
mortality are dependent on the volume of the air
entrained and the rate of accumulation. Airway. The upper airway includes the mouth, nose,
Air in the heart is compressed with each beat and not pharynx and larynx. Maintenance of the airway in the
expelled, causing foaming and interruption of blood unconscious or anaesthetised patient is achieved by
flow. Pulmonary vessels may become obstructed. Small combined flexion of the neck and extension at the
bubbles may have little effect. Paradoxical air emboli atlanto-occipital joint (the sniffing position), and lifting
the angles of the mandible forward. The tongue is lifted
forward by the genioglossus muscle which is attached to
Table 4 Constituents of dry natural air by volume the back of the point of the jaw; the hyoid bone and
larynx are pulled forward by the hyoglossus, mylohyoid,
Nitrogen 78.03% Hydrogen 0.001% geniohyoid and digastric muscles. Upward pressure on
O2 20.99% Helium 0.0005% the soft tissues of the floor of the mouth may cause
Argon 0.93% Krypton 0.0001% obstruction, particularly in children, and should be
CO2 0.03% Xenon 0.000008% avoided. In the lateral (recovery) position, the tongue
Neon 0.0015% and jaw fall forward under gravity, improving the airway.
Airway obstruction during anaesthesia has traditionally
 Airway obstruction 19

been attributed to the tongue falling back against the - increasing gas flow: heliumO2 mixtures.
posterior pharyngeal wall. Radiological and electromyo- - bypassing the obstruction: tracheal intubation,
graphic studies suggest that obstruction by the soft tracheostomy or cricothyrotomy. The last two
palate or epiglottis secondary to reduced local muscle may be difficult if the anatomy is distorted.
activity may also be responsible. IPPV:
See also, Airways; Tracheobronchial tree - causes of increased airway pressure and hypoven-
tilation other than obstruction due to equipment
Airway exchange catheter. Device placed into the (e.g. bronchospasm, pneumothorax, inadequate
trachea both to maintain oxygenation after tracheal neuromuscular blockade and coughing) should be
extubation (i.e. inserted through the tracheal tube before considered.
the latter is removed), and to facilitate reintubation - while ventilating by hand, all tubing should be
should it be required. Available devices share similar checked for kinks. A suction catheter will not pass
features: they are long, hollow catheters, able to be down the tracheal tube if the latter is obstructed,
attached to an O2 supply at their proximal end (e.g. using e.g. by kinks, mucus, herniated cuff. If auscultation
a detachable 15-mm connector) and stiff enough to act of the chest does not suggest bronchospasm or
as a guide for a tracheal tube passed over them. The pneumothorax, the cuff should be deflated and
distal end may be angulated, allowing the catheter also the tracheal tube pulled back slightly. If ventila-
to be used as an introducer, e.g. during direct laryngos- tion does not improve, the tube should be removed
copy. A specific type of exchange catheter (the Aintree and ventilation attempted by facemask.
catheter) has been designed for exchanging an LMA Anaesthesia for patients with airway obstruction:
with a tracheal tube via a flexible fibrescope. preoperatively:
- preoperative assessment for the above features
Airway obstruction. Obstruction may occur at the and management as above.
mouth, pharynx, larynx, trachea and large bronchi. It - useful pre-induction investigations include:
may be caused by the tongue, laryngospasm, strictures, - radiography, including tomograms, thoracic
tumours and soft tissue swellings, oedema, infection inlet views and CT scanning.
(e.g. diphtheria, epiglottitis) and foreign objects, includ- - flexible nasendoscopy images.
ing anaesthetic equipment. Hypotonia of the muscles - arterial blood gas interpretation.
involved in upper airway maintenance is common during - flowvolume loops.
anaesthesia. During IPPV, mechanical obstruction may - premedication may aid smooth induction of
occur at any point along the breathing system. anaesthesia but excessive sedation should be
Airway obstruction results in hypoventilation and avoided.
increased work of breathing. It may present as an acute perioperatively:
medical emergency requiring immediate management. - severe/critical obstruction may warrant securing
Features: of the airway using an awake technique (e.g.
spontaneous ventilation: tracheostomy under local anaesthesia or awake
- dyspnoea, noisy respiration, stridor. fibreoptic intubation). The choice depends on
- use of accessory muscles of respiration, with patient compliance, operator experience and
tracheal tug, supraclavicular and intercostal site/severity of the obstruction (e.g. large
indrawing, and paradoxical see-saw movement glottic tumours may be impassable with an
of abdomen and chest. endoscope).
- tachypnoea, tachycardia and other features of - if general anaesthesia is deemed preferable and/
hypoxaemia, hypercapnia and respiratory failure. or necessary it should be induced with full moni-
- pulmonary oedema may occur if negative intra- toring and facilities for resuscitation and trache-
thoracic pressures are excessive. ostomy/cricothyrotomy immediately available.
- during anaesthesia, poor movement of the reser- - patients with proximal airway obstruction usually
voir bag may occur. adopt the optimal head and neck position for
IPPV: maximal air movement; muscle relaxation caused
- increased airway pressures with reduced chest by iv induction may therefore lead to sudden
movement; noisy respiration or wheeze. complete obstruction. It may be impossible to
- features of hypoxaemia and hypercapnia. ventilate the patient by facemask, and tracheal
Management: intubation may be difficult or impossible. IV
O2 therapy (increased FIO2 during anaesthesia). anaesthetic agents and neuromuscular blocking
spontaneous ventilation: drugs should therefore be used with extreme
- general measures in unconscious/anaesthetised caution. Inhalational induction (e.g. sevoflurane in
patients: O2) is traditionally advocated, although induction
- turn to the lateral position if practical. may be slow and difficult. If obstruction worsens,
- correct positioning of the head, elevation of anaesthesia is allowed to lighten. Tracheal intuba-
the jaw, and use of oropharyngeal or nasopha- tion is performed without paralysis; lidocaine
ryngeal airways. Tracheal intubation may be spray may be useful.
required as below. postoperatively: as for difficult intubation (see
- specific treatment, e.g.: Intubation, difficult).
- antibacterial drugs for infection. Classical management of patients with large airway com-
- fresh frozen plasma or C1 esterase inhibitor for pression, e.g. by mediastinal tumours, also employs inha-
hereditary angio-oedema. lational induction and anaesthesia. This avoids acute
- nebulised adrenaline for croup. exacerbation of airway obstruction caused by sudden
- Heimlich manoeuvre for choking. muscle relaxation.
20 Airway pressure

In the recovery room or casualty department, all support the tracheal tube.
unconscious patients should be positioned in the recov- allow suction.
ery position, to protect them from aspiration and airway act as a conduit for fibreoptic intubation.
obstruction. facilitate CPR.
See also, Intubation, awake Thus usually employed during anaesthesia and in uncon-
scious patients.
Airway pressure. Pressure within the breathing system Types:
and tracheobronchial tree. Useful as an indicator of oropharyngeal: Guedel airway is most commonly
mechanical obstruction to expiration during spontane- used. Modifications include a side port for attach-
ous ventilation. During IPPV, changes in airway pressure ment to a fresh gas source (Waters airway), 15mm
may indicate disconnection, dynamic hyperinflation, connectors for attachment to a breathing system,
mechanical obstruction, decreased lung compliance or caps with side ports, and airways used for fibreoptic
increased airway resistance, and the risk of barotrauma. intubation (Fig. 6). A cuffed oropharyngeal airway
The pressure measured at the mouth may considerably (COPA) with a 15mm connector was described in
exceed alveolar pressure during positive pressure 1991 but is not widely used. Oropharyngeal airways
breaths, especially if airway resistance and gas flow rates are the commonest cause of damage to teeth in
are high. During expiration, mouth pressure falls to zero, anaesthetised patients. They must be placed with
but alveolar pressure may lag behind. In some ventila- care, particularly in children where soft tissue
tors airway pressure is measured in the expiratory limb damage can easily occur.
of the breathing system. oral supraglottic: designed to be placed close to,
but above, the larynx, resulting in a better seal
Airway pressure release ventilation (APRV). CPAP and therefore the ability to control ventilation.
with intermittent release to ambient pressure (or a lower Include (Fig. 7):
level of CPAP) causing expiration. Spontaneous venti - LMA: the most widely used.
lation may continue between APRV breaths. Allows - laryngeal tube: requires less mouth opening. Has
reduction of mean airway pressure, and has been used two cuffs, inflated by a single inflation tube. Avail-
to support respiration in ARDS. Weaning is achieved by able in seven sizes, suitable for babies up to adults.
reducing the frequency of CPAP release until the patient Performs better for IPPV in studies than for
is breathing spontaneously with CPAP maintained. spontaneous ventilation. A new double-lumen
Esan A, Hess DR, Raoof S, George L, Sessler CN (2010). version (laryngeal tube Sonda) is similar in func-
Chest; 137: 120316 tion to the Combitube (see Oesophageal obtura-
tors and airways).
Airway resistance - i-gel: similar in function to the LMA but the
cuff is made of soft gel and non-inflatable; incor-
driving pressure porates a gastric channel and bite block. Available
Resistance =
gas flow in sizes 35.
Driving pressure is the difference between alveolar and - others have been described but are not widely
mouth pressures, and may be measured using the body used:
plethysmograph. Alternatively, gas flow may be halted - Airway Management Device (AMD): has a
repeatedly for a tenth of a second at a time with a single lumen and two cuffs, inflated indepen-
shutter; during the brief period of no flow, alveolar pres- dently. The lower cuff compresses the devices
sure may be measured at the mouth. Gas flow can be lumen when inflated; when the cuff is deflated,
measured with a pneumotachograph. a suction catheter may be passed into the
Most of the resistance resides in the large and medium- oesophagus. Available in three adult sizes.
sized bronchi; severe damage to the small airways may - Streamlined Liner of the Pharyngeal Airway
occur before a measurable increase in resistance. (SLIPA): similar to the LMA but with a soft
At low lung volumes, the radial traction produced hollow pharyngeal portion instead of a cuff, that
by lung parenchyma surrounding the airways, and that acts both as a seal and as a sump for collecting
holds them open, is reduced; thus airway calibre is liquid should regurgitation occur. Available in
reduced, and resistance increased. During forced expira- six adult sizes (4757), corresponding to the
tion, some airways may close, causing air trapping. Bron- width of the thyroid cartilage.
choconstriction and increased density or viscosity of the - Cobra: single-use device similar in function to
inspired gas also increase resistance (density because the LMA; available in eight sizes.
flow is not purely laminar in the airways). Resistance is nasopharyngeal: usually smooth non-cuffed tubes
increased in chronic bronchitis due to airway narrowing. with a flange to prevent pushing them completely
In emphysema the airways close because of lung paren- into the nose. Avoids risk to capped teeth, but may
chymal destruction. cause epistaxis. Cuffed nasal airways may be held in
Airway resistance increases during anaesthesia; this place by the inflated cuff, and allow attachment to
may be caused by bronchospasm, reduction in FRC and a breathing system.
lung volume, or by the tubes and connections of the Insertion of an airway may cause gagging, coughing
breathing system. and laryngospasm unless the patient is comatose or
See also, Closing capacity; Compliance adequately anaesthetised; these may also occur on
waking.
Airways. Devices placed in the upper airway (but not [Robert Alvin Berman (19141999), US anaesthetist;
into the larynx); used to: Andranik Ovassapian (19362010), Iranian-born US
relieve airway obstruction. anaesthetist; R Tudor Williams, Canadian anaesthetist]
prevent biting and occlusion of the tracheal tube. McIntyre JWR (1996). Can J Anaesth; 43: 62935
 Albendazole 21

(a)
(a)

(b) (b)

(c)

(c)

(d)

(d)

(e)

Fig. 6 Examples of oropharyngeal airways: (a) Guedel; (b) Berman

intubating; (c) Ovassapian; (d) Williams. The latter three are used for
fibreoptic intubation; the Berman and Ovassapian allow the airway to
be removed without dislodging the tracheal tube once placed

Fig. 7 Examples of supraglottic airways: (a) laryngeal tube; (b) i-gel;

(c) AMD; (d) SLIPA; (e) Cobra. (See Fig. 97 for LMA.)
AIS, see Abbreviated injury scale

AKI, Acute kidney injury, see Renal failure Dose: up to 800mg orally/day in divided doses for 28
days, followed by a 14-day treatment-free period. Up
Albendazole. Agent used (off-licence) in conjunction to three cycles may be given.
with surgery to treat hydatid disease. May be used alone Side effects: GIT upset, headache, dizziness, hepatic
in inoperable cases. impairment, pancytopenia.
22 Albumin

Albumin. The most abundant plasma protein (mw pure methanol may result in permanent blindness,
69000): normal plasma levels: 3550g/l. Important in the with the fatal adult dose around 30ml (methylated
maintenance of plasma oncotic pressure, as a buffer, and spirits contains 5% methanol and 95% ethanol, the
in the transport of various molecules such as bilirubin, latter causing the most toxicity). Blood levels
hormones, fatty acids and drugs. It is synthesised by the greater than 500mg/ml (15mmol/l) indicate severe
liver and removed from the plasma into the interstitial poisoning.
fluid. It may then pass via lymphatics back to the plasma, Management includes gastric lavage if within 2h
or into cells to be metabolised. May have a role as a free of ingestion, administration of bicarbonate, inhibi-
radical scavenger. Depletion occurs in severe illness, tion of further methanol metabolism with ethanol
infection and trauma. Available for transfusion as 4.5% (50g orally/iv followed by 1020g/h iv to produce
and 20% solutions; currently the most expensive non- blood levels of 100200g/dl [2030mmol/l]). More
blood plasma substitute. Has been used as a colloid when recently, fomepizole has gained acceptance as an
providing iv fluid therapy for critically ill patients but alternative to alcohol and may reduce the need for
hypoalbuminaemia in these patients usually results from haemodialysis, which may still be required in severe
increased metabolism of circulating albumin; adminis- cases. Folic acid or its metabolites have also been
tration does not generally result in maintained plasma used (utilised in formate metabolism). Haemodialy-
albumin levels and no improvement in outcome has sis has been used in severe poisoning.
been found when compared with cheaper alternatives. isopropanol: effects are caused by the alcohol itself,
The effect of albumin administration on mortality in not its metabolites. Effects are similar to those of
critically ill patients remains controversial, although ethanol but longer lasting. Gastritis, renal tubular
recent studies suggest mortality is not increased, except acidosis, myopathy and haemolysis may occur.
possibly in patients with traumatic brain injury. The lack Management is with gastric lavage if within 2h
of any clear advantage of using albumin solutions for of ingestion and supportive thereafter.
resuscitation, and its expense, has led to a decline in ethylene glycol: toxicity results from metabolism by
its use. alcohol dehydrogenase to glycoaldehyde and oxalic/
Hartog CS, Bauer M, Reinhart K (2011). Anesth Analg; formic acids. The former causes cerebral impair-
112: 15664 ment, while the latter produce severe metabolic
See also, Blood products; Protein-binding acidosis and acute tubular necrosis. The fatal
adult dose is ~100g, although patients have sur-
Albuterol, see Salbutamol vived much larger doses. Features include intoxica-
tion, vomiting, haematemesis, coma, convulsions,
Alcohol, see Alcohols depressed reflexes, myoclonus, nystagmus, papilloe-
dema and ophthalmoplegia within the first 12h;
Alcohol poisoning. Problems, features and management tachycardia, hypertension, pulmonary oedema and
depend on the alcohols ingested: cardiac failure within the next 12h; and renal failure
ethanol: commonly complicates or precipitates over the subsequent 23 days. Investigations may
acute illness or injury, especially trauma. Results reveal severe lactic acidosis, a large anion gap and
in depressed consciousness (hindering assessment osmolar gap, hypocalcaemia and hyperkalaemia.
of head injury), potentiation of depressant drugs Blood levels exceeding ~200mg/l (~35mmol/l)
and disinhibition. Patients are often uncooperative. indicate severe poisoning.
Other effects of acute intoxication include vaso- Management includes haemodialysis, ethanol
dilatation, tachycardia, arrhythmias, vomiting, and fomepizole; thiamine and pyridoxine have also
reduced lower oesophageal sphincter pressure, gas- been used.
tric irritation, delayed gastric emptying, hypo Jammalamadaka D, Raissi S (2010). Am J Med Sci; 339:
glycaemia (typically 636h after ingestion, especially 27681
in a starved or malnourished individual), metabolic
acidosis, dehydration (due to diuretic effect), coma Alcohol withdrawal syndromes. May be precipitated
and convulsions. Intoxication occurs at blood levels by acute illness or surgery, even if regular intake of
~100150mg/dl (2233mmol/l), loss of muscle alcohol (ethanol) is apparently not excessive and without
coordination at ~150200mg/dl (3343mmol/l), the other features of alcoholism.
decreased level of consciousness at ~200300mg/dl Features:
(4365mmol/l) and death at ~300500mg/dl (65 most commonly, tremulousness, agitation, nausea,
109mmol/l). The fatal adult dose is about 300 vomiting: usually within 68h of abstinence.
500ml absolute alcohol (5001200ml strong spirits) hallucinations: usually visual; occur 1030h after
within 1h. abstinence and in under 10% of cases.
Management is mainly supportive, as for poison- convulsions: occur up to 48h after abstinence and
ing and overdoses. Haemodialysis has been used in in about 5% of cases.
severe poisoning. Features of alcoholism require delirium tremens: includes the above symptoms
attention if present. plus confusion, disorientation, sweating, tachycardia
methanol: toxicity results from hepatic metabo- and hypertension. Occurs up to 23 days after absti-
lism of methanol to formaldehyde and thence nence and in about 5% of cases.
formic acid, the latter being a potent inhibitor of Management includes sedative drugs (e.g. benzodiaze-
mitochondrial cytochrome oxidase. Features occur pines, carbamazepine, clomethiaziole) and reassurance.
after 836h and include intoxication, vomiting, More recently, clonidine has been used successfully to
abdominal pain, coma, visual disturbances, severe smooth withdrawal. Vitamin B6 supplements are usually
metabolic acidosis with a large anion gap and administered, but if there is a risk of encephalopathy a
osmolar gap, and hyperglycaemia. About 10ml mixture of vitamins is best prescribed.
 Alfentanil hydrochloride 23

McKeon A, Frye MA, Delanty N (2008). J Neurol Neu- ethylene glycol (glycol; (CH2OH)2): used as an
rosurg Psychiatry; 79: 85462 antifreeze.
propylene glycol (CH3.CHOH.CH2OH): used as a
Alcoholism. Form of substance abuse in which there is solvent in drugs, e.g. etomidate, GTN.
narrowing of the drinking repertoire (loss of day-to-day All are CNS depressants, rapidly absorbed from the
variation in drinking habits), increased tolerance to upper GIT (also by inhalation and, to varying degrees,
alcohol (ethanol), symptoms of alcohol withdrawal syn- percutaneously) and metabolised by hepatic alcohol
dromes when intake is stopped, a craving for alcohol dehydrogenase to the aldehyde; all except isopropanol
and drinking in the early part of the day/middle of the are metabolised further to the corresponding acid by
night. May precipitate admission to hospital as a conse- aldehyde dehydrogenase.
quence of acute alcohol poisoning or intoxication, or See also, Alcohol poisoning; Alcohol withdrawal
impaired organ function resulting from chronic abuse; syndromes
may also complicate the management of incidental
disease or surgery. Alcuronium chloride. Non-depolarising neuromuscular
Effects of chronic alcohol intake:
blocking drug, introduced in 1961 and withdrawn in the
cerebral/cerebellar degeneration, peripheral neu- UK in 1994. Caused mild histamine release and hypoten-
ropathy, psychiatric disturbances (Wernickes sion, but anaphylaxis, when it occurred, was often severe.
encephalopathy, Korsakoffs psychosis).
withdrawal may lead to tremor, anxiety, hallucina-
Aldosterone. Mineralocorticoid hormone secreted by
tions, convulsions, delirium tremens.
the outer layer (zona glomerulosa) of the cortex of the
gastritis, peptic ulcer disease, oesophageal varices;
adrenal gland. Secreted in response to reduced renal
may lead to gastrointestinal haemorrhage.
blood flow (via renin/angiotensin system), trauma and
pancreatitis.
anxiety (via ACTH release), and hyperkalaemia and
fatty liver, hepatic enzyme induction, cirrhosis
hyponatraemia (direct effect on the adrenal cortex).
causing hepatic failure, coagulopathy.
Increases sodium and water reabsorption from renal
malnutrition, immunodeficiency.
tubular filtrate, sweat and saliva. Acts via mineralocorti-
myopathy, cardiomyopathy.
coid receptors to upregulate basolateral sodium/potas-
[Karl Wernicke (18481904), German neurologist;
sium pumps at the distal renal tubule and collecting duct.
Sergei Korsakoff (18531900), Russian neurologist and
Sodium and water are retained while potassium and
psychologist]
hydrogen ion excretion is increased.
Schuckit MA (2009). Lancet; 373: 492501
Hyperaldosteronism results in hypertension and
hypokalaemia. In cardiac failure and cirrhosis, aldoste-
Alcohols. Group of aliphatic (i.e. non-cyclic) organic
rone levels may be raised, although the mechanism is
chemicals containing one or more hydroxyl (OH)
unclear.
groups and that form esters (containing the OO
Aldosterone antagonists, e.g. spironolactone, potas-
linkage) with acids. Used as solvents and cleaning agents.
sium canrenoate and eplerenone, cause sodium loss and
Those of particular medical/anaesthetic relevance
potassium retention.
include:
ethanol (ethyl alcohol; C2H5OH): commonly
referred to as alcohol; widely drunk throughout ALERT, see Acute life-threatening events recognition
the world and often abused, resulting in acute toxic- and treatment
ity or alcoholism. Used in the past as an anaesthetic
agent and as a tocolytic drug. May be added to irrig- Alfentanil hydrochloride. Opioid analgesic drug
ant solution to monitor the latters uptake during derived from fentanyl. Developed in 1976. In compari-
TURP. Also used for destructive injection, e.g. into son with fentanyl, alfentanil has a:
neural tissue in chronic pain management. In the faster onset of action (< 1min).
ICU, iv alcohol may be used to treat methanol poi- lower pKa (6.5 vs. 8.4), rendering it mostly (90%)
soning; it may also be useful for sedating alcoholics unionised at body pH.
(110g/h of a 510% solution). shorter elimination half-life due to its lower volume
Metabolised mostly to acetaldehyde, then of distribution (in spite of a lower clearance).
acetate, acetyl coenzyme A and finally CO2 and lower potency (approximately one-tenth).
water via the tricarboxylic acid cycle. Five per cent Has minimal cardiovascular effects, although bradycar-
is excreted unchanged, mostly in the urine but also dia and hypotension may occur. Other effects are similar
in the breath. The rate of metabolism is 10ml/h at to those of fentanyl. Metabolised in the liver to
concentrations above 100mg/dl (22mmol/l); below noralfentanil.
this level it is subject to first-order kinetics with a Dosage:
half-life of about 1h (see MichaelisMenten kinet- for spontaneously breathing patients, up to 500mg
ics). Produces 30 kJ/g (7 Cal/g); it has been used as initially, followed by increments of 250mg. Slow
an iv energy source. injection reduces the incidence of apnoea.
methanol (methyl alcohol; CH3OH): derived from 3050g/kg to obtund the hypertensive response to
distillation of wood or from coal or natural gas. tracheal intubation. Up to 125g/kg is used in
Used in the petroleum and paint industries. Con- cardiac surgery.
tained with ethanol in methylated spirits. Extremely for infusion, a loading dose of 50100g/kg, fol-
toxic if ingested. lowed by 0.51g/kg/min. Higher rates have been
isopropanol (isopropyl alcohol; (CH3)2CHOH): used in TIVA. The infusion is discontinued 10
used as a solvent and to clean the skin before inva- 30min before surgery ends. Also used for sedation
sive procedures. Oxidised in the liver to acetone. in ICU at 3060g/kg/h initially.
24 Alimemazine tartrate

Alimemazine tartrate (Trimeprazine). Phenothiazine- Effects: those of hypocapnia.

derived antihistamine drug, used for premedication in Treatment: of underlying cause.
children. More sedative than other antihistamines. Has See also, Acidbase balance
antiemetic properties.
Dosage: up to 2mg/kg orally 12h preoperatively. Alkylating drugs, see Cytotoxic drugs
Side effects include dry mouth, circumoral pallor and
dizziness. May cause postoperative restlessness due to Allens test. Originally described for assessing arterial
antanalgesia. Has been implicated in causing pro- flow to the hand in thromboangiitis obliterans. Modified
longed respiratory depression on rare occasions. for assessment of ulnar artery flow before radial arterial
cannulation. The ulnar and radial arteries are com-
Aliskiren, see Renin/angiotensin system pressed at the wrist, and the patient is asked to clench
tightly and open the hand, causing blanching. Pressure
Alkalaemia Arterial pH > 7.45 or H+ concentration < over the ulnar artery is released; the colour of the palm
35nmol/l. normally takes less than 510 s to return to normal,
See also, Acidbase balance; Alkalosis with over 15 s considered abnormal. A similar manoeu-
vre may be performed with the radial artery before
Alkalosis. A process in which arterial pH > 7.45 (or ulnar artery cannulation. Although widely performed,
H+ concentration < 35nmol/l), or would be > 7.45 if it is inaccurate in predicting risk from ischaemic
there were no compensatory mechanisms of acidbase damage.
balance. [Edgar Van Nuys Allen (19001961), US physician]
See also, Alkalosis, metabolic; Alkalosis, respiratory Brzezinski M, Luisetti T, London MJ (2009). Anesth
Analg; 109: 176381
Alkalosis, metabolic. Inappropriately high pH for the
measured arterial PCO2. Allergic reactions, see Adverse drug reactions
Caused by:
acid loss, e.g. vomiting, nasogastric aspiration. Allodynia. Pain from a stimulus that is not normally
base ingestion: painful.
- bicarbonate (usually iatrogenic).
- citrate from blood transfusion. Alpha-adrenergic ..., see -Adrenergic
- milk-alkali syndrome.
- forced alkaline diuresis. Alprostadil. Prostaglandin E1, used to maintain patency
potassium/chloride depletion leading to acid urine of a patent ductus arteriosus in neonates with congenital
production. heart disease in whom the ductus is vital for survival, e.g.
Primary change: increased bicarbonate/decreased pulmonary atresia/stenosis, Fallots tetralogy, coarcta-
hydrogen ion. tion, transposition of the great arteries.
Compensation: Dosage: 510ng/kg/min initially via the umbilical
hypoventilation: reaches its maximum within 24h, artery or iv, titrated to a maximum of 100ng/kg/min.
usually with an upper limit for arterial PCO2 of 78 Side effects include apnoea, brady- or tachycardia,
kPa (5060mmHg). Initial increase in HCO3 is hypotension, pyrexia, diarrhoea, convulsions, DIC,
about 0.76mmol/l per kPa change in arterial PCO2 hypokalaemia. Undiluted preparation reacts with
above 5.3 kPa (1mmol/l per 10mmHg above 40), plastic containers, so care in preparation is required.
although the level of compensatory change is less
predictable than in metabolic acidosis. ALS, see Advanced Cardiac Life Support; Advanced life
decreased renal acid secretion. support, adult; Advanced Life Support in Obstetrics;
Effects: Advanced Paediatric Life Support; Advanced Trauma
confusion. Life Support; Neonatal Resuscitation Programme
paraesthesia/tetany (reduced free ionised calcium
concentration due to altered protein-binding). ALSO, see Advanced Life Support in Obstetrics
Treatment:
correction of ECF and potassium depletion. Alteplase (rt-PA, tissue-type plasminogen activator).
rarely, acid therapy, e.g. ammonium chloride or Fibrinolytic drug, used in acute management of MI, PE
hydrochloric acid: deficit = base excess body and acute ischaemic CVA. Becomes active when it binds
weight (kg) mmol. to fibrin, converting plasminogen to plasmin, which dis-
See also, Acidbase balance solves the fibrin. Thought to be non-immunogenic.
Dosage:
Alkalosis, respiratory. Alkalosis due to decreased arte- within 6h of MI: 15mg iv bolus followed by
rial PCO2. Caused by alveolar hyperventilation, e.g. fear, 50mg/30min, then 35mg/60min.
pain, hypoxia, pregnancy, or during IPPV. within 612h of MI: 10mg bolus, then 50mg/60min,
Primary change: decreased arterial PCO2. then 40mg/2h.
Compensation: PE: 10mg followed by 90mg/2h.
initial fall in plasma bicarbonate due to decreased acute stroke (within 3h): 0.9mg/kg (up to 90mg);
carbonic acid formation and dissociation. 10% by iv injection, the remainder by infusion.
decreased acid secretion/increased bicarbonate Maximum dose: 1.5mg/kg if under 65kg body weight.
excretion by the kidneys. Side effects: as for fibrinolytic drugs.
In acute hypocapnia, bicarbonate concentration falls by
about 1.3mmol/l per 1 kPa fall in arterial PCO2. In chronic Althesin. IV anaesthetic agent introduced in 1971, com-
hypocapnia, the fall per 1 kPa is 4.0mmol/l. posed of two corticosteroids, alphaxalone 9mg/ml and
 Alveolar gas transfer 25

alphadolone 3mg/ml. Withdrawn in 1984 because of a Alveolar air equation. In its simplified form:
high incidence of adverse drug reactions, mostly minor PA CO2
but occasionally severe. These were thought to be due to alveolar PO2 = FIO2 ( PB PA H 2O)
Cremophor EL, the solubilising agent. Previously widely R
used because of its rapid onset and short duration of PA CO2
or PIO2
action; still used in veterinary practice. R
where PB = ambient barometric pressure
Altitude, high. Problems include: PAH2O = alveolar partial pressure of water (nor-
lack of O2: e.g. atmospheric pressure at 18000 ft mally 6.3 kPa [47mmHg])
(5486m) is half that at sea level. FIO2 is constant, PACO2 = alveolar PCO2; approximately equals
but PO2 is lowered. This effect is offset initially by arterial PCO2
the shape of the oxyhaemoglobin dissociation R = respiratory exchange ratio, normally 0.8
curve, which maintains haemoglobin saturation PIO2 = inspired PO2
above 90% up to 10000 ft (3048m). Compensatory Useful for estimating alveolar PO2, e.g. when determin-
changes due to hypoxia include hyperventilation, ing alveolararterial O2 difference and shunt fractions.
increased erythropoietin secretion resulting in poly- The equation also illustrates how hypercapnia may be
cythaemia, increased 2,3-DPG, proliferation of associated with a lower PAO2. Another form of the equa-
peripheral capillaries and alterations in intracellular tion allows for differences between inspired and expired
oxidative enzymes. Alkalaemia is reduced after a gas volumes, and is unaffected by inert gas exchange:
few days, via increased renal bicarbonate loss. CSF
pH is returned towards normal. Pulmonary vaso- P O PEO 2
alveolar PO2 = PIO2 PA CO 2 I 2
constriction may result in right heart strain. High- PECO 2
altitude illness is thought to be related to acute where PEO2 = mixed expired PO2
hypoxia and alkalosis; it consists of headache, PECO2 = mixed expired PCO2
malaise, nausea and diarrhoea, and may lead to pul-
monary or cerebral oedema. Alveolararterial oxygen difference (AadO2). Alveo-
low temperatures, e.g. ambient temperature is 20C
lar PO2 minus arterial PO2. Useful as a measure of V/Q
at 18000 ft (5486m). mismatch and anatomical shunt. Alveolar PO2 is esti-
expansion of gas-containing cavities, e.g. inner ear.
mated using the alveolar air equation; arterial PO2 is
decompression sickness.
measured directly. The small shunt V /Q and mismatch
anaesthetic apparatus at high altitude:
in normal subjects result in a normal AadO2 of less than
- vaporisers: SVP is unaffected by atmospheric 2.0 kPa (15mmHg) breathing air; this may reach 4.0 kPa
pressure; thus the partial pressure of volatile (30mmHg) in the elderly. It increases when breathing
agent in the vaporiser is the same as at sea level. high O2 concentrations because the shunt component is
Because atmospheric pressure is reduced, the not corrected; i.e. normally up to 15 kPa (115mmHg)
delivered concentration is increased from that breathing 100% O2.
marked on the dial, but since anaesthetic action
depends on alveolar partial pressure, not concen- Alveolar gases. Normal alveolar gas partial pressures
tration, the same settings may be used as at sea and intravascular gas tensions are shown in Table 5. End-
level. However, reduced temperature may alter tidal gas approximates to alveolar gas in normal subjects
vaporisation. and may be monitored, e.g. during anaesthesia.
- flowmeters: since atmospheric pressure is reduced, See also, End-tidal gas sampling
a given amount of gas occupies a greater volume
than at sea level; i.e. has reduced density. Thus a Alveolar gas transfer. Depends on:
greater volume is required to pass through a alveolar ventilation.
Rotameter flowmeter to maintain the bobbin at diffusion across alveolar membrane, fluid interface
a certain height, because it is the number of gas and capillary endothelium (normally less than
molecules hitting the bobbin that support it. The 0.5 m).
flowmeters therefore under-read at high altitudes. solubility of gases in blood.
However, since the clinical effects depend on the cardiac output.
number of molecules, not volume of gas, the flow- For gases transferred from the bloodstream to the alveo-
meters may be used as normal. lus, e.g. CO2, and anaesthetic vapours during recovery,
Leissner KB, Mahmood FU (2009). J Anesth; 23: the same factors apply.
54353

Altitude, low. Problems are related to high pressure:

those of hyperbaric O2 (see Oxygen, hyperbaric). Table 5 Normal respiratory gas partial pressures and tensions
inert gas narcosis. in kPa (mmHg)
neurological impairment, e.g. tremor,
disorientation. Inspired Alveolar Arterial Venous Expired
pressure reversal of anaesthesia.
effects on equipment: O2 21 (160) 14 (106) 13.3 (100) 5.3 (40) 15 (105)
- implosion of glass ampoules. CO2 0.03 (0.2) 5.3 (40) 5.3 (40) 6.1 (46) 4 (30)
- deflation of air-filled tracheal tube cuffs. Nitrogen 80 (600) 74 (560) 74 (560) 74 (560) 75 (570)
- functioning of vaporisers and flowmeters is H2O Variable 6.3 (47) 6.3 (47) 6.3 (47) 6.3 (47)
normal, as above.
26 Alveolar hypoventilation syndrome

With normal cardiac output, blood cells take about There is no specific treatment, although cortico-
0.75s to pass through pulmonary capillaries. O2 transfer steroids and cyclophosphamide or azathioprine
is usually complete within 0.25s; part of the time is taken may be used. Ciclosporin has theoretical benefits.
for the reaction with haemoglobin. CO2 diffuses 20 times Lung transplantation may be possible.
more quickly through tissue layers; transfer is also com- extrinsic allergic alveolitis (hypersensitivity pneu-
plete within 0.25s. Transfer of highly soluble gases, e.g. monitis): causative agents include aspergillus (farm-
carbon monoxide, is limited by diffusion between alveo- ers lung, malt-workers lung), pituitary extracts
lus and capillary, since large volumes can be taken up by (pituitary snuff takers lung) and avian proteins
the blood once they reach it. Transfer of insoluble gases, (bird-fanciers lung). May be:
e.g. N2O, is limited by blood flow from alveoli, since - acute: requires initial sensitisation to an antigen.
capillary blood is rapidly saturated. Subsequent exposure results in repeated episodes
See also, Carbon dioxide transport; Diffusing capacity; of dyspnoea, cough, malaise, fever, chills, aches
Oxygen transport and lethargy. Wheezing is uncommon. Severity
depends on the dose of antigen; in very severe
Alveolar hypoventilation syndrome, see Obesity cases, life-threatening respiratory failure occurs.
hypoventilation syndrome Recovery is accelerated by corticosteroids.
- chronic: less dramatic onset, with a slow increase
Alveolar recruitment manoeuvre. Technique used in in dyspnoea with minimal other systemic
patients receiving IPPV, aiming to recruit collapsed upset and no acute episodes. May cause cor
alveoli. Typically, CPAP of 3040 cmH2O is applied for pulmonale.
2040s; alternatively, three sighing breaths at a pres- CXR may be normal, but widespread ground-glass
sure of 45 cmH2O may be given. May result in improved appearance in mid and lower zones is common.
oxygenation, although evidence of outcome benefit in Lung function is as above, although it may be
patients with acute lung injury is inconsistent. May result normal between acute attacks. Other investigations
in reduced cardiac output and hypotension due to and treatment as above.
reduced venous return. drug-induced alveolitis: patients may present with
acute cough, fever and dyspnoea or with slowly
Alveolar ventilation. Volume of gas entering the progressive dyspnoea. Causal agents include: O2,
alveoli per minute; normally about 44.5 l/min. Equals nitrofurantoin, paraquat, amiodarone and cytotoxic
(tidal volume minus dead space) respiratory rate; thus drugs.
rapid small breaths result in a much smaller alveolar others: include physical agents (e.g. radiation), con-
ventilation than slow deep breaths, even though minute nective tissue diseases.
ventilation remains constant. In the upright position, All forms may lead to pulmonary fibrosis, which may
apical alveoli receive less ventilation than basal ones, also occur without generalised alveolitis, e.g. following
because the former are already expanded by gravity local disease or aspiration of irritant substances.
and are thus less able to expand further on inspiration.
Since all the exhaled CO2 comes from the alveoli, the Alveolus. Terminal part of the respiratory tree; the
amount exhaled in a minute equals alveolar ventilation site of gas exchange. About 3 108 exist in both lungs,
alveolar concentration of CO2. Thus alveolar (and with estimated total surface area 7080m2. Their walls
hence arterial) CO2 concentration is inversely propor- are composed of a capillary meshwork covered in
tional to alveolar ventilation, at any fixed rate of CO2 cytoplasmic extensions of type I pneumocytes. Tradi
production. tionally thought to conform to the bubble model; i.e.
See also, Ventilation/perfusion mismatch spherical in structure with a thin water lining, with
surfactant molecules preventing collapse. Electron
Alveolitis. Generalised inflammation of lung paren- microscopy, and experimental and mathematical models,
chyma. Classified into: have led to alternative theories, e.g. pooling of water at
cryptogenic fibrosing alveolitis: cause is unknown, septal corners with dry areas of surfactant in between,
therefore a diagnosis of exclusion. Characterised by and surface tension helping return water to interstitial
differing amounts of inflammation and fibrosis of fluid.
the pulmonary air spaces and interstitium. Most
common at 5060 years and in smokers. Possible, Amantadine hydrochloride. Drug with both antipar-
but unproven, triggers include viral infection and kinsonian and antiviral effects. In Parkinsons disease,
exposure to metal dusts or wood fires. Has an it improves tremor, rigidity and mild dyskinesia, but
aggressive course with 50% mortality at 5 years, only in a small percentage of sufferers. Has been used
despite therapy. for the treatment of herpes zoster infections, both
Symptoms include progressive dyspnoea without during the acute phase and in the treatment of posther-
wheeze, dry cough, weight loss and lethargy. Club- petic pain. Has also been used for prophylaxis of influ-
bing occurs in 7080%. Most striking signs are the enza A in very selective groups, but is no longer
very distinctive, fine, end-expiratory crepitations recommended.
heard at the lung bases and mid-axillary lines. Pro- Dosage:
gresses to central cyanosis, pulmonary hyperten- parkinsonism: 100mg orally od (doubled after
sion, cor pulmonale and a restrictive pattern of 1 week).
pulmonary impairment as for pulmonary fibrosis. herpes zoster: 100mg bd for 14 days.
CXR may reveal small lung fields with reticulo- influenza A: 100mg od for 45 days as treatment,
nodular shadowing at lung peripheries and bases. 100mg/day for 6 weeks as prophylaxis.
CT scanning, radioisotope scanning and lung biopsy Side effects: nausea, dizziness, convulsions, hallucina-
may help with the diagnosis. tions, GIT disturbance.
 -Aminobutyric acid receptors 27

Ambu-bag, see Self-inflating bags between the amino group of one and the carboxyl group
of another, with the elimination of water.
Ambu-E valve, see Non-rebreathing valves Amino acids from the breakdown of ingested and
endogenous proteins form an amino acid pool from
American Board of Anesthesiology (ABA). Recog- which new proteins are synthesised. Amino acids are
nised as an independent Board by the American Board involved in carbohydrate and fat metabolism; amino
of Medical Specialties in 1941, having been an affiliate groups may be removed or transferred to other mole-
of the American Board of Surgery since 1938. Issues the cules (deamination and transamination respectively).
Diploma of the ABA. Deamination results in the liberation of ammonia, which
may be excreted as urea, or taken up by other amino
American Society of Anesthesiologists (ASA). acids to form amides.
Formed from the American Society of Anesthetists in Eight dietary amino acids are essential for life in
1945, to distinguish medically qualified anesthesiolo- humans: valine, leucine, isoleucine, threonine, methio-
gists from anesthetists. The American Society of Anes- nine, phenylalanine, tryptophan and lysine. Arginine and
thetists had been formed in 1936 from the New York histidine are required for normal growth. Other amino
Society of Anesthetists, which until 1911 had been the acids may be synthesised from carbohydrate and fat
Long Island Society of Anesthetists, founded in 1905. breakdown products.
The ASA is concerned with improving the standards, Glutamine, the most abundant amino acid in the
education and audit of anaesthesia, and publishes the body, has a key role in muscle synthesis and immune
journal Anesthesiology. function, as a neurotransmitter and as a major metabolic
fuel for enterocytes. Inclusion of glutamate in enteral
Amethocaine, see Tetracaine feeds appears to reduce gut permeability and prevents
the mucosal atrophy that occurs when food is not given
Amfetamine poisoning. Overdosage of amfetamines by the enteral route.
may cause anxiety, hyperactivity, tachycardia, hyper Synthetic crystalline amino acid solutions (containing
tension, hallucinations and hyperthermia. Intracranial the l-isomers) are used as a nitrogen source during TPN.
haemorrhage may accompany acute severe hyperten- The composition of solutions varies considerably by
sion. The toxic dose is not well defined, as there is a wide manufacturer, although all provide the essential, and
variation in response related to tolerance in chronic most of the non-essential, amino acids. Enteral feed solu-
abusers. Diagnosis is made on the history and clinical tions also include a mixture of amino acids.
grounds, supported by qualitative laboratory analysis See also, Nitrogen balance
(plasma levels are unhelpful in guiding management).
Patients should have continuous ECG and core tem- -Aminobutyric acid (GABA). Inhibitory neurotrans-
perature monitoring, and urine analysed for myoglobin. mitter found in many parts of the CNS. Binds to specific
Treatment includes general supportive care as for poi- GABA receptors, both pre- and postsynaptic, resulting
soning and overdoses, and the use of chlorpromazine in reduced neuronal excitability by increasing chloride
and -adrenergic receptor antagonists (although 2- conductance. Many anticonvulsant drugs facilitate the
receptor-mediated vasoconstriction in skeletal muscle action of GABA, emphasising its role in epilepsy and the
vessels may increase BP). Forced acid diuresis increases regulation of central activity. It is also an important regu-
excretion but this should not be undertaken if there is lator of muscle tone.
associated rhabdomyolysis.
-Aminobutyric acid (GABA) receptors. Trans
Amfetamines (Amphetamines). Group of drugs membrane receptors activated by GABA, present
that promote the release and inhibit the uptake of throughout the CNS. Two classes have been identified:
noradrenaline, dopamine and serotonin at the synaptic GABAA: pentameric ligand-gated ion channel com-
cleft, thereby causing stimulation of the central and posed of numerous subunit isoforms (e.g , , , ,
sympathetic nervous systems. Commonly abused, ) arranged around a central chloride ion pore (Fig.
they cause addiction and are controlled drugs. Used in 8). GABA binds at the interface between and
narcolepsy. Increase MAC of inhalational anaesthetic subunits, allowing Cl to flow into the cell; this
agents. lowers the membrane potential and therefore neu-
See also, Amfetamine poisoning ronal excitability. Site of action for benzodiazepines,
barbiturates, propofol and volatile anaesthetic
Amikacin. Antibacterial drug; an aminoglycoside with agents, almost all of which potentiate the action
bactericidal activity against some Gram-positive and
many Gram-negative organisms, including pseudo
monas. Indicated for the treatment of serious infections
caused by Gram-negative bacilli resistant to gentamicin. GABA
Not absorbed from the GIT, it must be given parenter-
ally. Excreted via the kidney. Benzodiazepines
Dosage: 7.5mg/kg im or slowly iv bd/tds up to 15g
over 10 days. One-hour (peak) concentration should
not exceed 30mg/l and pre-dose (trough) level should Ethanol
be less than 10mg/l. Volatile anaesthetics
Side effects: as for gentamicin.
Propofol
GABA
Barbiturates
Amino acids. Organic acid components of proteins; they
produce polypeptide chains by forming peptide bonds Fig. 8 GABAA receptor showing GABA and drug binding sites
28 Aminoglycosides

of endogenous GABA at low concentrations, hepatic failure, and during therapy with cimetidine,
while directly activating the receptor at higher erythromycin and ciprofloxacin. Phenytoin, carba-
concentrations. mazepine and other enzyme inducers may decrease
GABAB: G protein-coupled receptor, linked to its half-life.
K+ and Ca2+ channels via phospholipase C and ade- Side effects: arrhythmias, agitation and convulsions,
nylate cyclase. Activation results in increased K+ GIT disturbances.
and decreased Ca2+ conductance, reducing neuronal Care should be taken when patients already on oral
excitability. Mediate long-acting, tonic inhibitory treatment are given iv aminophylline, since the drug has
signalling. Site of action for baclofen. a low therapeutic ratio. Plasma levels should be mea-
Franks NP (2008). Nat Rev Neurosci; 9: 37086 sured; therapeutic range is 1020mg/l.

Aminoglycosides. Group of bactericidal antibacterial Aminopyridine. Originally 4-aminopyridine, a drug pre-

drugs. Includes amikacin, gentamicin, neomycin, netilmi- viously used to reverse non-depolarising neuromuscular
cin, streptomycin and tobramycin. blockade, and to treat myasthenic syndrome. Does not
Active against some Gram-positive and many inhibit acetylcholinesterase, but acts presynaptically to
Gram-negative organisms. Amikacin, gentamicin and increase acetylcholine release, thereby increasing the
tobramycin are also active against pseudomonas. force of muscle contraction. It also enters the brain and
Not absorbed from the GIT; must be given parenter- may cause convulsions. Replaced by 3,4-diaminopyri-
ally. Excretion is via the kidney and delayed in renal dine, which does not cross the bloodbrain barrier.
impairment. Side effects include ototoxicity (especially
with concurrent furosemide therapy) and nephrotoxic- Amiodarone hydrochloride. Antiarrhythmic drug,
ity. In pregnancy, they may cross the placenta and cause used for treating SVT, VT and WolffParkinson
fetal ototoxicity. They may also impair neuromuscular White syndrome. Acts by blocking cardiac K+ channels,
function and therefore avoidance has been suggested in thereby prolonging the cardiac action potential and
myasthenia gravis. Monitoring of plasma levels should refractory period. Hence traditionally designated a class
ideally be performed in all cases but is especially impor- III antiarrhythmic, although also demonstrates class I, II
tant in the elderly, children, those with renal impairment, and IV activity. Causes minimal myocardial depression.
the obese, and if high dosage or prolonged treatment is Half-life is over 4 weeks. Acts rapidly following iv
used. Monitored using 1h (peak) and pre-dose (trough) administration.
samples. Dosage:
200mg orally, tds for 1 week, reducing to bd for a
-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate further week, then od for maintenance.
(AMPA) receptors Transmembrane tetrameric ligand- as an iv infusion: 5mg/kg over 20120min followed
gated ion channel, activated by glutamate. Most abun- by up to 1.2g/24h, with ECG monitoring. Brady-
dant receptor in the CNS, it mediates fast synaptic cardia and hypotension may occur. May cause
transmission and has a major role in synaptic plasticity inflammation of peripheral veins. The dose should
and memory formation. Activation by glutamate results be reduced after 12 days.
in channel opening and influx of cations, mainly Na+ and Side effects: prolonged administration commonly
Ca2+ (depending on subunit composition). results in corneal microdeposits (reversible, and
rarely affecting vision), and may cause photosensitiv-
2-Amino-2-hydroxymethyl-1,3-propanediol (THAM/ ity, peripheral neuropathy, hyper- or hypothyroidism,
Tris). Buffer solution that acts both intra- and extracel- hepatitis and pulmonary fibrosis.
lularly, used extensively in molecular biology. Has been
studied for the control of metabolic acidosis (e.g. post Amitriptyline hydrochloride. Tricyclic antidepressant
cardiac arrest) or increased ICP, but not currently rec- drug. Competitively blocks neuronal uptake of nor-
ommended for clinical practice. adrenaline and serotonin. Also has anticholinergic and
Holmdahl M, Wicklund L, Wetterburg T etal (2000). antihistaminergic properties; thus has marked sedative
Acta Anaesthesiol Scand; 44: 5247 effects and is well suited for patients with agitated
depression. Also used in chronic neuropathic pain
Aminophylline. Phosphodiesterase inhibitor, a mixture management, especially when pain prevents sleeping
of theophylline and ethylenediamine. Much more soluble at night. Antidepressant and analgesic effects become
than theophylline alone, hence its use iv. Used as a bron- apparent after 24 weeks treatment.
chodilator drug (but not as first-line therapy), and as an Dosage:
inotropic drug, especially in paediatrics. depression: 75mg orally/day (less in the elderly), in
Causes bronchodilatation, increased diaphragmatic divided doses or as a single dose at night, increased
contractility, vasodilatation, increased cardiac output up to 150200mg/day.
(direct effect on the heart), diuresis (direct effect on the pain: 2575mg at night.
kidney), and CNS stimulation. Side effects: muscarinic effects include arrhythmias,
Dosage: heart block, dry mouth, urinary retention, blurred
100500mg orally bdqds (depending on the prepa- vision, constipation; hypersensitivity, blood dyscrasias,
ration), usually as slow-release preparations. Rectal hepatic impairment, confusion and convulsions may
preparations are no longer used, as they were asso- also occur. Should be avoided in cardiovascular
ciated with proctitis and unpredictable response. disease.
for emergency iv use, injection of 57mg/kg over See also, Tricyclic antidepressant drug poisoning
30min may be followed by an infusion of 0.5mg/
kg/h (up to 1mg/kg/h in smokers), with ECG moni- Ammonia (NH3). Toxic, colourless pungent-smelling
toring. Dosage should be reduced in cardiac and gas, highly soluble in water. Produced in the GIT by the
 Amplifiers 29

action of enteric organisms on dietary proteins and Amoxicillin (Amoxycillin). Derivative of ampicillin,
amino acids, and detoxified by transformation in the differing only by one hydroxyl group; has similar anti-
liver into urea. Normal blood level is 100200mg/l; bacterial activity but oral absorption is better and unaf-
levels rise in the presence of severe liver disease or a fected by food in the stomach. Enteral administration
portalsystemic blood shunt. Ammonia intoxication produces higher plasma and tissue levels than ampicillin.
causes tremor, slurred speech, blurred vision and coma. Combined with -lactamase inhibitor clavulanic acid in
There is a weak association between blood ammonia co-amoxiclav.
level and the degree of hepatic encephalopathy in Dosage: 2501000mg orally, 500mg im or 500mg
hepatic failure. Rare genetic disorders of the urea cycle 1g iv tds.
(e.g. ornithine carbamoyltransferase deficiency) lead to Side effects: as for ampicillin.
hyperammonaemia; similarly, treatment with sodium
valproate may result in raised ammonia levels due to AMPA receptors, see -Amino-3-hydroxy-5-methyl-4-
interference with the urea cycle. isoxazolepropionate (AMPA) receptors
Ammonia is also produced in the proximal tubule of
the kidney from the breakdown of glutamine. It com- Ampere. SI unit of current, one of the seven base (fun-
bines intracellularly with H+ to form the ammonium ion damental) units. Defined as the current flowing in two
(NH4+) which is secreted by the proximal tubule cells straight parallel wires of infinite length, 1m apart in a
into the tubular filtrate, thereby facilitating regulation of vacuum, that will produce a force of 2 107 N/m length
acidbase balance and cation conservation. Ammonia on each of the wires. In practical terms, represents the
formed from the dissociation of NH4+ is reabsorbed, amount of charge passing a given point per unit time; a
recycled and resecreted, primarily by the collecting flow of one coulomb of electrons per second equates to
tubule. one ampere of current.
See also, Nitrogen balance [Andre Ampre (17751836), French physicist]

Amnesia. Impairment of memory. May occur with Amphetamine poisoning, see Amfetamine poisoning
intracranial pathology, dementia, metabolic distur-
bances, alcoholism and psychological disturbances. May Amphetamines, see Amfetamines
be caused by head injury and drugs. Patients who recover
from critical illness may have poor recall of events Amphotericin (Amphotericin B). Polyene antifungal
afterwards. drug, active against most fungi and yeasts. Not absorbed
Retrograde amnesia (between the causative agent/ enterally. Highly protein-bound, it penetrates tissues
event and the last memory beforehand) is common after poorly. Administered orally as a treatment for intestinal
head injury. Anterograde amnesia (loss of memory for candidiasis, or iv for systemic fungal infections. Ampho-
the period following the causative agent/event) may tericin is available encapsulated in liposomes or as a
occur after head injury, and is common after admini complex with sodium cholesteryl sulphate, both of which
stration of certain drugs, typically benzodiazepines and reduce its toxicity.
Dosage: 15mg/kg/day iv, depending on the
hyoscine. Awareness during anaesthesia, with amnesia
preventing subsequent conscious recall, may be more formulation.
Side effects: renal and hepatic impairment, nausea
common than previously thought.
and vomiting, electrolyte disturbance, especially
hypokalaemia, arrhythmias, blood dyscrasias, convul-
Amniotic fluid embolism. Condition originally thought sions, peripheral neuropathy, visual and hearing dis-
to be a mechanical embolic phenomenon caused by turbances. A test dose is recommended before iv
entry of amniotic fluid and fetal cells into the maternal administration because of the risk of anaphylaxis.
circulation; now generally accepted to have a major
immunologic component, involving an inflammatory Ampicillin. Broad-spectrum semisynthetic bactericidal
response similar to anaphylaxis. The incidence is quoted penicillin. Active against many Gram-positive and nega-
as 1:80001:80000 deliveries, the wide range reflecting tive organisms; ineffective against -lactamase pro
difficulty in diagnosis. Quoted mortality is 3060%, with ducing bacteria, including Staphylococcus aureus and
many dying within 5h of presentation and a high inci- Escherichia coli. Only moderately well absorbed orally
dence of serious neurological morbidity in survivors. (~50% of dose) and this is further diminished by food
Implicated in 1015% of maternal deaths. in the gut. Excreted into bile and urine.
Usually occurs during labour or delivery, although it Dosage: 250mg1g orally qds; 5002000mg iv or im,
can present up to 48h postpartum and also during cae- 46-hourly, depending on indication.
sarean section. Said to be more common in multiparous, Side effects: nausea, rash, diarrhoea.
older women, and with forceful labour, although this has
been questioned. Amplifiers. Electrical devices used to increase the
Typical features include fetal distress, shock (often power of an input signal using an external energy source.
profound), cardiac arrest, pulmonary hypertension, Widely used in clinical measurement to amplify mea-
pulmonary oedema, acute lung injury, cyanosis, DIC, sured biological electrical potentials (e.g. ECG).
vomiting, drowsiness, convulsions. May be described in terms of:
Management involves aggressive supportive treat- degree of gain (ratio of output to input signal
ment, including correction of DIC. amplitude).
Gist RS, Stafford IP, Leibowitz AB, Beilin Y (2009). bandwidth (range of frequencies over which the
Anesth Analg; 108: 1599602 device provides reliable and constant amplification).
noise compensation (most clinical amplifiers em-
Amoebiasis, see Tropical diseases ploy common-mode rejection, whereby only the
30 Amrinone lactate

difference between two signal sources is amplified, Effects:

and interference that is common to both signals is reduced O2-carrying capacity of blood: fatigue,
rejected). dyspnoea on exertion, angina.
increased cardiac output, to maintain O2 flux: palpi-
Amrinone lactate. Phosphodiesterase inhibitor, used as tations, tachycardia, systolic murmurs, cardiac
an inotropic drug. Active iv and orally. Increases cardiac failure. Reduced viscosity increases flow but turbu-
output and reduces SVR via inhibition of cardiac and lence is more likely.
vascular muscle phosphodiesterase. MAP and heart rate increased 2,3-DPG.
are unaltered. Half-life is 36h. Not available in the UK. maintenance of blood volume by haemodilution.
Milrinone, a more potent derivative, is less likely to Unexpected anaemia should be investigated before
cause side effects (e.g. GIT upset, thrombocytopenia). routine surgery. The traditional minimal safe haemo-
globin concentration for anaesthesia has been 10g/dl,
Amylase. Group of enzymes secreted by salivary glands unless surgery is urgent; below this level, reduced O2
and the pancreas. Salivary amylase (an -amylase carriage was felt to outweigh the advantage of reduced
ptyalin) breaks down starch at an optimal pH of 6.7; blood viscosity and increased flow. More recently, 710g/
consequently it is inactivated by gastric acid. In the small dl has been suggested, reflecting the concerns over the
intestine, both salivary and pancreatic -amylase act on complications of transfusion (except in ischaemic heart
ingested polysaccharides. disease, in which postoperative mortality increases as
Plasma amylase measurements may be useful for preoperative haemoglobin concentration falls below
the diagnosis of numerous conditions, particularly acute around 10g/dl). Reduction of cardiac output during
pancreatitis. About 3540% of total plasma amylase anaesthesia is particularly hazardous. FIO2 of 0.5 is often
activity is contributed by the pancreatic isoenzyme. advocated to reduce risk of perioperative hypoxia by
Amylase levels > 5000U/l are suggestive of acute pan- increasing the O2 reserve within the lungs.
creatitis (peak reached within 2448h); other intra- In the ICU, recent evidence suggests that lowering
abdominal emergencies (e.g. perforated peptic ulcer, the threshold for transfusion from 10g/dl to 7g/dl may
mesenteric infarction) are usually associated with lower decrease mortality, organ dysfunction and cardiac
plasma levels. complications.
See also, Carbohydrates Transfused stored blood takes up to 24h to reach its
full O2-carrying capacity; ideally transfusion should
Anaemia. Reduced haemoglobin concentration; usually occur at least 1 day preoperatively. Slow transfusion also
defined as less than 13g/dl for males, 12g/dl for females. minimises the risk of fluid overload in chronic anaemia.
In children, the figure varies: 18g/dl (12 weeks of age);
11g/dl (6 months6 years); 12g/dl (612 years). Anaerobic infection. Caused by:
Caused by: obligate anaerobes: only grow in the absence of O2.
reduced production: microaerophilic organisms: only grow under condi-
- deficiency of iron, vitamin B12, folate. tions of reduced O2 tension.
- chronic disease, e.g. malignancy, infection. facultative anaerobes: capable of growing aerobi-
- endocrine disease, e.g. hypothyroidism, adreno- cally or anaerobically.
cortical insufficiency. The most clinically important are species of clostridium,
- bone marrow infiltration, e.g. leukaemia, bacteroides and actinomyces. Predisposing factors
myelofibrosis. include disruption of mucosal barriers, impaired blood
- aplastic anaemia, including drug-induced, e.g. supply, tissue injury and necrosis. Most infecting organ-
chloramphenicol. isms are endogenous. Infections are accompanied by foul-
- reduced erythropoietin secretion, e.g. renal failure. smelling, putrid pus. Specimens for analysis of possible
- abnormal red cells/haemoglobin, e.g. sideroblastic anaerobic infections may require special anaerobic trans-
anaemia, thalassaemia. port systems as some anaerobic species die if exposed to
increased haemolysis. O2. Metronidazole is especially active against anaerobes.
haemorrhage:
Anaerobic threshold. Conventionally defined as the
- acute.
work rate at which metabolic acidosis and associated
- chronic.
Investigated by measuring the size and haemoglobin
changes in gas exchange occur. A theoretical measure of
overall cardiopulmonary function, derived from cardio-
content of erythrocytes:
pulmonary exercise testing. Commonly estimated using
hypochromic, microcytic: e.g. thalassaemia, iron
the inflection point of the oxygen consumption/carbon
deficiency, including chronic haemorrhage, chronic
dioxide production curve (Fig. 9). The sudden increase
disease.
in V CO 2 /V O 2 is traditionally ascribed to increased buffer-
normochromic, macrocytic: vitamin B12 or folate
ing of lactic acid by HCO3 (thereby generating excess
deficiency, alcoholism.
CO2), although this is controversial. Has been used to
normochromic, normocytic: chronic disease, e.g.
predict outcome from major surgery, an anaerobic
infection, malignancy, renal failure, endocrine
threshold of < 1011ml/kg/min suggesting a greater risk
disease; aplastic anaemia, bone marrow disease or
of death, especially if associated with high-risk surgery
infiltration.
and/or ischaemic heart disease.
Other investigations include examination of blood
Hopker JG, Jobson SA, Pandit JJ (2011). Anaesthesia;
film (e.g. for sickle cells, parasites, reticulocytes
66: 11123
suggesting increased breakdown or haemorrhage),
measurement of platelets and white cells, bone Anaesthesia. Official journal of the Association of
marrow aspiration and further blood tests, e.g. iron, Anaesthetists of Great Britain and Ireland, first pub-
vitamin B12. lished in 1946.
 Anaesthesia, history of 31

Anaesthesia (from Greek: an + aisthesis; without - cerebral function monitor and analysing monitor:
feeling). Term suggested by Oliver Wendell Holmes in easier to use and read, but less informative than
1846 to describe the state of sleep produced by ether; the conventional EEG.
word had been used previously to describe lack of - power spectral analysis: graphic display of compli-
feeling, e.g. due to peripheral neuropathy. He introduced cated data; easier to interpret than conventional
derived terms, e.g. anaesthetic agent. EEG. The bispectral index monitor and entropy
monitor (describing non-linear dynamics) are
Anaesthesia and Intensive Care. Official journal of the now commonly used. These monitors use propri-
Australian Society of Anaesthetists (formed in 1935) etary algorithms to convert raw EEG data into a
since its launch in 1972. Also the official journal of the single number that is claimed to represent global
Australian and New Zealand Intensive Care Society and activity; titration of anaesthesia in order to keep
the New Zealand Society of Anaesthetists. the value within defined limits may thus reduce
both awareness and overdosage, although their
Anaesthesia, balanced, see Balanced anaesthesia place is controversial.
evoked potentials: similar effects are produced by
Anaesthesia crisis resource management, see Crisis different anaesthetic agents.
resource management oesophageal contractility: affected by smooth
muscle relaxants and ganglion blocking drugs, also
Anaesthesia, depth of. Anaesthesia is generally by disease, e.g. achalasia.
accepted as being a continuum in which increasing depth EMG: particularly of the frontalis muscle. Requires
of anaesthesia results in loss of consciousness, recall, and separate monitoring of peripheral neuromuscular
somatic and autonomic reflexes. Some would argue that, blockade in addition.
whilst these are the effects of anaesthetic drugs in Kent CD, Domino KB (2009). Curr Opin Anesthesiol;
increasing dosage, anaesthesia itself occurs at a particu- 22: 7827
lar undefined point, and is therefore either present or
absent. Anaesthesia dolorosa. Pain in an anaesthetic area, typi-
Assessment is important in order to avoid inadequate cally following destructive treatment of trigeminal neu-
anaesthesia with awareness and troublesome reflexes, or ralgia. Unpleasant symptoms, ranging from paraesthesia
overdose. to severe pain, develop in the area of the face rendered
Methods of assessment: anaesthetic, and may be more distressing than the origi-
clinical: nal symptoms. Anaesthesia dolorosa may develop many
- stages of anaesthesia (see Anaesthesia, stages of). months after the lesion, and is often refractory to further
- signs of inadequate anaesthesia: treatment, including surgery. Limited success has been
- lacrimation. reported with gabapentin.
- tachycardia.
- hypertension. Anaesthesia, history of
- sweating. Early attempts at pain relief:
- reactive dilated pupils. opium used for many centuries, especially in the Far
- movement, laryngospasm. East. First injected iv by Wren in 1665.
These signs may be altered by anaesthetic drugs use of other plants and derivatives for many centu-
themselves, and by others, e.g. opioids, atropine, ries, e.g. cocaine (cocada), mandragora, alcohol.
neuromuscular blocking drugs. acupuncture.
- isolated forearm technique. unconsciousness produced by carotid compression.
EEG: analgesia produced by cold (refrigeration anaesthe-
- conventional EEG: bulky and difficult to inter- sia), compression and ischaemia: 15001600s.
pret. Poor correlation between different anaes- mesmerism: 17001800s.
thetic agents. General anaesthesia:
effects of diethyl ether on animals described by
Paracelsus: 1540.
understanding of basic physiology, especially respi-
ratory and cardiovascular, and isolation of many
gases, e.g. O2, CO2, N2O: 16001700s.
5 N2O suggested for analgesia by Davy in 1799.
CO2 inhalation to produce insensibility described
4 by Hickman in 1824.
use of diethyl ether for anaesthesia by Long, Clarke:
VCO2 (l/min)

3 1842.
use of N2O for anaesthesia by Wells, Colton: 1844.
2 first public demonstration of ether anaesthesia in
Boston by Morton: 16 October 1846 (see Bigelow;
1 Holmes; Warren).
first UK use by Scott in Dumfries, Scotland, on 19
0 December 1846, news of Mortons demonstration in
0 1 2 3 4 5 Boston having travelled to Dumfries with Fraser,
VO2 (l/min) ships surgeon aboard the Royal Mail steamship
Acadia. Used in London by Squire 2 days later (see
Fig. 9 Anaerobic threshold (arrowed) Liston).
32 Anaesthesia, mechanism of

chloroform introduced by Simpson: 1847. Previously suggested but now discarded theories:
first deaths, e.g. Greener: 1848. disruption of lipid bilayers/non-specific membrane
development in UK led by Snow, then Clover. expansion; initially suggested by the observation
rectal administration of anaesthetic agents that the potency of volatile agents is related to their
described. lipid solubility (MeyerOverton rule). However,
iv anaesthesia produced with chloral hydrate by this does not explain the cut-off effect or the lack
Or: 1872. of potentiation of anaesthetics by heat.
ether versus chloroform: the former was favoured clathrate theory (water hydrates of anaesthetic
in England and northern USA, the latter in Scot- agents).
land and southern USA. Other agents introduced Fergusons thermodynamic activity theory: related
(see Inhalational anaesthetic agents). Boyle machine activity to the chemical composition of the agent
described 1917. concerned, by determining the energy contained
iv anaesthesia popularised by Weese, Lundy and within the chemical bonds of its molecules. Related
Waters: 1930s (see Intravenous anaesthetic agents). to lipid solubility and other physical properties.
Neuromuscular blockade introduced by Griffith: Bernard suggested that anaesthetics caused intra-
1942. Halothane introduced 1956. cellular protein coagulation.
UK pioneers: Hewitt, Macewen, Magill, Rowbo- [J Ferguson (described 1939), English scientist]
tham, Macintosh (first UK professor), Hewer, Brown EN, Lydic R, Schiff ND (2010). N Engl J Med;
Organe. 363: 263850
USA pioneers: Waters (first university professor),
Guedel, Mckesson, Crile, McMechan, Lundy. Anaesthesia, one-lung, see One-lung anaesthesia
UK: Association of Anaesthetists founded 1932;
DA examination 1935; Faculty of Anaesthetists Anaesthesia Practitioners, see Physicians Assistants
1948; FFARCS examination 1953; College of (Anaesthesia)
Anaesthetists 1988; Royal College of Anaesthetists
1992. Anaesthesia, stages of. In 1847, Snow described five
USA: American Society of Anesthesiologists stages of narcotism, although a less detailed classifica-
founded 1945. tion had already been described. The classic description
World Federation of Societies of Anaesthesiologists of anaesthetic stages was by Guedel in 1937 in unpre-
founded 1955. medicated patients, breathing diethyl ether in air:
Local anaesthesia: stage 1 (analgesia):
cocaine isolated 1860. - normal reflexes.
topical anaesthesia produced by Koller: 1884. - ends with loss of the eyelash reflex and
spinal anaesthesia by Corning: 1885; Bier: 1898. unconsciousness.
epidural anaesthesia 1901. stage 2 (excitement):
pioneers: Braun, Lawen, Labat. - irregular breathing, struggling.
[Sir Christopher Wren (16321723), English scientist - dilated pupils.
and architect; William Scott (18201887) and William - vomiting, coughing and laryngospasm may occur.
Fraser (18191863), Scottish surgeons; Helmut Weese - ends with the onset of automatic breathing and
(18971954), German pharmacologist] loss of the eyelid reflex.
See also, Cardiopulmonary resuscitation; Intermittent stage 3 (surgical anaesthesia):
positive pressure ventilation; Intensive care, history of; - plane I:
Intubation, tracheal; Local anaesthetic agents - until eyes centrally placed with loss of conjunc-
tival reflex.
- swallowing and vomiting depressed.
Anaesthesia, mechanism of. The precise mechanism is - pupils normal/small.
unknown, but theories are as follows: - lacrimation increased.
anatomical level: - plane II:
- ascending reticular activating system, thalamus, - until onset of intercostal paralysis.
and cerebral cortex are considered the most likely - regular deep breathing.
anatomical sites of action. - loss of corneal reflex.
- spinal cord is also affected by anaesthetics. - pupils becoming larger.
- synaptic sites are thought to be more important - lacrimation increased.
than axonal sites, since the former are blocked - plane III:
more easily than the latter at clinically effective - until complete intercostal paralysis.
concentrations of anaesthetic agent. - shallow breathing.
cellular level: - light reflex depressed.
- now accepted to act at specific neuronal protein - laryngeal reflexes depressed.
targets, including: - lacrimation depressed.
- type A GABA receptors: known target for - plane IV:
barbiturates, benzodiazepines, propofol and - until diaphragmatic paralysis.
volatile agents, all of which potentiate GABA- - carinal reflexes depressed.
mediated inhibition of neuronal activity. stage 4 (overdose):
- NMDA receptors: known target for ketamine. - apnoea.
- two-pore domain K+ channels: activated by vol- - dilated pupils.
atile agents, resulting in membrane hyperpolari- With modern agents and techniques, the stages often
sation and reduced excitability. occur too rapidly to be easily distinguished.
 Anaesthetic breathing systems 33

The stages may be seen in reverse order on emer-

gence from anaesthesia. A
See also, Anaesthesia, depth of
Anaesthesia, total intravenous, see Total intravenous FGF
anaesthesia
Anaesthetic accidents, see Anaesthetic morbidity and
mortality
Anaesthetic agents, see Inhalational anaesthetic agents;
Intravenous anaesthetic agents; Local anaesthetic agents
B FGF
Anaesthetic breathing systems
Definitions:
open: unrestricted ambient air as the fresh gas
supply.
semi-open: as above, but some restriction to air
supply, e.g. enclosed mask.
closed: totally closed circle system. FGF
C
semi-closed: air intake prevented but venting of
excess gases allowed. Divided by Mapleson into five
groups, A to E, in 1954; a sixth (F) was added later
(Fig. 10). Arranged in order of decreasing efficiency
in eliminating carbon dioxide during spontaneous
ventilation.
Maplesons nomenclature (excludes open drop tech-
D
niques, circle systems, and use of non-rebreathing FGF
valves):
Mapleson A (Magill attachment):
- most efficient for spontaneous ventilation, because
exhaled dead-space gas is reused at the next inspi-
ration, and exhaled alveolar gas passes out
through the valve. Thus fresh gas flow (FGF) E FGF
theoretically may equal alveolar minute volume
(70ml/kg/min).
- inefficient for IPPV, because some fresh gas is lost
through the valve when the bag is squeezed, and
exhaled alveolar gas may be retained in the
system and rebreathed. High gas flows are there- F FGF
fore needed (23 times minute volume).
Mapleson B and C: rarely used, other than for resus-
citation. Inefficient; thus 23 times minute volume
is required.
Mapleson D:
- inefficient for spontaneous ventilation, because Fig. 10 Nomenclature of anaesthetic breathing systems (see text)
exhaled gas passes into the reservoir bag with
fresh gas, and may be rebreathed unless FGF is
high. Suggested values for FGF range from 150 to breathing during spontaneous ventilation. Sug-
300ml/kg/min (i.e. 24 times minute ventilation); gested FGF: 24 times minute volume for spontane-
resistance to breathing may be a problem at ous ventilation. For IPPV, 200ml/kg/min has been
high FGF. suggested, although more complicated formulae
- efficient for IPPV; exhaled dead-space gas passes exist.
into the bag and is reused but when alveolar gas Modifications include:
reaches the bag, the bag is full of fresh gas and coaxial versions of the A and D systems (Lack and
dead-space gas; alveolar gas is thus voided through Bain respectively): the valve is accessible to the
the valve. Theoretically, 70ml/kg/min will main- anaesthetist for adjustment and scavenging, and
tain normocapnia. the tubing is longer and lighter.
Mapleson E (Ayres T-piece): used for children, Humphrey ADE system: valve and bag are at the
because of its low resistance to breathing. To prevent machine end, with a lever incorporated within the
breathing of atmospheric air, the reservoir limb valve block; may be converted into type A, D or E
should exceed tidal volume. A FGF of 24 times systems depending on requirements.
minute volume is required to prevent rebreathing. enclosed afferent reservoir system: resembles the
May be used for IPPV by intermittent occlusion of Mapleson D with an additional reservoir placed on
the reservoir limb outlet. the FGF limb. This reservoir is enclosed within
Mapleson F (JacksonRees modification): adapted a chamber that connects to the main limb such
from Ayres T-piece. The bag allows easier control that compressing the original reservoir bag (e.g.
of ventilation, and its movement demonstrates manually) causes the additional reservoir to be
34 Anaesthetic drug labels

compressed too, increasing the tidal volume deliv- - linkage between N2O and O2 Rotameters, so
ered. The system (in a more sophisticated form, that less than 25% O2 cannot be dialed up, e.g.
including a bellows as the additional reservoir) has Quantiflex apparatus and newer machines.
been incorporated within a ventilator system; - to avoid O2 leak: O2 flowmeter feeds downstream
although it has been shown to be efficient during from the others; thus a cracked CO2 Rotameter
both spontaneous and controlled ventilation, it is leaks N2O in preference to O2.
not widely used. - to avoid risk of O2 delivery failure:
British and International Standard taper sizes of breath- - O2 pressure gauge.
ing system connections are 15mm for tracheal tube con- - O2 failure warning device; preferably switching
nectors and paediatric components, and 22mm for adult off other gas flows and allowing air to be
components. Some components have both external breathed.
tapers of 22mm, and internal tapers of 15mm. Some - O2 analyser.
paediatric equipment has 8.5mm diameter fittings, delivering excessive CO2 (e.g. caused by the CO2
although not standard. Upstream parts of connections flowmeter opened fully, with the bobbin hidden at
are traditionally male, and fit into the female down- the top of the flowmeter tube):
stream parts. - maximal possible CO2 flow is limited, e.g. to
[William W Mapleson, Cardiff physicist; Philip Ayre 500ml/min.
(19021980), Newcastle anaesthetist; Gordon Jackson - bobbin is clearly visible throughout the length of
Rees (19182000), Liverpool anaesthetist; David Hum- the Rotameter tube.
phrey, South African physiologist and anaesthetist] - CO2 cylinder is connected to the machine only
Conway CM (1985). Br J Anaesth; 57: 64957 when specifically required.
See also, Adjustable pressure-limiting valve; Catheter delivering excessive pressures:
mounts; Coaxial anaesthetic breathing systems; Face- - adjustable pressure-limiting valve on breathing
masks; Tracheal tubes; Valveless anaesthetic breathing systems: modern ones allow maximal pressures of
systems ~70 cmH2O when fully closed. Many ventilators
also have cut-off maximal pressures.
Anaesthetic drug labels, see Syringe labels - distensible reservoir bag; maximal pressure attain-
able is about 60 cmH2O. Pressure reaches a
Anaesthetic machines. Term commonly refers to plateau as the bag distends, falling slightly
machines providing continuous flow of anaesthetic gases (Laplaces law) before bursting.
(cf. intermittent-flow anaesthetic machines). The original Other safety features:
Boyle machine was developed in 1917 at St Bar- switches to prevent soda lime being used with tri-
tholomews Hospital, although similar apparatus was chloroethylene (older machines).
already being used in America and France. key filling system for vaporisers.
Usual system: negative and positive pressure relief valves within
piped gas supply or cylinders. scavenging systems.
pressure gauges may indicate pipeline, cylinder antistatic precautions.
or regulated (reduced) pressure (see Pressure Thompson PW, Wilkinson DJ (1985). Br J Anaesth; 57:
measurement). 6408
pressure regulators provide constant gas pressure, See also, Checking of anaesthetic equipment
usually about 400 kPa (4 bar) in the UK. Pipelines
are already at this pressure. Anaesthetic morbidity and mortality. Complications
flowmeters, usually Rotameters. during and following anaesthesia are difficult to quantify,
vaporisers. since many may be related to surgery or other factors.
pressure relief valve downstream from the vaporis- Many are avoidable, and may be more disturbing to the
ers protects the flowmeters from excessive pressure; patient than the surgery itself.
it opens at about 3840 kPa. May be combined with Examples:
a non-return valve. tracheal intubation difficulties (see Intubation, com-
O2 flush; bypasses flowmeters and vaporisers, deliv- plications of).
ering at least 35 l/min. sore throat.
O2 failure warning device. damage to teeth, mouth, eyes, etc.
ventilators, monitoring equipment, suction equip- respiratory complications: hypoventilation, atelec-
ment and various anaesthetic breathing systems tasis, chest infection, PE, pneumothorax, aspiration
may be incorporated. Some machines contain pneumonitis, airway obstruction, bronchospasm.
microprocessors for digitalised control of functions, cardiovascular complications: MI, hypertension/
e.g. gas flow. hypotension, air embolism, arrhythmias.
Modern safety features reduce the risk of: blood transfusion hazards.
delivering hypoxic gas mixtures: thrombophlebitis/pain at injection or infusion sites.
- to avoid incorrect gas delivery: extravasation of injectate/intra-arterial injection.
- pin index system for cylinders and non-inter- severe neurological complications: CVA, brain
changeable connectors for piped gas outlet. damage, spinal cord infarction; they often follow
- colour coding of pipelines and cylinders. severe hypotension/cardiac arrest/hypoxia.
- O2 analyser. awareness.
- O2 flowmeter control is bigger and has a differ- drowsiness, confusion, psychological changes.
ent profile from others; it is positioned in the PONV.
same place on all machines (on the left in the headache: often related to perioperative dehydra-
UK; on the right in the USA). tion and starvation. Post-dural puncture headache.
 Analgesic drugs 35

nerve injury and damage related to positioning of monitoring is disconnected during transfer of the
the patient. patient.
muscle pains following suxamethonium. transfer and positioning for surgery are more haz-
backache: especially after lithotomy position. ardous with the patient anaesthetised than when
Reduced by lumbar pillows. awake.
falls during transfer from/to trolleys. equipment, iv fluids and drugs may not be immedi-
burns, e.g. from diathermy. ately available in the operating theatre.
adverse drug reactions, e.g. halothane hepatitis, The above disadvantages lead many anaesthetists to
MH. induce anaesthesia in the operating theatre for high-risk
drug overdose. patients. Continued existence of anaesthetic rooms is
renal impairment, e.g. following uncorrected controversial. Holding areas capable of processing many
hypotension. patients at once (allowing premedication and perfor-
death. mance of regional blocks) have been suggested as an
Mortality may be related to anaesthesia, surgery alternative.
or the medical condition of the patient. Mortality Meyer-Witting M, Wilkinson DJ (1992). Anaesthesia; 47:
studies in the UK, USA, Canada, Scandinavia, 10212
Europe and Australia have all implicated similar
factors: Anaesthetic simulators, see Simulators
preoperatively:
- inadequate assessment. Anaesthetists non-technical skills (ANTS). Defined
- hypovolaemia and inadequate resuscitation. as the cognitive, social and personal resource skills that
perioperatively: complement technical skills, contributing to the safe and
- aspiration. efficient delivery of anaesthesia. Long recognised to play
- inadequate monitoring. a major role in crisis management and error prevention;
- intubation difficulties. recent interest in objectively assessing and developing
- delivery of hypoxic gas mixtures and equipment these skills has led to the development of the ANTS
failure. taxonomy. This consists of an assessment system address-
- inexperience/inadequate supervision. ing skills relating to four categories: team working; deci-
postoperatively: sion-making; task management; and situation awareness.
- inadequate observation. Each skill is assessed on a four-point scale.
- hypoventilation due to respiratory depression, Largely used in the simulator setting; elements of the
residual neuromuscular blockade and respiratory system have recently been incorporated into formal
obstruction. workplace-based assessment tools.
Morbidity and mortality are thus reduced by: Flin R, Patey R, Glavin R, Maran N (2010). Br J Anaesth;
thorough preoperative assessment and adequate 105: 3844
resuscitation. See also, Crisis resource management; Fixation error
checking of anaesthetic equipment and drugs.
adequate monitoring. Analeptic drugs. Drugs causing stimulation of the CNS
anticipation of likely problems. as their most prominent action (many other drugs also
attention to detail. have stimulant properties, e.g. aminophylline).
adequate recovery facilities. Mechanism of action:
adequate supervision/assistance. block inhibition, e.g. strychnine (via glycine antago-
Clear contemporaneous record-keeping promotes nism), picrotoxin (via GABA antagonism).
careful perioperative monitoring and assists retrospec- increase excitation, e.g. doxapram, nikethamide.
tive analysis of complications and future anaesthetic Doxapram increases respiration via stimulation of
management. peripheral chemoreceptors. All the analeptics may cause
See also, Audit; Confidential Enquiries into Maternal cardiovascular stimulation, and convulsions at sufficient
Deaths, Report on; Confidential Enquiry into Periopera- doses.
tive Deaths
Analgesia. Lack of sensation of pain from a normally
Anaesthetic rooms (Induction rooms). Usual in the painful stimulus.
UK but not used in many other countries. See also, Analgesic drugs
Advantages:
quiet area for induction of anaesthesia and Analgesic drugs. May be divided into:
teaching. opioid analgesic drugs.
less frightening for the patient than lying on the inhibitors of prostaglandin synthesis:
operating table. Allows parents to be present during - NSAIDs.
induction of anaesthesia in children. - paracetamol.
anaesthetists domain; i.e. without pressure from others:
surgeons. - inhalational anaesthetic agents, e.g. N2O,
store for anaesthetic drugs and equipment. trichloroethylene.
increased throughput of the operating suite, if - ketamine.
another anaesthetist is available to start whilst pre- - clonidine.
vious cases are being completed in theatre. - nefopam, ethoheptazine.
Disadvantages: - local anaesthetic agents.
expensive duplication of equipment is required, e.g. adjuncts: i.e. reduce pain or pain sensation by
anaesthetic machine, monitoring, scavenging. alternative means: e.g. antidepressant drugs,
36 Anaphylaxis

corticosteroids, carbamazepine, gabapentin, muscle adrenaline im (0.51.0ml of 1:1000 every 10min

relaxants, e.g. diazepam. Used widely in chronic as required) or iv (0.51.0ml of 1:10000 slowly,
pain management. Caffeine is often included in oral repeated as required). IV infusion of adrenaline or
analgesic preparations. noradrenaline may be required after initial treat-
Analgesic drugs are distinguished from anaesthetic ment. Alternative vasoconstrictors, e.g. metarami-
agents by their ability to reduce pain sensation without nol, have been successfully used in resistant cases.
inducing sleep; thus N2O is a good analgesic but a poor Bronchodilator drugs, e.g. salbutamol, may be
anaesthetic, and halothane has poor analgesic properties required.
but is a potent anaesthetic. In practice the distinction is Secondary management includes antihistamine drugs,
not precise, as analgesic drugs, e.g. opiates, will cause e.g. chlorphenamine 1020mg slowly iv (H2-receptor
unconsciousness at high doses, and anaesthetic drugs, e.g. antagonists have been suggested but current UK
halothane, will abolish pain sensation at deep planes of guidelines do not support their use), and hydrocorti-
anaesthesia. sone 100200mg iv. Bicarbonate therapy may be
required according to blood gas interpretation.
Anaphylaxis. Severe, life-threatening, generalised or Blood samples should be taken for subsequent testing
systemic hypersensivity reaction. The term has tradition- (see Adverse drug reactions).
ally been reserved for type I immune reactions in which Kroigaard M, Garvey LH, Gillberg L (2007). Acta
cross-linking of two immunoglobulin type-E (reagin) Anaesthesiol Scand; 51: 65570
molecules by an antigen on the surface of mast cells
results in the release of histamine and other vasoactive Aneroid gauge, see Pressure measurement
substances, e.g. kinins, 5-HT and leukotrienes. Type G
immunoglobulin may also be involved. True anaphy- Anesthesia and Analgesia. Oldest current journal of
laxis requires previous exposure to the antigen respon- anaesthesia, first published in 1922 as Current Researches
sible, sometimes many exposures; e.g. anaphylaxis to in Anesthesia and Analgesia (the journal of the National
thiopental classically occurs after more than 10 expo- Anesthesia Research Society, which became the Inter-
sures. However, in 80% of cases no prior exposure is national Anesthesia Research Society in 1925). Also the
evident. official journal of the Society of Cardiovascular Anes-
Reactions not involving IgE cross-linking (and there- thetists, the Society of Pediatric Anesthesia, the Society
fore not requiring prior exposure to the causative agent, of Ambulatory Anesthesia, the International Society
unless the classical complement pathway is involved) for Anaesthetic Pharmacology, the Society for Technol-
have been termed anaphylactoid, but current Euro- ogy in Anesthesia and the Anesthesia Patient Safety
pean guidelines recommend avoidance of this term, Foundation.
since the clinical presentation and management of both Craig DB, Martin JT (1997). Anesth Analg; 85: 23747
types are identical. Such reactions may involve direct
histamine release from mast cells (typically radiological
Anesthesiology. Journal of the American Society of
contrast media, certain neuromuscular blocking drugs,
Anesthesiologists, first published in 1940. Also the offi-
e.g. atracurium, tubocurarine), or activation of comple-
cial journal of the Society of Obstetric Anesthesia and
ment via either classical or alternative pathways (e.g.
Perinatology, and the American Society of Critical Care
Althesin).
Anesthetists.
More common in women, which has led to the
suggestion that exposure to cosmetics may prime the
reaction. Incidence is estimated at 1 in 1000020000 Anesthesiology. American term describing the
anaesthetics, but with considerable variation between practice of anaesthesia by trained physicians (anesthesi-
countries. More common when drugs are given iv. Agents ologists) as opposed to others who might administer
most commonly implicated are the neuromuscular anaesthetics (e.g. nurse anesthetists). Formally accepted
blocking drugs (6070%), especially suxamethonium, as a specialty by the American Medical Association in
latex (1020%), and antibacterial drugs (1015%; N.B. 1940. In the UK, the term anaesthetist implies medical
current opinion is that patients allergic to penicillin are qualification.
not more likely to react to third- or fourth-generation
cefalosporins). Mortality is approximately 5%. Has been Angina, see Ischaemic heart disease; Myocardial
classified clinically into five grades: ischaemia
I: cutaneous: erythema, urticaria, angio-oedema.
II: as above plus hypotension, tachycardia, Angio-oedema. Tissue swelling resulting from allergic
bronchospasm. reactions. Spread of oedema through subcutaneous
III: as above but severe; collapse, arrhythmias. tissue often involves the periorbital region, lips, tongue
IV: cardiac and/or respiratory arrest. and oropharynx. Life-threatening airway obstruction
V: death. may occur. Common precipitants include plants, food-
Clinical presentation is variable, although 7090% of stuffs (e.g. shellfish, nuts) and drugs (especially angio
patients have cutaneous features and 2040% have tensin converting enzyme inhibitors). Acute swelling
bronchospasm. Hypotension is the only feature in often settles after about 6h, although treatment of a
~10%. severe life-threatening attack should follow the manage-
Immediate management: ment of anaphylaxis.
removal of potential triggers; call for help. Certain forms of angio-oedema result from a defi-
ABC approach to assessment and treatment; intu- ciency of C1-esterase inhibitor, either acquired or hered-
bate if necessary and administer 100% O2 and iv itary. Colicky abdominal pain or severe respiratory
fluids. The patients legs should be raised if there is obstruction often occurs. Treatment of attacks resulting
hypotension. CPR if indicated. from these forms includes androgens, e.g. danazol,
 Ankle, nerve blocks 37

plasminogen inhibitors or replacement of C1-esterase Animal bites, see Bites and stings
inhibitor (as fresh frozen plasma or in a synthetic form).
See also, Complement, Hereditary angio-oedema Anion gap. Difference between measured cation and
anion concentrations in the plasma. Sodium concentra-
Angioplasty, see Percutaneous coronary intervention tions exceed chloride plus bicarbonate concentrations
by 411mmol/l (the range has changed in recent years
Angiotensin II receptor antagonists. Antihypertensive as modern methods of measuring electrolytes give rise
drugs, also being investigated for treatment of heart to higher normal values for chloride concentrations).
failure; competitively inhibit angiotensin II at its AT1 Anionic proteins, phosphate and sulphate make up the
receptor subtype on arteriolar smooth muscle, thus less difference. Of use in the differential diagnosis of meta-
likely than angiotensin converting enzyme inhibitors to bolic acidosis; anionic gap increases when organic anions
cause systemic side effects, including those related to accumulate, e.g. in lactic acidosis, ketoacidosis, uraemia.
interaction with other hormone systems (e.g. involving It does not increase in acidosis due to loss of bicarbonate
kinins), or renin/angiotensin system imbalance. However, or intake of hydrochloric acid. Not an infallible tool
may cause hypotension or hyperkalaemia, and should be since other cations such as potassium, calcium and mag-
used with caution in renal artery stenosis. Other side nesium may influence the calculation. Anion gap has
effects include rash, urticaria, angio-oedema, myalgia, also been compared to alterations in plasma bicarbonate
GIT disturbance and dizziness. Losartan was the first to levels (AG/HCO3 ratio). It has also been calculated
be developed, valsartan, candesartan, eprosartan, irbe- for urine electrolytes.
sartan, olmesartan and telmisartan subsequently.
Ankle Brachial Pressure Index (ABPI). Measure of
Angiotensin converting enzyme inhibitors (ACE peripheral vascular disease, calculated by dividing the
inhibitors). Originally isolated from snake venom. Used systolic pressure in the leg (best results are obtained if
in the treatment of hypertension and cardiac failure, the dorsalis pedis and posterior tibial artery pressures
they have been shown to reduce mortality in cardiac are averaged) by the systolic pressure in the arms
failure associated with MI. They block the action of (average of left and right brachial artery pressures). Nor-
angiotensin converting enzyme; apart from converting mally 0.911.3, with values > 1.3 suggesting poor arterial
angiotensin I to angiotensin II, this enzyme breaks down compressibility due to medial arterial calcification while
kinins, naturally occurring vasodilators. The ACE inhibi- values of < 0.9, < 0.7 and < 0.4 indicate mild, moderate
tors cause vasodilatation and a drop in BP that may be and severe disease respectively. Has been used to predict
profound after the first dose. Side effects include hypo- cardiovascular morbidity and mortality and distinguish
tension, rashes, leucopenia, renal and hepatic damage, atherosclerosis from other causes of leg pain.
loss of taste, angio-oedema, pancreatitis, GIT distur-
bance, myalgia, dizziness, headache and cough. Severe Ankle, nerve blocks. Useful for surgery distal to the
hypotension may follow induction of anaesthesia or ankle.
perioperative haemorrhage, especially if the patient is Nerves to be blocked are as follows (Fig. 11):
fluid- and/or sodium-depleted (e.g. taking diuretics). tibial nerve (L5S3): lies posterior to the posterior
Should be used with caution in patients with renovascu- tibial artery, between flexor digitorum longus and
lar disease. flexor hallucis longus tendons. Divides into lateral
Captopril and enalapril were the first and second and medial plantar nerves behind the medial mal-
ACE inhibitor introduced respectively; newer ones leolus. Supplies the anterior and medial parts of the
include cilazapril, fosinopril, lisinopril, moexipril, perin- sole of the foot. A needle is inserted lateral to the
dopril, quinapril, ramipril and trandolapril. posterior tibial artery at the level of the medial mal-
See also, Renin/angiotensin system leolus, or medial to the Achilles tendon if the artery
cannot be felt. It is passed anteriorly and 510ml
Angiotensins, see Renin/angiotensin system local anaesthetic agent injected as it is withdrawn.

Saphenous Cutaneous branch of

common peroneal

Lateral Medial plantar

plantar

Superficial peroneal Superficial peroneal

Sural Medial plantar Sural

Fig. 11 Cutaneous innervation of the ankle and foot

38 Ankylosing spondylitis

sural nerve (L5S2): formed from branches of the dilatation. Treatment includes behavioural and psy-
tibial and common peroneal nerves. Accompanies chotherapy; chlorpromazine has also been used.
the short saphenous vein behind the lateral malleo- Seller CA, Ravalia A (2003). Anaesthesia; 58: 43743
lus and supplies the posterior part of the sole, the
back of the lower leg, the heel and lateral side of Anrep effect. Intrinsic regulatory mechanism of the
the foot. Subcutaneous infiltration is performed heart; contractility increases in response to acute
from the Achilles tendon to the lateral malleolus, increases in afterload. Initial reduction in stroke volume
using 510ml solution. and increase in left ventricular diastolic pressure are
deep and superficial peroneal nerves (both L4S2): followed by restoration to near original values. May be
the deep peroneal nerve supplies the area between related to changes in myocardial perfusion.
the first and second toes. It lies between anterior [Gleb V Anrep (18901955), Russian-born Egyptian
tibial (medially) and extensor hallucis longus (later- physiologist]
ally) tendons, lateral to the anterior tibial artery. A Yentis SM (1998). J Roy Soc Med; 91: 20912
needle is inserted between these tendons; a click
may be felt as it penetrates the extensor retinacu- Anrep, Vassily (18521927). Russian scientist and med-
lum. 5ml solution is injected. The superficial pero- ico-politician. Described the pharmacology of cocaine in
neal nerve is blocked by subcutaneous infiltration 1880 and was the first person to describe the numbing
from the lateral malleolus to the front of the tibia. effect of sc injection; he went on to perform the first
It supplies the dorsum of the foot. nerve blocks (intercostal), publishing his results in
saphenous nerve (L34): the terminal branch of the Russian in 1884 but failing to publicise his work more
femoral nerve; blocked by subcutaneous infiltration widely. His son Gleb described the Anrep effect.
above and anterior to the medial malleolus. It sup- Yentis SM (1999). Anesthesiology; 90: 8905
plies the medial side of the ankle joint.
Antacids. Used to relieve pain in peptic ulcer disease,
hiatus hernia and gastro-oesophageal reflux by increas-
Ankylosing spondylitis. Disease characterised by ing gastric pH. Used preoperatively in patients at high
inflammation and fusion of the sacroiliac joints and risk of aspiration of gastric contents (e.g. in obstetrics)
lumbar vertebrae; may also involve the thoracic and cer- to reduce the risk/severity of ensuing pneumonitis,
vical spine. Commonest in males, with a high proportion should aspiration occur. Also used on ICU as prophy-
carrying tissue type antigen HLA B27. laxis against stress ulcers. Many preparations are avail-
Features: able; sodium citrate is most commonly used in anaesthetic
backache and stiffness. Spinal cord compression practice. Chronic overuse of antacids may result in alka-
may occur; atlantoaxial subluxation or cervical frac- losis, hypercalcaemia (calcium salts), constipation (alu-
ture may also occur. Spinal/epidural anaesthesia minium salts) and diarrhoea (magnesium salts).
may be difficult.
restricted ventilation if thoracic spine or costover- Antagonist. Substance that opposes the action of an
tebral joints are severely affected; increased dia- agonist.
phragmatic movement usually preserves good lung Antagonism may be:
function. Pulmonary fibrosis is rare. competitive: the substance reversibly binds to a
tracheal intubation may be difficult due to a receptor, and causes no direct response within the
stiff or rigid neck, or temporomandibular joint cell (i.e. has no intrinsic activity), but may cause a
involvement. response by displacing an agonist, e.g. naloxone.
aortitis may occur (in less than 5% of chronic suf- non-competitive: as above, but with irreversible
ferers), causing aortic regurgitation. Cardiomyopa- binding, e.g. phenoxybenzamine.
thy and conduction defects are rare. physiological: opposing actions are produced by
amyloidosis may occur. binding at different receptors, e.g. histamine and
Woodward JL, Kam PCA (2009). Anaesthesia; 64: adrenaline causing bronchoconstriction and bron-
5408 chodilatation respectively.
See also, Doseresponse curves; Receptor theory

Anorexia nervosa. Psychiatric condition, most common Antanalgesia. Increased sensitivity to painful stimuli
in young women. Characterised by loss of weight, distor- caused by small doses of depressant drugs, e.g. thiopen-
tion of body image and amenorrhoea; the last results tal. Thought to result from suppression of the inhibitory
from weight loss, and psychological and endocrine action of the ascending reticular activating system,
factors. Quoted mortality is 418% the highest of any allowing increased cortical responsiveness (decreased
psychiatric condition. pain threshold). Larger doses depress the activating
Anaesthetic considerations: system and induce sleep. Antanalgesia may also occur as
electrolyte disturbances, especially hypokalaemia, blood drug levels fall, e.g. causing postoperative restless-
are associated with laxative abuse or self-induced ness when barbiturates or alimemazine are used as pre-
vomiting. medication, especially in children.
tendency towards hypothermia, hypotension and
bradycardia. Antecubital fossa (Cubital fossa). Triangular fossa,
reduced lean body mass. anterior to the elbow joint (Fig. 12).
anaemia. Borders:
psychiatric co-morbidity, including depression. proximal: a line between the humeral epicondyles.
rarer complications: myopathy, cardiomyopathy, lateral: brachioradialis muscle.
peripheral neuritis, hepatic impairment, gastric medial: pronator teres.
 Antiarrhythmic drugs 39

risk if associated with abnormal placentation; the

Biceps muscle Medial epicondyle placenta may invade (placenta accreta) or even
Brachialis muscle penetrate (placenta percreta) the uterine wall.
Brachial artery Haemorrhage may be torrential, requiring hysterec-
tomy. Placenta accreta/percreta is more common if
Medial cutaneous
there has been prior uterine surgery, e.g. myomec-
nerve of the forearm
tomy or caesarean section, the risk increasing with
Lateral epicondyle each previous procedure.
placental abruption: haemorrhage behind the pla-
centa. May present with abdominal pain and fetal
Lateral cutaneous distress, usually in the third trimester; vaginal bleed-
nerve of the forearm ing is not always present. Caesarean section should
not be delayed since there is a risk of developing
Radial artery DIC if the fetus is not delivered, this risk increasing
the longer the wait. Has been associated with renal
Brachioradialis muscle cortical necrosis.
Anaesthetic management includes standard resuscita-
Radial nerve tion and techniques of obstetric analgesia and anaes-
(under brachioradialis)
thesia; the choice of regional versus general anaesthesia
depends on the cardiovascular stability, estimated
Deep head of
pronator teres
blood loss, presence of fetal distress, whether there is a
coagulopathy and the preferences of the anaesthetist,
Median nerve obstetrician and patient. Postpartum observation is
important since adequate fluid balance and urine
Ulnar artery output must be maintained; in addition placenta
praevia in particular predisposes to postpartum haem-
Ulnar nerve
orrhage since the uterine lower segment is not able to
Fig. 12 Anatomy of the antecubital fossa contract as effectively as the more muscular upper
segment.
Walfish M, Neuman A, Wlody D (2009). Br J Anaesth;
103: i4756

floor: supinator and brachialis muscles, with the Anterior spinal artery syndrome. Infarction of the
joint capsule behind. spinal cord due to anterior spinal artery insufficiency.
roof: deep fascia with the median cubital vein and
May follow profound hypotension, e.g. in spinal or epi-
medial cutaneous nerve on top. dural anaesthesia. May also occur after aortic surgery.
Contents from medial to lateral (embedded in fat):
Results in lower motor neurone paralysis at the level of
median nerve.
the lesion, and spastic paraplegia with reduced pain and
brachial artery, dividing into radial and ulnar
temperature sensation below the level. Because the pos-
arteries. terior spinal arteries supply the dorsal columns and pos-
biceps tendon.
terior horns, joint position sense and vibration sensation
posterior interosseus and radial nerves.
are preserved.
The bicipital aponeurosis lies between the superficial
veins and deeper structures, protecting the latter during
venepuncture. Damage may still be caused to nerves and Anthrax, see Biological weapons
arteries during this procedure; anomalous branches are
relatively common. Accidental intra-arterial injection of Antiarrhythmic drugs. Classified by Vaughan Williams
drugs is a particular hazard. into four classes, depending on their effects on the action
See also, Venous drainage of arm potential in vitro. A fifth class has been suggested that
includes a number of miscellaneous drugs (e.g. digoxin,
Antepartum haemorrhage (APH). Defined as vaginal and other cardiac glycosides, adenosine, magnesium)
bleeding after 22 weeks gestation. Occurs in up to 5% that do not fit into the standard four classes (Table 6).
of all pregnancies. Most cases are not severe and are More usefully classified for clinical purposes according
associated with various conditions, including infection. to their site of action:
Two conditions affecting the placenta are of particular atrioventricular node: calcium channel blocking
importance to the anaesthetist since they may cause drugs, digoxin, -adrenergic receptor antagonists,
sudden and severe collapse and rapid exsanguination, adenosine (used for supraventricular arrhythmias).
although this extreme is fortunately rare: atria, ventricles and accessory pathways: quini-
placenta praevia: the placenta encroaches upon or dine, procainamide, disopyramide, amiodarone
covers the cervical os. Presents with vaginal bleed- (used for supraventricular and ventricular
ing, usually in the third trimester; there may be fetal arrhythmias) and dronedarone (used to maintain
distress. Unless the mother is at risk of exsanguina- sinus rhythm after successful cardioversion for
tion, delivery of the fetus by caesarean section atrial fibrillation).
should wait until adequate blood has been obtained ventricles only: lidocaine (lignocaine), mexiletine,
and appropriate staff are present, since the mother phenytoin (used for ventricular arrhythmias).
is not at risk of developing coagulopathy unless [EM Vaughan Williams, English pharmacologist]
massive transfusion is required. Particularly high See also, individual arrhythmias
40 Antibacterial drugs

Antibiotics, see Antibacterial drugs

Table 6 Classification of antiarrhythmic drugs

Class Action Examples Antibodies, see Immunoglobulins

I Slow depolarisation rate by
inhibiting sodium influx Anticholinergic drugs. Strictly, should include all
a Prolong action potential Quinidine drugs impairing cholinergic transmission, although the
Procainamide term usually refers to antagonists at muscarinic acetyl-
Disopyramide choline receptors. Antagonists at nicotinic receptors
b Shorten action potential Lidocaine are classified as either ganglion blocking drugs or
Mexiletine neuromuscular blocking drugs. In general effects are
Phenytoin
antiparasympathetic, and include tachycardia, bron-
c No effect on action Flecainide
potential
chodilatation, mydriasis, reduced gland secretion, smooth
Propafenone muscle relaxation, and sedation or restlessness. Anaes-
Encainide thetic uses include the treatment of bradycardia, as a
II Diminish effect of -adrenergic receptor component of premedication and antagonism of the
catecholamines antagonists cardiac effects of acetylcholinesterase inhibitors.
Bretylium In anaesthesia, the most commonly used agents are
III Prolong action potential, Amiodarone atropine, hyoscine and glycopyrronium. Comparison
without affecting Sotalol of actions:
depolarisation rate Bretylium atropine:
IV Inhibit calcium influx Calcium channel blocking drugs
- central excitation.
V Miscellaneous Digoxin
Adenosine
- greater action than hyoscine on the heart, bron-
Magnesium chial smooth muscle and GIT.
hyoscine:
- central depression; amnesia (may cause excite-
ment in the elderly).
- greater action than atropine on the pupil and
sweat, salivary and bronchial glands.
Antibacterial drugs. Drugs used to kill bacteria (bacte- glycopyrronium:
ricidal) or inhibit bacterial replication (bacteriostatic). - minimal central effects (quaternary ammonium
Antibiotics are synthesised by micro-organisms and ion; crosses the bloodbrain barrier less readily
kill or inhibit other micro-organisms. Drugs synthesised than atropine and hyoscine, both tertiary ions).
in vitro, e.g. sulphonamides, are not antibiotics. - similar peripheral actions to atropine, but with
Main groups: greater antisialagogue effect and less effect on the
-lactams: bactericidal; act by inhibiting cell wall heart. Less antiemetic action than hyoscine and
synthesis. Include penicillins, cephalosporins, aztre- atropine.
onam, carbapenems. - longer duration of action.
macrolides: bacteriostatic; act by inhibiting protein Other uses of anticholinergic drugs include:
synthesis. Include erythromycin and related drugs. antispasmodic effect (on bowel and bladder), e.g.
aminoglycosides: bactericidal; inhibit protein syn- propantheline.
thesis. Include gentamicinh, netilmicin. ulcer healing, e.g. pirenzepine.
tetracyclines: bacteriostatic; inhibit protein bronchodilatation, e.g. ipratropium.
synthesis. mydriasis and cycloplegia (dilatation of pupil and
sulphonamides and trimethoprim: each alone is paralysis of accommodation), e.g. atropine.
bacteriostatic; the combination (cotrimazole) is Anticholinergic antiparkinsonian drugs, e.g. benzatro-
bactericidal. pine, procyclidine, orphenadrine, are used for their
4-quinolones: bactericidal; impair nucleic acid rep- central effects.
lication. Include nalidixic acid and ciprofloxacin. See also, Central anticholinergic syndrome
glycopeptides, e.g. teicoplanin and vancomycin:
bactericidal.
Anticholinesterases, see Acetylcholinesterase inhibitors
others, e.g. clindamycin, chloramphenicol, metroni-
dazole, polymyxins, fusidic acid, linezolid, quinu-
pristin/dalfopristin. Anticoagulant drugs. Mechanisms of action:
antituberculous drugs. prevent synthesis of coagulation factors, e.g.
Choice of antibacterial drug depends on the organism warfarin.
involved (or suspected), the severity of the condition and inhibit existing factors, e.g. heparin, factor Xa inhib-
the site of the infection. In many conditions, initial itors, thrombin inhibitors.
therapy is based on a best guess principle with broad- inhibit platelet aggregation, i.e. antiplatelet drugs.
spectrum drugs, narrower therapy being continued break down circulating fibrinogen, e.g. ancrod
when the results of culture and sensitivity studies are (snake venom derivative; not commonly used).
known. The requirement for prompt treatment in severe Fibrinolytic drugs break down thrombus once formed.
illness may conflict with the need to obtain adequate Warfarin and heparin are more effective at preventing
samples for culture before therapy is started. Much venous thrombus than arterial thrombus, as the former
concern exists about the increasing problem of bacterial contains relatively more fibrin. Antiplatelet drugs are
resistance. more effective in arterial blood, where thrombus con-
See also, Antifungal drugs; Antiviral drugs tains many platelets and little fibrin.
 Antiemetic drugs 41

Anticonvulsant drugs. Heterogeneous group of drugs deficiency. Further evidence is that central depletion
used to treat epilepsy classified according to their main (e.g. by reserpine) may cause depression.
mechanism of action, although many act in several ways: May be classified thus:
neuronal sodium channel blockade, e.g. sodium val- tricyclic antidepressant drugs: block noradrenaline
proate, phenytoin, carbamazepine, oxcarbazepine, and 5-HT uptake from synapses.
lamotrigine, zonisamide, lacosamide. selective serotonin reuptake inhibitors (SSRIs):
calcium channel blockade, e.g. carbamazepine, specifically block reuptake of 5-HT, e.g. fluoxetine.
ethosuximide. Nefazodone blocks serotonin uptake and its recep-
increase in GABA levels: tors, whilst venlafaxine is a serotonin and noradren-
- GABAA receptor agonists, e.g. benzodiazepines, aline reuptake inhibitor.
barbiturates. monoamine oxidase inhibitors (MAOIs): prevent
- GABA transaminase inhibitors, e.g. vigabatrin. catecholamine breakdown.
- GABA uptake inhibitors, e.g. tiagabine. others, e.g. lithium (mechanism of action is
- glutamic acid decarboxylase inhibitors, e.g. gaba- unknown), reboxetine (selective noradrenaline
pentin, sodium valproate. reuptake inhibitor), mirtazapine (presynaptic
glutamate receptor blockers, e.g. felbamate, 2-antagonist).
topiramate Perioperative problems arising from concurrent antide-
unknown action: levetiracetam. pressant therapy may occur, particularly with MAOIs.
Choice of drug depends on the type of seizures,
absence of side effects and teratogenesis in women of
Antidiuretic hormone, see Vasopressin
child-bearing age:
broad-spectrum agents, e.g. sodium valproate,
lamotrigine, levetiracetam: used to treat generalised Antiemetic drugs.
epilepsy (tonic-clonic or absence seizures). Absence Site of action (Fig. 13):
seizures may also respond to ethosuximide and vomiting centre: anticholinergic and antihistamine
myoclonic epilepsy to clonazepam. drugs.
narrow-spectrum agents, e.g. carbamazepine, phe- chemoreceptor trigger zone (CTZ): dopamine
nytoin, vigabatrin, gabapentin: reserved for simple receptor antagonists (e.g. phenothiazines, butyro-
or complex partial seizures. phenones and metoclopramide) and 5-HT3 receptor
About 50% of epileptic patients can be managed with antagonists.
one anticonvulsant drug. GIT: metoclopramide increases lower oesophageal
First-line management of status epilepticus involves sphincter tone and gastric emptying by a peripheral
use of iv lorazepam. Diazepam, phenytoin, fosphenytoin action.
and thiopental are also used. neurokinin-1 receptor antagonists (e.g. aprepi-
For patients undergoing surgery, anticonvulsant tant): originally developed for use in cancer
therapy should continue up to operation, and recom- chemotherapy.
mence as soon as possible postoperatively. If oral therapy others:
is delayed postoperatively, parenteral administration - dexamethasone: mechanism of action is
may be substituted. Phenobarbital and phenytoin cause uncertain.
hepatic enzyme induction, increasing the metabolism of - cannabis derivatives have been used in the treat-
certain drugs. ment of chemotherapy-induced emesis.
See also, -Aminobutyric acid (GABA) receptors - midazolam on induction of anaesthesia has been
shown to reduce PONV.
Antidepressant drugs. Most increase central amine Dopamine antagonists are suitable for treatment of
concentrations (e.g. dopamine, noradrenaline, 5-HT), vomiting associated with morphine, which stimulates the
supporting the theory that depression results from amine CTZ. Increased vestibular stimulation of the vomiting

Chemoreceptor
trigger zone 5-HT3, dopamine and
Circulating
5-HT3, dopamine and emetic agents
neurokinin-1 antagonists
neurokinin-1 receptors

Vomiting centre Anticholinergic drugs

Vestibular
muscarinic cholinergic and
input
histamine receptors Antihistamine drugs

5-HT3 and neurokinin-1

receptor antagonists
Gastrointestinal tract
5-HT3 and neurokinin-1
receptors

Fig. 13 Sites of action of different antiemetic drugs

42 Anti-endotoxin antibodies

centre, e.g. in motion sickness, is best treated with drugs prevention/treatment of nausea and vomiting, e.g.
acting on the vomiting centre, e.g. hyoscine. Sedation is cinnarizine, cyclizine (act on vomiting centre).
a common side effect, particularly of antihistamines, They have anticholinergic effects (e.g. dry mouth, blur-
anticholinergic drugs and phenothiazines. In addition, ring of vision, urinary retention). Newer drugs, e.g. terf-
phenothiazines may cause hypotension, and all dopa- enadine, cross the bloodbrain barrier to a lesser extent,
mine antagonists may cause dystonic reactions. causing less sedation.
See also, H2 receptor antagonists
Anti-endotoxin antibodies. Antibodies directed against
various parts of Gram-negative endotoxins; they have Antihypertensive drugs. Drugs used to reduce BP may
been investigated as possible treatments of severe act at different sites (Fig. 14):
sepsis. Theoretically, antibodies against the inner core of diuretics: reduce ECF volume initially and also
endotoxin (which is conserved among many different cause vasodilatation (1).
bacteria) should be useful in protecting against many vasodilator drugs: act on the vascular smooth muscle
organisms. They have conferred protection against (2), either directly, e.g. hydralazine, sodium nitro-
Gram-negative infection in animal models, but their prusside, or indirectly, e.g. -adrenergic receptor
place in clinical practice is controversial. One (HA-1A; antagonists, calcium channel blocking drugs, angio-
Centoxin) was introduced in 1991 for use in humans, but tensin II receptor antagonists, potassium channel
was withdrawn in 1993 following evidence that it might activators. Angiotensin converting enzyme inhibi-
increase mortality in patients without Gram-negative tors also decrease water and sodium retention.
bacteraemia. Another, E5, produced conflicting results -adrenergic receptor antagonists: lower cardiac
in human trials and was never released. output (3).
adrenergic neurone blocking drugs (4): e.g. gua-
Antifibrinolytic drugs. Drugs that prevent dissolution of nethidine depletes nerve endings of noradrenaline,
fibrin. Include -aminocaproic acid (no longer available preventing its release. Reserpine prevents storage
in the UK) and tranexamic acid, which inhibit plasmino- and release of noradrenaline. -Methyl-p-tyrosine
gen activation and thus reduce fibrinolysis. Used periop- inhibits dopa formation from tyrosine.
eratively to reduce surgical blood loss (e.g. in cardiac ganglion blocking drugs (5).
surgery and obstetric haemorrhage), and in trauma. centrally acting drugs (6): reduce sympathetic
Cardone D, Klein AA (2009). Eur J Anaesthesiol; 26: activity, e.g. reserpine, -methyldopa, clonidine,
7229 moxonidine.
See also, Coagulation In addition, anaesthetic agents and techniques may
reduce BP; e.g. halothane depresses baroreceptor activ-
Antifungal drugs. Heterogeneous group of drugs active ity (7) and also reduces sympathetic activity and cardiac
against fungi; includes: output; spinal and epidural anaesthesia block sympa-
polyenes (amphotericin, nystatin). thetic outflow (8).
imidazoles (e.g. clotrimazole, ketoconazole, In the treatment of hypertension, thiazide diuretics,
miconazole). -adrenergic receptor antagonists and oral vasodilators
triazoles (fluconazole, itraconazole, voriconazole).
others (caspofungin, flucytosine, griseofulvin).

Antigen. Substance that may provoke an immune Vasomotor centre

response, then react with the cells or antibodies pro-
duced. Usually a protein or carbohydrate molecule.
Some substances (called haptens), too small to provoke
immune reactions alone, may combine with host
molecules, e.g. proteins, to form a larger antigenic
combination.
7
Baroreceptors
Antigravity suit. Garment used to apply pressure to the 6
lower half of the body, in order to increase blood volume
in the upper half and prevent hypotension, e.g. in the
sitting position in neurosurgery. Systolic BP and CVP
are increased; the latter may aid prevention of air embo- 8
lism. Modern suits are inflated pneumatically around the
legs and abdomen, to a pressure of 28 kPa.
Military antishock trousers (MAST) have been used 5
in trauma to produce similar effects. They also splint 4
broken bones and apply pressure to bleeding points. 3

Antihistamine drugs. Refers to H1 histamine receptor

antagonists.
Uses:
prevention or treatment of allergic disorders, 2
e.g. hayfever, urticaria, drug reactions, e.g.
chlorphenamine. 1
for sedation or in premedication, e.g. promethazine
and alimemazine. Fig. 14 Sites of action of antihypertensive drugs (see text)
 Antipsychotic drugs 43

(except for -adrenergic receptor antagonists) are used - bromocriptine, lisuride, pergolide and apomor-
most commonly. More recently, the AB/CD algorithm phine: dopamine agonists. Ropinirole is a selec-
has been suggested: ACE inhibitors or -antagonists for tive D2 receptor agonist. Pramipexole is a D2 and
high-renin hypertension, typically younger and non- D3 agonist.
black patients, and calcium channel blocking drugs and/or - amantadine: increases release of endogenous
diuretics for low-renin hypertension, typically older and dopamine.
black patients. NICE guidelines suggest an ACE inhibitor - selegiline: monoamine oxidase inhibitor type B.
or angiotensin-II receptor blocker initially for young - amfetamines have been used.
patients, and a thiazide-like diuretic or calcium blocker anticholinergic drugs, e.g. atropine, benzatropine,
in older or black patients, with combination therapy if trihexyphenidyl, procyclidine: most effective for
required (- and -antagonists as fourth-line drugs). rigidity, tremor and treatment of drug-induced par-
Ganglion blockers, adrenergic neurone blocking kinsonism. For acute drug-induced dystonic reac-
drugs and the centrally acting drugs are seldom used, tions, benzatropine 12mg or procyclidine 510mg
because of their side effects. may be given iv. There is a higher risk of intraopera-
In the treatment of a hypertensive crisis, vasodilator tive arrhythmias and labile BP in patients taking
drugs are often given iv. For patients undergoing surgery, these drugs.
antihypertensive drugs should be continued up to
operation, and recommenced as soon as possible Antiphospholipid syndrome, see Coagulation
postoperatively. disorders
See also, Hypotensive anaesthesia

Anti-inflammatory drugs, see Non-steroidal anti- Antiplatelet drugs. Reduce platelet adhesion and
inflammatory drugs; Corticosteroids aggregation, thereby inhibiting intraluminal thrombus
formation. May act via different mechanisms:
inhibition of platelet cyclo-oxygenase and throm-
Antimalarial drugs. Used for:
prophylaxis: no drugs give absolute protection
boxane 2 production; may be reversible, e.g. pros-
against malaria. Treatment should begin at least 1 tacyclin, or irreversible, e.g. low-dose aspirin, and
week before travel to an endemic area (to ensure other NSAIDs.
patient tolerance) and continued for at least 4 increased intraplatelet cAMP levels, e.g.
weeks after leaving. Drugs used depend upon the dipyridamole.
glycoprotein IIb/IIIa receptor antagonists (e.g.
area to be visited and include chloroquine, progua-
nil, mefloquine and doxycycline. abciximab, eptifibatide, tirofiban); block the site at
treatment:
which fibrinogen, von Willebrand factor and adhe-
- falciparum malaria: chloroquine is not used sive proteins bind to platelets. Reversible and
because of worldwide resistance. Quinine, meflo- short-acting.
platelet ADP receptor antagonists, e.g. clopidogrel,
quine and halofantrine are the main treatments.
Halofantrine is rarely used today; it can cause prasugrel, ticagrelor, ticlopidine. Inhibition blocks
prolonged QT syndrome. Mefloquine is contra- the glycoprotein IIb/IIIa pathway. Irreversible and
indicated in epilepsy. Artemether with lumefan- long-acting.
trine has recently been introduced. Used to improve cerebral, peripheral and coronary
- benign malaria: chloroquine is the drug of choice blood supply in vascular disease, and to prevent throm-
primaquine. boembolism. Glycoprotein IIb/IIIa inhibitors are recom-
Baird JK (2005). N Engl J Med; 352: 156577 mended for high-risk patients with unstable angina or
non-Q wave MI and for those undergoing percutaneous
Antimitotic drugs, see Cytotoxic drugs transluminal coronary angioplasty. Dextran also has an
antiplatelet action and has been used to prevent postop-
Antiparkinsonian drugs. Treatment of Parkinsons erative DVT and PE.
disease is directed towards increasing central dopami- Patients receiving these drugs who present for surgery
nergic activity, or decreasing cholinergic activity: may be at increased risk of bleeding. The place of
increasing dopamine:
regional anaesthesia in such patients is controversial
- levodopa: crosses the bloodbrain barrier and is because of the possibly increased risk of spinal
converted to dopamine by dopa decarboxylase. haematoma.
Decarboxylase inhibitors (carbidopa, bensera- Hall R, Mazer CD (2011). Anesth Analg; 112: 292318
zide), which do not cross the bloodbrain barrier, See also, Anticoagulant drugs; Coagulation
prevent peripheral dopamine formation, thus
reducing the dose of levodopa required and the Antipsychotic drugs (Neuroleptics). Drugs used for the
incidence of side effects. Entacapone prevents management of psychosis (e.g. hallucinations, delusions,
peripheral breakdown of levodopa by inhibiting thought disorder) and acute agitation. Previously termed
catechol-O-methyl transferase and is used in com- major tranquillisers. All act via antagonism of D2 dopa-
bination with decarboxylase inhibitors in severe mine receptors, with other effects (e.g. sedation, anti-
cases. muscarinic effects) mediated via antagonism of other
Levodopa is most effective for bradykinesia. receptors, e.g. histamine receptors, 5-HT2 receptors, mus-
Its use may be limited by nausea and vomiting, carinic acetylcholine receptors). Other side effects
dystonic movements, postural hypotension and include: prolonged QT syndromes; dystonic reactions;
psychiatric disturbances. Improvement is usually parkinsonian symptoms; hyperglycaemia; and neurolep-
only temporary and may exhibit onoff tic malignant syndrome. Should be used with caution
effectiveness. and at lower dosage in the elderly, in whom they have
44 Antispasmodic drugs

been shown to be associated with a slightly increased Antituberculous drugs. Used for:
mortality and increased risk of CVA. prophylaxis: advised for susceptible close contacts
Classification: or following treatment of TB in immunocompro-
phenothiazines (e.g. prochlorperazine, chlorpro mised patients. Comprises isoniazid alone daily for
mazine). 6 months, or combined with rifampicin daily for
butyrophenones (e.g. haloperidolh, droperidol). 3 months.
atypical (e.g. olanzapine, risperidone, quetiapine). treatment is carried out in two phases:
There is no evidence that any one agent is superior to - initial phase (2 months) using four drugs: intended
any other; choice of drug is determined by individual to reduce the number of viable organisms as
response and tolerability of side effects. quickly as possible to avoid resistance. Usually
includes isoniazid, rifampicin, pyrazinamide and
Antispasmodic drugs. Used as adjunctive therapy in ethambutol. Streptomycin is rarely used today
the management of non-ulcer dyspepsia, irritable bowel but sometimes added if resistance to isoniazid is
syndrome and diverticular disease. Also administered present.
during GIT endoscopy and radiology, and when con- - continuation phase (further 4 months) using two
structing bowel anastomoses. drugs: intended to eradicate the bacteria from the
Include: body (longer treatment may be required in bone,
antimuscarinic agents (e.g. atropine, dicycloverine, joint, CNS and resistant infections). Usually com-
hyoscine, propantheline). Produce dry mouth, prises continuation of isoniazid and rifampicin
blurred vision, urinary retention and constipation. therapy.
Also relax the oesophageal sphincter, causing gas- Other drugs used in resistant cases or when side effects
tro-oesophageal reflux. are limiting include capreomycin, cycloserine, azithro-
others: e.g. alverine, mebeverine, peppermint oil: mycin, clarithromycin, 4-quinolones and rifabutin.
direct intestinal smooth muscle relaxants. Treatment must be supervised if non-compliance is
Antispasmodics should not be used in patients with ileus. suspected since partial completion of treatment courses
is a major factor in producing resistance. During use of
Antistatic precautions. Employed in operating suites, antituberculous drugs (especially pyrazinamide, isonia-
to prevent build-up of static electricity with possible zid and rifampicin), monitoring of liver function is man-
sparks, explosions and fires. Surfaces and materials datory. Streptomycin and ethambutol should be avoided
should have relatively low electrical resistance, to allow in patients with renal impairment.
leakage of charge to earth, but not so low as to allow
electrocution and electrical burns.
Precautions include: Antiviral drugs. Heterogeneous group of drugs with
avoidance of wool, nylon and silk, which may generally non-specific actions. Parenteral use is usually
generate static charge. Cotton blankets and clothing reserved for severe life-threatening systemic infections,
are suitable (resistance is very low in moist especially in immunocompromised patients. Available
atmospheres). drugs can best be classified according to the infections
antistatic rubber (containing carbon) for tubing. in which they are used:
Coloured black with yellow labels for identification. herpes simplex/varicella zoster:
Resistance is 10000010000000 ohms/cm. - aciclovir: purine nucleoside analogue; after
terrazzo floor (stone pieces embedded in cement phosphorylation, it inhibits viral DNA poly-
and polished): resistance should be 200005 000000 merase. Phosphorylated by, and therefore active
ohms between two points 60cm apart. against, herpes simplex and varicella zoster
trolleys and other equipment have conducting viruses. Early initiation of treatment is important.
wheels; staff wear antistatic footwear. May also be useful in HIV infection. May be given
Sparks are more likely in cold dry atmospheres, there- topically, orally or iv; side effects include GIT
fore relative humidity should exceed 50% and tempera- upset, rashes, and deteriorating renal and liver
ture exceed 20C. function.
The requirement for expensive antistatic flooring and - famciclovir, valaciclovir, idoxuridine, inosine,
other precautions are rarely followed in modern UK amantadine: used for simplex and zoster infection
operating suites, since the use of flammable anaesthetic of the skin and mucous membranes.
agents such as cyclopropane and diethyl ether has ceased HIV:
in the UK, and although fires may still occur with other - nucleoside reverse transcriptase inhibitors: e.g.
substances (e.g. alcohol skin cleansers), ignition is usually zidovudine, abacavir, zalcitabine, didanosine,
caused by a high-energy source such as diathermy or stavudine, lamivudine, tenofovir.
laser rather than static electricity. - protease inhibitors: e.g. indinavir, ritonavir, lopi-
navir, nelfinavir, amprenavir, saquinavir. May
Antithrombin III. Cofactor of heparin and natural cause metabolic derangement, including hyper-
inhibitor of coagulation. Often deficient in critical illness lipidaemia and redistribution of body fat, insulin
such as sepsis; hence its investigation as a possible treat- resistance and hyperglycaemia.
ment, though evidence suggests that therapy causes no - non-nucleoside reverse transcriptase inhibitors:
improvement in outcome whilst increasing bleeding e.g. efavirenz, nevirapine. May cause severe skin
complications. A hereditary antithrombin III deficiency reactions and hepatic impairment.
may result in recurrent thromboembolism; patients with cytomegalovirus: ganciclovir, valganciclovir,
the deficiency require higher doses of heparin. foscarnet.
Torossian A, Graf J, Bauhofer (2007). Br Med J; 335: respiratory syncytial virus: tribavirin.
121920 In addition, interferons are used in hepatitis infections.
 Aortic dissection 45

Antoine equation. Describes the theoretical variation often given before aortic clamping, to encour-
of SVP with temperature. Empirically relates SVP to age diuresis.
three constants, derived from experimental data for - GIT ischaemia and infarction may occur if the
each substance. mesenteric arterial supply is interrupted. The
[Louis Charles Antoine (described 1888), French anterior spinal artery syndrome may also occur.
scientist] Attempts to reduce the effects of renal and GIT
ischaemia have also included hypothermia and
ANTS, see Anaesthetists Non-Technical Skills use of metabolic precursors, e.g. inosine.
postoperatively: ICU or HDU. Elective IPPV may
Aortic aneurysm, abdominal. Manifestation of periph- be required. Epidural analgesia is often used.
eral vascular disease, most often due to atherosclerosis. For emergency surgery, prognosis is generally poor;
Usually occurs in males over 60 years old. Often presents 50% die in the prehospital setting, and a further 50%
with abdominal or back pain, or as an asymptomatic, die in hospital. The following are important:
pulsatile abdominal swelling, increasingly detected by wide-bore peripheral venous access (and ideally an
ultrasound screening. May rupture or dissect acutely, arterial line) pre-induction; insertion of invasive
leading to death; leakage is amenable to urgent surgical monitoring should not delay surgery
intervention. Elective surgery is indicated when the preparation and draping of the patient before
diameter of the aneurysm exceeds 5cm. The traditional induction.
open procedure is usually performed via an abdominal availability of blood, O negative if necessary.
incision from xiphisternum to pubis. Alternatives include rapid sequence induction. Etomidate or ketamine is
endoluminal repair, in which a graft is placed via per often used.
cutaneous arterial puncture, or a semi-laparoscopic Abdominal muscular relaxation following induction
method, in which much of the mobilisation is achieved of anaesthesia may result in decreased abdominal tam-
via small incisions before grafting. Preparation should be ponade of the leaking aneurysm, resulting in further
as for the open technique since the risk of proceeding or haemorrhage and hypotension.
of severe, sudden haemorrhage is always present. Endo- Vaughn SB, LeMaire SA, Collard CD (2011). Anesthe-
luminal repair in particular has been shown to reduce siology; 115: 1093102
blood loss, organ dysfunction, hospital stay and early See also, Aortic aneurysm, thoracic; Blood transfusion,
mortality, although mortality at 1 year is thought to be massive; Induction, rapid sequence
the same as after open repair.
Anaesthetic considerations for elective repair: Aortic aneurysm, thoracic. Usually results from aortic
preoperative assessment is particularly directed to dissection. Surgical approach is via left thoracotomy;
the effects of widespread atherosclerosis, i.e. affect- one-lung anaesthesia facilitates surgery. Concurrent
ing coronary, renal, cerebral and peripheral arteries. aortic valve replacement may be required. General
Hypertension is also common. anaesthetic management is as for abdominal aneurysm
perioperatively: repair. Cardiovascular instability may be more dramatic
- monitoring: ECG; direct arterial, central venous because of the proximity of the aortic clamp to the heart,
and possibly pulmonary artery pressure measure- and the reduction of venous return and cardiac output
ment; temperature; urine output. during surgical manoeuvres. Complications include
- at least two large-bore iv cannulae. haemorrhage and infarction of spinal cord, liver, gut,
- warming blanket and warming of iv fluids. Humid- kidneys and heart. Perioperative drainage of CSF is
ification of inspired gases. commonly performed to reduce spinal cord ischaemia.
- cardiovascular responses: Operative techniques include atriofemoral cardiopul-
- hypertension during tracheal intubation. monary bypass, or use of a shunt across the clamped
- increased afterload caused by aortic cross- aortic section.
clamping. Hypertension and left ventricular See also, Aortic aneurysm, abdominal
failure may occur. Anticipatory use of vasodila-
tor drugs may help to reduce hypertension and Aortic bodies. Peripheral chemoreceptors near the
left ventricular strain. aortic arch. Similar in structure and function to the
- reduction of afterload, return of vasodilator carotid bodies. Afferents pass to the medulla via
metabolites from lower part of the body, and the vagus.
possible haemorrhage following aortic unclamp-
ing (declamping syndrome). Myocardial con- Aortic coarctation, see Coarctation of aorta
tractility is reduced by the acidotic venous
return. Anticipatory volume loading before Aortic counter-pulsation balloon pump, see Intra-
unclamping, with termination of vasodilator aortic counter-pulsation balloon pump
therapy before slow controlled release of the
clamp, may reduce hypotension. Bicarbonate Aortic dissection. Passage of blood into the aortic wall,
therapy is guided by arterial acidbase analysis; usually involving the media of the vessel. Degeneration
it is often not required if clamping time is less of this layer is usually caused by atherosclerosis but is
than 11.5h. also seen in Marfans syndrome and EhlersDanlos syn-
- blood loss and effects of massive blood drome. Often associated with hypertension. Dissection
transfusion. may involve branches of the aorta, including the coro-
- postoperative visceral dysfunction: nary arteries. Additionally, rupture into pericardium,
- renal failure may follow aortic surgery; it is pleural cavity, mediastinum or abdomen may occur. May
more likely to occur after suprarenal cross- also follow chest trauma. Classified thus (DeBakey
clamping. Mannitol, furosemide or dopamine is classification):
46 Aortic regurgitation

type I: starts in the ascending aorta, extending prox- enlargement/failure. Echocardiography and cardiac
imally to the aortic valve and distally around the catheterisation are also useful.
aortic arch (least common). Anaesthetic management:
type II: limited to the ascending aorta. antibiotic prophylaxis as for congenital heart
type IIIa: starts distal to the left subclavian artery, disease.
extending proximally and distally, but remaining general principles: as for cardiac surgery/ischaemic
above the diaphragm. heart disease. Myocardial ischaemia and left ven-
type IIIb: starts near the left subclavian artery, tricular failure may occur.
extending distally only, and continuing below the the following should be avoided:
diaphragm (i.e. intra-abdominally). - bradycardia: increases time for regurgitation.
Features: - peripheral vasoconstriction and increased dia-
severe tearing central chest pain; may mimic MI. stolic pressure: increases afterload and therefore
May radiate to the back or abdomen. regurgitation. Peripheral vasodilatation reduces
signs of aortic regurgitation. regurgitation and increases forward flow.
signs of haemorrhage or cardiac tamponade. cardioplegia solution is infused directly into the
progressive loss of radial pulses and CVA may indi- coronary arteries during cardiac surgery, since if
cate extension along the aortic arch. Coronary injected into the aortic root it will enter the
artery involvement may cause MI. Renal vessels ventricle.
may be involved. left ventricular end-diastolic pressure may be much
CXR may reveal a widened mediastinum or pleural greater than measured pulmonary capillary wedge
effusion. Echocardiography, CT/MRI scanning and pressure, if the mitral valve is closed early by the
aortography may be used in diagnosis. regurgitant backflow.
Management: postoperative hypertension may occur.
analgesia. [Alfred de Musset (18101857), French poet; Austin
control of BP, e.g. using vasodilator drugs. Flint (18121886), US physician]
surgery is increasingly employed, especially if the See also, Heart murmurs; Preoperative assessment;
aortic valve is involved, dissection progresses or Valvular heart disease
rupture occurs. Management: as for thoracic aortic
aneurysm. Aortic stenosis. Narrowed aortic valve with obstruction
[Edward Ehlers (18631937), Danish dermatologist; to the left ventricular outflow, resulting in a pressure
Henri Alexandre Danlos (18441912), French derma- gradient between the left ventricle and aortic root. Ini-
tologist; Michael E DeBakey (19082008), US cardiac tially, left ventricular hypertrophy and increased force of
surgeon] contraction maintain stroke volume. Compliance is
Karthikesalingam A, Holt PJ, Hinchliffe RJ, Thompson decreased. Coronary blood flow is decreased due to
MM, Loftus IM (2010). Vasc Endovascular Surg; 44: increased left ventricular end-diastolic pressure and
1659 involvement of the coronary sinuses, whilst left ventricu-
See also, Aortic aneurysm, thoracic lar work increases. Ultimately, contractility falls, with left
ventricular dilatation and reduced cardiac output.
Aortic regurgitation. Retrograde flow of blood through Caused by:
the aortic valve during diastole. Causes left ventricular rheumatic fever: may present at any age (usually
hypertrophy and dilatation, with greatly increased stroke also involves the mitral valve).
volume. Later, compliance decreases and end-diastolic congenital bicuspid valve: usually presents in middle
pressure increases, with ventricular failure. age.
Caused by: degenerative calcification: usually in the elderly.
rheumatic fever; usually affects the mitral value too. Features:
aortic dissection. angina (3040%), syncope, left ventricular failure.
endocarditis (especially acute regurgitation). sudden death.
Marfans syndrome. low-volume slow-rising pulse with reduced pulse
congenital defect (associated with aortic stenosis). pressure (plateau pulse). AF usually signifies coex-
chest trauma, ankylosing spondylitis, rheumatoid istent mitral disease.
disease, syphilis, SLE. ejection systolic murmur, radiating to the neck.
Features: Loudest in the aortic area, with the patient sitting
collapsing pulse with widened pulse pressure (water forward in expiration. The second heart sound
hammer). Bobbing of the head in synchrony with is quiet, with reversed splitting if stenosis is
the pulse (Mussets sign) may occur. severe (due to delayed left ventricular emptying).
early diastolic murmur, high-pitched and blowing. A thrill, fourth sound and ejection click may
Loudest in expiration and with the patient leaning be present.
forward, and heard at the left sternal edge, some- investigations: ECG may show left ventricular
times at the apex. The third heart sound may be hypertrophy; CXR may show ventricular enlarge-
present. A thrill is absent. An aortic ejection murmur ment/failure, possibly with calcification and postste-
is usually present, radiating to the neck; a mid-dia- notic dilatation. Echocardiography and cardiac
stolic mitral murmur may be present due to obstruc- catheterisation are especially useful. The gradient
tion by aortic backflow (Austin Flint murmur). across the valve exceeds 50mmHg in severe steno-
left ventricular failure. sis, falling as left ventricular failure supervenes.
angina is usually late. Normal valve area is 2.63.5cm2; in moderate and
investigations: ECG may show left ventricular severe stenosis the area is reduced to < 1.0 and <
hypertrophy; CXR may show ventricular 0.7cm2 respectively.
 APACHE IV scoring system 47

Anaesthetic management: each physiological parameter in the first 24h after ICU
antibiotic prophylaxis as for congenital heart admission (range 04), age and chronic health (Table 7);
disease. selection of criteria and weightings is based upon the
general principles: as for cardiac surgery/ischaemic opinions of a panel of experts. Definitions of chronic
heart disease. Myocardial ischaemia, ventricular health are more specific than in the original APACHE
arrhythmias and left ventricular failure may occur. system. The assigned weights for all physiological mea-
Percutaneous transcatheter valve replacements are surements, age and chronic health are summated to give
now being performed. an APACHE II score (maximum 71), which is further
the following should be avoided: integrated with the patients diagnosis to calculate the
- loss of sinus rhythm: atrial contraction is vital to predicted mortality.
maintain adequate ventricular filling. APACHE II has been validated in many large centres
- peripheral vasodilatation: cardiac output is rela- and is thought to be a reliable method for estimating
tively fixed, therefore BP may fall dramatically, group outcome amongst ICU patients. Survival rates of
causing myocardial ischaemia. 50% have been reported for an admission score of about
- excessive peripheral vasoconstriction: further 25 points, with 80% mortality for scores above 35 points.
reduces left ventricular outflow. More recently, repeated assessments (i.e. change in
- tachycardia: ventricular filling is impaired and APACHE II score over time) have been used to chart
coronary blood flow reduced. patients progress.
- myocardial depression. Vincent JL, Moreno R (2010). Crit Care; 14: 20715
postoperative hypertension may occur. See also, APACHE III scoring system; APACHE IV
See also, Heart murmurs; Preoperative assessment; Val- scoring system; Mortality/survival prediction on intensive
vular heart disease care unit

Aortocaval compression (Supine hypotension syn-

APACHE III scoring system (Acute physiology, age
drome). Compression of the great vessels against the
and chronic health evaluation). Further development of
vertebral bodies by the gravid uterus in the supine posi-
the APACHE II scoring system, introduced in 1991.
tion in mid- to late-pregnancy. Vena caval compression
Consists of a numerical score (range 0299) reflecting
reduces venous return and cardiac output with a com-
the weights assigned to the variables of three principal
pensatory increase in SVR; this may be symptomless
data categories: physiological measurements, chrono-
(concealed), or associated with hypotension, bradycar-
logical age (the emphasis on age reflected in the reas-
dia or syncope (revealed). Reduced placental blood
signment of the second A in APACHE) and chronic
flow may result from the reduced cardiac output, vaso-
health status. APACHE III uses data from 16 physio-
constriction and compression of the aorta. During
logical measurements. Unlike earlier versions, weight-
uterine contractions, the compression may worsen
ing of physiological abnormalities is derived from
(Poseiro effect). Reduced cardiac output is more likely
multiple logistic regression. Physiological abnormalities
to occur if vasoconstrictor reflexes are impaired, e.g.
have a greater relative importance in the APACHE
during regional or general anaesthesia. May be reduced
III score and predictive equations. The chronic health
by manual displacement of the uterus or tilting the
component has been modified and is based on seven
mother to one side (usually the left is preferred), e.g.
variables referring to the presence or absence of hae-
with a wedge. Up to 45 tilt may be required.
matological malignancies, lymphoma, AIDS, metastatic
See also, Obstetric analgesia and anaesthesia
cancer, immunosuppression, hepatic failure and liver
cirrhosis.
Aortovelography. Use of a Doppler ultrasound probe
APACHE III uses 78 mutually exclusive disease defi-
in the suprasternal notch to measure blood velocity and
nitions to group patients according to the principal
acceleration in the ascending aorta. Used for cardiac
reason for ICU admission. Patients admitted directly
output measurement.
from the operating or recovery room are classified as
operative (surgical), and are further subdivided accord-
APACHE scoring system (Acute physiology and
ing to the urgency of the operation (elective versus
chronic health evaluation). Tool described in 1981 for
emergency). All other patients are classified as non-
assessing the severity of illness of individual patients
operative (medical). The APACHE III score is inte-
and predicting the risk of hospital mortality for groups
grated with the patients diagnosis and source before
of patients treated in ICUs. Consists of two parts: an
ICU to calculate the estimate of hospital mortality and
acute physiology score (APS) and an assessment of the
length of ICU stay. Although its performance is slightly
patients pre-illness health status. Rarely used now
better than that of APACHE II, APACHE III is less
because of acknowledged superiority of other systems,
widely used because the predictive equations it employs
e.g. APACHE II, APACHE III, APACHE IV, SAPS,
are commercially protected.
MPM.
Vincent JL, Moreno R (2010). Crit Care; 14: 20715
Vincent JL, Moreno R (2010). Crit Care; 14: 20715
See also, Mortality/survival prediction on intensive
See also, Mortality/survival prediction on intensive
care unit
care unit

APACHE II scoring system (Acute physiology and APACHE IV scoring system (Acute physiology, age
chronic health evaluation; version II). Revised version and chronic health evaluation). Further development of
of the prototype APACHE scoring system, described in the APACHE III scoring system, published in 2006.
1985. The number of physiological measurements used Derived from a more refined statistical analysis of
in the acute physiology score is reduced to 12, with data from 100 ICUs and > 110000 patients. Like the
weightings allocated for the degree of derangement of APACHE III, it utilises multiple logistic regression and
Table 7 APACHE II scoring system

High abnormal range Low abnormal range

Physiological variable +4 +3 +2 +1 0 +1 +2 +3 +4

Temperature rectal
(C) 41 3940.9 38.538.9 3638.4 3435.9 32.233.9 3031.9 29.9
Mean arterial pressure
(mmHg) >160 130159 110129 70109 5069 49
Heart rate
(ventricular response) 180 140179 110139 70109 5569 4054 39
Respiratory rate
(non-ventilated or ventilated) 50 3549 2534 1224 1011 69 5
Oxygenation: AadO2 or PaO2
(kPa [mmHg])

(a) FIO2 0.5 record AadO2 >67 4766.9 2746.9 <27

(>500) (350499) (300349) (<200)

(b) FIO2 <0.5 record only >9.3 8.19.3 7.38.0 < 7.3
PaO2 (>70) (6170) (5560) (<55)
Arterial pH
7.7 7.67.69 7.57.59 7.337.49 7.257.32 7.157.24 <7.15
Serum sodium
(mmol/l) 180 160179 155159 150154 130149 120129 111119 110
Serum potassium
(mmol/l) 7 66.9 5.55.9 3.55.4 33.4 2.52.9 <2.5
Serum creatinine (mol/l
[mg/100 ml]) (double point >301 170300 130169 50129 <50
score for acute kidney injury) (3.5) (23.4) (1.51.9) (0.61.4) (<0.6)
Haematocrit
(%) 60 5059.9 4649.9 3045.9 2029.9 <20
White blood count
(total/mm3) (in 1000s) 40 2039.9 1519.9 314.9 12.9 <1
Glasgow coma scale (GCS)
Score = 15 minus actual
GCS
A Total acute physiology
score (APS): a sum of
the 12 individual variable
points
Serum HCO3 (venous
mmol/l) (not preferred, 52 4151.9 3240.9 2231.9 1821.9 1517.9 <15
use if no arterial blood
gases)

B Age points C Chronic health points APACHE II SCORE

Assign points to age If the patient has a history of severe organ system insufficiency or is
as follows: immunocompromised, assign points as follows: Sum of:
Age (years) Points (a) for non-operative or emergency postoperative patients +5 points or A APS points
(b) for elective postoperative patients +2 points
44 0 B Age points
Definitions
4554 2 Organ insufficiency or immunocompromised state must have been evident C Chronic health points
5564 5 before this hospital admission and conform to the following criteria:
Liver: Biopsy-proven cirrhosis and documented portal hypertension; episodes Total APACHE II
6574 5
of past upper gastrointestinal bleeding attributed to portal hypertension, or prior
75 6 episodes of hepatic failure/encephalopathy/coma
Cardiovascular: New York Heart Association Class IV (inability to perform
physical activity)
Respiratory: Chronic restrictive, obstructive, or vascular disease resulting in severe
exercise restriction, i.e. unable to climb stairs or perform household duties, or
documented chronic hypoxia, hypercapnia, secondary polycythaemia, severe
pulmonary hypertension (> 40 mmHg), or respiratory dependency
Renal: Receiving chronic dialysis
Immunocompromised: The patient has received therapy that suppresses
resistance to infection, e.g. immunosuppression, chemotherapy, radiation, long-term
or recent high-dose corticosteroids, or has a disease that is sufficiently advanced
to suppress resistance to infection, e.g. leukaemia, lymphoma, AIDS
 Apudomas 49

gasping and possibly spontaneous respiration may be

Table 8 Apgar scoring system
induced by stimulation; the gasp reflex is also active.
Sign Score 0 Score 1 Score 2
During secondary apnoea, active resuscitation and oxy-
genation are required to restore breathing.
Heart rate (beats/min) Absent <100 >100 See also, Cardiopulmonary resuscitation, neonatal; Sleep
Respiratory effort Absent Weak cry Strong cry apnoea
Muscle tone Limp Poor tone Good tone
Reflex irritability No response Some Strong Apnoeahypopnoea index, see Sleep apnoea/
movement withdrawal hypopnoea
Colour Blue, pale Pink body, Pink
blue Apnoeic oxygenation. Method of delivering O2 to the
extremities
lungs by insufflation during apnoea. A catheter is passed
into the trachea, its tip lying at the carina. O2 passed
through it at 46 l/min reaches the alveoli mainly by
mass diffusion, with O2 utilised faster than CO2 is pro-
generates an estimate of predicted mortality and length duced. The technique does not remove CO2, which rises
of ICU stay. at a rate of approximately 0.5 kPa/min (3.8mmHg/min)
Vincent JL, Moreno R (2010). Crit Care; 14: 20715 at normal rates of CO2 production. Hypercapnia may
therefore occur during prolonged procedures.
Apgar scoring system. Widely used method of evaluat- May be used to maintain oxygenation, e.g. during
ing the condition of the neonate, described in 1953. bronchoscopy, or during the diagnosis of brainstem
Points are awarded up to a maximum total of 10 accord- death.
ing to clinical findings (Table 8). Assessments are com- See also, Insufflation techniques
monly performed at 1 and 5min after birth, but may be
repeated as necessary. Colour may be omitted from the Apomorphine hydrochloride. Alkaloid derived from
observed signs to give a maximum score of 8 (Apgar morphine, with a powerful agonist action at both D1 and
minus colour score). D2 dopamine receptors. Used to treat refractory motor
[Virginia Apgar (19091975), US anaesthetist] fluctuations in Parkinsons disease that are inadequately
controlled by levodopa or other dopaminergic drugs.
Apixaban. Orally active direct factor Xa inhibitor, Overdosage causes respiratory depression that is
licensed in adults for DVT prophylaxis after elective hip reversed by naloxone. Causes intense stimulation of the
or knee replacement surgery. More effective than enoxa- chemoreceptor trigger zone, resulting in vomiting. Needs
parin at preventing DVT and PE, with comparable risks to be prescribed with an antiemetic drug. Previously
of haemorrhagic side effects. used as an emetic drug to empty the stomach.
Rapidly absorbed via the oral route (peak plasma Dosage: 330mg/day as sc boluses (max 10mg per
concentration within 34h), with 50% oral bioavailabil- bolus) or 14mg/h sc by infusion, up to 100mg/day
ity. Half-life is ~12h; 70% undergoes hepatic metabo- (changing the injection site every 12h).
lism (by the cytochrome P450 system) to inactive products, Side effects: vomiting, salivation, worsening dyskine-
and 30% is excreted unchanged in urine. Thus, caution sia, sedation, local ulceration.
is required in patients with severe hepatic or renal
failure, or those taking drugs that cause hepatic enzyme Aprepitant. Neurokinin-1 receptor antagonist, licensed
induction/inhibition. Bleeding risk is increased with con- as an antiemetic drug as part of combination therapy
comitant antiplatelet drugs. (with a corticosteroid and a 5-HT3 receptor antagonist)
Dosage: 2.5mg orally bd, starting 1224h after in cancer chemotherapy. Has been studied in PONV.
surgery, for 2 (knee) or 5 (hip) weeks after surgery Dosage: 125mg, 80mg and 80mg orally on 3 succes-
respectively. sive days.
Side effects: nausea, haemorrhage. Side effects: hiccups, fatigue.

APLS, see Advanced Paediatric Life Support Aprotinin. Proteolytic enzyme inhibitor. Inhibits:
plasmin (at low dose, causing reduced fibrinolysis).
Apneustic centre, see Breathing, control of kallikrein (at higher dose, causing reduced
coagulation).
Apnoea. Absence of breathing. Causes are as for trypsin.
hypoventilation. Results in hypercapnia and hypoxae- Intermediate doses cause reduced platelet aggregation.
mia. The rate of onset and severity of hypoxaemia Previously used to reduce perioperative blood loss
are related to the FIO2, FRC and O2 consumption. Thus cardiac surgery; subsequently shown to increase mortal-
preoxygenation delays the onset of hypoxaemia follow- ity in this setting, when compared with tranexamic acid
ing apnoea. In pregnancy, hypoxaemia develops more and aminocaproic acid. No longer available.
quickly, due to reduced FRC and increased O2 Kay WA, Stein CM (2008). N Engl J Med; 358:
consumption. 2398400
Alveolar PCO2 rises at about 0.5 kPa/min (3.8mmHg/
min) when CO2 production is normal. APRV, see Airway pressure release ventilation
In paediatrics, prematurity is a major cause of recur-
rent apnoea. In newborn animals, induced hypoxaemia APS, see Acute physiology score
results in vigorous efforts to breathe, followed by primary
apnoea and bradycardia, then secondary (terminal) Apudomas. Tumours of amine precursor uptake and
apnoea after a few gasps. During primary apnoea, decarboxylation (APUD) cells. APUD cells are present
50 Arachidonic acid

Lipoxygenase
Leukotrienes
Phospholipase
Phospholipids Arachidonic acid Prostaglandins
Cyclo-oxygenase
Steroids Endoperoxides Prostacyclin

Thromboxanes
Indicates inhibition NSAIDs

Fig. 15 Arachidonic acid pathways

in the anterior pituitary gland, thyroid gland, adrenal prolonged when cardiac output is reduced). Useful con-
gland medulla, GIT, pancreatic islets, carotid body and ceptually when comparing different iv induction agents;
lung. Originally thought to arise from neural crest tissue; thus thiopental acts within one armbrain circulation
now thought to be derived from endoderm. They have time, whereas midazolam takes longer.
similar structural and biochemical properties, secreting
polypeptides and amines. They may secrete hormones
that cause systemic disturbances, e.g. insulin, glucagon, Arrhythmias. Deviation from normal sinus rhythm.
Classification:
catecholamines, 5-HT, somatostatin, gastrin and vasoac-
disorders of impulse formation:
tive intestinal peptide.
See also, Carcinoid syndrome; Multiple endocrine adeno- - supraventricular:
matosis; Phaeochromocytoma - sinus arrhythmia, bradycardia and tachycardia.
- SVT.
- sick sinus syndrome.
Arachidonic acid. Essential fatty acid synthesised from
- AF, atrial flutter, atrial ectopic beats.
phospholipids and metabolised by lipoxygenase and
- junctional arrhythmias.
cyclo-oxygenase to leukotrienes and endoperoxides
- VF, ventricular tachycardia, ventricular ectopic
respectively (Fig. 15). Endoperoxides form prostaglan-
beats.
dins, prostacyclin and thromboxanes via separate path-
disorders of impulse conduction:
ways. The pathways are inhibited by corticosteroids and
- slowed/blocked conduction (e.g. heart block).
NSAIDs as shown.
- abnormal pathway of conduction (e.g. Wolff
Arachidonic acid may also undergo peroxidation
ParkinsonWhite syndrome).
during oxidative stress, under the action of free radicals,
Arrhythmias, especially tachycardias, are common in
with the production of isoprostanes.
acute illness. During anaesthesia, ECG monitoring is
mandatory. Bradycardia, junctional rhythm and ventric-
Arachnoiditis. Inflammation of the arachnoid and pial ular ectopic beats (including bigeminy) are common, but
meninges. Has occurred after spinal and epidural anaes- usually not serious.
thesia; antiseptic solutions and preservatives in drug Arrhythmias are more likely with:
solutions (e.g. sodium bisulphite) have been implicated. pre-existing cardiac disease.
Also occurs after radiotherapy, trauma and myelography hypoxaemia and hypercapnia.
with oil-based contrast media. May occur months or acidbase disturbances.
years after the insult. Progressive fibrosis may cause electrolyte abnormalities, especially of potassium,
spinal canal narrowing, ischaemia and permanent nerve calcium, magnesium.
damage. The cauda equina is usually affected, with pain, drugs, e.g. inotropic drugs, antiarrhythmic
muscle weakness and loss of sphincter control. May drugs, theophylline, cocaine. During anaesthesia,
rarely spread cranially. Response to treatment is gener- halothane sensitises the myocardium to
ally poor. catecholamines.
See also, Cauda equina syndrome mechanical stimulation of heart chambers (e.g.
central venous/pulmonary artery catheterisation).
ARAS, see Ascending reticular activating system pacemaker malfunction.
certain diseases, e.g. thyrotoxicosis, subarachnoid
ARDS, see Acute respiratory distress syndrome haemorrhage.
manoeuvres that activate powerful reflex pathways,
Argatroban. Hirudin, studied as an alternative to e.g. during dental surgery, oculocardiac reflex, vis-
heparin. Similar to lepirudin but excreted via the liver as ceral manipulation, tracheobronchial suctioning.
opposed to the kidneys. Half-life is 3060min, thus
requiring administration by continuous infusion.
Arterial blood pressure. The pulsatile ejection of the
stroke volume gives rise to the arterial waveform, from
Arginine vasopressin/argipressin, see Vasopressin
which systolic, diastolic and mean arterial pressures may
be determined.
Armbrain circulation time. Time taken for a sub-
stance injected into an arm vein (traditionally ante- MAP = cardiac output SVR
cubital) to reach the brain. If a bile salt is injected, Thus arterial pressure may vary with changes in cardiac
the time until arrival of the bitter taste at the tongue output (stroke volume heart rate) and vascular
may be measured (normally 1020s; this may be greatly resistance.
 Arterial waveform 51

Control of BP: - continuous arterial tonometry: a pressure trans-

short-term: ducer is positioned over the radial artery, com-
- intrinsic regulatory properties of the heart: Anrep pressing it against the radius. The transducer
effect, Bowditch effect, Starlings law. output voltage is proportional to the arterial BP,
- autonomic pathways involving baroreceptors, which is displayed as a continuous trace. Periodic
vasomotor centre and cardioinhibitory centre. calibration is performed using an automatic oscil-
- hormonal mechanisms: lometric cuff on the arm.
- renin/angiotensin system. [Stephen Hales (16771761), English curate and
- vasopressin. naturalist; Scipione Riva-Rocci (18631937), Italian
- adrenaline and noradrenaline as part of the physician]
sympathetic response. See also, Pressure measurement
intermediate/long-term: renin/angiotensin system,
aldosterone, vasopressin, atrial natriuretic peptide, Arterial cannulation. Used for direct arterial BP mea-
endocannibinoids. surement, and to allow repeated arterial blood gas inter-
See also, Arterial blood pressure measurement; Diastolic pretation. Peripheral cannulation, e.g. of radial and
blood pressure; Hypertension dorsalis pedis arteries, produces higher peak systolic
pressure than more central cannulation, but is usually
Arterial blood pressure measurement. First attempted preferred because of reduced complication rates. Other
by Hales in 1733, who inserted pipes several feet long sites available include brachial, ulnar, posterior tibial
into the arteries of animals. The BP cuff was introduced and femoral arteries. Allens test is sometimes per-
by Riva-Rocci in 1896. Measurement and recording of formed before radial artery catheterisation, but is of
BP were introduced into anaesthetic practice by Cushing doubtful value. Continuous slow flushing with heparin-
in 1901. ised saline (34ml/h) reduces blockage and is preferable
May be direct or indirect:
to intermittent injection. The need for addition of
direct:
heparin has been questioned. Flushing with excessive
- gives a continuous reading; i.e. changes may be volumes of solution may introduce air into the carotid
noticed rapidly. circulation, especially in children.
- provides additional information from the shape of System consists of:
the arterial waveform. cannula: ischaemia, emboli and tissue necrosis are
- requires arterial cannulation. uncommon if a 2022 G parallel-sided Teflon
- requires calibration and zeroing of the monitoring cannula is used, and removed within 2448h.
system. connecting catheter: short and stiff to reduce
- resonance and damping may cause inaccuracy. resonance.
indirect:
transducer placed level with the heart. Requires
- palpation (unreliable). calibration and zeroing.
- mercury or aneroid manometer attached to a electrical monitor and connections. An adequate
cuff: the brachial artery is palpated and the cuff frequency response of less than 40Hz is required.
inflated to 3060 mmHg above the pressure at Bubbles, clots and kinks may cause damping.
which the pulsation disappears. Cuff pressure is Intravascular transducers may be placed within large
released at 23 mmHg/s, and pressure measured arteries, but are expensive and not routinely used.
by detecting pulsation by using the Korotkoff
sounds, a pulse detector or Doppler probe. The
cuff width must be 20% greater than the arms Arterial gas tensions, see Blood gas interpretation
diameter or half its circumference; narrower
cuffs will over-read. Error may arise between dif- Arterial waveform. The shape of the pressure wave
ferent observers. BP should be recorded to the recorded directly from the aorta differs from that
nearest 2 mmHg. recorded from smaller arteries; the peak systolic pres-
- oscillotonometer. sure and pulse pressure increase, and the dicrotic notch
- automatic oscillometry devices that use the same becomes more apparent, peripherally (Fig. 16a). The
cuff for inflation and detection of movement of aorta and large arteries are distended by the stroke
the arterial walls. Systolic pressure and diastolic volume during its ejection; during diastole, elastic recoil
pressures correspond to onset and offset of pulsa- maintains diastolic blood flow (Windkessel effect).
tions respectively; MAP to the maximum oscilla- Smaller vessels are less compliant and therefore less
tion amplitude. Some devices measure only distensible; thus the pressure peaks are higher and travel
systolic and mean pressures while calculating faster peripherally. In the elderly, decreased aortic com-
diastolic pressure. Tend to under-read when pres- pliance results in higher peak pressures.
sures are high and over-read when low. Inconsis- Abnormal waveforms (Fig. 16b):
tencies occur if the cardiac cycle is irregular, e.g. anacrotic: aortic stenosis.
in atrial fibrillation. collapsing:
- plethysmographic methods: a cuff is inflated - hyperdynamic circulation, e.g. pregnancy, fever,
around a finger, and its pressure varied continu- anaemia, hyperthyroidism, arteriovenous fistula.
ously to keep its volume constant, using photo - aortic regurgitation.
metry/oximetry to measure volume. Cuff pressure bisferiens: aortic stenosis + aortic regurgitation.
is proportional to finger arterial pressure; a con- alternans: left ventricular failure.
tinuous display of the arterial pressure waveform excessive damping: e.g. air bubble.
is obtained. May be unreliable if peripheral vas- excessive resonance: e.g. catheter too long or
cular disease is present. flexible.
52 Arteriovenous oxygen difference

Information that may be derived from the normal

(a)
waveform:
Aorta arterial BP.
stroke volume and cardiac output, from the area
under the systolic part of the waveform.
myocardial contractility, as indicated by rate of
pressure change per unit time (dP/dt).
outflow resistance; estimated by the slope of the
Radial artery diastolic decay. A slow fall may occur in vasocon-
striction, a rapid fall in vasodilatation.
hypovolaemia is suggested by a low dicrotic notch,
narrow width of the waveform and large falls in
peak pressure with IPPV breaths.
[Windkessel, German, wind chamber]
See also, Arterial blood pressure; Cardiac cycle; Mean
Dorsalis pedis artery arterial pressure

Arteriovenous oxygen difference. Difference between

arterial and mixed venous O2 content, normally 5ml
O2/100ml blood. Increased with low cardiac ouput or
exercise (high O2 extraction). Decreased with peripheral
arteriovenous shunting, or when tissue O2 extraction is
Time impaired, e.g. sepsis or cyanide poisoning.
(b) See also, Oxygen transport

Anacrotic Arthritis, see Connective tissue diseases; Rheumatoid

arthritis

Articaine hydrochloride (Carticaine). Local anaes-

Collapsing thetic agent containing both ester and amide groups, first
used clinically in 1974. Although used in Canada and
continental Europe for several years, was only intro-
duced in the UK (only in combination with adrenaline)
in 2001. Chemically similar to prilocaine and of similar
potency. Suggested as being particularly suitable for
dental anaesthesia because of its low toxicity (maximal
safe dose 7mg/kg), an ability to diffuse readily through
Bisferiens tissues and its metabolism by blood and tissue esterases.
Elimination half-life is about 1.6h, with 50% excreted
in the urine. Duration of action is about 24h.

Artificial heart, see Heart, artificial

Artificial hibernation, see Lytic cocktail

Alternans Artificial ventilation, see Expired air ventilation; Inter-

mittent positive pressure ventilation

ASA physical status. Classification system adopted by

the American Society of Anesthesiologists in 1941 for
categorising preoperative physical status. Originally with
six categories (the last two referring to emergency cases),
Damped trace a seventh (moribund patient) was later added and in
1962 the ASA adopted a modified five-category system
with the postscript E indicating emergency surgery. A
sixth category was added in 1984/5 in the ASAs relative
Resonance value guide for billing purposes:
1: normal healthy patient.
2: mild systemic disease.
3: severe systemic disease.
4: severe systemic disease that is a constant threat
to life.
5: moribund patient; not expected to survive without
Time
the operation.
Fig. 16 (a) Arterial tracing from different sites. (b) Abnormal arterial 6: declared brain-dead organ donor.
waveforms Extremes of age, smoking and late pregnancy are some-
times taken as criteria for category 2.
 Aspiration pneumonitis 53

Although not an indicator of anaesthetic or operative - hiatus hernia.

risk, there is reasonable correlation with overall outcome. - drugs, e.g. opioid analgesic drugs.
Widely used in clinical trials to standardise fitness of - pregnancy.
patients. However, use of the scoring system may be inefficient lower oesophageal sphincter:
inconsistent between anaesthetists. - hiatus hernia.
See also, Preoperative assessment - drugs, e.g. opioids, atropine.
- pregnancy with heartburn.
Ascending cholangitis, see Cholangitis, acute - presence of a nasogastric tube.
raised intra-abdominal pressure:
Ascending reticular activating system (ARAS). - pregnancy.
Group of neuronal circuits extending from medulla to - lithotomy position.
midbrain, implicated in regulating sleepwake transi- - obesity.
tions and level of cortical arousal. Its main pathway is oesophagus not empty:
the central tegmental tract, conveying impulses to the - achalasia.
hypothalamus and thalamus and thence to the cortex. - strictures.
Any lesion interrupting the ARAS tends to cause coma. - pharyngeal pouch.
Because of close proximity to other brainstem nuclei, ineffective laryngeal reflexes:
lesions often cause cardiovascular or respiratory distur- - general anaesthesia/sedation.
bances. A possible site of action for general anaesthetic - topical anaesthesia.
agents. - neurological disease.
May result in:
Ascites. Excessive free fluid within the abdominal cavity; stimulation of the airway(s), causing breath-
may exceed 2030 l in extreme cases. Initially asymptom- holding, cough, bronchospasm.
atic but features include weight gain, abdominal discom- impaired laryngoscopy if it occurs during induction
fort, fullness in the patients flanks, shifting dullness to of anaesthesia.
percussion and a fluid thrill. May be sufficient to restrict obstruction of the upper airway by solid or semi-
ventilation if gross, via increased intra-abdominal pres- solid matter, causing complete or partial airway
sure or pleural effusions. There may be dependent obstruction.
oedema despite evidence of hypovolaemia. obstruction of smaller airways causing distal
Causes include hepatic failure, cardiac failure, abdom- atelectasis.
inal malignancy, hepatic vein or portal vein occlusion, aspiration pneumonitis. Silent and continuous aspi-
constrictive pericarditis, nephrotic syndrome, malnutri- ration of small amounts of material may cause
tion, pancreatitis, trauma (haemoperitoneum), ovarian repeated episodes of moderate respiratory impair-
hyperstimulation syndrome and bacterial peritonitis. ment, especially in patients with chronically
Analysis of the ascitic fluid may help in the differential impaired protective reflexes. The diagnosis may be
diagnosis, as for pleural effusion. easy to confuse with other conditions, e.g. repeated
Management includes treatment of the underlying small PEs or chest infections.
cause, reducing sodium intake, diuretics (traditionally Measures to reduce risk:
spironolactone and furosemide) and paracentesis. Fluid starvation.
often reaccumulates; if losses are severe and continuous empty stomach:
the fluid may be recirculated into the venous system via - via nasogastric tube.
a simple shunt or following filtration in an extracorpo- - metoclopramide.
real circuit. increase lower oesophageal sphincter tone, e.g. with
Hou W, Sanyal AJ (2009). Med Clin North Am; 93: metoclopramide, prochlorperazine.
80117 rapid sequence induction of anaesthesia.
induction in the lateral or sitting position.
ASCOT, see A severity characterisation of trauma reduction of the severity of aspiration pneumonitis:
e.g. H2 receptor antagonists, antacids, proton pump
Aspiration of gastric contents. Potentially a risk in all inhibitors.
unconscious, sedated or anaesthetised patients, as lower If aspiration occurs:
oesophageal sphincter tone decreases and laryngeal the patient should be placed in the head-down
reflexes are depressed. Aspiration may follow passive lateral position.
regurgitation of gastric contents or vomiting, and is not material is aspirated from the pharynx and larynx,
necessarily prevented by the presence of a cuffed tra- and O2 administered.
cheal or tracheostomy tube. tracheal intubation may be necessary to protect the
Factors predisposing to aspiration: airway, and to allow tracheobronchial suction.
full stomach: further management is as for aspiration
- recent oral intake. In all but extreme emergencies, pneumonitis.
patients are starved of food for 46h before Apfel CC, Roewer N (2005). Curr Opin Anesth; 18:
anaesthesia, although recent evidence suggests 15762
that total fluid restriction may be unnecessary. See also, Induction, rapid sequence
- gastrointestinal obstruction.
- gastrointestinal bleeding. Aspiration pneumonitis (Mendelsons syndrome).
- ileus. Inflammatory reaction of lung parenchyma following
- trauma/shock/anxiety/pain. After trauma, gastric aspiration of gastric contents, originally described in
emptying may be delayed for several hours, espe- obstetric patients. A critical volume of 25ml of aspirate,
cially in children. of pH 2.5, has been suggested to be required to produce
54 Aspirin

the syndrome, although these figures have been disputed Association of Anaesthetists of Great Britain and
since they are based on animal studies. The more acidic Ireland. Founded in 1932 to represent anaesthetists
the inhaled material, the less volume is required to interests and to establish a diploma in anaesthetics (DA
produce pneumonitis. examination). Before this, the London Society of Anaes-
Particulate antacids, e.g. magnesium trisilicate, thetists (founded 1893) had formed the Anaesthetic
may themselves be associated with pneumonitis if Section of the Royal Society of Medicine in 1908, its
aspirated. purpose to advance the science and art of anaesthesia.
The acid gastric contents cause chemical injury and Also publishes the journal Anaesthesia and regular
loss of surfactant. Pneumonitis occurs within hours of guidelines on various aspects of anaesthetic practice.
aspiration, with decreased FRC and pulmonary compli- Has over 10000 members. The Group of Anaesthetists
ance, pulmonary hypertension, shunt and increased in Training (GAT; formerly the Junior Anaesthetists
extravascular lung water. Features include dyspnoea, Group; JAG) has over 3500 members.
tachypnoea, tachycardia, hypoxia and bronchospasm, Helliwell PJ (1982). Anaesthesia; 37: 91323
with or without pyrexia. Crepitations and wheezes may
be heard on chest auscultation. Irregular fluffy densities Asthma. Reversible airways obstruction, resulting from
may appear on the CXR from 8 to 24h. Movement of bronchoconstriction, bronchial mucosal oedema and
fluid into the lungs results in hypovolaemia and hypoten- mucus plugging. Causes high airways resistance, hypox-
sion. The syndrome is often considered part of the aemia, air trapping and increased work of breathing. Two
ARDS spectrum. Differential diagnosis includes cardiac main forms exist:
failure, sepsis, PE, amniotic fluid embolism and fat extrinsic allergic: begins in childhood; may have an
embolism. associated family history of atopy (e.g. hayfever,
Treatment is mainly supportive, with O2 therapy, eczema), is episodic and tends to respond to therapy.
bronchodilator drugs, and removal of aspirate and secre- intrinsic: adult onset; no allergic family history.
tions by physiotherapy and suction. Bronchoscopy may Nasal polyps are common and exacerbations occur
be required to remove large particulate matter. Second- with infection and aspirin. Less responsive to
ary infection may occur, and prophylactic antibacterial treatment.
drugs are sometimes given, although this is controversial. Patients bronchi show increased sensitivity to triggering
Use of high-dose corticosteroids is declining but inhaled agents, constricting when normal bronchi may not.
corticosteroids may be beneficial for treatment of bron- During anaesthesia, surgical stimulation or stimulation
chospasm. CPAP or IPPV with PEEP may be required of the pharynx or larynx may cause bronchospasm.
in severe cases. Mortality is high. Chronic drug treatment:
[Curtis L Mendelson (19132002), US obstetrician] 2-adrenergic receptor agonists, e.g. salbutamol.
Marik PE (2001). N Engl J Med; 344: 66571 aminophylline and related drugs.
corticosteroids.
Aspirin. Acetylsalicylic acid, synthesised in the early sodium cromoglicate.
1900s in Germany. Commonest salicylate in use. Uses, anticholinergic drugs, e.g. ipratropium.
effects and pharmacokinetics as for salicylates. Used leukotriene receptor antagonists.
widely as an antiplatelet drug. Should not be given to Acute severe asthma:
children under 16 years of age, and inadvisable in ado- signs of a severe attack:
lescents, because of the risk of Reyes syndrome. - inability to talk.
Dosage: - tachycardia > 110 beats/min.
analgesia: 300900mg orally 46-hourly, up to a - tachypnoea > 25 breaths/min.
total of 4g daily. - pulsus paradoxus > 10mmHg.
secondary prevention of thrombotic cerebrovascu- - peak expiratory flow rate (PEFR) < 50% of pre-
lar or CVS disease: 75100mg orally od. dicted normal.
acute coronary syndromes: 150300mg orally od. signs of life-threatening attack:
following cardiac surgery: 75100mg orally od. - silent chest on auscultation.
Over-the-counter sale of 300mg tablets/capsules in the - cyanosis.
UK is limited to packs of 32 (packs of 100 tablets/cap- - bradycardia.
sules may be purchased from pharmacists in special - exhausted, confused or unconscious patient.
circumstances). arterial blood gas measurement: hypoxaemia,
See also, Salicylate poisoning largely from V/Q mismatch, may be severe. It may
worsen following bronchodilator treatment due to
Assisted ventilation. Positive pressure ventilation sup- increased dead space and mismatch. Arterial PCO2
plementing each spontaneous breath made by the V /Q is usually reduced because of hyperventilation,
patient. May be useful during transient hypoventilation but may rise in severe cases, indicating requirement
caused by respiratory-depressant drugs in spontaneously for IPPV. There is poor correlation between FEV1
breathing anaesthetised patients. Also used in ICU, e.g. and arterial PCO2.
in weaning from ventilators. other problems: pneumothorax, infection, dehydra-
Different modes: tion. Hypokalaemia is common due to corticoste-
assist mode ventilation: delivery of positive pres- roids, catecholamine administration and respiratory
sure breaths triggered by inspiratory effort. alkalosis.
assist-control mode ventilation: assist mode ventila- general medical and ICU management:
tion against a background of regular IPPV. - first-line therapies:
inspiratory pressure support. - humidified O2 with high FIO2 is required.
inspiratory volume support. - nebulised salbutamol 2.55mg or terbutaline
proportional assist ventilation. 510mg 4-hourly (may be given continuously
 Atenolol 55

in severe asthma); iv salbutamol 250g may Tubocurarine and atracurium may cause hista-
be given, followed by 520g/min, although mine release, whilst vecuronium, pancuronium,
in general, iv administration of 2-agonists is rocuronium and fentanyl do not.
thought to have no advantage over the inhaled - although many opioid analgesic drugs may release
route. histamine, they are commonly given. For patient-
- nebulised ipratropium 0.10.5mg is tradition- controlled analgesia fentanyl may be a good
ally alternated with 2-agonists, although in alternative if morphine has previously provoked
modern practice they are often combined in the bronchospasm.
same nebuliser. - tracheal intubation and the presence of a tracheal
- corticosteroids; e.g. hydrocortisone 100200mg tube may cause bronchospasm. This may be
4-hourly iv, or by infusion. reduced by spraying the larynx and trachea with
- second-line therapies: lidocaine; iv lidocaine, 12mg/kg, has been used
- magnesium sulphate 1.22.0g iv over 20min as to reduce the incidence of bronchospasm on intu-
a single dose has recently been introduced to bation and extubation. Alternatively, techniques
UK guidelines. avoiding tracheal intubation may be employed.
- aminophylline 36mg/kg iv, followed by 0.5mg/ - -adrenergic receptor antagonists should be
kg/h (with caution if the patient is already avoided.
taking theophyllines). - dehydration should be avoided.
- diethyl ether, halothane, ketamine and adrena- Sellers WFS (2013). Br J Anaesth; 110: 18390
line have been used in resistant cases. See also, Bronchodilator drugs
supportive therapies:
- antibacterial drugs, physiotherapy, iv rehydration. Astrup method. Used for the analysis of blood acid
- IPPV: base status. The pH of a blood sample is measured, and
- intubation may provoke cardiac arrhythmias in the sample equilibrated with two gases of different CO2
severe hypoxia/hypercapnia. concentration, usually 4% and 8%. pH is measured after
- sedation and muscle relaxation are required to each equilibration, and the standard bicarbonate and
aid IPPV. base excess calculated. The original CO2 tension is cal-
- high inflation pressures risk barotrauma and culated from the pH of the original sample, using the
decreased cardiac output. Siggaard-Andersen nomogram.
- a flow generator ventilator is required, to ensure [Poul Astrup (19152000), Danish chemist]
adequate tidal volumes.
- because expiration may not be complete before Asystole. Absent cardiac electrical activity. Common in
the next breath, FRC increases with gas trap- cardiac arrest due to hypoxia or exsanguination, espe-
ping, usually reaching equilibrium after 510 cially in children. Must be distinguished from accidental
breaths. Despite the resultant auto-PEEP ECG disconnection. Management: as in CPR.
(intrinsic PEEP) and traditional teaching that
PEEP should not be used in asthma because of Atelectasis. Collapse of lung tissue affecting all or part
the increased risk of barotrauma, PEEP has of the lung. Caused by inadequate aeration of alveoli,
been applied to good effect and may actually with subsequent absorption of gas. The latter occurs
reduce FRC by an unknown mechanism. because the total partial pressure of dissolved gases in
- adequate ventilation may be difficult; permis- venous blood is less than atmospheric pressure; gas
sive hypercapnia is often practised. Gas trapped behind obstructed airways, e.g. by secretions, is
exchange may be improved by a slow inspira- therefore slowly absorbed. Nitrogen, being relatively
tory flow rate, low minute volume (68 l/min) insoluble in blood, tends to splint alveoli open when
and low ventilatory rate (1214 breaths/min). breathing air. Absorption atelectasis may follow high
Expiration should occupy at least 50% of the FIO2, since O2 is readily absorbed into the blood and the
ventilatory cycle duration. nitrogen has been washed out of the alveoli.
bronchoalveolar lavage has been used. Has been shown by CT scanning to occur in depen-
Anaesthetic management of patients with asthma: dent parts of the lung during anaesthesia in normal
preoperatively: patients, contributing to impaired gas exchange. May
- preoperative assessment is directed towards also follow accidental endobronchial placement of a tra-
respiratory function, frequency and severity cheal tube. It may persist postoperatively, particularly in
of attacks, and drug therapy (including patients with poor lung function and sputum retention,
corticosteroids). and when chest movement is reduced, e.g. by pain after
- investigations: CXR; PEFR/spirometry (espe- upper abdominal surgery or fractured ribs. Hypoxaemia,
cially pre- and postbronchodilator); arterial blood tachypnoea and tachycardia result, with reduced air
gas interpretation. entry to the affected area of lung that may then become
- premedication: nebulised bronchodilators may be infected. Treatment of atelectasis includes physiother-
given with premedication. Preoperative physio- apy, incentive spirometry, humidification, intermittent
therapy may also be useful. Steroid cover may be lung inflations using a ventilator, CPAP and, occasion-
required. ally, bronchoscopy.
perioperatively: Duggan M, Kavanagh BP (2005). Anesthesiology; 102:
- regional anaesthesia is often suitable. 83854
- thiopental has been implicated as causing
bronchospasm, although this is controversial. Pro- Atenolol. Water-soluble -adrenergic receptor antago-
pofol, etomidate and ketamine are suitable alter- nist, available for oral and iv administration. Relatively
natives. Volatile agents cause bronchodilatation. selective for 1-receptors. Uses and side effects are as for
56 Atherosclerosis

-adrenergic receptor antagonists in general. properties but causes less histamine release). At body
Dosage: temperature and pH, undergoes spontaneous Hofmann
hypertension: 50mg/day orally; angina and arrhyth- elimination to laudanosine. Up to 50% ester hydrolysis
mias: 50100mg/day. also occurs. Often considered the drug of choice in renal
acute arrhythmias: 150g/kg iv over 20min, or hepatic impairment. Its cardiostability, low risk of
repeated 12-hourly as required. accumulation and spontaneous reversal are also advan-
after acute MI: 510mg slowly iv, then 50mg iv tages. Stored at 28C; at room temperature, activity
after 15min and 12h, then 100mg/day orally. decreases by only a few per cent per month.
perioperatively in patients at risk from ischaemic
heart disease: 510mg iv before surgery, then 50 Atrial ectopic beats. Impulses arising from abnormal
100mg orally during the hospital stay (up to a pacemaker sites within the atria. The P waves are usually
week). abnormal, and arise early in the cardiac cycle. They are
Side effects: as for -adrenergic receptor usually conducted to the ventricles in the normal way,
antagonists. producing normal QRS complexes (Fig. 17). Very early
ectopics may produce abnormal QRS complexes,
Atherosclerosis. Disease involving the intima of because the ventricular conducting system may still be
medium and large arteries, resulting in fat accumulation refractory when the ectopic impulse reaches it. The
and fibrous plaques that narrow the vessel lumen. resultant QRS may then be mistaken for a ventricular
Further stenosis may follow thrombosis and haemor- ectopic beat. Several ectopic sites may give rise to the
rhage. Thought to be at least partly inflammatory in aeti- wandering pacemaker, producing differently shaped P
ology, although the precise roles of proinflammatory and waves with differing PR intervals. Rarely require
prothrombotic mediators are uncertain. Causes isch- treatment.
aemic heart disease, cerebrovascular disease and periph- See also, Arrhythmias; Electrocardiography
eral arterial insufficiency, especially in the legs. Thus
patients with peripheral vascular disease frequently Atrial fibrillation (AF). Lack of coordinated atrial con-
have occult atherosclerotic disease involving other traction, resulting in impulses from many different parts
organs. of the atria reaching the atrioventricular (AV) node in
A rigid arterial tree results in a high systolic arterial quick succession, only some of which are transmitted.
BP with normal diastolic pressure, a common finding in Ventricular response may be fast, resulting in inadequate
the elderly, since virtually all elderly patients have some ventricular filling, and reduced stroke volume and
atherosclerosis. cardiac output. Cardiac failure, hypotension and sys-
Hansson GK (2005). N Engl J Med; 352: 168595 temic emboli from intra-atrial thrombus may occur.
Features:
ATLS, see Advanced Trauma Life Support irregularly irregular pulse. Ventricular rate depends
upon the conducting ability of the AV node; usually
Atmosphere. Unit of pressure. One atmosphere equals rapid, the ventricular activity is slow and regular if
760mmHg (101.33 kPa), the average barometric pres- complete heart block exists.
sure at sea level. no P waves on the ECG (Fig. 18).
See also, Bar May be idiopathic or caused by:
ischaemic heart disease (most common cause),
ATN, Acute tubular necrosis, see Renal failure including acute MI.
mitral valve disease.
Atopy. Tendency to asthma, hayfever, eczema and other hyperthyroidism.
allergic conditions, including adverse drug reactions. Suf- PE.
ferers are sensitive to antigens that usually cause no cardiomyopathy.
reaction in normal subjects. May be familial. IgE levels thoracic surgery/central venous cannulation.
may be raised. Drugs associated with histamine release acute hypovolaemia.
should be avoided. Treatment:
drug therapy is aimed at reducing AV node conduc-
Atorvastatin, see Statins tion and ventricular rate. Sinus rhythm may be
restored. Examples include digoxin, -adrenergic
ATP, see Adenosine triphosphate and diphosphate receptor antagonists, verapamil, diltiazem, amioda-
rone and disopyramide.
ATPD and ATPS. Ambient temperature and pressure, cardioversion if haemodynamically unstable or
dry; and ambient temperature and pressure, saturated recent onset (< 3 days).
with water vapour. Used for standardising gas volume catheter ablation of the AV node or atrial foci
measurements. where AF originates; largely reserved for cases
intolerant of or refractory to other treatment.
Atracurium besylate. Non-depolarising neuromuscular anticoagulation should be considered if AF has per-
blocking drug, first used in 1980. A bisquaternary nitrog- sisted for more than 23 days, especially before car-
enous plant derivative. Initial dose: 0.30.6mg/kg. Intu- dioversion. In chronic AF, aspirin or warfarin is
bation is possible approximately 90s after a dose of used depending on the absence or presence of other
0.5mg/kg. Effects last 2030min. Supplementary dose: risk factors, e.g. age > 75, diabetes, hypertension,
0.10.2mg/kg. Has been given by iv infusion at 0.3 previous CVA.
0.6mg/kg/h. May cause histamine release, usually mild, Somasundaram K, Ball J (2013). Anaesthesia; 68 s1:
but severe reactions have been reported (an isomer of 84101
atracurium, cisatracurium, has similar neuromuscular See also, Arrhythmias
 Atrioventricular dissociation 57

Actions:
increases GFR, and urinary sodium and water
excretion. Decreases reabsorption of sodium ions in
the proximal convoluted tubule of the nephron.
relaxes vascular smooth muscle; renal vessels are
more sensitive than others.
inhibits plasma renin activity and aldosterone
Fig. 17 Example of an atrial ectopic beat (arrowed)
release.
releases free fatty acids from adipose tissue.
Thought to act via specific receptors. ANP and
related peptides have been investigated as markers
of cardiac failure and myocardial ischaemia. Inhibi-
tion of their breakdown has been investigated as
possible therapy in hypertension, cardiac failure
and myocardial ischaemia, whilst infusion of
ANP has been investigated for its renal protective
effect in oliguric acute tubular necrosis. A synthetic
ANP is available for treatment of advanced heart
failure.
de Lemos JA, McGuire DK, Drazner MH (2003). Lancet;
Fig. 18 Atrial fibrillation
362: 31622
See also, B-type natriuretic hormone

Atrial septal defect (ASD). Accounts for up to 15% of

congenital heart disease.
Normal septal development is as follows:
the septum primum grows down from the top of the
F F F F heart, separating the right and left halves of the
common atrium.
the foramen secundum appears in its upper part.
the septum secundum grows down to the right

F, flutter waves
of the septum primum, usually just covering the
foramen secundum.
Fig. 19 Atrial flutter the foramen ovale is formed from the foramen
secundum and overlapping septum secundum.
Features of ASD:
pulmonary flow murmur with or without a tricuspid
murmur, increasing on inspiration. Fixed splitting of
Atrial flutter. Arrhythmia resulting from rapid atrial the second heart sound.
discharge (usually 300/min), caused by a re-entrant right ventricular hypertrophy, right bundle branch
circuit within the atria and usually initiated by an atrial block and right axis deviation may be present.
ectopic beat. May be paroxysmal or sustained. Com- pulmonary hypertension.
monly occurs with 4:1 or 2:1 atrioventricular block; i.e. Over 90% of defects are secundum ASDs; they may
with ventricular rates 75/min or 150/min respectively. present in later life with pulmonary hypertension, right-
Features: sided cardiac failure, Eisenmengers syndrome and AF.
usually regular pulse. Suturing of the defect is usually quick if a patch is not
saw-tooth flutter (F) waves on the ECG (Fig. 19); required.
with 2:1 block the second flutter wave of each pair Ostium primum defects may involve the atrioven-
may be hidden in the QRS or T waves, leading to tricular valves; they often present early. Repair is more
the incorrect diagnosis of sinus tachycardia. Carotid complicated. Valve regurgitation and conduction defects
sinus massage may slow the ventricular rate enough may follow surgery.
to reveal rapid flutter waves. Anaesthetic management: as for congenital heart
Causes: as for AF. disease and cardiac surgery.
Treatment: See also, Heart murmurs; Preoperative assessment
aimed at restoring sinus rhythm: cardioversion
using low-energy (2550 J), rapid atrial pacing, and Atrial stretch receptors, see Baroreceptors
drug therapy as for AF.
digoxin may convert flutter to AF. Atrioventricular block, see Heart block
See also, Cardiac pacing
Atrioventricular dissociation. Unrelated ventricular
Atrial natriuretic peptide (ANP). Hormone isolated and atrial activity. The term is usually reserved for when
from myocytes of the right atrium; similar peptides are the ventricular rate exceeds the atrial rate, to distinguish
present in the cardiac ventricles and vascular endothe- it from complete heart block (in which the reverse
lium. Released in response to atrial stretching, e.g. in occurs). Ventricular activity may arise from the atrioven-
fluid overload (i.e. not to increased atrial pressure tricular node or an ectopic pacemaker. It may occur
per se), sympathetic stimulation and presence of angio- during bradycardia as an escape mechanism, and during
tensin II. anaesthesia. On the ECG, P waves and QRS complexes
58 Atrioventricular node

of a particular aspect of practice (e.g. reducing

PONV).
assessment of how that practice is carried out
P P P (e.g. measuring nausea scores, recording usage of
antiemetics).
judgement by peer review whether certain stan-
dards are being met (e.g. deciding in advance that
Fig. 20 Atrioventricular dissociation
more than 10% of patients suffering severe nausea
is unacceptable. National standards exist for many
areas of practice, e.g. issued by professional bodies).
are unrelated, the former more widely spaced than the identification of areas for improvement where prac-
latter (Fig. 20). Rarely clinically significant. tice is substandard (e.g. prophylactic antiemetics
See also, Arrhythmias not being given for high-risk surgery).
addressing the deficiency (e.g. education, institution
Atrioventricular node, see Heart, conducting system of protocols).
reassessment after a period to check that practice
Atropine sulphate. Anticholinergic drug (competitive has improved and standards are being met; i.e.
antagonist at muscarinic acetylcholine receptors), an closing the audit loop. In order to be effective,
ester of tropic acid and tropine. Found in deadly night- specific audits require repeating regularly.
shade. Used to reduce muscarinic effects of acetylcho- Audit (is the correct management being used?) should
linesterase inhibitors, for premedication and in the be distinguished from research (what is the correct man-
treatment of bradycardia. Has also been used as an anti- agement?), although both may involve similar methods
spasmodic drug and as a mydriatic. of data collection and analysis.
Effects: Anaesthetic/ICU applications include monitoring:
CVS: organisation of services, e.g. appropriate allocation
- tachycardia (may cause bradycardia initially; of trainees, cancellation of surgery because of insuf-
thought to be due to central vagal stimulation). ficient staff, leave allocations and costs.
- cutaneous vasodilatation (cause unknown). management of patients drug usage and clinical
CNS: policies.
- excitement, hallucinations and hyperthermia, complications, e.g. unplanned admission to ICU,
especially in children. specific events. Methods include analysis of cur-
- antiparkinsonian effect. rently held data (e.g. anaesthetic record-keeping)
RS: or specific studies into particular aspects of care
- bronchodilatation and increased dead space. (e.g. National Confidential Enquiry into Patient
- reduced secretions. Outcome and Death and Confidential Enquiries
GIT: into Maternal Deaths). Audit is now a mandatory
- reduced salivation. part of medical practice in the UK, despite contro-
- reduced motility. versy over its value in relation to costs.
- reduced secretion. See also, Quality assurance; Risk management
- reduced lower oesophageal sphincter tone.
others: Auriculotemporal nerve block, see Mandibular nerve
- reduced sweating. blocks
- mydriasis and cycloplegia.
- reduced bladder and ureteric tone. Auscultatory gap. During auscultatory arterial BP
Standard doses: measurement, the Korotkoff sounds may disappear at
0.10.6mg increments iv for bradycardia. A larger a point below systolic pressure, to reappear at a
maximum dose (3mg) is no longer recommended lower pressure before disappearing again at diastolic
for the management of asystole/pulseless electrical pressure. The significance is unknown, but it emphasises
activity. the importance of palpating the artery before ausculta-
0.30.6mg im as premedication; 0.010.02mg/kg tion, in order to ensure that the absence of sounds is
for children. because the pressure is above systolic, and not within the
0.010.02mg/kg when given with acetylcholinester- silent gap.
ase inhibitors.
0.61.2mg orally at night in irritable bowel disease, Australia antigen, see Hepatitis
diverticulitis.
Atropine should be avoided in pyrexial patients, particu- Autoimmune disease. Characterised by activation of
larly children. the immune system, directed against host tissue. May
Applied directly to the eye, it may provoke closed- involve antibody production, attacking intracellular,
angle glaucoma in susceptible patients, the iris obstruct- extracellular or cell membrane antigens. Pathogenesis is
ing drainage of aqueous humour when the pupil is not fully understood, but involves imbalance of suppres-
dilated. sor and helper T lymphocyte cell function. May affect
See also, Anticholinergic drugs, for comparison with specific organs, e.g. adrenocortical insufficiency, or many
hyoscine and glycopyrronium; Tracheal administration tissues, e.g. connective tissue diseases.
of drugs May follow triggering agents, e.g.:
drugs: SLE-like syndrome after procainamide or
Audit. Systematic process by which medical practice is hydralazine therapy, haemolytic anaemia after
assessed and improved. Involves the following steps: -methyldopa therapy.
 Avogadros hypothesis 59

infection: haemolysis following mycoplasma pneu- Autonomic neuropathy. May be:

monia, rheumatic fever following streptococcal central:
infection. Viral infections are often implicated. - primary, e.g. progressive autonomic failure (Shy
Genetic factors are also important, hence the association Drager syndrome).
between certain diseases and HLA types, e.g. myasthenia - secondary to CVA, infection or drugs.
gravis, thyroid disease, pernicious anaemia and vitiligo. peripheral, e.g. due to diabetes mellitus, amyloido-
More than one of these diseases may occur in the same sis, autoimmune diseases, porphyria, GuillainBarr
patient, suggesting common mechanisms. Testing for syndrome, myasthenic syndrome.
autoantibodies may be useful in the diagnosis and treat- Results in postural hypotension, cardiac conduction
ment of these conditions. defects, bladder dysfunction and GIT disturbances,
including delayed gastric emptying. Diabetics with auto-
nomic neuropathy have increased risk of perioperative
Autologous blood transfusion, see Blood transfusion, cardiac or respiratory arrest.
autologous Useful bedside tests of autonomic function include:
pulse and BP measurement lying and standing; a

Autonomic hyperreflexia. Increased sensitivity of sym- postural drop of over 30mmHg indicates auto-
pathetic reflexes in patients with spinal cord injury nomic dysfunction.
Valsalva manoeuvre.
above T5/6. Cutaneous or visceral stimuli below the level
effect of breathing on pulse rate (normally slows on
of the lesion may result in mass discharge of sympathetic
nerves, causing sweating, vasoconstriction and hyper expiration).
sustained hand grip (normal response: tachycardia
tension, with high levels of circulating catecholamines.
Baroreceptor stimulation results in compensatory brady and over 15mmHg increase in diastolic BP).
cardia. Distension of hollow viscera, especially of the ECG is useful for the latter two tests. Other tests
bladder, is a potent stimulus. It may also occur during include observation of sweating and pupillary
abdominal surgery and labour. Onset of susceptibility is responses, and catecholamine studies.
usually within a few weeks of injury. Patients with autonomic neuropathy are at risk of devel-
In anaesthesia, both general and regional techniques oping severe hypotension during anaesthesia, particu-
have been used; spinal anaesthesia has been suggested larly with spinal or epidural anaesthesia, and IPPV. They
as the technique of choice, if appropriate. Control of may also show reduced response to hypoglycaemia.
hypertension has been successfully achieved with vaso- There may be increased risk of aspiration of gastric
dilator drugs. Hypotension may also occur. contents.
[George Shy (19191967) and Glenn Drager (1917
1967), US neurologists]
Autonomic nervous system. System that regulates See also, Peripheral neuropathy
non-voluntary bodily functions, by means of reflex path-
ways. Efferent nerves contain medullated fibres that Autoregulation. Mechanism by which an organ, e.g.
leave the brain and spinal cord to synapse with non- kidney, brain, heart, maintains a constant blood flow
medullated fibres in peripheral ganglia. Closely related despite variations in the mean arterial pressure perfus-
to the CNS, anatomically and functionally; thus, sensory ing the organ.
input may affect autonomic activity and also conscious- Several theories exist:
ness and voluntary behaviour, e.g. pain, temperature and myogenic theory: postulates that muscle in the
sensation. vessel wall contracts as intraluminal pressure
Divided into the parasympathetic and sympathetic
increases, thus maintaining wall tension by reducing
nervous systems, on the basis of anatomical, pharma- radius, in accordance with Laplaces law.
cological and functional differences (Fig. 21): metabolic theory: argues that vasodilator substances
parasympathetic: (nitric oxide, hydrogen ions, CO2, adenosine) accu-
- output in cranial and sacral nerves; ganglia near mulate in the tissues at low blood flow; the resultant
to target organs. vasodilatation results in increased flow and the
- acetylcholine released as a transmitter at pre- and vasodilator metabolites are washed away.
postganglionic nerve endings. tissue theory: states that, as blood flow increases, the
- increases GIT activity, and reduces arousal and vessels are compressed by the increased amount of
cardiovascular activity. interstitial fluid that has accumulated. Usually
sympathetic: occurs at MAP of 60160mmHg in normotensive
- output in thoracic and lumbar segments of subjects; it may be impaired by volatile anaesthetic
the spinal cord; ganglia form the sympathetic agents, vasodilator drugs or disease states (e.g. cere-
trunk. bral blood flow in head injury).
- acetylcholine released at preganglionic nerve See also, Systemic vascular resistance
endings, adrenaline and noradrenaline (in general)
at postganglionic nerve endings.
Autotransfusion, see Blood transfusion, autologous
- increases arousal and cardiovascular activity
(fight or flight reaction), reduces visceral
activity. Average, see Mean
Some organs receive only sympathetic innervation (e.g.
piloerector muscles, adipose tissue, juxtaglomerular Avogadros hypothesis. At constant temperature and
apparatus), others only parasympathetic innervation pressure, equal volumes of all ideal gases contain the
(e.g. lacrimal glands); most are under dual control. same number of molecules. One mole of a substance at
See also, Acetylcholine receptors standard temperature and pressure contains 6.023 1023
60 AVP

Parasympathetic Sympathetic

Eye III Midbrain

Ciliary ganglion

Submandibular, sublingual
VII
+ lacrimal glands
Medulla
Pterygopalatine +
submandibular ganglia

Lungs, larynx,
IX
tracheobronchial tree
Otic ganglion
Eye, salivary glands
Heart X

Parotid gland T1
Heart, lungs, larynx, tracheobronchial tree
Proximal GIT

T4
T5

Coeliac ganglion
Proximal GIT + blood vessels
Adrenal medulla
Kidney
T12 Superior mesenteric
L1
ganglion
Distal GIT + blood vessels
bladder, genitalia
L3 Inferior mesenteric
ganglion

Paravertebral
sympathetic
Distal GIT
chain
S2
Bladder S3
S4
Genitalia

Fig. 21 Autonomic nervous system

particles (Avogadros number), and one mole of a gas painful (P) stimuli, or unresponsive (U). Easier and
occupies 22.4 litres. faster to perform than other more complicated trauma
[Count Amedeo Avogadro (17761856), Italian scales and systems such as the Glasgow coma scale.
scientist]
Awareness. Postoperative recall of events occurring
AVP, Arginine vasopressin, see Vasopressin during general anaesthesia. Ranges from being fully con-
scious and in pain intraoperatively with explicit recall,
AVPU scale. Simple scale of responsiveness, commonly to non-specific postoperative psychological symptoms
used to assess the neurological status of patients, e.g. with only vague recollections or dreams. Signs of inad-
following trauma, cardiac arrest. Records whether the equate anaesthesia (tachycardia, sweating, hypertension,
patient is alert (A), responsive only to vocal (V) or large pupils, lacrimation) may not be present. Quoted
 Azumolene sodium 61

incidence is 0.010.2%; its rarity and diagnostic variabil- pulsation in the axilla. The medial cutaneous nerve
ity contribute to the wide range. Importantly, in most may be at risk with this approach.
cases patients do not report awareness while in the
recovery room. Ayres T-piece, see Anaesthetic breathing systems
Associated with significant psychological and psychi-
atric morbidity, including post-traumatic stress disorder.
Azathioprine. Non-specific cytotoxic drug, used as an
Postoperative interview or hypnosis may reveal recall
immunosuppressive drug in organ transplantation,
of pain, events, comments or specific messages played
myasthenia gravis and inflammatory disease. Metabo-
to patients. The significance of non-conscious recall is
lised to mercaptopurine.
unknown. Dose: 35mg/kg orally/iv initially; maintenance
Risk factors and associations:
14mg/kg per day.
previous history of awareness under anaesthesia.
Side effects: myelosuppression, fever, rigors, arthral-
administration of low doses (< 0.8 MAC) of volatile
gia, myalgia, interstitial nephritis, liver toxicity. Moni-
anaesthetic agents (e.g. in caesarean section, major
toring of therapy requires regular full blood counts.
trauma, cardiac surgery or anaesthesia for mori-
The iv preparation is alkaline and very irritant.
bund patients), especially in combination with neu-
romuscular blocking drugs.
reliance on iv agents given by bolus without inhala- Azeotrope. Mixture of two or more liquids whose com-
tional agents, leading to awareness between doses; ponents cannot be separated by distillation. The boiling
e.g. during bronchoscopy, or repeated attempts at point of each is altered by the presence of the other
difficult intubation. substance; thus the components share the same boiling
equipment failure. point, and the vapour contains the components in the
Use of high-dose opioid drugs may not prevent aware- same proportions as in the liquid mixture. Halothane
ness, although the patient may not feel pain. and ether form an azeotrope when mixed in the ratio of
May be reduced by: 2:1 by volume.
ensuring adequate administration of anaesthetic
agent, including use of end-expiratory gas monitor- Azidothymidine, see Zidovudine
ing (with alarms enabled).
thorough checking of equipment. Azithromycin. Macrolide, similar to erythromycin but
avoidance of neuromuscular blocking drugs. less active against Gram-positive bacteria and more
use of amnesic drugs, e.g. benzodiazepines. active against certain Gram-negative ones. Used in
use of cerebral function monitors (e.g. bispectral respiratory and other infections and as an antituber
index monitor). culous drug in resistant TB. Extensively tissue-bound.
All cases of possible or confirmed awareness should be Dosage: 500mg orally od for 3 days.
adequately followed up, with counselling and psychiatric Side effects: as for clarithromycin.
referral if indicated.
Mashour GA, Orser BA, Avidan MS (2011). Anesthesi-
AZT, Azidothymidine, see Zidovudine
ology; 114: 121833
See also, Anaesthesia, depth of; Isolated forearm tech-
nique; Traumatic neurotic syndrome Aztreonam. Monocyclic -lactam (monobactam) active
against Gram-negative aerobes (including Pseudomo-
Axillary venous cannulation. Route of central venous nas) but not Gram-positive or anaerobic organisms; thus
cannulation, usually used when alternative sites are reserved for specific (as opposed to blind) therapy.
unsuitable. Advantages include venous puncture outside Resistant to some, but not all, -lactamases. Synergistic
the ribcage, thus reducing the risk of pneumothorax, and with aminoglycosides against many bacteria.
Dosage: 0.51.0g iv over 35min or by deep im injec-
the ability to compress the axillary artery directly if acci-
dentally punctured. A number of techniques have been tion tds/qds (or 2g iv bd); in severe infections 2g iv
described, classified into: tds/qds.
Side effects: as for penicillin. May cause phlebitis and
proximal: with the arm abducted to 45, a needle is
introduced three fingers breadth (5cm) below the pain on injection.
coracoid process and directed at the junction of the
medial one-quarter and lateral three-quarters of Azumolene sodium. Analogue of dantrolene; has
the clavicle. been investigated as an alternative because of its
distal: with the arm abducted to 90, a needle is greater water solubility and a smaller volume of
introduced 1cm medial to the axillary arterial administration.
 B
BACCN, see British Association of Critical Care Nurses - aerobes:
- cocci, e.g. neisseria species.
Backward failure, see Cardiac failure - bacilli, e.g. enterobacteria (enterobacter,
escherichia, klebsiella, proteus, salmonella, ser-
Baclofen. Synthetic GABAB receptor agonist and skel- ratia, shigella, yersinia), vibrio, acinetobacter,
etal muscle relaxant, used to treat muscle spasticity, e.g. pseudomonas, brucella, bordetella, campylo-
following spinal injury and in multiple sclerosis. Acts at bacter, haemophilus, helicobacter, legionella,
both spinal and supraspinal levels. Has also been used chlamydia, rickettsia, mycoplasma, leptospira,
to treat alcohol withdrawal syndromes. treponema species.
Dosage: 5mg orally tds, increased slowly up to - anaerobes:
100mg/day. Has also been given intrathecally: 25 - cocci, e.g. veillonella species.
50g over 1min, increased by 25g/24h up to - bacilli, e.g. bacteroides species.
100g to determine an effective dose, then 12 Bacteria may also be classified according to antigenic
2000g/day by infusion for maintenance. properties of the cell surface, and by their susceptibility
Side effects: sedation, nausea, confusion, convulsions, to various viral phages and antibiotics.
hypotension, GIT upset, visual disturbances, rarely [Hans Gram (18531938), Danish physician]
hepatic impairment. See also, individual infections
See also, -Aminobutyric acid receptors
Bacterial contamination of breathing equipment, see
Bacteraemia. Presence of bacteria in the blood. May be Contamination of anaesthetic equipment
present in SIRS and sepsis, but is not necessary for either
diagnosis to be made. Bacterial resistance. Ability of bacteria to survive in
See also, Blood cultures; Endotoxins the presence of antibacterial drugs. An increasingly sig-
nificant problem in terms of cost, pressure on develop-
Bacteria. Micro-organisms with a bilayered cytoplasmic ment of new antibiotics and impaired ability to treat
membrane, a double-stranded loop of DNA and, in most infections both in critically ill patients and the commu-
cases, an outer cell wall containing muramic acid. nity as a whole.
Responsible for many diseases; mechanisms include the Mechanisms:
initiation of inflammatory pathways by endotoxins or impermeability of the cell wall to the drug, e.g. pseu-
exotoxins; direct toxic effects on/destruction of tissues domonas and many antibiotics.
or organ systems; impairment of host defensive mecha- lack of intracellular binding site for the antibiotic,
nisms; invasion of host cells; and provocation of auto e.g. Streptococcus pneumoniae and penicillin
immune processes. Early claims that bacterial infections resistance.
had been conquered by the development of antibacterial lack of target metabolic pathways, e.g. vancomycin
drugs are now seen as premature in light of the increas- is only effective against Gram-positive organisms
ing problem of bacterial resistance. Classified according because it affects synthesis of the peptidoglycan cell
to their ability to be stained by crystal violet after wall components that Gram-negative bacteria do
iodine fixation and alcohol decolorisation (Gram stain- not possess.
ing), various aspects of their metabolism and their production of specific enzymes against the drug, e.g.
morphology: penicillinase.
Gram-positive: cell wall consists of peptidoglycan the presence of bacterial biofilms communities of
(made up of glucosamine, muramic acid and amino bacteria held within a polysaccharide and protein
acids), lipoteichoic acid and polysaccharides; matrix that make them resistant to normal treat-
include: ment regimens of antibacterial agents.
- aerobes: Resistance may be a natural or acquired property.
- cocci (spherical-shaped), e.g. staphylococci, Bacteria may acquire resistance via activation of a
enterococci, streptococci species. dormant gene or transfer of the responsible gene from
- bacilli (rod-shaped), e.g. bacillus, corynebacte- other bacteria (horizontal evolution).
rium, mycobacterium species. Factors that increase the likelihood of resistance
- anaerobes: occurring include indiscriminate use of antibacterial
- cocci, e.g. peptococcus species. drugs, inappropriate choice of drug and use of subopti-
- bacilli, e.g. actinomyces, propionibacterium, mal dosage regimens (including poor compliance by
clostridium species. users, e.g. long-term anti-TB drug therapy). Regular
Gram-negative: have an additional outer cell consultation with microbiologists, use of antibiotic
wall layer containing lipopolysaccharide (endo- guidelines and infection control procedures, and micro-
toxin); include: biological surveillance may limit the problem. In the UK,

63
64 Bacterial translocation

the Department of Health has run several campaigns to of anociassociation in 1911, and Lundys refinement
increase awareness of the problem and encourage sen- in 1926.
sible prescribing of antibiotics. Antimicrobial steward-
ship programmes (particularly in ITUs) strive to reduce Ballistocardiography. Obsolete method for measure-
the emergence of bacterial resistance, improve clinical ment of measure cardiac output and stroke volume via
outcomes and control costs, through the logical prescrib- detection of body motion resulting from movement of
ing of antibacterial drugs. blood within the body with each heartbeat.
Resistance may also occur in other micro-
organisms, although the problem is greatest in bacteria. Balloon pump, see Intra-aortic counter-pulsation balloon
Gandhi TN, DePestel DD, Collins CD, Nagel J, Washer pump
LL (2010). Crit Care Med; 38 (Suppl.): S31523
Bar. Unit of pressure. Although not an SI unit, com-
Bacterial translocation. Passage of bacteria across the monly used when referring to the pressures at which
bowel wall via lymphatics into the hepatic portal circula- anaesthetic gases are delivered from cylinders and piped
tion, and thence possibly into the systemic circulation. gas supplies.
Implicated in the pathophysiology of intra-abdominal or 1 bar = 10 5 N/m 2 (Pa) = 100 kPa = 10 6 dyn/cm 2
generalised sepsis and MODS, with increased bowel wall
permeability resulting from inadequate oxygen delivery = 14.5 lb/in 2 1 atmosphere
allowing bacteria or their components (e.g. endotoxins)
to enter the circulation and activate various inflamma- Baralyme. Calcium hydroxide 80% and barium octahy-
tory mediator pathways, including cytokines. The inflam- drate 20%. Used to absorb CO2. Although less efficient
matory response may thus be initiated or maintained. than soda lime, it produces less heat and is more stable
Resting the bowel is thought to increase the chances of in dry atmospheres. Used in spacecraft. Carbon monox-
bacterial translocation; therefore early enteral feeding ide production may occur when volatile agents contain-
of critically ill patients (especially with a glutamine- ing the CHF2 moiety (desflurane, enflurane or isoflurane)
enriched feed) is believed to be beneficial. are passed over dry warm baralyme, e.g. at the start of a
Although much evidence supports the occurrence of Monday morning operating session following prolonged
bacterial translocation, its actual significance in SIRS passage of dry gas through the absorber.
and MODS is disputed.
Tsujimoto H, Ono S, Mochizuki H (2009). Dig Surg; 26: Barbiturate poisoning. Causes CNS depression with
1009 hypoventilation, hypotension, hypothermia and coma.
Skin blisters and muscle necrosis may also occur.
Bactericidal/permeability-increasing protein. Protein Treatment:

normally released by activated polymorphonuclear leu- general measures as for poisoning and overdoses.
cocytes. Binds to and neutralises endotoxin and is bac- of the above complications.
tericidal against Gram-negative organisms (by increasing forced alkaline diuresis, dialysis or haemoperfusion
permeability of bacterial cell walls). May have a role in may be indicated.
the future treatment of severe Gram-negative infections, Now rare, with the declining use of barbiturates.
e.g. meningococcal disease. Lipopolysaccharide-binding See also, Forced diuresis
protein is closely related.
See also, Sepsis; Sepsis syndrome; Septic shock; Systemic Barbiturates. Drugs derived from barbituric acid, itself
inflammatory response syndrome derived from urea and malonic acid and first synthesised
in 1864. The first sedative barbiturate, diethyl barbituric
Bain breathing system, see Coaxial anaesthetic breath- acid, was synthesised in 1903. Many others have been
ing systems developed since, including phenobarbital in 1912, hexo-
barbital in 1932 (the first widely used iv barbiturate),
Bainbridge reflex. Reflex tachycardia following an thiopental in 1934, and methohexital (methohexitone)
increase in central venous pressure, e.g. after rapid infu- in 1957.
sion of fluid. Activation of atrial stretch receptors results Substitutions at certain positions of the molecule

in reduced vagal tone and tachycardia. Absent or dimin- confer hypnotic or other properties to the compound
ished if the initial heart rate is high. Of uncertain signifi- (Fig. 22). Chemical classification:
cance but has been proposed to be involved in respiratory oxybarbiturates: as shown. Slow onset and pro-
sinus arrhythmia and to act as a counterbalance to the longed action, e.g. phenobarbital.
baroreceptor reflex.
[Francis Bainbridge (18741921), English physiologist]
Crystal GJ, Salem MR (2012). Anesth Analg; 114:
52032 O H
BAL, see Bronchoalveolar lavage C N
R 6 1
Balanced anaesthesia. Concept of using a combination C 5 2 O
of drugs and techniques (e.g. general and regional 4 3
anaesthesia) to provide adequate analgesia, anaesthesia R
C N
and muscle relaxation (triad of anaesthesia). Each drug
reduces the requirement for the others, thereby reduc- O R
ing side effects due to any single agent, while also allow-
ing faster recovery. Arose from Criles description Fig. 22 Structure of the barbiturate ring
 Baroreceptors 65

thiobarbiturates: sulphur atom at position 2. Rapid measures have failed and patients are fit enough for
onset, smooth action, and rapid recovery, e.g. anaesthesia and surgery.
BMI > 50kg/m as first-line treatment, if patients
2
thiopental.
methylbarbiturates: methyl group at position 1. are fit enough for anaesthesia and surgery.
Rapid onset and recovery, with excitatory phenom- Patients must be able to receive intensive specialist
ena, e.g. methohexital. management and be committed to the need for long-
methylthiobarbiturates: both substitutions. Very term follow-up.
rapid, but too high an incidence of excitatory Surgical techniques:
phenomena to be useful clinically. restrictive: laparoscopic adjustable gastric band-
Long side groups are associated with greater potency ing (AGB), sleeve gastrectomy, gastric balloon
and convulsant properties. Phenyl groups confer anti- insertion.
convulsant action. malabsorptive: biliopancreatic diversion duodenal
Exist in two structural isomers, the enol and keto forms. switch.
The enol form is water-soluble at alkaline pH and under- restrictive/malabsorptive: Roux-en-Y gastric bypass
goes dynamic structural isomerism to the lipid-soluble (laparoscopic or open).
keto form upon exposure to physiological pH (e.g. after Of these, laparoscopic AGB and Roux-en-Y bypass
injection). constitute the vast majority of performed procedures.
Divided clinically into: Some evidence suggests that the latter is more effec-
long-acting, e.g. phenobarbital. tive in severely obese patients, although there is
medium-acting, e.g. amobarbital. increased potential for serious surgical complications.
very short-acting, e.g. thiopental. AGB is quicker and easier to perform and its adjust-
Speed of onset of action reflects lipid solubility, and ability and reversibility confer specific advantages.
thus brain penetration. The actions of long- and May achieve losses of 50% of excess weight and
medium-acting drugs are terminated by metabolism; improvement of associated morbidity (e.g. hyperten-
the shorter duration of action of thiopental and sion, diabetes mellitus).
methohexital is due to redistribution within Anaesthetic considerations are as for all patients with
the body. morbid obesity.
Bind avidly to the alpha subunit of the GABAA [Jean Charles Roux (18571934), French surgeon]
receptor, potentiating the effects of endogenous
GABA. Antagonism of AMPA-type glutamate
receptors (-amino-3-hydroxy-5-methyl-4-isoxazo Barker, Arthur E (18501916). English Professor of
lepropionic acid receptors) also contributes to CNS Surgery at University of London. Helped popularise
depression. Actions: spinal anaesthesia in the UK. In 1907, became the first
general CNS depression, especially cerebral cortex
to use hyperbaric solutions of local anaesthetic agents,
and ascending reticular activating system. combined with alterations in the patients posture, to
central respiratory depression (dose-related).
vary the height of block achieved. Studied the effects of
antanalgesia.
baricity of various local anaesthetic preparations by
reduction of rapid eye movement sleep (with
developing a glass spine model. Used specially prepared
rebound increase after cessation of chronic use). solutions of stovaine (combined with 5% glucose)
anticonvulsant or convulsant properties according
from Paris.
to structure. Lee JA (1979). Anaesthesia; 34: 88591
cardiovascular depression. Central depression is
usually mild; the hypotension seen after thiopental Baroreceptor reflex (Pressoreceptor, Carotid sinus or
is largely due to direct myocardial depression and Depressor reflex). Reflex involved in the short-term
venodilatation. control of arterial BP. Increased BP stimulates barore-
hypothermia.
ceptors in the carotid sinus and aortic arch, increasing
Oxidative and conjugative hepatic metabolism is fol- afferent discharge in the glossopharyngeal and vagus
lowed by renal excretion. Cause hepatic enzyme nerves respectively, that is inhibitory to the vasomotor
induction. centre and excitatory to the cardioinhibitory centre in
Contraindicated in porphyria. the medulla. Vasomotor inhibition (reduced sympathetic
Used mainly for induction of anaesthesia, and as anti- activity) and increased cardioinhibitory activity (vagal
convulsant drugs. Have been replaced by benzodiaze- stimulation) result in a lowering of BP and heart rate.
pines for use as sedatives and hypnotics, as the latter The opposite changes occur following a fall in BP, with
drugs are safer. sympathetic stimulation and parasympathetic inhibition.
See also, -Aminobutyric acid receptors; Barbiturate Resultant peripheral vasoconstriction occurs mainly in
poisoning non-vital vascular beds, e.g. skin, muscle, GIT.
The reflex is reset within 30min if the change in BP
Bariatric surgery. Performed to induce significant is sustained. It may be depressed by certain drugs, e.g.
and sustained weight loss in severe obesity, thereby halothane and possibly propofol.
preventing and indirectly treating the complications of Guyenet PG (2006). Nat Rev Neurosci; 7: 33546
obesity. Delivered as part of a multidisciplinary pro- See also, Valsalva manoeuvre
gramme including diet/lifestyle modifications drug
therapy.
Indications (issued by NICE): Baroreceptors. Stretch mechanoreceptors in the walls
body mass index (BMI) 40kg/m or 3540kg/m
2 2
of blood vessels and heart chambers. Respond to disten-
in the presence of related significant disease sion caused by increased pressure, and are involved in
(e.g. diabetes, hypertension), where non-surgical control of arterial BP.
66 Barotrauma

Exist at many sites: O2 consumption: the subject breathes via a sealed

carotid sinus and aortic arch: circuit (containing a CO2 absorber) from an O2-
- at normal BP, discharge slowly. Rate of discharge filled spirometer. As O2 is consumed, the volume
is increased by a rise in BP, and by increased rate inside the spirometer falls, and a graph of volume
of rise. against time is obtained. O2 consumption per unit
- send afferent impulses via the carotid sinus nerve time is corrected to standard temperature and pres-
(branch of glossopharyngeal nerve) and vagus sure. Average energy liberated per litre of O2 con-
(afferents from aortic arch) to the vasomotor sumed = 20.1kJ (4.82Cal; some variation occurs
centre and cardioinhibitory centre in the medulla. with different food sources); thus BMR may be cal-
Raised BP invokes the baroreceptor reflex. culated. A similar derivation can be obtained elec-
atrial stretch receptors: tronically by the bedside metabolic cart, e.g. when
- found in both atria. Involved in both short-term calculating energy balance in critically ill patients.
neural control of cardiac output and long-term Normal BMR (adult male) is 197kJ/m2/h (40Cal/m2/h).
humoral control of ECF volume. BMR values are often expressed as percentages above
- some discharge during atrial systole while others or below normal values obtained from charts or tables.
discharge during diastolic distension (more so Metabolic rate is increased by:
when venous return is increased or during IPPV). circulating catecholamines, e.g. due to stress.
The latter may be involved in the Bainbridge muscle activity.
reflex. Discharge also results in increased urine raised temperature.
production via stimulation of ANP secretion and hyperthyroidism.
inhibition of vasopressin release. pregnancy.
ventricular stretch receptors: stimulation causes recent feeding (specific dynamic action of foods).
reduced sympathetic activity in animals, but the age and sex (higher in males and children).
clinical significance is doubtful. May also respond to Measurement of metabolic rate under basal conditions
chemical stimulation (BezoldJarisch reflex). eliminates many of these variables.
coronary baroreceptors: importance is uncertain. See also, Metabolism
Other baroreceptors may be present in the mesentery,
affecting local blood flow. Basal narcosis, see Rectal administration of anaesthetic
agents
Barotrauma. Physical injury caused by an excessive
pressure differential across the wall of a body cavity; in
anaesthesia, the term usually refers to pneumothorax, Base. Substance that can accept hydrogen ions, thereby
pneumomediastinum, pneumoperitoneum or subcuta- reducing hydrogen ion concentration.
neous emphysema resulting from passage of air from
the tracheobronchial tree and alveoli into adjacent Base excess/deficit. Amount of acid or base (in mmol)
tissues. Risk of barotrauma is increased by raised airway required to restore 1 litre of blood to normal pH at PCO2
pressures, e.g. with IPPV and PEEP (especially if exces- of 5.3kPa (40mmHg) and at body temperature. By con-
sive tidal volume or air flow is delivered, or if the vention, its value is negative in acidosis and positive in
patient fails to synchronise with the ventilator). High alkalosis. May be read from the Siggaard-Andersen
frequency ventilation may reduce the risk. Diseased nomogram. Useful as an indication of severity of the
lungs with reduced compliance are more at risk of metabolic component of acidbase disturbance, and in
developing barotrauma, e.g. in asthma, ARDS; limiting the calculation of the appropriate dose of acid or base
inspiratory pressures at the expense of reduced minute in its treatment. For example, in acidosis:
volume and increased arterial PCO2 is increasingly used
to reduce the risk of barotrauma in these patients (per- Total bicarbonate deficit (mmol) = base deficit (mmol/l)
missive hypercapnia). Evidence of pulmonary intersti- treatable fluid compartment (l);
tial emphysema may be seen on the CXR (perivascular estimated to be 30% of body weight, composed of
air, hilar air streaks and subpleural air cysts) before
development of severe pneumothorax. In all cases, N2O ECF and exchangeable intracellular fluid:
will aggravate the problem. body weight
Risk of barotrauma during anaesthesia is reduced = base deficit
3
by various pressure-limiting features of anaesthetic
machines and breathing systems. Because of problems associated with bicarbonate admin-
See also, Emphysema, subcutaneous; Ventilator-associated istration, half the calculated deficit is given initially.
lung injury See also, Acidbase balance; Blood gas analyser; Blood
gas interpretation
Basal metabolic rate (BMR). Amount of energy liber-
ated by catabolism of food per unit time, under stan- Basic life support, adult (BLS). Component of CPR
dardised conditions (i.e. a relaxed subject at comfortable without any equipment or drugs (i.e. suitable for anyone
temperature, 1214h after a meal). May be expressed to administer). Known as the ABC of resuscitation. Use
corrected for body surface area. with simple equipment, e.g. airways, facemasks, self-
Determined by measuring: inflating bags, oesophageal obturators, LMA; it has been
heat produced by the subject enclosed in an insu- defined as basic life support with airway adjuncts.
lated room, the outside walls of which are main- Latest European recommendations (2010):
tained at constant temperature. The heat produced ensure own safety and that of the victim.
raises the temperature of water passing through assess: e.g. shake the victim, ask if he/she is all right.
coils in the ceiling, allowing calculation of BMR. If responsive, leave the patient in the same position
 Bellows 67

(provided safe) and get help. If unresponsive, shout of the posterior surface of each vertebral body, and with
for help, turn the patient on to his/her back, open sacral, lumbar, thoracic and cervical veins. It thus con-
the airway and remove any obstruction. nects pelvic veins with intracranial veins. Provides an
Airway: tilt the head back and lift the chin. Remove alternative route for venous blood to reach the heart
food and dentures from the airway. Use airway from the legs. Originally described to explain a route for
adjuncts if available. metastatic spread of tumours. Distends when vena caval
Breathing: check first look, listen and feel for up venous return is obstructed, e.g. in pregnancy, thus
to 10s. If breathing, turn into the recovery position, reducing the space available for local anaesthetic solu-
unless spinal cord injury is suspected. Summon help, tion in epidural anaesthesia.
asking for an automated external defibrillator [Oscar V Batson (18941979), US otolaryngologist]
(AED) if one is available; a solo rescuer should See also, Epidural space
phone first since the chance of successful defibril-
lation falls with increasing delay (although children, Beclometasone dipropionate (Beclomethasone).
trauma or drowning victims, and poisoned or Inhaled corticosteroid, used to prevent bronchospasm in
choking patients may benefit from 1min of CPR asthma by reducing airway inflammation.
before calling for help). If not breathing, summon Dosage: 0.20.8mg bd, depending on clinical severity
help and, on returning, start cardiac massage; after and drug preparation. A nebuliser preparation is
30 compressions give two slow effective breaths available but is relatively inefficient since the drug is
(7001000ml, each over 1s) followed by another 30 poorly soluble.
compressions. Rapid breaths are more likely to Side effects: as for corticosteroids, although systemic
inflate the stomach. Cricoid pressure should be uptake is low. Hoarse voice and oral candidiasis may
applied if additional help is available. Risk of HIV occur with high dosage.
infection and hepatitis is considered negligible.
Inflating equipment and 100% O2 should be used if Becquerel. SI unit of radioactivity. One becquerel =
available. amount of radioactivity produced when one nucleus dis-
Circulation: apply external cardiac massage (56cm integrates per second.
chest depressions) at 100120/min, with the hands [Antoine Becquerel (18521908), French physicist]
in the centre of the chest, stopping only if the patient
starts breathing. It is important to deliver uninter- Bed sores, see Decubitus ulcers
rupted compressions since this improves chances of
survival. Do not stop to check the victim or discon-
tinue CPR unless the victim starts to show signs of Bee stings, see Bites and stings
regaining consciousness, e.g. coughing, eye opening,
speaking or moving purposefully. External bleeding BeerLambert law. Combination of two laws describ-
should be stopped and the feet raised. ing absorption of monochromatic light by a transparent
if there is a second rescuer, the two rescuers substance through which it passes:
Beers law: intensity of transmitted light de
should swap every 12min to minimise fatigue. The
recommended ratio of compressions:breaths is creases exponentially as concentration of substance
30:2 for both single- and two-operator CPR. Chest- increases.
Lamberts law: intensity of transmitted light
compression-only CPR is acceptable if the rescuer
is unable or unwilling to give rescue breaths. decreases exponentially as distance travelled
in cases of choking, encourage coughing in
through the substance increases.
conscious patients; clear the airway manually and Forms the basis for spectrophotometric techniques, e.g.
use 5 back slaps then 5 abdominal thrusts enzyme assays, oximetry, near infrared spectroscopy.
(Heimlich manoeuvre) if not breathing or unable [August Beer (18251863) and Johann Lambert (1728
to speak, repeated as necessary; use basic life 1777), German physicists]
support (as above) if the patient becomes
unconscious. BellMagendie law. The dorsal roots of the spinal cord
All medical and paramedical personnel should be able are sensory, the ventral roots motor.
to administer basic life support (ideally every member [Sir Charles Bell (17741842), Scottish surgeon; Franois
of the public). Ability of hospital staff has been consis- Magendie (17831855), French physiologist]
tently shown to be poor. Regular training sessions are
thought to be necessary, using training mannikins. Bellows. Expansible container used to deliver controlled
European Resuscitation Council Guidelines (2010). volumes of pressurised gas. May describe bellows incor-
Resuscitation; 81: 121976 porated into ventilators or hand-operated devices. The
See also Advanced life support, adult; Cardiac arrest; latter have been used in CPR and animal experiments
Cardiopulmonary resuscitation, neonatal; Cardiopulmo- for several centuries. More modern devices allow
nary resuscitation, paediatric; International Liaison manual-controlled ventilation, and are either applied
Committee on Resuscitation; Resuscitation Council (UK) directly to the patients face or used in draw-over
techniques.
BASICS, see British Association for Immediate Care Examples:
Cardiff bellows: mainly used for resuscitation
Batsons plexus. Valveless epidural venous plexus com- (rarely used now, self-inflating bags being pre-
posed of anterior and posterior longitudinal veins, com- ferred). Design:
municating at each vertebral level with venous rings that - concertina bellows with a facemask at one end.
pass transversely around the dural sac. Also communi- - non-rebreathing valve between the bellows and
cates with basivertebral veins passing from the middle facemask.
68 Bends

- one-way valve at the other end of the bellows that

prevents air or O2 leaks during compression,
whilst allowing fresh gas entry during expansion.
Oxford bellows (Fig. 23): used for resuscitation or
draw-over anaesthesia. Design:
- concertina bellows mounted on a block contain-
ing one-way valves.
- held open by an internal spring, but may be manu-
ally compressed. Expansion draws in air or O2
through a side port.
- unidirectional gas flow is ensured by the one-way To
valves, one on either side of the bellows. A non- patient
rebreathing valve is required between the bellows
and patient.
In earlier models, an O2 inlet opened directly into
the closed bellows system. This could allow build-up
of excessive pressure, with risk of barotrauma.

Bends, see Decompression sickness

Benzatropine mesylate (Benztropine). Anticholinergic

drug, used to treat acute dystonic reactions and parkin- Oxygen
sonism, especially drug-induced.
Dosage:
Fig. 23 Oxford bellows
14mg orally od.
12mg iv/im, repeated as required.
Side effects: sedation, dry mouth, blurred vision, GIT
lorazepam: 12h.
upset, urinary retention, tachycardia. May worsen diazepam, clonazepam: 2448h.
tardive dyskinesia. Metabolism often produces active products with long
half-lives that depend upon renal excretion, e.g. diaze-
Benzodiazepine poisoning. Commonest overdose pam to temazepam and nordiazepam (the latter has a
involving prescription drugs. Generally considered to be half-life of up to 900h and is itself metabolised to oxaz-
less serious than overdose with other sedatives, although epam). In chronic use, benzodiazepines have largely
death may occur, usually due to respiratory depression replaced barbiturates as hypnotics and anxiolytics, since
and aspiration of gastric contents. Of the benzodiaze- they cause fewer and less serious side effects. Overdos-
pines, temazepam is most sedating, and oxazepam least age is also less dangerous, usually requiring supportive
sedating, when taken in overdose. Often accompanied treatment only. Hepatic enzyme induction is rare. A
by alcohol poisoning. chronic dependence state may occur, with withdrawal
Features are mainly those of CNS depression; featuring tremor, anxiety and confusion. Flumazenil is a
hypoventilation and hypotension may also be present. specific benzodiazepine antagonist.
Treatment is largely supportive. Flumazenil may be used See also, -Aminobutyric acid receptors; Benzodiazepine
but large doses may be required and the effects may be poisoning
temporary; acute withdrawal and convulsions may be
provoked in patients on chronic benzodiazepine therapy,
Benztropine, see Benzatropine
those with alcohol dependence, or in cases of mixed drug
overdoses (tricyclic antidepressants drug poisoning in
particular). Benzylpenicillin (Penicillin G). Antibacterial drug,
the first penicillin. Used mainly in infections caused
Benzodiazepines. Group of drugs with sedative, anxio- by Gram-positive and -negative cocci, although its use is
lytic and anticonvulsant properties. Also cause amnesia hampered by increasing bacterial resistance. The drug of
and muscle relaxation. Bind to the and subunits of choice in meningococcal disease, gas gangrene, tetanus,
the GABAA receptor complex, potentiating the increase anthrax and diphtheria. Inactivated by gastric acid, thus
in chloride ion conductance caused by endogenous poorly absorbed orally.
Dosage: 0.61.2g im/iv qds; up to 2.4g 46-hourly in
GABA. They thus enhance GABA-mediated inhibition
in the brain and spinal cord, especially the limbic system meningococcal meningitis or anthrax.
Side effects: allergic reactions, convulsions following
and ascending reticular activating system.
Anaesthetic uses: high doses or in renal failure.
premedication, e.g. diazepam, temazepam,
lorazepam. Bernard, Claude (18131878). French physiologist,
sedation, e.g. diazepam, midazolam. whose many contributions to modern physiology include:
as anticonvulsant drugs, e.g. diazepam, lorazepam, demonstrating hepatic gluconeogenesis; proving that
clonazepam. pancreatic secretions could digest food; discovering
induction of anaesthesia, e.g. midazolam. vasomotor nerves; and investigating the effects of curare
Half-life: at the neuromuscular junction. Also suggested the
midazolam: 13h. concept of the internal environment (milieu intrieur)
oxazepam: 38h. and homeostasis.
temazepam: 68h. Lee JA (1978). Anaesthesia; 33: 7417
 Bioavailability 69

Bernoulli effect. Reduction of pressure when a fluid Presented as 8.4%, 4.2% and 1.26% solutions
accelerates through a constriction. As velocity increases (1000mmol/l, 500mmol/l and 150mmol/l respectively).
during passage through the constriction, kinetic energy See also, Base excess/deficit
increases. Total energy must remain the same, therefore
potential energy (hence pressure) falls. Beyond the con- Bier, Karl August Gustav (18611949). Renowned
striction, the pressure rises again. A second fluid may German surgeon, Professor in Bonn and then Berlin.
be entrained through a side arm into the area of lower Introduced spinal anaesthesia using cocaine, describing
pressure, causing mixing of the two fluids (Venturi its use on himself, his assistant and a series of patients,
principle). in 1899. Gave a classic description of the post-dural
[Daniel Bernoulli (17001782), Swiss mathematician] puncture headache he later suffered, and suggested CSF
leakage during/after the injection as a possible cause.
Bert effect. Convulsions caused by acute O2 toxicity, Also introduced IVRA, using procaine, in 1908. As con-
seen with hyperbaric O2 therapy (3 atm). sulting surgeon during World War I, he introduced the
[Paul Bert (18331896), French physiologist] German steel helmet.
See also, Oxygen therapy, hyperbaric van Zundert A, Goerig M (2000). Reg Anesth Pain Med;
25: 2633
Beta-adrenergic , see -Adrenergic
Biers block, see Intravenous regional anaesthesia
Beta-lactams, see -Lactams
Bigelow, Henry Jacob (18181890). US surgeon at the
BezoldJarisch reflex. Bradycardia, vasodilatation and Massachusetts General Hospital, Boston, he sponsored
hypotension following stimulation of ventricular recep- Wells abortive attempt at anaesthesia in 1845 and
tors by ischaemia or drugs, e.g. nicotine and veratridine. promoted and published the first account of Mortons
Thought to involve inhibition of the baroreceptor use of diethyl ether anaesthesia for surgery in 1846.
reflex. Although of disputed clinical significance, a role Described several operations and the intraoperative
in regulation of BP and the response to hypovolaemia events that occurred during them. Later, as a Professor,
has been suggested. The reflex may be activated during he became renowned for many contributions to surgery,
myocardial ischaemia or MI, and in rare cases of including inventing a urological evacuator.
unexplained cardiovascular collapse following spinal/
epidural anaesthesia. Biguanides. Hypoglycaemic drugs, used to treat non-
[Albert von Bezold (18361868), German physiologist; insulin-dependent diabetes mellitus. Act by decreasing
Adolf Jarisch (18501902), Austrian dermatologist] gluconeogenesis and by increasing glucose utilisation
Campagna JA, Carter C (2003). Anesthesiology; 98: peripherally. Require some pancreatic islet cell function
125060 to be effective. May cause lactic acidosis, especially in
renal or hepatic impairment. Lactic acidosis is particu-
Bicarbonate. Anion present in plasma at a concentra- larly likely with phenformin, which is now unavailable
tion of 2433mmol/l, formed from dissociation of car- in the UK. Metformin, the remaining biguanide, is used
bonic acid. Intimately involved with acidbase balance, as first-line treatment in obese patients in whom diet
as part of the major plasma buffer system. Filtered in the alone is unsuccessful, or when a sulphonylurea alone is
kidneys and reabsorbed to a variable extent, according inadequate.
to acidbase status. 80% of filtered bicarbonate is reab-
sorbed in the proximal tubule via formation of carbonic Biliary tract. Bile produced by the liver passes to the
acid, which in turn forms CO2 and water aided by car- right and left hepatic ducts, which unite to form the
bonic anhydrase. The bicarbonate ion itself does not pass common hepatic duct. This is joined by the cystic duct,
easily across cell membranes. which drains the gallbladder, to form the common bile
Sodium bicarbonate may be administered iv to raise
duct; the latter drains into the duodenum (with the pan-
blood pH in severe acidosis, but with potentially creatic duct) through the ampulla of Vater, the lumen of
undesirable effects: which is controlled by the sphincter of Oddi. Both infec-
increased formation of CO2, which passes readily
tion of the biliary tree (cholangitis) and inflammation of
into cells (unlike bicarbonate), worsening intracel- the gallbladder (cholecystitis) may occur during critical
lular acidosis. illness.
increased blood pH shifts the oxyhaemoglobin dis-
[Ruggero Oddi (18451906), Italian physiologist and
sociation curve to the left, with increased affinity of anatomist; Abraham Vater (16841751), German anato-
haemoglobin for O2 and impaired O2 delivery to the mist and botanist]
tissues. See also, Jaundice
solutions contain 1mmol sodium ions per mmol
bicarbonate ions, representing a significant sodium Binding of drugs, see Pharmacokinetics; Protein-
load. binding
8.4% solution is hypertonic: increased plasma
osmolality may cause arterial vasodilatation and Bioavailability. Fraction of an administered dose of
hypotension. a drug that reaches the systemic circulation unchanged;
severe tissue necrosis may follow extravasation.
iv injection thus provides 100% bioavailability. For
For these reasons, treatment is usually reserved for pH an orally administered dose, it equals the area under
below 7.17.2. the resultant concentration-against-time curve divided
base deficit body weight (kg) by that for an iv dose (Fig. 24). Low values of bioavail-
Dose: mmol ability occur with poorly absorbed oral drugs, or those
3
Half of this dose is given initially. that undergo extensive first-pass metabolism. Various
70 Biofeedback

pneumonic plague: Gram-negative bacillus causing

mucopurulent sputum, chest pain and hemoptysis.
If untreated, mortality approaches 100%.
Bioavailability = AUCpo x 100
tularaemia: Gram-negative coccobacillus causing
AUCiv
bronchopneumonia, pleuritis and hilar lymphade-
nopathy. Overall mortality for virulent strains is
515%, but up to 3060% in pulmonic or septicae-
mic tularaemia without antibiotics.
iv viral haemorrhagic fevers: influenza-like illness with
Plasma haemorrhage, petechiae and ecchymoses or multi-
[drug] ple organ failure. Mortality approaches 100% for
the most virulent forms.
botulism: a paralytic illness characterised by sym-

oral metric, descending flaccid paralysis of motor and

autonomic nerves, usually beginning with the cranial
nerves. Mortality is approximately 6% if appropri-
Time ately treated.
smallpox: febrile illness followed by a generalised
Fig. 24 Bioavailability
macular or papular-vesicular-pustular eruption.
Mortality is approximately 30%.
Management includes specific and general supportive
formulations of the same drug may have different measures; consideration should also be directed towards
bioavailability. Bioinequivalence is a statistically signifi- protection of staff, decontamination of clinical areas and
cant difference in bioavailability, whereas therapeutic equipment, disposal of bodies and other aspects of major
inequivalence is a clinically important difference, e.g. as incidents.
may occur with different preparations of digoxin. White SM (2002). Br J Anaesth; 89: 30624
See also, Pharmacokinetics See also, Incident, major; Chemical weapons

Biofeedback. Technique whereby bodily processes Biotransformation, see Pharmacokinetics

normally under involuntary control, e.g. heart rate,
are displayed to the subject, enabling voluntary control BIPAP. Bi-level positive airway pressure, see Non-
to be learnt. Has been used to aid relaxation, and in invasive positive pressure ventilation
chronic pain management when increased muscle
tension is present, using the EMG as the displayed Bispectral index monitor. Cerebral function monitor
signal. that uses a processed EEG obtained from a single
frontal electrode to provide a measure of cerebral activ-
Bioimpedance cardiac output measurement, see ity. Used to monitor anaesthetic depth in an attempt to
Impedance plethysmography prevent awareness. Produces a dimensionless number
(the BIS number) ranging from 100 (fully awake) to 0
Biological weapons. Living organisms or infected mate- (no cerebral activity). The algorithm used to calculate
rial derived from them, used for hostile purposes, either the BIS value is commercially protected but is based on
by certain nations in legitimate biological warfare or by power spectral analysis of the EEG, the synchrony of
(bio)terrorists. The agents depend for their effects on slow and fast wave activity and the burst suppression
their ability to multiply in the person, animal or plant ratio. Targeting a BIS number of 4060 is advocated to
attacked. Although not pathognomonic of a bioterrorist reduce awareness and allow more rapid emergence
attack, the following should raise suspicion: from anaesthesia, although the evidence does not
an unusual clustering of illness in time or space. support its routine use.
an unusual age distribution of a common illness (e.g. See also, Anaesthesia, depth of
apparent chickenpox in adults).
a large epidemic. Bisphosphonates. Group of drugs that inhibit osteoclast
disease that is more severe than expected. activity; used in Pagets disease, osteoporosis, metastatic
an unusual route of exposure. bone disease and hypercalcaemia. They are adsorbed on
disease outside its normal transmission season. to hydroxyapatite crystals, interfering with bone turn-
multiple simultaneous epidemics of different over and thus slowing the rate of calcium mobilisation.
diseases. May be given orally or by slow iv infusion, e.g. in severe
unusual strains or variants of organisms or antimi- hypercalcaemia of malignancy:
crobial resistance patterns. disodium pamidronate: 1560mg, given once or
Potential diseases include: divided over 24 days, up to a maximum of 90mg
anthrax: Gram-negative bacillus causing fever, skin in total.
eschars (dry scabs) and associated lymphadenopa- ibandronic acid: 24mg by a single infusion.
thy, chest pain, dry cough, nausea and abdominal sodium clodronate: 300mg/day for 710 days or
pain, followed by sepsis, shock, widened mediasti- 1.5g by a single infusion.
num, hemorrhagic pleural effusions and respiratory zoledronic acid: 45mg (depending on the prepara-
failure. Mortality rates vary depending on exposure: tion) over 15min by a single infusion.
approximately 20% for cutaneous anthrax without Side effects include hypocalcaemia, hypophosphatae-
antibiotics, 2575% for gastrointestinal anthrax and mia, pyrexia, flu-like illness, vomiting and headache.
over 80% for inhalation anthrax. Blood dyscrasias, hyper- or hypotension, renal and
 Blood 71

hepatic dysfunction may rarely occur, especially with assessment of all systems and degree of swelling
disodium pamidronate. Osteonecrosis of the jaw and are important. Antitetanus immunisation should be
atypical femoral fractures have also been reported, given. Broad-spectrum antibacterial drugs are often
mainly associated with long-term administration. given.
[Sir James Paget (18141899), English surgeon] Singletary EM, Rochman AS, Bodmer JC, Holstege CP
(2005). Med Clin North Am; 89: 1195224
Bites and stings. May include animal bites, and animal
or plant stings. Problems are related to: Bivalirudin. Recombinant hirudin used as anticoagulant
local tissue trauma itself: damage to vital organs, in acute coronary syndromes.
haemorrhage, oedema. Importance varies with the Dosage:
size, location and number of the wound(s). in patients undergoing percutaneous coronary
effect of venom or toxin delivered: may cause an intervention (PCI), including those with S-T
intense immune and inflammatory reaction, usually segment elevation MI: 750g/kg iv initially fol-
with severe pain and swelling. Systemic features lowed by 1.75mg/kg/h for up to 4h after
usually present within 14h; they may vary but procedure.
typically include: in patients with unstable angina or non S-T segment
- respiratory: bronchospasm, pulmonary oedema, elevation MI: 100g/kg iv initially followed by
respiratory failure (type I or II), airway obstruc- 250g/kg/h for up to 72h. For those proceeding to
tion (from oedema). PCI, an additional bolus dose of 500g is given
- cardiovascular: hypertension (from neuro followed by an infusion of 1.75mg/kg/h.
transmitter release), hypotension (from cardiac Side effects: bleeding, hypotension, angina,
depression, hypovolaemia, vasodilatation), headache.
arrhythmias.
- neurological: confusion, coma, convulsions. Bladder washouts. Main types used in ICU:
- neuromuscular: cranial nerve palsies and periph- to remove debris and exclude catheter blockage as
eral paralysis (from pre- or postsynaptic neuro- a cause of oliguria: sterile saline. Various solutions
muscular junction blockade), muscle spasms are available to remove phosphate deposits.
(from neurotransmitter release), rhabdomyolysis. to dissolve blood clots: sterile saline or sodium
- gastrointestinal: nausea, vomiting. citrate 3% irrigation. Streptokinase-streptodornase
- haematological: coagulation disorders, haemo enzyme preparation may also be used (allergic reac-
lysis. tions and burning may occur).
- renal: impairment from myoglobinuria, hypoten- for urinary tract infection: chlorhexidine 1:5000
sion and direct nephrotoxicity. (may cause burning and haemorrhage); ineffective
wound infection, either introduced at the time of in pseudomonal infections. Saline may also be used.
injury or acquired secondarily. Amphotericin may be used in fungal infection.
systemic transmitted disease, e.g. tetanus, rabies, Also used to treat local malignancy.
plague.
Venoms are typically mixtures of several compounds, Blast injury, see Chest trauma
including enzymes and other proteins, amino acids, pep-
tides, carbohydrates and lipids. The age and health of the Bleeding time, see Coagulation studies
victim, and the site and route of envenomation, may
affect the severity of the injury. Identification of the Bleomycin. Antibacterial cytotoxic drug, given iv or im
offending animal or plant is particularly important, since to treat lymphomas and certain other solid tumours. Side
prognosis and management may vary considerably effects include alveolitis, dose-dependent progressive
between species. Certain venoms may be identified by pulmonary fibrosis, skin and allergic reactions (common)
blood testing. and myelosuppression (rare). Pulmonary fibrosis is
Management: thought to be exacerbated if high concentrations of O2
initial resuscitation as for trauma, anaphylaxis. are administered, e.g. for anaesthesia. Suspicion of fibro-
Rapid transfer of victims of envenomation to hos- sis (CXR changes or basal crepitations) is an indication
pital is the most important prehospital measure. to stop therapy.
Jewellery should be removed from the affected limb
as swelling may be marked. Blood. Circulating body fluid composed of blood cells
specific management: (red cells, white cells and platelets) suspended in plasma.
- application of a pressure dressing and immobilisa- Normal adult blood volume is 7080ml/kg, of which
tion of the affected body part in order to reduce ~45% is cellular. Cell formation occurs in the liver,
systemic absorption. spleen and bone marrow before birth, after which it
- neutralisation of venom already absorbed. Many occurs in bone marrow only. In adults, active bone
antivenoms are derived from horses, and severe marrow is confined to vertebrae, ribs, sternum, ilia and
allergic reactions may occur. humeral and femoral heads. Stem cells differentiate into
- previously employed measures, now agreed to be mature cells over many divisions. Primary stem cells
unhelpful or harmful, include suction to remove may give rise to the lymphocyte series of stem cells or
venom from the wound and application of limb to secondary stem cells. The secondary stem cells may
tourniquets. give rise to the erythrocyte, granulocyte, monocyte or
general supportive management according to the megakaryocyte series of stem cells (the latter forming
system affected. IV fluids are usually required. platelets).
Blood should be taken early as certain venoms and See also, Blood volume; Erythrocytes; Leucocytes;
antivenoms may interfere with grouping. Frequent Plasma; Platelets
72 Blood, artificial

Blood, artificial. Synthetic solutions capable of O2 trans- neuromuscular blocking drugs and glycopyrronium, are
port and delivery to the tissues. Circumvent many of the permanently charged, and cross to a very limited extent
complications of blood transfusion and avoid the need (cf. atropine).
for blood compatibility testing. Two types have been The effectiveness of the barrier is reduced in neo-
investigated: nates compared with adults: hence the increased passage
haemoglobin solutions: of drugs (e.g. opioid analgesic drugs) and other sub-
- must be free of red cell debris (stroma-free) to stances (e.g. bile salts, causing kernicterus). Localised
avoid renal damage, that has also occurred with pathology, e.g. trauma, malignancy and infection, may
certain stroma-free solutions. Other effects may also reduce the integrity of the barrier.
include impairment of macrophage activity, vaso-
constriction and activation of various inflamma- Blood compatibility testing. Procedures performed on
tory pathways. Free haemoglobin solutions are donor and recipient blood before blood transfusion, to
also hyperosmotic and are quickly broken down determine compatibility. Necessary to avoid reactions
in the blood. caused by transfusion of red cells into a recipient whose
- the oxyhaemoglobin dissociation curve of free plasma contains antibodies against them. ABO and
haemoglobin is markedly shifted to the left of that Rhesus are the most relevant blood group systems clini-
for intraerythrocyte haemoglobin, reducing its cally, although others may be important.
usefulness. Antibodies may be intrinsic (e.g. ABO system) or
- must be stored in O2-free atmosphere to avoid develop only after exposure to antigen (e.g. Rhesus).
oxidisation to methaemoglobin. Methods:
Various modifications of the haemoglobin molecule group and screen: if red cells have serum added that
have been made in order to prolong its half-life contains antibody against them, agglutination of the
from under 1h to over 24h, including polymerisa- cells occurs; serum of known identity is thus used to
tion with glutaraldehyde, linking haemoglobin with identify the recipients ABO blood group and
hydroxyethyl starch or dextran, cross-linking the Rhesus status. The recipients serum is also screened
or chains, and fusing the chains end to end (the for atypical antibodies against other groups. Usually
latter has been done with recombinant human hae- takes 3040min.
moglobin). Bovine haemoglobin, and encapsulation cross-match: in addition to group and screen, the
of haemoglobin within liposomes, has also been recipients serum is added to red cells from each
used. Many of these preparations are currently donor unit to confirm compatibility. Usually takes
undergoing clinical trials. 4560min.
perfluorocarbon solutions (e.g. Fluosol DA20) carry computer cross-match (electronic issue): uncross-
dissolved O2 in an amount directly proportional to matched ABO and Rhesus-compatible blood may
its partial pressure, and have been used to supple- be issued within a few minutes with no further
ment O2 delivery in organ ischaemia due to shock, testing, provided the patient does not have irregular
arterial (including coronary) insufficiency and antibodies.
haemorrhage. Have been used for liquid ventilation. Uncross-matched O Rhesus-negative blood is reserved
Even with high FIO2, O2 content is less than that of for life-threatening emergencies. Fresh frozen plasma is
haemoglobin (newer compounds may be more effi- not cross-matched, but chosen as type-specific (ABO) so
cient at O2 carriage). Accumulation in the reticulo- that antibodies are not infused into a recipient who
endothelial system is of unknown significance. might have the corresponding antigens on his or her
Clinical trials are continuing. cells. Platelets are suspended in plasma, so are also
Spiess BD (2009). J Appl Physiol; 106: 144452 selected as type-specific, but in this case according to
Rhesus typing too.
Bloodbrain barrier. Physiological boundary between
the bloodstream and CNS, preventing transfer of hydro- Blood cultures. Microbiological culture of blood, per-
philic substances from plasma to brain. The original formed to detect circulating micro-organisms. Blood is
concept was suggested by the lack of staining of brain taken under aseptic conditions and injected into (usually
tissue by aniline dyes given systemically. Passage of two) bottles containing culture medium, for aerobic and
hydrophilic molecules is impeded by tight junctions anaerobic incubation. Diluting the sample at least 45
between capillary endothelial cells in the brain and epi- times in the culture broth reduces the antimicrobial
thelial cells in the choroid plexus; glial cells also con activity of serum and of any circulating drugs. Changing
tribute. Active transport may still occur for specific the hypodermic needle between taking blood and injec-
molecules, e.g. glucose. Certain areas of the brain lie tion into the bottles is not now thought to be necessary,
outside the barrier, e.g. the hypothalamus and areas although contamination of the needle and bottles must
lining the third and fourth ventricles (including the che- be avoided. Sensitivity depends on the type of infection,
moreceptor trigger zone). the number of cultures and volume of blood taken. At
In the absence of active transport, the ability of chem- least 23 cultures, each using at least 1030ml blood, are
icals to cross the barrier is proportional to their lipid usually recommended. More samples may be required
solubility, and inversely proportional to molecular size when there is concurrent antibacterial drug therapy (the
and charge. Water, O2 and CO2 cross freely; charged ions sample may be diluted several times or the drug removed
and larger molecules take longer to cross, unless lipid- in the laboratory to increase the yield) or when endo-
soluble. All substances eventually penetrate the brain; carditis is suspected. False-positive results may be sug-
the rate of penetration is important clinically. Some gested by the organism recovered (e.g. bacillus species,
drugs only cross the barrier in their unionised, non- coagulase-negative staphylococci, diphtheroids) and
protein-bound form, i.e. a small proportion of the their presence in only a single culture out of many and
injected dose, e.g. thiopental. Quaternary amines, such as after prolonged incubation.
 Blood gas interpretation 73

Many different culture systems exist, some directed

Table 9 Blood flow to and O2 consumption of heart, brain,
at particular organisms. Different systems may be used
liver and kidneys
together to increase their yield. Modern microbiological
techniques may involve automatic alerting of staff when Blood flow O2 consumption
significant microbial growth interrupts passage of light
through the bottles. The organisms may then be identi- (ml/100g (ml/100g
fied and sensitivity to antimicrobials determined. Organ (ml/min) tissue/min) (ml/min) tissue/min)
Thompson F, Madeo M (2009). J Infect Prevention; 10:
s246 Heart 250 80 30 10
Brain 700 50 50 3
See also, Sepsis
Liver 1400 50 50 2
Kidneys 1200 400 20 6
Blood filters. Devices for removing microaggregates
during blood transfusion. Platelet microaggregates form
early in stored blood, with leucocytes and fibrin aggre-
gates occurring after 7 days storage. Pulmonary micro- arteries and in the hyperdynamic circulation, particu-
embolism has been suggested as a cause of pulmonary larly in anaemia, when viscosity is reduced (see Reyn-
dysfunction following transfusion. olds number).
Types of filters: Measurement:
screen filters: sieves with pores of a certain size. direct measurement of blood from the arterial
depth filters: remove particles mainly by adsorption. supply.
Pore size varies, and effective filtration may be electromagnetic flow measurement.
reduced by channel formation within the filter. Doppler measurement.
combination filters. indirect methods:
Most contain woven fibre meshes, e.g. of polyester or - Fick principle.
nylon. Filtration results from both a physical sieving - dilution techniques.
effect and the presence of a positive or negative charge - plethysmography.
on the surface of the material that traps cellular compo- Approximate blood flow to, and O2 consumption of,
nents and large molecules. various organs are shown in Table 9.
Standard iv giving sets suitable for blood transfusion
contain screen filters of 170m pore size. Filtration of Blood/gas partition coefficients, see Partition
microaggregates requires microfilters of 2040m pore coefficients
size. The general use of microfilters is controversial; by
activating complement in transfused blood they may Blood gas analyser. Device used to measure blood gas
increase formation of microaggregates within the recipi- tensions, pH, electrolytes, metabolites and haemoglobin
ents bloodstream. They add to expense, increase resis- derivatives. Incorporates a series of measuring elec-
tance to flow and may cause haemolysis. They have, trodes a co-oximeter. Directly measured parameters
however, been shown to be of use in extracorporeal include pH, PO2, PCO2. Bicarbonate, standard bicarbon-
circulation. ate and base excess are derived. Inaccuracy may result
Leucodepletion filters are used in cell salvage, e.g. to from excess heparin (acidic), bubbles within the sample
remove cellular fragments, but their routine use has been and metabolism by blood cells. The latter is reduced by
questioned because of rare reports of severe hypoten- rapid analysis after taking the sample, or storage of the
sion in recipients, possibly related to release of bradyki- sample on ice. O2, CO2 and pH electrodes require regular
nin and/or other mediators when blood is passed over maintenance and two-point calibration.
filters with a negative charge. See also Blood gas interpretation; Carbon dioxide mea-
A filter capable of removing prion proteins that cause surement; Oxygen measurement; pH measurement
CreutzfeldtJakob disease is under evaluation.
Blood gas interpretation. Normal ranges are shown in
Blood flow. For any organ: Table 10.
Suggested plan for interpretation:
perfusion pressure
flow = oxygenation:
resistance - knowledge of the FIO2 is required before interpre-
thus the haemodynamic correlate of Ohms law. tation is possible.
Perfusion pressure depends not only on arterial and - calculation of the alveolar PO2 (from alveolar gas
venous pressures but also on local pressures within the equation).
capillary circulation. - calculation of the alveolararterial O2 difference.
Resistance depends on: acidbase balance:
vessel radius, controlled by humoral, neural and - identification of acidaemia or alkalaemia, repre-
local mechanisms (autoregulation). senting acidosis or alkalosis respectively.
vessel length. - identification of a respiratory component by
blood viscosity. Reduced peripherally due to plasma referring to the CO2 tension.
skimming, which results in blood with reduced hae- - identification of a metabolic component by refer-
matocrit leaving vessels via side branches. Reduced ring to the base excess/deficit or standard bicar-
in anaemia. bonate (both are corrected to a normal CO2
Flow is normally laminar; i.e. it roughly obeys the tension, thus eliminating respiratory factors).
HagenPoiseuille equation, although blood vessels are - knowledge of the clinical situation helps to decide
not rigid, arterial flow is pulsatile and blood is not an whether the respiratory or metabolic component
ideal fluid. Turbulent flow may occur in constricted represents the primary change.
74 Blood groups

solutions (the latter in about 23 times the volume of the

Table 10 Normal values (ranges or mean 2 SD) for blood gas
former).
interpretation, for young adults breathing room air at sea level
Blood loss may be reduced by:
hypotensive anaesthesia.
Arterial pH 7.357.45
PO2 10.613.3kPa (80100mmHg) tourniquets.
PCO2 4.66.0kPa (3545mmHg) local infiltration with vasopressor drugs.
HCO3 2226mmol/l appropriate positioning, e.g. head-up for ENT
SaO2 95100% surgery.
spinal and epidural anaesthesia.
Mixed venous pH 7.327.36
Bleeding may be increased by:
PO2 4.75.3kPa (3540mmHg)
PCO2 5.66.1kPa (4246mmHg) raised venous pressure:
HCO3 2428mmol/l - raised intrathoracic pressure, e.g. due to respira-
S v O2 6080% tory obstruction, coughing, straining.
- fluid overload and cardiac failure.
- inappropriate positioning.
- venous obstruction.
See also, Blood gas analyser; Carbon dioxide measure- hypercapnia.
ment; Carbon dioxide transport; Oxygen measurement; coagulation disorders:
Oxygen transport; pH measurement - pre-existing.
- dilutional coagulopathy.
Blood groups. Each individuals red cells bear certain - incompatible blood transfusion.
antigens capable of producing an antibody response in - anticoagulant drugs.
another person. Some are only present on red cells, e.g. - DIC.
Rhesus antigens; others are also present on other tissue hypertension.
cells, e.g. ABO antigens. Immunoglobulins may be poor surgical technique.
present intrinsically, e.g. ABO and Lewis, or following See also, Blood transfusion, massive; Haemorrhage
exposure to the antigen, e.g. Rhesus; they are usually IgG
or IgM. Administration of blood cells to a recipient who Blood patch, epidural. Procedure for the relief of post-
has the corresponding antibody causes haemolysis and dural puncture headache. 1020ml of the patients blood
a severe reaction. is drawn from a peripheral vein under sterile conditions,
Minor blood groups may be important clinically fol- and injected immediately into the epidural space. Blood
lowing ABO-typed uncross-matched blood transfusion, is thought to seal the dura, thus preventing further CSF
or multiple transfusions; an atypical antibody in a recipi- leak, although cranial displacement of CSF resulting
ent makes the finding of suitable donor blood difficult. from epidural injection may also be important, at least
Minor groups include the Kell, Duffy, Lewis and Kidd initially. Maintaining the supine position for at least
systems. Many more have been described; the signifi- 24h after patching is recommended to increase the
cance of such diversity is unclear. chance of success, by reducing dislodgement of the clot
See also, Blood compatibility testing from the dural puncture site. Should be avoided if the
patient is febrile, in case of bacteraemia and subsequent
Blood loss, perioperative. Important as a guide to peri- epidural abscess. The sending of blood for culture at the
operative fluid requirements, and also as indicator of time of patching has been suggested, in case infection
potential development of a coagulation disorder related does occur.
to major haemorrhage. Effective in 70100% of cases, although symptoms
Methods of estimation: may recur in 3050%, sometimes necessitating a repeat
clinical judgement of the patients volume status. blood patch. Relief of headache may occur immediately
observation of wound and swabs. or within 24h. Spectacular results have been claimed,
weighing swabs and subtracting their dry weight. even when performed up to several months after dural
Weighing swabs may underestimate blood loss if puncture. Prophylactic use has been less consistently
fluid is lost by evaporation or soaked into drapes. successful. Complications are rare, and include transient
Overestimation may occur if saline is weighed bradycardia, back and neck ache, root pain, pyrexia, tin-
without correction. nitus and vertigo. Subsequent epidural anaesthesia is
measuring the volume removed by suction devices. thought to be unaffected.
washing of all swabs and drapes in a known volume
of water and measuring haemoglobin concentra- Blood pressure, see Arterial blood pressure; Diastolic
tion. Volume of blood lost may then be calculated. blood pressure; Mean blood pressure; Systolic blood
Measurement of potassium released from lysed pressure
cells has also been used.
measurement of blood volume. Blood products. Many products may be obtained from
Replacement with blood has been suggested if losses donated blood (Fig. 25), including:
exceed 1520% of blood volume in adults, or 10% in whole blood: stored at 26C for up to 35 days.
children, although greater losses may be allowed if the 70ml citrate preservative solution is added to
preoperative haemoglobin concentration is high. Recent 420ml blood. The use of whole blood for blood
guidelines suggest that, under stable conditions, a hae- transfusion is restricted in the UK. Heparinised
moglobin concentration of 710g/dl should be a general whole blood (lasts for 2 days) has been used for
indication for blood transfusion, depending on the cir- paediatric cardiac surgery.
cumstances. Until blood transfusion becomes neces- packed red cells (plasma reduced): stored at
sary, losses may be replaced with colloid or crystalloid 26C for up to 35 days. Should be kept at room
 Blood products 75

temperature for no more than 24h. Haematocrit is or kept at room temperature and given within 4h.
approximately 0.55. Produced by removing all but Contains all clotting factors, including fibrinogen,
20ml residual plasma from a unit of whole blood and is also a source of plasma cholinesterase. Con-
and suspending the cells in 100ml SAG-M (saline tains added citrate. Viral infection risk is as for
adenineglucosemannitol) solution to give a mean whole blood. In the UK, one unit of FFP is derived
volume per unit of 280ml. Since 1998, routinely from plasma from a single donor, and FFP for chil-
depleted of leucocytes to decrease the risk of trans- dren born after 1995 is derived from unpaid US
mitting variant CreutzfeldtJakob disease. One unit donors. Indicated for treatment of various coagu-
typically increases haemoglobin concentration in a lopathies e.g. multifactor deficiencies associated
70-kg adult by 1g/dl. with major haemorrhage and/or DIC. One adult
microaggregate-free blood: leucocytes, platelets therapeutic dose is 1215ml/kg or 4 units for a
and debris removed (i.e. the buffy coat). Used 70-kg adult, and would typically increase the fibrin-
to prevent reactions to leucocyte and platelet ogen concentration by 1g/l.
antigens. cryoprecipitate: obtained by controlled thawing of
leucocytes: separated from blood donated by FFP to precipitate high-molecular-weight proteins
patients whose leucocyte count has been increased (e.g. factor VIII, fibrinogen and von Willebrands
by pretreatment with corticosteroids, or those with factor). Frozen and stored at 20C; thawed imme-
chronic granulocytic leukaemia. diately before use. Indicated for the treatment of
frozen blood: used by the armed forces but too ongoing bleeding in the presence of low fibrinogen
expensive and time-consuming for routine use. levels (< 1g/l). A typical adult dose is two 5-unit
Glycerol is added to prevent haemolysis. Requires pools, in total containing 36g fibrinogen in 200
thawing and washing. May be stored for many 500ml; this would increase fibrinogen levels by
years. ~1g/l. Viral infection risk is as for whole blood.
platelets: stored at 22C for up to 5 days. Obtained human albumin solution (HAS; previously called
either from a single donor by plateletpheresis plasma protein fraction, PPF): stored at room
(one donation yielding 13 therapeutic dose units) temperature for 25 years depending on the prepa-
or from multiple units of donated whole blood ration. Heat-treated to kill viruses. Contains virtu-
(one unit of platelets derived from four donors). ally no clotting factors. Available as 4.5% and
Transfusion thresholds vary according to the clinical 20% (salt-poor albumin) solutions; both contain
situation, the level of platelet function and labora- 140150mmol/l sodium but the latter contains less
tory evidence of coagulopathy, but typically include sodium per gram of albumin. Licensed for blood
a platelet count of 50 109/l or less for surgery, volume expansion with or without hypoalbuminae-
unless platelet function is abnormal. One therapeu- mia. Use is controversial owing to its high cost and
tic dose unit (approximate volume 210310ml) nor- the absence of evidence demonstrating its superior-
mally increases the platelet count by 2040 109/l, ity to other colloids. UK supplies are now sourced
although some patients may exhibit refractoriness from the USA.
(e.g. those with circulating antiplatelet antibodies). factor concentrates, e.g. VIII and IX: now obtained
Filtered by microfilters; ordinary iv giving sets are by recombinant gene engineering, removing the risk
suitable. Preferably should be ABO-compatible. of viral infection. Recombinant activated factor VII
Contains added citrate. (rFVIIa) is licensed for the treatment of patients
fresh frozen plasma (FFP): stored at 30C for up with acquired or congenital haemophilia, von
to 2 years. Must be ABO-compatible. Once thawed, Willebrands disease and inhibitors to factors VIII
can be stored at 4C and must be given within 24h, or IX of the clotting cascade. Factor VIIa enhances

Whole blood

Centrifuge

Frozen red cells Packed red cells Platelet-rich plasma

Freezing/microfiltration Centrifuge 20C

Leucocyte-poor red cells Leucocytes Plasma Platelets

Freezing 20C FFP

70C and rapid thawing

Cryoprecipitate Supernatant

Factor IX
Factor VIII
Immunoglobulins
Fibrinogen
Products obtained from pooled plasma Albumin

Fig. 25 Blood products available from whole blood

76 Blood storage

thrombin generation on the surfaces of activated transfused within 4h or discarded. Details of each unit
platelets, thus having a mainly local effect with little given and the total volume transfused should be recorded
impact on systemic coagulation. Increasingly used in the patients notes and/or anaesthetic record.
off-licence for arresting major traumatic, surgical See also, Blood products; Blood transfusion
and obstetric haemorrhage, although use is restricted
owing to extremely high cost. Blood substitutes, see Blood, artificial
See also, Blood, artificial; Blood storage
Blood tests, preoperative, see Investigations,
Blood storage. Viability of red cells is defined as at least preoperative
70% survival 24h post-transfusion.
The following occur in stored blood: Blood transfusion. Reports of transfusion between
reduced pH, as low as 6.77.0, mainly due to high animals, and between animals and humans, date from the
PCO2. seventeenth century. Transfusions between humans were
increased lactic acid. performed in the early nineteenth century. Adverse
increased potassium ion concentration, up to reactions in recipients, and clotting of blood, were major
30mmol/l. problems. ABO blood groups were discovered in 1900;
reduced ATP and glucose consumption. improvements in blood compatibility testing and antico-
shift to the left of oxyhaemoglobin dissociation agulation followed.
curve (ValtisKennedy effect). In the UK, NHS Blood and Transplant, a Special
reduced 2,3-DPG levels. Health Authority, relies on voluntary donors, and is
reduced viability of other blood constituents, e.g. increasingly hard-pressed to meet demand for blood
platelets and leucocytes, and formation of microag- products. Perioperative use accounts for about 50% of
gregates. Coagulation factors V and VIII are almost total blood usage. Recent guidelines suggest that, under
completely destroyed, XI is reduced, and IX and X stable conditions, a perioperative haemoglobin concen-
are reduced after 7 days. tration of 710g/dl should be maintained, depending on
Storage solutions: the circumstances.
SAG-M (saline 140mmol/l, adenine 1.5mmol/l, Complications of transfusion:
glucose 50mmol/l and mannitol 30mmol/l). The immunological (reactions are associated with 2% of
standard solution used in the UK. Used to resus- all transfusions):
pend concentrated red cells after removal of plasma - immediate haemolysis (e.g. ABO incompatibil-
from CPD anticoagulated blood (see below), allow- ity). Incidence is 1in 2500001 000000. Features
ing a greater amount of plasma to be removed for include rapid onset of fever, back pain, skin rash,
other blood products. Has similar preserving prop- hypotension and dyspnoea. DIC and renal failure
erties to CPD-A. Mannitol prevents haemolysis. may occur. Hypotension and increased oozing
BAGPM (bicarbonate-added glucosephosphate of blood from wounds may be the only indication
mannitol) is similar. of incompatible transfusion in an anaesthetised
ACD (acidcitratedextrose): trisodium citrate, patient. Immediate treatment is as for anaphy-
citric acid and dextrose. Introduced in the 1940s. laxis, although the underlying mechanisms are
Red cell survival is 21 days. 2,3-DPG is greatly different. Samples of recipient and donor blood
reduced after 7 days. should be taken for analysis. Mortality is up to
CPD (citratephosphatedextrose): citrate, sodium 50%. Most cases arise from clerical errors (e.g.
dihydrogen phosphate and dextrose. Described in incorrect labelling or administration to the wrong
the late 1950s. Red cell survival: 28 days. 2,3-DPG patient).
is greatly reduced after 14 days. - delayed haemolysis (e.g. minor groups). Usually
CPD-A. Addition of adenine increases red cell ATP occurs 710 days after transfusion, with fever,
levels. Red cell survival: 35 days. 2,3-DPG is low anaemia and jaundice. Renal failure may occur.
after 14 days. Used for whole blood. - reactions to platelets and leucocytes (HLA anti-
Storage at 26C is optimum for red cells but reduces gens). Slow onset of fever, dyspnoea and tachy-
platelets and clotting factors. 22C is optimum for plate- cardia; shock is rare.
lets (survival time 35 days). Freezing of blood is expen- - reactions to donor plasma proteins (often IgA).
sive and time-consuming, but allows storage for many May cause anaphylaxis. Transfusion-related
years. It requires 2h of thawing, and removal of glycerol acute lung injury (TRALI), a form of ALI
(used to prevent haemolysis). caused by donor antibodies reacting with recipi-
After rewarming and transfusion, potassium is taken ent leucocyte antigens and defined as occurring
up by red cells. 2,3-DPG levels are restored within 24h. within 6h of transfusion, occurs in 1:500010000
Plastic collection bags, permeable to CO2 without transfusions.
altering the blood itself, were introduced in the 1960s. - graft-versus-host disease in immunosuppressed
In the closed triple-bag system, blood passes from patients.
the donor to the first collection bag, from which plasma - febrile reactions of unknown aetiology, with or
and red cells are passed into separate bags if required. without urticaria.
The closed system prevents exposure to air and - infusion of Rhesus-positive blood into Rhesus-
infection. negative women of child-bearing age may cause
Before transfusion, the correct identity of the unit of haemolytic disease of the newborn in future
blood (including expiry date) and the patient must be pregnancies.
confirmed (by checking against an identification band). - increased tumour recurrence has been reported
The integrity of the bag should be checked. Blood left in patients undergoing surgery for colonic, ovarian
out of the fridge for more than 30min should be and prostatic cancer, who receive perioperative
 Blood transfusion 77

Table 11 Exclusions and screening applying to donation of blood (NB primarily applies to the UK, though similar procedures apply to other
Western countries)

Donors excluded Blood screening Comments

Brucellosis Past history of infection

Cytomegalovirus For immunocompromised About 55% of the population are
(CMV) patients only CMV-positive
Glandular fever Infection within last 2 years
Hepatitis Hepatitis or jaundice within last year Hepatitis B surface antigen: No carrier state for hepatitis A, therefore
Acupuncture (unless by registered routine not screened for
practitioner), tattoo or other skin Hepatitis C antibodies/RNA: If post-transfusion hepatitis occurs,
piercing within 6 months routine the donor may be traced and further
investigated
Risk of transmission ~1:500000 units
for hepatitis B and 1:32 million for
hepatitis C
HIV At-risk groups: either permanent (iv drug HIV-1 and HIV-2 antibodies: Risk of transmission ~1:45 million units
users, sex workers, previous HIV-positive routine
test) or within 1 year of sex with
someone from an at-risk group
HTLV-I Past history of infection Antibodies: routine Infection may result in adult T-cell leukaemia
Malaria Visit to endemic areas within last 6 months,
with only plasma collected for next 5
years unless cleared by antibody testing
vCJD Recipients of: transfusion in the UK after Leucodepletion (removal of white cells) of
1980; iv immunoglobulins prepared from all blood components
UK plasma; human pituitary extract Plasma for fractionation to make plasma
Donors whose blood has been tranfused to derivatives imported from outside the UK
recipients who later develop vCJD FFP for patients < 16 years old imported
without other explanation from outside the UK
Family member with vCJD A filter that removes the prion protein
responsible for vCJD is under investigation
Syphilis Past history of infection Antibodies: routine
Others Blood donation within last 12 weeks Trypanosoma cruzi antibodies
Chesty cough, sore throat, active cold sore and West Nile virus RNA
or any infection within last 2 weeks if recent travel to
Antibiotic medication within last week endemic areas
Currently pregnant or 9 months
postpartum

HTLV-I, human T-cell leukaemia and lymphoma virus type I; vCJD, variant CreutzfeldtJakob disease.

transfusion, possibly via immunosuppression due - citrate toxicity: citrate is normally metabo-
to transfused leucocytes. Leucodepleted blood lised to bicarbonate within a few minutes. Rapid
has been suggested as a better alternative to transfusion of citrated blood may cause hypo
whole blood, if transfusion is absolutely necessary calcaemia, and calcium administration may be
in these groups. required. Alkalosis may follow citrate metabolism
infective: transmission of infective agents is reduced/ to bicarbonate. With the modern practice of using
prevented by excluding certain groups from donat- SAG-M (salineadenineglucosemannitol) solu-
ing blood, and screening donated blood (Table 11). tion, citrate toxicity is rare unless large volumes
Bacterial contamination of donor units, typically of plasma or platelet preparations are given, since
with Gram-negative organisms, e.g. pseudomonas these do contain citrate.
or coliforms, may result in fever and cardiovascular - acidosis due to transfused blood is rarely a
collapse. Risk is 1 in 500000 units transfused. problem (see above).
Platelet concentrates harbouring staphylococcus, circulatory overload and cardiac failure. More likely
yersinia and salmonella have been reported. Risk is in the elderly, and in the correction of chronic
about 1 in 50000. anaemia. Diuretics (e.g. furosemide 40mg) may be
metabolic: given with transfusion.
- hyperkalaemia: rarely a problem, unless with hypothermia. Rapid infusion of cold blood may
rapid transfusion in hyperkalaemic patients, as cause cardiac arrest. All transfused blood should be
potassium is rapidly taken up by red cells after warmed, especially when infused rapidly. Excessive
infusion and warming. heat may cause haemolysis.
78 Blood transfusion, autologous

in the ICU, recent evidence suggests that lowering impaired O2 delivery to tissues.
the threshold for transfusion from 10g/dl to 7g/dl impaired coagulation. Fresh frozen plasma and
may decrease mortality, organ dysfunction and platelets should be given only when there is clinical
cardiac complications. and laboratory evidence of abnormal coagulation.
impaired O2 delivery to tissues, due to the leftward hypothermia.
shift of oxyhaemoglobin dissociation curve in stored hypocalcaemia (if rapid transfusion).
blood that lasts up to 24h. In addition, red cells in hyperkalaemia may occur, although this is rarely a
stored blood are thought to be more likely to cause problem; hypokalaemia may follow potassium
blockage of capillaries owing to their reduced phys- uptake by red cells.
ical flexibility, further impairing O2 delivery. metabolic acidosis may occur initially; alkalosis may
impaired coagulation caused by dilution and/or follow as citrate is metabolised to bicarbonate (rare
consumption of circulating clotting factors and with modern blood products).
platelets. DIC is rare. hypovolaemia or fluid overload.
microaggregates (see Blood filters). ARDS may follow many situations where large
thrombophlebitis and extravasation. blood transfusions are required.
air embolism. Sihler KC, Napolitano LM (2010). Chest; 137: 20920
iron overload (chronic transfusions). See also, Blood products; Blood storage
interaction when stored blood is administered
following iv fluids, e.g. clotting (gelatin solu- Blood urea nitrogen (BUN). Nitrogen component of
tions, Hartmanns solution), haemolysis (dextrose blood urea. Gives an indication of renal function in a
solutions). similar way to urea measurement. Normally 1.5
Klein HG, Spahn DR, Carson JL (2007). Lancet; 370: 3.3mmol/l (1020mg/dl).
41526
See also, Blood groups; Blood storage; Blood transfusion, Blood volume. Total blood volume is approximately
massive; Intravenous fluid administration; Rhesus blood 70ml/kg in adults, 80ml/kg in children and 90ml/kg in
groups neonates (although the latter may vary widely, depend-
ing on how much blood is returned from the placenta at
Blood transfusion, autologous. Transfusion of a birth. The formula: [% haematocrit + 50]ml/kg has been
patients own blood. Interest in it has increased over the suggested for neonates).
last two decades because of the risks of infection and Distribution (approximate):
transfusion reactions, and an increasing shortfall between 6070% venous
the demand and supply of donated blood. 15% arterial
Different methods used: 10% within the heart
26 units are taken over a period of days or 5% capillary.
weeks before surgery. Concurrent oral iron therapy Measured by dilution techniques; plasma volume is
ensures an adequate bone marrow response. Eryth- found by injecting a known dose of marker (e.g. albumin
ropoietin has been used. Pretransfusion testing labelled with dyes or radioactive iodine) into the blood
varies between centres, from ABO grouping to full and measuring plasma concentrations. Rapid exchange
cross-matching. Labelling of blood must be meticu- of albumin between plasma and interstitial fluid leads to
lous and this requirement, together with wastage of slight overestimation using this method; larger mole-
unused blood (which may be up to 20%), results cules, e.g. immunoglobulin, may be used.
in the administration costs being higher than for
Total blood volume
allogeneic transfusion. Only suitable for elective
surgery. 100
= plasma volume
perioperative haemodilution: simultaneous collec- 100 %haematocrit
tion of blood and replacement of removed volume
Red cell volume may be found by labelling erythrocytes
with colloid or crystalloid. The collected blood is
with radioactive markers, e.g. 51Cr.
available for transfusion when required, usually
during or shortly after blood loss has stopped.
peri- or postoperative retransfusion of blood sal-
Bloody tap, see Epidural anaesthesia
vaged from the operation site during surgery.
Washing and filtering remove debris and contami- Blow-off valve, see Adjustable pressure-limiting valve
nants. Methods range from simple closed collecting/
reperfusion systems to expensive centrifuging BMI, see Body mass index
machines (the latter referred to as cell salvage).
Ashworth A, Klein AA (2010). Br J Anaesth; 105: BMR, see Basal metabolic rate
40116
See also, Blood transfusion Bodok seal. Metal-edged rubber bonded disk, used to
prevent gas leaks from the cylinder/yoke interface on
Blood transfusion, massive. Definitions vary but anaesthetic machines.
include:
transfusion of 10 units of blood within 6h. Body mass index (BMI). Indication of body fat derived
transfusion of 5 units of blood within 1h. from a persons weight and height: BMI = weight (kg)
replacement of blood volume with transfused blood height (m)2. Widely used as a measure of obesity,
within 24h. although it doesnt account for body build and muscle
Adverse effects are those of blood transfusion gener- mass. Also used to refer to degrees of underweight. Has
ally; in particular: been incorporated into most international and national
 Bone marrow harvest 79

Bohr effect. Shift to the right of the oxyhaemoglobin

Table 12World Health Organization classification of obesity dissociation curve associated with a rise in blood PCO2
according to body mass index (kg/m2)
and/or fall in pH. Results in lower affinity of haemoglo-
Underweight < 18.5 bin for O2, favouring O2 delivery to the tissues, where
CO2 levels are high.
Normal 18.524.99 The double Bohr effect refers to pregnancy, when
Overweight 25.029.9 CO2 passes from fetal to maternal blood at the placenta,
Obese: class I 30.034.9 causing the following changes:
class II 35.039.9 maternal blood: CO2 rises, i.e. shift of curve to right
class III 40.0 and reduced O2 affinity.
fetal blood: CO2 falls, i.e. shift of curve to left and
increased O2 affinity.
The net effect is to favour O2 transfer from maternal to
classifications of obesity (Table 12), although some fetal blood.
national variations in definitions exist. [Christian Bohr (18551911), Danish physiologist]
See also, Oxygen transport
Body plethysmograph. Airtight box, large enough to
enclose a human, used to study lung volumes and pres- Bohr equation. Equation used to derive physiological
sures. Once a subject is inside, air pressure and volume dead space.
may be measured before and during respiration. Expired CO2 = inspired CO 2 + CO2 given out by lungs,
May be used to measure: or: FE VT = (FI VT ) + (FA VA )
FRC: the subject makes inspiratory effort against a
where FE = fractional concentration of CO2 in expired
shutter. Box volume is decreased due to lung expan-
gas
sion, and box pressure increased because of the
FI = fractional concentration of CO2 in inspired
decrease in volume. Applying Boyles law:
gas
original pressure volume FA = fractional concentration of CO2 in alveolar
= new pressure new volume gas
where new volume = original volume change in VT = tidal volume
lung volume. VA = alveolar component of tidal volume.
Thus change in lung volume may be calculated. If
Since inspired CO2 is negligible, it may be ignored:
airway pressures are also measured:
i.e. FE VT = FA VA
original airway pressure resting lung volume
= new airway pressure new lung volume But VA = VT VD, where VD = dead space
Therefore:
where resting lung volume = FRC
and new volume = FRC + change in lung volume FE VT = FA (VT VD )
= (FA VT ) (FA VD )
Thus FRC may be calculated.
airway resistance: or: FA VD = (FA VT ) (FE VT )
= VT (FA FE )
alveolar pressure mouth pressure
= VD FA FE
airflow Therefore =
VT FA
The subject breathes the air in the box. Box volume
is reduced by the change in alveolar volume during Since partial pressure is proportional to concentration:
inspiration, measured as above. Lung volume may VD PA CO2 PECO2
be measured at the same time, as above: =
VT PA CO2
lung volume starting alveolar pressure where PACO2 = alveolar partial pressure of CO2
= new lung volume new alveolar pressure; PECO2 = mixed expired partial pressure of CO2
where starting alveolar pressure = box pressure, and
Since alveolar PCO2 approximately equals arterial PCO2,
new lung volume = lung volume + alveolar volume
VD Pa CO2 PECO2
Alveolar pressure may thus be calculated. Also, =
mouth pressure = box pressure, and flow may be VT Pa CO2
measured using a pneumotachograph. where PaCO2 = arterial partial pressure of CO2.
pulmonary blood flow: the subject breathes from a
See also, Bohr effect
bag containing N2O and O2 within the box. As the
N2O is taken up by the blood, the volume of the Boiling point (bp). Temperature of a substance at which
bag decreases. Since N2O uptake is flow-limited its SVP equals external atmospheric pressure. Addi-
(see Alveolar gas transfer), uptake occurs in steps tional heat does not raise the temperature further, but
with each heartbeat. The decrease in bag size provides the latent heat of vaporisation necessary for the
therefore occurs in steps, and is calculated by mea- liquid to evaporate. If external pressure is raised, e.g.
suring bag pressure, and box volume and pressure. within a pressure cooker, bp is also raised; thus the
If the N2O-carrying capacity of blood is known, maximal temperature attainable is raised, and food
pulmonary blood flow may be calculated and dis- cooks more quickly.
played as a continuous trace showing pulsatile flow.
Bone marrow harvest. Taking of bone marrow for
Body surface area, see Surface area, body bone marrow transplantation, from either a healthy
80 Bone marrow transplantation

donor (allograft) or the patient recipient before radio- may be especially prolonged after allogeneic
or chemotherapy (autograft). Usually performed under transplantation, when prolonged immunosup-
general anaesthesia, especially in children, although pressive therapy is required. Antibacterial and
local anaesthetic techniques may be used. antiviral drugs are often given prophylactically;
Anaesthetic considerations: immunoglobulins have also been used (see
preoperatively: Immunoglobulins, intravenous). Blood products
- allografts: donors are usually fit. are often required to restore red cell, white
- autografts: usually performed for blood malig- cell and platelet numbers. Recently, macrophage
nancy; i.e. patients may be anaemic or thrombo- and granulocyte colony-stimulating factors have
cytopenic and prone to infections. Cardiovascular, been used.
respiratory and renal function may be impaired. rejection: may require repeat transplantation.
Drug treatment may include cytotoxic drugs and graft-versus-host disease.
corticosteroids. interstitial pneumonitis may occur; it may be unclear
perioperatively: whether this is related to cytomegalovirus or other
- marrow is usually taken from the posterior atypical infection, or directly related to radiother-
and anterior iliac crests and sternum, requiring apy. Mortality is up to 80%.
positioning first supine, then prone, although
the lateral position may suffice. Tracheal intuba- Boott, Francis (17921863). US-born London physician;
tion and IPPV are usually employed. Avoid- qualified in Edinburgh. Having read a letter from Big-
ance of N2O has been suggested, but this is elows father about Mortons demonstration of diethyl
controversial. ether, he arranged a dental extraction by Robinson (who
- large-bore iv cannulation is required, since there also administered the ether) on 19 December 1846 at his
may be large volume losses. Autologous blood house in Gower Street, London (now a nursing home
transfusion is usually performed, especially for and formerly the location of part of the FCAnaes exami-
allografts. Non-autologous blood is irradiated nation). He then informed Liston, who operated using
before transfusion to kill any leucocytes present. ether 2 days later.
The volume of marrow harvested is up to 2030% [James Robinson (18131861), English dentist]
of estimated blood volume, to provide the required Ellis RH (1977). Anaesthesia; 32: 197208
leucocyte count.
- heparin may be given to stop the marrow clotting; Bosentan monohydrate. Endothelin receptor antago-
it may also protect against fat embolism, which nist (both type A and type B) licensed as a treatment for
may occur during harvesting. pulmonary hypertension. Decreases both pulmonary
postoperatively: large volumes of iv fluids are often and systemic BP without affecting heart rate. May cause
required. hepatic impairment. Sitaxsentan is similar but has greater
action at type A receptors and is less hepatotoxic.
Bone marrow transplantation. Performed for leukae-
mias, lymphomas, certain solid tumours, and various Bosun warning device, see Oxygen failure warning
non-malignant disorders including aplastic anaemia, devices
haemoglobinopathies and rare genetic diseases. Involves
donation of bone marrow (usually under general anaes- Botulinum toxins. Group of exotoxins responsible for
thesia), and its subsequent infusion via a central vein botulism. Act on presynaptic cholinergic nerve terminals
into the recipient, whose own bone marrow has been blocking release of acetylcholine. Eight have been char-
ablated with chemotherapy + radiotherapy. acterised (labelled AH), each produced by a distinct
May be one of three types: strain of Clostridium botulinum. Types A, B and E
autologous: the recipients own bone marrow is (rarely, F and G) cause disease in humans. Types A and
taken and treated to remove neoplastic cells before B have been used therapeutically in minute quantities in
being frozen and stored while ablation is performed. order to cause selective muscle weakness that may last
Mortality is up to 10%. for several months, e.g. in strabismus, blepharospasm,
syngeneic: the donor and recipient are identical hemifacial spasm, torticollis, dystonias, spasmodic dys-
twins. Treatment of the collected cells is not phonia and as a cosmetic procedure. Also used as a tool
required. to investigate neurotransmitter function.
allogeneic: the donor is HLA-matched as closely
as possible to the recipient; they usually come from Botulism. Clinical syndrome caused by ingestion of
the same family or racial group. Mortality is up exotoxins (botulinum toxins) produced by the anaerobic
to 30%. Gram-positive bacillus Clostridium botulinum. Exotoxin
Problems occur with all three types but to different binds irreversibly to cholinergic nerve endings, prevent-
extents, and may be related to: ing acetylcholine release. Affects the neuromuscular
the procedure itself: junction, autonomic ganglia and parasympathetic post-
- ablative therapy includes cyclophosphamide, ganglionic fibres. Classified according to the source of
busulfan and other cytotoxic and immuno infection:
suppressive drugs. Toxic effects include vomiting, foodborne botulism: caused by ingestion of Clos-
cardiomyopathy, convulsions, pulmonary fibrosis, tridium spores or exotoxin produced under anaero-
GIT mucositis and hepatic veno-occlusive disease. bic conditions (e.g. home canning).
- impaired bone marrow function: bacterial, viral, wound botulism: due to contamination of surgical
fungal and pneumocystis infections may be prob- or other wounds. Also seen in drug abusers
lems in the first 46 months after autologous injecting black-tar heroin subcutaneously (skin-
and syngeneic transplantation; immunodeficiency popping).
 Brachial plexus 81

infant botulism: due to absorption of exotoxin pro- Treatment:

duced within the GIT, classically after eating con- supportive measures, including antibacterial drugs,
taminated honey. restoration of cardiac output vasodilator drugs.
adult infectious botulism: similar to the infant form intra-arterial infusion of vasodilators, e.g. papaver-
but follows GIT surgery. ine 3060mg/h, has been used via the angiography
inadvertent botulism: follows accidental overdose catheter.
of botulinum toxin given for treatment of move- surgery to resect necrotic bowel remove embolus
ment disorders (e.g. dystonia). or thrombus.
Features occur within 1272h:
nausea, vomiting and abdominal pain. Boyle, Henry Edmund Gaskin (18751941). English
symmetrical descending paralysis initially affecting anaesthetist, best known for the anaesthetic machine
cranial nerves, with diplopia, facial weakness, dys- named after him. Originally introduced in 1917, it con-
phagia, dysarthria, limb weakness and respiratory sisted of N2O and O2 cylinders, pressure gauges, water-
difficulty. sight flowmeters and ether vaporiser (Boyles bottle)
autonomic disturbance: ileus, unresponsive pupils, set in a wooden case. Being left-handed, he placed all
dry mouth, urinary retention. controls on the left side of the machine, a practice that
sensory deficit, mental disturbance and fever do not continues today. His name is also attached to the instru-
occur. ment used to maintain jaw opening during tonsillectomy
Diagnosed by inoculation of the patients serum into (BoyleDavis gag). Boyle practised at St Bartholomews
mice that have been treated or untreated with antitoxin. Hospital, London, was involved in the advancement and
Different strains of toxin may be identified. EMG improvement of anaesthesia in the UK, and performed
studies may aid diagnosis while waiting for inoculation much work into the use of N2O, including under battle
studies. conditions.
Management:
[John S Davis (18241885), US surgeon]
supportive. IPPV may be necessary. Hadfield CF (1950). Br J Anaesth; 22: 10717
wound debridement if indicated.
antitoxin to neutralise circulating exotoxin. Hyper-
Boyles law. At constant temperature, the volume of
sensitivity may occur. A human botulism immuno-
a fixed mass of a perfect gas varies inversely with
globulin is used for treatment of infant botulism and
pressure.
those allergic to the antitoxin.
[Robert Boyle (16271691), English chemist]
penicillin to kill live bacilli.
See also, Charles law; Ideal gas law
Complete recovery may take months.
See also, Biological weapons, Paralysis, acute
Brachial artery. Continuation of the axillary artery,
Bougie, see Intubation aids running from the lower border of teres minor to the
antecubital fossa, where it divides into the radial and
Bourdon gauge, see Pressure measurement ulnar arteries. Lies at first medial, then anterior to the
humerus. Around its midpoint, crossed from lateral to
Bovie machine, see Diathermy medial by the median nerve. Protected from the medial
cubital vein in the antecubital fossa by the bicipital apo-
Bowditch effect. Intrinsic regulatory mechanism of neurosis. Occasionally divides in the upper arm.
cardiac muscle in response to increased rate of stimula- May be used for arterial cannulation, although seldom
tion. As rate increases, contractility increases. Also called as the site of first choice because of possible distal
the treppe effect. ischaemia.
[Henry Bowditch (18401911), US physiologist; Treppe,
German for steps] Brachial plexus. Nerve plexus supplying the arm. Arises
from the ventral rami of the lower cervical and first
Bowel ischaemia. May affect any part of the GIT thoracic spinal nerves, and emerges between the scalene
(although rarely stomach) but usually affects the large muscles in the neck. The plexus invaginates the scalene
bowel. May be caused by thrombus, embolism (e.g. from fascia and passes down over the first rib (Fig. 26a). It
mural thrombus after MI), vascular spasm or low mes- accompanies the subclavian artery (which becomes the
enteric perfusion with vasoconstriction (non-occlusive axillary artery) within a perivascular sheath of connec-
mesenteric ischaemia [NOMI]). May occur in patients tive tissue.
with intra-abdominal pathology, especially following Anatomy of the scalene muscles:
vascular surgery, or in any patient with low cardiac scalenus anterior arises from the anterior tubercles
output. May also occur in severe intestinal obstruction. of the 3rd6th cervical transverse processes, and
Vasoconstriction often persists after correction of the inserts into the scalene tubercle on the first rib.
initial insult. Bowel infarction may follow as a result of scalenus medius arises from the posterior tubercles
reduced tissue oxygenation or reperfusion injury. of the 2nd6th cervical transverse processes and
Associated with high mortality because diagnosis inserts into the first rib behind the groove for the
may be difficult, and bowel infarction may continue subclavian artery.
despite treatment. Gastric tonometry has been used to scalenus posterior is the portion of the previous
monitor GIT perfusion in critical illness. muscle attached to the second rib.
Features include abdominal pain and distension, GIT The roots lie in the interscalene groove; the trunks
bleeding, nausea and vomiting, tachycardia, pyrexia, leu- cross the posterior triangle of the neck; the divisions
cocytosis and metabolic acidosis. Angiography may be lie behind the clavicle; the cords lie in the axilla.
useful to diagnose ischaemia and differentiate its causes. Branches arise at different levels (Fig. 26b):
82 Brachial plexus

roots: nerves to the rhomboids, scalene muscles and - medial:

serratus anterior (long thoracic nerve), and a con- - medial pectoral nerve to pectoralis major and
tribution to the phrenic nerve (C5). minor.
trunks: nerve to subclavius, and the suprascapular - medial cutaneous nerves of the arm and forearm:
nerve (to supraspinatus and infraspinatus). supply the medial aspect of the upper arm and
cords: forearm respectively.
- lateral: - ulnar nerve.
- lateral pectoral nerve to pectoralis major. - medial part of median nerve.
- musculocutaneous nerve: passes through the - posterior:
belly of coracobrachialis in the upper arm, sup- - subscapular nerves to subscapularis and teres
plying coracobrachialis, biceps and brachialis major.
muscles and the elbow joint. Continues as the - nerve to latissimus dorsi.
lateral cutaneous nerve of the forearm, supply- - axillary nerve: passes posterior to the neck of
ing the radial surface of the forearm. the humerus. Supplies deltoid and teres minor
- lateral part of the median nerve. and the shoulder joint, and continues as the

(a)

Cervical vertebrae

C2

C3
Scalenus medius muscle
C4 Scalenus anterior muscle
C5 Brachial plexus
C6
C7
Subclavian artery
T1

Clavicle
Subclavian vein

1st rib 2nd rib

(b)
Roots Trunks Divisions Cords

To rhomboids
C5
Suprascapular Lateral pectoral pectoralis major
Upper Lateral

To subclavius Musculocutaneous
C6

Axillary
Middle Posterior
C7 Radial Median
Subscapular

To latissimus dorsi
C8
Subscapular Ulnar
Lower Medial
Medial cutaneous of forearm
Medial cutaneous of arm
T1 Medial pectoral
pectorals

Long thoracic
serratus
anterior

Fig. 26 (a) Relations of the upper brachial plexus.

(Continued)
 Brachial plexus block 83

(c)
Anterior Posterior

Upper lateral cutaneous n Upper lateral cutaneous n

of the arm (from axillary nerve) of the arm

Lower lateral cutaneous n Medial cutaneous n Posterior cutaneous n of the

of the arm (from radial nerve) of the arm arm (from radial nerve)

Lateral cutaneous n of forearm Medial cutaneous n Lateral cutaneous n

(from musculocutaneous nerve) of the forearm of the forearm

Radial nerve Radial nerve

Ulnar nerve

Median nerve

Fig. 26 (Continued) (b) Plan of the brachial plexus. (c) Cutaneous nerve supply of the arm

upper lateral cutaneous nerve of the arm, - produces adequate block for shoulder
supplying the skin of the outer shoulder. manipulations.
- radial nerve. - ulnar nerve may be missed.
The plexus thus supplies the skin of the upper limb - complications include phrenic nerve block, recur-
(Fig. 26c). rent laryngeal nerve block, Horners syndrome,
Characteristic motor lesions of the plexus: inadvertent epidural or spinal block and injection
upper roots: waiters tip position; arm internally into the vertebral artery. Bilateral blocks, or
rotated and pronated, with wrist flexed (Erbs blocks in patients with contralateral phrenic nerve
paralysis). palsy, should be avoided.
lower roots: claw hand (Klumpkes paralysis). supraclavicular:
[Wilhelm Erb (18401921), German physician; Augusta - with the patients head turned away from the side
Klumpke (18591927), French neurologist] to be blocked, a needle is inserted immediately
See also, Brachial plexus block; Dermatomes posterior and lateral to the subclavian pulsation
behind the mid-clavicle. In the classic technique,
Brachial plexus block. May be performed by injecting it is directed caudally, medially and posteriorly to
local anaesthetic solution into the fascial compartment the upper surface of first rib, and walked along
surrounding the brachial plexus at several levels. Needle the rib until the needle position is confirmed;
placement is routinely guided by use of a nerve stimula- 810ml solution is injected per division.
tor (eliciting contractions in the appropriate muscle - median nerve may be missed.
group) or ultrasound imaging: - complications: phrenic and recurrent laryngeal
interscalene: nerve blocks, Horners syndrome, subclavian
- with the patients head turned away from the side puncture, pneumothorax. Bilateral blocks should
to be blocked, a needle is inserted in the intersca- be avoided.
lene groove, lateral to the sternomastoid, and subclavian perivascular:
level with the cricoid cartilage. It is directed - with the patients head turned away from the side
towards the transverse process of C6 (medially, to be blocked, a needle is inserted in the intersca-
caudally and posteriorly). Accidental epidural, lene groove, caudal to the level of the cricoid
intrathecal or intravascular injections are more cartilage, and cranial and posterior to a finger pal-
likely if the needle is directed cranially. pating the subclavian artery. It is directed caudally
- 3040ml solution is injected when the needle only, until the needle position is confirmed (for
position is confirmed. If a nerve stimulator is used, nerve stimulation, contractions elicited in the
contractions should be sought in the shoulder, arm/hand, not in the shoulder, which may be
arm or forearm. caused by stimulation of the suprascapular nerve).
84 Bradycardia

- 2030ml solution is injected. been described, with injection of 2040ml solu-

- complications: as for supraclavicular block, but tion at a depth of 57cm. Horners syndrome is
pneumothorax is less likely. common; difficulty breathing may also occur and
axillary: epidural and spinal blockade have been reported.
- with the patients head turned away, the arm Suitable solutions:
abducted to 90 and the hand under the head, a prilocaine or lidocaine 11.5% with adrenaline:
needle is inserted just above the axillary artery onset within 2030min and lasts for 1.52h.
pulsation, as high in the axilla as possible. A click bupivacaine 0.3750.5%: onset up to 1h; lasts for
is felt as the perivascular sheath is entered. up to 12h. Combination with 1% lidocaine speeds
- 2550ml solution is injected, with digital pres- onset.
sure or a tourniquet below the injection site to The area blocked is increased by using larger volumes
encourage upward spread of solution. Careful of solution. Motor block is increased by increasing con-
aspiration before application of digital pressure centration, and intensity of block by increasing total
excludes placement of the needle in the axillary dose. Although maximal safe doses have been exceeded
vein. The arm is returned to the patients side without serious effects or high blood levels of agent, this
after injection, to avoid compression of the proxi- cannot be recommended routinely. Systemic uptake of
mal sheath by the humeral head, or before injec- agent is greatest following interscalene block, and least
tion if a cannula technique is used. following axillary block. Incidence of neurological
- a cannula, e.g. iv type 1820G, may be inserted damage is thought to be reduced by using short bevelled
and used for repeated injection. needles, and using a nerve stimulator rather than elicit-
- may miss the musculocutaneous and axillary ing paraesthesia as the end-point for localisation.
nerves. See also, Regional anaesthesia
The former may be blocked thus:
- upper arm: at the time of axillary block, 510ml Bradycardia, see Heart block; Junctional arrhythmias;
is injected above the perivascular sheath, into Sinus bradycardia
coracobrachialis muscle. Bradykinin, see Kinins
- elbow: 10ml is injected in the groove between
biceps tendon and brachioradialis in the ante- Brain. Intracranial part of the CNS. Forms from
cubital fossa, and infiltrated subcutaneously tubular neural tissue, developing into hindbrain (rhomb-
around the lateral elbow. encephalon), midbrain (mesencephalon) and forebrain
the intercostobrachial nerve, supplying the inner (prosencephalon):
upper arm, may be blocked by superficial infiltra- hindbrain:
tion as the needle is withdrawn from the axillary - medulla: continuous with the spinal cord. Com-
block. municates with the cerebellum via the inferior
fascial sheets within the neurovascular sheath may cerebellar peduncle. Forms the posterior part of
cause a patchy block. Puncture both above and the fourth ventricle floor. Contains the decussa-
below the artery has been suggested as a remedy. tion of pyramidal tracts, gracile and cuneate
Alternatively, separate identification of the differ- nuclei, nuclei of cranial nerves IX, X, XI and XII,
ent nerves with a nerve stimulator has been advo- and vital centres, e.g. for respiration and cardio-
cated (median: causes contraction of flexor carpi vascular homeostasis.
radialis; ulnar: flexor carpi ulnaris; radial: extensor - pons: communicates with the cerebellum via the
muscles of hand/wrist; musculocutaneous: biceps), middle cerebellar peduncle. Forms the anterior
with the total dose divided between them. Inten- part of the fourth ventricle floor. Contains the
tional transfixion of the artery has also been nuclei of cranial nerves V, VI, VII and VIII, and
described: blood is aspirated as the needle is pontine nuclei. Also houses the apneustic and
advanced through the artery; when aspiration pneumotactic centres of breathing control.
ceases, solution is deposited posterior to the artery. - cerebellum: occupies the posterior cranial fossa.
infraclavicular: Consists of grey cortex covering white matter.
- with the patients arm abducted, a needle is Communicates via the medulla, pons and mid-
inserted 23cm caudal to the midpoint of a line brain with the thalamus, cerebral cortex and
drawn between the medial head of the clavicle spinal cord. Regulates posture, coordination and
and the coracoid process. The needle is advanced muscle tone. Lesions cause ipsilateral effects.
laterally parallel to this line and at 45 to the midbrain: communicates with the cerebellum via
skin until twitches are seen in the hand (pectoral the superior cerebellar peduncle. Contains the
contraction indicates superficial placement of pineal body and cranial nerve nuclei III and IV.
the needle, and biceps contraction may be forebrain:
achieved by stimulating the musculocutaneous - diencephalon: consists of the hypothalamus
nerve outside the plexus sheath). Has also been (forming the floor of the lateral wall of the third
described with the needle directed directly poste- ventricle) with the pituitary gland below, and
riorly at a point 1cm medial and 2cm caudal to thalamus (lateral to the third ventricle). The thal-
the coracoid process. amus integrates sensory pathways.
- 3045ml solution is injected. - basal ganglia: grey matter within cerebral hemi-
posterior: spheres. The internal capsule, containing the
- with the patient sitting or lying, and the cervical major ascending and descending pathways to and
spine flexed, a needle is inserted 3cm from the from the cerebral cortex, passes between the
midline level with the C67 interspace. A loss of basal ganglia. They receive and relay information
resistance technique or nerve stimulation has concerned with fine motor control.
 Breathing, control of 85

- cerebral cortex: water into the ear canal (normal response is a

- frontal lobes: contain motor cortices, including tonic deviation of the eyes towards the side
areas for speech and eye movement; areas being irrigated followed by a faster phase back
for intellectual and emotional functions lie towards the midline). Each ear is tested in turn,
anteriorly. having checked that the canal is not blocked. (In
- parietal lobes: contain sensory cortices, and the UK, testing for dolls eye movements is not
areas for association and integration of sensory used as a component of brainstem testing.)
input. - gag reflex (CN IX and X).
- temporal lobes: contain auditory cortices, and - cough reflex (CN X).
areas for integration and association of auditory - absent motor responses within cranial nerve dis-
input and memory. Also constitutes part of the tribution, to any peripheral stimuli (corticospinal
limbic system, which integrates endocrine, auto- tract runs through the brainstem).
nomic and motivational functions. - absent respiratory efforts despite arterial PCO2 of
- occipital lobes: contain the visual cortices, and 6.6kPa (50mmHg), and adequate oxygenation
areas for association and integration of visual (e.g. with apnoeic oxygenation). Must be con-
sensory input. firmed using blood gas interpretation.
See also, Ascending reticular activating system; Brain- All the above requirements must be met for the diagno-
stem; Cerebral circulation; Cerebrospinal fluid; Motor sis of brainstem death to be made. Two sets of tests
pathways; Sensory pathways should be performed by two doctors (registered for 5
years) who have skill in the field, one of whom is a con-
Brainstem. Composed of midbrain, pons and medulla. sultant, neither of whom should be part of the organ
Contains neurone groups involved in the control of donation team.
breathing, cardiovascular homeostasis, GIT function, The tests may be carried out together or separately.
balance and equilibrium, and eye movement. Also inte- No specific time interval has been recommended
grates ascending and descending pathways between the between testing. Although EEG, cerebral angiography
spinal cord, cranial nerves, cerebellum and higher and oesophageal contractility testing are performed in
centres, partly via the ascending reticular activating some countries, they are not required to make the diag-
system. nosis of brainstem death in the UK. The legal time of
See also, Brain; Brainstem death; Breathing, control of death is recorded as the time the first set of tests shows
no activity.
Brainstem death. Irreversible absence of brainstem Although the clinical criteria remain unchanged
function despite artificial maintenance of circulation and for paediatric patients, the interval between the two
gas exchange. Clinical experience has shown that, once tests differs. No UK recommendations exist; therefore
it is diagnosed, cardiac arrest is inevitable, usually within the US ones are usually followed for children of differ-
a few days. Guidelines have been established for the ent ages:
withdrawal of artificial support and, where appropriate, newborn to 2 months (usually performed for medi-
arrangement for organ donation. These guidelines colegal reasons): interval 48h.
include: 212 months: 24h.
necessary preconditions: 118 years: 12h.
- apnoeic coma (i.e. the patient is unresponsive and Vegetative state associated with absent cortical function
requiring IPPV). or cortical disconnection may occur with intact brain-
- irreversible structural brain damage caused stem reflexes. Such patients may have spontaneous res-
by a disorder that can lead to brain death piration and may live for years without recovery, and do
(e.g. subarachnoid haemorrhage, head injury, not satisfy the criteria for brainstem death.
meningitis). Gardiner D, Shemie S, Manara A, Opdam H (2012). Br
necessary exclusions: J Anaesth; 108: i1428
- absence of primary hypothermia, i.e. core tem-
perature > 35C (N.B. secondary hypothermia Braun, Heinrich Friedrich Wilhelm (18621934).
often follows brainstem death). German surgeon who also practised and investigated
- absence of primary metabolic or endocrine distur- anaesthesia. One of the pioneers of local anaesthesia,
bance (N.B. secondary endocrine abnormalities he described many local blocks, and published exten-
often follow brainstem death, e.g. diabetes insipi- sively on the subject. Introduced adrenaline to local
dus, hypothyroidism, hypoprolactinaemia). anaesthetic solutions to prolong their action in 1902
- absence of drug intoxication, including sedatives and in 1903 suggested its possible use in resuscitation.
given in ICU. Popularised procaine in 1905.
- absence of paralysis caused by neuromuscular
blocking drugs (neuromuscular blockade moni- Breathing, control of. The exact origin of the signal
toring is useful) or neuromuscular disorders (e.g. for regular breathing is unknown. Brainstem centres
GuillainBarr syndrome). involved in the control of breathing have been identified;
- absence of abnormal posturing (e.g. decorticate or their precise roles are unclear. There are three such
decerebrate) or convulsions. centres:
necessary clinical findings: medullary centre:
- absent cranial nerve (CN) reflexes: - dorsal respiratory group neurones arising from
- pupillary light reflex (CN II and III). the nucleus tractus solitarius are involved in inspi-
- corneal reflex (CN V and VII). ration; when stimulated they cause diaphragmatic
- oculovestibular reflex (CN VIII), i.e. no eye contraction via contralateral phrenic nerves; they
movement following injection of 4060ml icy also project to ventral neurones.
86 Breathing, muscles of

- ventral respiratory group neurones arising the area enclosed by the broken line represents
from the nucleus ambiguous are predominantly work done to overcome elastic forces.
involved in expiration, causing contraction of ipsi- area A represents work done to overcome resis-
lateral accessory muscles (via vagus nerves) and tance during inspiration.
intercostal muscles. They also inhibit the apneus- area B represents work done to overcome resis-
tic centre. tance during expiration.
apneustic centre in the lower pons: causes excitation The greater the tidal volume or lung volume, the more
of medullary dorsal respiratory group neurones work is required to overcome elastic recoil. The faster
causing inspiration whilst inhibiting ventral respira- the flow rates, the greater the amount of work required
tory group neurones. Surgical section above it to overcome resistance. Normally, energy is provided for
causes prolonged pauses at end-inspiration. expiration by potential energy stored in the stretched
pneumotactic centre (nucleus parabrachialis) in the elastic tissues (i.e. area B lies within the broken line), but
upper pons: curtails inspiration and thus regulates extra energy may be required in airway obstruction.
respiratory rate. Total work of breathing is difficult to measure in
The respiratory centre composed of these groups of spontaneous respiration. Volume may be measured with
neurones receives afferents from chemoreceptors and a pneumotachograph; oesophageal pressure, indicating
other structures: intrapleural pressure, may be measured with an oesoph-
chemoreceptors : ageal balloon. Normally, the work of breathing accounts
- peripheral (aortic and carotid bodies): afferents for less than 3% of the total body O2 consumption at
pass via the vagus and glossopharyngeal nerves rest, but may be much higher in disease states, e.g.
respectively. Stimulated by a fall in arterial PO2, COPD, cardiac failure and during exercise.
also by a rise in PCO2 and hydrogen ion concentra- Expiratory valves in anaesthetic breathing systems
tion. Their response to reduced O2 increases increase work of expiration, particularly when not fully
markedly below 810kPa (6075mmHg). The open. Coaxial anaesthetic breathing systems increase
response to increased CO2 is roughly linear. expiratory resistance, the Lack by virtue of its small-
- central: present on the ventral surface of the calibre expiratory tube, and the Bain because of the high
medulla, but separate from the respiratory centre. flow rate of fresh gas directed at the patients mouth.
Stimulated by a rise in hydrogen ion concentra- Banner MJ, Jaeger MJ, Kirby RR (1994). Crit Care Med;
tion in CSF, due to increased PCO2 or metabolic 22: 51523
acidosis. See also, Airway resistance; Compliance
Hypoxaemia increases the sensitivity of the chemo-
receptors to hypercapnia, and vice versa. Hypoxae- Bretylium tosylate. Class II and III antiarrhythmic
mia causes direct depression of the respiratory drug, originally introduced as an antihypertensive drug.
centres, in addition to reflex stimulation. In chronic Reduces sympathetic drive to the heart and prolongs the
lung disease, the central chemoreceptors may not action potential. Taken up by adrenergic nerve endings,
respond to increased CO2 levels, either due to che- causing release of noradrenaline followed by inhibition
moreceptor resetting or due to correction of CSF of release. Excreted largely unchanged in the urine. Pre-
pH. Hypoxaemia then becomes the main drive to viously reserved for treatment of resistant ventricular
respiration (of importance in O2 therapy). arrhythmias, now no longer available in the UK.
other structures: Dosage: 510mg/kg iv by slow infusion, repeated
- lungs: 12hlater up to 30mg/kg. Followed by 12mg/min
- pulmonary stretch receptors, involved in the or 510mg/kg tds/qds. May also be given im.
HeringBreuer and deflation reflexes. Initial hypertension may be followed by severe hypoten-
- juxtapulmonary capillary receptors, involved in sion. May cause nausea and vomiting.
dyspnoea due to pulmonary disease and pulmo-
nary oedema.
- pulmonary irritant receptors, responding to
noxious stimuli.
- proprioceptors in joints and muscles, thought to
be important during exercise.
- baroreceptors; hypertension inhibits ventilation,
but this is of little clinical significance.
- higher centres, responding to pain and fear.
During anaesthesia, the responses to hypercapnia and
Lung volume

hypoxaemia are depressed, the latter severely.

See also, Carbon dioxide response curve; Expiration
Hypoventilation B A
Inspiration
Breathing, muscles of, see Respiratory muscles

Breathing systems, see Anaesthetic breathing systems

Breathing, work of. Equals the product of pressure FRC

change across the lung and volume of gas moved. During Negative intrapleural pressure
inspiration, most of the work of breathing is done to
overcome elastic recoil of the thorax and lungs, and the Fig. 27 Graph of intrapleural pressure against lung volume during
resistance of the airways and non-elastic tissues (Fig. 27): breathing (see text)
 Bronchiectasis 87

BrewerLuckhardt reflex. Laryngospasm in response Types:

to remote stimulation, e.g. anal or cervical dilatation. small cell (~20%): may arise from APUD cells (see
[Nathan R Brewer (19042009)and Arno B Luckhardt Apudomas), and secrete hormones. Extensive
(18851957), US physiologists] spread is usual at presentation. Extremely poor
prognosis.
British Association for Immediate Care (BASICS). non-small cell:
Voluntary charitable organisation, formed in 1977, - adenocarcinoma (~40%).
whose members provide medical assistance at the scene - squamous cell (~30%): most present with bron-
of an accident or medical emergency or during primary chial obstruction. Better prognosis than the other
transport to hospital. Acts as the national coordinating common forms.
body for schemes and individual doctors providing - large cell (~10%); particularly related to smoking.
immediate care throughout the UK. Organises educa- - others:
tional courses for doctors, nurses, paramedics, occupa- - bronchiolar alveolar, carcinoid: least related to
tional health professionals, the emergency services and smoking.
those involved in healthcare at sporting and other events. - carcinoma in situ.
Features:
British Association of Critical Care Nurses (BACCN). local:
Formed in 1984 from the amalgamation of various - haemoptysis, cough, dyspnoea.
groups of UK critical care nurses. Exists to support per- - wheeze, stridor, chest discomfort.
sonal and professional development of members (who - chest infection, pleural effusion.
include nurses, managers, educationalists, researchers invasion of:
and others with an interest in critical care) and to - mediastinum, chest wall. May cause superior vena
promote the art and science of critical care nursing. Its caval obstruction, dysphagia, cardiac arrhythmias,
official journal is Nursing in Critical Care. pericardial effusion.
- vertebrae.
British Journal of Anaesthesia. Second oldest journal of - recurrent laryngeal nerve, usually on the left.
anaesthesia (first published in 1923), and the first to be - sympathetic trunk at C8/T1, causing Horners
published monthly (in 1955). Previously unaffiliated with syndrome.
any association, institution or society, it became the offi- - brachial plexus at lung apex, causing pain and
cial journal of the College of Anaesthetists in 1990. wasting in the hand/arm (with Horners syndrome,
Spence AA (1988). Br J Anaesth; 60: 6057 rib or vertebral erosion, superior vena caval
obstruction, = Pancoast syndrome).
Bromage scale. Scoring system used to assess the metastases: commonly lymph nodes, bone, liver,
degree of motor block, originally described in the context brain.
of epidural anaesthesia for surgery. Consists of four other features:
grades (Table 13). Various modifications have been - fatigue, anorexia, weight loss, anaemia.
described (e.g. with or without detectable weak hip - hormone secretion, e.g. causing the syndrome
flexion); in some modifications a score of 1 indicates no of inappropriate antidiuretic hormone secretion,
block instead of complete block, as in the original Cushings syndrome, hypercalcaemia due to para-
scale. thyroid hormone secretion, carcinoid syndrome.
[Philip Bromage, English-born Canadian/US Most common with small cell tumours. Thyroid
anaesthetist] and sex hormone secretion may occur.
- sensory or motor neuropathy; cerebellar atrophy.
Bromethol (Tribromethanol; Avertin). CBr3CH2OH. - myasthenic syndrome, muscle weakness, dermato-
Obsolete rectal and iv sedative drug introduced in 1927 myositis.
and used for deep sedation or anaesthesia. - finger clubbing and hypertrophic pulmonary
osteoarthropathy.
Bronchial blockers, see Endobronchial blockers May present for bronchoscopy, mediastinoscopy or tho-
racic surgery. Anaesthetic considerations are related to
Bronchial carcinoma. Commonest cause of death from the above features, effects of smoking and malignancy;
cancer in Western men and women. Mostly associated thus preoperative assessment of respiratory, cardiovas-
with smoking, but also occurs following exposure to cular and neurological systems, and hormonal and meta-
asbestos, and certain industrial chemical and radioactive bolic status, is particularly important.
substances. Air pollution may also be a causative factor. Radiotherapy is used mainly for palliative treatment
Five-year survival in the UK is less than 10%; in the of pain and obstructive lesions (e.g. superior vena
USA and certain parts of Europe it is ~15%. caval obstruction), especially due to small cell carci-
noma. Chemotherapy is also used, particularly in small
cell carcinoma.
[Henry Pancoast (18751939), US radiologist]
Sculier JP, Berghmans T, Meert AP (2010). Am J Respir
Table 13 Bromage scale for motor block Crit Care Med; 181: 77381
See also, Polymyositis
1 Complete Unable to move legs or feet
2 Almost complete Able to move feet only Bronchial tree, see Tracheobronchial tree
3 Partial Just able to flex knees only
4 None Full movement of legs and feet Bronchiectasis. Permanent abnormal bronchial dilata-
tion, usually suppurative. May follow pneumonia,
88 Bronchiolitis

bronchial obstruction, chronic repeated chest infections, Postulated mechanisms of action:

e.g. in cystic fibrosis and immunological impairment. 2-adrenergic receptor agonists, e.g. salbutamol:
Features: - inhibit degranulation of mast cells.
haemoptysis. - stimulate adenylate cyclase in smooth muscle
chronic cough with purulent sputum. cells, increasing cAMP levels and thus causing
chronic respiratory insufficiency, of restrictive and/ reduced intracellular calcium and relaxation.
or obstructive pattern. phosphodiesterase inhibitors, e.g. theophylline,
empyema, abscesses, cor pulmonale, clubbing. aminophylline:
CXR: increased lung markings, patchy shadowing, - inhibit the breakdown of cAMP in smooth muscle
thick-walled dilated bronchi. cells.
Treatment includes antibiotic therapy, physiotherapy - possible effect via release of catecholamines via
and postural drainage, and lung resection if disease is adenosine inhibition.
localised. - possible effect on myosin light chains, reducing
Anaesthetic management: contraction.
preoperatively: anticholinergic drugs, e.g. ipratropium:
- early admission for preoperative assessment, - block muscarinic acetylcholine receptors, decreas-
medical treatment and physiotherapy. ing intracellular guanine monophosphate (cGMP;
- CXR, arterial blood gas interpretation, lung func- opposes the bronchodilating action of cAMP).
tion tests as appropriate. - possible effect via reduction in intracellular
perioperatively: soiling of the unaffected lung is calcium.
reduced by appropriate positioning. Double-lumen corticosteroids:
endobronchial tubes may assist surgery and allow - anti-inflammatory action.
isolation and suction of copious secretions. - reduced capillary permeability.
postoperatively: adequate analgesia and physio- - possibly increase the effects of -adrenergic
therapy to reduce risk of respiratory complications. receptor agonists.
ODonnell AE (2008). Chest; 134: 81523 Sodium cromoglicate and leukotriene receptor antago-
nists are not bronchodilators, but help to prevent bron-
Bronchiolitis. Inflammation of the bronchioles; usually choconstriction by reducing inflammation.
refers to acute infection in children but may also occur See also, Asthma; Bronchospasm
chronically in early COPD in adults. In children, respira-
tory syncytial virus accounts for 70% of cases, but many Bronchopleural fistula. Abnormal connection between
other viruses may also be responsible. Usually affects the tracheobronchial tree and pleura. Most commonly
children under 1 year old, causing non-specific upper occurs 210 days after pneumonectomy, although it may
respiratory tract symptoms that may progress over 12 follow trauma, chronic infection and erosion by tumour.
days to respiratory distress with diffuse crackles per- Features:
sistent wheezing. Hypoxaemia results from hypoventila- fever, productive cough, malaise.
tion and V/Q mismatch. May be associated with apnoea, X-ray evidence of infection in the remaining lung
especially in premature babies. Treatment is supportive, with fall in fluid level on the affected side.
including humidified O2 therapy, fluid replacement and Problems caused:
occasionally IPPV. Inhaled adrenaline and dexametha- source of (usually) infected material in one pleural
sone are also used. Ribavirin may reduce the severity of cavity, with potential contamination of the normal
illness if given early. lung through the fistula. Repeated spillage may
Usually self-limiting, lasting under 10 days; mortality cause pulmonary function impairment before cor-
in infants admitted to hospital is about 1% if previously rective surgery.
fit. Has been implicated in the development of subse- IPPV may force fresh gas through the fistula,
quent asthma. without inflating the remaining lung. Increased pres-
Ducharme FM (2011). Br Med J; 342: 7734 sure in the affected pleura increases the likelihood
See also, Tracheobronchial tree of contamination, and may impair cardiac output.
Management:
Bronchoalveolar lavage (BAL). Performed for pulmo- chest drainage.
nary alveolar proteinosis, to remove accumulated lipo- sitting the patient up, with affected side lowermost.
proteinaceous material. Has also been used in asthma classical method for induction of anaesthesia: inha-
and cystic fibrosis. Usually performed under general lational induction and intubation with a double-
anaesthesia, and involves instillation and drainage under lumen endobronchial tube, with spontaneous
gravity of 2040 litres warm buffered saline (heparin ventilation. IPPV may be started once the affected
may be added) through one lumen of a double-lumen side has been isolated. However, deep anaesthesia
endobronchial tube, whilst ventilating via the other. The with volatile agents may cause profound cardiovas-
other lung is treated after a few days. Main problems are cular effects, and coughing may increase contamina-
related to the pre-existing state of the patient, one-lung tion risk. Alternatives include awake intubation
anaesthesia and avoidance of soiling of the ventilated under local anaesthesia, or preoxygenation, iv
lung. Cardiopulmonary bypass has also been used. induction and intubation using suxamethonium
Lavage using small volumes is sometimes used to aid (only advocated by, and for, experienced thoracic
diagnosis of atypical chest infections, and may be carried anaesthetists).
out via flexible bronchoscopy under local anaesthesia. postoperatively, IPPV may be necessary. High-
frequency ventilation and differential lung ventila-
Bronchodilator drugs. Drugs that increase bronchial tion have been used.
diameter. See also, Thoracic surgery
 Bronchoscopy 89

Bronchopulmonary lavage, see Bronchoalveolar lavage - airway management:

- tracheal intubation in airway obstruction. Also
Bronchoscopy. Inspection of the tracheobronchial tree useful for changing tracheal tubes.
by passing an instrument down its lumen. May be: - confirmation of correct placement of tra-
rigid: usually performed in the operating theatre cheal/tracheostomy/endobronchial tubes. Also
for diagnosis of bronchial disease, removal of used in percutaneous tracheostomy.
foreign bodies and management of haemoptysis. - assessment of the tracheobronchial tree before
Anaesthetic management: extubation. In cases of potential postextubation
- preoperatively: airway obstruction, e.g. caused by oedema, the
- preoperative assessment is directed at the fibreoptic bronchoscope can be left in situ whilst
respiratory and cardiovascular systems. Many the tracheal tube is removed and the airway
patients will have bronchial carcinoma or other assessed; the tube may be resited over the bron-
smoking-related diseases. Secretions may be choscope if required.
improved by preoperative physiotherapy. Neck - diagnostic:
mobility and the teeth should be assessed. - chest infection, especially atypical. Washings,
- premedication reduces awareness. The antisial- brushings or transbronchial/endobronchial
agogue effects of anticholinergic drugs may be biopsies or needle aspiration may be used.
useful. Repeated instillation of 20ml sterile saline with
- perioperatively: subsequent aspiration (bronchoalveolar lavage)
- in the absence of a foreign body in the airway, may be useful in both infective and non-infective
iv induction of anaesthesia is usual. Inhalational processes.
induction may be indicated if airway obstruc- - other lesions, e.g. tumours, tears, thermal
tion is present, particularly in children. Neuro- damage. May be used to investigate abnormali-
muscular blockade is usually achieved with a ties on CXR.
short-acting neuromuscular blocking drug. - therapeutic:
- spraying of the larynx with lidocaine may reduce - aspiration of sputum and aspirated material.
perioperative and postoperative coughing and Mucolytic drugs can be instilled on to mucus
laryngospasm. plugs. Bronchoalveolar lavage has been used in
- ventilation: several methods may be used: severe asthma.
- injector techniques; air entrainment through - removal of foreign body.
the bronchoscope using intermittent jets of - for haemoptysis; saline lavage may be useful for
O2. Automatic jet ventilators have been used small areas of bleeding; the bronchoscope itself
for long procedures. can be used to compress bleeding points; or it
- IPPV via a side arm on the bronchoscope, may facilitate passage of a balloon-tipped cath-
the proximal end of which is occluded by a eter into the affected segment.
window or the operators thumb. Management for bronchoscopy in the ICU:
- deep anaesthesia with spontaneous ventila- coagulation studies should be performed if biopsies
tion. Often used in children, classically using are planned. Electrolyte imbalance should be
diethyl ether, then halothane, but now sevo- corrected.
flurane. Anaesthetic gases may be delivered secretions may be improved by physiotherapy.
via a side arm on the bronchoscope; before Anticholinergic drugs may reduce secretions
these ventilating bronchoscopes became but may also make them thick and difficult to
available, the patient breathed air and bron- aspirate.
choscopy was performed as anaesthesia light- awake patients may be managed under local anaes-
ened (a possible disadvantage of sevoflurane thesia as for awake intubation. In those with tra-
being that anaesthesia might lighten too cheal tubes, the bronchoscope may be passed
quickly). through a rubber-sealed connector at the tubes
- insufflation techniques, particularly apnoeic proximal end and IPPV continued. Leaks may
oxygenation. Suitable for short procedures occur around the scope, especially if airway pres-
only. sures are high; a swab coated in lubricant jelly
- intermittent IPPV via a tracheal tube placed wrapped around the leak may improve the seal.
in the proximal end of the bronchoscope. 5.0mm diameter bronchoscopes require an 8.0mm
- high-frequency ventilation has been used. tracheal tube to ensure adequate gas flow around
- monitoring as standard. the bronchoscope. Passage of the bronchoscope
- awareness is a particular problem, especially alongside the tracheal tube has also been used, as
with jet ventilation using 100% O2, or apnoeic has high-frequency ventilation.
oxygenation. Regular supplements or continu- increased sedation and neuromuscular blockade
ous infusion of iv anaesthetic agents, typically are usually required in ventilated patients.
propofol, reduce the incidence, as does premed- hypoxaemia may worsen during bronchoscopy;
ication, or the use of midazolam. 100% O2 is usually administered. Severe hypoxae-
- recovery should be in the lateral, head-down mia is usually considered a contraindication.
position, to encourage drainage of blood and arrhythmias, hypertension, coughing, broncho-
secretions. spasm or laryngospasm may occur during and after
fibreoptic: commonly performed for diagnostic pur- stimulation of the tracheobronchial tree. Topical
poses under local anaesthesia as for awake intuba- lidocaine may reduce airway irritation. Bleeding
tion, but also used by anaesthetists and intensivists and pneumothorax may also occur.
during general anaesthesia and on the ICU. Uses: See also, Foreign body, inhaled; Intubation, awake
90 Bronchospasm

Bronchospasm. May occur during anaesthesia due to: [A ]

surgical stimulation.
pH = pK + log
[HA]
presence of airway adjunct or tracheal tube.
pharyngeal/laryngeal/bronchial secretions or When pH equals pK of the buffer system, maximal buff-
blood. ering may occur, because HA and A exist in equal
aspiration of gastric contents.
amounts.
Body buffer systems:
anaphylaxis.
blood:
pulmonary oedema.
use of -adrenergic receptor antagonists.
- carbonic acid/bicarbonate: H2CO3 H+ + HCO3.
Particularly likely in smokers or in patients with asthma The pK is 6.1; i.e. the system is not very efficient
or COPD, and if anaesthesia is inadequate. at buffering alkaline at body pH (although it is
Features: quite efficient at buffering acid, efficiency increas-
polyphonic expiratory wheeze.
ing as pH falls). However, because there is a large
reduced movement of reservoir bag.
reservoir of plasma bicarbonate, and CO2 may
increased expiratory time.
be readily eliminated via the lungs and bicarbon-
increased airway pressures.
ate excretion can be regulated via the kidneys,
Must be distinguished from: this system constitutes the main buffer system in
pneumothorax.
the blood.
mechanical obstruction.
- haemoglobin: dissociation of histidine residues
laryngospasm.
gives haemoglobin six times the buffering capac-
pulmonary oedema.
ity of plasma proteins. Deoxygenated haemoglo-
Treatment: bin is a better buffer than oxygenated haemoglobin
of primary cause.
(Haldane effect).
increased FIO2.
- plasma proteins: carboxyl and amino groups dis-
increased inspired concentration of volatile inhala-
sociate to form anions; this accounts for a small
tional anaesthetic agent. amount of buffering capacity.
salbutamol 250500g sc/im or 250g iv slowly.
- phosphate: H2PO4 H+ + HPO42. Plays a small
Delivery by nebuliser or aerosol may also be used part in buffering in the ECF.
intracellular:
but may be technically difficult.
aminophylline 36mg/kg iv slowly, followed by
- proteins.
0.5mg/kg/h infusion. - phosphate.
further management as for asthma.
See also, Acidbase balance

Bumetanide. Loop diuretic, similar to furosemide in its

Brown fat. Specialised adipose tissue used for thermo- actions. 1mg is approximately equivalent to 40mg furo-
genesis because of its chemical make-up and structural semide. Diuresis begins within minutes of an iv dose and
composition. Of particular importance in temperature lasts for 2h.
regulation in neonates. Laid down from about 22 weeks Dosage:
of gestation around the base of the neck, axillae, medi- 15mg orally odtds.
astinum and between the scapulae; gradually replaced 12mg iv, repeated after 20min if required. May
by adult white adipose tissue after birth, the process also be given by infusion at 15mg/h.
taking several years. Fat breakdown and thermogenesis Side effects: as for furosemide; myalgia may also
are increased by -adrenergic neurone activity. occur, especially with high doses.
Enerbck S (2009). N Engl J Med; 360: 20213
BUN, see Blood urea nitrogen
BTPS. Body temperature and pressure, saturated with
water vapour. Bundle branch block (BBB). Interruption of impulse
propagation in the heart conducting system distal to the
Buccal nerve block, see Mandibular nerve blocks atrioventricular node. Causes are as for heart block.
May involve right or left bundles:
right BBB:
Buffer base. Blood anions that can act as bases and - common; usually clinically insignificant.
accept hydrogen ions. Mainly composed of bicarbonate, - ECG findings (Fig. 28a):
haemoglobin and negatively charged proteins. - QRS duration > 0.12s.
See also, Acidbase balance; Buffers - large S wave, lead I.
- RSR pattern, lead V1.
Buffers. Substances that resist a change in pH by absorb- - incomplete BBB may be due to an enlarged right
ing or releasing hydrogen ions when acid or base is ventricle, e.g. due to cor pulmonale or ASD.
added to the solution. In aqueous solutions this com- left BBB:
prises either a weak acid and its conjugate base (see - represents more widespread disease, as the left
below), or a weak base and its conjugate acid. bundle is a bigger and less discrete structure, con-
For the equation HA H+ + A, where HA = undis- sisting of anterior and posterior fascicles. If
sociated acid and A = anion, the equation shifts to the present preoperatively, it serves as an indicator of
left if acid is added, and to the right if base is added; existing heart disease.
changes in H+ concentration are thus minimised. - ECG findings (Fig. 28b):
The HendersonHasselbalch equation describes - QRS duration > 0.12s.
these relationships: - wide R waves, leads I and V46.
 Burns 91

- may be due to left ventricular hypertrophy, e.g. Bupivacaine hydrochloride. Amide local anaesthetic
due to hypertension or valvular heart disease. agent, introduced in 1963. Widely used for peripheral
hemiblock (involving individual fascicles of the left nerve/plexus blocks, spinal and epidural anaesthesia. In
bundle): comparison with lidocaine, bupivicaine:
- left anterior hemiblock: has a slower onset of action (pKa 8.1).
- QRS may be normal or slightly widened. is more potent (~6 more lipid-soluble); 0.5%
- left axis deviation > 60. bupivicaine is equivalent to 2% lidocaine.
- left posterior hemiblock: causes less vasodilatation; addition of adrenaline
- less common, because the posterior fascicle is neither prolongs the effect nor restricts systemic
better perfused than the anterior. absorption of bupivacaine.
- QRS normal or slightly widened. is extensively bound to tissue and plasma proteins
- right axis deviation > 120. (95%); thus has a longer duration of action
bifascicular block: (34hfor epidural block and up to 12hfor some
- composed of right BBB and one hemiblock: nerve blocks, e.g. brachial plexus).
- anterior: is more cardiotoxic.
- right BBB ECG pattern and left axis Mainly metabolised by the liver, a small amount is
deviation. excreted unchanged in the urine. 0.250.5% solutions
- may lead to complete heart block later in life, are used for most purposes. 0.75% produces more
but this is rare during anaesthesia. prolonged motor block when given epidurally; this con-
- posterior: centration is contraindicated in obstetric practice
- right BBB ECG pattern and right axis because of toxicity. Contraindicated for use in IVRA
deviation. because of its cardiotoxicity. A hyperbaric 0.5% solution
- rare. (with glucose 8%) spinal administration was introduced
- at risk of developing complete heart block. in 1982. Maximal safe dose: 2mg/kg; toxic plasma levels:
- bifascicular block plus prolonged PR interval > 24g/ml.
(i.e. partial trifascicular block) is particularly The original preparation of bupivacaine is a racemic
likely to progress to complete heart block. mixture of l- and d-isomers. A preparation of the pure
BBB itself is not a contraindication to anaesthesia, but enantiomer l-bupivacaine (levobupivacaine) was devel-
progression to complete heart block during anaesthesia oped in 1997 and is equivalent to the racemic mixture in
remains the main risk. Temporary perioperative cardiac terms of action and potency, whilst having reduced pro-
pacing should be considered if BBB is associated with pensity to CVS and CNS toxicity. It is available in the
either a history of syncope or a prolonged PR interval. same concentrations as the racemic preparation.
Anaesthetic management is as for heart block. See also, Isomerism; individual blocks

Bungarotoxins. Snake venom neurotoxins. -

Buprenorphine hydrochloride. Opioid analgesic drug
Bungarotoxin binds irreversibly to postsynaptic acetyl-
derived from thebaine, with partial agonist properties.
choline receptors at the neuromuscular junction; -
Synthesised in 1968. 0.4mg is equivalent to 10mg mor-
bungarotoxin acts presynaptically to block acetylcholine
phine; it has slower onset and its effects last longer
release. They have been used to study neuromuscular
(about 8h). May be given iv or im (0.30.6mg), or sub-
transmission.
lingually (0.20.4mg) 68-hourly. A slow-release patch
(3570g/h, equivalent to 0.841.68mg/day) has been
produced for severe chronic pain. Respiratory depres-
sion does occur, but reaches a plateau that cannot be
(a) (b)
exceeded by increasing the dose. Respiratory depression
I I is not readily reversed by naloxone. Carries a low risk of
dependence and has been used in the treatment of drug
addiction.
See also, Opioid receptors

Burns. Burned patients may suffer from:

V1 V1 direct thermal injury to body and airway.
smoke inhalation, with e.g. carbon monoxide (CO)
or cyanide (CN) poisoning.
extensive fluid loss into the dermis, into blisters and
from skin surfaces.
Patients suffering from electrocution and electrical
burns may have suffered widespread internal tissue
injury, whilst those suffering from chemical burns may
V6 V6 also have features of systemic toxicity/metabolic distur-
bance. General management of electrical and chemical
burns is similar to that for thermal burns.
Management:
high FIO2 O2 therapy. Tracheal intubation and IPPV
are required in:
Fig. 28 ECG findings in bundle branch block: (a) right BBB; (b) left - severe CO or CN poisoning. It has been suggested
BBB that CN poisoning should be assumed if there
92 Burns, during anaesthesia

is unexplained severe metabolic acidosis, and prevention of Curling ulcers, e.g. with H2 receptor
treated accordingly. antagonists.
- apparent or impending upper airway obstruction tetanus toxoid as necessary.
due to inhalational injury. Obstruction due to consider transfer to a specialist burns unit if:
oedema may develop over a few hours; thus tra- - burn > 10% total body surface area (adult) or >
cheal intubation with an uncut tube should be 5% (child), or any full-thickness burn > 5%.
performed early if burns to the airway are present. - burn to face, hands, genitalia, major joints.
The latter may be indicated by burns or soot - significant inhalational injury.
around the face and in the mouth, and are con- - < 5 and > 60 years of age (poorer prognosis).
firmed by fibreoptic bronchoscopy. Obstruction - circumferential burn to limbs or chest.
usually resolves within 24 days. - high-voltage electrical or chemical burn > 5%
- an unconscious patient. total body surface area.
- respiratory failure. Complications:
Measurement of blood gas tensions, carboxyhaemo- infection and sepsis.
globin and possibly cyanide levels, should be per- respiratory failure and ARDS.
formed. A CXR is mandatory. renal failure, with myoglobinuria or haemoglobin-
assessment of the extent of burns (rule of nines is uria. Suggested by low urine osmolarity and urine/
appropriate for adults; a paediatric burn chart is blood urea ratio < 10.
used for children). hypercatabolism.
fluid replacement: many different regimens exist, Mortality is related to the extent and site of burn, and
using colloid, crystalloid or hypertonic solutions. age. Recent evidence suggests that area of burn > 40%,
Average total requirements = water 24ml/kg/% age > 60 years and the presence of inhalational injury
burn and sodium 0.5mmol/kg/% burn. Constant are the three risk factors most strongly associated with
reassessment is the most important factor. Common death; absence of these risk factors is associated with
UK regimen: 0.3% mortality; a single risk factor with 3% mortality,
- replacement volume (V) in ml: two risk factors with 33% mortality, and all three risk
body weight (kg) %surface area burnt factors with 90% mortality.
V= Anaesthetic considerations in patients with burns:
2 patients often require repeat anaesthetics, e.g. for
3 V is infused in the first 12 h from the time change of dressings, plastic surgery.
of burn; difficult airway and/or intubation if burns exist

2 V in the next 12 h; around the head and neck, especially if contractures

develop.
1 V in the next 12 h. a life-threatening enhanced increase in plasma
- choice of fluid: colloid is thought to be best. Blood potassium may follow use of suxamethonium;
is given to keep haematocrit 3545%. Rough cardiac arrest has been reported. Most likely 310
guide: 1 unit per 10% burn, excluding the first 10%. weeks after the burn, but has been reported between
Normal maintenance fluids are given in addition. 9 days and 2 months. An increased number of extra-
- alternative regimen, using crystalloid: junctional acetylcholine receptors is thought to be
2 weight % burn in first 8 h (ml); responsible.
increased requirement for non-depolarising neuro-
2 weight % burn in next 16 h. muscular blocking drugs. The mechanism is unclear
Frequent reassessment is crucial. Urine output but may involve altered pharmacokinetics, e.g.
should be maintained at 0.51 ml/kg/h with osmo- changes in protein-binding, clearance, volume of
lality 6001000 mosmol/kg (high due to high circu- distribution. An alternative theory suggests the
lating levels of vasopressin). Low urine flow with release of a specific, yet undiscovered, substance fol-
high osmolality indicates under-replacement; high lowing burns that reduces drug interaction with the
flow with low osmolality indicates over-replacement, neuromuscular junction, or affects the latter directly.
in the absence of renal failure. The fluid regimen limited venous access.
is altered as necessary. hypermetabolism/catabolism.
Oral rehydration is acceptable in burns of up to heat loss during prolonged surgery.
10% (children) to 15% (adults). Oral rehydration extensive blood loss is possible; e.g. during grafting
fluid mixtures are suitable for children. For adults, procedures approximately 2% blood volume lost
water containing 75mmol/l sodium chloride and per 1% surface burn.
15mmol/l sodium bicarbonate has been suggested, suggested techniques:
at 23 times normal water intake. - iv opioid analgesic drugs, traditionally combined
escharotomy (incision of contracted full-thickness with butyrophenones (neuroleptanaesthesia),
burn that prevents ventilation or limb perfusion) though this is less common now.
may be necessary. - inhalational analgesia with Entonox or volatile
monitoring of: agents.
- urine output (via catheter if > 25% burn). - ketamine other iv agents, e.g. midazolam,
- haematocrit and plasma electrolytes. propofol.
- respiratory function. - standard general anaesthesia.
- CVP. Latenser BA (2009). Crit Care Med; 37: 281926
analgesia: opioid infusions are often required.
adequate nutrition (enteral if possible via a naso- Burns, during anaesthesia, see Diathermy; Electrocution
gastric or -jejunal tube). and electrical burns; Explosions and fires; Laser surgery
 Bypass, cardiopulmonary 93

BURP, Backward, upward and rightward pressure, see tranquillisers (a term no longer used). They produce a
Intubation, difficult state of detachment from the environment and inhibit
purposeful movement via GABA receptor antagonism.
Burst suppression, see Electroencephalography They may cause distressing inner restlessness that may
be masked by outward calmness. They are powerful anti-
Busulfan (Busulphan). Alkylating agent cytotoxic drug, emetic drugs, acting as dopamine antagonists at the che-
given orally to treat chronic myeloid leukaemia. Causes moreceptor trigger zone. Although some -adrenergic
myelosuppression that may be irreversible, and, rarely, blocking effect has been shown, cardiovascular effects
pulmonary fibrosis. Thus important in patients present- are minimal. May cause extrapyramidal side effects, and
ing for bone marrow transplantation. the neuroleptic malignant syndrome, especially after
chronic usage. Used to treat psychoses (especially
Butorphanol tartrate. Obsolete opioid analgesic drug schizophrenia and mania), in neuroleptanaesthesia and
with partial agonist properties, withdrawn in the UK in as antiemetics. Droperidol has a faster onset of action
1983, similar in actions to pentazocine. and shorter half-life than haloperidol.
See also, Opioid receptors

Butyrophenones. Group of centrally acting drugs, Bypass, cardiopulmonary, see Cardiopulmonary

originally described with phenothiazines as major bypass
 C
CABG, see Coronary artery bypass graft The above points inform the decision to employ general
or regional anaesthesia.
Regimens used to reduce the risk of aspiration
Cachectin, see Cytokines
pneumonitis:
fasting during labour: this practice has been ques-
Cachexia, see Malnutrition tioned, and many centres allow clear fluids or
certain foods (low fat and sugar content) for low-
Caesarean section (CS). Operative delivery of a fetus risk women in labour (if not receiving opioids),
by surgical incision through the abdominal wall and although this is still controversial.
uterus. Unless specifically indicated, the classical midline antacid therapy: 0.3M sodium citrate (30ml)
upper uterine segment approach has been largely directly neutralises gastric acidity; it has a short
replaced by the transverse lower segment incision; the duration of action and should be given immediately
latter is associated with lower rates of ileus, infection and before induction of anaesthesia.
bleeding. The CS rate in the UK has steadily increased H2 receptor antagonists: different regimens are
to ~25%, from ~810% in the 1980s. employed in different units, with most reserving
Indications include: previous CS; pre-existing mater- prophylaxis, e.g. with ranitidine, for women at risk
nal morbidity (e.g. cardiac disease); complications of of operative intervention or receiving pethidine
pregnancy (e.g. pre-eclampsia); obstetric disorders (causing reduced gastric emptying). For elective CS,
(e.g. placenta praevia); fetal compromise; failure to ranitidine 150mg orally the night before and 2h
progress. before surgery is often given. For emergency CS,
Specific anaesthetic considerations: ranitidine 50mg iv may be given; cimetidine 200mg
physiological changes of pregnancy. im is an alternative as it has a more rapid onset than
difficult tracheal intubation and aspiration of gastric ranitidine.
contents associated with general anaesthesia (GA) omeprazole and metoclopramide have also been
have been major anaesthetic causes of maternal used, to reduce gastric acidity and increase gastric
mortality. Mortality is higher for emergency CS emptying, respectively.
than for elective CS. Sedative premedication is usually avoided because of
aortocaval compression must be minimised by the risk of neonatal respiratory depression and difficul-
avoiding the supine position at all times. ties over timing.
uterine tone is decreased by volatile anaesthetic Anaesthetic techniques:
agents; however, consideration of this should for all types of anaesthesia:
not result in the administration of inadequate - wide-bore iv access (16G or larger).
anaesthesia. - cross-matched blood available within 30min.
placental perfusion may be reduced by severe and/ - routine monitoring and skilled anaesthetic assis-
or prolonged hypotension and/or reduction in tance, with all necessary equipment and resuscita-
cardiac output. tive drugs available and checked.
contraction of the uterus upon delivery results in - aortocaval compression is reduced by positioning
autotransfusion of about 500ml blood, helping to the patient laterally during transport to theatre
offset the average blood loss of 5001500ml (GA) and surgery.
or 300700ml (regional anaesthesia). - ergometrine has been superseded by oxytocin as
neonatal depression should be avoided, but mater- the first-line uterotonic following delivery because
nal awareness may occur if depth of anaesthesia is of the formers side effects (e.g. hypertension and
inadequate. vomiting).
The usual preoperative assessment should be made, general anaesthesia:
with particular attention to: - rapid sequence induction with an adequate dose
the indication for CS (e.g. pre-eclampsia) and other of anaesthetic agent is required to prevent aware-
obstetric or medical conditions. ness; a maximal allowed dose based on weight
whether CS is elective or emergency, and whether may be insufficient. Neonatal depression due to
the fetus is compromised. iv induction agents is minimal. Suxamethonium
assessment of the airway. is still considered the neuromuscular blocking
maternal preference for general or regional drug of choice by most authorities, although
anaesthesia. rocuronium (especially with the advent of sugam-
if used in labour, the quality of existing epidural madex) is an alternative.
analgesia should be assessed. - difficult and failed intubation (the latter ~1:300
assessment of the lumbar spine and any contraindi- 500) is more likely in obstetric patients than in the
cations to regional anaesthesia. general population. Contributory factors include

95
96 Caesarean section

a full set of teeth, increased fat deposition, (e.g. fentanyl) is common (though may not be
enlarged breasts and the hand applying cricoid necessary if many epidural doses have been given
pressure hindering insertion of the laryngoscope during labour). Bicarbonate has also been added
blade into the mouth. Laryngeal oedema may be to shorten the onset time, (e.g. 2ml 8.4% added
present in pre-eclampsia. Apnoea rapidly results to 20ml lidocaine or lidocaine/bupivacaine
in hypoxaemia because of reduced FRC and mixture), but risks errors from mixing up to 45
increased O2 demand. different drugs, especially in an emergency.
- IPPV with 50% O2 in N2O is commonly recom- Commercial premixed solutions of lidocaine/
mended until delivery; however, in the absence of bupivacaine and adrenaline may be unsuitable as
fetal distress, 33% O2 is associated with similar they have a low pH (3.55.5) and contain preser-
neonatal outcomes. vatives. Ropivacaine 0.50.75% or levobupiva-
- 0.50.6 MAC of volatile agents (with 50% N2O) caine 0.5% is also used. 0.75% bupivacaine is
reduces the incidence of awareness to 1% without associated with a high incidence of toxicity, and
increasing uterine atony and bleeding, or neonatal has been withdrawn from obstetric use. Chloro-
depression; however, at 0.81.0 MAC, awareness procaine is available in the USA and a small
falls to 0.2% and the uterus remains responsive to number of European countries (but not the UK);
uterotonics. Placental blood flow is thought to it has a rapid onset and offset. Etidocaine has also
be maintained by vasodilatation caused by the been used in the USA.
volatile agents, and high levels of vasoconstricting - L34 interspace is usually chosen.
catecholamines associated with awareness are - on average, 1520ml solution is required for ade-
avoided. Delivery of higher concentrations of quate blockade (from S5 to T46). Loss of normal
volatile agents (overpressure) in 66% N2O has light touch sensation is a stronger predictor of
been suggested for the first 35min whilst alveo- intraoperative comfort than loss of cold sensation,
lar concentrations are low, to reduce awareness. although either may be used to assess the block.
Factors increasing the likelihood of awareness Smaller volumes are required for a specified level
include lack of premedication, reduced con of block than in non-pregnant patients, as dilated
centrations of N2O and volatile agents, and with- epidural veins reduce the available volume in the
holding opioid analgesic drugs until delivery. epidural space.
Up to 26% awareness was reported in early - injection of solution in 5-ml increments at 5-min
studies using 50% N2O and no volatile anaes- intervals reduces the risk of hypotension and
thetic agent. extensive blockade (e.g. due to accidental spinal
- normocapnia (4 kPa/30mmHg in pregnancy) is injection), but increases anaesthetic time and
considered ideal; excessive hyperventilation may total dose. A single injection of 1520ml is advo-
be associated with fetal hypoxaemia and acidosis cated by some as producing a more rapid block.
due to placental vasoconstriction, impairment of A catheter technique is used most frequently,
O2 transfer associated with low PCO2, and reduced although injection through the epidural needle
venous return caused by excessive IPPV. may be performed.
- all neuromuscular blocking drugs cross the pla- - opioids (e.g. diamorphine 24mg or fentanyl
centa to a very small extent. Shorter-acting drugs 50100g) are routinely given epidurally for peri-
(e.g. vecuronium and atracurium), are usually and postoperative analgesia; maternal respiratory
employed, since postoperative residual paralysis depression has been reported, albeit rarely.
associated with longer-lasting drugs has been a - hypotension associated with blockade of sympa-
significant factor in some maternal deaths. thetic tone may be reduced by preloading with iv
- opioid analgesic drugs are withheld until delivery fluid; however, the use of vasopressors to prevent
of the infant, to avoid neonatal respiratory and treat hypotension in the euvolaemic patient
depression. is thought to be a more effective and rational
- aspiration may also occur during recovery from approach. Ephedrine 36mg or phenylephrine
anaesthesia (when the effect of sodium citrate 50100g is commonly given by intermittent
may have worn off). Routine gastric aspiration bolus; continuous infusions are also effective.
during anaesthesia has been suggested, especially Phenylephrine appears to be associated with a
in emergency cases. Before tracheal extubation, better neonatal acidbase profile than large doses
the patient should be awake and on her side. of ephedrine (thought to be due to ephedrine
- advantages: usually quicker to perform in emer- crossing the placenta and causing increased
gencies. May be used when regional techniques anaerobic glycolysis in the fetus via -adrenergic
are inadequate or contraindicated, e.g. in coagula- stimulation).
tion disorders. Safer in hypovolaemia. - nausea and vomiting may be caused by hypoten-
- disadvantages: risk of aspiration, difficult intuba- sion and/or bradycardia.
tion, awareness and neonatal depression. Hypo- - routine administration of O2 by facemask has
tension and reduced cardiac output may result been questioned on the grounds of being ineffec-
from anaesthetic drugs and IPPV. Postoperative tive and even possibly harmful to the fetus, due to
pain, drowsiness, PONV, blood loss and DVT risk generation of free radicals.
all tend to be greater. - during surgery many women feel pressure and
epidural anaesthesia (EA): movement, which may be unpleasant; all women
- facilities for GA should be available. should be warned of this possibility and of the
- bupivacaine 0.5% or lidocaine 2% (the latter with potential requirement for general anaesthesia.
adrenaline 1:200000) is most commonly used in Inhaled N2O, further epidural top-ups, small doses
the UK, often in combination. Addition of opioids of iv opioid drugs (e.g. fentanyl or alfentanil), iv
 Calcium 97

paracetamol and ketamine may be useful. Shoul- as a last resort if other techniques are unavailable or
der tip pain may result from blood tracking up to unsuccessful. It may also be used to supplement inhala-
the diaphragm and may be reduced by head-up tional anaesthesia following failed intubation. Trans-
tilt. Good communication between mother, anaes- verse abdominis plane block has been used, e.g. for
thetist and obstetrician is especially important postoperative analgesia.
when performing CS under regional anaesthesia, [Julius Caesar (10044 BC), Roman Emperor; said to
and the obstetrician should warn the anaesthetist have been born by the abdominal route; his name alleg-
before exteriorising the uterus or swabbing the edly derived from caedare, to cut. An alternative sugges-
paracolic gutters. tion is related to a law enforced under the Caesars
- advantages: the risks of GA are avoided. Onset of concerning abdominal section following death in late
hypotension is usually slow, the mother may be pregnancy]
able to warn of it early and it may be corrected See also, Confidential Enquiries into Maternal Deaths;
before becoming severe. Minimal neonatal Fetus, effects of anaesthetic agents on; ID interval;
depression occurs compared with GA. The mother Induction, rapid sequence; Intubation, difficult; Intuba-
is not drowsy and is able to hold the baby soon tion, failed; Obstetric analgesia and anaesthesia; UD
after delivery. Her partner is able to be present interval
during the procedure. Epidural analgesia pro-
vided in labour can be extended for operative Caffeine. Xanthine present in tea, coffee and certain soft
delivery. The catheter can be used for further top- drinks; the worlds most widely used psychoactive sub-
up during surgery if required, and for postopera- stance. Also used as an adjunct to many oral analgesic
tive analgesia. drug preparations, although not analgesic itself. Causes
- disadvantages: risk of dural tap, total spinal block- CNS stimulation; traditionally thought to improve per-
ade, local anaesthetic toxicity, severe hypotension. formance and mood, whilst reducing fatigue. Increases
It may be slow to achieve adequate blockade with cerebral vascular resistance and decreases cerebral
a risk of patchy block. Inability to move the legs blood flow. Half-life is about 6h. Has been used iv and
may be disturbing. orally for treatment of post-dural puncture headache.
spinal anaesthesia (SA): Acts via inhibition of phosphodiesterase, increasing
- general considerations as for EA. levels of cAMP and as an antagonist at adenosine
- 0.5% bupivacaine is used in the UK; plain bupi- receptors.
vacaine (e.g. 3ml) produces a more variable block Dosage: up to 30mg in compound oral preparations.
than hyperbaric bupivacaine (e.g. 1.82.8ml), 150300mg orally tds/qds for post-dural puncture
which is the only form licensed for spinal anaes- headache; 250mg iv (with 250mg sodium
thesia. Plain levobupivacaine is also licensed in benzoate).
the UK. Hyperbaric tetracaine (amethocaine) Side effects: as for aminophylline, especially CNS and
0.5% (1.21.6ml) is used in the USA. cardiac stimulation.
- injection is usually at the L34/L45 interspace.
- advantages: as for EA, but of quicker onset. Caisson disease, see Decompression sickness
Blockade is more intense and not patchy. Smaller
doses of local anaesthetic drug are used. Calcitonin. Hormone (mw 3500) secreted from the
- disadvantages: single shot; i.e. may not last long parafollicular (C) cells of the thyroid gland. Involved in
enough if surgery is prolonged. Spinal catheter calcium homeostasis; secretion is stimulated by hyper-
techniques allow more control over spread and calcaemia, catecholamines and gastrin. Decreases serum
duration but are technically more difficult. Risk calcium by inhibiting mobilisation of bone calcium,
of post-dural puncture headache (reduced to decreasing intestinal absorption and increasing renal
under 1% if 2527G pencil-point needles are calcium and phosphate excretion. Acts via a G protein-
used). Hypotension is of faster onset and thus coupled receptor on osteoclasts. Calcitonin derived from
may be more difficult to control; has been associ- salmon is used in the treatment of severe hypercalcae-
ated with poorer neonatal acidbase status com- mia, postmenopausal osteoporosis, Pagets disease and
pared with EA/GA. Remains the most popular intractable pain from bony metastases.
anaesthetic technique for CS in the UK. [Sir James Paget (18141899), English surgeon]
combined spinalepidural anaesthesia (CSE): See also, Procalcitonin
- general considerations as for EA and SA.
- allows the fast onset and dense block of SA but Calcium. 99% of body calcium is contained in bone;
with the flexibility of EA. Also allows a small plasma calcium consists of free ionised calcium (50%)
subarachnoid injection to be extended by epidu- and calcium bound to proteins (mainly albumin) and
ral injection of either saline (thought to act via a other ions. The free ionised form is a second messenger
volume effect) or local anaesthetic, with greater in many cellular processes, including neuromuscular
cardiovascular stability. transmission, muscle contraction, coagulation, cell
- usually performed at a single vertebral interspace division/movement and certain oxidative pathways.
(needle-through-needle method) Binds to intracellular proteins (e.g. calmodulin), causing
(For contraindications and methods, see individual configurational changes and enzyme activation. Intracel-
techniques) lular calcium levels are much higher than extracellular,
CS is possible using local anaesthetic infiltration of due to relative membrane impermeability and active
the abdominal wall (e.g. with 0.5% lidocaine or prilo- transport mechanisms. Calcium entry via specific chan-
caine). Large volumes are required, with risk of toxicity. nels leads to direct effects (e.g. neurotransmitter release
Infiltration of each layer is performed in stages. The pro- in neurones), or further calcium release from intracel-
cedure is lengthy and uncomfortable, but may be used lular organelles (e.g. in cardiac and skeletal muscle).
98 Calcium channel blocking drugs

Extracellular hypocalcaemia has a net excitatory effect Classified according to pharmacological effects in
on nerve and muscle; hypocalcaemic tetany can result in vitro and in vivo:
life-threatening laryngospasm. class I: potent negative inotropic and chronotropic
Ionised calcium increases with acidosis, and decreases effects, e.g. verapamil. Acts mainly on the myocar-
with alkalosis. Thus for accurate measurement, blood dium and conduction system; reduces myocardial
should be taken without a tourniquet (which causes contractility and O2 consumption and slows conduc-
local acidosis), and without hyper-/hypoventilation. tion of the action potential at the SA/AV nodes.
Ionised calcium is measured in some centres, but total Thus mainly used to treat angina and SVT (less
plasma calcium is easier to measure; normal value is useful in hypertension). Severe myocardial depres-
2.122.65mmol/l. Varies with the plasma protein level; sion may occur, especially in combination with
corrected by adding 0.02mmol/l calcium for each g/l -adrenergic receptor antagonists.
albumin below 40g/l, or subtracting for each g/l above class II: acts on vascular smooth muscle, reducing
40g/l. vascular tone; minimal direct myocardial activity
Regulation: (although may cause reflex tachycardia):
vitamin D: group of related sterols. Cholecal- - nifedipine: acts mainly on coronary and periph-
ciferol is formed in the skin by the action of ultra- eral arteries, with little myocardial depression.
violet light, and is converted in the liver to Used in angina, hypertension and Reynauds syn-
25-hydroxycholecalciferol (in turn converted to drome. Systemic vasodilatation may cause flush-
1,25-dihydroxycholecalciferol in the proximal renal ing and headache, especially for the first few days
tubules). Formation is increased by parathyroid of treatment.
hormone and decreased by hyperphosphataemia. - nicardipine: as nifedipine, but with even less myo-
Actions: cardial depression.
- increases intestinal calcium absorption. - amlodipine and felodipine: similar to nifedipine
- increases renal calcium reabsorption. and nicardipine, but with longer duration of action
- increases bone mineralisation. and therefore taken once daily.
parathyroid hormone: secretion is increased - nimodipine: particularly active on cerebral vascu-
by hypocalcaemia and hypomagnesaemia, and lar smooth muscle, it is used to relieve cerebral
decreased by hypercalcaemia and hypermagnesae- vasospasm following subarachnoid haemorrhage.
mia. Actions: class III: slight negative inotropic effects, without
- mobilises bone calcium. reflex tachycardia: diltiazem is used in angina and
- increases renal calcium reabsorption. hypertension.
- increases renal phosphate excretion. The above drugs act mainly on the L-type calcium (long-
- increases formation of 1,25-dihydroxy- lasting) channels; these are more widely distributed than
cholecalciferol. the T-type (transient) channels which are confined to the
calcitonin: secreted by the parafollicular cells of the sinoatrial node, vascular smooth muscle and renal neu-
thyroid gland. Secretion is increased by hypercal- roendocrine cells. N-type calcium channels are concen-
caemia, catecholamines and gastrin. Actions: trated in neural tissue and are the binding site of omega
- decreases intestinal absorption of dietary calcium. toxins produced by certain venomous spiders and cone
- inhibits mobilisation of bone calcium. snails. A derivative of the latter, ziconotide, is available
- increases renal calcium and phosphate excretion. for the treatment of chronic pain.
Calcium is used clinically to treat hypocalcaemia, e.g. Additive effects might be expected between these
during massive blood transfusion. It is also used as an drugs and the volatile anaesthetic agents, all of which
inotropic drug. Although ionised calcium concentration decrease calcium entry into cells. Reduction in cardiac
may be low after cardiac arrest, its use during CPR is no output, decreased atrioventricular conduction and
longer recommended unless persistent hypocalcaemia, vasodilatation may occur to different degrees, but
hyperkalaemia or overdose of calcium channel blocking severe interactions are rarely a problem in practice.
drugs is involved. This is because of its adverse effects Non-depolarising neuromuscular blockade may be
on ischaemic myocardium and on coronary and cerebral potentiated.
circulations. Overdose causes hypotension, bradycardia and heart
Calcium chloride 10% contains 6.8mmol/10ml and block. Treatment includes iv calcium chloride, glucagon
14.7% contains 10mmol/10ml; calcium gluconate 10% and catecholamines. Heart block is usually resistant to
contains 2.22.3mmol/10ml, depending on the formula- atropine and hypotension may not respond to inotropes
tion. 510ml calcium chloride or 1020ml calcium glu- or vasopressors. High-dose insulin has been successful in
conate is usually recommended by slow iv bolus. The reversing refractory hypotension.
chloride preparation is usually recommended for CPR,
although equal rises in plasma calcium are produced Calcium resonium, see Polystyrene sulphonate resins
by gluconate, if equal amounts of calcium are given.
Arrhythmias and prolonged hypercalcaemia may follow Calcium sensitisers. New class of inotropic drugs, now
their use. established as effective treatment of acute heart failure;
Aguilera IM, Vaughan RS (2000). Anaesthesia; 55: examples include levosimendan and pimobendan. Act
77990 directly on cardiac myofilaments without increasing
intracellular calcium, thus improving myocardial con-
Calcium channel blocking drugs. Structurally diverse tractility without impairing ventricular relaxation. Levo-
group of drugs that block Ca2+ flux via specific Ca2+ chan- simendan also has vasodilatory effects through opening
nels (largely L-type, slow inward current). Effects vary of K+ channels.
according to relative affinity for cardiac or vascular Parissis JT, Rafouli-Stergiou P, Mebazaa A etal (2010).
smooth muscle Ca2+ channels. Curr Opin Crit Care; 16: 43241
 Capreomycin 99

Calibration. Process of standardising the output of a Capacitance. Ability to retain electrical charge; defined
measuring device against another measurement of as the charge stored by an object per voltage difference
known and constant magnitude. Reduces measurement across it. The unit of capacitance is the farad (F), 1 farad
error due to drift. One-point calibration is sufficient to being the capacity to store 1 coulomb of charge for an
address offset drift; two-point calibration is required for applied potential difference of 1 volt.
the mitigation of gradient drift. Essential for the accu- A capacitor composed of conductors separated by
rate functioning of many measurement devices (e.g. arte- an insulator may be charged by a potential difference
rial blood pressure monitor, blood gas analyser, expired across it, but will not allow direct current to flow. Its
gas analyser). stored charge may subsequently be discharged, e.g. in
defibrillation. Repeated charging and discharging
Calorie. Unit of energy. Although not an SI unit, widely induced by an alternating current results in current flow
used, especially when describing energy content of food. across a capacitor.
[Michael Faraday (17911867), English chemist]
1 cal = energy required to heat 1g water by 1C.
1kcal (1 Cal) = energy required to heat 1kg water Capacitance vessels. Composed of venae cavae and
by 1C = 1000 cal. large veins; normally only partially distended, they may
1 cal = 4.18 joules. expand to accommodate a large volume of blood before
venous pressure is increased. Innervated by the sympa-
Calorimetry, indirect, see Energy balance thetic nervous system in the same way as the arterial
system (resistance vessels), they act as a blood reservoir.
CAM-ICU, see Confusion in the intensive care unit 6070% of blood volume is within the veins normally.

cAMP, see Adenosine monophoshate, cyclic Capacitor, see Capacitance

CampbellHowell method, see Carbon dioxide Capillary circulation. Contains 5% of circulating blood
measurement volume, which passes from arterioles to venules via cap-
illaries, usually within 2s. Controlled by local autoregu-
Canadian Journal of Anesthesia. Official journal of the latory mechanisms, and possibly by autonomic neural
Canadian Anesthetists Society. Launched in 1954 as reflexes. Substances that readily cross the capillary walls
the Canadian Anaesthetists Society Journal. Became the (mainly by diffusion) include water, O2, CO2, glucose and
Canadian Journal of Anaesthesia in 1987 and the Cana- urea. Hydrostatic pressure falls from about 30mmHg
dian Journal of Anesthesia in 1999. (arteriolar end) to 15mmHg (venous end) within the
capillary. Direction of fluid flow across capillary walls is
Candela. SI unit of luminous intensity, one of the base determined by hydrostatic and osmotic pressure gradi-
(fundamental) units. Definition relates to the luminous ents (Starling forces).
intensity of a radiating black body at the freezing point
of platinum. Capillary refill time. Time taken for capillaries to refill
after blanching pressure is applied for 5s. Normally
Cannabis. Hallucinogenic drug obtained from the < 2s; prolonged in hypoperfusion and hypothermia. May
Cannabis sativa plant. A mixture of at least 60 chemicals be measured centrally, over the sternum, or peripherally,
(cannabinoids) including the main psychoactive -9- on the soft pad of a digit.
tetra-hydrocannibinol. Cannabinoid receptors have
been identified in central and peripheral neurones (CB1 Capnography. Continuous measurement and pictorial
receptors) and lymphoid tissue (e.g. spleen) and macro- display of CO2 concentration (capnometry refers to
phages (CB2); both types are G protein-coupled measurement only). During anaesthesia, used to display
receptors. end-tidal CO2; this may be achieved using:
Therapeutic uses include treatment of glaucoma and spectroscopy (most commonly infrared).
as an antiemetic agent during chemotherapy. Also has mass spectrometer.
analgesic, anticonvulsant and possibly antispasmodic The equipment used must have a very short response
properties, hence its use in chronic pain and multiple time in order to produce a continuous display (for
sclerosis. Mild psychological dependence is common, uses and capnography traces, see Carbon dioxide,
although physiological withdrawal states do not occur. end-tidal).
Cognitive impairment, including psychosis with chronic Whitaker DK (2011). Anaesthesia; 66: 5449
usage, has been reported. Usually combined with tobacco See also, Carbon dioxide measurement
and smoked; anaesthetic concerns are as for smoking
generally. Capreomycin. Cyclic polypeptide antibacterial drug
Present law prohibits prescription of cannabis used to treat TB resistant to other therapy (especially
without a Home Office Licence and has hampered in immunocompromised patients). Also used in other
clinical trials; there has been pressure to allow freer mycobacterial infections. Poorly absorbed orally, peak
administration in certain chronic conditions and even to levels occur within 2h of im injection. Excreted
decriminalise it altogether. Reclassified as a Class C unchanged in the urine.
drug under the Misuse of Drugs Act 1971 in 2004. Nabi- Dosage: 1g/day by deep im injection for 24 months,
lone is a synthetic cannabinoid used as an antiemetic in then 1g 23 times weekly, reduced in renal failure.
chemotherapy-induced nausea and vomiting. Side effects: renal and hepatic impairment, ocular dis-
Hosking RD, Zajicek JP (2008). Br J Anaesth; 101: turbances, ototoxicity, blood dyscrasias, electrolyte
5968 disturbances, neuromuscular blockade.
100 Capsaicin

Capsaicin. Component of hot chilli peppers; activates although they are not true hydrates. a usually exceeds 3,
heat-sensitive Ca2+ channels (vanilloid receptors), and may or not equal b. Notable examples of monosac-
located on A and C pain fibres, producing a burning charides are ribose and glucose, where a = 5 and 6
sensation. Initial stimulation is followed by depletion of respectively (pentoses and hexoses). Disaccharides are
substance P by reducing its synthesis, storage and trans- formed from condensation reactions between two
port. Applied topically for the treatment of neuralgias monosaccharides (e.g. sucrose = glucose + fructose).
(e.g. postherpetic neuralgia) and arthritis. Should be Large polysaccharides include starch, cellulose and gly-
applied 68-hourly. Takes 14 weeks to produce its cogen. Metabolites often contain phosphorus. Some
effect. Application of a single high-concentration (8%) polysaccharides are combined with proteins, e.g. muco-
capsaicin patch can produce 3 months relief from neu- polysaccharides. Act as a source of energy in food, e.g.:
ropathic pain. C 6 H 12O6 + 6O2 6CO2 + 6 H 2O + energy
Captopril. Angiotensin converting enzyme inhibitor, 1g carbohydrate yields about 17 kJ energy (4 Cal).
Ingested carbohydrates are broken down thus:
used to treat hypertension and cardiac failure (including
mouth: salivary amylase: starch smaller units
following MI), and diabetic nephropathy. Shorter acting
small intestine:
than enalapril; onset is within 15min, with peak effect
at 3060min. Half-life is 2h. Interferes with renal auto- - pancreatic amylase: starch as above.
regulation; therefore contraindicated in renal artery ste- - maltase: maltose glucose.
nosis or pre-existing renal impairment. - lactase: lactose glucose + galactose.
Dosage: 6.2550mg orally bd/tds. - sucrase: sucrose glucose + fructose.
Side effects: severe hypotension after the first dose, Hexoses and pentoses absorbed from the GIT pass to
cough, taste disturbances, rash, abdominal pain, the liver for storage molecule synthesis or use in alterna-
agranulocytosis, hyperkalaemia, renal impairment. tive metabolic pathways.
Severe hypotension may occur after induction of See also, Metabolism
anaesthesia and in hypovolaemia.
Contraindicated in pregnancy and porphyria. Carbon dioxide (CO2). Gas produced by oxidation of
carbon-containing substances. Average rate of produc-
Carbamazepine. Anticonvulsant drug, used to treat all tion under basal conditions in adults is about 200ml/
types of epilepsy, except petit mal. Acts by stabilising min, although it varies with the energy source (see Respi-
the inactivated state of voltage-gated sodium channels. ratory quotient).
Has fewer side effects than phenytoin, and has a greater Partial pressures of CO2:

therapeutic index. Also used for pain management inspired: 0.03 kPa (0.2mmHg).
(e.g. in trigeminal neuralgia) and in manic-depressive alveolar: 5.3 kPa (40mmHg).
disease. arterial: 5.3 kPa (40mmHg).
Dosage: initially 100200mg orally od/bd, increasing venous: 6.1 kPa (46mmHg).
to up to 1.6g/day in divided doses. Monitoring plasma expired: 4 kPa (30mmHg).
levels may help determination of optimal dosage Isolated in 1757 by Black. CO2 narcosis was used for
(target levels 2050mol/l). anaesthesia in animals by Hickman in 1824. Used to
Side effects: dizziness, visual disturbances, GIT upset, stimulate respiration during anaesthesia in the early
rash, hyponatraemia, cholestatic jaundice, hepatitis, 1900s, to maintain ventilation and speed uptake of vola-
syndrome of inappropriate ADH secretion. Blood tile agents during induction; also used to assist blind
dyscrasias may occur rarely. Enzyme induction may nasal tracheal intubation. Administration is now gener-
cause reduced effects of other drugs, e.g. warfarin. ally considered hazardous because of the adverse effects
Contraindicated in atrioventricular conduction defects of hypercapnia; CO2 cylinders have now been largely
and porphyria. removed from anaesthetic machines. Manufactured by
heating calcium or magnesium carbonate, producing
Carbapenems. Group of bactericidal antibacterial CO2 and calcium/magnesium oxide.
drugs; contain the -lactam ring and thus, like the peni- Properties:

cillins, impair bacterial cell wall synthesis. Include imipe- colourless gas, 1.5 times denser than air.
nem, meropenem and ertapenem. mw 44.
boiling point 79C.
Carbetocin. Analogue of human oxytocin, licensed for critical temperature 31C.
prevention of uterine atony after delivery by caesarean non-flammable and non-explosive.
section under regional anaesthesia. Acts within 2min of supplied in grey cylinders; pressure is 50 bar at 15C,
injection, its effects lasting over an hour. about 57 bar at room temperature.
Dosage: 100g iv. Effects: as for hypercapnia.
Side effects: as for oxytocin. [Joseph Black (17281799), Scottish chemist]
See also, Acidbase balance; Alveolar gas transfer;
Carbicarb. Experimental buffer composed of 0.3M Carbon dioxide absorption, in anaesthetic breathing
sodium carbonate and 0.3M sodium bicarbonate; unlike systems; Carbon dioxide dissociation curve; Carbon
bicarbonate, there is no net generation of CO2, when dioxide, end-tidal; Carbon dioxide measurement; Carbon
treating acidosis. dioxide response curve; Carbon dioxide transport

Carbocisteine, see Mucolytic drugs Carbon dioxide absorption, in anaesthetic breathing

systems. Investigated and described by Waters in the
Carbohydrates (Saccharides). Class of compounds early 1920s, although used earlier. Exhaled gases
with the general formula Ca(H2O)b, hence their name, are passed over soda lime or a similar material (e.g.
 Carbon dioxide measurement 101

baralyme) and reused. In closed systems, only basal O2 Carbon dioxide, end-tidal. Partial pressure of CO2
requirements need be supplied; absorption may also be measured in the final portion of exhaled gas. Approxi-
used with low fresh gas flows and a leak through an mates to alveolar PCO2 in normal anaesthetised subjects;
expiratory valve. the difference is normally 0.40.7 kPa (35mmHg),
Advantages: increasing with V/Q mismatch and increased CO2 pro-
less wastage of inhalational agent. duction. Continuous monitoring (e.g. using infrared cap-
less pollution. nography or mass spectrometry) is considered mandatory
warms and humidifies inhaled gases. during general anaesthesia.
Disadvantages: Measurement is useful for assessing adequacy of
if N2O is also used, risk of hypoxic gas mixtures ventilation, whether controlled or spontaneous, and
makes an O2 analyser mandatory. allows normo- or hypocapnia to be produced as
failure of CO2 absorption may be due to exhaustion required during IPPV. Measurement also aids detec-
of soda lime or inefficient equipment; thus capnog- tion of:
raphy is required. efficient cardiac massage or return of spontaneous
resistance and dead space may be high with some cardiac output in CPR.
systems, and inhalation of dust is possible. oesophageal intubation, since CO2 is only present
trichloroethylene is incompatible with soda lime. in the oesophagus and stomach in small amounts, if
chemical reactions between the volatile agent and at all.
soda lime if the latter dries out excessively (see Soda PE (including fat and air embolism): PECO2 falls due
lime). to increased alveolar dead space and reduced
Methods: cardiac output.
circle systems. rebreathing.
Waters canister: cylindrical drum containing 0.45kg disconnection.
soda lime. Reservoir bag at one end, facemask with MH: PECO2 rises as muscle metabolism increases.
fresh gas supply and expiratory valve at the other; Display of a continuous trace is more useful than
exhaled gases pass to and fro through it. Most effi- values alone (Fig. 30a):
cient when tidal volume equals the contained air phase 1: zero baseline during inspiration; a raised
space (400450ml). Smaller canisters are used for baseline indicates rebreathing (Fig. 30b).
children. Dead space equals the volume between phase 2: dead-space gas (containing no CO2) is
the patient and soda lime; it increases during use as followed by alveolar gas, represented by a sudden
the soda lime nearest the patient is exhausted. Effi- rise to a plateau. Excessive sloping of the upstroke
ciency is also reduced by channelling of exhaled may indicate obstruction to expiration (Fig. 30c).
gases through gaps in the soda lime if loosely packed phase 3: near-horizontal plateau indicates mixing
and allowed to settle. Also heavy and bulky to use. of alveolar gas. A steep upwards slope indicates
obstruction to expiration or unequal mixing, e.g.
Carbon dioxide dissociation curve. Graph of blood COPD (Fig. 30c).
CO2 content against its PCO2 (Fig. 29). The curve is much phase 4: rapid fall to zero at the onset of
steeper than the oxyhaemoglobin dissociation curve, and inspiration.
more linear. Different curves are obtained for oxygen- additional features may be present:
ated and deoxygenated blood, the latter able to carry - superimposed regular oscillations corresponding
more CO2 (Haldane effect). The difference between the to the heartbeat (Fig. 30d).
dissolved CO2 and the oxygenated haemoglobin curves - small waves representing spontaneous breaths
represents the CO2 carried as bicarbonate ion and carb- between ventilator breaths, e.g. if neuromuscular
amino compounds. blockade is insufficient (Fig. 30e).
See also, Carbon dioxide measurement

Carbon dioxide measurement. Estimation of arterial

CO2 content (ml/100 ml blood)

60 PCO2:
direct: Severinghaus CO2 electrode consisting of a
50 glass pH electrode separated from arterial blood
40 sample by a thin membrane. CO2 diffuses into bicar-
bonate solution surrounding the glass electrode,
30 lowering pH. pH is measured and displayed in
terms of PCO2. Requires maintenance at 37C, and
20 calibration with known mixtures of CO2/O2 before
use. Samples are stored on ice or analysed immedi-
10
ately, to reduce inaccuracy due to blood cell
0 metabolism.
0 1 2 3 4 5 6 7 8 9 10 Indwelling intravascular CO2 electrodes are available
Pco2 (kPa) for continuous monitoring of PCO2.
indirect:
Deoxygenated - from gas:
Oxygenated - to obtain gas for analysis:
Dissolved CO2 - end-tidal gas sampling (end-tidal PCO2
approximates to alveolar PCO2, which approx-
Fig. 29 Carbon dioxide dissociation curve imates to arterial PCO2).
102 Carbon dioxide narcosis

- rebreathing technique of Campbell and

(a) Howell: rebreathing from a 2 litre bag con-
taining 50% O2 for 90s, then a further 30s
after 3min rest. Bag PCO2 then approximates
3 to mixed venous PCO2. Arterial PCO2 is nor-
Pco2

mally 0.8 kPa (6mmHg) less than mixed

venous PCO2.
2 4 - subsequent gas analysis:
- chemical: formation of non-gaseous com-
1 pounds, with reduction of overall volume of
the gas mixture (Haldane apparatus).
I E
- physical: capnography and mass spectrometry
Time are most widely used. An interferometer or
I, inspiration gas chromatography may also be used.
E, expiration - from blood/tissues:
- transcutaneous electrode: requires heating of
(b) the skin; relatively inaccurate and slowly
responsive.
- measurement of venous PCO2 and capillary
PCO2: inaccurate and unreliable.
- Siggaard-Andersen nomogram: equilibration of
Pco2

the blood sample with gases of known PCO2.

- van Slyke apparatus: liberation of gas from
blood sample with subsequent chemical
analysis.
- fibreoptic sensors: under development.
Time [John W Severinghaus, San Francisco anaesthetist; EJ
Moran Campbell (19252004), English-born Canadian
(c) physiologist; John BL Howell, Southampton physician]

Carbon dioxide narcosis. Loss of consciousness caused

by severe hypercapnia, i.e. arterial PCO2 exceeding
approximately 25 kPa (200mmHg). Thought to be due
Pco2

to a profound fall in pH of CSF (under 6.9). Increasing

central depression is seen at arterial PCO2 greater than
13 kPa (100mmHg), and CSF pH under 7.1. Other fea-
tures of hypercapnia may be present.
Used by Hickman in 1824 to enable painless surgery
Time on animals.

(d) Carbon dioxide response curve. Graph defining the

relationship between minute ventilation and arterial CO2
tension. May be obtained by rebreathing from a 6 litre
bag containing 50% O2 and 7% CO2, measuring minute
ventilation and bag PCO2 periodically. This is easier than
Pco2

increasing inspired CO2 levels and measuring the

response after equilibration at each new level. The curve
may be used to indicate depression of respiratory drive
(Fig. 31); increased threshold is represented by a shift of
the curve to the right (1), and decreased sensitivity by
Time depression of the slope (2). Both may follow administra-
tion of opioid and other depressant drugs, and in chronic
(e) hypercapnia; the opposite occurs in hypoxaemia.
See also, Breathing, control of

Carbon dioxide transport. In arterial blood, approxi-

Pco2

mately 50ml CO2 is carried per 100ml blood, as:

bicarbonate: 45ml.
carbonic acid: 2.5ml.
carbamino compounds with proteins, mainly hae-
moglobin: 2.5ml.
In venous blood, 54ml is carried per 100ml blood, as:
Time
bicarbonate: 47.5ml.

Fig. 30 End-tidal PCO2 traces: (a) normal; (b) rebreathing; carbonic acid: 3.0ml.
(c) expiratory obstruction; (d) superimposed heartbeats; carbamino compounds: 3.5ml.
(e) spontaneous breaths CO2 is rapidly converted by carbonic anhydrase in red
cells to carbonic acid, which dissociates to bicarbonate
 Carboxyhaemoglobin 103

O2 saturation measured by pulse oximetry may be

misleading because carboxyhaemoglobin (which
has a unique spectrophotometric profile) is inter-
preted as oxygenated haemoglobin by some devices.
Newer co-oximeters (e.g. Masimo Rainbow) are
Minute ventilation

specifically able to determine blood carboxyhaemo-

1 globin levels by measuring the absorbance of light
across a range of wavelengths, thus distinguishing
2 between different species of haemoglobin.
neurological symptoms (e.g. dystonia, ataxia, par-
kinsonism), personality changes and impaired
memory may follow recovery from CO coma.
Treatment:
O2 therapy: speeds carboxyhaemoglobin dissocia-
Alveolar Pco2 tion. Tracheal intubation and IPPV may be neces-
sary. Elimination half-life of carbon monoxide is
Fig. 31 Carbon dioxide response curve (see text) reduced from 4h to under 1h with 100% O2; it is
reduced further to under 30min with hyperbaric O2
at 2.53 atm. At this pressure, dissolved O2 alone
satisfies tissue O2 requirements. Hyperbaric O2 has
and hydrogen ions. Bicarbonate passes into plasma in been suggested if the patient is unconscious, has
exchange for chloride ions (chloride shift); hydrogen arrhythmias, is pregnant or has carboxyhaemoglo-
ions are buffered mainly by haemoglobin. Haemoglo- bin levels above 40%.
bins buffering ability increases as it becomes deoxygen- carboxyhaemoglobin levels correlate poorly with
ated, as does its ability to form carbamino groups severity of symptoms, because of variable effects of
(Haldane effect). tissue toxicity. Values often quoted:
See also, Acidbase balance; Buffers; Carbon dioxide dis- - 0.32%: normal non-smokers (some CO from
sociation curve pollution, some formed endogenously).
- 56%: normal smokers.
Carbon monoxide (CO). Colourless, odourless and - 1030%: mild symptoms common.
tasteless gas produced by the partial oxidation of carbon- - above 60%: severe symptoms common.
containing substances. Produced endogenously from the Hampson NB, Piantadosi CA, Thom SR, Weaver LK
breakdown of haemoglobin, it acts as a neurotransmitter (2012). Am J Respir Crit Care Med; 186: 1095101
and may have a role in modulating inflammation and
mitochondrial activity. Carbon monoxide poisoning may
Carbon monoxide transfer factor, see Diffusing
result from exposure to high levels of exogenous CO.
capacity
Carbon monoxide diffusing capacity, see Diffusing
capacity Carbonic anhydrase. Zinc-containing enzyme catalys-
ing the reaction of CO2 and water to form carbonic acid,
Carbon monoxide poisoning. May result from inhala- which rapidly dissociates to bicarbonate and hydrogen
tion of fumes from car exhausts, fires, heating systems or ions. Absent from plasma, but present in high concentra-
coal gas supplies. Often coexists with cyanide poisoning. tions in:
Although not directly toxic to the lungs, carbon monox- red blood cells: important in buffering, CO2 trans-
ide (CO) binds to haemoglobin with 200250 times the port and O2 transport.
affinity of O2, forming carboxyhaemoglobin, which dis- renal tubular cells: important for maintaining acid
sociates very slowly. The amount of carboxyhaemoglo- base balance.
bin formed depends on inspired CO concentration and gastric mucosa: important in hydrochloric acid
duration of exposure. production.
Production of CO in circle systems has been reported ciliary body: involved in aqueous humour formation.
under certain circumstances. Inhibited by acetazolamide and sulphonamides.
Effects:
reduced capacity for O2 transport.
Carboprost. Prostaglandin F2 analogue, used for the
oxyhaemoglobin dissociation curve shifted to the
induction of second-trimester abortion; also used to
left.
treat postpartum haemorrhage unresponsive to first-line
inhibition of the cellular cytochrome oxidase
therapy. Given as the trometamol salt.
system; tissue toxicity is proportional to the length Dosage: 250g by deep im injection repeated as
of exposure.
required every 1590min, up to 2mg. May also be
aortic and carotid bodies do not detect hypoxia,
injected directly into the myometrium, although this
since the arterial PO2 is unaffected.
Features:
carries increased risk of accidental iv administration
and represents off-licence use.
non-specific if chronic, e.g. headache, weakness, diz-
Side effects: vomiting, diarrhoea, leucocytosis, fever,
ziness, GIT disturbances.
bronchospasm, uterine rupture.
if acute: as above, with hypoxia, convulsions and
coma if severe.
the cherry red colour of carboxyhaemoglobin may Carboxyhaemoglobin, see Carbon monoxide
be apparent. poisoning
104 Carcinogenicity of anaesthetic agents

Carcinogenicity of anaesthetic agents, see Environ- electromechanical dissociation (EMD)/pulseless

mental safety of anaesthetists; Fetus, effects of anaesthetic electrical activity (PEA). May occur in widespread
agents on myocardial damage. The least common ECG
finding, with the worst prognosis, unless due to
Carcinoid syndrome. Results from secretion of vasoac- mechanical causes of circulatory collapse, e.g. PE,
tive and other substances from certain tumours, found cardiac tamponade, pneumothorax.
in the GIT (70%) or the bronchopulmonary system. Asystole and EMD/PEA may convert to VF,
Secreted compounds are metabolised by the liver so that which eventually converts to asystole if untreated.
symptoms are absent until hepatic metastases are Only 1520% of patients leave hospital after cardiac
present. May be associated with neurofibromatosis. arrest. Up to 3040% survival is thought to be possible
Features: if prompt CPR is instituted. Permanent hypoxic brain
flushing, mainly of the head and neck. May be asso- damage usually occurs within 45min unless CPR
ciated with vasodilatation, hypotension, wheezing, is instituted. The prognosis is better if the patient
skin wheals and sweating. regains consciousness within 10min of the circulation
diarrhoea, sometimes with nausea and vomiting. restarting.
Typically episodic, along with flushing. Weight loss See also, Advanced life support, adult; Basic life support,
is common. adult; Cerebral ischaemia
endocardial fibrosis involving the tricuspid and
pulmonary valves may cause right-sided cardiac Cardiac asthma. Acute pulmonary oedema resembling
failure. asthma. Both may feature dyspnoea, decreased lung
Symptoms are traditionally ascribed to secretion of compliance and widespread rhonchi, although pink
5-HT (diarrhoea) and kinins (flushing), but many more frothy sputum is suggestive of pulmonary oedema.
substances have been implicated, e.g. dopamine, sub- Increased airway resistance may result from true bron-
stance P, prostaglandins, histamine and vasoactive chospasm or from bronchial oedema.
intestinal peptide. Diagnosis includes measurement of
urinary 5-hydroxyindole acetic acid, a breakdown Cardiac catheterisation. Passage of a catheter into the
product of 5-HT. heart chambers for measurement of intracardiac pres-
Anaesthetic management: sures and O2 saturations, or for injection of radiological
perioperative treatment with various drugs has contrast media for radiological imaging (angiocardiog-
been used to reduce hyper-/hypotensive episodes raphy). Used to investigate ischaemic heart disease, val-
and bronchospasm: vular heart disease and congenital heart disease; also
- somatostatin analogues, e.g. octreotide: inhibits used therapeutically (e.g. balloon valvotomy, atrial sep-
release of inflammatory mediators and has tostomy for transposition of the great arteries and per-
become the first-line treatment of many cutaneous transluminal coronary angioplasty).
authorities. Technique:
- 5-HT antagonists: ketanserin, cyproheptadine, commonly performed under local anaesthesia
methysergide. except in small children, in whom general anaesthe-
- antihistamine drugs. sia is required.
invasive cardiovascular monitoring and careful fluid access is via a peripheral vein or artery, e.g.
balance. femoral or brachial vessels, using either a cut-down
use of cardiostable drugs where possible; avoidance technique or percutaneous guidewire (Seldinger
of drugs causing histamine release. technique).
suxamethonium has been claimed to increase medi- the right side of the heart is approached as for pul-
ator release via fasciculations but this is uncertain. monary artery catheterisation.
drugs should be prepared for treatment of broncho- the left side of the heart is approached retrogradely
spasm and hyper-/hypotension. under X-ray control, via a peripheral artery or from
admission to HDU/ICU postoperatively. the right side through the atrial septum or a defect
Kinney MA, Warner ME, Nagorney DM, etal (2001). Br thereof.
J Anaesth; 87: 44752 Information gained:
pressure values, waveforms and gradients between
Cardiac arrest. Sudden circulatory standstill. Common chambers.
cause of death in cardiovascular disease, especially saturation values; greater than expected values on
ischaemic heart disease. May also be caused by PE, elec- the right side indicate a left-to-right shunt.
trolyte disturbances (e.g. of potassium or calcium), cardiac output may be measured using the Fick
hypoxaemia, hypercapnia, hypotension, vagal reflexes, principle.
hypothermia, anaphylaxis, electrocution, drugs (e.g. angiocardiography: cardiac function may be
adrenaline) and instrumentation of the heart. assessed on cine film, or the coronary vessels filled
Features: unconsciousness within 1530s, apnoea or with dye to assess patency.
gasping respiration, pallor, cyanosis, absent pulses. Approximate normal pressures and measurements are
Pupillary dilatation is usual. shown in Table 14.
May be due to:
VF: usually associated with myocardial ischaemia. Cardiac compressions, see Cardiac massage
The most common ECG finding (about 60%), with
the best prognosis. Cardiac contractility, see Myocardial contractility
asystole: occurs in about 30%. More likely in hypo-
volaemia and hypoxia, especially in children. May Cardiac cycle. Sequence of events occurring during
also follow vagally mediated bradycardia. cardiac activity; often represented by the Wiggers
 Cardiac failure 105

phase 5: passive ventricular filling: most rapid at the

Table 14 Normal pressures and O2 saturations obtained during
start of diastole.
cardiac catheterisation
May also be described in terms of the changes in pres-

Site Pressure (mmHg) Saturation (%) sure and volume within the left ventricle during the
cardiac cycle the left ventricular pressurevolume
Right atrium 14 75 loop (Fig. 33):
Right ventricle 25/4 75 consists of four phases corresponding to phases 25
Pulmonary artery 25/12 75 of the Wiggers diagram, as described above the
Left atrium 210 97 transition between phases is marked by opening/
Left ventricle 120/10 97 closure of mitral/aortic valves (MV/AV) (Fig. 33a).
Aorta 120/70 97 stroke volume (SV) is the difference between end-
diastolic volume (EDV) and end-systolic volume
(ESV).
stroke work corresponds to the area within the loop.
changes in preload, afterload and myocardial con-
Systole tractility result in predictable changes in the shape
of the loop, with corresponding changes in SV and
work (Fig. 33bd):
P R T - increased preload or EDV results in increased
force of contraction (see Starlings law); SV and
Q S work increase.
- increased afterload results in increased ESV; SV
100 decreases.
Pressure (mmHg)

- increased contractility results in decreased ESV;

stroke volume and work are increased.
[Carl J Wiggers (18831963), US physiologist]
See also, Arterial waveform; Pulse; Venous waveform

Cardiac enzymes. Enzymes normally within cardiac

a v y cells; released into the blood after injury (e.g. after MI
c
0 or cardiac contusion), thus aiding diagnosis:
x creatine kinase (CK or CPK):
- normally < 190 iu/l.
A P - rises 46h after MI, peaks at 12h, falls at 23
days.
S1 S2
- three specific isoenzymes exist for skeletal muscle
(CKMM), brain (CKBB) and myocardium
Time (0.1 s) (CKMB). Presence of CKMB in the plasma indi-
cates myocardial necrosis.
Phases 1 2 3 4 5 aspartate aminotransferase (AST):

ECG P/Q/R/S/T: see ECG - normally < 35 iu/l.

Aorta a/c/x/v/y: see Venous waveform - rises after 12h, peaks at 12 days.
Left atrium S1/S2: 1st/2nd heart sounds lactate dehydrogenase (LDH):
Left ventricle A/P: aortic/pulmonary valve closure - normally < 300 iu/l (depends on the assay).
Phonocardiography - rises after 12h, peaks at 23 days, falls after 57
days.
Fig. 32 Cardiac cycle (see text) - five isoenzymes exist; an increase in the level of
LDH1 or the ratio of LDH1:LDH2 indicates
myocardial necrosis.
diagram, which details changes in vascular pressures Have been largely replaced by troponins as indicators of
(especially arterial BP), heart chamber pressures, ECG myocardial damage (see Acute coronary syndromes).
and phonocardiography tracings during normal sinus
rhythm (Fig. 32). Cardiac failure. Usually defined as inability of the heart
Divided into five phases: to produce sufficient output for the bodys requirements.
phase 1: atrial contraction: responsible for about The diagnosis is clinical, ranging from mild symptoms on
30% of ventricular filling. Some blood regurgitates exertion only to cardiogenic shock. Several terms have
into the venae cavae and pulmonary veins. been used to describe different forms of cardiac failure:
phase 2: isometric ventricular contraction: lasts left or right ventricular failure (the most commonly
from the closing of the tricuspid and mitral valves used classification). The left ventricle is usually
until ventricular pressures exceed aortic and pulmo- affected by general disease because its workload is
nary artery pressures, and the aortic and pulmonary much greater than that of the right.
valves open. forward or backward failure: the former refers to
phase 3: ventricular ejection: most rapid at the start failure with reduced cardiac output; the latter refers
of systole. Lasts until the aortic and pulmonary to failure with venous congestion.
valves close. congestive cardiac failure: the term sometimes
phase 4: isometric ventricular relaxation: lasts until refers to backward failure, but is often reserved for
the tricuspid and mitral valves open. left-sided failure leading to right-sided failure.
106 Cardiac failure

(a) (b)
200 200
Left ventricular pressure (mmHg)

Left ventricular pressure (mmHg)

100 AV closes 3 100
AV opens
4 SV
2

MV opens 5 MV closes
0 0
0 100 200 0 100 200
ESV EDV
Left ventricular volume (ml)
Left ventricular volume (ml)
(c) (d)
200 200
Left ventricular pressure (mmHg)

Left ventricular pressure (mmHg)

100 100

0 0
0 100 200 0 100 200
Left ventricular volume (ml) Left ventricular volume (ml)

Fig. 33 Left ventricular pressurevolume loops (see text): (a) baseline; (b) increased preload; (c) increased afterload; (d) increased contractility
(shaded loops show the effect of changes)

high-output failure: associated with increased reduced filling:
preload and increased cardiac output. - tricuspid/mitral stenosis.
diastolic failure: recently recognised form in which - cardiac tamponade, constrictive pericarditis (right
the ejection fraction may be normal but ventricular side).
filling is impaired. - reduced ventricular compliance, e.g. amyloid
Caused by: infiltration.
increased workload: Effects:
- preload: ventricular end-diastolic pressure increases, leading
- aortic/mitral regurgitation. to compensatory mechanisms:
- ASD/VSD. - ventricular hypertrophy.
- severe anaemia, fluid overload, hyper - increased force of contraction (Starlings law).
thyroidism. - neuroendocrine response: mainly increased sym-
- afterload: pathetic activity, with tachycardia, vasoconstric-
- hypertension. tion and increased contractility. Aldosterone,
- pulmonary/aortic stenosis, hypertrophic renin/angiotensin and vasopressin activity are
obstructive cardiomyopathy. increased, especially in chronic failure, but mecha-
- pulmonary hypertension, PE. nisms are unclear. Salt and water retention result.
reduced force of contraction: ventricular compliance is reduced, leading to
- MI, ischaemic heart disease. increased atrial pressure and atrial hypertrophy.
- cardiomyopathy. Eventually, ventricular dilatation occurs, with higher
- arrhythmias. wall tension required to produce a given pressure
- myocarditis. (Laplaces law).
 Cardiac glycosides 107

coronary blood flow is reduced by tachycardia,

3:
raised end-diastolic pressure and increased muscle - drug combinations, e.g. inotropes + vasodilators;
mass. often produce the greatest improvement
left-sided failure may lead to pulmonary oedema, - intra-aortic counter-pulsation balloon pump.
pulmonary hypertension, V/Q mismatch, decreased Anaesthetic considerations:
lung compliance and right-sided failure. cardiac failure is consistently associated with
right ventricular failure: CVP and JVP increase, increased perioperative morbidity and mortality; it
with peripheral oedema and hepatic engorgement. should therefore be treated preoperatively when-
reduced peripheral blood flow leads to increased O2 ever possible.
uptake and reduction of mixed venous PO2. treatment as above. Electrolyte disturbances and
sodium and water retention exacerbate oedema. digoxin toxicity may occur.
Features: anaesthetic drugs should be given in small doses
reduced cardiac output may result in hypotension, and slowly, because:
confusion and coma. - armbrain circulation time is increased.
left-sided failure: - increased proportion of cardiac output goes to
- dyspnoea, typically worse on lying flat (orthop- vital organs, e.g. brain and heart; thus greater
noea) and sometimes waking the patient at night effects are seen on these organs than in normal
(paroxysmal nocturnal dyspnoea). cardiac output states.
- peripheral shutdown, basal crepitations, left danger of myocardial depression, hypoxia,
ventricular hypertrophy. Extra heart sounds, e.g. arrhythmias.
gallop rhythm and heart murmurs, may be present. use of epidural/spinal anaesthesia is controversial;
CheyneStokes respiration may accompany low the benefit of reduction of SVR may be offset by
output. the risk of hypotension. Perioperative risk is not
- acute pulmonary oedema. diminished.
right-sided failure: McMurray JJV (2010). N Engl J Med; 362: 22838
- raised JVP.
- dependent oedema, e.g. ankles if ambulant, Cardiac glycosides. Drugs derived from plant extracts;
sacrum if bed-bound. used to control ventricular rate in atrial fibrillation and
- hepatomegaly/ascites; the liver may be tender. atrial flutter and for symptomatic relief in cardiac failure.
- right ventricular hypertrophy. Actions are due to inhibition of the sodium/potassium
CXR may reveal cardiomegaly, upper-lobe blood pump and increased calcium mobilisation. The drugs
diversion, fluid in the pulmonary fissures, Kerley have long half-lives (e.g. ouabain 20h; digoxin 36h; digi-
lines, pleural effusion and pulmonary oedema. toxin 4 days), large volumes of distribution (e.g. digoxin
ECG may reveal ventricular hypertrophy and strain 700 litres) and low therapeutic index.
and arrhythmias. Actions:
Management: increase myocardial contractility and stroke volume.
general: of underlying cause, rest, sodium restric- decrease heart rate via direct effects on atrioven-
tion; O2 therapy if acute. tricular conduction and sinus node discharge; also
ACE inhibitors: inhibit ventricular remodelling, act indirectly by increasing vagal tone.
reducing mortality and morbidity. Angiotensin II Side effects: as for digoxin. They are increased by
receptor antagonists have similar efficacy. hypokalaemia, hypercalcaemia and hypomagnesae-
diuretics: reduce salt and water retention, pro mia. Toxicity is also more likely in renal failure and
viding symptomatic relief; a thiazide in combina- pulmonary disease.
tion with a loop diuretic is frequently used.
Spironolactone may be added in low dosage to
ACE inhibitor/diuretic therapy in severe, non-
responsive failure.
-adrenergic receptor antagonists (e.g. carvedilol,
bisoprolol): first-line agents in stable left ventricular Normal
systolic failure, reducing mortality and morbidity.
other vasodilator drugs (e.g. nitrates, hydralazine)
have been used in patients unable to tolerate ACE 3
1
inhibitors.
Cardiac output

inotropic drugs: oral drugs are mostly disappointing. Failure

The most effective drugs are administered by iv 2
infusion.
digoxin: may improve symptoms and performance
but not mortality.
calcium sensitisers, e.g. levosimendan.
atrial-synchronised biventricular pacemakers have
been shown to improve symptoms and mortality in
patients with severe failure.
emergency treatment: as for pulmonary oedema
and cardiogenic shock. Left ventricular end-diastolic pressure
Response to treatment (Fig. 34):
1: inotropic drugs/arterial vasodilators. Fig. 34 Response to treatment of cardiac failure by Starlings curve
2: diuretics/venous vasodilators. (see text)
108 Cardiac index

Digoxin is most widely used. Ouabain is more rapidly Intrathoracic pressures may be maximised by syn
acting. chronising compressions with IPPV breaths, with or
without abdominal binding or compression (new
Cardiac index (CI). Cardiac output corrected for body CPR). Devices used to augment the thoracic pump
size, expressed in terms of body surface area: mechanism include:
cardiac output (1/ min) - automatic chest compressor (chest thumper).
CI = - active compression/decompression device:
surface area (m 2 ) applies suction to the chest wall between com-
Normal value is 2.54.2 l/min/m2. pressions to increase venous return.
- impedance valve inserted in the ventilating
Cardiac massage. Periodic compression of the heart or system: impedes passive inspiration during the
chest in order to maintain cardiac output, e.g. during release phase, thus increasing intrathoracic neg-
CPR. Both open (internal) and closed (external) cardiac ative pressure and increasing venous return.
massage were developed in the late 1800s. The latter During compression the extra venous return
became more popular in the 1960s following clear dem- results in greater cardiac output.
onstration of its value in dogs and humans, and was Improved blood flows and outcome have been
subsequently adopted by the American Heart Associa- claimed but further studies are awaited.
tion and the Resuscitation Council (UK) as method Open cardiac massage:
of choice. increasingly used, because blood flows and cardiac
Closed cardiac massage: output are greater than with closed massage. Also,
with the patient supine on a rigid surface, the heel direct vision and palpation are useful in assessing
of one hand is placed on the lower half of the cardiac rhythm and filling, and defibrillation and
sternum. The other hand is placed on the first, intracardiac injection are easier.
with fingers clear of the chest. With elbows skin and muscle are incised in an arc under the left
straight and shoulders vertically above the hands, nipple in the fourth or fifth intercostal space, stop-
regular compressions are applied, with a compres- ping 23cm from the sternum to avoid the internal
sion:relaxation ratio of 1:1. The sternum should be thoracic artery. Pericardium is exposed using blunt
depressed 56cm at each compression, at a rate of dissection and pulling the ribs apart. The heart is
100120/min. squeezed from the patients left side using the left
efficacy is assessed by feeling the femoral or carotid hand, with fingers anteriorly over the right ventricle
pulse, although palpable peak pressures may not and thumb posteriorly over the left ventricle. The
reflect blood flow. End-tidal CO2 measurement rate of compressions is determined by cardiac
has been used to assess adequacy of massage; an filling. The descending aorta may be compressed
increase reflects improved cardiac output. with the other hand. The pericardium is opened for
may produce up to 30% of normal cardiac output defibrillation or intracardiac injection. Because of
with corresponding carotid and cerebral blood flow. the emergency nature of the procedure and the low
Coronary flow is low during cardiac massage, and risk of infection, sterile precautions are usually
falls rapidly when massage is stopped. waived.
Technique in children up to 8 years: may also be performed per abdomen through the
- under 1 year: tips of two fingers placed on the intact diaphragm; the heart is compressed against
sternum, one fingers breadth below a line joining the sternum. Minimally invasive direct cardiac
the nipples. The sternum is depressed by one-third massage via a small thoracostomy has recently been
of the depth of the childs chest at a rate of 100 described.
120/min. usually reserved for trauma, perioperative use,
- up to 8 years: heel of one hand placed over the intra-abdominal or thoracic haemorrhage, massive
lower half of the sternum, the fingers lifted to PE, hypothermia, chest deformity and ineffective
avoid applying pressure on the ribs. The sternum closed massage.
is depressed by one-third of the depth of the European Resuscitation Council (2010). Resuscitation;
childs chest at a rate of 100120/min. 81: 121976
theories of mechanism (both may occur): See also, Cardiac output measurement
- cardiac pump (as originally suggested): the heart
is squeezed between sternum and vertebrae
during compressions, expelling blood from the Cardiac output (CO). Volume of blood ejected by the
ventricles. During relaxation, blood is drawn into left ventricle into the aortic root per minute. Equals
the chest by negative intrathoracic pressure, and stroke volume (litres) heart rate (beats/min). Normally
the ventricles fill from the atria (thoracic dias- about 5 l/min (0.07 litres 70 beats/min) in a fit 70-kg
tole). Thought to be more important in children man at rest; may increase up to 30 l/min, e.g. on vigorous
and when the heart is large. exercise. Often corrected for body surface area (cardiac
- thoracic pump: the theory arose from arterial and index).
cardiac chamber pressure measurements during Of central importance in maintaining arterial BP
CPR, and from the phenomenon of cough-CPR. (equals cardiac output SVR) and O2 delivery to the
Positive intrathoracic pressure pushes blood out tissues (O2 flux).
of heart and chest during compressions; reverse Affected by metabolic rate (e.g. increased in preg-
flow is prevented by cardiac and venous valves, nancy, sepsis, hyperthyroidism and exercise), drugs, and
and collapse of the thin-walled veins. During many other physiological and pathological processes
relaxation, blood is drawn into the chest by nega- that affect heart rate, preload, myocardial contractility
tive intrathoracic pressure. and afterload.
 Cardiac output measurement 109

Distribution of normal CO (approximate values): measured by a thermistor at the catheter tip.

heart: 5%. Injection is usually performed at end-expiration.
brain: 15%. A plot of temperature drop against time is pro-
muscle: 20%. duced as for dye dilution but without the sec-
kidneys: 20%. ondary peak. Cardiac output is calculated by a
liver: 25%. bedside computer using the StewartHamilton
rest: 15%. equation and an average of at least three mea-
(for comparisons of blood flow and oxygen consumption, surements. Sources of inaccuracy include: the
see Blood flow) presence of intracardiac shunts or tricuspid
Effects of iv anaesthetic agents on CO: regurgitation; inaccurate measurement of injec-
reduced by propofol > thiopental > etomidate, tate volume or temperature; variation in the
mostly via decreased contractility, though propofol speed of injection; or if the thermistor is against
may also cause vasodilatation and bradycardia. a vessel wall. Repeated measurements are not
increased by ketamine. affected by previous ones.
Effects of inhalational anaesthetic agents on CO: In transpulmonary thermodilution cardiac output
reduced by enflurane > halothane > isoflurane/ measurement, ice-cold saline is injected via a
desflurane > sevoflurane > N2O. Proposed mecha- central venous catheter and is dispersed into both
nisms include direct myocardial depression (via intra- and extravascular spaces during passage
reduced concentration or modified activity of intra- through the lungs. Pulse contour cardiac output
cellular calcium ions during systole), inhibition of derived from rapid beat-to-beat analysis of the
central or peripheral sympathetic nervous system arterial (aortic) pressure wave is calibrated with
outflow, and altered baroreceptor activity. an arterial thermodilution measurement to give a
maintained by diethyl ether via sympathetic stimu- continuous indication of cardiac output. Use of an
lation despite a direct myocardial depressant effect. intra-arterial fibreoptic catheter and injection of
See also, Cardiac output measurement; Cardiac cycle cold dye allows measurement of intrathoracic
blood volume and extravascular lung water. If
Cardiac output measurement. Methods that have indocyanine green is used, the intravascular dye
been used include: distribution volume during the first cardiopulmo-
Fick principle: most commonly O2 consumption is nary passage equals intrathoracic blood volume;
measured using samples of mixed venous and arte- indocyanine green is extracted selectively from the
rial blood. Alternatively, CO2 production may be blood by the liver and this can therefore be used
measured, deriving arterial PCO2 from end-tidal as a liver function test. Total circulating blood
expired partial pressure. Mixed venous PCO2 may volume can be calculated after complete mixing of
be derived from analysis of expired gas collected the indocyanine green with the blood has occurred.
in a closed rebreathing bag, using a mass spectrom- - continuous: employs a specially modified pulmo-
eter. Both methods are lengthy, complicated and nary artery catheter, containing a thermal fila-
unsuitable for routine use. A new technique, ment extending 1425cm from its distal tip (thus
NiCO, employs partial PCO2 rebreathing and end- lying within both the right atrium and the right
expiratory CO2 measurement. ventricle during use), which adds an average of
dilution techniques: 7.5 W heat to the blood in a repetitive onoff
- dye dilution: a known amount of dye is injected sequence every 3060s. Changes in blood tem-
into the pulmonary artery, and its concentration perature are measured by a thermistor 4cm
measured peripherally using a photoelectric spec- from the catheter tip. A typical thermodilution
trometer. Indocyanine green is used because of its washout curve is constructed by applying a
low toxicity, short half-life and absorption charac- formula to correlate the thermistor temperature
teristics (i.e. unaffected by changes in O2 satura- with the thermal energy input sequence. Cardiac
tion). Semilogarithmic plotting of the data curve output is computed from the curve as above.
is required, with extrapolation of the straight line
obtained to correct for recirculation of the dye
(Fig. 35). Cardiac output is calculated from the
injected dose, the area under the curve within the
extrapolated line and its duration. Curves of short
Concentration of dye

duration are produced by high cardiac output; Secondary peak, due to

curves of long duration are produced by low recirculation of dye
cardiac output. Recirculation of dye may cause
data from repeated injections to be affected by
previous ones.
Lithium is an alternative to indocyanine green;
it is injected via a central venous catheter and
measured by a lithium-sensitive electrode incor-
porated into an arterial cannula, e.g. placed in the
radial artery.
Time
- thermodilution: suitable for use in the ICU or
operating theatre: Ordinary plot
- intermittent: 510ml cold dextrose or saline is Semilogarithmic plot
injected through the proximal port of a pulmo-
nary artery catheter, with temperature changes Fig. 35 Dilution technique for measuring cardiac output
110 Cardiac pacing

- PiCCO: a technique combining transpulmonary repositioned if necessary. Dual-chamber pacing

thermodilution and arterial pulse contour may be achieved using a special atrial wire in
analysis. addition to the ventricular one.
echocardiography: two-dimensional echocar - tachyarrhythmias, e.g. SVT, atrial flutter: A00
diography can be used to measure left ventricular pacing is used, stimulating via a right atrial lead.
ejection fraction and subsequent derivation of The rate is slowly increased from 60/min to the
stroke volume. This relies on the shape of the spontaneous rate, held for 30s, and pacing
ventricular cavity being ellipsoid, which may not stopped. If unsuccessful, pacing at 400800/min
always be the case. Three-dimensional and trans may be used to provoke AF, which usually reverts
oesophageal echocardiography may produce better spontaneously to sinus rhythm. VT may be treated
results. by slow ventricular V00 pacing, atrial pacing or
a Doppler probe (oesophageal or suprasternal) may ventricular pacing at 1030% faster rate than
be used; the velocity of blood in the ascending aorta spontaneous for 510 beats only (burst pacing),
is measured using the Doppler effect, allowing esti- with defibrillation available. Advantages over car-
mation of the length of a column of blood passing dioversion include avoidance of anaesthesia and
through the aorta per unit time. This is multiplied the adverse effects of electrical shock, easier rep-
by the cross-sectional area of the aorta to give etition if unsuccessful and availability of pacing if
cardiac output. bradycardia or asystole occurs.
cardiac catheterisation and angiography allow esti- - the pacing wire may conduct extraneous currents
mation of left ventricular volume and ejection frac- directly to the heart (e.g. from diathermy) with
tion, as does radioisotope scanning. risk of electrocution (microshock).
impedance plethysmography and induction cardi- - transthoracic pacing may also be used, with large
ography: thought to be useful in estimating changes surface area skin electrodes (e.g. one over the
in individual subjects, but not useful for absolute cardiac apex, one over the right scapula or clavi-
measurements. cle) and pulse duration of up to 50 ms to reduce
aortovelography and ballistocardiography: cutaneous nerve and muscle stimulation. Avoids
inaccurate. complications of transvenous pacing, and quicker
electromagnetic flow measurement may be achieved to perform.
during surgery by placing a probe around the root - transoesophageal pacing has also been used but
of the aorta, but its use is obviously limited. is less reliable.
de Waal EE, Wappler F, Buhre WF (2009). Curr Opin permanent: a pulse generator (pacemaker) is
Anesth; 22: 717 implanted subcutaneously. Electrodes are usually
unipolar, i.e. one intracardiac electrode, with current
Cardiac pacing. Repetitive electrical stimulation of returning to the pacemaker via the body. The heart
myocardium, used to treat brady- or tachyarrhythmias. electrode is usually endocardial, passed via a central
May be: vein; epicardial electrodes have been used.
temporary:
- transvenous: pacing wire passed via a central vein
to the right ventricle under X-ray control. Usually Cardiac risk indices. Scoring systems for preoperative
bipolar, with two electrodes at the end of the wire; identification of patients at risk from major periopera-
current passes from the distal to the proximal tive cardiovascular complications. The first, described by
electrode, stimulating adjacent myocardium. Goldman in 1977, was derived retrospectively from data
Wires may be rigid, or flexible and balloon-tipped. from 1001 patients undergoing non-cardiac surgery;
Complications and technique of insertion are as analysis identified nine differentially weighted variables
for central venous cannulation; the procedure correlating with increased risk:
may be technically difficult. In biventricular third heart sound/elevated JVP: 11 points.
pacing (for heart failure) a lead is also placed in MI within 6 months: 10 points.
the left ventricle via the coronary sinus. ventricular ectopic beats > 5/min: 7 points.
Indications include acute MI (inferior MI often rhythm other than sinus: 7 points.
requires temporary pacing; anterior often requires age > 70 years: 5 points.
permanent pacing). Preoperative use should be emergency operation: 4 points.
considered in: severe aortic stenosis: 3 points.
- heart block: third-degree, sometimes second- poor medical condition of patient: 3 points.
degree (e.g. if Mobitz type II, associated with abdominal or thoracic operation: 3 points.
symptoms or intended surgery is extensive). Patients with scores above 25 points had 56% incidence
- bundle branch block, e.g. symptomatic bifas- of death, with 22% incidence of severe cardiovascular
cicular block or PR prolongation. complications. Corresponding figures for scores below
- bradyarrhythmias. 26 points were 4% and 17% respectively, with 0.2% and
Technique of pacing: 0.7% for scores less than 6.
- bradyarrhythmias: once the wire is in place, the The more recent Revised Cardiac Risk Index identi-
pacemaker box is set to V00 (see below) and the fies six independent predictors of major cardiac compli-
minimal current is determined (usually about cations following non-cardiac surgery:
12mA). The pacing output is set 23 times high-risk surgery (intraperitoneal, intrathoracic or
higher and the system changed to VVI. Failure suprainguinal vascular surgery).
to pace may result from disconnections, over- history of ischaemic heart disease.
sensing or failure to capture. The pacing box history of heart failure.
should be converted to V00 and the wire cerebrovascular disease.
 Cardiac surgery 111

insulin-dependent diabetes mellitus. commonly used. Ketamine is usually avoided.

preoperative serum creatinine > 177mol/l. Benzodiazepines have been used.
Relative risk of major cardiac events for no factors is standard neuromuscular blocking drugs are suit-
~0.4%; for one factor it is ~1%, for two factors ~2% and able; pancuronium is often used as it is long-
for three or more factors ~6%. acting and maintains BP, although it may cause
Confirmed by other studies as having high specificity tachycardia.
but low sensitivity; i.e. high-scoring patients are high risk, opioid analgesic drugs are used to provide a smooth
but not all high-risk patients are identified. induction and avoid the hypertensive response to
Other scoring systems are used for patients undergo- intubation, e.g. fentanyl 510g/kg, alfentanil 30
ing cardiac surgery (e.g. Parsonnet risk stratification 50g/kg or remifentanil 1g/kg followed by 0.05
scheme). 2g/kg/min. High-dose techniques (e.g. fentanyl or
[Lee B Goldman, Boston cardiologist; Victor Parsonnet, alfentanil up to 100125g/kg) have been used but
New Jersey cardiac surgeon] may necessitate prolonged postoperative IPPV.
Ford MK, Beattie S, Wijeysundera DN (2010). Ann N2O is often avoided because of myocardial depres-
Intern Med; 152: 2635 sion, especially in combination with high-dose
See also, Ischaemic heart disease; Preoperative opioids. It may also increase SVR and the size of air
assessment bubbles. Volatile inhalational anaesthetic agents are
commonly used. Isoflurane was found to cause cor-
onary steal in early animal models, but this concern
Cardiac surgery. First performed in the late 1800s but has been refuted; there is now good evidence that
limited by the effects of circulatory interruption. Use of volatile agents (including isoflurane) protect against
hypothermia increased the range of surgery possible, but subsequent ischaemic injury (anaesthetic precondi-
open heart surgery, i.e. employing cardiopulmonary tioning). TIVA with propofol is also commonly
bypass (CPB), was not developed until the 1950s. used. No primary anaesthetic agent has been found
Indications: to be superior to any other.
requiring CPB: maintenance of myocardial oxygen balance and
- ischaemic heart disease, i.e. coronary artery minimisation of ischaemia are of overriding impor-
bypass graft (CABG; but see below). tance; aims include avoidance of tachycardia, main-
- congenital heart disease, e.g. VSD, ASD, Fallots tenance of oxygenation and adequate diastolic
tetralogy. coronary perfusion pressure.
- others, e.g. heart transplantation, pulmonary Monitoring:
embolectomy for PE, chest trauma. 5-lead ECG.
not requiring CPB: patent ductus arteriosus, aortic direct arterial BP measurement.
coarctation, pericarditis, cardiac tamponade. CABG CVP measurement.
is increasingly performed off-pump. pulmonary artery catheterisation may be used in
percutaneous procedures, e.g. percutaneous translu- complex cases. Left-sided pressures may be mea-
minal coronary angioplasty and stent insertion and sured directly via a needle during surgery.
pacemaker insertion, are usually performed under transoesophageal echocardiography is routinely
local anaesthesia. General anaesthesia is required used. An oesophageal Doppler probe may be used
for electrophysiological studies and insertion of to assess perioperative myocardial workload and
implantable defibrillators. myocardial ischaemia.
Preoperative assessment and management: temperature measurement (core and peripheral).
as for ischaemic and congenital heart disease. electrolyte and blood gas interpretation should be
Cardiac risk index may be used for assessing risk. readily available. Activated clotting time (ACT)
Cardiac failure is particularly important. Respira- may be determined in the operating theatre (see
tory and cerebrovascular disease is common. Inves- Coagulation studies).
tigations include assessment of respiratory, renal, a urinary catheter is usual unless surgery is straight-
and liver function and coagulation studies. CXR, forward and short.
ECG, cardiac catheterisation studies and echocar- Pre-CPB management:
diography are routine. Carotid Doppler studies may stimulation during sternotomy may require further
be indicated. analgesia to prevent tachycardia and hypertension.
most cardiovascular drugs are continued. Oral anti- after baseline ACT measurement, heparin 23mg/
coagulant drugs are usually stopped or changed to kg (90mg/m2 surface area) is injected via a tested
heparin. central line. Prostacyclin has been used but is
traditional heavy premedication regimens have expensive and its role is uncertain. ACT measured
largely been replaced with single-agent anxiolysis after 1min should be > 480s or three times base-
(e.g. temazepam) if required. Premedication is often line; aortic and right atrial cannulation may then be
omitted in emergency surgery. Antibiotic prophy- performed for CPB.
laxis is usual. Management during CPB:
Induction and maintenance of anaesthesia: circulation is gradually taken over by the pump.
preoxygenation is usually employed. drugs are diluted by the crystalloid prime, thus
venous and arterial cannulation is usually per- further iv boluses are often required, e.g. opioid,
formed under local anaesthesia. Central venous benzodiazepine, induction agent, neuromuscular
cannulation is often reserved until the patient is blocking drug. Fentanyl may be taken up by the
anaesthetised. oxygenator membrane. Drugs, including inhala-
iv induction employs standard agents in small tional agents, may be added to the CPB circuit.
doses, as for ischaemic heart disease. Etomidate is haemodilution occurs.
112 Cardiac tamponade

hypothermia is used to reduce myocardial O2 - vasodilators (often combined with inotropes).

requirements and provide neuroprotection; the - correction of potassium/acidbase imbalance.
aorta is cross-clamped and cardioplegia used, low- - intra-aortic counter-pulsation balloon pump is
ering heart temperature to 1015C. Intentional occasionally required.
fibrillation is sometimes used, avoiding cardiople- heparin is reversed with protamine, injected slowly
gia. Mild hypothermia (3235C) is often used to reduce side effects, especially pulmonary hyper-
to provide some neuroprotection while avoiding tension. 1mg/mg heparin is usually used.
problems of moderate (2832C) and profound hypertension is common if left ventricular function
(2227C) hypothermia, especially disturbed coagu- is good, especially in aortic valve disease; vasodila-
lation. Lower temperatures (1520C) are used tors may be required.
during circulatory arrest. temperature may fall as core heat is transferred to
IPPV is stopped; continuous positive pressure is the periphery.
sometimes applied to maintain some lung expan- arrhythmias and heart block may occur.
sion. Air is thought to be better than 100% O2 pericardial and pleural drains are inserted before
because of increased atelectasis with the latter; N2O sternal closure.
is avoided because of the risk of air embolism. transfer to ICU must be carefully managed because
optimal perfusion pressure is controversial; of the potential dangers from interrupted monitor-
50mmHg is generally thought to be the minimum. ing and infusions, and movement.
CPB details are also controversial, e.g. type of oxy- specific postoperative concerns include:
genator, pulsatile/non-pulsatile flow. - bleeding: may be surgical, or caused by consump-
SVR decreases as haemodilution occurs; vasopres- tion or dilution of platelet and coagulation
sor drugs (e.g. phenylephrine or metaraminol) may factors during CPB, the effects of massive blood
be needed to maintain perfusion pressure. SVR transfusion, or inadequate reversal of heparin.
then slowly increases due to absorption of the Perioperative aprotinin, antifibrinolytic drugs and
crystalloid and vasodilatation with GTN or phentol- desmopressin have been used to reduce blood
amine may be needed. Some cardiovascular drugs requirements.
such as nicorandil and angiotensin converting - treatment of hyper-/hypotension and
enzyme inhibitors may exacerbate hypotension. arrhythmias.
ACT is checked every 30min, with further heparin - low-output state, as above. Cardiac tamponade
given if necessary, e.g. one-quarter to one-half initial may necessitate thoracotomy on ICU.
dose. Potassium is added as required. Arterial - maintenance of fluid balance and urine output.
blood gas analysis is performed at 37C in most The crystalloid load from CPB usually causes
machines; values have been traditionally corrected diuresis but pulmonary oedema may occur, espe-
to body temperature to account for increased cially if cardiac output is low.
solubility of CO2 at low temperatures (pH stat), - rewarming; central/peripheral temperature differ-
but this is now considered unnecessary and man- ence is a useful indication.
agement conducted according to uncorrected - maintenance of electrolyte, acidbase and blood
values (alpha stat). Bicarbonate is usually not gas balance. Hypokalaemia is common.
administered unless base deficit exceeds 78mmol/l. - IPPV is usually continued for a few hours,
Blood is transfused to keep the haematocrit above sometimes overnight. Opioid/benzodiazepine
0.20.3. boluses are commonly used for sedation. Immedi-
after repair of the lesion, the cross-clamp is removed ate extubation after surgery is increasingly per-
and rewarming undertaken. Cardiac activity (usually formed in appropriately selected cases. Usual
VF but sometimes sinus rhythm) usually returns criteria for weaning include cardiovascular and
spontaneously. Internal defibrillation is performed respiratory stability, adequate warming and
at 3032C, and normal PO2, pH and electrolyte perfusion, good urine output, minimal blood loss
concentration. 2050 J is usually used. Cardiac and good conscious level. Impaired gas exchange
pacing is sometimes required; epicardial wires may may be associated with pre-existing lung disease,
be inserted prophylactically for postoperative use. atelectasis, and CPB-related factors (e.g. emboli-
CPB blood flow is gradually decreased as cardiac sation with bubbles and platelet aggregates,
output increases. Drug boluses are given iv as complement activation), especially if CPB was
before. Manual IPPV helps expel air from the pul- prolonged.
monary vessels. - CNS changes: CVA occurs in less than 2% of
Post-CPB and postoperative care: patients undergoing open-heart surgery, but
left atrial pressure is optimised to 812mmHg; subtle changes are found in up to 60%, thought
vasodilators are used to accommodate CPB fluid to be related to embolisation (e.g. bubbles, aggre-
volume. gates during CPB) and/or inadequate perfusion.
a low-output state may occur, especially if ventricu- Effects are possibly reduced by filtering the arte-
lar function was poor preoperatively and ischaemia rial inflow line.
time was prolonged. It may be improved by:
- inotropic drugs: calcium is often used as a tempo-
rary measure but may worsen reperfusion injury. Cardiac tamponade. Compression of the heart by
Others include dopamine, dobutamine, adrena- fluid (e.g. blood) within the pericardium, restricting
line and isoprenaline; more recently enoximone, ventricular filling and reducing stroke volume and
milrinone and dopexamine. The choice is accord- cardiac output.
ing to individual patient and drug characteristics, Myocardial O2 supply is reduced by hypotension,
and personal experience. increased end-diastolic pressure, tachycardia and
 Cardiomyopathy 113

compression of epicardial vessels. Tamponade should be Cardioinhibitory centre (Cardioinhibitory area). Con-
differentiated from pneumothorax and cardiac failure. sists of the nucleus ambiguus and adjacent neurones in
Features: the ventral medulla, with some input from the dorsal
dyspnoea, restlessness, oliguria, hypotension, motor nucleus and nucleus of the tractus solitarius. Pro-
peripheral vasoconstriction. JVP, CVP and left duces vagal tone, increased by baroreceptor discharge.
atrial pressure are raised, and pulsus paradoxus is Also receives afferents from higher centres. Efferents
present. Jugular venous distension may occur during pass to the vasomotor centre, inhibiting it, and thence to
inspiration or when pressure is applied over the the heart via the vagus nerve. Thus involved centrally in
liver (Kussmauls sign). Cardiovascular collapse and controlling arterial BP.
death may occur, especially if acute (e.g. following
chest trauma).
ECG complexes may be small, and the heart shadow Cardiomyopathy. Encompasses disorders of myocar-
globular and enlarged on the CXR. Confirmed by dial function from any cause, categorised by the World
echocardiography. Health Organization as either extrinsic (specific pathol-
Immediate management is pericardiocentesis; surgery ogy secondary to a well-defined cause, e.g. ischaemic,
may be required subsequently. hypertensive, valvular, inflammatory) or intrinsic (gen-
Anaesthetic considerations: drugs or manoeuvres eralised pathology with less discrete aetiology).
which reduce venous return, heart rate or myocardial Intrinsic myocardial disorders are defined according
contractility should be avoided, especially with to pathophysiology:
coexistent hypovolaemia. IPPV should be performed dilated (congestive):
cautiously. - reduced contractility and ejection fraction, with
[Adolf Kussmaul (18221909), German physician] ventricular dilatation.
See also, Cardiac surgery - causes cardiac failure, arrhythmias, angina and
systemic embolism from mural thrombus.
Cardiogenic shock. Shock due to primary cardiac pump - prognosis is poor; death is usually within a few
failure. Diagnosis is suggested by acute haemodynamic years of cardiac failure.
changes, including: - may be associated with alcoholism, viral infection,
systolic BP 30mmHg below basal levels for more cytotoxic drugs, connective tissue diseases, and
than 30min. metabolic and infiltrative disorders, e.g. sarcoid-
cardiac index < 2.2 l/min/m .
2
osis. Peripartum cardiomyopathy is defined as
arteriovenous oxygen difference > 5.5ml/100ml. that occurring in the absence of other causes and
pulmonary capillary wedge pressure (PCWP) > in the last month (the last trimester has been sug-
15mmHg. gested) of pregnancy or the first 5 months after
Most commonly caused by acute MI affecting either pregnancy. It typically presents as cardiac failure
right or left ventricle, but it may also follow cardiac and may recur in subsequent pregnancies.
surgery, chest trauma and acute myocarditis. Heart - treatment includes digoxin, diuretics, antiarrhyth-
rate and SVR are usually increased to compensate for mic drugs, vasodilator drugs and anticoagulant
hypotension, exacerbating myocardial O2 supply/ drugs.
demand imbalance. Acidosis resulting from poor perfu- - anaesthetic management: as for ischaemic heart
sion further impairs myocardial contractility. disease and cardiac failure. Myocardial depres-
Features: sion, hypovolaemia and increased SVR are par-
as for shock. ticularly hazardous.
increased left ventricular end-diastolic pressure and hypertrophic (obstructive; HOCM):
pulmonary oedema are usual. However, relative - familial disorder, with left ventricular hypertro-
hypovolaemia may be present due to redistribution phy especially affecting the upper interventricular
of fluid to lungs, previous fluid restriction, diuretic septum, causing left ventricular outflow obstruc-
therapy and sweating. Right-sided failure may tion. Epidemiological screening studies suggest a
occur, e.g. in right ventricular infarction. prevalence of 1 in 500 in the general population,
Management: with the majority undiagnosed.
treatment of underlying cause; if caused by coro- - causes arrhythmias, syncope, angina, cardiac
nary artery occlusion, early percutaneous translu- failure and sudden cardiac death. Infective endo-
minal coronary angioplasty or coronary artery carditis may occur.
bypass graft improves prognosis. - treatment includes diuretics, antiarrhythmics
optimising left ventricular end-diastolic pressure; and -adrenergic receptor antagonists; the last
PCWP is a more useful guide than CVP, unless reduce force and rate of contraction, reducing
failure is predominantly right-sided. A PCWP of outflow obstruction. Conversely, digoxin should
1822mmHg is thought to be optimal for the failing be avoided. Anticoagulants are often used in sus-
heart, even though this is higher than normal. tained arrhythmias. Surgical myectomy or alcohol
Colloid is usually given if PCWP is low; inotropic ablation is used to relieve obstruction and severe
and vasodilator drugs if PCWP is high. refractory symptoms.
intra-aortic counter-pulsation balloon pump and - anaesthetic management includes avoidance of
cardiac surgery may be required. tachycardia and increased myocardial work,
Prognosis is generally poor, especially after MI (mortal- arrhythmias, hypovolaemia and reduced SVR.
ity 7090%) and without aggressive therapy. restrictive:
Topalian S, Ginsberg F, Parillo JE (2008). Crit Care Med; - very rare; due to fibrosis or infiltration.
36: S6674 - effects and management are as for constrictive
See also, Cardiac failure pericarditis.
114 Cardioplegia

ECG is usually non-specific, showing arrhythmias, Usual solution pH is 5.57.8 and osmolality 285300
bundle branch block, ventricular hypertrophy and isch- mosmol/kg.
aemia. CXR may show cardiac enlargement and pulmo-
nary oedema. Echocardiography, cardiac catheterisation Cardiopulmonary bypass (CPB). Developed largely by
and nuclear cardiology may be useful. Gibbon in the 1950s from animal experiments performed
Davies MJ (2000). Heart; 83: 46974 in 1937. Haemolysis was caused by initial disc/bubble
oxygenators; improved membrane oxygenators were
developed in the late 1950s. Used in cardiac surgery;
Cardioplegia. Intentional cardiac arrest caused by coro- similar techniques are used for extracorporeal mem-
nary perfusion with cold electrolyte solution, to allow brane oxygenation and extracorporeal CO2 removal in
cardiac surgery. After establishment of cardiopulmonary respiratory failure.
bypass, a cannula is inserted into the ascending aorta and Principles:
connected to a bag of solution (traditionally at 4C), venous drainage: under gravity via a right atrial
having excluded air bubbles. After aortic cross-clamping cannula or separate superior/inferior vena caval can-
distal to the cannula, the solution is passed under 200 nulae if the right atrium is opened. Blood also drains
300mmHg pressure into the aortic root, closing the via right atrial and left heart suckers/vents to avoid
aortic valve and perfusing the coronary arteries. In aortic pooling of blood in the operative field. Blood passes
valve incompetence, individual coronary artery cannula- through a filter and defoaming chamber, which may
tion may be required. Severe coronary stenosis may be combined with a reservoir and/or oxygenator.
require further injection of solution through the bypass oxygenator: older bubble oxygenators have been
graft or retrograde perfusion via the coronary sinus. replaced by membrane oxygenators since the 1980s,
Asystole usually occurs after 100200ml, but 1 litre is the latter being associated with greater haemody-
used (20ml/kg in children) in order to cool the heart to namic stability, reduced coagulopathy and fewer
1012C. embolic phenomena.
Further infusion may be required in prolonged Consist of hollow capillary fibres through which
surgery. Cold saline is placed around the heart to main- blood passes, with gas exchange across their walls.
tain hypothermia. Flat membrane oxygenators are also available. Can
Solutions used may contain: also be used for concurrent ultrafiltration. Most
NaCl 110140mmol/l: prevents excess water accu- incorporate temperature exchangers, and may
mulation. May increase calcium entry if sodium therefore be used in the treatment of severe, refrac-
concentration is too high. tory hypothermia. CO2 and O2 are supplied inde-
KCl 1020mmol/l: causes depolarisation and pendently to the oxygenator as required, e.g. 2.5%
cardiac arrest in diastole, reducing myocardial O2 CO2 in O2.
demand. Higher concentrations may cause arterial pumps: usually rotating roller pumps using wide
spasm. tubing. Rotating chambers (centrifugal pumps) are
MgCl2 16mmol/l and CaCl2 1.22.2mmol/l: reduce also used, reducing damage to blood components.
automatic rhythmogenicity and protect against Flow is traditionally non-pulsatile but pulsatile flow
potassium-induced damage post-bypass. Excessive may provide better organ perfusion, with lower
calcium may cause persistent myocardial contrac- vasopressin and angiotensin levels; however, the
tion (stone heart). Magnesium reduces calcium equipment required is more complex and expen-
entry. sive. Pulsations may be synchronised with the ECG
NaHCO3 010mmol/l. if the heart is pumping. Flows used vary between
procaine 01mmol/l: membrane stabiliser, reducing centres but are usually 1.02.4 l/min/m2 surface area
arrhythmias post-bypass. (up to 80ml/min/kg).
other additives are more controversial, and arterial return: via ascending aorta (rarely, femoral
include: artery) using a short wide cannula to reduce resis-
- buffers, e.g. histidine and tromethamine: help tance and avoid accidental cannulation of aortic
maintain normal intracellular pH and encourage branches. The return is filtered to remove platelet
ATP generation. aggregates, fibrin and debris. 5-40 m filters are
- metabolic substrates, e.g. glucose and amino acids: standard; the smaller filters reduce microemboli but
increase ATP generation. increase platelet consumption and risk of comple-
- mannitol: reduces water accumulation and may ment activation.
improve cardiac function. Use:
- free radical scavengers. disposable systems are usually employed.
- corticosteroids. the system is primed with 1.52.5 litres crystalloid
- calcium channel blocking drugs. usually, although colloid may be used. The resulting
Other controversies: haemodilution improves perfusion at low tempera-
use of blood instead of crystalloid: improved oxy- tures, and is usually corrected postoperatively by an
genation with optimal osmotic, buffer and meta- appropriate diuresis.
bolic make-up, but increased viscosity limits the use anticoagulation, introduction and termination of
of hypothermia. CPB: as for cardiac surgery.
oxygenation of the solution. Complications:
use of warm solution: may cause better myo technical, e.g. leaks, bubbles, disconnections, obstruc-
cardial relaxation, with reduced membrane tion, coagulation, power failure. Vascular damage
and protein damage associated with low tempera- may occur during cannulation.
tures. embolisation with clot, debris, bubbles and defoam-
continuous versus intermittent injection. ing agent. Bubbles may enter via the heart cavity
 Cardiopulmonary resuscitation, neonatal 115

during surgery, especially at end of bypass. Subtle advanced life support: as above, plus use of spe-
neurological changes are thought to be related to cialised equipment, techniques (e.g. tracheal intuba-
microembolisation. tion), drugs and monitoring.
related to surgery or anticoagulation. Regular updates on guidelines are provided by the
[John H Gibbon (19031974), US surgeon] Resuscitation Council (UK), European Resuscitation
Council, International Liaison Committee on Resuscita-
Cardiopulmonary exercise testing (CPX/CPEX tion and the American Heart Association (see Basic life
testing; CPET). Integrated assessment of cardiopulmo- support, adult; Advanced life support, adult).
nary function at rest and during incrementally increasing See also, Brainstem death; Cardiopulmonary resuscita-
levels of exercise. BP, ECG, ventilatory parameters and tion, neonatal; Cardiopulmonary resuscitation, paediat-
respiratory gases are measured throughout, and used to ric; Cough-CPR
derive two major indicators of cardiopulmonary func-
tion: maximum oxygen uptake (V O2 max ) and anaerobic Cardiopulmonary resuscitation, neonatal. Prompt
threshold. Several protocols exist, most utilising a tread- resuscitation is important in order to prevent permanent
mill or exercise bicycle for approximately 10min. A mental or physical disability. Neonatal cardiac arrest
bicycle is most commonly used for perioperative assess- is almost always caused by hypoxaemia and thus
ment as it is more stable and measurements are less prompt management of apnoea and airway obstruction
prone to movement artefact. is vital.
Indications include: Equipment required includes:
preoperative evaluation and risk stratification. a tilting resuscitation surface, with radiant heater,
evaluation for heart/lung transplantation. clock and pulse oximetry.
investigation of undiagnosed exercise intolerance. suction equipment.
evaluation of exercise tolerance, functional capacity, O2 with funnel and facemasks.
disability or response to treatment. self-inflating bag (volume 250ml, with pressure
Thought to predict the patients capacity to respond relief valve set at 3035 cmH2O).
to the physiological stress of major surgery. Estab- pharyngeal airways (sizes 000, 00 and 0).
lished predictor of perioperative morbidity and mortal- tracheal tubes (uncuffed). Suitable sizes:
ity in patients undergoing pulmonary resection. More - 2.02.5mm for babies under 750g weight or 26
recent evidence suggests that testing may also be useful weeks gestation.
in other contexts (e.g. aortic aneurysm repair, laparot- - 2.53.0mm for 7502000g or 2634 weeks.
omy in elderly patients), both for initial patient - 3.03.5mm for over 2000g or 34 weeks.
selection and guiding the level of postoperative care laryngoscope, usually with straight blade (size 01).
required. iv cannulae, including umbilical venous and arterial
Smith TB, Stonell C, Purkayastha S, Paraskevas P (2009). catheters.
Anaesthesia; 64: 88393 Requirement for resuscitation may be anticipated from
the course of pregnancy and labour and fetal monitoring.
Cardiopulmonary resuscitation (CPR). Over many Elements of the Apgar score may also be useful.
centuries, numerous techniques have been tried in Greater emphasis is placed on maintaining a patent
order to restore life; early attempts included use of airway and providing adequate ventilation than for adult
heat, smoke, cold water, beating and suspension from CPR; cardiac massage is only started once adequate ven-
ropes. tilation has been achieved:
Artificial ventilation was developed within the last dry, stimulate and wrap the baby. Babies < 30 weeks
400 years: gestation should be wrapped in food-grade plastic
use of bellows via the mouth or nose is attributed without drying; all neonates should be placed under
to Paracelsus in the early 1500s. Used via tracheal a radiant heater in the first instance.
tubes in the 1700s, e.g. by Kite. airway management: early aggressive suctioning of
postural techniques, e.g. compressing the chest and pharynx and trachea is no longer recommended.
abdomen from behind with the victim prone, Suction is only indicated if there is copious thick
moving the arms, or using tilting boards: used from meconium visible in the mouth and the baby is non-
the 1850s. vigorous. To open the airway the head should be
expired air ventilation: developed in the 1700s, placed in the neutral position (with the aid of a
although reported earlier. towel placed under the shoulders) and a jaw thrust
Cardiac massage, external and internal, was first manoeuvre applied if required.
attempted in the late 1800s; external massage was initial assessment of the respiratory effort, heart
popularised in the early 1960s. rate, colour and tone:
Defibrillation was investigated in animals in the - adequate respiration, heart rate > 100 beats/min,
1700s/1800s; internal defibrillation was performed in the baby is centrally pink with good tone: no
humans in the 1940s and external defibrillation in further treatment required.
the 1950s. - heart rate < 100 beats/min or absent/inadequate
CPR is divided into: respiration: 5 inflation breaths lasting for 23s, to
basic life support (BLS): traditionally without any aid lung expansion. Airway pressures should not
equipment, and therefore suitable for lay-person exceed 3035 cmH2O (20 cmH2O in the preterm
resuscitation. Increasingly includes the use of neonate). Air should be used in the first instance,
simple equipment (although this has been defined switching to oxygen if there is poor initial response.
as basic life support with airway adjuncts), e.g. If there is no response, adequacy of ventilation
airways, face-pieces, self-inflating bags, oesopha- (i.e. good chest wall movement) should be checked
geal obturators, LMAs. and a further five inflations attempted, with
116 Cardiopulmonary resuscitation, paediatric

airway adjuncts if appropriate. If still no response, two fingers; in older children the heel of the
tracheal intubation should be considered. palm or both hands may be used. Whatever the
if heart rate < 60 beats/min despite good ventilation, technique, compressions should be applied to
cardiac massage should be instituted, with both the lower half of the sternum, compressing the
hands encircling the chest or using two fingers (see chest by one-third of its total depth.
Cardiopulmonary resuscitation, paediatric). Com- - ratio for cardiac massage:breaths of 15:2.
pressions should occur at 120 beats/min, depressing advanced life support:
the sternum one-third of the depth of the chest, and - iv access/monitoring/airway management as for
with a compression:ventilation ratio of 3:1. Stan- adults. An intraosseous needle should be used if
dard ventilation breaths are 1s in duration. Cardiac venous access is difficult (see Intraosseous fluid
massage is futile unless adequate ventilation is administration). For monitoring small children via
provided. the defibrillator, it may be easier to apply the
if heart rate remains < 60 beats/min after 30s of paddles to the front and back of the chest.
cardiac massage, drugs should be given: - asystole/pulseless electrical activity:
- umbilical venous catheterisation is usually the - adrenaline 10g/kg iv/im, repeated every
most accessible route for iv administration of 35min. Tracheal administration is no longer
drugs (N.B. the umbilical cord contains a single recommended, but was previously given at 10
vein and two arteries). times the iv dose.
- initial iv drugs: adrenaline 1:10000: 0.1ml/kg ini- - BLS for a further 2min.
tially, then 0.3ml/kg, then 1ml/kg after 4.2% - VF/VT:
bicarbonate 12ml/kg (higher concentrations - defibrillation using 4 J/kg (one paddle below the
have been associated with intraventricular haem- right clavicle, the other at the left anterior axil-
orrhages). The cannula should be flushed with lary line).
saline after each drug. - BLS for further 2min, then repeat the above.
- administration of adrenaline via the tracheal tube - repeat as necessary; after the third shock give
is not recommended, but if it is given would amiodarone 5mg/kg and an immediate fourth
require doses of 0.51ml/kg. Bicarbonate must shock. Consider reversible causes of cardiac
not be given via the tracheal route. arrest.
- others: Special situations: choking, electrocution, near-
- crystalloid (e.g. NaCl 0.9%) 10ml/kg if hypovo- drowning, trauma, neonatal CPR (see Cardiopulmo-
laemia or sepsis is suspected. nary resuscitation, neonatal).
- 10% dextrose 22.5ml/kg if hypoglycaemia is Other drugs:
present. atropine is no longer recommended for non-
- naloxone 10mg/kg im, iv or sc, repeated shockable rhythms.
every 23min or 60g/kg im as a single injec- bicarbonate: 1mmol/kg iv (1ml/kg 8.4%
tion, if the mother has received opioids during solution).
labour. calcium chloride: 0.2mmol/kg iv (0.3ml/kg 10%
Congenital abnormalities (e.g. diaphragmatic hernia, solution).
tracheo-oesophageal fistula) should be considered in glucose 10%: 1g/kg iv (10ml/kg).
babies who do not respond to resuscitation. Fluid bolus in hypovolaemia: 10ml/kg colloid (tradi-
European Resuscitation Council (2010). Resuscitation; tionally 4.5% albumin initially).
81: 121976 European Resuscitation Council (2010). Resuscitation;
See also, Pugh, Benjamin 81: 121976
See also, Paediatric anaesthesia
Cardiopulmonary resuscitation, paediatric. The same
principles apply as for adult CPR, but primary cardiac Cardioversion, electrical. Restoration of sinus rhythm
disease is uncommon. Sinus bradycardia progressing to by application of synchronised DC current across
asystole is more common, especially if due to hypoxae- the heart. Current delivery is synchronised to occur
mia or haemorrhage. Thus cardiac arrest is often second- with the R wave of the ECG, since delivery during
ary to respiratory arrest or exsanguination, and usually ventricular repolarisation may produce VF (R on T
represents a severe insult. phenomenon).
2010 Recommendations of the Resuscitation Council Used for:
(UK), adapted from European Resuscitation Council AF, particularly of recent onset.
Guidelines: atrial flutter; usually successful with low energy.
basic life support (BLS): VT, usually successful with low energy.
- assess as for adults. a lone rescuer should continue SVT.
for about a minute before seeking help. Energy levels of 20200 J are usually used.
- ABC of resuscitation: Digoxin-induced arrhythmias may convert to serious
- Airway: as for adults. ventricular arrhythmias; therefore digoxin is usually
- Breathing: 5 initial rescue breaths by expired air withheld for at least 24h.
ventilation, each over 11.5s; mouth to mouth In chronic atrial arrhythmias, anticoagulation is often
and nose if < 1 year, mouth to mouth otherwise. administered to reduce risk of systemic embolisation.
Only 5 breaths should be attempted; if unsuc- Preparation of the patient, drugs and equipment, and
cessful, move on to circulation. monitoring should be as for any anaesthetic. The proce-
- Circulation: up to 10s to check for pulse or dure is painful, therefore requiring brief sedation/
signs of life, then external cardiac massage at anaesthesia. A single iv agent is commonly used, e.g.
100/min. In infants this may be delivered using thiopental, etomidate, propofol or diazepam. Further
 Carotid endarterectomy 117

injections may be required if repeated shocks are - branches, from below upwards:
delivered. - ascending pharyngeal.
See also, Defibrillation - superior thyroid.
- lingual.
Care bundles. Group of evidence-based clinical inter- - facial.
ventions used in the management of specific conditions - occipital.
or procedures. Originally conceived in the critical care - posterior auricular.
setting, they aim to deliver improved outcomes by stan- - superficial temporal.
dardising care. Although broadly similar between insti- - maxillary.
tutions, each care bundle is adapted for local use. See also, Carotid body; Carotid endarterectomy; Cerebral
Commonly used as criteria for clinical audit; implemen- circulation
tation of a care bundle element is a dichotomous state,
and compliance requires completion of all elements.
Carotid body. Small (23mm) structure situated above
Examples include: the ventilator care bundle for the
the carotid bifurcation on each side; involved in the
prevention of ventilator-associated pneumonia; the
chemical control of breathing. Contains:
central venous cannulation care bundle for the preven-
glomus cells (type I cells): depolarise in response to
tion of catheter-related sepsis; and the severe sepsis care
hypoxia and cyanide, releasing dopamine that stim-
bundle.
ulates the nerve endings via D2 receptors.
glial cells (type II cells): provide structural support
Care of the critically ill surgical patient (CCrISP).
to glomus cells.
Course run by the Royal College of Surgeons of England,
nerve endings: glossopharyngeal nerve afferents.
primarily aimed at basic surgical trainees. Using a sys-
Afferents pass via the glossopharyngeal nerve to the
tematic means of patient assessment (similar to other
brainstem regulatory centres.
ALS, ATLS, APLS courses), candidates are taught to
Below arterial PO2 of 13.3 kPa (100mmHg), rate of
manage immediate life-threatening events (e.g. airway
discharge rises greatly for any further decrease. Response
obstruction, haemorrhage, sepsis, injury) and to organise
time is rapid enough to cause fluctuations in discharge
subsequent care (monitoring, pain relief, nutrition) in
rate with breathing. Discharge rate is also increased by
the general ward, operating theatre, HDU or ICU.
a rise in arterial PCO2, or fall in arterial pH.
Consists of lectures, workshops and simulated patient
Each carotid body receives 0.04ml blood/min, equiv-
assessments.
alent to 2 l/100g tissue/min (the highest blood flow per
Anderson ID (1997) Br J Hosp Med; 57: 2745
100g tissue in the body). Because of such high blood
flow, dissolved O2 alone is enough to provide the require-
Carfentanil. Opioid analgesic drug, developed in 1974.
ment for O2; thus discharge is not increased by anaemia
About 10000 times as potent as morphine, and used to
or carbon monoxide poisoning, where O2 carriage by
immobilise large animals.
haemoglobin is reduced but arterial PO2 is not.
Fitzgerald RS, Eyzaquirre C, Zapata A (2009). Adv Exp
Carotid arteries. Anatomy is as follows (see Fig. 113;
Med Biol; 648: 1928
Neck, cross-sectional anatomy):
See also, Breathing, control of
common carotids:
- right: arises from the brachiocephalic artery
behind the sternoclavicular joint. Carotid endarterectomy. Performed in patients with
- left: arises from the aortic arch medial to the left carotid stenosis with the aim of reducing the risk of
lung, vagus and phrenic nerves, then passes behind stroke. Endarterectomy significantly reduces the risk of
the sternoclavicular joint. CVA in symptomatic patients with severe stenosis (>
- ascends in the neck within the carotid sheath. 70% occlusion); surgery is less beneficial in moderate
- divides level with C4 into internal and external (5070%) stenosis and harmful in minor (< 30%) steno-
carotids. sis and near-occlusion. Benefit in asymptomatic stenosis
internal carotid: is less well established. Perioperative CVA occurs in up
- bears the carotid sinus at its origin. to 7% of cases; risks are greatest in the elderly (though
- runs firstly lateral, then behind and medial to the the benefits of surgery have also been shown to be great-
external carotid, with the internal jugular vein est in this group). Nerve injury in the neck (usually tran-
laterally and vagus and sympathetic chain sient) may occur in up to 20% of cases. Perioperative
posteriorly. mortality is about 5% for symptomatic and 34% for
- passes medial to the parotid gland, styloid process, asymptomatic stenosis, mostly from MI or CVA. Mortal-
glossopharyngeal nerve and pharyngeal branches ity is greatest in older women and those with symptom-
of the vagus (with the external carotid lateral to atic cardiovascular co-morbidity. Percutaneous carotid
these structures). artery stenting is not as effective as endarterectomy in
- passes through the carotid canal at the base of the preventing CVA (see Neuroradiology).
skull, with the internal jugular now lying posteri- Anaesthetic considerations:
orly. After a tortuous path through the canal, it preoperatively: often elderly patients with gener-
divides into the middle and anterior cerebral alised arteriopathy. Smoking, diabetes mellitus and
arteries. hypertension are common. Drug therapy may
external carotid: include aspirin, dipyridamole and other antiplatelet
- lies first deep, then lateral to the internal carotid, drugs.
with the internal jugular posteriorly. intraoperatively:
- enters the parotid gland, ending behind the neck - direct arterial BP monitoring is mandatory, with
of the mandible. meticulous avoidance of hypotension.
118 Carotid sinus

- performed under general or regional anaesthesia The sinus is gently massaged below the angle of the
(cervical plexus block); choice of technique does jaw, where the carotid pulse is palpable. Concurrent
not affect outcomes. Regional anaesthesia in the ECG recording should be available. Only one side (the
awake patient allows early recognition of isch- right is usually more effective) should be massaged
aemic symptoms, but may not be tolerated by all at one time and for not longer than 5s, or excessive
patients. General anaesthesia with inhalational reduction in cerebral blood flow may occur. It should be
anaesthetic agents may provide a degree of neu- performed with care in patients with evidence of cere-
roprotection; methods of neurological monitoring brovascular disease. May restore sinus rhythm in SVT,
include transcranial Doppler ultrasound, EEG and may aid diagnosis of other arrhythmias by slowing
and measurement of evoked potentials and inter- the ventricular rate, e.g. AF and atrial flutter. In sinus
nal carotid artery stump pressure. tachycardia, it causes gradual slowing of rate with speed-
- evidence of cerebral ischaemia (e.g. after carotid ing up when massage is stopped. May also demonstrate
clamping) should prompt consideration of shunt SA and AV node disease by causing severe bradycardia
insertion or administration of vasopressor drugs or sinus arrest.
to increase perfusion pressure. Syncope, transient ischaemic attacks and CVA, asys-
- positioning of the patient and restricted access, tole and VT are rare complications.
with risks of tracheal tube kinking/displacement
and injury to the eyes. Vertebrobasilar insuffi- Carticaine, see Articaine
ciency (often occurring with cervical spondylosis)
is common and necessitates careful positioning of Caspofungin. Antifungal drug used for treatment of
the neck during intubation and surgery. invasive aspergillosis or candida infection.
- capnography allows adjustment of IPPV to nor- Dosage: 70mg by iv infusion on the first day, 50mg
mocapnia and aids detection of air embolism. daily thereafter.
- manipulation of the carotid sinus may lead to bra- Side effects: GIT upset, tachycardia, flushing, dysp
dycardia and hypotension. Infiltration of lido- noea, electrolyte disturbances, allergic reactions.
caine around the sinus prevents this, but may be
followed by hypertension postoperatively. Catabolism. Metabolic breakdown of complex mole-
postoperatively: cules into simple, smaller ones, often associated with the
- patients may require HDU/ICU admission for liberation of energy.
monitoring and further care. Includes:
- assessment of neurological function: deficit occurs digestion of foodstuffs as in metabolism of carbo-
in < 7% of patients. The hyperperfusion syndrome hydrate, fat and protein.
is caused by increased blood flow (in vessels with mobilisation of body stores, e.g. in malnutrition,
poor autoregulation) following relief of stenosis. severe illness and the stress response to surgery.
It may result in headache, convulsions and intra- These may occur in combination in ICU because of:
cranial haemorrhage. - inadequate nutrition, e.g. nil by mouth, ileus, fluid
- control of BP: hypertension is common and may restriction.
be related to pain, agitation, dysfunction of carotid - increased energy and O2 consumption associated
sinus baroreceptors or impending neurological with injury, especially multiple trauma, burns and
damage. Commonly used agents include labetalol sepsis.
and hydralazine. Hypotension is less common and Includes breakdown of:
may be associated with bradycardia. - protein: causes increased urinary urea excretion
- airway obstruction may occur if bleeding occurs. and may contribute to reduced plasma albumin.
Even after uncomplicated cases, some degree of Nitrogen loss may exceed 2030g/day, i.e. up
airway oedema is common. to 5-kg body weight/week (mainly lost from
Howell SJ (2007). Br J Anaesth; 99: 11931 muscle). Amino acids produced are used for syn-
thesis of glucose, acute-phase reactants and cell
Carotid sinus. Dilatation of the internal carotid artery, components.
just above the carotid bifurcation. Baroreceptors present - fat: triglycerides from adipose tissue are broken
in the walls respond to increased distension caused by down to fatty acids (used as an energy source) and
raised arterial BP by increasing the rate of discharge via glycerol (used to synthesise glucose).
the carotid sinus nerve, a branch of the glossopharyngeal - carbohydrates: glycogen is broken down to
nerve. Resultant inhibition of the vasomotor centre and glucose.
stimulation of the cardioinhibitory centre cause reduc- See also, Nutrition, total parenteral
tion in sympathetic tone and increase in vagal tone
respectively. BP and heart rate therefore fall (the baro- Catecholamines. Group of substances containing cat-
receptor reflex). The baroreceptors also respond to the echol (benzene ring with OH groups at positions 1 and
rate of increase of BP. Similar baroreceptors exist in the 2) and amine portions; includes naturally occurring (e.g.
walls of the aortic arch. dopamine, adrenaline, noradrenaline) and synthetic (e.g.
See also, Carotid sinus massage dobutamine, isoprenaline) compounds. Catecholamines
act at dopaminergic and adrenergic receptors in the
Carotid sinus massage. Manual stimulation of the CNS and sympathetic nervous system; although many
carotid sinus baroreceptors, causing reflex inhibition of other substances may produce similar effects (i.e. are
the vasomotor centre and activation of the cardioinhibi- sympathomimetic drugs), they may not be true
tory centre. Depression of sinoatrial (SA) and atrioven- catecholamines.
tricular (AV) nodes results in bradycardia and may Synthesis of naturally occurring catecholamines pro-
reduce myocardial contractility. ceeds in many steps from the amino acid phenylalanine
 Catheter-related sepsis 119

(a)
Phenylalanine hydroxylase Tyrosine hydroxylase DOPA decarboxylase
HO HO

CH2 CH NH2 HO CH2 CH NH2 HO CH2 CH NH2 HO CH2 CH2 NH2

CO2H CO2H CO2H

Phenylalanine L-Tyrosine Dihydroxyphenylalanine Dopamine
(DOPA)
Dopamine
HO Phenylethanol-amine HO b-hydroxylase
N-methyl transferase
HO CH CH2 NH CH3 HO CH CH2 NH2

OH OH
Adrenaline Noradrenaline

(b)

HO CH3O CH3O
COMT MAO
HO CH CH2 NH CH3 (or H) HO CH CH2 NH CH3 (or H) HO CH CHO

OH OH OH
(nor) Adrenaline (nor) Metanephrine
CH3O

HO CH COOH

OH
4-Hydroxy 3-methoxy mandelic acid
(HMMA; vanillylmandelic acid; VMA)

Fig. 36 (a) Catecholamine synthesis. (b) Catecholamine metabolism

(Fig. 36a). The rate-limiting step is the hydroxylation of standard 22-mm taper. Some contain heatmoisture
tyrosine to DOPA (dihydroxyphenylalanine). Formation exchangers.
of dopamine occurs in the cytoplasm; it is then taken up
by an active process into vesicles and converted to Catheter-related sepsis. Strictly, nosocomial infection
noradrenaline. involving a catheter at any site, but the term usually
Catecholamines are metabolised via catechol-O- refers to intravascular devices (peripheral, central
methyl transferase (COMT) and monoamine oxidase venous or arterial). Defined in clinical practice as isola-
(MAO) (Fig. 36b). tion of the same organism from both a percutaneous
See also, Inotropic drugs blood culture and a catheter segment from a patient with
symptoms and signs of bloodstream infection, in the
Catechol-O-methyl transferase (COMT). Enzyme absence of any other septic focus. Occurs in about 5%
present in most tissues (especially liver and kidneys) of cases in ICU. Should be differentiated from colonisa-
except nerve endings; catalyses the transfer of a methyl tion (growth of > 15 colony-forming units from a cath-
group from adenosylmethionine (a methionine deriva- eter segment in the absence of local or systemic
tive) to the 3-hydroxy group of the catechol part of infection), which occurs in about 25% of cases, and local
catecholamines. Involved in the metabolism of circulat- infection (erythema, tenderness, induration and puru-
ing catecholamines and their derivatives, whilst catechol- lence within 2cm of the skin insertion site). In all cases,
amines at nerve endings are metabolised by monoamine organisms are thought to grow in biofilms on the
oxidase. surface of the catheter.
Inhibitors of COMT (e.g. entacapone) are used as Risk factors include:
adjuncts to levodopa in Parkinsons disease; they block site of catheter: affects central lines > arterial lines
metabolism of levodopa in the tissues, thus increasing its > peripheral lines. Subclavian lines are the least
activity. likely to become infected. Femoral lines are usually
considered more susceptible to infection but this
Catheter mounts (Tracheal tube adaptors). Original may not be so if proper care is taken during and
term refers to adaptors connecting the fresh gas supply after placement.
to a catheter passed through the larynx into the trachea age < 1 year or > 60 years.
(insufflation technique), before tracheal intubation immunodeficiency or use of immunosuppressive
became popular. Now refers to adaptors connecting the drugs.
tracheal tube to the end of the anaesthetic breathing severity of underlying illness.
system. Various connectors fit between the distal end presence of other focus of infection.
and the tracheal tube; the proximal end should be of use of cut-down to insert line.
120 Cauda equina syndrome

use of the line for parenteral feeding. malignancy. May also follow spinal anaesthesia, espe-
length of time the line is in situ is usually cited as a cially if a continuous microcatheter technique is used.
risk factor, but evidence is weak if adequate atten- Possible mechanisms of injury include:
tion has been paid to aseptic insertion. direct trauma from lumbar puncture, intraneural
Organisms involved usually come from the patients injection, trauma from the catheter or epidural
own skin flora or from medical or nursing staff. Staphy- haematoma.
lococcus aureus or S. epidermidis are most commonly poor mixing of local anaesthetic, especially hyper-
responsible, although Gram-negative organisms may be baric, in the CSF. This results in pooling of anaes-
involved. Candida may also be responsible. thetic in the terminal dural sac, with associated
Management: neurotoxicity (especially with lidocaine).
taking of blood cultures peripherally and via the passage of the catheter into the subdural space with
line. Use of an endoluminal brush has been high local concentrations of local anaesthetic
described. around the cauda equina.
exclusion of other sources of infection. It has been suggested that the cauda equina nerve fibres
antibacterial drugs. are more vulnerable to damage because they lack pro-
removal, and sending for culture, of the distal part tective sheaths. Symptoms may appear soon after surgery
of the line involved. and may be permanent.
if possible, insertion of a new line at the same site Lavy C, James A, Wilson-MacDonald J, Fairbank J
should be avoided, as should changing a suspected (2009). Br Med J; 338: 8814
line over a guide-wire. See also, Transient radicular irritation syndrome
the following has been used for lines whose removal
is considered especially undesirable (e.g. being used Caudal analgesia. Produced by injection of local anaes-
for long-term parenteral nutrition and poor venous thetic agent into the sacral canal, a continuation of the
access elsewhere): concomitant antibiotic (in high epidural space. First described independently by Cathe-
concentration) and fibrinolytic agent into the cath- lin and Sicard in 1901, predating lumbar epidural anaes-
eter as a lock, with parenteral antibacterial therapy. thesia. Easily performed, but with a high failure rate in
The line should be removed if the patients condi- adults due to variations in sacral anatomy. Produces
tion has not improved after 36h; use of the catheter block of the sacral and lumbar nerve roots; thus ideal for
may be restarted after 48h if improvement occurs. perineal surgery. Higher blocks require greater volumes
Prevention: of anaesthetic solution, and are more unpredictable.
use of care bundles to support best practice Useful as a supplement to general anaesthesia, and for
use of intravascular catheters only where definitely provision of postoperative analgesia. Catheter insertion
indicated, and removal when no longer needed. has been performed for continuous caudal block.
scrupulous aseptic technique during insertion and Technique:
aftercare. Chlorhexidine 2% is more effective than usually performed with the patient in the lateral
10% povidone-iodine and 70% alcohol for cleans- position, with the knees drawn up to the chest. The
ing the skin. prone and kneeelbow positions may also be used.
regular replacement of catheters (e.g. every 37 the sacral hiatus lies at the third point of an equi-
days) is often advocated, but there is little evidence lateral triangle formed with the two posterior supe-
supporting this. rior iliac spines (each overlain by a skin dimple).
daily inspection of insertion sites and regular chang- The sacral cornua are palpable on either side of the
ing of sterile dressings (2448h). Clear plastic hiatus.
dressings have been associated with increased rates using an aseptic technique, a needle is introduced in
of infection in some studies, but evidence is conflict- a slightly cranial direction through the hiatus. Ordi-
ing. Use of antimicrobial ointment or chlorhexidine- nary iv needles and cannulae are commonly used,
impregnated sponges at the skin entry sites may be although specific caudal needles are available.
beneficial. when the canal is entered (a click may be felt as the
use of a separate dedicated lumen for parenteral sacrococcygeal membrane is pierced), the needle is
nutrition. directed cranially, and advanced not more than
measures of unproven benefit include tunnelling 2cm into the canal (in adults). The dura normally
of catheters, routine flushing and the use of in-line ends at S2, level with the posterior superior iliac
filters. Catheters incorporating antibacterial or spines, but may extend further.
heparin-treated coatings have been claimed to after aspirating to confirm absence of blood or CSF,
reduce colonisation with organisms, especially when local anaesthetic is injected, feeling for accidental
tunnelling is also performed. subcutaneous injection with the other hand. There
Chittick P, Sherertz RJ (2010). Crit Care Med; 38(Suppl): should be little resistance to injection with a 19
S36372 21G needle. If the patient is awake, pain is felt if
See also, Central venous cannulation; Central venous can- the needle tip is under the periosteum of the ante-
nulation, long-term; Infection control; Intravenous fluid rior wall of the canal. Caudal needles may bear a
administration; Sepsis side hole to prevent this complication.
Doses:
Cauda equina syndrome. Syndrome of lower back 2030ml 0.250.5% bupivacaine, or 12% lidocaine
pain, sciatica, leg weakness, perineal sensory loss, impo- with adrenaline, in young adults, reduced in the
tence and urinary and faecal incontinence. Caused by elderly. The average volume of the sacral canal is
radiculopathy affecting the nerve roots of the cauda 3035ml.
equina (L2S5). Causes include central intervertebral 0.5ml/kg 0.25% bupivacaine is used for sacro
disc prolapse, spinal stenosis, vertebral fracture and lumbar block in children; 1ml/kg for upper
 Cell salvage 121

abdominal blockade and 1.25ml/kg for midthoracic Dosage: 0.51.0g iv/im bd/tds/qds.
blockade. 0.125% bupivacaine provides analgesia Side effects: as for cefazolin.
with less motor block.
Complications are as for epidural anaesthesia, but much Ceftazidime. Third-generation cephalosporin especially
less common. Insertion of the needle into the rectum, active against multiresistant Gram-negative bacteria and
or presenting part of the fetus in obstetrics, has been pseudomonas. Largely unmetabolised and 90% excreted
reported. in the urine.
[Fernand Cathelin (18731945), French surgeon; Jean- Dosage: 12g iv/im bd/tds.
Athanase Sicard (18721929), French neurologist and Side effects: painful im injections, diarrhoea, hepatic
radiologist] impairment.
See also, Vertebral ligaments
Ceftriaxone. Third-generation cephalosporin structur-
Causalgia, see Complex regional pain syndrome ally related to cefotaxime, with similar spectrum of
activity, although more active against enterobacter.
Caval compression, see Aortocaval compression Increasingly used as the first choice for empirical treat-
ment of bacterial meningitis. Has the longest half-life of
Cave of Retzius block, see Retzius cave block all the cephalosporins (59h). Undergoes biliary and
renal excretion.
CAVH, Continuous arteriovenous haemofiltration, see Dosage: 14g iv/im od.
Haemofiltration Side effects: pain on injection, leucopenia, hepatic and
renal impairment, precipitation (as calcium salt) in
CAVHD, Continuous arteriovenous haemodiafiltration, urine or gallstones.
see Haemodiafiltration
Cefuroxime. Second-generation cephalosporin, most
CCF, Congestive cardiac failure, see Cardiac failure closely related to cefamandole. Has a wide spectrum of
activity against both Gram-positive and -negative organ-
CCrISP, see Care of the critically ill surgical patient isms, including -lactamase-producing staphylococcus,
haemophilus and some enterobacter species. Penetrates
CCT, Central conduction time, see Evoked potentials well into CSF. The only second-generation agent that
achieves therapeutic CSF levels. Excreted unchanged in
CCU, see Coronary care unit the urine.
Dosage: 0.751.5g iv/im tds/qds. Surgical prophylaxis:
Cefazolin (Cephazolin). Antibacterial drug; first- 1.5g iv (two further doses of 750mg may be given
generation cephalosporin used to treat respiratory, for high-risk procedures).
urinary tract and soft tissue infections. Not recom- Side effects: GIT upset, rashes, rarely blood
mended in meningitis as it crosses the bloodbrain dyscrasias.
barrier poorly. 80% protein-bound and excreted largely
unchanged in the urine. Cell salvage. Intraoperative collection and processing of
Dosage: 0.51.0g iv/im bd/qds. blood from the surgical field for subsequent reinfusion
Side effects: blood dyscrasias, hepatic impairment. of autologous red cells. Increasingly used during proce-
dures involving significant blood loss (e.g. cardiac, ortho-
Cefotaxime. Antibacterial drug; third-generation ceph- paedic), particularly in patients who refuse allogeneic
alosporin active against Gram-positive and -negative blood products (e.g. Jehovahs Witnesses).
organisms including haemophilus, klebsiella, streptococ- Consists of three phases:
cus, staphylococcus (but less so than cefuroxime), collection; via a dedicated double-lumen suction
proteus, serratia, enterobacter and escherichia species. tube. One lumen is used for collection of blood,
Also used for empirical treatment of bacterial meningitis while the other is used to add heparinised saline
in adults and children. Half-life is about 1h; extensively to it.
protein-bound, it undergoes hepatic metabolism to an processing; the anticoagulated salvaged blood is
active metabolite, with 5080% excreted unchanged in then filtered, centrifuged (to separate out the red
the urine. cell component), washed (to remove free haemo-
Dosage: 12g bd iv/im, up to 12g/day in divided globin, plasma and heparin) and suspended in
doses in severe infections. normal saline. The final haematocrit is 5080%.
Side effects: phlebitis, rash, GIT upset, colitis. storage/transfusion; recommended maximum
storage time of salvaged blood is 6h.
Cefpirome. Fourth-generation cephalosporin with good The main benefit of cell salvage is the reduction of the
activity against Gram-positive organisms, including need for allogeneic blood transfusion and its associated
staphylococcus. Excreted largely unchanged by the risks/costs. Autologous blood may also provide superior
kidney; thus reduced dosage is required in renal oxygen delivery compared with allogeneic blood owing
impairment. to higher levels of 2,3-DPG and greater mean red cell
Dosage: 12g iv bd. viability. There is evidence of improved outcomes (e.g.
Side effects: headache, nausea, hepatic impairment, cardiac events, infection rates) in specific types of surgery
skin rashes, taste disorders. (e.g. major orthopaedic, oesophagectomy).
General risks include air embolism, haemolysis, con-
Cefradine (Cephradine). First-generation cephalospo- tamination with infective agents and coagulation disor-
rin similar to cefazolin. 10% protein-bound and excreted ders. Complications are rare and are no greater than
unchanged in the urine. with allogeneic transfusion.
122 Cellulitis

Areas of controversy: nausea, vomiting.

obstetrics: use during caesarean section was previ- muscle incoordination.
ously controversial due to theoretical risk of causing convulsions, coma.
amniotic fluid embolism; now considered safe since peripheral anticholinergic effects, e.g. tachycardia,
levels of amniotic fluid in washed, salvaged blood dry mouth and skin, blurred vision, urinary
are very low. retention.
malignancy: previously an absolute contraindica- Treatment: physostigmine 0.51mg slowly iv; 0.02mg/
tion due to risk of disseminating tumour cells; kg in children. It usually acts within 5min; features
now increasing evidence supports its use (with leu- may recur after 12h.
cocyte depletion filters, LDFs) in specific proce-
dures (e.g. radical prostatectomy/cystectomy for Central conduction time, see Evoked potentials
urological malignancies).
microbiological contamination: although contrain- Centre for Maternal and Child Enquiries (CMACE),
dicated by manufacturers, use in the presence of see Confidential Enquiries into Maternal Deaths
contamination with enteric contents and systemic
sepsis is not associated with increased adverse out- Central pain. Diffuse continuous pain, usually burning
comes; use of LDFs, prophylactic antibiotics and and unilateral, with or without increased sensitivity and
increased saline wash volumes significantly reduces altered sensation. Due to CNS lesions (e.g. CVA) classi-
infection risk. cally involving the thalamus (thalamic syndrome). Often
sickle cell anaemia: generally avoided in these associated with anxiety and depression. Associated signs
patients, but has been safely used in those with and distribution of pain are related to the site of lesion.
sickle cell trait. May be helped by phenothiazines, tricyclic antidepres-
Jehovahs Witnesses: potentially life-saving in these sant drugs, gabapentin and carbamazepine.
patients, cell salvage is usually acceptable to them, Nicholson BD (2004). Neurology; 62: S306
although consent must be sought on an individual
basis. May require a special set-up, e.g. continuous Central pontine myelinolysis. Demyelination occur-
flow of blood rather than intermittent. ring within the pons. Most common cause is rapid cor-
Ashworth A, Klein AA (2010). Br J Anaesth; 105; rection of hyponatraemia with resultant osmotic shifts.
40116 Thought to be avoided by slow correction (< 12mmol/l
per 24h), with avoidance of overcorrection. May also
Cellulitis. Skin infection resulting in local inflammation occur in alcoholism, malnutrition, HIV infection, follow-
(warmth, erythema and pain), usually with fever and ing diuretic therapy and following liver transplantation.
leucocytosis. Lymphangitis and lymphadenitis may be Accompanied by extrapontine demyelination in 10%
present. Modes of pathogen entry include local trauma of cases.
(including insertion of iv catheters) and abrasions. More May be asymptomatic, or present with the locked-in
common in those with impaired lymphatic drainage and syndrome, behavioural disturbances, tetraplegia, pseu-
in iv drug abusers. Organisms commonly responsible dobulbar palsy, convulsions or coma. Diagnosis is con-
include -haemolytic streptococci and Staphylococcus firmed by MRI scanning.
aureus, thus guiding initial antibacterial drug therapy if Martin RJ (2004). J Neurol Neurosurg Psychiatry; 75: iii
microbiological identification is uncertain (e.g. phenoxy- 228
methylpenicillin with flucloxacillin, or erythromycin or
co-amoxiclav alone). Central venous cannulation. Cannulation of a vein
Swartz MN (2004). N Engl J Med; 350: 90412 within the thorax via peripheral venepuncture.
See also, Staphylococcal infections; Streptococcal Performed for:
infections vascular access, e.g. for dialysis, TPN, infusion of
irritant or potent drugs.
CEMACH, Confidential Enquiries into Maternal and measurement of CVP.
Child Health, see Confidential Enquiries into Maternal cardiac catheterisation, pulmonary artery catheteri-
Deaths sation and transvenous cardiac pacing.
The catheter tip should ideally lie in the superior vena
CENSA, see Confederation of European National Soci- cava above the pericardial reflection, to reduce risk
eties of Anaesthesiology of arrhythmias and cardiac tamponade should erosion
and bleeding occur. However, a tip placed too high may
Central anticholinergic syndrome. Syndrome caused be associated with thrombosis.
by the use of anticholinergic drugs (especially hyoscine), May be performed at different sites:
thought to be due to a decrease in inhibitory acetylcho- internal jugular vein:
line activity in the brain. Other drugs with anticholiner- - easy to perform and reliable.
gic activity may cause it, including antihistamine drugs, - may cause pneumothorax or damage the common
phenothiazines, antidepressant drugs, antiparkinsonian carotid artery, brachial plexus, phrenic nerve, tho-
drugs and pethidine. Has also been reported after vola- racic duct (on left) or sympathetic chain.
tile anaesthetic agents, ketamine and benzodiazepines. - uncomfortable for the patient.
Reported incidence varies but has been up to 510% subclavian vein:
after general anaesthesia. - more convenient and comfortable for long-term
Features: use.
confusion, agitation, restlessness, anxiety, amnesia, - less chance of correct placement.
hallucinations. - greater chance of pneumothorax or
speech disturbance, ataxia. haemothorax.
 Cephalosporins 123

- may damage the subclavian artery; direct pressure central catheter (PICC) can be introduced via the basilic,
cannot be applied to stop bleeding. cephalic or brachial vein and advanced into the superior
external jugular vein: vena cava; successful placement can be confirmed with
- easy to perform since the vein is more superficial CXR or by using fluoroscopy.
than the internal jugular or subclavian veins. Catheters are inserted under sterile conditions via a
- it may be difficult to thread the catheter through surgical cut-down procedure, or percutaneously using
the junction with the subclavian vein. A J-shaped the Seldinger technique. In the latter, the catheter is
guide-wire may help. passed into the vein through a sheath which is split and
femoral vein: peeled away as the catheter is advanced.
- often easier than other routes, especially in obese Catheters may remain in place for years if required,
patients. with regular heparinised flushing and aseptic handling.
- avoids the pleura and lungs completely. [John W Broviac, US physician; Robert O Hickman, US
- useful in superior vena caval obstruction. paediatrician]
- traditionally avoided because of the risk of See also, Central venous
infection.
Thromboembolism and femoral arterial puncture
Central venous pressure (CVP). Pressure within the
may also occur.
right atrium and great veins of the thorax. Measured via
axillary vein:
central venous cannulation, using a manometer or trans-
- since venepuncture is extrathoracic, risk of pneu-
ducer. An estimate may be made by observing the dis-
mothorax is reduced.
tension of neck veins (JVP). CVP is measured relative
- the axillary artery may be compressed directly if
to a point 5cm below the sternal angle, or the mid-
accidentally punctured.
axillary line (if the patient is supine). Normally 08
- may damage the medial cutaneous nerve.
cmH2O in the spontaneously breathing patient. By con-
arm vein:
vention, it is measured at the end of expiration. The
- minimal risk of serious complications.
venous waveform may be seen on a pressure tracing,
- threading of a long line is often difficult, espe-
with the effects of ventilation superimposed (see below).
cially via the cephalic vein because of valves at Increased by:
the junction with the axillary vein. Abduction of
raised intrathoracic pressure, e.g. IPPV, coughing.
the arm may help.
CVP normally rises in expiration during spontane-
Air embolism, subcutaneous emphysema and sepsis are
ous ventilation.
risks of all techniques. Patients should be in the head-
impaired cardiac function, e.g. outlet obstruction,
down position for jugular and subclavian cannulation to
cardiac failure, cardiac tamponade. Primarily
prevent air embolism. An aseptic technique is used to
reflects right-sided function; thus CVP may be
avoid catheter-related sepsis. Introduction of a catheter
normal in the presence of left ventricular failure
into the heart may cause arrhythmias (therefore ECG
and pulmonary oedema, or raised in right-sided
monitoring is required) or cardiac perforation. Reintro-
failure with normal left-sided function. With normal
duction of the needle into the cannula should never be
cardiac function, pressures on both sides move
performed whilst the tip is in the patient, as pieces
together. Left-sided function may be assessed by
of cannula are easily sheared off. Endocardial damage
pulmonary artery catheterisation.
and central vein thrombosis may also occur, especially
circulatory overload.
with pulmonary artery catheters and with prolonged
venoconstriction.
placement.
superior vena caval obstruction (the normal venous
Successful placement is suggested by easy aspiration
waveform may be lost).
of non-pulsatile blood and obtaining the venous wave- Decreased by:
form. Placement of the catheter in the right ventricle
reduced venous return, e.g. due to hypovolaemia,
results in excessive swinging of central venous pressure
venodilatation.
with each heartbeat. Catheter position must be checked
reduced intrathoracic pressure, e.g. in inspiration
by X-ray, and pneumothorax excluded. Guidelines
during spontaneous ventilation.
issued by NICE support the routine use of ultrasound
Useful in indicating right ventricular preload and cardiac
guidance for internal jugular venous cannulation.
function; e.g. a volume challenge of 200300ml saline
Taylor RW, Palagiri AV (2007). Crit Care Med; 35:
causing a persistent rise in CVP of 25 cmH2O suggests
13906
poor ventricular function in a normovolaemic patient.
See also: Axillary venous cannulation; Central venous
Also used to monitor haemorrhage, and in estimating
cannulation, long-term; Femoral venous cannulation;
the adequacy of volume replacement; e.g. hypovolaemia
Subclavian venous cannulation
is suggested if a volume challenge of 300500ml saline
causes an increase in CVP that is not sustained for more
Central venous cannulation, long-term. Usually
than 1015min. Serial measurements are thus more
employed for long-term TPN, administration of drugs,
informative than single readings.
e.g. chemotherapy and antibiotics, and blood sampling.
Measurement is indicated in shock, hypovolaemia
First developed in the 1970s. Silastic catheters (Hickman
and major surgery, particularly if on a background of
Broviac) are usually inserted via the subclavian vein and
significant cardiovascular disease.
tunnelled subcutaneously (emerging from the skin
Magder S (2006). Crit Care Med; 34: 22247
between the sternum and nipple). A Dacron cuff on the
subcutaneous part incites an inflammatory reaction,
providing fixation and a possible barrier to infection Cephalosporins. Semi-synthetic antibacterial drugs,
within 12 weeks. Single- and double-lumen catheters derived from the natural substance cephalosporin
are available. Alternatively, a peripherally inserted C. Bactericidal, they act by inhibiting the synthesis of
124 CEPOD

bacterial cell walls. Similar in pharmacology to penicil- neurological function deteriorates despite antibac-
lins; cross-sensitivity in penicillin-allergic individuals is terial therapy.
rare with second- to fourth-generation cephalosporins.
The generation classification is based partly on their Cerebral blood flow. Normally 14% of cardiac output,
antibacterial activity and when they were introduced approximately 700ml/min (50ml/100g/min). Grey
(generally, successive generations have greater activity matter receives about 70ml/100g/min whereas white
against Gram-negative organisms): matter receives about 20ml/100g/min. Maintenance of
first-generation, e.g. cephalothin (largely replaced CBF is critical: EEG slows if it falls to 20ml/100g/min;
by cefazolin and cefradine): good activity against at 15ml/100g/min EEG is flat, and at 10ml/100g/min
Gram-positive organisms, including penicillinase- irreversible cerebral damage occurs.
producing staphylococci; poor activity against Measurement:
enterococci and Gram-negative organisms. applying the Fick principle, using N2O (Kety
second-generation, e.g. cefamandole, cefuroxime: Schmidt technique). Values are obtained for the
slightly less active than cephalothin against Gram- whole brain; regional variations in flow are not
positive organisms but greater stability against demonstrated.
enterobacteria and Haemophilus influenzae. The detection of radioactive decay over different parts
cephamycin antibacterial drugs, e.g. cefoxitin, are of the head, following inhalation of radioactive
classified as second-generation, although they have xenon or injection of dissolved radioactive xenon
greater activity against anaerobes, especially Bacte- into a carotid artery. Regional differences are
roides fragilis. detected.
third-generation, e.g. cefotaxime, ceftriaxone: yet regional flow may also be measured by positron
more stable against Gram-negative bacteria, emission tomography, functional MRI and Doppler
although less active against Gram-positive organ- probes placed extracranially.
isms than first-generation drugs (but still very active Affected by:
against streptococci). Ceftazidime has enhanced metabolic factors: CBF increases in metabolically
activity against pseudomonas. active areas (flow-coupled metabolism).
fourth-generation, e.g. cefpirome. chemical factors:
- arterial PCO2 (Fig. 37a): hypercapnia (with resul-
CEPOD, see National Confidential Enquiry into Patient tant acidosis) increases CBF via cerebral vasodi-
Outcome and Death latation. Hypocapnia decreases CBF; a reduction
from 5.3 to 4 kPa (40 to 30mmHg) reduces CBF
Cerebral abscess. Collection of infected material, often
encapsulated, within the brain parenchyma. More
common in males, with peak incidence in the third
decade. Mortality has fallen to 5% with better imaging
and antibacterial agents. Infection often arises from local
(a)
spread (e.g. following paranasal sinusitis, otitis or cere-
bral trauma) or metastatic spread (e.g. following bacte- 100 Pco2
rial endocarditis or lung abscess) when cerebral abscesses
CBF (ml/100 g/min)

are often multiple. May also occur in cyanotic heart

disease when cardiac output is no longer filtered by
the lungs. Po2
Causative organisms (often multiple):
50
most commonly: Gram-positive Streptococcus
milleri; Gram-negative anaerobic bacteroides
species; and aerobic Gram-negative organisms (e.g.
proteus, escherichia coli and pseudomonas). 0
0 5 10 15 (kPa)
in immunocompromised patients: nocardia; actino-
mycetes; and toxoplasma. 50 100 150 (mmHg)
Features:
pyrexia, headache, hyper- or hypothermia, nausea,
Gas tension
neck stiffness, convulsions, coma. Focal neurological (b)
signs depend on the location of the abscess.
CT scan with contrast (or MRI scan) reveals typical 100
CBF (ml/100 g/min)

ring enhancement of the abscess.

lumbar puncture (once raised ICP has been
excluded by a brain scan) may yield normal CSF
unless the abscess has ruptured into the subarach- 50
noid or ventricular spaces.
Treatment:
antibacterial drugs directed against the most likely
organism (must be able to penetrate the abscess 0
wall), e.g. benzylpenicillin, metronidazole and cefo- 0 50 100 150
taxime if otitis/sinusitis is suspected, may be required MAP (mmHg)
for up to 2 years.
surgical drainage or excision is indicated for cere- Fig. 37Variation of cerebral blood flow with: (a) arterial PO2 and
bellar abscesses, if ICP is markedly raised or PCO2; (b) blood pressure
 Cerebral function monitor 125

by 30%. Reduction may not be sustained for more well as overall activity. Thus the relative proportions of
than 2448h of hypocapnia. the four standard EEG waveforms are presented. Said
- arterial PO2 (Fig. 37a): minimal effect until PO2 to be more useful than the cerebral function monitor,
falls below 6.7 kPa (50mmHg). but suffers from similar drawbacks.
autoregulation (Fig. 37b): CBF remains constant
between a MAP of 60 and 160mmHg (limits Cerebral function monitor. Device adapted from the
are raised in the hypertensive patient). Autoregula- conventional EEG, e.g. for use during anaesthesia. The
tion is impaired by cerebral trauma, hypoxaemia, signal from two parietal electrodes is filtered and ampli-
hypercarbia and inhalational anaesthetic agents. fied to produce a display of average peak voltage, charted
temperature: hypothermia decreases cerebral on slow-moving paper. Thus monitors overall cerebral
metabolism, which results in a decrease in CBF (a activity. Has been used to monitor depth of anaesthesia,
~5% drop per C drop in temperature). but unreliable, especially using volatile anaesthetic
neural control: sympathetic stimulation causes cere- agents. Used in neurosurgery, cardiac surgery and carotid
bral vasoconstriction, parasympathetic stimulation endarterectomy, where trends in activity may reflect
causes cerebral vasodilatation. changes in cerebral perfusion. Has also been used in
drugs: all the volatile anaesthetic agents cause dose- ICU, e.g. for head injury, poisoning and overdoses, status
dependent vasodilatation and attenuation of auto- epilepticus.
regulation. Hyperventilation may reduce this effect. See also, Anaesthesia, depth of
Ketamine also increases CBF; thiopental, etomi-
date, benzodiazepines and propofol reduce it.
Opioid drugs cause little change if PaCO2 is kept
within normal levels.
See also, Cerebral circulation; Cerebral ischaemia; Cere-
bral steal

Cerebral circulation (a)

Arterial supply: two-thirds via the two internal carotid Anterior communicating
arteries and one-third via the two vertebral arteries. artery
These two systems are connected via the anterior and
posterior communicating arteries, thus forming the Anterior cerebral artery
anastomosis (patent in 50% of individuals) known as Posterior
the circle of Willis (Fig. 38a): Internal carotid artery communicating artery
anterior cerebral artery: supplies superior and
medial parts of the cerebral hemisphere.
middle cerebral artery: supplies most of the lateral Middle cerebral
side of the hemisphere. Internal branches supply artery
the internal capsule, through which most ascending
and descending pathways pass. Commonly affected
by CVA. Posterior cerebral artery
Superior cerebellar
posterior cerebral artery: supplies the occipital lobe
Basilar artery artery
and the medial side of the temporal lobe.
Venous drainage (Fig. 38b): Anterior inferior
deep structures drain via the internal cerebral vein cerebellar artery
Posterior inferior
on each side; these form the midline great cerebral cerebellar artery Posterior spinal
vein which passes back to join the inferior sagittal artery
sinus.
cerebral and cerebellar cortices drain via dural Anterior spinal artery Vertebral artery
sinuses:
- superior and inferior sagittal sinuses in the
midline, between the layers of dura of the falx (b)
cerebri. The superior usually drains into the right
transverse sinus; the inferior via the straight sinus
into the left transverse sinus. Falx cerebri Superior sagittal sinus
- transverse sinuses within the tentorium cerebelli:
pass via the sigmoid sinuses through the jugular
foramina to become the internal jugular veins.
- cavernous sinuses on either side of the pituitary Inferior sagittal sinus vein Tentorium cerebelli
fossa: receive blood from the eyes and nearby
Great cerebral vein
parts of the brain, draining into the transverse
sinuses and internal jugular veins.
Both arterial and venous circulations may be imaged Sigmoid sinus
using conventional or CT or MRI angiography.
[Thomas Willis (16211675), English physician] Internal jugular
vein
Cerebral function analysing monitor. Development of Transverse sinus Straight sinus
the cerebral function monitor that provides information
about the frequency distribution of the EEG signal as Fig. 38 Cerebral circulation: (a) arterial; (b) venous
126 Cerebral ischaemia

Cerebral ischaemia. Inadequate blood supply to brain. e.g. barbiturates, benzodiazepines, volatile anaesthetic
May be: agents; increased by seizures, ketamine and possibly
global: N2O.
- complete, e.g. cardiac arrest or severely raised
ICP with hypotension. Cerebral metabolism. Glucose is the main substrate,
- incomplete, e.g. hypotension and cerebrovascular although ketone bodies, amino acids and fats may be
disease. utilised, e.g. in starvation. 9095% of glycolysis is aerobic,
focal or regional, e.g. cerebrovascular disease, hence the requirement for a continuous supply of O2. O2
emboli, local lesions, e.g. tumours; may also be com- consumption is about 3.5ml/100g/min; CO2 output is
plete or incomplete. The periphery of a focal infarct the same.
is termed the penumbra; recovery of this area is the Cerebral metabolic rate for O2 (CMRO2) is used as a
focus of therapeutic interventions. measure of global cerebral metabolism, and does not
Effects of ischaemia: reflect regional variations; neuronal cells consume more
anaerobic metabolism increases, with greater O2 than glial cells, grey matter more than white. Similar
acidosis if a glucose source is available (e.g. with measurements may be made using glucose consumption
incomplete ischaemia). (cerebral metabolic rate for glucose; normally about
impaired cell membrane pump activity results in 4.5mg/100g/min) and lactate production (cerebral
depolarisation due to leak of potassium out of cells, metabolic rate for lactate; normally about 2.3mg/
and calcium into cells. 100g/min).
excitatory neurotransmitters (e.g. glutamate) are Under normal conditions cerebral blood flow is
released and accumulate, contributing to excito- closely related to cerebral metabolism.
toxic cell death. See also, Cerebral ischaemia
free radicals are liberated.
permanent histological damage and associated neu- Cerebral microdialysis. Method of measuring levels of
rological deficits occur after about 45min. neurotransmitters or metabolites present in the ECF of
reduction in cerebral blood flow from the normal the brain, e.g. glucose, pyruvate, lactate, glycerol and glu-
50ml/100g/min causes the following changes: tamate. First used in humans in 1990, with bedside analy-
- 3040ml/100g/min: EEG slows. sers becoming available in the 2000s. Has been used to
- 20ml/100g/min: no spontaneous electrical activ- detect and measure physiological and pathophysiologi-
ity. Lactate rises. cal chemical changes, e.g. in Parkinsons disease, cerebral
- 15ml/100g/min: evoked potentials disappear. ischaemia, cerebral neoplasia, subarachnoid haemor-
Anaerobic metabolism occurs and pH decreases. rhage and head injury. A small microdialysis catheter is
Ionic changes begin. placed in the brain tissue and a perfusion fluid passed
- 10ml/100g/min: oedema and irreversible damage through it. Substances within the ECF pass into the per-
occur if flow is not rapidly restored. fusion fluid by diffusion, forming a dialysate, chemical
Hypoxaemia with uninterrupted blood supply is better analysis of which allows assessment of the local, as
tolerated because of continued removal of waste prod- opposed to global, cerebral metabolism.
ucts despite O2 lack. Tisdall M, Smith M (2006). Br J Anaesth; 97: 1825
Damage is thought to result from increased intracel-
lular calcium levels, free radicals, arachidonic acid Cerebral oedema. Increased brain water content with
metabolites or lactic acid production; these have been associated tissue swelling. May be diagnosed by CT
the targets of investigated lines of treatment (cerebral scanning.
protection/resuscitation). Severity depends on duration, Causes may be:
site and cause of ischaemia, and patient factors, e.g. age, vasogenic: increased vascular permeability and
co-morbidity. Watershed areas between the main cere- defective bloodbrain barrier, e.g. associated with
bral arteries are most at risk from ischaemia, particularly inflammatory conditions, tumours, trauma. Plasma
in the elderly, if vessels are diseased, or if blood viscosity protein and fluid penetrate the brain, tracking along
is high. Chronic ischaemia may predispose to transient fibre tracts. Exacerbated by raised hydrostatic
ischaemic attack, CVA or dementia. During anaesthesia, pressures.
excessive hyperventilation combined with hypotension cytotoxic: cell damage due to cerebral ischaemia,
may cause ischaemia. hypoxia, encephalitis, toxins, metabolic distur-
Zauner A, Daugherty WP, Bullock MR, Warner DS bances; cells become depleted of ATP and accumu-
(2002). Neurosurgery; 51: 289302 late water and sodium.
See also, Brainstem death; Cerebral circulation; Cerebral osmotic: occurs when brain osmolality exceeds
metabolism; Cerebral steal plasma osmolality, e.g. severe hyponatraemia,
during haemodialysis, rapid reduction of plasma
Cerebral metabolic rate for oxygen (CMRO2). glucose in diabetic ketoacidosis.
Volume of O2 consumed by the brain per unit time. hydrostatic: seen in severe hypertension when fluid
Equals cerebral blood flow arteriovenous O2 content is forced out of cerebral capillaries.
difference (see Fick principle). Normally about 50ml/ interstitial: in hydrocephalus the CSF may be forced
min (20% of total basal requirement), or 3.5ml/100g/ from the ventricular system into white matter.
min. Indicative of global cerebral metabolism, over 90% high-altitude cerebral oedema (HACE): may have
of which is aerobic; the relationship may not hold if O2 similar mechanism to vasogenic cerebral oedema.
or glucose supplies are reduced and alternate metabolic Effects:
pathways employed. raised ICP: reduced cerebral perfusion pressure,
Reduced by hypothermia (about 5% reduction per compression of blood vessels and vital structures,
C drop). Also reduced in old age and by certain drugs, papilloedema and coning.
 Cerebrospinal fluid 127

increased distance for O2 diffusion from capillaries - experimental agents include free radical scaven-
to cells. gers (e.g. lazaroids) and glutamate antagonists.
impaired consciousness, convulsions and coma. Fukuda S, Warner DS (2007). Br J Anaesth; 99: 1017
Management:
of primary cause. Cerebral salt-wasting syndrome. Loss of sodium (and
IPPV, with hypocapnia to arterial PCO2 3.84.2 kPa water) via the kidneys associated with intracranial
(2832mmHg). The beneficial effects of hyperven- disease (e.g. subarachnoid haemorrhage, head injury).
tilation may be reduced after 24h. Fluid restriction May be mediated by excessive secretion of atrial natri-
to 1.52 l/day is usually instituted. Venous drainage uretic peptide. Results in hyponatraemia and decreased
is encouraged by head-up posture, good sedation/ plasma volume (unlike the syndrome of inappropriate
paralysis and unobstructed jugular veins, as for ICP antidiuretic hormone secretion, in which plasma volume
reduction. Measures are usually carried out for is increased). Treatment is with fluid and sodium
2448h after the insult. replacement.
corticosteroids (e.g. dexamethasone) are effective Yee AH, Burns JD, Wijdicks EF (2010). Neurosurg Clin
in vasogenic oedema but have limited or no effect North Am; 21: 33952
in other types.
diuretics: Cerebral steal. Diversion of blood flow away from
- mannitol 0.251g/kg iv; relies on an intact blood abnormal areas of brain (e.g. tumours and infarcts), sec-
brain barrier. Effective in vasogenic and cytotoxic ondary to vasodilatation of normal cerebral blood
oedema. Urea is rarely used now. vessels, e.g. due to hypercapnia. The reverse may occur
- furosemide 1040mg. Effective in cytotoxic but in hypocapnia; thus general vasoconstriction may
not vasogenic oedema. increase blood flow to abnormal areas (inverse steal).
hypertonic intravenous solutions (e.g. 7.5% saline)
have been used. Cerebral venous thrombosis. Most commonly affects
the superior sagittal, lateral, cavernous or straight
sinuses, although cerebral veins may be involved (see
Cerebral perfusion pressure (CPP). Difference
Cerebral circulation).
between MAP and ICP; represents the pressure head Aetiology:
available for cerebral blood flow. Normally 7075mmHg;
infective:
critical level for cerebral ischaemia is thought to be
- local, e.g. cerebral abscess, meningitis, sinusitis,
3040mmHg. In the presence of raised ICP, MAP
otitis.
increases in order to maintain CPP (Cushings reflex).
- systemic, e.g. endocarditis, TB, HIV infection,
bacteraemia, viraemia.
Cerebral protection/resuscitation non-infective:
Possible techniques: - local, e.g. head injury, neurosurgery, cerebral
general measures: tumour, hyperosmolar infusion via jugular veins.
- maintaining normotension and oxygenation. - general, e.g. hypercoagulable coagulation disor-
- maintaining metabolic stability and other organ ders, including pregnancy.
function. Features depend on the site but include those of raised
increasing or maintaining cerebral perfusion ICP, cranial nerve palsies and CVA. Cavernous venous
pressure: thrombosis results in facial oedema and swelling of
- nimodipine in subarachnoid haemorrhage: the eye.
thought to reduce vasospasm and maintain blood Diagnosed clinically and by CT or MRI scanning, and
flow. Of uncertain benefit in other intracranial cerebral angiography. MRI is now the investigation of
pathology. choice.
- reduction of ICP, e.g. hypocapnia or mannitol. Treatment is directed at the underlying cause; sys-
- haemodilution. temic heparin and direct infusion of fibrinolytic drugs
- cerebral angioplasty/endovascular thrombolysis have been used.
in focal ischaemia. Stam J (2005). N Engl J Med; 352: 17918
reducing metabolic rate for O2:
- hypothermia: used in cardiac surgery and after Cerebrospinal fluid (CSF). Clear fluid bathing the CNS,
cardiac arrest. Appears to have sustained benefit providing support and protection against trauma, and
pre- and post-ischaemic injury. helping to regulate ICP. Total volume is 100150ml in
- barbiturates: efficacy in animal studies has not the adult, 50ml in newborns; one-third is contained in
been repeated in human trials; routine use is thus the spinal canal.
controversial, unless for sedation or treatment of Production:
convulsions. Profound hypotension is a major side by choroid plexuses mainly in the lateral but also in
effect. the third and fourth ventricles at about 500ml/day.
- isoflurane: possibly beneficial in incomplete global formed by secretion, and filtration of plasma. For-
ischaemia; cerebral steal is possible in focal isch- mation is largely independent of ICP, but removal
aemia. Efficacy has not been established in increases with increasing pressure.
humans. Circulation (Fig. 39):
reducing cell damage: from the lateral ventricles to the third ventricle via
- avoidance of hyperglycaemia. Shown to have sus- the foramina of Monro, thence to the fourth ven-
tained benefits pre- and post-ischaemic injury. tricle via the aqueduct.
- xenon has a neuroprotective effect via NMDA leaves the fourth ventricle via the foramina of
receptor antagonism. Magendie (midline posteriorly) and Luschka
128 Cerebrovascular accident

paresis, hemisensory loss and homonymous hemi-

3rd ventricle Foramen of Monro anopia. Single limbs and the face may be affected.
Choroid plexus Speech disorders are common if the dominant
Corpus callosum hemisphere is affected.
signs of raised ICP (more likely in haemor-
rhagic stroke): headache, vomiting, impaired
consciousness.
meningism (indicative of blood in the subarachnoid
space).
Treatment:
supportive: includes control of arterial BP and
Aqueduct
blood glucose levels (hyperglycaemia is associated
Pons with worse outcome). Early enteral nutrition and
4th ventricle
Choroid plexus normothermia also improve prognosis.
in ischaemic stroke, outcome is improved if intrave-
Medulla
nous thrombolysis is performed within 3h of onset
Foramen of Magendie of symptoms. Local intra-arterial thrombolysis may
be used in basilar artery occlusion. Aspirin decreases
Cerebellum recurrence of ischaemic episodes. Full anticoagula-
tion has no place in treatment but low-dose heparin
is given to decrease the incidence of DVT and PE.
in haemorrhagic stroke, in addition to supportive
care, treatment aims include the prevention of vaso-
Fig. 39 Circulation of CSF spasm (e.g. with nimodipine) and rebleeding (e.g.
with coiling or clipping of intracerebral aneurysms).
Large haematomas (especially in the posterior
fossa) may be surgically removed.
(laterally) to pass down to the spinal cord or up over Anaesthetic considerations:
the cerebral hemispheres. assessment for predisposing conditions, e.g. hyper-
passes into dural venous sinuses via arachnoid villi, tension, coagulation disorders, embolic conditions,
and possibly from spinal nerve cuffs into spinal trauma, arteritis due to connective tissue diseases,
veins. infections.
Normal constituents: immobility, contractures: may affect drip sites. Risk
sodium: 135145mmol/l. of DVT.
chloride: 115125mmol/l. bulbar lesions and laryngeal incompetence, and
calcium: 11.5mmol/l. autonomic disturbances.
potassium: 2.53.5mmol/l. communication difficulties.
glucose: 2.74.2mmol/l (if blood glucose normal). severe hyperkalaemia after suxamethonium has
pH: 7.37.5. been reported up to 6 months after CVA.
protein: 0.20.4g/l. hyperventilation and reduction of cerebral blood
urea: 1.56.0mmol/l. flow, and hypotension, should be avoided during
lymphocytes: 05 10 /l.
6
anaesthesia. Cerebral steal may occur.
[Alexander Monro (17331817), Scottish anatomist; confusion is common postoperatively.
Francois Magendie (17831855), French physiologist; Risk of CVA during anaesthesia is increased in cardiac
Hubert von Luschka (18201875), German anatomist] surgery, carotid endarterectomy and neurosurgery.
See also, Bloodbrain barrier; Lumbar puncture Lukovits TG, Goddeau RP (2011). Chest; 139: 694700
See also, Brain; Cerebral circulation; Cerebral
Cerebrovascular accident (CVA; Stroke). Third com- ischaemia
monest cause of death in developed countries.
Caused by: Certoparin, see Heparin
infarction (8085%), e.g. caused by atheroma,
embolism, arteritis/arterial spasm or hypotension. If Cervical plexus block. Provides analgesia of the upper
symptoms resolve within 24h, defined as a transient cervical dermatomes; used for head and neck surgery
ischaemic attack, although CT scanning may reveal and treatment of chronic pain.
evidence of permanent damage. Multiple small The plexus is formed from the anterior branches of
emboli may cause dementia. the upper four cervical nerves, lying between the ante-
haemorrhage, usually (60%) associated with bleed- rior and posterior tubercles of the cervical vertebral
ing from an intracerebral vessel in the presence of transverse processes.
hypertension. More common in patients taking Technique:
anticoagulant drugs and those with intracranial the patient is placed supine, looking away from the
aneurysms and arteriovenous malformation. Sub- side to be blocked, with the neck partially extended.
arachnoid haemorrhage usually occurs from con- The transverse processes of C24 are palpated pos-
genital aneurysms. terior to a line between the mastoid process and
Features include: transverse process of C6.
upper and lower motor neurone lesions; distribu- a fine needle is introduced perpendicular to the
tion depends on the site and extent of the lesion, skin, 13cm towards each transverse process in
e.g. lesions may cause contralateral hemiplegia/ turn until contact is made or paraesthesia elicited.
 Checking of anaesthetic equipment 129

after careful aspiration, 35ml solution (e.g. 0.5% Checking of anaesthetic equipment. Should be per-
lidocaine with adrenaline) is injected at each level formed before anaesthetising any patient. The require-
to block the deep branches. A further 35ml is ment for following a checklist is mandatory in many
injected as the needle is withdrawn. The superficial countries, including the UK.
branches are blocked by injecting 1520ml along The following should be checked before every oper-
the posterior border of the middle third of the ster- ating theatre session (Association of Anaesthetists
nomastoid muscle. guidelines):
Complications include intravascular injection or punc- anaesthetic machine:
ture (e.g. vertebral artery), subarachnoid injection, sym- - check electricity supply/back-up as appropriate.
pathetic block, phrenic nerve block and recurrent - note any information/service labels present.
laryngeal nerve block. - check the identity and attachments of all
pipelines.
Cervical spine. Composed of seven cervical vertebrae. - CO2 cylinders should only be present if specifi-
Important in the positioning of the neck in airway man- cally requested. Blanking plugs should be fitted to
agement, including tracheal intubation. Injury may often unused yokes.
accompany head injury. - check the O2 supply and reserve cylinders.
See also, Intubation, difficult; Spinal cord injury; Verte- - check the other gases are connected (confirm with
bral ligaments a tug test) and that all pipeline pressure gauges
read 400 kPa (4 bar).
CFAM, see Cerebral function analysing monitor - check each flow valve and flowmeter throughout
its whole range.
CFM, see Cerebral function monitor - check the antihypoxic device linking the O2 and
N2O flowmeters, and the O2 flush.
cgs system of units. System based on the centimetre, - check the vaporisers are seated properly, filled
gram and second; replaced in 1960 by the SI system and able to be turned on. Test the vaporiser fit-
based on the metre, kilogram and second. tings for leaks by setting a gas flow of 5 l/min and
See also, Units, SI obstructing the common gas outlet with the vapo-
riser turned on and off (unless the manufacturer
Charcoal, activated. Charcoal meeting certain adsor- suggests alternative testing).
bence standards. - obstruct the gas outlet with a set gas flow of 5 l/
Uses: min, ensuring that the flowmeter bobbin dips
administered orally or via a nasogastric tube to (indicating pressurisation of the machine back
reduce gastrointestinal absorption of certain toxic bar) and that the pressure relief valve opens
compounds (e.g. barbiturates, tricyclic antidepres- (unless the manufacturer suggests alternative
sant drugs) in the treatment of poisoning and over- testing, e.g. using a negative-pressure leak-testing
doses. In addition to adsorbing toxins present in the device consisting of a rubber bulb to be fitted to
stomach, it reduces blood levels by preventing the gas outlet)
enterohepatic recirculation. Most effective when scavenging: check correct connection.
substances toxic in small amounts have been anaesthetic breathing system:
ingested, and within 1h of ingestion (prehospital - ensure correct configuration and firm attachment
administration has been suggested). Adult dosage: of connections.
50100g 4-hourly, or 25g 2-hourly. - ensure there is no obstruction by foreign
during anaesthesia, containers of activated material.
charcoal (the Aldasorber) have been used in breath- - close the expiratory valve. Obstruct the distal end
ing systems to adsorb volatile agents, thereby reduc- of the tubing to fill the reservoir bag; ensure no
ing pollution. N2O is not adsorbed. Remaining leaks. Use a two-bag test to confirm.
adsorption capacity is monitored by weighing the - open the valve, checking the bag empties.
container. - coaxial breathing systems: as above, plus testing
coated activated charcoal is used during for correct attachment of the inner tubing of Bain
haemoperfusion. system:
Bond GR (2002). Ann Emerg Med; 39: 27386 - obstruct the distal end of the inner tube; the
flowmeters should fall as pressure builds up
Charge, electric. Physical property of matter causing it behind the obstruction.
to experience a force when in proximity to other charged - close the expiratory valve and fill the bag by
matter. May be positive or negative, indicating a relative occluding the distal end of the outer tube. Use
deficit or excess of electrons respectively. Flow of charge the O2 flush with the tube now unobstructed: the
constitutes a current. SI unit is the coulomb. reservoir bag should empty due to gas entrain-
ment, unless the inner tube is detached (Peth-
Charles law. At constant pressure, the volume of a fixed icks test; N.B. has been shown to be less efficient
mass of gas is proportional to its temperature. at detecting leaks from the inner tube than the
[Jacques Charles (17461823), French chemist] obstruction test).
See also, Boyles law; Ideal gas law - circle systems: check one-way valves and bag.
Ensure the soda lime is properly packed and not
Chassaignacs tubercle. Transverse process of C6, expired.
against which the common carotid artery may be felt and - ventilator: check on manual settings as above, and
compressed. Useful landmark for stellate ganglion block. on automatic settings with the outlet obstructed,
[Charles Chassaignac (18041879), French surgeon] for adequate ventilating pressures and pressure
130 Chelating agents

relief. Check the disconnect alarm and that alter- may cause vomiting by stimulating the CTZ, which sends
native means of IPPV are available, e.g. self- efferents to the vomiting centre of the medulla. Some
inflating bag. antiemetic drugs (e.g. phenothiazines) act by inhibiting
ancillary equipment (before each case): receptors within the CTZ.
- drugs, iv fluids.
- tracheal tubes, cuffs, introducers, laryngoscopes Chemoreceptors. Receptors responding to chemical
(including spare), suction apparatus, tipping stimulation, producing action potentials when triggered
trolley. Check the entire breathing system, includ- by certain (often specific) molecules.
ing catheter mount, angle piece, filter and connec- Examples:
tions are patent (i.e. no obstructions) before each taste and smell receptors.
case. Single-use equipment should be kept pack- O2, CO2 and hydrogen ion receptors.
aged until the point of use to avoid obstruction chemoreceptor trigger zone cells.
with solid objects. See also, Aortic bodies; Breathing, control of; Carotid
- check all monitoring devices, including O2 analy- bodies
ser, are functioning and have appropriate alarm
limits (and for BP, an appropriate measuring fre- Chest drainage. Removal of air or liquid from the
quency) set. pleural space via pleural aspiration (thoracocentesis) or
It is also recommended that performance of a check is chest drain insertion. Used in the management of pneu-
recorded on each patients anaesthetic chart, and a mothorax, haemothorax and pleural effusions.
logbook kept with each anaesthetic machine. Pleural aspiration:
[Simon L Pethick, Canadian anaesthetist] indications include: spontaneous pneumothorax;
Hartle A, Anderson E, Bythell V, et al (2012). Anaesthe- diagnosis or symptomatic relief of malignant effu-
sia; 67: 6608 sion; and diagnosis of parapneumonic effusion.
technique:
Chelating agents. Chemicals that bind to certain metal - choice of patient position is dependent on the site
ions forming soluble complex molecules; the bound ions of the pathology and operator preference. Options
are usually rendered inactive as a result. include: seated and leaning forward (with elbows
Examples (with the metals chelated): resting on a table); lying semi-supine on a bed;
dimercaprol (antimony, arsenic, bismuth, mercury, and lateral decubitus.
gold). - use of ultrasound guidance reduces failure and
sodium calcium edetate (lead, copper, radioactive complication rates, and is now strongly recom-
metals). mended where available.
penicillamine (copper, lead, gold, mercury, zinc). - insertion point is almost always either in the
desferrioxamine (iron, aluminium). second intercostal space in the mid-clavicular line,
trisodium edetate (calcium). or within a triangle bound by the lateral border
of pectoralis major, the lateral edge of latissimus
Chemical weapons. Substances used for hostile pur- dorsi and the line of the fifth intercostal space (the
poses, either by certain nations in legitimate chemical triangle of safety).
warfare or by terrorists. The agents may be targeted at - after infiltration with local anaesthetic agent
people, animals and/or plants. Usually classified accord- down to the periosteum of the upper surface of
ing to their physiological effects: the chosen rib, the needle or cannula (with syringe
toxins derived from living organisms, e.g. botulinum attached) is advanced above the upper edge of the
toxins, ricin (derived from castor bean), saxitoxin rib to avoid the nerve and vessels in the intercos-
(derived from marine organisms). tal space. Air entry is prevented by continuous
nerve agents, e.g. acetylcholinesterase inhibitors aspiration during advancement, until the pleura is
(e.g. sarin, soman, VX gas and tabun). penetrated and fluid/air is withdrawn.
blood agents, e.g. cyanide. - a three-way tap may then be connected to the
blistering or choking agents, e.g. mustard gas, chlo- cannula and used to aspirate and expel fluid/
rine, phosgene. air. Aspiration should be stopped if the patient
vomiting agents, e.g. adamsite. develops chest discomfort or 1.5 l fluid is with-
tear gas. drawn (larger volumes are associated with post-
Management includes specific and general supportive expansion pulmonary oedema).
measures; consideration should also be directed towards complications: pneumothorax, failure, visceral
protection of staff, decontamination of clinical areas and injury and bleeding.
equipment, disposal of bodies and other aspects of major Chest drain insertion:
incidents. indications include: pneumothorax in a ventilated
White SM (2002). Br J Anaesth; 89: 30624 patient; tension pneumothorax (after initial needle
See also, Biological weapons; Cyanide poisoning; Inci- decompression); empyema; traumatic haemopneu-
dent, major mothorax.
technique:
Chemoreceptor trigger zone (CTZ). Area situated in - positioning is as for pleural aspiration; insertion
the area postrema of the medulla, on the lateral walls of site is within the triangle of safety described
the fourth ventricle. Lies outside the bloodbrain barrier; above.
chemoreceptor cells within it are thus directly exposed - when draining effusions, use of ultrasound guid-
to blood-borne chemicals. Stimulated by noradrenaline, ance is recommended where available.
dopamine, acetylcholine, 5-HT and opioid receptor ago- - small-bore drains (e.g. 1016 FG [French gauge])
nists. Circulating emetics (e.g. opioid analgesic drugs) are associated with lower complication rates and
 Chest infection 131

greater comfort (whilst having similar efficacy in as a fluid trap, e.g. for accurate measurement of
most situations) and are recommended as first blood. Bottle B provides the underwater seal. Bottle
choice for drainage of pneumothorax, simple C allows suction; the height of the water level deter-
pleural effusion and empyema. They are inserted mines the amount of suction applied before air is
using a Seldinger technique, employing the same drawn in through tube D as a safety suction-limiting
approach as for pleural aspiration, above. Minimal device. Modern systems incorporate all three bottles
force should be used and the dilator inserted no in one plastic unit.
more than 1cm beyond the depth of the pleura. Havelock T, Teo R, Laws D, Gleeson F (2010). Thorax;
- large-bore drains (> 20 FG) are usually chosen in 65 (Suppl 2): ii6176
haemopneumothorax and if blockage of smaller
drains is problematic. After local anaesthetic infil- Chest infection (Lower respiratory tract infection).
tration as above, the chest wall is incised about Includes tracheitis, laryngotracheobronchitis (croup),
2cm below the proposed site of pleural incision, acute bronchitis, bronchiolitis, acute exacerbations of
cutting down on to the rib below. Blunt dissection COPD/bronchiectasis and pneumonia.
with artery forceps is performed through to the Commonly used classification for pneumonia:
pleural cavity, and the tip of a finger inserted to community-acquired: often due to one of a limited
sweep adherent lung away from the insertion site. number of pathogens, which may be deduced from
If possible, IPPV should be paused at end- epidemiological factors (e.g. exposure to animals,
expiration when the pleura is actually punctured, alcoholism, iv drug abuse):
to reduce damage to the lung. The drain is inserted - bacteria, e.g. Streptococcus pneumoniae (the com-
into the pleural cavity and slid into position monest causative agent, often resulting in classical
(aimed apically for pneumothorax or basally for lobar pneumonia), Haemophilus influenzae, Kleb-
fluid). Use of a rigid trocar has been abandoned siella pneumoniae.
due to high risk of trauma to the lung. Analgesia - viruses, e.g. influenza, parainfluenza, measles.
(e.g. iv morphine) should be given to cover the - others, e.g. legionella, mycoplasma, rickettsia,
procedure and prescribed regularly when the chlamydia, Mycobacterium tuberculosis.
chest drain is in place. opportunistic: occurs in immunodeficiency, e.g. hae-
complications: pain; visceral injury; bleeding; infec- matological malignancies and AIDS. Bacterial
tion; blockage. Rates for all complications (except pneumonia with the usual organisms is common;
drain blockage) are higher with large-bore drains. other pathogens more likely to cause disease in the
the drain is connected to an underwater seal device immunocompromised include Pneumocystis jir-
(see below), observing the water level for swinging/ oveci, cytomegalovirus, herpes, tuberculosis and
bubbling with respiration. One-way flutter valves fungi (e.g. aspergillus and candida).
may also be used, e.g. Heimlich valve (flattened nosocomial pneumonia: up to 5% of hospital inpa-
rubber tube within a clear plastic tubing). tients develop pneumonia, e.g. following anaesthe-
a suture is inserted around the puncture site to aid sia, ICU admission, atelectasis, aspiration of gastric
sealing after removal, and dressings are applied. contents and hypoventilation. Thought to result
plastic tubes are most commonly employed. Most from microaspiration of bacteria from the GIT;
tubes have side holes to aid drainage, and a radio-
opaque longitudinal line.
CXR demonstrates the position and effect of the
(a)
drain. C
the drain is usually removed 1224h after cessation Patient
of air or fluid loss, often after a trial period of clamp- A
ing. CXR is mandatory following removal.
Features of the underwater seal (Fig. 40a):
tube A must be wide to minimise resistance. Its
volumetric capacity should exceed half of the
B
patients maximal inspiratory volume or water may
be aspirated into the chest during inspiration.
the volume of water above the end of tube B
should exceed half of the patients maximal inspira-
tory volume to prevent indrawing of air during
inspiration. (b)
the end of tube B should not be more than 5cm Patient
below the surface of the water, or its resistance may
prevent air being blown off.
the drain should always be at least 45cm below the
patient.
tube A should be temporarily clamped when the
underwater seals integrity may be disrupted, e.g. D
during transfer from bed to trolley.
suction may be applied to tube C, although this is
controversial. 1020 cmH2O suction is usually
employed.
A B C
a three-bottle system is often used, especially after
cardiac or thoracic surgery (Fig. 40b). Bottle A acts Fig. 40 Chest drainage systems: (a) one-bottle; (b) three-bottle
132 Chest trauma

Gram-negative (e.g. Pseudomonas aeruginosa and non-penetrating:

Escherichia coli) and anaerobic bacteria are com- - blunt trauma, e.g. deceleration injury in RTAs.
monly responsible. Damage is caused by direct impact (e.g. rib frac-
Features: tures, myocardial contusion) and shearing forces
malaise, pyrexia, tachycardia. Legionnaires disease (e.g. aortic rupture, tracheobronchial tears).
may cause back pain and renal impairment. - blast injuries: sudden external chest and
cough, sputum, haemoptysis, dyspnoea, tachypnoea. abdominal compression may cause alveolar
increased V/Q mismatch and shunting causing and pulmonary vessel rupture, with oedema and
hypoxaemia and respiratory failure. haemorrhage.
clinical and radiological features of consolidation Immediately life-threatening conditions:
and collapse, possibly leading to pleural effusion severe hypoventilation caused by:
and empyema. Severe pulmonary destruction and - airway obstruction (especially likely with associ-
abscess formation may follow, especially in staphy- ated head injury).
lococcal infection. - pneumothorax/haemothorax.
may lead to severe sepsis with multiorgan dysfunc- - flail chest.
tion or failure. reduced cardiac output caused by:
may also produce no systemic signs of infection - hypovolaemia caused by haemorrhage. Major
(particularly in the elderly). vessel damage often accompanies fracture of the
Assessment and investigations include: first two ribs. Aortic rupture usually occurs just
clinical assessment combined with CXR, arterial beyond the left subclavian artery.
blood gas interpretation, full blood count, C-reactive - cardiac tamponade.
protein, renal and liver function tests. - tension pneumothorax.
blood cultures, sputum culture, urinary legionella Other conditions less immediately dangerous:
and pneumococcal antigen. HIV serological testing respiratory:
should be considered if indicated. - sternal/rib fractures.
severity scoring systems exist to aid risk stratifica- - tracheobronchial tears.
tion. The CURB-65 score is validated for this - diaphragmatic rupture.
purpose, and consists of five criteria, scoring one - lung contusion.
point for each if present: confusion; urea > 7mmol/l; - aspiration of gastric contents (especially with
respiratory rate > 30 breaths/min; BP < 90mmHg head injury).
systolic or 60mmHg diastolic; and age > 65 years. - blast injury: symptoms may occur 23 days later.
A score of 0 predicts a 30-day mortality rate of There may be associated smoke inhalation.
0.6%; this rises to 17% with a score of 3, and 57% - V/Q mismatch and shunt result in hypoxaemia.
with a score of 5. Ventilatory failure may also occur. Infection and
Microbiological diagnosis should not delay prompt ARDS may ensue.
empirical treatment according to the most likely cardiovascular:
organism. Serology or bronchial biopsy/washings may - myocardial contusion: may present as arrhyth-
be useful in atypical cases. mias, cardiac failure or valve rupture.
Treatment: - damage to the coronary vessels and great vessels.
antimicrobial drugs. other injuries: head injury, vertebral and limb inju-
supportive therapy; i.e. O2 therapy, iv fluids, ries. Oesophageal rupture may occur, with risk of
physiotherapy. mediastinitis.
Anaesthetic/ICU relevance: Management:
preoperative assessment and optimisation of chest immediate assessment and management of the
disease. above life-threatening conditions, i.e. sealing of any
prevention of aspiration and atelectasis. penetrating wound with dressings, O2 therapy, iv
postoperatively: physiotherapy, adequate analgesia fluid administration. Airway patency and adequate
and avoidance of hypoventilation are important, respiratory movement should be checked. Chest
especially in pre-existing chest disease. percussion and auscultation may suggest pneumo-
treatment of respiratory failure on ICU, or develop- thorax or haemothorax. Heart sounds may be
ment of nosocomial pneumonia in patients receiv- muffled in tamponade. Pulsus paradoxus may indi-
ing IPPV. Selective decontamination of the digestive cate tamponade or tension pneumothorax, whilst
tract may help to reduce the incidence of nosoco- unequal pulses may suggest aortic dissection or
mial pneumonia on ICU, although its use is not rupture. Hypotension may occur in hypovolaemia,
routine. tamponade, tension pneumothorax and myocardial
See also, Mycoplasma infections; Nosocomial infection; contusion.
Pseudomonas infections; Streptococcal infections subsequent assessment:
- CXR: may reveal pneumothorax, surgical emphy-
sema, fractures, evidence of aspiration and
Chest trauma. Causes include road traffic accidents widened mediastinum (may represent aortic
(RTAs), falls, assault including stabbings and shootings, rupture, especially if associated with left haemo-
and explosions. Trauma may be: thorax, depressed left main bronchus and oesoph-
penetrating: in stabbing injuries, trauma tends to be ageal displacement to the right). Lung contusion
localised to the track of the implement. In gunshot may appear as fluffy, patchy shadowing within a
wounds, a small entry point may disguise major few hours of injury.
internal disruption (because of rapid dissipation of - arterial blood gas interpretation/pulse oximetry
kinetic injury). are especially useful.
 Chest X-ray 133

(a) (b)

Trachea Brachiocephalic vessels

Superior Anterior borders Sternum
vena cava Aortic knuckle of scapulae
Left pulmonary Upper lobe bronchi Aorta
Horizontal arteries Right pulmonary
fissure Left pulmonary artery
artery
Heart Heart
Oblique fissures

Gastric air bubble

(c) (d)

Superior vena cava

Superior vena cava
Aorta
Aorta
Right pulmonary Left pulmonary
arteries arteries
P
Left atrial Left atrium A
P
A appendage M
M Right ventricle
Left ventricle T

T Left ventricle

Diaphragm

Inferior vena cava Right ventricle Diaphragm Inferior vena cava

Fig. 41 Normal-appearance chest X-ray: (a) PA; (b) lateral; (c) mediastinal structures, PA; (d) mediastinal structures, lateral. Position of valves:
P, pulmonary; A, aortic; M, mitral; T, tricuspid

- ECG as a baseline. Serial ECG and cardiac Plan for the interpretation of CXRs (Fig. 41):
enzyme changes may occur in myocardial describe the film:
contusion. - the date, patients name and clinical history should
- for other injuries. be noted.
chest drainage/pericardiocentesis as appropriate. - orientation (i.e. right/left marker) and projection.
methods of analgesia include iv opioid analgesic In posteroanterior (PA) films the scapulae
drugs in small doses (but with risk of respiratory shadows are projected laterally. Anteroposterior
and cerebral depression), intercostal nerve block, (AP) films are usually portable films. Lateral
interpleural analgesia and epidural anaesthesia films allow three-dimensional localisation of
with local anaesthetic agent or opioids. pathology.
nasogastric tube to prevent gastric dilatation. - penetration/exposure: appropriate penetration
surgery may be required for severe haemorrhage or should allow the thoracic spine to be just visible
trauma to the aorta, diaphragm, tracheobronchial behind the heart.
tree or oesophagus. - rotation: clavicular heads should be equidistant
physiotherapy/antibiotics. Lung contusion is exacer- from vertebral processes; particularly important
bated by overhydration, but hypovolaemia must be for assessment of the mediastinum.
avoided. - position (upright/supine): important when com-
menting on pneumothoraces and pleural
effusions.
Chest X-ray (CXR). Commonly performed diagnostic - inspiratory effort: 910 posterior rib portions or
and screening test. Usually taken on deep inspiration; an 56 anterior ribs should be visible; inadequate
expiratory film may be used to aid identification of a inspiration may give the appearance of basal lung
pneumothorax. consolidation.
134 CheyneStokes respiration

describe any obvious abnormality first; otherwise occur in cerebral disease, head injury and opioid
continue with the plan. poisoning.
heart shadow: prolonged circulation time between the lungs and
- normal width is < 50% of thoracic diameter brain, e.g. in cardiac failure. Hyperventilation con-
(PA film). tinues until hypocapnia is registered by central che-
- abnormal border may indicate aneurysm, chamber moreceptors, although the CO2 tension at the lungs
dilatation or overlying lesion; indistinct border is much lower. When the CO2 content of blood
may represent lung collapse/consolidation. arriving centrally is high enough to restart breath-
- calcified/prosthetic valves: the aortic valve lies ing, the CO2 content of blood at the lungs is much
above a line drawn from the anterior costophrenic higher, causing hyperventilation as it arrives at the
angle to the hilum on the lateral X-ray; the mitral chemoreceptors.
valve lies below. Cherniack NS, Longobardo G, Evangelista CJ (2005).
upper mediastinum (i.e. width, aortic shadow, Neurocrit Care; 3: 2719
hila): [John Cheyne (17771836), Scottish-born Irish physi-
- hilar enlargement may be due to pulmonary vas- cian; William Stokes (18041878), Irish physician]
cular or lymph node enlargement, or overlying See also, Breathing, control of
lesion. The left hilum is usually higher than the
right by 12cm. CHI, Commission for Health Improvement, see Health-
- the carina usually overlies T45 on inspiration. care Commission
lung fields:
- upper zone (above anterior part of second rib). Chi-square analysis, see Statistical tests
- midzone (between second and fourth rib).
- lower zone (below fourth rib).
- compare each with the other side for translucency. Chloral hydrate. Sedative prodrug, introduced in 1869.
Look for pneumothorax or hyperexpansion. Metabolised to trichloroethanol, which has a half-life of
- the left hemidiaphragm is usually lower than the 810h. Causes minimal cardiovascular or respiratory
right by 2cm. depression. Gastric irritation may occur; it is less fre-
- lung consolidation: a distinct border with neigh- quent with triclofos or dichloralphenazone, both of
bouring structures is lost, aiding identification of which are also metabolised to trichloroethanol.
Dosage: 2550mg/kg (children) orally/rectally; 0.5
the affected lung portion; e.g. an indistinct heart
border represents consolidation anteriorly, since 2g (adults).
the heart lies anteriorly in the chest.
- lung collapse: as for consolidation, with volume Chloramphenicol. Bacteriostatic antibacterial drug;
loss on the affected side, mediastinal shift or tra- inhibits bacterial ribosomal activity and thus protein
cheal deviation. The collapsed portion of lung synthesis. Has a broad spectrum of activity but, because
may be visible against neighbouring structures. of its potential toxicity, systemic use is usually reserved
- pleural effusion: seen as an opacity sloping for life-threatening infections, e.g. due to Haemophilus
upwards and outwards at the lung base; if hori- influenzae and typhoid. Penetrates into CSF extremely
zontal, it represents a gas/fluid interface. well, thus often used in meningitis. 70% protein-bound,
- Kerleys lines may be present. it undergoes extensive hepatic metabolism. Half-life
- prominent upper lobe pulmonary veins (upper is 4h.
Dosage: 50100mg/kg orally/iv daily in four divided
lobe blood diversion), caused by raised pulmo-
nary venous pressure; may be visible in left doses.
ventricular failure and left-to-right cardiac Side effects:

shunts. Proximal dilatation with peripheral aplastic anaemia (often irreversible and may
narrowing (pruning) may represent pulmonary be fatal), peripheral or optic neuritis, nausea, vomit-
hypertension. ing, diarrhoea, erythema multiforme, nocturnal
bones: ribs (metastases, fractures, notching); scapu- haemoglobinuria.
lae; vertebrae; humerus. the grey-baby syndrome (cardiovascular collapse)

soft tissues: below diaphragm; above clavicles; neck; may occur in neonates unable to metabolise the
axillae; breasts. drug. Plasma concentrations should be monitored
foreign bodies, including central lines, tracheal in children under 4 years old; recommended peak
tubes. and trough levels are 1525g/ml and < 15g/ml
review areas: apices; behind the heart; costo- respectively.
phrenic angles. may enhance the effect of warfarin.
See also, Thoracic inlet
Chlordiazepoxide hydrochloride. Benzodiazepine,
CheyneStokes respiration. Abnormal pattern of used for anxiolysis and treatment of alcohol withdrawal
breathing characterised by alternating periods of hyper- syndromes. Half-life is 630h, with formation of active
ventilation and apnoea. Ventilation increases in depth metabolites (that are renally excreted) including demox-
and frequency to a peak, then decreases to apnoea. The epam (half-life up to 78h), desmethyldiazepam and
cycle then repeats. oxazepam. As with other benzodiazepines, drowsiness,
Caused by: respiratory depression, anterograde amnesia, tolerance
central disturbance of control of breathing. and dependence may occur.
Hypoventilation causes hypercapnia, which causes Dosage:
hyperventilation. Resultant hypocapnia causes for severe anxiety: 10mg orally tds (increased to
apnoea until the arterial PCO2 rises again. May 100mg daily if necessary).
 Choking 135

for alcohol withdrawal: 1050mg orally qds, reduced may cause rapidly developing arrhythmias and
over 710 days. convulsions.

Chloride shift (Hamburger shift). Movement of chlo- Chlorphenamine maleate (Chlorpheniramine). Anti-
ride ions into red blood cells as O2 is given up and histamine drug; competitive antagonist at histamine H1
exchanged for CO2 in the tissues. CO2 enters the cells, is receptors. Used to treat allergic reactions, both mild (e.g.
converted to carbonic acid by carbonic anhydrase and hayfever) and severe (e.g. anaphylaxis). Also used to
dissociates into hydrogen ions and bicarbonate. H+ ions treat generalised itching, e.g. in obstructive jaundice or
are buffered by the reduced haemoglobin; HCO3 ions after spinal opioids. Duration of action is up to 6h.
pass into the plasma. Chloride ions enter the cells to Dosage:
maintain electrical equilibrium. The reverse occurs in 4mg orally 46-hourly.
the lungs. 1020mg im, sc or iv by slow injection, up to 40mg/
[Hartog J Hamburger (18591924), Dutch physiologist] day.
Side effects:
Chlormethiazole, see Clomethiazole drowsiness, anticholinergic effects.
hypotension and CNS excitability may follow iv
Chloroform. CHCl3. Inhalational anaesthetic agent; injection.
used in 1847 by Simpson, although it had been used
earlier. Rapidly became more popular than diethyl Chlorpromazine hydrochloride. Phenothiazine, used
ether, and was administered to Queen Victoria during primarily as an antipsychotic drug. First used in the early
childbirth. Sweet-smelling and pleasant to inhale, 1950s, and called Largactil because of its large number
with similar properties to halothane, including non- of actions. Has been used before and during anaesthesia
flammability. Given by pouring on to a towel or by inhal- (e.g. lytic cocktail). Has powerful sedative and anti-
ers. Risk of sudden death, usually during induction, was emetic properties, with anticholinergic, antidopaminer-
attributed to respiratory depression in Scotland and gic and -adrenergic receptor antagonist effects.
cardiac standstill in England. The First and Second Dosage: 2550mg orally or im tds (larger doses may
Hyderabad Commissions in 1888 and 1889 respectively, be required). May also be given iv (off-licence),
financed by the Nizam of Hyderabad (18661911), con- diluted to avoid thrombophlebitis. Hypotension may
cluded that sudden death by respiratory depression pre- follow iv injection. May be given rectally as chlor-
ceded cardiac arrest. The reverse was generally accepted promazine base 100mg.
over 20 years later. VF occurred most commonly. Also Side effects are as for phenothiazines.
caused severe hepatic failure. Gradually replaced by
diethyl ether by the early/mid-1900s. Choanal atresia. Congenital blockage of one or both
Payne JP (1981). Br J Anaesth; 53: 11S15S nasal passages. Incidence is 1:8000 births. If bilateral, it
For physical properties, see Inhalational anaesthetic causes severe airway obstruction from birth, since neo-
agents nates are obligatory nose breathers. Respiratory distress
and cyanosis are characteristically reduced during crying,
Chloroprocaine hydrochloride. Ester local anaesthetic when mouth breathing occurs. May be demonstrated by
agent, introduced in 1952. Of rapid onset and short attempting to pass a soft catheter through the nostrils.
duration of action (approximately 45min), with low Other congenital defects and syndromes may be associ-
systemic toxicity. Hydrolysed by plasma cholinesterase. ated, e.g. VSD.
Used for epidural anaesthesia, particularly for caesar- Management:
ean section in the USA and a few European countries, oropharyngeal airway insertion, with secure taping
but not available in the UK. Used in 23% solutions. to the face.
Neurological deficits (after accidental intrathecal injec- puncture of membrane/bone is usually performed
tion) and backache have followed use of preparations within a few days, and plastic tubes inserted.
containing preservative. Maximal safe dose is about Anaesthetic management: classically, awake tracheal
15mg/kg. intubation is performed following preoxygenation,
using an oral tube and throat pack; modern manage-
Chloroquine. Antimalarial drug, also used to treat rheu- ment and general considerations are as for any
matoid arthritis. Should be used with caution in patients neonate. Extubation is performed awake.
with hepatic or renal impairment, pregnancy and epi-
lepsy. No longer recommended in falciparum malaria Choking. Acute airway obstruction in a conscious
since most strains are resistant. person. May be due to foreign body, upper airway
Dosage: pathology or strangulation. There may be wheezing,
treatment: 600mg orally, then 300mg after 6h and coughing and obvious distress; if obstruction is complete
300mg daily for 2 days. the victim is silent.
for sensitive strains of severe falciparum malaria, iv Management of choking by foreign body:
therapy may be used: 10mg base/kg iv over 8h, blind finger sweeps inside the mouth may push
then 5mg/kg 8-hourly 3. Oral therapy is started objects further down the airway and should be
when possible to a total dose of 25mg/kg. avoided.
prophylaxis: 300mg once weekly 1 week before adults:
travel and for 6 weeks after returning. - assess severity; if able to cough or speak, encour-
Side effects: GIT upset, headache, visual disturbance, age coughing while continuing to observe for
skin and hair reactions, blood dyscrasias, psychosis, deterioration.
ECG changes, neuromuscular and myopathic weak- - if unable to cough or cough is inadequate,
ness. Has a low therapeutic index and overdosage perform a series of up to five sharp slaps between
136 Cholangitis, acute

the shoulder blades, with the victim leaning should improve myasthenic crises but worsen or have no
forward. effect on cholinergic crises. Usually treated by stopping
- if this is unsuccessful, perform the Heimlich acetylcholinesterase inhibitor therapy, giving atropine,
manoeuvre (or upper abdominal thrusts aiming and providing respiratory support if required.
towards the diaphragm if the victim is supine) up
to five times, then five back slaps, etc. Cholinergic receptors, see Acetylcholine receptors
- if the victim becomes unconscious or has a respi-
ratory arrest, start CPR. Cholinesterase, plasma (Pseudocholinesterase). Circu-
children: as for adult management but chest thrusts
lating enzyme produced by the liver, of unknown primary
are performed in children < 1 year; abdominal function but which hydrolyses suxamethonium. Removes
thrusts may cause visceral rupture in infants. choline groups to produce first succinylmonocholine and
European Resuscitation Council (2010). Resuscitation; then succinic acid. Also present in other tissues, e.g. brain
81: 121976 and kidneys.
Reduced enzyme activity causes prolonged paralysis
Cholangitis, acute. Acute bacterial infection of the after suxamethonium, and may be due to:
biliary tract. Varies from mild illness to acute fulminant inherited atypical cholinesterase. Several autosomal
cholangitis, with 50% mortality. Almost always associ- recessive genes have been identified, using the
ated with complete or partial biliary obstruction, e.g. degree of enzyme inhibition by various substances
caused by gallstones or surgery. May occur in critically (e.g. dibucaine or fluoride) to describe the enzyme
ill patients as an unsuspected cause of SIRS. characteristics:
Features:
- normal enzyme (designated E1u): 94% of the
Charcots triad: fever, abdominal pain and jaundice;
population are homozygotes. Dibucaine number
occurs in 60% of cases. (DN) is 7585, and fluoride number (FN) 60.
increased bilirubin, alkaline phosphatase and trans-
- atypical enzyme (E1a): 0.03% of the population
aminases in 90% of cases. are homozygotes, with DN 1525 and FN 20.
positive blood culture (most commonly Escherichia
- silent gene (E1s): 0.001% of the population are
coli, enterococci, klebsiella) in 45% of cases. homozygotes, with no plasma cholinesterase
Ultrasound and/or hepatobiliary scanning may confirm activity.
the diagnosis. - fluoride-resistant enzyme (E1f): 0.0001% of the
Management:
population are homozygotes; DN is 6575 but
supportive: iv fluids, O2 therapy, analgesia, antibac-
FN is 30.
terial drugs. Full ICU support may be required in Paralysis may last 24h in homozygotes for silent
fulminant cases. and atypical genes, and 12h in homozygotes for
emergency percutaneous, open or endoscopic gall-
the fluoride-resistant gene. In addition, heterozy-
bladder drainage. gotes with one normal and one abnormal gene (e.g.
[Jean M Charcot (18251893), Paris neurologist] E1u/E1a; 5% of the population) with DN 4060
may show prolonged paralysis of about 1020min.
Cholecystitis, acute. Inflammation of the wall of the Most of these have the atypical gene. Combinations
gallbladder. A recognised complication of critical illness, of abnormal genes comprise less than 0.01% of the
it may occur in the absence of gallstones. Aetiology population and also show slight or marked prolon-
includes gallbladder ischaemia, biliary sludging and gation of paralysis.
cystic duct obstruction; contributory factors include acquired deficiency of normal cholinesterase, e.g. in
fever, sepsis, dehydration, opioid analgesic drugs and hepatic failure, hypoproteinaemia, pregnancy, mal-
TPN. Mortality may be 50%. nutrition, burns and following plasmapheresis.
Features:
inhibition of cholinesterase by drugs, e.g. echothio-
fever, leucocytosis, abdominal pain/tenderness and
phate, cyclophosphamide, tetrahydroaminocrine,
loss of bowel sounds. hexafluorenium or phenelzine.
increased alkaline phosphatase and bilirubin in
Plasma cholinesterase also hydrolyses other drugs, e.g.
50% of cases. mivacurium, ester local anaesthetic drugs, diamorphine,
diagnosis is confirmed by ultrasonography and hep-
aspirin and propanidid. Although esmolol and remifen-
atobiliary scanning. tanil are readily hydrolysed by non-specific cholinester-
Management:
ases, plasma cholinesterase itself is not important in their
broad-spectrum antibacterial drugs to cover aerobic
breakdown.
and anaerobic organisms.
emergency percutaneous, endoscopic or open drain-
age of the gallbladder may be required if clinical Chronic bronchitis, see Chronic obstructive pulmonary
deterioration continues despite antibacterial disease
therapy.
See also, Biliary tract Chronic obstructive airways disease (COAD), see
Chronic obstructive pulmonary disease.
Cholinergic crisis. Syndrome caused by relative over-
dose of acetylcholinesterase inhibitors causing excess Chronic obstructive pulmonary disease (COPD;
nicotinic (muscle weakness, fasciculation) and musca- Chronic obstructive airways disease; COAD). Term
rinic (sweating, miosis, lacrimation, abdominal colic) encompassing chronic bronchitis and emphysema, which,
stimulation by acetylcholine. May occur in myasthenia although different histologically, often coexist. The main
gravis, when differentiation from myasthenic crisis may features are lower airway obstruction, hyperinflated
be difficult. Administration of edrophonium 2mg iv lungs and impaired gas exchange.
 Ciclosporin 137

Chronic bronchitis: blood gas interpretation and lung function tests

defined clinically by productive cough each morning may be useful.
for at least 3 months per year, for at least 2 succes- - improvement by physiotherapy and antibiotics
sive years. if infection is present, and bronchodilator drugs
results from chronic bronchial irritation (e.g. by if there is a reversible element to airway
smoke, dust or fumes), causing mucosal hypersecre- obstruction.
tion, mucosal oedema and bronchoconstriction. - premedication: increased sensitivity to respiratory
features: cough, dyspnoea, wheeze, tendency to depressants, especially in chronic bronchitis, is
develop chest infection causing acute exacerbations. rarely a problem. Pethidine, promethazine and
Sufferers are typically described as blue bloaters atropine are often used; the latter may help
because of cyanosis and oedema. prevent perioperative bronchospasm and reduce
FEV1, expiratory flow rate and FEV/FVC are secretions, but may increase their tenacity.
decreased, with increased residual volume and perioperatively:
FRC, and V/Q mismatch. - regional techniques are often suitable; problems
hypoxaemia and hypercapnia result, with possible may include inability to lie flat, possibility of
loss of the central response to CO2 (the mechanism coughing and sensitivity to sedative drugs if used.
is unclear). Hypoxic pulmonary vasoconstriction - general anaesthesia:
may lead to pulmonary hypertension with cor pul- - inhalational techniques with a facemask are
monale and right ventricular failure. suitable for short procedures, with minimal
Emphysema: airway manipulation.
defined histologically by dilated alveoli and/or - if tracheal intubation is undertaken, topical or
respiratory bronchioles, often in upper areas of the iv lidocaine may be used to reduce irritation
lungs. Different patterns of dilatation are identified. by the tracheal tube. Tracheal suction is often
Elastic recoil is reduced. required. Bronchospasm and coughing may
causes: as above, plus 1-antitrypsin deficiency; the occur. Capnography allows maintenance of
latter typically affects the lung bases. expired PCO2 at the patients normal (i.e. preop-
features: dyspnoea. Air trapping and increased erative) level.
airflow resistance result from airway collapse during - IPPV may cause expansion/rupture of emphy-
forceful expiration. Breath sounds are usually quiet. sematous bullae and hypotension.
Sufferers are typically described as pink puffers - drugs causing histamine release are usually
because of absent cyanosis and marked dyspnoea. avoided.
work of breathing is markedly increased, with hypo- postoperative problems include:
capnia (i.e. hyperventilation as opposed to hypo - sputum retention, bronchospasm, atelectasis
ventilation as in chronic bronchitis), but only mild and infection. Physiotherapy and bronchodila-
hypoxaemia. tor therapy are important. Respiratory failure
FEV1 is reduced and FRC increased, as above. may occur. Doxapram may be useful. Ventila-
Diffusing capacity is decreased in both conditions. tion is often improved in the sitting position.
Respiratory muscle fatigue may be a factor. - hypoventilation may be exacerbated by pain,
Patients may present with respiratory failure requir- depressant drugs and high FIO2. Adequate post-
ing non-invasive positive pressure ventilation or operative analgesia is vital; regional techniques
IPPV on ICU/HDU. Main considerations: are particularly useful, as excessive use of sys-
the decision to intubate/ventilate is sometimes dif- temic opioids must be avoided. Parenteral
ficult, since weaning from ventilators may be impos- opioids should be given cautiously.
sible. Useful information in making the decision - patients with severe disease or those receiving
concerning IPPV: spinal opioids should be managed on ICU/
- level of normal activity and lifestyle. HDU.
- previous admissions, whether ventilated and ease - elective IPPV may allow adequate gas
of weaning. exchange whilst depressant anaesthetic drugs
- whether the current crisis represents gradual are cleared. It also covers the period of worst
decline or an acute treatable event, e.g. superim- postoperative pain and allows stabilisation
posed acute infection. before weaning.
management is as for respiratory failure. Doxapram
may be used in an attempt to prevent the require-
Churchill, Frederick, see Liston, Robert
ment for IPPV: 1.54mg/min according to response,
with frequent arterial blood gas interpretation.
IPPV via a tightly fitting mask is increasingly used Ciclosporin (Cyclosporin). Isomerase-binding immuno-
for acute exacerbations of COPD. Minitracheotomy suppressive drug which interferes with proliferation of
or tracheostomy may assist weaning. activated T lymphocytes. Main use is to prevent and treat
Anaesthetic management: rejection following organ transplantation. Has also been
preoperatively: used in myasthenia gravis and other autoimmune dis-
- preoperative assessment for exercise tolerance, eases. Oral administration has 30% bioavailability.
bronchospasm, cor pulmonale and history of pre- Eliminated via hepatic metabolism, its half-life
vious admissions. Patients are likely to be smokers; assuming normal liver function is 19h.
thus cardiovascular assessment including ECG is Dosage: 25mg/kg/day iv, followed by 1215mg/kg/
important. CXR may reveal a hyperexpanded day orally. After 12 weeks, the dose is reduced by
chest, flattened diaphragm, narrow mediastinum, 510% per week. Therapeutic blood levels vary
emphysematous bullae or infection. Arterial between centres and should be monitored.
138 Cigarette smoking

Side effects: Ciprofloxacin. 4-Quinolone type antibacterial drug;

reduces GFR by at least 20% in almost all patients; acts by inhibiting bacterial DNA replication. Has a
renal function returns to normal within 2 weeks of broad spectrum of activity, but especially against Gram-
stopping the drug, even following prolonged use. negative bacteria, including klebsiella, Escherichia,
Irreversible nephrotoxicity occurs in a minority of Salmonella, Shigella, Campylobacter, Neisseria, Pseudo-
cardiac and renal transplant patients. monas, Haemophilus and Enterobacter species. Less
GIT upset, gum hyperplasia, hirsutism, hyperkalae- active against Gram-positive bacteria (e.g. Streptococ-
mia, mild hepatic impairment, hypertension, tremor, cus) and anaerobes. Also active against Chlamydia and
occasionally convulsions and encephalopathy. certain mycobacteria.
interacts with other drugs that cause hyperkalaemia Dosage:
or nephrotoxicity, and increases plasma concentra- 250750mg orally bd.
tions of several drugs, including diclofenac and 200400mg iv bd (given over 3060min).
digoxin. Side effects:
GIT upset, skin reactions, renal/hepatic impairment,
tendon inflammation/damage; less commonly, blood
Cigarette smoking, see Smoking
dyscrasias, haemolytic anaemia, convulsions.
may enhance the effects of theophyllines and
Ciliary activity. Continuous beating of the cilia of respi- warfarin.
ratory epithelial cells results in flow of thick mucus from
the nose to the pharynx, and from the bronchi to the Circle of Willis, see Cerebral circulation
larynx. The mucus is then swallowed or expectorated. A Circle systems. Anaesthetic breathing systems incorpo-
more watery mucus layer lies between the thick layer rating unidirectional valves and CO2 absorption with
and the epithelium, lubricating the cilia. Important in soda lime. First used by Sword in 1926.
aiding removal of foreign particles and microbes and Features:
clearing of the airways. Reduced by smoking, extremes consist of CO2 absorber, two one-way valves, adjust-
of temperature, volatile inhalational anaesthetic agents, able pressure-limiting (APL) valve, reservoir bag,
opioid analgesic drugs and prolonged exposure to high tubing to and from the patient and for fresh gas
O2 levels. Prolonged inhalation of dry gases, anticholin- supply (FGF). Efficiency is increased by placing:
ergic drug administration and volatile agents may impair - FGF downstream to APL valve (avoids venting
mucus production or flow. of fresh gas).
Patients with inborn deficiency of cilia protein - bag and patient on opposite sides of the one-way
are predisposed to bronchiectasis; if associated with valves (maintains circulatory gas flow).
decreased spermatic activity, situs inversus and chronic Examples of arrangements (Fig. 42): system A is
sinusitis, this constitutes Kartageners syndrome. efficient for spontaneous ventilation and IPPV;
[Manes Kartagener (18971975), Swiss physician] dead space gas is conserved beyond the APL valve
during expiration whilst alveolar gas is flushed by
Cimetidine. H2 receptor antagonist, of faster onset and FGF via the APL valve. System B is less efficient
shorter-acting than ranitidine, lasting about 4h. Half-life because the APL valve is further away from the
is 2h; up to 5h in renal failure. patient; dead space and alveolar gases mix more
Dosage: before reaching it. System B is more convenient
400mg orally od/bd. Effective if given 90min practically, however, since all components are away
preoperatively. from the patient.
200mg im/iv by infusion (may cause bradycardia ready-assembled circle systems are usual now,
and hypotension after rapid iv injection). arranged as in system B within one housing. Older
Side effects: systems had a switch that could bypass the soda
gynaecomastia, rarely impotence (binds to andro- lime; to prevent this happening accidentally these
gen receptors). are not present on newer systems.
hepatic enzyme inhibition (binds to microsomal resistance is reduced by using wide-bore tubing.
cytochrome P450). The actions of drugs such as war- Advantages:
farin, phenytoin and theophylline may be pro- low gas flows may be used, allowing conservation of
longed, and toxic effects seen. volatile agent with reduced cost and pollution.
confusion, especially in the elderly and very ill.
rarely, liver impairment and blood dyscrasias.
System A System B

Cinchocaine hydrochloride. Amide local anaesthetic Patient Patient

agent, synthesised in 1925. Formerly widely used in the
UK for spinal anaesthesia, in doses of 0.52.0ml of
1:200 in 6% dextrose heavy solution. Now unavailable
except in compound ointments for haemorrhoids. Has
been used for epidural anaesthesia (1:600 solution),
infiltration and nerve blocks (1:10002000 with adrena-
line), and surface analgesia, up to 2mg/kg maximum. Of
slower onset and duration of action than lidocaine, and Absorber Absorber
FGF FGF
more toxic.
Used to estimate plasma cholinesterase activity
(dibucaine number). Fig. 42 Examples of circle systems (see text)
 ClapeyronClausius equation 139

reduced risk of explosions and fires with inflam- greatest, unless high FGFs are used. The time to
mable agents. reach equilibrium is least for less soluble agents.
warmth and humidity of expired gases are retained, - in circle (VIC):
with further warming and humidification in the CO2 - low-resistance vaporisers are required, e.g.
absorber, although efficiency is reduced by passage Goldmans (see Vaporisers). Delivered concen-
through lengths of tubing. tration is related to gas flow through the
spontaneous/controlled ventilation is easily per- vaporiser.
formed without changing the system. - as volatile agent is present in exhaled gas
allows easy monitoring of O2 uptake/CO2 output. entering the vaporiser, high concentrations are
Disadvantages: possible. During spontaneous ventilation, respi-
production of carbon monoxide may occur when ratory depression increases as the concentration
volatile agents containing the CHF2 moiety (desflu- increases, reducing gas flow through the vapo-
rane, enflurane or isoflurane) are passed over dry riser. Thus dangerous levels of agent are not
warm absorbent (especially baralyme), e.g. at the reached. During IPPV, this feedback mecha-
start of a Monday morning operating session fol- nism is absent; i.e. dangerous levels are
lowing prolonged passage of dry gas through the attainable.
absorber. - liquid anaesthetic may be injected directly into
accumulation of other substances in the system the tubing.
(especially if very low fresh gas flows are used over [Brian Sword (18891956), US anaesthetist]
a long time): alcohol derived from the patient; com-
pound A and bromochlorodifluoroethylene follow- Circulation, respiration, abdomen, motor and speech
ing use of sevoflurane and halothane respectively; scale (CRAMS scale). Trauma scale for use in adult
acetone in some starved patients. None of these has pre-hospital triage when categorising severity of injury.
been associated with adverse clinical effects. Scores of 2 (normal), 1 or 0 are assigned to each of the
higher resistance and thus work of breathing. five systems assessed. Rarely used in isolation now.
bulky equipment. Gormican SP (1982). Ann Emerg Med; 11: 1325
slow changes in anaesthetic concentrations at low
gas flows. Cisapride. Prokinetic drug chemically related to meto-
risk of hypoxic gas mixtures if N2O is used. clopramide but without antidopaminergic activity or
more connections to come apart and valves to CNS-depressant effects. Increases lower oesophageal
stick. pressure and increases gastric emptying and intestinal
Use: motility. Acts by increasing acetylcholine release in the
if N2O is used, nitrogen contained in the lungs and myenteric plexus. Reverses morphine-induced gastric
dissolved in the body will be washed out; build-up stasis. Withdrawn from use in July 2000 because of
of nitrogen in the system may lead to a low FIO2. A reports of serious ventricular arrhythmias, often result-
high initial FGF (57 l/min) for 710min is suffi- ing from concomitant use of other drugs such as antifun-
cient to remove most body nitrogen. N2O concen- gal and antibacterial drugs.
tration within the system as its uptake decreases
may also contribute to low FIO2. Cisatracurium besylate. Non-depolarising neuromus-
if only O2 is used, hypoxic mixtures do not occur, cular blocking drug, one of the 10 stereoisomers of atra-
but absorption atelectasis and O2 toxicity are more curium (the 1R cis-1R cis isomer; makes up 15% of
likely. atracurium, contributing about 60% of its activity).
with high flow, the APL valve is open. Introduced in 1995, it causes minimal histamine release
low flow is defined as < 11.5 l/min FGF: with cardiovascular stability. Also, although up to 70%
- APL valve totally closed: FGF supplies basal metabolised by Hofmann elimination (cf. atracurium,
requirements only, i.e. 220250ml/min O2 (closed 5060%), produces about 10 times less laudanosine than
system). atracurium after prolonged infusion, because of its
- APL valve slightly open, i.e. allowing a small leak: greater potency and thus smaller total dosage. Initial
13 l/min is often used as a compromise between dose: 0.10.2mg/kg. Intubation is possible approxi-
the closed and high-flow systems (semi-closed). mately 120s after a dose of 0.15mg/kg. Effects last 30
IPPV is achieved by hand or by switching the res- 40min. Supplementary dose: 0.03mg/kg. Has been given
ervoir bag to a bellows which may be compressed by iv infusion at 0.060.18mg/kg/h (13mg/kg/min).
intermittently by an integral ventilator (if present Storage requirements are as for atracurium. Faster deg-
in the anaesthetic machine). If there is no integral radation occurs when diluted in Hartmanns solution
ventilator, a suitable ventilator (e.g. Penlon Nuff- and 5% dextrose than in other iv fluids.
ield) may be attached to the reservoir bag attach- See also, Isomerism
ment by tubing of adequate length to prevent
mixing of the driving gas (O2) and the FGF. Citrate and citrate solutions, see Blood storage;
continuous gas analysis is particularly important. Sodium citrate
vaporisers:
- out of circle (VOC): CJD, see CreutzfeldtJakob disease
- usual plenum vaporisers are used on the back
bar of the anaesthetic machine. ClapeyronClausius equation. Equation characterising
- the concentration of volatile agent within the the discontinuous phase change between two states of
circle is less than that delivered by the vaporiser, matter. Describes the relationship between SVP, tem-
because of dilution by exhaled gas. The differ- perature and latent heat (LH). Used practically to
ence is highest initially, when uptake of agent is predict changes in state in response to alterations in
140 Clark electrode

pressure/temperature. Assumes LH is independent of Clearance, creatinine, see Creatinine clearance

temperature, and that the volume of liquid is negligible
compared to that of the vapour. Clearance, free water. Volume of plasma cleared of
[Benoit-Paul Clapeyron (17991864), French engineer; solute-free water per minute. Equals urine volume (ml/
Rudolf Clausius (18221888), German physicist] min) minus osmotic clearance (ml/min). Normally nega-
tive, i.e. water is being conserved, and hypertonic urine
Clark electrode, see Oxygen measurement produced. Positive in water diuresis.
See also, Clearance, osmotic
Clarke, William E (18181878). US physician; used
diethyl ether to allow dental extraction in January 1842
in New York, but only reported this after Mortons dem- Clearance, osmotic. Volume of plasma cleared of solute
onstration in 1846. per unit time. Equals:
urine osmolality (mosmol/l) urine volume (ml/min)
Clarithromycin. Macrolide, antibacterial drug derived plasma osmolality (mosmol/l)
from erythromycin and with similar mechanism of action
and spectrum of activity, although more active against If urine is hypotonic, urine volume exceeds osmotic
Streptococcus pneumoniae and Staphylococcus aureus, clearance; if hypertonic, osmotic clearance is greater.
and with greater penetration of tissues. GIT side effects The difference between them is free water clearance.
are less common than with erythromycin. Normally under 3ml/min; increased by osmotic
Dosage: 250500mg orally or 500mg iv bd.
diuretics.
Side effects: nausea, vomiting, hepatic impairment,
See also, Clearance, free water
phlebitis, StevensJohnson syndrome.
Cleft lip and palate, see Facial deformities, congenital
Clathrates. Compounds comprising a crystal lattice
of one type of molecule trapping and containing another. Clindamycin. Bacteriostatic antibacterial drug, a semi-
Formation of clathrates consisting of volatile agent synthetic derivative of lincomycin. Although active
and water (gas hydrates) in neuronal cell membranes against aerobic and anaerobic Gram-positive organisms,
(thereby disrupting their function) was suggested by its use is limited to the treatment of staphylococcal bone
Pauling and Miller in 1961 as a basis for the mechanism and joint infection, peritonitis and endocarditis because
of action of inhalational anaesthetic agents. of its side effects (especially infection with Clostridium
Now considered incorrect since: difficile and the development of pseudomembranous
for some fluorocarbons, potency is not related to colitis). 95% protein-bound, it undergoes hepatic
clathrate formation. metabolism to inactive metabolites, with 20% excreted
some inhalational agents do not form clathrates at unchanged in the urine. Poor levels are attained in CSF.
body temperature and pressure. Dosage:
effects of combining different agents are not 150450mg orally qds.
accounted for. 0.64.8g/day in 24 divided doses im or by iv infu-
[Linus Pauling (19011994) and Stanley L Miller (1930 sion (maximal single iv dose 1.2g).
2007), US chemists] Side effects: GIT upset, pseudomembranous colitis,
See also, Anaesthesia, mechanism of hepatic impairment, rashes, blood dyscrasias, pain on
injection, thrombophlebitis.
Clavulanic acid. -Lactamase inhibitor, used in combi-
nation with amoxicillin (as co-amoxiclav) and ticarcillin
in order to prevent their breakdown by penicillinase Clinical governance. Term denoting a particular aspect
produced by Staphylococcus aureus and other bacteria. of risk management and quality assurance in which
Has been associated with cholestatic jaundice. responsibility for maintaining standards of care is
defined and placed with specified individuals and depart-
Clearance. Theoretical value representing removal of a ments. In the NHS, the chief executive of each Trust is
substance from plasma or blood by passage through an responsible for the care provided, although each depart-
organ. Defined as the volume of plasma completely ment is expected to take steps to ensure high standards
cleared of a given substance per unit time. Thus for the and both detect and act upon deficiencies at individual
kidney it equals (in ml/min): and departmental levels. Requires that evidence-based
medicine is in routine use, that good practice and innova-
amount of substance excreted in urine per unit time tions are systematically disseminated and applied, and
plasma concentration of substance that high-quality data are collected to monitor clinical
urinary concentration urine volume care. Two bodies were set up in 1999 to monitor these
processes: the National Institute for Clinical Excellence
(mmol/l) (ml/min)
= (NICE) and the Commission for Health Improvement
plasma concentration (mmol/l) (CHI), (subsequently the Healthcare Commission). The
The concept is useful in comparing excretion rates of concept arose formally from political and medical reac-
different drugs; it is also used to determine renal blood tions to well-publicised examples of inadequate care, its
flow and GFR. introduction achieving particular impetus following the
If there is incomplete removal by the kidney, clear- high death rate after paediatric cardiac surgery in Bristol
ance for a substance is less than GFR. If the substance in the 1980s/early 1990s. As a result of disciplinary
is secreted into the urine by tubular cells, clearance rulings following this case, all clinicians are now expected
exceeds GFR. to monitor their own performance and undergo regular
See also, Pharmacokinetics appraisal and revalidation.
 Clopidogrel besilate/hydrochloride/hydrogen sulphate 141

Clinical trials. Performed to determine whether an - if any predetermined stopping criteria are met,
intervention is useful, how it compares with others, e.g. the treatment is found to have drastically
whether it affects different groups of patients differently superior or inferior outcomes compared with
and how it is best delivered (e.g. drug dosage regimen, control.
route, timing). See also, Drug development; Meta-analysis; Statistics
Setting up a trial:
aims of the trial are defined. Clomethiazole edisylate (Chlormethiazole). Sedative
the number of patients is defined; ideally, the drug, structurally related to vitamin B1. Has been used
number is calculated by first defining the size of for sedation and as an anticonvulsant drug, e.g. in pre-
difference considered clinically important, and then eclampsia. Traditionally used to treat acute alcohol with-
the sample size required to enable such a difference drawal syndromes. No longer available for iv use because
to be revealed if present (i.e. power analysis). of the risk of severe CVS/RS depression.
Groups should usually be of equal size if possible. Dosage: 14 capsules (equivalent to 520ml elixir
subjects: which contains 50mg/ml) orally, 34-hourly.
- patients with other diseases and those taking Side effects: nasal irritation, GIT upset, headache,
other drugs are excluded where possible. agitation.
- controls:
- pairs may be matched for age, sex, race, degree Clonazepam. Benzodiazepine, used mainly to treat epi-
and duration of illness and one of each pair lepsy. Has also been used in disorders of movement (e.g.
assigned to each treatment. dystonias) and as an adjunct to pain management. Has
- cross-over studies: patients act as their own con- similar effects to diazepam. 50% protein-bound after iv
trols by receiving first one treatment then injection. Metabolised in the liver and excreted in the
another. The effect of the first treatment on the urine. Elimination half-life is 2448h.
second must be excluded. Dosage:
- randomisation into groups. 18mg/day orally in adults, titrated to response.
- historical controls are avoided where possible. 0.251mg/day in infants.
- treatment is compared with no treatment, 0.51mg diluted in water for iv injection.
placebo or existing treatment. Side effects include sedation (occasionally excita-
bias is further reduced by blinding: tion), bronchial and salivary hypersecretion, and,
- single-blind (patient is unaware of group rarely, hepatic impairment and blood dyscrasias.
allocation).
- double-blind (care-provider and patient are Clonidine hydrochloride. -Adrenergic receptor
unaware). agonist, used as an analgesic, sedative and antihyperten-
- triple-blind (as double-blind, plus those assessing sive drug. Previously used in the prophylaxis of migraine.
outcome data are unaware) Licensed in the USA for use via the epidural route for
variability is reduced by using the same location, pain therapy. Has also been used as an adjuvant drug in
time of day, medical/nursing staff and technique for spinal anaesthesia and peripheral nerve blockade.
all patients. Stimulates central presynaptic 2-adrenergic recep-
approval by a Research Ethics Committee: includes tors, causing suppression of catecholamine release (i.e.
qualified and lay persons. Considers whether expo- activates a negative-feedback control system). Its main
sure of patients to the new treatment or denial of effect is on vasomotor centre output, but also has anal-
the old treatment to controls, or vice versa, is justi- gesic and sedative actions. It reduces MAC of inhala-
fied, whether adequate information is given to tional anaesthetic agents and postoperative analgesic
potential participants, and whether proper consent requirements. May have some 1-agonist action periph-
is obtained. No patient should be worse off than if erally, causing initial transient hypertension.
the trial were not running. Its half-life is about 23h. Metabolised in the liver,
approval is also required from the institution (e.g. with about 65% excreted unchanged in the urine and
Trust Research and Development Department) and 20% in the faeces.
regulatory authorities if drugs or devices are Dosage:
involved (in the UK, the Medicines and Healthcare 150300g/day orally in divided doses, up to 1.2mg.
products Regulatory Agency; in the USA, the Food 150300g by slow iv injection. Effects occur within
and Drug Administration). 10min, and last 37h. Transient hypertension and
data: bradycardia may occur.
- what to measure, according to defined aims. 30g/h via epidural route, adjusted according to
- objective measurements are less prone to observer response (boluses of 100300mg have been used
bias than subjective assessment. for acute pain, although not licensed for this use).
- how many measurements; measurement of too Hypotension may occur.
many variables increases the likelihood of at least Side effects: sedation, dry mouth, depression, urinary
one being significantly different due to chance retention, reduced gastric motility. Rebound hyper-
alone. tension can occur if it is suddenly withdrawn.
- which statistical test to use, and how to express
results, e.g. use of the null hypothesis or confi- Clopidogrel besilate/hydrochloride/hydrogen sul-
dence intervals. phate. Thienopyridine antiplatelet drug, used for the
end-point of the trial: treatment of acute coronary syndromes, secondary pre-
- according to the numbers studied. vention of ischaemic events or primary prevention in
- sequential analysis: the trial stops when results patients with atrial fibrillation for whom warfarin is
attain significance. unsuitable. Usually combined with aspirin. Recently
142 Closing capacity

shown to be less effective than newer antiplatelet drugs, increased intrathoracic pressures, e.g. asthma.

e.g. prasugrel, ticagrelor. smoking.

Oral bioavailability is approximately 50% but is CC may encroach upon a FRC reduced by obesity, the
highly variable. Clopidogrel itself is an inactive prodrug; supine position and anaesthesia. PEEP and CPAP may
it is converted to an active metabolite by P450 cytochrome reduce airway closure.
oxidase system (mostly CYP3A4/5). Has reduced activ- Drummond GB, Milic-Emili J (2007). Br J Anaesth; 99:
ity when given with other CYP3A substrates (e.g. ator- 7724
vastatin) and increased activity with P450 enzyme inducers
(e.g. rifampicin). The active metabolite is rapidly excreted Closing volume, see Closing capacity
in bile and urine but irreversibly antagonises platelet
P2Y12 ADP receptors, thereby inhibiting ADP-mediated Clostridial infections. Caused by bacteria of the genus
platelet aggregation by blocking the glycoprotein IIb/ Clostridium. They are Gram-positive, anaerobic, spore-
IIIb pathway. Restoration of platelet function requires forming and toxin-producing. Species include:
synthesis (or transfusion) of new platelets. Withdrawal C. perfringens: causes gas gangrene.
for a week before surgery has been recommended C. tetani: causes tetanus.
(unless the patient has coronary artery stents in situ see C. botulinum: causes botulism.
Percutaneous coronary intervention for details). C. difficile: causes pseudomembranous colitis.
Dosage:
Bobo LD, Dubberke ER, Kollef M (2011). Chest; 140:
acute coronary syndromes: 300mg orally initially
164353
followed by 75mg od.
prevention of ischaemic events: 75mg orally od.
Side effects: bleeding, GI upset, rash, rarely throm- Clover, Joseph Thomas (18251882). Pioneering English
botic thrombocytopenic purpura. anaesthetist. A medical student at University College
Hospital, London, said to have been present at Listons
Closing capacity. Lung volume at which airway closure historic operation in 1846. Devised inhalers for chloro-
occurs, mainly in the dependent parts of the lung. Equals form and later diethyl ether that delivered accurate con-
closing volume plus residual volume. In fit young adults, centrations of agent. Also described the use of N2O,
closing capacity (CC) is considerably less than FRC; thus alone or in combination with volatile agents.
airway closure does not occur during normal quiet Buxton DW (1923). Br J Anaesth; 1: 5561
breathing. Airway closure occurring within FRC results
in increased shunt. Cm, see Minimal blocking concentration
Measurement: inspiration of a bolus of marker gas
(e.g. helium, He) at the end of maximal expiration (i.e. CMACE, Centre for Maternal and Child Enquiries, see
residual volume), followed by inspiration of air to Confidential Enquiries into Maternal Deaths
total lung capacity (Fig. 43). Expired He concentra-
tion is measured during slow expiration: the same CMRO2, see Cerebral metabolic rate for oxygen
phases are seen as in Fowlers method (which may
also be used to measure CC). Initially, dead space gas
CMV, see Cytomegalovirus
is exhaled, containing no He. Then, a mixture of dead
space and alveolar gas, followed by alveolar gas. As
CC is reached there is a sharp rise in expired He; this COAD, Chronic obstructive airways disease, see Chronic
is because the alveoli that are still open at CC contain obstructive pulmonary disease
a higher concentration of He than the mean (because
they received a larger amount of the initial inspired Coagulation. Clot formation; follows vasospasm and
bolus). platelet plug formation, which cause temporary
Increased by: haemostasis.
age: CC = FRC in neonates and infants. Normal sequence of events:
CC = FRC in the supine position at 40 years. vasospasm, thought to be mediated by vasoconstric-
CC = FRC in the upright position at 65 years. tor substances released from platelets, e.g. 5-HT and
thromboxane.
platelet plug: platelets are attracted by collagen
exposed by damaged vascular endothelium. Adher-
ence is followed by release of 5-HT and ADP, the
latter causing further aggregation.
Helium concentration

clot formation: the platelet plug is bound by resul-

tant fibrin to form the definitive clot. Clot retraction
is caused by platelet contractile microfilaments. The
classical explanation of the coagulation pathway
involves many circulating factors in a cascade mech-
anism; each factor, when activated, activates the
next in turn (Fig. 44). Most are produced by the
liver. Nomenclature of factors is largely historical,
0 Closing Residual according to the chronological order of discovery.
capacity volume The intrinsic pathway is initiated by exposure of
Volume blood to collagen, or in vitro by contact with glass,
e.g. test tubes. The extrinsic pathway is initiated by
Fig. 43 Measurement of closing capacity substances released from damaged tissues. Each
 Coagulation disorders 143

Intrinsic pathway Extrinsic pathway

Collagen Tissue damage

XII Active XII Active VII VII

XI Active XI
Ca2+ III
Ca2+
IX Active IX
VIII
Ca2+
PL
X Active X XIII
Common pathway V
Ca2+
PL
II (prothrombin) Thrombin

I (fibrinogen) Loose fibrin

Active XIII
Ca2+

Tight fibrin
'brings about' 'becomes' PL, phospholipid

Fig. 44 Coagulation cascade

may activate the common pathway, which culmi-

Table 15 Change in prothrombin time (PT), activated partial
nates in formation of a tight fibrin clot.
thromboplastin (APPT), thrombin time (TT), fibrin degradation
More recently, a single pathway has been proposed, products (FDPs), platelet count and fibrinogen levels in various
in which tissue factor (TF; a membrane glycoprotein not coagulation disorders
normally exposed on the surface of intact blood vessels)
binds to circulating factor VII, resulting in a complex Disorder PT APPT TT FDPs Platelets Fibrinogen
(VII/TF), which then activates the coagulation cascade
mainly via factors IX and X (and thence the common Thrombocytopenia
pathway). The central role of factor VIIa is reflected in DIC
the use of its recombinant human form eptacog alfa in Heparin therapy *
haemophilia and intractable haemorrhage. Warfarin therapy
Normally, the clotting mechanism is balanced by Hepatic failure
Massive blood
opposing reactions preventing coagulation, e.g. anti-
transfusion
thrombin III (formed from activated factor X) which Primary fibrinolysis
inhibits active factors II, IX, X, XI and XII. Prostacyclin
secreted by the vascular endothelium inhibits platelet , Increase; , decrease; , no change.
aggregation. *But thrombocytopenia may follow several days of heparin therapy.
Other pathways may be involved in the coagulation Note: DIC may complicate hepatic failure and massive blood
cascade, e.g. active factor XII leads to activation of fibri- transfusion.
nolysis and kinin formation.
See also, Anticoagulant drugs; Coagulation disorders;
Coagulation studies
coagulation:

Coagulation disorders. May result in impaired coagula- - congenital, e.g. haemophilia, von Willebrands
tion or hypercoagulability. The former is more common disease (also associated with blood vessel and
and may arise from defects in: platelet defects).
blood vessels: - heparin, warfarin, hepatic failure, vitamin K defi-
- infection, e.g. meningococcal disease, sepsis. ciency, DIC.
- metabolic disease, e.g. hepatic failure, renal - increased fibrinolysis.
failure, scurvy. Blood transfusion may be associated with dilution of
- congenital, e.g. hereditary telangiectasia. platelets and coagulation factors by fluids and blood
platelets: components deficient in them. Impaired organ function
- thrombocytopenia. and DIC may contribute.
- DIC. Diagnosed by the underlying problem, aided by coag-
- impaired function, e.g. antiplatelet drugs. ulation studies (Table 15).
144 Coagulation studies

Treatment: of coagulation is avoided by using non-wettable

of underlying disease. plastic tubes. Normal plasma is used as a control:
administration of appropriate blood products. - prothrombin time (PT): tests the extrinsic and
Abnormal hypercoagulability may lead to recurrent common pathways. Plasma, then calcium, is added
DVT and PE. It may result from: to brain extract and phospholipid. Normal value
primary disorders: is 1115s. International Normalised Ratio (INR;
- protein C deficiency: protein C is a circulating formerly British Ratio) is the ratio of sample time
anticoagulant protein; when activated by throm- to a standard. A target ratio of 22.5 is used for
bin it inactivates factors V and VIII. Deficiency prophylaxis of DVT with warfarin; 23 for treat-
(the extent of which is variable) thus results in ment of DVT, PE and transient ischaemic attacks;
increased tendency to thrombosis. 34.5 for prophylaxis of recurrent DVT or PE,
- protein S deficiency: protein S is a cofactor and for patients with prosthetic heart valves and
for protein C; deficiency also results in other arterial prostheses. A ratio of 1.5 is consid-
thrombophilia. ered safe for surgery.
- activated protein C resistance: inherited abnor- - activated partial thromboplastin time (APTT;
mality of factor V, resulting in resistance to also partial thromboplastin time with kaolin,
cleavage by protein C. A particular form of PTTK): tests the intrinsic and common pathways.
factor V, factor V Leiden, is present in about 2% Plasma, phospholipid and calcium are added to
of Northern European individuals; the risk of kaolin. Normal value is 3540s. A target ratio of
thrombosis in homozygotes is estimated at up 24 compared with normal plasma is used for
to 50%. treatment of DVT or PE with heparin. A ratio of
- antithrombin III deficiency: may result in throm- 1.5 is considered safe for surgery.
bophlebitis, thrombosis and PE. - mixture tests: if PT or APTT is prolonged, the
- others, e.g. prothrombin gene variants, deficiency patients plasma may be mixed with normal
of fibrinolytic components or factor XII. plasma and the test repeated. If the test is normal,
secondary to malignancy, pregnancy, diabetes mel- factor deficiency is present; if still prolonged,
litus, platelet and vessel wall abnormalities, hyper- the sample plasma contains an inhibitor, e.g.
viscosity and venous stasis. Circulating inhibitors antibody.
(lupus anticoagulant and anticardiolipin antibod- - specific factor assays, e.g. factor VIII assay.
ies) may develop spontaneously or in patients with - reptilase time (RT): snake venom is added to
SLE, resulting in the antiphospholipid syndrome. In plasma, converting fibrinogen to fibrin. Unaf-
this condition, activated partial thromboplastin fected by heparin; thus if normal but the thrombin
time may be prolonged, although patients are at time is prolonged, presence of heparin is sug-
increased risk of thrombosis, possibly related to gested. A prolonged RT suggests fibrinogen
inhibition of factor XII activation or prostacyclin deficiency.
production from vascular endothelium. platelets:
[Leiden; city in the Netherlands where the factor was - platelet count: normally 150400 109/l.
first identified in 1993] - bleeding time: a standard incision is made on the
Martlew VJ (2000). Br J Anaesth; 85: 44655 forearm using a pricking device or template; a BP
cuff is inflated around the upper arm to 40mmHg.
Coagulation studies. May test different parts of the The incision is dabbed with filter paper every 30s
coagulation pathways: until the bleeding stops. Normal value is 29min.
whole blood coagulation: Susceptible to considerable variation; therefore
- whole blood clotting time: bedside test of intrin- infrequently used.
sic and common pathways (i.e. spontaneous - commercially available devices: used as a rapid
coagulation occurring in a glass tube without indicator of coagulation status, e.g. during liver
external reactive substances, e.g. tissue fluid). transplantation:
1 ml blood is added to each of three glass tubes, - thromboelastography (TEG).
kept at body temperature. The first is tilted every - Sonoclot: a tubular probe oscillates up and
15 s until clotted, then the second, third, etc. The down within the sample and the resistance to
time until the third is clotted is normally about motion encountered is plotted on a graph. As
912 min. the blood clots, resistance increases; it then
- activated clotting time (ACT): bedside test; com- peaks and falls as a result of clot retraction and
monly used to monitor heparin anticoagulation disruption of the clot, giving a characteristic
during cardiac surgery. Similar to whole blood tracing (clot signature).
clotting time, but celite is added to the blood for - PFA-100: blood is aspirated through a micro-
quicker results. Automated devices are usually scopic hole in a membrane coated with collagen
used to detect fibrin formation, with a small bar and adrenaline or ADP; the time for a platelet
magnet within the test tube. The tube is placed plug to occlude the hole completely is the
within the device and rotated slowly; when fibrin closure time and is related to platelet function.
forms in the tube, the magnet starts to rotate, fibrinolysis:
thereby activating the detector. Normal value is - fibrinogen assay: normally 1.54.0g/l.
100140s. Values of 34 times the pre-heparin - thrombin time (TT): tests conversion of fibrino-
value are considered adequate during extracorpo- gen to fibrin. Exogenous thrombin is added to
real circulation. plasma. Normal value is 1015s. Inhibited by
clotting factors: performed on fresh citrated plasma, fibrin degradation products resulting from fibri-
with cells and platelets removed; physical activation nolysis. Also inhibited by heparin.
 Coaxial anaesthetic breathing systems 145

- fibrinogen degradation products: normally < failure. Often associated with cerebral aneurysms, bicus-
10mg/l. D-dimer concentration is normally pid aortic valve, patent ductus arteriosus, VSD and
<500ng/ml. mitral and aortic abnormalities.
- plasminogen assay. Repaired surgically via left thoracotomy; more
- clot lysis times: euglobulin is precipitated from recently, balloon angioplasty and stenting of the con-
plasma by adding acid. Contains fibrinogen, plas- stricted segment have been performed.
minogen and plasminogen activator. Addition of Anaesthetic management is similar to that for tho-
thrombin causes clot formation; subsequent lysis racic aortic aneurysm, in particular:
depends on the amount of plasminogen activating preoperative treatment of hypertension and cardiac
capacity present. Whole blood clot lysis and other failure.
variants are also used. antibiotic prophylaxis as for congenital heart
disease.
Co-amoxiclav. Broad-spectrum antibacterial drug; a arterial BP should be monitored in the right arm as
mixture of amoxicillin and clavulanic acid in varying the left subclavian artery is usually clamped during
proportion. Active against Gram-negative and -positive resection.
organisms; uses include respiratory, middle ear and complications include:
urinary infections. - haemorrhage.
Dosage: (expressed as amoxicillin): - hypertension following aortic clamping, ischaemia
250500mg orally tds. to the spinal cord, bowel and kidneys, and acidosis
1g iv tds/qds. and hypotension following unclamping.
Side effects: as for amoxicillin; also cholestatic jaun- hypertension may persist postoperatively and
dice, erythema multiforme and interstitial nephritis. require treatment, especially in older patients.
simultaneous BP measurement in the arms and legs
Coanda effect. Development of reduced pressure is often performed.
between a fluid jet from a nozzle and an adjacent surface, See also, Cardiac surgery
resulting in adherence of the jet to the surface. Reduced
pressure results from entrainment of surrounding mol- Coaxial anaesthetic breathing systems. Functionally,
ecules into the turbulent jet, with those next to the they are versions of Mapleson A (Lack) and D (Bain)
surface quickly used up. If the jet has two surfaces to anaesthetic breathing systems, but more convenient
which it might adhere, it will attach to one only, without to use:
splitting. A small signal jet across the nozzle may switch Lack (Fig. 45a): the expiratory valve is at the anaes-
the main jet from one surface to the other; this has thetic machine end (cf. Magill system). Thus easier
formed the basis of control mechanisms in fluidics, e.g. to adjust and scavenge waste gases, especially when
control of ventilators. the patients head is covered. The patient end is also
Similar behaviour of fluids has been suggested to lighter. The outer tube is wider than usual to accom-
occur beyond constrictions in blood vessels, e.g. coronary modate the inner tube, itself as wide as possible to
arteries, contributing to ischaemia and infarction. reduce resistance to expiration. The system is there-
The effect was originally applied to the development fore bulky and relatively inflexible. It has greater
of jet engines. resistance to expiration than the Magill system.
Coman IM (2007). J Cardiovasc Med; 8: 2512 Required fresh gas flows are as for the Magill
[Henri Coanda (18851972), Romanian engineer] system. Parallel versions are also available, in which
the inner tube is replaced by a second external tube
Coarctation of aorta. Accounts for 510% of congeni- running alongside the main tube. Both tubes are
tal heart disease. More common in males. May be associ- wide-bore and thus of low resistance.
ated with Turners and Marfans syndromes. Acquired
coarctation is rare and usually follows chest trauma or
vasculitides.
Over 95% are post-ductal, often presenting in later
life. May be associated with cerebral aneurysms and a (a)
bicuspid aortic valve.
Features:
hypertension, left ventricular hypertrophy and FGF
cardiac failure. BP is high in the arms, normal or low
in the legs. CVA and endocarditis may occur.
weak femoral pulses, delayed compared with the
radials.
systolic heart murmur; may be loudest posteriorly.
ECG findings include left ventricular hypertrophy. (b)
characteristic CXR findings:
- double aortic knuckle (3 sign).
FGF
- small descending aorta.
- rib notching; seen at the middle of the lower
border of the ribs posteriorly; caused by enlarged
collateral vessels.
- left ventricular enlargement/failure.
The preductal (proximal to the ductus arteriosus) form
is more severe, usually presenting in infancy with cardiac Fig. 45 Coaxial breathing systems: (a) Lack; (b) Bain
146 Cocada

Bain (Fig. 45b): lighter and longer than the standard The toxic dose depends on the individuals tolerance
systems, with the expiratory valve at the machine and route of administration but doses above 1g are
end, allowing easy adjustment and scavenging. likely to be fatal. Effects are enhanced and prolonged by
Some resistance to expiration results from the flow alcohol. Detectable in urine but serum levels are unhelp-
of fresh gas directed at the patients mouth from the ful because of a large volume of distribution and rapid
inner tube. Ideal fresh gas flow rates for spontane- metabolism.
ous ventilation are controversial, as high flows cause Clinical features:
greater resistance. Suggested values range from 100 CNS: euphoria, anxiety, agitation, psychosis, halluci-
to 250ml/kg. May be used for IPPV using a ventila- nations, convulsions, hyperthermia, intracranial
tor, e.g. Penlon Nuffield attached to the reservoir haemorrhage, coma. Status epilepticus suggests
bag fitting (bag removed) by a length of tubing continued drug absorption (e.g. following rupture of
whose volume exceeds tidal volume. Disconnection cocaine-filled packets swallowed for smuggling pur-
of the inner tube from the fresh gas source (result- poses), intracranial haemorrhage or hyperthermia.
ing in the whole length of tubing becoming dead CVS: ventricular tachyarrhythmias, severe hyper-
space) must be excluded before use (see Checking tension (may result in CVA or aortic dissection),
of anaesthetic equipment). myocardial infarction caused by coronary thrombo-
A coaxial version of the circle system is available, which sis or spasm, dilated cardiomyopathy. The actions of
connects to the inspiration and expiration ports of a sympathomimetic drugs may be greatly enhanced.
standard CO2 absorber. It is claimed that the countercur- RS: non-cardiogenic pulmonary oedema, bron
rent heat exchange mechanism, in which the expiratory chospasm, pulmonary infiltrates (crack lung),
gases warm the inspiratory gases as they pass in opposite pulmonary haemorrhage, pneumothorax/
directions along the coaxial tubes length, results in pneumomediastinum.
greater transfer of heat to the inspiratory gas than in the renal: renal failure caused by renal artery spasm,
conventional non-coaxial circle. hypotension or rhabdomyolysis.
[J Alistair Lack, Salisbury anaesthetist; JA Bain, Cana- Management:
dian anaesthetist] supportive: resuscitation, sedation, antiarrhythmic
drugs, antihypertensive drugs (avoiding -blockade
Cocada. Ball of coca leaves, mixed with guano and corn- alone since it may result in cardiovascular collapse
starch, thought to be chewed by South American Incas due to unopposed 1-agonism), general manage-
to release free cocaine base. Dribbling of saliva on to ment as for poisoning and overdoses.
laparotomy may occasionally be required to remove
wounds then allowed relatively painless surgery.
ingested bags of the drug.
general anaesthesia may be hazardous because of
Cocaine/cocaine hydrochloride. Ester local anaes- the risk of severe hypertension and arrhythmias fol-
thetic agent, the first one discovered. An alkaloid origi- lowing laryngoscopy and tracheal intubation.
nally extracted from the leaves and bark of South
American coca plants. Used in 1884 for topical analgesia Cockpit drill, see Checking of anaesthetic equipment
of the eye (by Koller), intercostal nerve block (by
Anrep), mandibular nerve block (by Halstead and Hall) Codeine phosphate. Naturally occurring opioid analge-
and other uses, including local infiltration. Now restricted sic drug, isolated in 1832. Used to relieve mild to moder-
to topical anaesthesia because of its toxicity. Commonly ate pain. Also used in diarrhoea, and to suppress the
used as a 10% spray or as component of Moffets solu- cough reflex, e.g. in palliative care. Has similar effects to
tion to reduce bleeding caused by nasal intubation. morphine, but with lower potency and efficacy. About
Causes vasoconstriction by preventing uptake of nor- 510% is metabolised to morphine via the cytochrome
adrenaline by presynaptic nerve endings; also inhibits P450 system; in about 510% of the population metabo-
monoamine oxidase. lism is reduced to under 3%, resulting in reduced anal-
Toxicity:
gesia. The specific enzyme involved is also inhibited by
CNS stimulation: convulsions at high doses, fol-
a number of drugs, including antidepressants.
lowed by central depression and apnoea. Although classically used as an analgesic in neurosur-
sympathetic stimulation: arrhythmias, tachycardia,
gery, its use has been superseded by morphine. Partly
hypertension and myocardial ischaemia may occur. excreted unchanged via the kidneys, and partly metabo-
addiction may occur with chronic use. Cerebral
lised in the liver.
aneurysms, cardiomyopathy and sudden death are Dosage: up to 60mg orally or im; 11.5mg/kg for
associated with chronic abuse. children. Available in combination with paracetamol
Maximum safe dose: 3mg/kg.
(8mg, 15mg and 30mg with 500mg paracetamol).
Excreted mainly via the liver; a small amount is excreted Codeine should not be given iv (severe hypotension
unchanged in the urine. may follow).
[Richard J Hall (18561897), Irish-born US surgeon]
See also, Cocaine poisoning Co-dydramol, see Dihydrocodeine

Cocaine poisoning. Increasing problem in the devel- COELCB, see Current-operated earth-leakage circuit
oped world, especially with the production of the more breaker
addictive freebase cocaine (crack) by dissolution of the
salt in alkaline solution and extraction with organic sol- Coeliac plexus block. Sympathetic nerve block involv-
vents (e.g. ether). Illegally obtained cocaine may contain ing blockade of the coeliac ganglions, one lying on each
caffeine, phencyclidine, ephedrine, amfetamines, strych- side of L1 (aorta lying posteriorly, pancreas anteriorly
nine and other contaminants. and inferior vena cava laterally) and closely related to
 Colloid/crystalloid controversy 147

the coeliac plexus. Through them pass afferent fibres Royal College of Surgeons in Ireland (RCSI) became
from abdominal (but not pelvic) viscera. the College of Anaesthetists at the RCSI in 1998.
Performed for relief of pain from non-pelvic intra- Mushin W (1989). Anaesthesia; 44: 2912
abdominal organs, especially due to pancreatic and
gastric malignancies. Has also been used in acute/chronic Colligative properties of solutions. Those properties
pancreatitis (relaxes the sphincter of Oddi) and to varying with the number, and not character, of solute
provide intra-abdominal analgesia during surgery. particles present. Thus, as concentration increases:
Usually performed percutaneously with the patient freezing point decreases.
prone, under X-ray guidance. CT scanning has been osmotic pressure increases.
used. boiling point increases.
Point of needle insertion: 510cm from the midline,
vapour pressure of solvent decreases (Raoults law).
level with the spinous process of L1, below the 12th Measurement of osmolarity/osmolality may utilise any
rib. A long (> 10cm) needle is inserted at 45 to the of the above properties, since the changes produced
skin, directed medially and slightly cranially. It is by addition of solute are proportional to the amount
passed until the needle tip lies anterior to the upper added.
part of the body of L1. 1525ml local anaesthetic
agent is injected on each side (e.g. prilocaine or lido-
caine 0.5% with adrenaline) followed by 25ml 50% Colloid. Substance unable to pass through a semiperme-
alcohol if required, e.g. on the following day if the able membrane, being a suspension of particles rather
block is successful. Flushing with saline prevents than a true solution (cf. crystalloid). When given as iv
alcohol deposition during needle withdrawal. Severe fluids have a greater tendency to remain in the intravas-
hypotension may result, even after unilateral block. cular compartment, at least initially. More useful than
[Ruggero Oddi (18451906), Italian surgeon] crystalloids when replacing a vascular volume deficit
See also, Sympathetic nervous system (e.g. in haemorrhage), but of less use correcting specific
water and electrolyte deficiencies, e.g. in dehydration.
Also more expensive. Sometimes called plasma substi-
Co-fluampicil. Broad-spectrum antibacterial drug; a
tutes or plasma expanders, because the increase in
mixture of ampicillin and flucloxacillin in equal parts.
plasma volume may be greater than the volume of
colloid infused, due to their higher osmolality than
Cognitive behavioural therapy (CBT). Method of plasma.
examining how subjects think about themselves and Available products:
their environment, and how their behaviour affects their blood products, e.g. blood, albumin, plasma: due to
thoughts and feelings, in order to change both aspects of cost and risks of blood transfusion they should only
their life. Focuses on identifying current patterns and be used for specific blood component deficiency.
problems, as opposed to the past, and developing coping Approximate current cost per unit: red cells 120;
strategies and skills. Particularly useful in disorders asso- platelets 200; fresh frozen plasma 30.
ciated with anxiety and depression; has been used to hydroxyethyl starch: solutions with differing degrees
complement chronic pain management. of substitution (4074%) have been produced, with
Morley S (2011). Pain; 152: S99106 varying duration of action and effects on circulating
See also, Operant conditioning volume. Incidence of severe reactions is about
1/1000016000; cost is 1020/500ml.
COLD, Chronic obstructive lung disease, see Chronic gelatin derivatives. Effects last a few hours only.
obstructive pulmonary disease Severe reactions: 1/13000 (succinylated), 1/2000
(urea-linked; lower incidence with the newer for-
Colistin. Antibacterial drug, also known as polymyxin mulation since 1981). Cost: 35/500ml.
E. Acts on the lipopolysaccharide and phospholipid dextrans. May affect renal function and coagulation.
components of Gram-negative bacterial cell walls, Severe reactions: 1/4500, reduced to 1/84000 with
including pseudomonas. Not absorbed when given orally; hapten pretreatment. Cost: 45/500ml.
therefore has been used in selective decontamination of See also, Colloid/crystalloid controversy
the digestive tract. Rarely given iv because of its side
effects. Colloid/crystalloid controversy. Arises from conflict-
Dosage:
ing theoretical, experimental and clinical evidence con-
1.53 million units orally tds.
cerning the use of iv colloid or crystalloid in shock,
1 million units by nebulised solution bd (dose
mostly in the context of haemorrhage.
halved if under 40kg). Arguments in favour of:
12 million units iv/im tds.
colloid:
Side effects: paraesthesia, vertigo, neuromuscular
- more logical choice for intravascular volume
blockade, renal impairment, dysarthria, visual distur- replacement, since a greater proportion remains
bance, confusion. in the intravascular space for longer after
infusion.
Colitis, see Bowel ischaemia; Inflammatory bowel - less volume is required to restore cardiovascular
disease; Pseudomembranous colitis parameters, e.g. BP, CVP, pulmonary artery capil-
lary wedge pressure. Thus initial resuscitation is
College of Anaesthetists. Founded in 1988, replacing more rapid.
the Faculty of Anaesthetists, Royal College of Surgeons - less peripheral/pulmonary oedema follows its use
of England; became the Royal College of Anaesthetists for the above reasons, and also because there is
in 1992. Similarly, the Faculty of Anaesthetists at the less reduction of plasma oncotic pressure.
148 Colloid oncotic pressure

crystalloid: Assessment of the pupils, dolls eye movements, posture

- expands the intravascular compartment ade- and motor responses (e.g. decerebrate and decorticate
quately if enough is used (traditionally said to be postures) and respiratory pattern is especially useful.
24 times the colloid requirements, although Investigations are directed towards the above causes.
more recent evidence suggests a ratio nearer 1.5:1 Initial management includes respiratory and cardio-
for the same degree of intravascular expansion). vascular support as for CPR, and treatment of the
- in haemorrhage, fluid moves from the interstitial underlying cause. In addition, longer-term management
space into the vascular compartment and third includes attention to pressure areas, mouth, eyes, phys-
space; this ECF depletion is better replenished by iotherapy, prophylaxis against DVT, nutrition and fluid
crystalloid. balance.
- if vascular permeability is increased, colloids will Coma may be followed by complete recovery, vegeta-
enter the interstitial space and increase interstitial tive state or brainstem death.
oncotic pressure, thus exacerbating oedema. Crys- Young GB (2009). Ann N Y Acad Sci; 1157: 3247
talloids do not increase interstitial oncotic pres- See also, Coma scales
sure to the same extent.
- peripheral oedema is usually not a problem. Coma scales. Scoring systems for assessing the degree
- risk of allergic reactions to colloids. of coma in unconscious patients and charting their prog-
- crystalloid is much cheaper than colloid. ress; may also give an indication of outcome.
Difficulties in assessing fluid resuscitation: Include general scales, e.g. AVPU scale or a simple
infusion is usually guided by cardiovascular end- 15 scoring system:
points but their relation to interstitial fluid and ECF 1 = fully awake.
is unclear. 2 = conscious but drowsy.
lung water may increase markedly before gas 3 = unconscious but responsive to pain with pur-
exchange is impaired. poseful movement, e.g. flexion.
other clinical processes may be involved (e.g. car- 4 = unconscious; responds to pain with extension.
diovascular disease): impaired gas exchange and 5 = unconscious with no response to pain.
increased vascular permeability due to sepsis and Other data (e.g. from eye reflexes) are ignored; hence
ARDS. The position is even less clear than in more complex or specific scoring systems are used:
uncomplicated haemorrhage. In the USA, crystal- Glasgow coma scale (GCS).
loid (e.g. Hartmanns solution) is widely used for iv the FOUR score (full outline of unresponsiveness;
resuscitation, whereas colloids are more commonly a 17-point scale assessing eye, motor and brainstem
used in the UK. Mixtures are favoured by many, responses, and breathing pattern).
guided by the nature of the deficit. for specific conditions, e.g. hepatic failure, subarach-
noid haemorrhage.
Colloid oncotic pressure, see Oncotic pressure Kornbluth J, Bhardwaj A (2011). Neurocrit Care; 14:
Colton, Gardner Quincy (18141898). US lecturer and 13443
showman; studied medicine but never qualified. Demon-
strated the exhilarating effects of N2O inhalation for Combined spinalepidural anaesthesia (CSE). Tech-
entertainment in 1844, inspiring Wells to suggest its use nique in which spinal anaesthesia is accompanied by
for dental analgesia. Said to have administered N2O to the placement of a catheter into the epidural space. May
Wells whilst the latters tooth was painlessly removed. be achieved by two completely separate punctures or,
Stopped lecturing to prospect for gold, returning to N2O more commonly, combined into a single one, in which
and popularising its reintroduction by founding the the epidural space is located in the usual way as for
Colton Dental Association in 1863. epidural anaesthesia, and spinal anaesthesia is per-
Smith GB, Hirsch NP (1991). Anesth Analg; 72: 38291 formed either alongside or, more commonly, by inserting
a long spinal needle through, the epidural needle to
Coma. State in which the patient is totally unaware of puncture the dura. The epidural catheter is then sited in
both self and external surroundings, and unable to the normal way.
respond meaningfully to external stimuli. Results from Advantages: speed of onset/density of block associ-
gross impairment of both cerebral hemispheres, and/or ated with spinal anaesthesia, combined with the flex-
the ascending reticular activating system. ibility of epidural anaesthesia. Also facilitates use of
Caused by: low-dose spinal anaesthesia with epidural volume
focal brain dysfunction, e.g. tumour, vascular events, expansion (see below).
demyelination, infection, head injury. Disadvantages (compared with single-shot spinal
diffuse brain dysfunction: injections): risk of dural puncture with epidural
- infection, e.g. meningitis, encephalitis. needle; longer time to perform; the possibility that the
- epilepsy. epidural catheter is inserted through the dural hole;
- hypoxia and hypercapnia. inadequate block if the catheter cannot be threaded
- drugs, poisoning and overdoses. easily (with the patient in the same position for a long
- metabolic/endocrine causes (e.g. diabetic coma; time); and a theoretical increased risk of infection. If
hepatic or renal failure; hypothyroidism), saline is used to identify the epidural space, the
electrolyte disturbance (e.g. hyponatraemia, appearance of clear fluid at the hub of the spinal
hypercalcaemia). needle may cause confusion if free flow is not
- hypotension, hypertensive crisis. obtained.
- head injury. Used commonly in obstetric analgesia and anaesthesia
- subarachnoid haemorrhage. and other types of surgery. Different needle systems
- hypothermia, hyperthermia. exist to ease CSE, including epidural needles with a
 Complement 149

back hole at the distal end to allow the spinal needle

to pass through the epidural needle without being bent Classical Alternative
by the latters curved tip, and double-lumen epidural pathway pathway
needles to enable the catheter to be threaded before C1 C3
intrathecal injection. Various locking devices, to prevent
C4
the spinal needle from moving relative to the epidural C4, 2
C2
needle once the intrathecal space has been located, are C3
B
also available. D
H
In epidural volume expansion (EVE), a bolus of epi- C4, 2, 3
dural saline, injected via either the needle or catheter,
is used to increase the cranial spread of a (usually C5 C5a + C5b Lytic pathway
small) spinal dose of local anaesthetic. The mechanism C6
is thought to be compression of the dural sac by the C7
epidural fluid, and has been implicated in the occasion- C8
ally very high block when a spinal is performed after C9
(inadequate) epidural anaesthesia. EVE has been
C5b, 6, 7, 8, 9
claimed to produce a reliably extensive block from a
smaller than usual dose of drug, whilst reducing side
effects such as hypotension and motor block. However, Lysis
it is not universally employed because the extra spread
is usually relatively modest (a few segments only) and Fig. 46 Complement system
use of a smaller dose increases the risk of discomfort/
inadequate block.
Cook TM (2000). Anaesthesia; 55: 4264

Combitube, see Oesophageal obturators and airways increased pressure within the compartment on pal-
pation and also when measured.
peripheral pulses may be present.
Commission for Health Improvement (CHI), see
Treatment includes release of tourniquets, dressings and
Healthcare Commission.
plaster casts; surgical fasciotomy may be required. The
abdominal compartment syndrome may occur, e.g. in
Committee on Safety of Medicines (CSM). Advisory abdominal trauma.
body, originally set up as the Committee on Safety of
Drugs in 1963 after the thalidomide disaster. Became the Competition, drug, see Antagonist; Doseresponse
CSM in 1971 when the Medicines Act became law. Was curves
the body responsible for granting certificates to new
drugs before clinical trials and product licences, and Complement. Part of the innate immune system;
for monitoring post-marketing safety. Joined with the describes a series of plasma proteins (labelled C1C9)
Medicines Commission in 2005 to form the Commission synthesised in the liver and involved in immunological
on Human Medicines (CHM), a committee of the Medi- and inflammatory reactions. Activation of the system
cines and Healthcare products Regulatory Agency, causes a cascade of protein cleavage and further activa-
charged with advising ministers on licensing policy, tion events, amplifying the initial stimulus.
taking responsibility for drug safety issues, advising on Pathways (Fig. 46):
appointments related to human medicines and hearing classical (discovered first):
evidence from drug companies if licence applications are - activated by antigenantibody complexes (i.e.
rejected. requires prior exposure to antigen), although it
See also, Adverse drug reactions; Drug development may follow prior exposure to a cross-reacting
antigen.
Compartment syndromes. Impaired circulation and - antibodyantigen complex binds to C1.
function of tissues within a fascial compartment, associ- - via C4, C2 and C3, forming a complex which acti-
ated with increased pressure within the compartment. vates C5.
May be caused by external compression (e.g. tourni- - C1 activity is regulated by circulating C1
quets, limb plasters) or increased volume of compart- inhibitor; deficiency results in hereditary
ment contents (e.g. following trauma, severe exercise, angio-oedema.
prolonged immobility, bleeding or ischaemia of the alternative:
underlying tissues). May lead to disruption of capillaries, - activated by aggregated IgA, infections or spon-
leakage of intravascular fluid into the tissues, impaired taneous reaction.
perfusion, myoglobinuria (crush syndrome) and gan- - via other factors: B, D and H forming a complex
grene. Total ischaemia leads to irreversible muscle activating C5.
changes after 4h. The forearm or lower leg is most com- - may amplify itself or the classical pathway via C3b
monly affected. Pressure within the lower leg compart- formation.
ments is normally under 15mmHg when supine, and lytic:
may be monitored using a simple manometer. - activated by products of the above pathways,
Features: causing C5 to form C5a and C5b. The latter binds
increasing pain despite immobilisation of the limb. to the target membrane.
altered sensation in dermatomes corresponding to - C5b binding in turn by C6, C7, C8 and C9.
nerves running through the compartment. - the resultant complex causes membrane lysis.
150 Complex regional pain syndrome

In addition, activated factors produced during all requires measurement of alveolar and ambient pressure
pathways may: difference, and equals about 0.85 l/kPa (85ml/cmH2O).
bind to mast cells and basophils, causing degranula- Compliance measurements are related thus:
tion and release of histamine. 1 1 1
be chemotactic for neutrophils and macrophages. = +
cause vasodilatation and increase capillary perme-
total thoracic chest wall lung
ability. Complement activation may be involved in Lung compliance is divided into two components:
many disease processes. IgM and IgG both bind static; i.e. alveolar stretchability; measured at
complement, and are involved in hypersensitivity steady state, as above.
reactions, e.g. adverse drug reactions. Assays for dynamic; related to airway resistance during equili-
individual components may assist determination of bration of gases throughout the lung at end-
the pathways involved; e.g. low levels of C4 indicate inspiration or expiration.
classical pathway activation. Time constant (resistance compliance) is a reflection
of combined static and dynamic compliance.
Compliance is related to body size; thus specific com-
Complex regional pain syndrome (CRPS). Chronic
pliance is often referred to (compliance divided by
neuropathic pain disorder associated with significant
FRC). It increases in old age and emphysema, due
autonomic features, typically developing in an extremity
to destruction of elastic lung tissue. It is reduced in pul-
several weeks after acute tissue trauma (e.g. fractures,
monary fibrosis, vascular engorgement and oedema;
sprains, surgery). Subdivided into CRPS type 1 (previ-
dynamic compliance is decreased in chronic bronchitis.
ously called reflex sympathetic dystrophy or Sudecks
It is also reduced at the extremes of lung volume, as well
atrophy) and type 2 (causalgia), distinguished respec-
as at the lung apices and bases in upright subjects.
tively by the absence or presence of documented nerve
See also, Breathing, work of
injury. Underlying pathophysiology is likely to be similar
in both types, as are clinical symptoms/signs and avail-
Complications of anaesthesia, see Anaesthetic morbid-
able treatment strategies.
Features:
ity and mortality
continuous pain with neuropathic characteristics
Compound A, Pentafluoroisopropenyl fluoromethyl
(usually allodynia or hyperalgesia), worsened by
ether, see Sevoflurane
movement.
in CRPS type 1 this does not correspond to the
Compressed spectral array, see Power spectral
distribution of a single peripheral nerve, but may do
analysis
so in CRPS type 2.
sympathetic hyperactivity, with cool clammy skin; it
Computed (axial) tomography (CAT scanning; CT
may proceed to a pale, cold, stiff extremity with
scanning). Imaging technique in which an X-ray source
tissue atrophy and osteoporosis.
Pathophysiology: now known to involve multiple
and detector are held opposite each other, with the
patient midway between. The source and detector are
mechanisms, including: central sensitisation;
rotated stepwise about the mid-point, thus scanning the
sympatho-afferent coupling; altered cutaneous inner-
patient from different angles. At each step, the amount
vation and changes in brain plasticity.
Treatment may be extremely challenging and
of X-rays reaching the detector is measured, and the
spatial arrangement of structures within the patient
includes physiotherapy, rehabilitation and sympa-
slice computed and displayed on a screen. In spiral CT
thetic nerve blocks, although the place of the latter is
scanning, the X-ray tube and detector are able to rotate
controversial.
around the patient as the latter moves through the
[Paul HM Sudeck (18661945), German surgeon]
scanner, resulting in a helical scan from which axial slices
Bruehl S (2010) Anesthesiology; 113: 71325
may be reconstructed. Spiral scanning is quicker than

Compliance. Volume change per unit pressure change;

thus a measure of distensibility, e.g. of lungs, chest wall,
heart. For measurement of lung compliance, transmural Total
pressure is required, i.e. the difference between alveolar lung
and intrapleural pressures. The former is measured at capacity
the mouth during periods of no gas flow (e.g. with the
lungs held partially inflated and a few seconds allowed Deflation
Lung volume

for stabilisation) or using a shutter at the mouth to inter-

rupt flow momentarily. Intrapleural pressure is mea- Inflation
sured using a balloon positioned in the lower third of the FRC
oesophagus. The resulting pressure/volume curve is
approximately linear at normal tidal volumes (Fig. 47).
Different curves are measured during lung inflation and Residual
deflation (hysteresis); this is thought to represent the volume
effects of surface tension.
Human lung compliance is about 1.52 l/kPa (150
200ml/cmH2O); reduced when supine because of 1 2 3
decreased FRC. Chest wall compliance is thought to be Pressure (kPa)
similar, but measurement is difficult because of the
effects of respiratory muscles. Total thoracic compliance Fig. 47 Pressure/volume curve of lung
 Confidential Enquiries into Maternal Deaths 151

conventional scanning and allows greater detail, espe- Northern Ireland were excluded until 1985), originally
cially during contrast studies. Used initially for brain conducted by the Royal College of Obstetricians and
scanning, now for all parts of the body. Spiral CT scan- Gynaecologists in the 1930s. Published initially by the
ning is increasingly used to diagnose PE. Department of Health, its first report covered 195254.
Patients must remain still during scanning, and may In 2003, combined with the Confidential Enquiries into
require sedation or general anaesthesia, e.g. children and Stillbirths and Deaths in Infancy (CESDI) to form the
patients with head injury. Choice of techniques and Confidential Enquiries into Maternal and Child Health
drugs is dictated by the patients condition; monitoring (CEMACH), which became an independent charity, the
and maintenance of the airway are particular concerns. Centre for Maternal and Child Enquiries (CMACE), in
Management is similar to that for radiotherapy. 2009, with its enquiries commissioned by the National
See also, Radiology, anaesthesia for Patient Safety Agency. After a series of reviews in 2010
11, the enquiries are now commissioned by the Health-
COMT, see Catechol-O-methyl transferase care Quality Improvement Partnership (HQIP) and run
by a consortium, MBRRACE-UK (Mothers and Babies:
Concentration effect. Phenomenon whereby increased Reducing Risk through Audits and Confidential Enqui-
inspired concentration of inhalation anaesthetic agent ries in the UK), involving a number of centres, groups
results in earlier equilibrium of pulmonary uptake. As and individuals around the UK and led by the National
concentration increases, the effect of alveolar absorption Perinatal Epidemiology Unit in Oxford.
of agent between breaths is reduced. Details of cases are collected from all involved
clinical staff, observing strict confidentiality, and asses-
Conductance. Reciprocal of resistance. For electrical sors (in anaesthetics, obstetric medicine, psychiatry,
circuits, the SI unit is the siemens. The term is often used general practice, pathology and midwifery) review and
to describe the permeability of cell membranes to categorise the deaths according to cause. Causes of
various ions. deaths may be:
[Sir William Siemens (18231883), German-born English direct: arising directly from pregnancy or an inter-
engineer] vention relating to it.
indirect: resulting from disease that pre-exists or
Confederation of European National Societies of develops during pregnancy, and is aggravated by
Anaesthesiologists (CENSA). Organisation founded in pregnancy, or from an intervention not related to
1998, originally created as the European Regional the pregnancy but influenced by it.
Section of the World Federation of Societies of Anaes- late: occur between 42 days and 1 year after the end
thesiologists. Organised European congresses and was of pregnancy.
involved in various educational projects throughout coincidental (previously fortuitous): unrelated to
Europe. Amalgamated with the European Society pregnancy.
of Anaesthesiologists and the European Academy of Direct deaths have numbered ~100130 per triennium
Anaesthesiology to form the European Society of in the last 20 years, while indirect deaths have increased
Anaesthesiology in 2005. from ~8090 to ~150160. In the last decade the main
Kettler D, Wilkinson D (2000). Eur J Anaesth; 17: 145 causes of death have been cardiac disease, thrombosis/
thromboembolism, suicide/psychiatric disease/substance
Confidence intervals. Range of values derived from abuse, pre-eclampsia/eclampsia, haemorrhage, sepsis,
sample data, relating the data to the actual population. amniotic fluid embolism and ectopic pregnancy.
95% confidence intervals (95% CI) contain the true Obesity and increasing maternal age are particularly
(population) value with a probability (P value) of 0.05. highlighted as recent contributing factors. In the latest
When used to express the results of statistical tests, (200608) report, rapidly progressive severe sepsis was
confidence intervals differ from null hypothesis testing a particular concern, accounting for 26 out of a total of
thus: 261 deaths.
null hypothesis testing indicates whether a differ- Anaesthesia was a consistent direct cause of death for
ence in data is statistically significant (i.e. unlikely many years, ranking third after hypertensive disease and
to be due to chance alone); the significance is thromboembolism in several previous reports (Table
expressed as a P value. 16). In the 200608 report seven deaths were directly
confidence intervals indicate the likely magnitude attributable to anaesthesia (two failed intubation/
of such a difference, by giving a range within which ventilation, one aspiration after extubation, one opioid
the true value is likely to lie. By using the same units toxicity, one probable transfusion incompatibility, one
as the data, they allow estimations of clinical rele- postanaesthetic cardiac arrest and one post-spinal leu-
vance to be made; for example, a statistically very koencephalitis). Anaesthesia may have contributed indi-
significant result may be clinically irrelevant if the rectly to a further 18 deaths.
actual differences involved are very small. Improvements in anaesthetic mortality are thought to
Confidence intervals are wide if the sample size is small reflect better training and facilities, and are likely to be
or standard deviation is large. If the 95% CI of a differ- greater than suggested by the above figures, since the
ence between groups do not include zero, this is equiva- number of anaesthetic procedures performed has mark-
lent to the difference having a P value < 0.05; if they edly increased. Most direct and indirect anaesthetic
include zero then P > 0.05. deaths in previous reports have involved caesarean
Asai T (2002). Br J Anaesth; 89: 8079 section; common factors have been lack of senior
See also, Statistical significance involvement, difficulty with tracheal intubation, aspira-
tion of gastric contents, haemorrhage and lack of ICU
Confidential Enquiries into Maternal Deaths. Report or HDU facilities. The need for proper training, facilities
into all maternal deaths in the UK (Scotland and and help is repeatedly stressed. In the more recent
152 Confidential enquiry into perioperative deaths

includes appropriate investigation and treatment of the

Table 16 Direct deaths attributable to anaesthesia in Confidential
underlying cause, reassurance, re-establishment of the
Enquiries into Maternal Deaths reports, 19702008
sleepwake cycle and promotion of a calm environment,
Period No. Proportion Rate per 100000 maternities e.g. by reducing noise levels. Sedation may sometimes be
appropriate.
197072 37 10.8 1.28 Pun BT, Ely EW (2007). Chest; 132: 62436
197375 27 11.9 1.05
197678 27 12.4 1.21 Confusion, postoperative. Occurs in 1060% of patients
197981 22 12.4 0.87 undergoing surgery, especially in the elderly. May be
198284 18 13.0 0.72 subdivided into: emergence delirium (related to drugs,
198587 6 4.3 0.26 pain and acute physiological derangements); delirium
198890 4 2.8 0.17
associated with postoperative complications; and longer-
199193 8 6.3 0.35
term impairment (postoperative cognitive dysfunction;
199496 1 0.7 0.05
199799 3 2.8 0.14
POCD).
Possible causes/contributing factors include:
200002 6 5.7 0.30
200205 6 4.5 0.28 drugs: e.g. opioids, ketamine, and those associated
2006-08 7 6.5 0.31 with the central anticholinergic syndrome.
hypoxaemia, hypercapnia.
hypotension.
restlessness due to pain or full bladder.
metabolic disturbances, e.g. hypoglycaemia, hyper-
reports, communication failures, lack of senior availabil- natraemia, hyponatraemia, acidosis.
ity, underestimation of severity of illness by trainees, alcohol and benzodiazepine withdrawal.
delayed resuscitation and administration of blood prod- sepsis.
ucts, inadequate ICU/HDU facilities, drug error and the intracranial pathology, e.g. raised ICP, CVA, post-
risks of rapid iv injection of large doses of oxytocin have ictal state.
been highlighted. pre-existing confusion.
McClure JH, Cooper GM, Clutton-Brock TH (2011). Br reduced cerebral blood flow resulting from periop-
J Anaesth; 107: 12732 erative hyperventilation (especially in the elderly)
See also, Audit; Obstetric analgesia and anaesthesia has been suggested as a cause.
Confusion within a few days of surgery may be caused
Confidential enquiry into perioperative deaths, see by any illness (e.g. sepsis, pulmonary disease). Appropri-
National Confidential Enquiry into Patient Outcome and ate investigation and treatment are required, rather than
Death simply administering sedation, which may exacerbate
the confusion. If sedation is necessary, haloperidol is
Confusion in the Intensive Care Unit. An acute con- often a suitable choice. POCD may occur (often after an
fusional state is the most common form of psychiatric initial lucid period), particularly in the elderly and those
disorder encountered in the ICU and may form part of with pre-existing cognitive deficit. The mechanism for
the syndrome of ICU delirium. Often represents an this is unclear, but may involve an inflammatory process
acute reaction to a number of pathological processes within the CNS as well as cerebrovascular impairment.
that may occur in the critically ill patient. The elderly are Sanders RD, Pandharipande PP, Davidson AJ, Ma D,
more susceptible. Symptoms include disorientation in Maze M (2011). Br Med J; 343: d4331
space and time, agitation, slow responses, slurred speech
and hallucinations; often worse at night. Congenital heart disease. Incidence: up to 1% of live
Causes include: births; 15% survive to adulthood without treatment.
systemic infection. May be associated with other congenital defects or
CVS disease, e.g. hypotension, MI, endocarditis. syndromes.
RS disease, e.g. hypoxaemia, hypercapnia, chest Simple classification:
infection. acyanotic (no shunt):
CNS disease, e.g. encephalitis, meningitis, head - coarctation of aorta (510%).
injury, space-occupying lesions, post-ictal states. - pulmonary and aortic stenosis (1015% together).
drug therapy/withdrawal, especially sedatives. potentially cyanotic (i.e. left-to-right shunt); may
drug abuse/withdrawal, e.g. alcohol, opioids, reverse and become cyanotic if pulmonary hyper-
amfetamines. tension develops (Eisenmengers syndrome):
metabolic disorders, e.g. hypo/hyperglycaemia, - ASD (1015%).
hypo/hypernatraemia, hypercalcaemia. - VSD (2030%).
hypo/hyperthermia. - patent ductus arteriosus (1015%).
thiamine deficiency. cyanotic, due to:
pain, full bladder. - right-to-left shunt:
sleep deprivation. - Fallots tetralogy (510%).
The CAM-ICU (confusion assessment method for ICU) - pulmonary atresia with septal defect.
is a tool for determining whether a patient is suffering - tricuspid valve lesions, including Ebsteins
from delirium by assessing if there is an acute mental anomaly, with septal defect.
status change, whether there is inattention to visual and - abnormal connections:
auditory prompts, whether there is an altered level of - transposition of the great arteries (5%).
consciousness and whether there is any disorganised - anomalous systemic or pulmonary venous
thinking as assessed by set questions. Management drainage, the latter with right-to-left shunt.
 Connective tissue diseases 153

- mixing of systemic and pulmonary blood, e.g. neoplasm, trauma. Supratentorial pressure may
single atrium or ventricle. result in:
Has also been classified functionally as: - central herniation: the diencephalon is forced
obstructive: e.g. coarctation, valve stenosis. through the tentorial opening. Early signs include
shunt; may be: altered alertness, sighing and yawning, small
- restrictive: amount of shunt is affected relatively pupils and conjugate roving eye movements.
little by changes in pulmonary or systemic vascu- Appropriate motor responses give way to
lar resistance, since the flow across the connection decorticate posture. As midbrain compression
itself is relatively fixed, e.g. small VSD. occurs, CheyneStokes respiration appears, pupils
- non-restrictive: amount of shunt depends largely become moderately dilated and decerebrate
on the relationship between pulmonary and sys- posture is seen. Medullary compression results
temic vascular resistance, since flow through the in hypertension, bradycardia and respiratory
connection is variable, e.g. large VSD. arrhythmias (Cushings reflex) and is a terminal
complex, i.e. involving both obstruction and shunt, event.
e.g. Fallots tetralogy. - uncal herniation: usually caused by a rapidly
Common features include feeding difficulty, failure to expanding mass (e.g. traumatic haematoma) in
thrive, cyanosis, dyspnoea, heart murmurs and cardiac the middle fossa or temporal lobe, which pushes
failure. Patients may present soon after birth. Investiga- the medial uncus over the edge of the tentorium.
tion includes echocardiography and cardiac catheterisa- Decreased consciousness occurs late and the ear-
tion. Increased risk of surgery within first year of life liest consistent sign is a unilateral dilating pupil
may be offset by a high mortality without surgery, caused by compression of the ipsilateral oculomo-
depending on the lesion. Palliative procedures are some- tor nerve (cranial nerve III) against the tentorial
times performed early, with later corrective surgery, e.g.: edge. Delay in decompression at this stage results
pulmonary balloon valvuloplasty in pulmonary in irreversible brainstem damage.
stenosis. infratentorial: caused by posterior fossa masses.
shunt procedures to increase pulmonary blood flow May result in:
in severe right-to-left shunt, e.g. Fallots tetralogy. A - upward cerebellar herniation causing midbrain
prosthetic graft is inserted between the subclavian compression, cerebellar infarction and hydro-
and pulmonary arteries (formerly involved direct cephalus.
anastomosis of the subclavian artery itself [Blalock - tonsillar herniation: the cerebellar tonsils are
Taussig procedure]). Balloon atrial septostomy is forced through the foramen magnum resulting in
sometimes performed in transposition of the great medullary compression. May follow lumbar punc-
arteries, to allow oxygenated blood to pass from left ture in the presence of increased ICP.
to right sides of heart.
pulmonary banding to reduce pulmonary blood Conjoined twins. Incidence is about 1 in 200000 births.
flow and prevent pulmonary hypertension in large Radiological assessment may require repeat anaesthe-
left-to-right shunts. sia. Each twin requires a separate anaesthetic team. Tra-
Principles of anaesthesia are as for cardiac surgery and cheal intubation and access may be difficult, depending
paediatric anaesthesia. Inhalational or iv techniques are on the site of union. If circulation is shared, induction of
suitable. Uptake of inhalational agents is slower when the first twin may be delayed, as anaesthetic drugs
right-to-left shunts exist. Ketamine is preferred by some are taken up by the second twin. Induction of the
anaesthetists. Air bubbles in iv lines are particularly haz- second twin may thus be rapid. Blood loss at separation
ardous in right-to-left shunts, due to risk of systemic may be massive. Adrenal insufficiency may be present in
embolism. Nasal tracheal tubes are preferred when post- one twin.
operative IPPV is required. Thomas JM, Lopez JT (2004). Paediatr Anaesth; 14:
Antibiotic prophylaxis for endocarditis in patients 11729
with congenital heart disease was previously routinely
administered for dental, genitourinary and gastrointesti- Connective tissue diseases. Group of diseases sharing
nal surgery. Current NICE guidance no longer recom- certain features, particularly inflammation of connective
mends this practice, unless the procedure involves tissue and features of autoimmune disease. Rheumatoid
operating on an area of suspected infection in which arthritis, SLE and systemic sclerosis (SS) are more
prophylaxis for surgical site infection would normally be common in women; polyarteritis nodosa (PN) is more
given; in these cases antibiotics should also be given that common in men.
cover organisms known to cause endocarditis. Features may include the following:
[Alfred Blalock (18991964), US surgeon; Helen Taussig autoimmune involvement: immunoglobulins may
(18981986), US physician] be directed against IgG (rheumatoid factors) and
Cannesson M, Collange V, Lehot JJ (2009). Curr Opin cell components, e.g. nuclear proteins, phospholip-
Anesth; 22: 8894 ids. Organ-specific antibodies are also common, e.g.
See also, Preoperative assessment; Pulmonary valve against thyroid and gastric parietal cells, smooth
lesions; Valvular heart disease muscle and mitochondria. T- and B-cell dysfunction,
immune complex deposition and complement acti-
Congestive cardiac failure, see Cardiac failure vation may also occur. Diagnosis of specific disease
is aided by the pattern of immune disturbance.
Coning. Herniation of brain structures caused by systemic involvement:
increased ICP. May be: - musculoskeletal: arthropathy, myopathy.
supratentorial, e.g. caused by CVA, subarachnoid - skin: rash, mouth ulcers. Thickening in SS, with
haemorrhage, cerebral abscess, encephalitis, characteristic pinched mouth.
154 Connectors, tracheal tube

- renal: glomerulonephritis, vasculitis, nephrotic law he/she may consent to treatment but not refuse
syndrome. it [Gillick competent]).
- fever, malaise. If the patient lacks capacity (e.g. is unconscious)
- cardiovascular: pericarditis, myocarditis, conduc- then life-saving treatment may proceed if it is felt
tion defects, vasculitis (affecting any organ). to be in his/her best interests (N.B. these may not
Raynauds phenomenon (fingers turn white, then be the same as medical best interests) and every
blue, then red on exposure to cold, stress or vibra- attempt should be made to find out the patients
tion) is common. views and wishes. In England and Wales, the Mental
- haematological: anaemia, leucopenia, thrombocy- Capacity Act 2005 laid down formal procedures for
topenia. Lupus anticoagulant may be present in the appointment of advocates for persons lacking
SLE. capacity, and also strengthens the status of advance
- hepatosplenomegaly. decisions (in Scotland, advocates for incapacitated
- central and peripheral nervous involvement, e.g. patients already had legal status).
central lesions, neuropathies and psychiatric dis- disclosure of relevant information: traditionally, in
turbances (especially with SLE). the UK, doctors have used their discretion to
- pulmonary: fibrosis, pleurisy, pleural effusions and explain risks and benefits as they feel appropriate
pulmonary infiltrates. Pulmonary hypertension for the patient concerned, as long as their decision
may occur. Haemorrhage with PN. is judged reasonable according to current medical
- Sjgrens syndrome (reduced tear and saliva for- opinion. In the USA, legally required informed
mation and secretion) may occur. consent (i.e. full explanation of risks, benefits and
- GIT: reduced oesophageal motility, oesophagitis alternatives) is judged according to what a reason-
and risk of regurgitation, especially in SS. able patient would expect to have explained to him/
Treatment includes corticosteroids and other immuno- her. Increasingly, in the UK, emphasis has shifted
suppressive drugs. Antimalarial drugs are used in SLE. towards what patients want to know, rather than
Anaesthetic considerations: what doctors think they should know.
careful preoperative assessment to identify the patients understanding of the options and their
above features, complications and drugs, with implications.
appropriate management. voluntary decision and the time in which to
mouth opening may be difficult in SS. make it.
general management: as for rheumatoid arthritis. Consent may be:
Other conditions without circulating rheumatoid verbal or written. The latter serves as proof of
factors may have systemic manifestations, e.g. ankylosing consent afterwards, but is no stronger than verbal
spondylitis and associated conditions. Arthritis may consent, which should be witnessed if possible.
accompany inflammatory bowel disease and intestinal express or implied (i.e. by allowing treatment or
infection. insertion of a cannula, the patient is demonstrating
[Maurice Raynaud (18341881), French physician; consent, without having specifically expressed it).
Henrik Sjgren (18991986), Swedish ophthalmologist] Consent forms are now standard for surgery and the
See also, Vasculitides consenting process was updated in guidance issued by
the UK Department of Health in 2001. A separate
Connectors, tracheal tube. Adaptors for connecting section for anaesthesia has been suggested, although the
tracheal tubes to anaesthetic breathing systems. Modern ability of junior surgeons (who traditionally have
connectors are plastic, and 15mm in size distally. They obtained consent) to inform the patient adequately in
fit to any standardised 15/22-mm equipment, e.g. directly this respect has led to some controversy. There is dis-
to breathing tubing or to catheter mounts. They may agreement about the requirement for consent forms in
connect directly or via angle pieces, which may swivel. other procedures (e.g. epidural analgesia in labour
Some incorporate a capped port for tracheobronchial requires written consent only in some UK units). The
suction or insertion of fibreoptic instruments. Association of Anaesthetists of Great Britain and
Ireland issued guidance in 2006 that did not recommend
Conns syndrome, see Hyperaldosteronism a separate anaesthetic consent form, although the impor-
tance of recording the discussion around consent was
Consent for anaesthesia. Required before general and stressed.
local anaesthetic techniques may be performed. Failure In the ICU/emergency setting, consent for invasive
to obtain consent may result in a charge of battery; in interventions (e.g. tracheal intubation, venous cannula-
addition, inadequate counselling whilst obtaining tion, surgery) often cannot be obtained from the patient
consent may result in charges of negligence. and similar procedures apply as above. Until the Mental
Consent requires: Capacity Act, no person could legally give consent for
adequate capacity of the patient to understand: the another, although it has been customary to obtain
patient should be over 16 years (in England and informed assent from the next of kin, though it had no
Wales) and of sound mind, i.e. unaffected by drugs, legal status.
extreme pain (this decision should be made by the [Victoria Gillick, British campaigner against the policy
treating doctor, although it may be aided by consult- that contraception could be prescribed to children under
ing with colleagues). Consent on behalf of children 16 without parental consent]
is given by their parents or legal guardians, although White SM, Baldwin TJ (2006). Anaesthesia; 61: 3819
this may be overruled by the courts. The emanci- See also, Medicolegal aspects of anaesthesia
pated minor is a child under the age of majority
who is able to understand and therefore make deci- Constipation. Common postoperatively as a result of
sions about his/her treatment (though in English opioid analgesic drug administration and immobility. On
 Controlled drugs 155

the ICU, may be related to lack of food, drugs (e.g. [Louis Pasteur (18221895), French bacteriologist]
opioids), altered GIT flora and impaired neurological See also, COSHH regulations
function, e.g. spinal cord injury. Patients should undergo
rectal examination to exclude faecal impaction. Treat- Continuous positive airway pressure (CPAP). Appli-
ment is with oral or rectal laxatives and attention to any cation of positive airway pressure throughout all phases
underlying cause. Manual evacuation may be required of spontaneous ventilation. May be achieved with
in unconscious patients. various systems, applied via a tightly fitting mask or tra-
cheal tube. In order to apply positive pressure through-
Contamination of anaesthetic equipment. The role of out ventilation, a reservoir bag, or a fresh gas flow
cross-infection involving anaesthetic equipment is exceeding maximal inspiratory gas flow, must be pro-
uncertain, although a common breathing system has vided. The latter may be achieved using a Venturi mixing
been implicated in the cross-infection of patients with device. Increases FRC, thereby reducing airway collapse
hepatitis C. Treatment of anaesthetic apparatus varies and increasing arterial oxygenation. FIO2 may thus be
between hospitals, although disposable equipment is reduced.
now routinely used for convenience and cheapness. Uses:
Breathing system filters are routinely placed between to aid weaning from ventilators.
the patient and breathing system. to improve oxygenation during one-lung
Particularly important in ICU, immunodeficiency anaesthesia.
states and in high-risk infectious cases, e.g. HIV infec- in conditions of chronic airway collapse and
tion, hepatitis, chest infection, TB (equipment is changed hypoventilation, e.g. obesity hypoventilation
after use and other precautions taken, e.g. bacterial syndrome.
filters). in acute respiratory failure to avoid tracheal
Methods of killing contaminating organisms: intubation.
disinfection: kills most organisms but not spores. in neonates, e.g. in respiratory distress syndrome,
Achieved by: bronchomalacia and tracheomalacia, especially if
- pasteurisation: 30min at 77C. Rubber/plastic associated with apnoeic episodes. May be applied
items may be distorted. via nasal cannulae.
- chemical agents: Complications: as for PEEP, but less severe. Baro-
- formaldehyde, formalin (no longer used). trauma and reduction in cardiac output are more
- alcohol 70%. likely in neonates. Some patients cannot tolerate the
- chlorhexidine 0.10.5%. sensation of CPAP.
- glutaraldehyde 2%: expensive and may irritate Nasal CPAP, using a tightly fitting nasal mask, is the
skin. mainstay of treatment of obstructive sleep apnoea.
- hypochlorite 10%: may corrode metal.
- hydrogen peroxide, phenol 0.62%. Contraceptives, oral. Main anaesthetic considerations
Must be followed by rinsing and thorough drying. are related to the risk of venous thromboembolism,
sterilisation: kills all organisms and spores. The term which is 26 times as common in patients taking the
sterility assurance level (SAL) is a measure of the combined contraceptive pill. Patients taking the com-
probability of complete sterility of the item. A SAL bined pill containing third-generation progesterones
of 106 (i.e. probability of an organism surviving on (desogestrel or gestodene) are at greatest risk. Other
the item following sterilisation is one in a million) risk factors (e.g. inherited hypercoagulable states,
is considered acceptable. Methods include: smoking, obesity) compound this risk. Although 4 weeks
- dry heat, e.g. 150C for 30min. discontinuation of therapy before major or leg surgery
- moist heat: has traditionally been advocated, it has been claimed
- autoclave (most common method), e.g.: that this is based on insufficient evidence. If other risk
- 30min at 1 atm at 122C; factors exist, discontinuation of therapy (or sc heparin
- 10min at 1.5 atm at 126C; in view of the risk of pregnancy) has been suggested. The
- 3min at 2 atm at 134C. pill is restarted after the first period beyond a fortnight
Steam is used to increase temperature. Indica- postoperatively. No extra precautions are generally
tor tape or tubes are used to confirm that the thought to be necessary for minor surgery, e.g. dilatation
correct conditions are reached. and curettage, or with oestrogen-free therapy.
- low-temperature steam + formaldehyde. Stone J (2002). Anaesthesia; 57: 60625
ethylene oxide: expensive and flammable (the latter See also, Hormone replacement therapy
risk is reduced by adding 8090% fluorohydrocar-
bons or CO2). Toxic and taken up by plastics; up to Contractility, myocardial, see Myocardial contractility
2 weeks elution time is suggested before use.
-irradiation: used commercially but expensive and Contrast media, see Radiological contrast media
inconvenient for most hospital use.
gas plasma sterilisation: new technique where Controlled drugs (CDs). Refers to those governed by
equipment is exposed to a mixture of highly ionised the Misuse of Drugs Act 1971 (the term is often reserved
gas and free radicals. Provides low-temperature, dry for drugs described in Schedule 2 of the Misuse of Drugs
sterilisation with short cycle times. Regulations, 1985). The Association of Anaesthetists
The above methods do not destroy the prion protein issued guidelines on the handling of CDs in the operat-
responsible for variant CreutzfeldtJakob disease; this ing theatre suite in 1995; their recommendations were:
has led to increasing interest in disposable instruments. preference for prefilled syringes or similar devices
New enzyme-based agents that disrupt prion structure to be licensed medicinal products rather than
are under investigation. special items produced in a licensed facility for
156 Convulsions

individual patients, with medicines prepared in other drugs used in the control of seizures include
an unlicensed site (e.g. pharmacy) being least paraldehyde and magnesium sulphate (in eclamp-
preferable. sia). If seizures persist following phenytoin the
local guidelines for ordering, storage, handling and patient should be treated as for status epilepticus.
administration of CDs, including doctors signatures
in the CD register; recording in the notes the Cooley, Samuel, see Wells
amount given; return of unopened ampoules; and
disposal of unused drug (e.g. by discarding on to COPD, see Chronic obstructive pulmonary disease
absorbent material before disposal).
ability for ODPs to issue and handle CDs (along Copper kettle, see Vaporisers
with registration of ODPs, etc.).
an end to the sharing of ampoules between Co-proxamol, see Dextropropoxyphene
patients.
See also, Abuse of anaesthetic agents Cordotomy, anterolateral. Destruction of lateral spi-
nothalamic tracts, classically in the cervical region (C1
Convulsions. Usually refer to tonicclonic epileptic sei- 2); used in chronic pain management. Usually performed
zures. They increase cerebral and whole-body O2 demand percutaneously with X-ray guidance, under sedation.
and CO2 production, whilst airway obstruction and chest Electrical stimulation is used to confirm correct position-
wall rigidity may result in hypoventilation. Thus hypox- ing of the needle before thermocoagulation.
aemia, acidosis, hypercapnia and increased sympathetic Provides contralateral analgesia lasting up to 3 years;
activity may occur. Patients may also injure themselves. thus it is usually reserved for patients with a life expec-
Fits may be generalised or focal. Anaesthetic involve- tancy below this, e.g. patients with malignancy. Descend-
ment is usually necessary when they occur periopera- ing respiratory fibres lie close to the sectioned fibres and
tively, or in status epilepticus. therefore cordotomy is usually not performed in patients
Caused by: with respiratory disease. May damage pyramidal path-
pre-existing epilepsy (i.e. a continuing susceptibility ways, or cause Horners syndrome, bladder disturbances
to fits; may include other causes listed below). and paraesthesiae. Complications are more likely if cor-
hypoxaemia. dotomy is bilateral.
metabolic, e.g. hypoglycaemia, hyponatraemia, See also, Sensory pathways
hypocalcaemia, uraemia.
anaesthetic drugs: Corning, James Leonard (18551923). New York neu-
- diethyl ether; convulsions classically occurred rologist; first described (and coined the term) spinal
postoperatively in pyrexial children. anaesthesia in 1885. He had intended to observe the
- enflurane, especially following perioperative effects of cocaine on the spinal cord by injecting it into
hyperventilation and hypocapnia. the interspinal space of a dog, believing erroneously that
- ketamine, methohexital and doxapram in suscep- the interspinal blood vessels communicated with those
tible patients. Although propofol may cause myo- of the cord. Hind-quarter paralysis and anaesthesia fol-
clonic jerking, initial reports of epileptic seizures lowed. Repeated the experiment on a human, and sub-
following its use are now thought to be unfounded. sequently suggested its use in the treatment of
Similarly, etomidate may cause non-epileptic neurological disease. Epidural anaesthesia may have
twitching. been produced in some of his studies. Published the first
- local anaesthetic drugs in overdose. textbook on local anaesthesia in 1886.
- pethidine in very high or prolonged dosage. Con- Gorelick PB, Zych D (1987). Neurology; 37: 6724
vulsions may also follow its interaction with
monoamine oxidase inhibitors. Coronary angioplasty, see Percutaneous coronary
other drugs, e.g. alcohol, phenothiazines, tricyclic intervention
antidepressant drugs, cocaine.
fat embolism, also clot or air embolism. Coronary artery bypass graft (CABG). Performed for
head injury, CVA, cerebral infections, meningitis, ischaemic heart disease unresponsive to medical treat-
neurosurgery, brain tumours and other cerebral ment and unsuitable for Percutaneous coronary inter-
disease. vention (see below). A vascular conduit (most frequently
eclampsia. long saphenous vein, internal thoracic [internal
pyrexia in children. mammary] artery or radial artery) is grafted between the
acute O2 toxicity (Bert effect). aorta and coronary artery distal to its obstruction.
Management: Minimal access coronary surgery involves internal
protection of the airway and maintenance of oxy- thoracic artery grafting through tiny incisions in the left
genation, with positioning on the side if possible. side of the chest, offering the advantages of arterial
Tracheal intubation and IPPV may be required, e.g. grafts to the left anterior descending coronary artery
if large doses of depressant drugs are needed. without the need for cardiopulmonary bypass, although
anticonvulsant drugs: one-lung ventilation is still required. More recently, a
- diazepam 5mg increments iv up to 20mg; may technique of off-pump CABG has been developed, in
be given rectally. Midazolam 510mg im has which median sternotomy is carried out enabling mul-
been used as an alternative when iv cannulation tiple grafts on the beating heart. Surgery requires good
is impossible. Lorazepam iv 75g/kg is the first- access (cardiac displacement), stabilisation of the hearts
line treatment for status epilepticus. wall at the site of anastomoses using special devices, and
- phenytoin iv, 15mg/kg slowly, with ECG the use of intracoronary shunts or strategies to limit
monitoring. periods of arterial occlusion. Anaesthesia is complicated
 Coronary sinus catheterisation 157

by the need for cardiovascular stability, normothermia Measurement:

and bradycardia during anastomoses to reduce move- Fick principle using N2O or argon. Requires coro-
ment (bradycardia is less important with stabilising nary sinus catheterisation.
devices). Complications and costs are felt to be less than thermodilution techniques to estimate coronary
with traditional CABG but long-term randomised trials sinus flow, thus providing an indication of left ven-
are relatively lacking. tricular drainage.
Life expectancy is improved following CABG (vs. nuclear cardiology may be used to indicate regional
percutaneous transluminal coronary angioplasty flow.
[PTCA]) in: See also, Coronary circulation; Ischaemic heart disease;
moderate/severe angina, triple-vessel disease and Myocardial metabolism
impaired ventricular function.
double-vessel disease, including severe stenosis of Coronary care unit (CCU). Specialised hospital ward
the proximal left anterior descending artery. for the management of patients with acute MI or other
severe stenosis of the left main stem coronary serious unstable cardiac disease. Features continuous
artery. ECG monitoring, and availability of defibrillators, drugs
Life expectancy is not improved in single-vessel disease and specially trained staff. Allows surveillance and
or if angina is not present. prompt treatment of arrhythmias and cardiac failure,
PTCA is an alternative but emergency CABG may and limitation of infarct size and restoration of coronary
be required if unsuccessful. blood flow using fibrinolytic drugs. With appropriate
Anaesthesia is as for ischaemic heart disease and patient selection, management on CCU results in con-
cardiac surgery. Combinations of aspirin, dipyridamole sistently better outcomes.
and full anticoagulation are used postoperatively to Anon (1988). Lancet; ii: 8301
maintain graft patency.
Mortality is under 1% for 12 grafts, but increases if Coronary circulation
more grafts are anastomosed. Mortality is greater in Arterial supply (Fig. 48a):
women. right coronary artery: arises from the anterior aortic
sinus. Passes between the pulmonary trunk and
right atrium, and runs in the right atrioventricular
Coronary artery disease, see Ischaemic heart disease
groove between the right atrium and ventricle.
Descends the anterior surface of the heart, continu-
Coronary blood flow. Normally approximately 5% of ing inferiorly to anastomose with the left coronary
cardiac output, i.e. 250ml/min or 80ml/100g/min. May artery. Supplies the right ventricle and sinoatrial
increase up to five times in exercise. The inner 1mm of node and, in 90% of the population, the atrioven-
the left ventricle obtains O2 via diffusion from blood in tricular node and posterior and inferior parts of the
the ventricular cavity; the remainder of the ventricle is left ventricle.
supplied via epicardial vessels. The left coronary vessels left coronary artery: arises from the left posterior
are compressed by the contracting myocardium during aortic sinus. Passes lateral to the pulmonary trunk
systole; thus flow to the subendocardium occurs during and runs in the left atrioventricular groove. Supplies
diastole only. Superficial areas receive more constant the anterior wall of the left ventricle and the inter-
flow. Atrial and right ventricular flow occurs throughout ventricular septum via its left anterior descending
the cardiac cycle. The left ventricle is therefore most at branch, and the lateral wall of the left ventricle via
risk from myocardial ischaemia. its circumflex branch.
Left ventricular blood flow is related to: The artery that supplies the posterior descending and
difference between aortic end-diastolic pressure the posterolateral arteries determines the dominant
and left ventricular end-diastolic pressure. coronary artery; in 60% of the population, the right coro-
duration of diastole (inversely related to heart nary artery is dominant.
rate). Venous drainage (Fig. 48b):
patency/radius of the coronary arteries; related to: one-third via venae cordis minimae (thebesian
- autoregulation: normally maintains blood flow veins) and anterior cardiac veins small veins
above MAP of 60mmHg, possibly via the action draining directly into the heart chambers (right
of adenine nucleotides, potassium, hydrogen ions, atrium receiving most; left ventricle least). Those
prostaglandins, lactic acid or CO2 released from draining into the left heart are a source of anatomi-
myocardial cells. cal shunt.
- autonomic neural input: has little direct influence, two-thirds via the coronary sinus, draining into the
being overridden by the effect on SVR and myo- right atrium near the opening of the inferior vena
cardial contractility. cava.
- coronary stenosis/spasm and the state of collat- [Adam Thebesius (16861732), German physician]
eral vessels (e.g. coronary steal). See also, Coronary blood flow
- drugs causing vasoconstriction/dilatation.
blood viscosity. Coronary sinus catheterisation. Performed using fluo-
The oxygen extraction of the myocardium is almost 75% roscopy. May be used to determine:
and therefore increased O2 demand can only be met by coronary sinus blood flow, using a thermodilution
increased flow and is important if ischaemia is to be technique.
prevented. Reductions in flow may be minimised by con- coronary blood flow, using the Fick principle.
trolling the above factors. Coronary perfusion pressure blood O2 and lactate levels. The latter are raised in
and duration of diastole may be assessed by the diastolic myocardial ischaemia, due to decreased uptake by
pressuretime index. myocardial tissue and increased production.
158 Coronary steal

(a) (b)

Superior
vena cava Aorta

Pulmonary trunk
Left coronary artery Oblique vein
Right coronary Coronary sinus
Circumflex artery
artery
Anterior Anterior Great cardiac vein
interventricular artery cardiac veins

Marginal branch Posterior interventricular artery Small cardiac vein Middle cardiac vein

Fig. 48 Coronary circulation: (a) arterial; (b) venous

Coronary steal. Diversion of blood from poorly per- it may have been suicide.
fused areas of myocardium to those already adequately it occurred during or shortly after detention in
perfused. May be caused by vasodilator substances police or prison custody.
acting on small coronary arteries but not on larger epi- Following referral, the coroner may hold an inquest in a
cardial vessels. Poorly perfused areas supplied by ste- small percentage of cases; a verdict may then be issued
nosed vessels may be dependent on collateral vessels for as to the manner and cause of death.
blood flow. Dilatation of normal small arteries increases
flow to normal areas, but the stenosed vessels are unable Cor pulmonale. Right ventricular hypertrophy second-
to dilate sufficiently, resulting in steal. Antianginal drugs, ary to increased pulmonary vascular resistance due to
e.g. nitrates, are thought to increase collateral flow by chronic lung disease. COPD is the commonest cause, but
acting predominantly on the large epicardial vessels. any disease that causes chronic hypoxaemia (e.g. pulmo-
Adenosine, dipyridamole, papaverine and isoflurane nary fibrosis) may result in hypoxic pulmonary vasocon-
have all been shown to cause steal in animal models, but striction, eventually with pulmonary vascular muscle
the significance of this in humans is disputed. Recent hypertrophy and pulmonary hypertension. Right ven-
work has demonstrated that isoflurane in fact has a pro- tricular failure may ensue. PE is included in some
tective effect against myocardial ischaemia (ischaemic definitions.
preconditioning). Features:
those of the underlying disease, including cyanosis
Coronary stents, see Percutaneous coronary and hypoxaemia.
intervention those of right-sided cardiac failure: peripheral
oedema, raised JVP, hepatomegaly, third heart
Coroner. Independent judicial officer of the Crown who sound.
has a duty to investigate the circumstances of some of pulmonary hypertension and underlying disease
deaths. Coroners are barristers, solicitors or legally quali- on CXR. The ECG may show right ventricular
fied medical practitioners, and are assisted by Coroners hypertrophy and axis deviation, peaked P waves (P
Officers. Cases are referred mostly from doctors, but also pulmonale), and T wave and ST segment changes
from registrars of births and deaths and from other in the right chest leads.
sources, e.g. police. A death should be reported if: Anaesthetic management:
its cause is unknown. as for COPD/underlying disease.
the deceased was not seen by the certifying doctor as for cardiac failure.
after death or within the fortnight preceding it. as for pulmonary hypertension.
it was violent, unnatural or suspicious.
it may have been caused by an accident (whenever Correlation, see Statistical tests
it occurred).
it may have been caused by neglect (by self or Corticosteroids. Steroid hormones released from the
others). cortex of the adrenal gland. Classified according to
it may have been caused by industrial disease or activity:
related to employment. mineralocorticoids: mainly aldosterone. Synthetic
it may have been caused by abortion. mineralocorticoids include fludrocortisone, used for
it occurred during an operation or before recovery replacement therapy and in congenital adrenal
from an anaesthetic. hyperplasia and postural hypotension.
 Co-trimoxazole 159

glucocorticoids: mainly cortisone (hydrocortisone). employers to assess the risk to employees, eliminate or
The term (cortico)steroid therapy usually refers to control the risk (e.g. with protective clothing, adequate
use of drugs with predominantly glucocorticoid ventilation), monitor the exposure and health of employ-
activity, although most have mineralocorticoid ees, and provide information and training. Employees
activity too. Corticosteroids are used in adrenocor- must make full use of any control measure provided.
tical insufficiency, and to suppress inflammatory Anaesthetic implications include concerns about the
and immunological responses, including: connective environmental safety of anaesthetists, scavenging and
tissue diseases; raised ICP due to tumours; skin dis- contamination of anaesthetic equipment.
eases; blood dyscrasias; allergic reactions; asthma;
myasthenia gravis; and following organ transplanta- Costs of anaesthesia. Intraoperative anaesthetic cost
tion. Have been used in ARDS but their efficacy is constitutes about 56% of total hospital costs, whereas
disputed. Use in severe sepsis remains controversial the total cost for intraoperative patient care is approxi-
and is usually reserved for patients with confirmed mately 30%. Anaesthetic costs may be divided into:
adrenocortical insufficiency and/or high vasopres- overhead costs:
sor requirements. - capital equipment, e.g. ventilators, anaesthetic
Prednisolone 5mg has equivalent anti-inflammatory machines. Often difficult to quantify since the life
activity to 20mg hydrocortisone, 4mg methylpred- of equipment may be uncertain.
nisolone and 0.75mg dexamethasone. All except - maintenance.
hydrocortisone have little mineralocorticoid activ- - staff salaries, e.g. anaesthetists, anaesthetic assis-
ity and are thus suitable for long-term disease tants, recovery nurses.
suppression. running costs:
The drugs have many side effects: - drugs, e.g. iv and inhalational anaesthetic agents,
related to mineralocorticoid activity: water and neuromuscular blocking drugs, opioids, antiemet-
sodium retention, hypokalaemia, hypertension. ics, iv fluids.
hyperglycaemia and diabetes mellitus, osteoporosis - piped gases (and those in cylinders).
and pathological fractures, skeletal wasting with - consumable items, e.g. iv cannulae, tracheal tubes,
proximal myopathy. airways.
GIT effects: dyspepsia, peptic ulcer disease. Estimates of the total costs of individual procedures have
mental changes: euphoria, depression. been made but vary widely according to the country and
spread of infection. Severe chickenpox is a particu- hospital, and the methods used for the calculations. In
lar risk. addition, techniques or drugs which appear more expen-
impaired wound healing. sive may have cost savings elsewhere, e.g. by reducing
cataract formation. postoperative complications and hospital stay. With
growth suppression in children. increasing scrutiny of healthcare costs, calculations of
Cushings syndrome may occur with high dosage. anaesthetic costs and value-based anaesthetic care may
adrenal suppression, due to inhibition of ACTH become more common and pressure applied to anaes-
release. Pituitaryadrenal axis function may take 6 thetic departments to reduce their costs, despite the rela-
months to recover following withdrawal of therapy; tively small amounts compared to those incurred by the
during this time patients are unable to mount a surgeons. However, it has been estimated that about half
normal cortisone response to stress (secretion the intraoperative anaesthetic costs could be influenced
increases from 25mg/day to 300mg/day), and may by the choice of drugs and anaesthetic techniques.
develop circulatory collapse. Patients at risk are
those who have: Costs of intensive care. Actual costs of ICU treatment
- received corticosteroid therapy for longer than 2 are difficult to quantify since no standardised model of
weeks within the previous 2 months (up to 1 year costing has been validated as being applicable to all types
has been suggested). of unit. Methods used have included dividing the total
- adrenocortical insufficiency or adrenalectomy. annual expenditure by the number of patients treated
Based on studies of normal cortisone responses fol- and the use of severity of illness and workload scoring
lowing surgery, estimated amounts required are systems. Costs have been divided into six cost blocks:
25mg hydrocortisone equivalent for minor surgery; capital equipment: includes depreciation, mainte-
5075mg/day for 12 days for moderate surgery; nance and lease charges (~6%).
and 100150mg/day for 23 days for major surgery. estates: includes building depreciation, water,
These estimates include current medication; thus sewage, energy and maintenance charges (~3%).
patients already taking the required amount do not non-clinical support: includes administration and
need supplementation. cleaning (~8%).
See also, Stress response to surgery clinical support: includes physiotherapy, radiology,
laboratory services, pharmacy, dietetics (~8%).
Corticotropin (Corticotrophin), see Adrenocorti consumables: includes drugs, fluids, nutrition, dis-
cotrophic hormone posables (~25%).
staff: medical, nursing, technical (~50%).
COSHH regulations (Control of Substances Hazard- ICU costs are significantly higher in the first 24h after
ous to Health). Came into force in 1989 in Scotland, admission and for patients with greater severity of illness
England and Wales, and in 1991 in Northern Ireland. The as defined by the various scoring systems.
latest regulations were published in 2011. Stipulate that
employers must identify and control any substances Co-trimoxazole. Synthetic antibacterial drug contain-
which may be hazardous to health, e.g. chemicals and ing one part trimethoprim to five of the sulphonamide
micro-organisms. Important guidance is given to allow sulfamethoxazole. The drugs inhibit bacterial DNA
160 Cough

replication and protein synthesis respectively. Previously CPAP, see Continuous positive airway pressure
widely used to treat exacerbations of COPD and urinary
tract infections; due to its toxicity and unfavourable CPD/CPD-A, Citratephosphatedextrose/Citrate
side-effect profile, routine use is now restricted to pro- phosphatedextroseadenine, see Blood storage
phylaxis and treatment of pneumocystis pneumonia and
toxoplasmosis. CPET/CPEX, see Cardiopulmonary exercise testing
Dosage: 960mg1.44g orally/iv bd.
Side effects: nausea, diarrhoea, erythema multiforme, CPR, see Cardiopulmonary resuscitation
pancreatitis, hepatic impairment, blood dyscrasias.
CPX, see Cardiopulmonary exercise testing
Cough. Reflex partially under voluntary control. A deep
inspiration is followed by forceful expiration against a Crack, see Cocaine
closed glottis which is suddenly opened to allow explo-
sive exhalation. An intrathoracic pressure of up to 40 CRAMS scale, see Circulation, respiration, abdomen,
kPa may be produced, and the peak expiratory flow may motor and speech scale
exceed 900 l/min. Solid objects, liquids and mucus are
thus expelled from the airways. Afferent pathways for Cranial nerves. Composed of 12 pairs, passing from the
coughing are from the mucosa of the larynx, trachea and brain via openings in the skull. Convey motor and
large bronchi via the vagus nerve and medulla, and are sensory fibres involved in somatic, parasympathetic
stimulated by physical or chemical irritants. (visceral) and special visceral (e.g. taste sensation)
Factors associated with coughing during anaesthesia pathways:
include: I: olfactory nerves (convey smell sensation from the

insertion of a pharyngeal airway or tracheal tube if nasal mucosa); pass through the cribriform plate of
depth of anaesthesia is inadequate. the ethmoid bone to the olfactory bulb.
introduction of inhalational anaesthetic agents (e.g. II: optic nerve (conveys visual sensation from the

isoflurane) at too high a concentration. retina); passes through the optic canal and via the
use of certain iv anaesthetic agents, e.g. optic chiasma, tract and radiation to the visual
methohexital. cortex in the occipital lobe of the brain (see Pupil-
presence/aspiration of blood, saliva or gastric lary reflex).
contents. III: oculomotor nerve (somatic motor fibres supply

increased airway reactivity, e.g. asthma, COPD, the extraocular muscles except superior oblique
upper respiratory tract infection, smoking. and lateral rectus; parasympathetic fibres supply the
In ICU, cough may be produced by airway manoeuvres pupillary sphincter and ciliary muscles after synaps-
such as tracheobronchial suctioning, especially if the ing in the ciliary ganglion). In the posterior fossa,
carina is stimulated. Persistent coughing may cause inad- the nerve passes from the upper midbrain between
equate ventilation, and excessive intrathoracic pressures the cerebral peduncles and lies near the edge of the
may reduce cardiac output (causing cough syncope in tentorium cerebelli (hence the early ipsilateral
non-anaesthetised patients). Deepening of anaesthesia, pupillary dilatation that occurs in acute rises of ICP,
increased FIO2 and neuromuscular blockade may be when the nerve is compressed against the edge of
required. the tentorium [Hutchinsons pupil]). In the middle
The reflex is protective, helping to prevent sputum cranial fossa, it passes forwards on the lateral wall
retention and atelectasis. Postoperatively, it may be of the cavernous sinus as far as the supraorbital
reduced by: fissure. Before entering the fissure it divides into
impaired mechanical movement, e.g. due to pain, superior and inferior branches.
muscle weakness, neuromuscular blockade or IV: trochlear nerve (motor supply to the superior

disease, central and peripheral nervous disorders. oblique muscle). Passes from the dorsum of the
depressed cough reflex, e.g. depressant drugs, central lower midbrain, then forwards in the lateral wall
lesions. of the cavernous sinus to enter the supraorbital
Opioid analgesic drugs, e.g. codeine, are sometimes used fissure.
to suppress cough, e.g. in malignant disease. V: trigeminal nerve (sensory fibres supply the ante-
rior dura, scalp and face, nasopharynx, nasal and
oral cavities and air sinuses; motor fibres supply the
Cough-CPR. Maintenance of cerebral perfusion and
muscles of mastication). The sensory nuclei are in
consciousness during severe arrhythmias, e.g. VF, by
the medulla, midbrain and pons. The nerve passes
repeated coughing. Each cough increases intrathoracic
from the pons to the trigeminal ganglion lateral to
pressure and expels arterial blood from the thorax; each
the cavernous sinus, where it divides into ophthal-
gasp draws in venous blood. Has been successful for up
mic, maxillary and mandibular divisions. The motor
to 12min pending availability of a defibrillator.
nucleus is in the pons; the root bypasses the gan-
See also, Cardiopulmonary resuscitation
glion to join the mandibular division. Branches.
- ophthalmic division (V1): branches (lacrimal,
Coulomb. Unit of charge. One coulomb is the amount frontal and nasociliary nerves) pass via the supe-
of charge passing any point in a circuit in 1s when a rior orbital fissure. Associated with the ciliary
current of 1 ampere is flowing. Equivalent to the charge ganglion.
carried by 6.242 1018 electrons. - maxillary division (V2): passes via the foramen
[Charles Coulomb (17381806), French physicist] rotundum. Associated with the pterygopalatine
ganglion. Branches (nasal, nasopalatine, pala-
COX, see Cyclo-oxygenase tine, pharyngeal, zygomatic, posterior superior
 Crash induction 161

alveolar and infraorbital nerves) are involved through the jugular foramen; the cranial root joins
with lacrimation and sensory and sympathetic the vagus (to the pharynx and larynx) and the spinal
supply to the nose, nasopharynx, palate and orbit. root passes to the sternomastoid.
- mandibular division (V3): passes via the foramen XII: hypoglossal nerve (motor supply to all muscles
ovale. Associated with the otic (parotid gland) of the tongue except palatoglossus). Passes from the
and submandibular (submandibular and sublin- medulla, then through the hypoglossal canal behind
gual glands) ganglia. Sensory branches are the the carotid sheath to the tongue.
meningeal, buccal, auriculotemporal, inferior Cranial nerves may be assessed by testing:
alveolar and lingual nerves. Somatic motor fibres I: ability to smell substances, e.g. peppermint, cloves.
supply the muscles of mastication (masseter, pter- Irritant substances are avoided, since they may act
ygoids, temporalis). via the Vth nerve.
(See Gasserian ganglion block; Mandibular nerve II:
blocks; Maxillary nerve blocks; Ophthalmic nerve - visual acuity using distant objects/charts.
blocks.) - visual fields, e.g. ability to discern peripheral
VI: abducens nerve (motor supply to the lateral movement whilst looking straight ahead. Size of
rectus). Passes from the lower pons through the blind spot.
cavernous sinus and supraorbital fissure. Often - appearance of optic discs.
involved in injury to the skull. - pupillary reflex to light and accommodation.
VII: facial nerve (mixed sensory and motor nerve): III, IV, VI: full eye movements without diplopia.
passes laterally from the lower pons through the Results of specific lower motor neurone lesions:
internal acoustic meatus to the geniculate ganglion. - III: eye displaced downwards and outwards,
Passes through the temporal bone to emerge pupil dilated, ptosis.
through the stylomastoid foramen. Runs forward to - IV: downward gaze impaired; eyeball rotated
the parotid gland. Branches: inwards by inferior rectus when attempted.
- motor supply to the muscles of facial expression: - VI: lateral gaze impaired. Upper motor
divides within the parotid gland into temporal, neurone lesions may cause impaired conjugate
zygomatic, buccal, mandibular and cervical movements.
branches from above down. Branches also pass to V:
the digastric, stylohyoid, auricular and occipital - skin sensation in each division (see Fig. 76; Gas-
muscles. serian ganglion block), e.g.:
- greater petrosal nerve: passes from the geniculate - ophthalmic: forehead, corneal reflex (afferent
ganglion to the pterygopalatine ganglion and arc V, efferent pathway VII).
fossa, to supply the lacrimal gland. - maxillary: cheek next to nose.
- chorda tympani: leaves the facial nerve before it - mandibular: side of jaw.
enters the stylomastoid foramen; conveys taste - ability to open/close jaw against resistance.
sensation from the anterior two-thirds of the VII:
tongue and parasympathetic fibres to the subman- - facial expression: ability to show teeth, raise eye-
dibular gland. brows, screw up eyes against resistance, blow out
VIII: vestibulocochlear nerve (special somatic cheeks. Movement in the upper part of the face is
sensory nerve): cochlear and vestibular components preserved in upper motor neurone lesions, and
are involved in hearing and balance respectively. lost in lower motor neurone lesions.
The nerve is formed in the internal acoustic meatus - taste sensation of the anterior tongue, e.g. to salt,
and passes to nuclei in the floor of the fourth ven- sugar, citric acid.
tricle. Connects centrally with cranial nerves III, IV, VIII:
VI, XI and descending pathways to the upper cervi- - ability to hear, e.g. fingers rubbing next to the ear.
cal cord. - using a tuning fork: air conduction is lost in middle
IX: glossopharyngeal nerve (conveys sensation ear disease, with preservation of bone conduction
from the pharynx, back of the tongue and tonsil, (Rinnes test). Both are impaired in nerve damage.
middle ear, carotid sinus and carotid body, taste If the tuning fork is placed on the forehead, the
from the posterior one-third of the tongue, and sound is heard best on the affected side in middle
parasympathetic fibres to the parotid gland; pro- ear disease, on the unaffected side in nerve disease
vides motor supply to stylopharyngeus). Passes (Webers test).
from the medulla through the jugular foramen, and IX, X:
then passes between the internal and external - taste sensation of the posterior tongue.
carotid arteries to the pharynx. - soft palate elevation is equal on both sides.
X: vagus nerve (provides parasympathetic afferent - gag reflex.
and efferent supply to the heart, lungs and GIT - voice and phonation.
as far as the splenic flexure, motor supply to the XI: ability to raise shoulders, and rotate head to the
larynx, pharynx and palate, and conveys taste sensa- side, against resistance.
tion from the valleculae and epiglottis, and sensa- XII: protrusion of tongue in the midline (to the
tion from the external ear canal and eardrum). affected side if abnormal). Absence of wasting and
Passes from the medulla via the jugular foramen. ability to move from side to side.
XI: accessory nerve (motor supply to the sterno- [Sir Jonathan Hutchinson (18281913), English surgeon;
mastoid and trapezius muscles). Arises from the Friedrich Rinne (18191868) and Friedrich Weber
upper five cervical segments of the spinal cord, (18321891), German otologists]
passing upwards through the foramen magnum to
join the smaller cranial root. Leaves the skull Crash induction, see Induction, rapid sequence
162 C-reactive protein

C-reactive protein (CRP). Plasma protein, so-called familial: caused by gene mutation, accounts for
because it reacts with the C polysaccharide of pneu 10% of cases.
mococci. Complexes formed when CRP binds to sac- iatrogenic: identical to sCJD but due to transmis-
charides of microorganisms to activate the classical sion of prion protein during neurosurgical proce-
complement pathway and stimulate cell-mediated cyto- dures, corneal grafts and administration of human
toxicity. Part of the acute-phase response, it is synthe- growth hormone. Accounts for < 5% of cases. Kuru,
sised in the liver in response to the cytokine interleukin-6. a prion disease caused by ingestion of infected
Plasma levels are normally under 10mg/l but increase neural tissue during cannibalism, is seen in the Fore
within 610h of tissue damage. Has therefore been used tribe of Papua New Guinea.
to aid diagnosis of acute inflammation (e.g. infection) variant (vCJD): first described in 1996 in young
and to monitor the response to treatment. Although in people. Due to ingestion of beef from cattle affected
the ICU, because of underlying critical illness, resting by bovine spongiform encephalopathy (BSE); the
plasma levels rarely lie within the normal < 10mg/l prion causing vCJD is identical to that present in
range (e.g. may exceed 200mg/l), a 25% change from the BSE. sCJD is caused by a different prion. Over 160
previous days value may still be used to indicate acute cases were reported in the UK between 1990 and
changes in inflammatory status. 2007, with the peak incidence in 2000.
Pvoa P (2002). Intensive Care Med; 28: 23543 The incubation period of the disease is variable and may
be up to 40 years with Kuru, but is considerably shorter
Creatinine. Basic compound formed mainly in skeletal with other forms (e.g. vCJD). Clinical features of vCJD
muscle from phosphorylcreatine. The latter is formed include early psychiatric changes, sensory disturbances,
from ATP and creatine, and is a source of ATP during ataxia, stimulus-sensitive myoclonus, dystonia and
exercise. Creatinine production remains fairly constant, dementia. Definitive diagnosis requires brain biopsy,
hence the value of plasma creatinine measurement as although high concentrations of prion protein are found
a reflection of renal function (cf. urea, whose produc- on tonsillar biopsy.
tion varies with the amount of protein breakdown Anaesthetic implications:
occurring). Normal value: 60130 mol/l; serial values high exposure rate of the population to BSE-
are more useful indicators of renal function than single infected beef may result in an epidemic of vCJD,
measurements. As GFR decreases, creatinine levels although this is now considered unlikely given the
rise slowly up to about 200 mol/l (GFR below 40 ml/ decline in the number of cases since 2003.
min), rising greatly thereafter for small decreases of conventional decontamination of instruments does
GFR. Thus measurement is less useful at high values, not destroy the prion protein; thus transmission
and values above 200 mol/l represent severe renal may occur via contaminated surgical and anaes-
impairment. thetic instruments. Tissues with high prion concen-
See also, Creatinine clearance trations (e.g. brain, spinal cord, tonsils, lymph nodes
and lower GIT) present greater risk. Disposable
Creatinine clearance. Clearance of creatinine, used as instruments are available for high-risk cases and
an approximation for GFR. Although some creatinine is care must be taken to use disposable or sheathed
secreted by renal tubules, this source of error tends to laryngoscope blades in these cases.
be cancelled out by the over-measurement of plasma vCJD has been transmitted by blood transfusion
creatinine at low levels. Commonly estimated, since cre- and, since 1998, blood products in the UK have
atinine is easily measured. Usually averaged over 24h been sourced from countries with no BSE and
to reduce error from inaccurate urine volume measure- blood for transfusion has been leucodepleted. The
ment. Normal value: 90130ml/min. Department of Health announced in 2002 that fresh
frozen plasma for children born after 1995 (who
Cremophor EL. Polyoxyethylated castor oil, formed should not have been exposed to BSE via the food
from ethylene oxide and castor oil. Used as an emulsify- chain) would be obtained from unpaid US blood
ing agent in preparations of certain drugs. Implicated in donors. In 2004, after the death of a patient who
causing adverse drug reactions, sometimes severe, after possibly contracted vCJD via transfused blood, UK
iv injection. Has led to the withdrawal of iv induction donors were banned from giving blood if they had
agents (e.g. Althesin, propanidid and the original formu- received a transfusion since 1980. A filter which
lation of propofol), although injectable preparations removes prion protein is undergoing trials.
of other drugs may still contain it (e.g. ciclosporin, [Hans G Creutzfeldt (18851964), German psychiatrist;
vitamin K). Alfons M Jakob (18841931), German neurologist]
Farling P, Smith G (2003). Anaesthesia; 58: 6279
CREST syndrome, see Systemic sclerosis
Cricoid pressure (Sellicks manoeuvre). Digital pres-
CreutzfeldtJakob disease (CJD). Group of transmis- sure against the cricoid cartilage of the larynx, pushing
sible human encephalopathies caused by infectious pro- it backwards. The oesophagus is thus compressed
teins known as prions. Infection results in the formation between the posterior aspect of the cricoid and the ver-
of an abnormal form of a cellular membrane protein tebrae behind. The cricoid cartilage is used since it forms
(prion-related protein) that causes destruction of neuro- the only complete ring of the larynx and trachea. Used
nal tissue and overgrowth of glial cells. At least four to prevent passive regurgitation of gastric and oesopha-
forms are recognised: geal contents, e.g. during induction of anaesthesia,
sporadic (sCJD): cause is unknown, accounts for although no randomised controlled trials concerning its
90% of cases. Occurs in the elderly; incidence is 1 efficacy have been conducted.
per million population/year. Dementia is prominent The cricoid cartilage is identified level with C6, and
and death occurs within 6 months. the index finger is placed against the cartilage in the
 Critical care 163

midline, with the thumb and middle finger on either side. and general anaesthesia, calling the concept anociasso-
Moderate pressure may be applied before loss of con- ciation (led to the concept of balanced anaesthesia).
sciousness, and firmer pressure maintained until the cuff Also investigated the pathogenesis and treatment of
of the tracheal tube is inflated. shock, and described a pneumatic garment for its treat-
Estimates of the force required vary from 20 N to ment in 1903.
over 40 N (approximately corresponding to a mass of Tetzlaff JE, Lautsenheiser F, Estafanous FG (2005). Reg
2kg to over 4kg), most recent guidance suggesting Anesth Pain Med; 29: 6005
2030 N as optimal. It must be released during active
vomiting, to reduce risk of oesophageal rupture. Incor- Crisis resource management. Strategy for coping with
rectly performed cricoid pressure may hinder laryngos- critical incidents, developed initially in the airline indus-
copy either by distorting the laryngeal anatomy or try (as Cockpit and then Crew resource management)
flexing the neck; the latter may be prevented by the as a means of dealing effectively with crises and prevent-
assistants second hand being placed behind the patients ing them from evolving into disasters. Has since been
neck. Cricoid pressure may also hinder placement of adapted to other high-risk industries and also to anaes-
an LMA. thesia. Consists of a number of components:
[Brian A Sellick (19181996), London anaesthetist] being aware of the immediate and wider environ-
See also, Induction, rapid sequence ment, e.g. knowing what equipment and staff
are available; manipulating the environment as
Cricothyrotomy. Puncture or incision of the cricothy- required (e.g. turning on the light in a dark operat-
roid membrane (passes between the thyroid cartilage ing theatre).
above and the cricoid cartilage below) of the larynx. use of all available resources and allocating them
Performed to allow ventilation in airway obstruction, e.g. appropriately, e.g. using cognitive aids (e.g. printed
as a last resort following failed intubation. algorithms); delegating personnel according to their
With the neck extended, the cricoid cartilage is identi- skills.
fied level with C6, and a cricothyrotomy device inserted planning and anticipation, e.g. rehearsing drills;
in the midline above the cartilage. Most devices consist mobilising resources when likely to be needed
of a needle with or without a cannula, connected to a rather than when they are actually needed; calling
standard 15-mm fitting or needle hub. Aspiration of air for help early.
confirms correct placement. Special tubes, introducers effective leadership.
and guide-wires are also available. effective communication, including specific and
In emergencies, a wide-bore needle or cannula may directed requests/orders (and receiving confirma-
be used, connected to a means of ventilation in a number tion that they have been understood correctly).
of different ways: Commonly forms part of training programmes involving
via a 3.5-mm tracheal tube connector, or via a 2-ml simulators but can be incorporated into many risk man-
syringe with its plunger removed and an 8-mm agement programmes.
tracheal tube connector inserted in its open end:
the connector attaches to a standard anaesthetic Critical care. System designed to look after seriously ill
breathing system but, even with 1015 l/min O2 patients, with levels of care allocated according to clini-
fresh gas flow, flow rates through the cannula may cal need (and not to staffing levels or location). Four
be less than 100ml/s and chest movement may not levels are recognised in the UK:
be seen. level 0: patients whose needs can be met by normal
via an iv fluid giving set or a three-way tap exten- ward care in an acute hospital, e.g. those requiring
sion, attached proximally to O2 tubing and thence oral or iv bolus medication or patient-controlled
to a standard wall- or cylinder-mounted O2 outlet. analgesia. Observations required less frequently
With gas flows of 1015 l/min, up to 400ml/s may than 4h.
be delivered through the cannula, usually adequate level 1: patients recently discharged from a higher
to produce visible chest movements. level of care, in need of additional and more fre-
via an injector device, e.g. as used for bronchoscopy; quent monitoring and clinical advice, or requiring
connects directly to the needle hub. As much as critical care outreach services.
800ml/s gas flow may be produced through the level 2: patients requiring single organ monitoring
cannula. or support (e.g. nasal CPAP), preoperative optimi-
Exhaled gases must be free to escape, or barotrauma sation or extended postoperative care, or those with
may result. In upper airway obstruction, further punc- major uncorrected physiological abnormalities (e.g.
tures may be required to allow exhalation. Incorrect increased respiratory rate, tachycardia, hypoten-
cannula placement may cause severe subcutaneous sion, decreased Glasgow coma scale) and at risk of
emphysema. Haemorrhage may occur. The cannula deterioration.
should be firmly fixed in place; in the initial emergency level 3: patients requiring advanced respiratory
it should be gripped firmly during attempts to ventilate monitoring and support, e.g. IPPV (but excluding
the lungs to prevent its dislodgement. electively IPPV for < 24h postoperatively), those
Cricothyroid puncture is also performed for transtra- requiring monitoring and support of two or more
cheal injection of lidocaine, during awake intubation. organ systems, or those with chronic impairment of
The minitracheotomy device may also be used for one or more organ systems who require support for
sputum aspiration. an acute reversible failure of another organ system
(e.g. severe ischaemic heart disease and major peri-
Crile, George Washington (18641943). Eminent US operative haemorrhage).
surgeon, a major contributor to regional anaesthesia. Thus the term encompasses care provided on both ICUs
Described the combination of opioids, regional block and HDUs.
164 Critical Care Medicine

Critical Care Medicine. Monthly journal of the Society - violations: e.g. not checking the drug with
of Critical Care Medicine. First published in 1972. another person when that is the policy of the
department.
Critical damping, see Damping In addition, human errors may be classified as knowledge-
based, rule-based or skill-based.
Critical flicker-fusion test, see Recovery testing In the UK, the National Patient Safety Agency was
established in 2001 to coordinate national reporting of
Critical illness polyneuropathy. Acute sensorimotor critical incidents and dissemination of lessons learned
axonopathy associated with critical illness, usually from them.
involving IPPV and sepsis and/or MODS but it may also Mahajan RP (2010). Br J Anaesth; 105: 6975
be seen in uncomplicated respiratory failure. Usually See also, Crisis resource management
self-limiting, its severity is related to the duration of
critical illness. Of unknown aetiology, although toxic, Critical pressure. Pressure required to liquify a vapour
metabolic, nutritional and vascular factors have been at its critical temperature. Examples:
suggested. Clinical manifestations include muscle O2: 50 bar.
wasting, decreased or absent tendon reflexes and diffi- N2O: 72 bar.
culty weaning from ventilators. Has been implicated in CO2: 73 bar.
cases of severe hyperkalaemia following administration
of suxamethonium. Accurate diagnosis requires electro- Critical temperature. Temperature above which a
physiological studies which demonstrate axonal degen- vapour cannot be liquified by any amount of pressure.
eration and exclude other causes such as demyelination, Above this temperature, the substance is a gas; below it,
compression neuropathies and disorders of the neuro- the substance is a vapour. Examples:
muscular junction (e.g. caused by prolonged treatment O2: 118C.
with neuromuscular blocking drugs). Often accompa- N2O: 36.5C.
nied by critical illness myopathy and the term critical CO2: 31C.
illness neuromyopathy has been used. See also, Isotherms; Pseudocritical temperature
Although complete clinical recovery usually occurs
following resolution of the critical illness, electrophysi- Critical velocity. Velocity above which laminar flow in
ological studies may show residual axonal dysfunction. a tube becomes turbulent.
Howard RS,Tan SV, ZGraggen WJ (2008). Pract Neurol; Proportional to
8: 28095
viscosity of fluid
Critical incidents. Term derived from the airline indus- density of fluid radius of tube
try; usually defined as any event which results in actual thus refers to a specific fluid within a tube of specific
harm, or would do so if not actively managed. Thus radius.
includes all complications of anaesthesia/intensive care, At critical velocity, Reynolds number is greater than
whether or not harm is done (e.g. breathing system dis- 2000.
connection, irrespective of whether hypoxaemia or
hypoxic brain damage occurs). In its broadest sense, the
term also includes harm to healthcare providers, e.g. Crohns disease, see Inflammatory bowel disease
back injury while lifting a patient. It has been argued
that critical incidents should exclude those considered Cromoglicate (Cromoglycate), see Sodium
outliers of normal practice, e.g. transient hypotension cromoglicate
following iv induction of anaesthesia.
Critical incident reporting schemes are a central part Cross-matching, see Blood compatibility testing
of risk management and a ready topic for audit, and have
become a useful tool in quality assurance. More useful Croup (Laryngotracheobronchitis). Upper respiratory
in analysing rare adverse events than traditional outcome obstruction and stridor in children due to viral infection
studies. A problem common to all reporting schemes is affecting the larynx, trachea and bronchi; most com-
the under-reporting of incidents, although this may be monly due to parainfluenza (especially type I), respira-
improved by education and guarantees of anonymity. In tory syncytial and influenza viruses. The typical barking
addition, they may not always suggest a means of improv- croupy cough, the childs age (usually 6 months2
ing care. years) and the gradual onset help distinguish it from
Terms used in critical incident reporting schemes epiglottitis, which is usually of more acute onset, affects
include: children of 25 years and is associated with greater sys-
latent errors: within the system, e.g. having two temic illness.
drugs presented in very similar ampoules stored Treatment is with corticosteroids (oral, parenteral or
next to each other. nebulised) and nebulised adrenaline: racemic solution
active errors: produce immediate effects. (equal amounts of d- and l-isomers) is widely used in the
human errors: those involving direct human contri- USA: 0.5ml of 2.25% solution is diluted to 4ml in saline.
bution, e.g. the giving of the incorrect drug; may be In the UK, (0.4ml) 400g/kg of the generally available
caused by: non-racemic preparation (comprising mostly the more
- slips: the action is unintended, e.g. picking up the active l-isomer) has been used, up to a maximum of
wrong syringe. 5ml (5mg). It may be repeated after 30min if required.
- lapses: the action is intended but the error is ECG monitoring should be instituted and therapy
related to memory, e.g. forgetting the patient is stopped if the heart rate exceeds 180 beats/min. Mucosal
allergic to penicillin. swelling may recur after treatment so careful monitoring
 Curare 165

is required. Helium/oxygen mixtures may provide short- CT scanning, see Computed (axial) tomography
term improvement. Tracheal intubation and mechanical
ventilation may be required. CTZ, see Chemoreceptor trigger zone
Bjornson CL, Johnson DW (2008). Lancet; 371: 32939
Cuffs, of tracheal tubes. Seal the trachea to avoid gas
CRP, see C-reactive protein leakage and contamination from above, e.g. blood,
gastric contents. Popularised by Waters and Guedel in
CRPS, see Complex regional pain syndromes the 1920s. Usually inflated with air following tracheal
intubation, until the audible gas leak is just eliminated.
Crush syndrome. Acute oliguric renal failure following The degree of distension of a pilot balloon, or measure-
trauma, usually involving impaired perfusion of a limb. ment of cuff pressure, indicates the extent of cuff
May occur in direct trauma and in comatose patients inflation.
who lie on a limb for a prolonged period. Muscle swell- Main problems are related to pressure exerted by
ing and necrosis lead to release of myoglobin with the cuff on the tracheal walls causing mucosal
resultant myoglobinuria. Renal impairment is com- ischaemia:
pounded by any associated hypotension and dehydra- may occur if capillary pressure is exceeded (i.e.
tion. Potassium is also released from the damaged greater than about 25mmHg). Cuff pressures of up
muscle; severe hyperkalaemia may be fatal unless dialy- to 60mmHg have been measured with high-volume
sis is instituted. low-pressure cuffs, and up to 200mmHg with low-
Hyperphosphataemia and hypocalcaemia also occur. volume high-pressure cuffs (see Laplaces law). The
Gonzalez D (2005). Crit Care Med; 33: S3441 former are therefore preferable, especially for pro-
longed intubation, e.g. in ICU. Hand-held cuff infla-
Cryoanalgesia. Use of extreme cold to damage periph- tors may incorporate pressure gauges to indicate
eral nerves and provide pain relief lasting up to several cuff pressure during inflation.
months. Causes axonal degeneration without epineurial cuff pressure may increase during anaesthesia due
or perineurial damage, allowing slow regeneration of the to increased temperature or diffusion of N2O into
axon without neuritis or neuroma formation. Has been the cuff. Saline/N2O mixtures have been used for
used in chronic pain management, and perioperatively cuff inflation, to avoid the latter. Monitoring of
to provide prolonged postoperative analgesia, e.g. cuff pressure, or intermittent deflation and inflation,
applied to intercostal nerves in thoracic surgery. has been suggested during long operations and
See also, Cryoprobe; Refrigeration anaesthesia in ICU.
mucosal inflammation may lead to ulcer formation
Cryoprecipitate, see Blood products over cartilaginous rings; infection, tracheal dilata-
tion and erosion of tracheal walls may follow. Tra-
Cryoprobe. Instrument used to freeze tissues. Com- cheal stenosis may occur after extubation.
pressed gas (e.g. CO2 or N2O) is passed through a narrow damage is worst after prolonged use, although some
tube and allowed to expand suddenly at its tip. Work degree of ciliary damage may occur within a few
done by the gas as it expands results in a temperature hours of inflation.
drop (JouleThomson effect; an example of an adiabatic damage is worse if wrinkles are formed by the cuff.
change) to as low as 70C in the metal sheath of the Similar problems may occur with tracheostomy tubes.
probe. Used to destroy superficial lesions, e.g. in gynae- Recurrent laryngeal nerve injury may be caused by a
cology and dermatology; also used in ophthalmology cuff inflated just below the vocal cords. Cuff placement
and to provide cryoanalgesia. should be 1.52cm below the cords. Trauma may be
caused if tracheal extubation is performed without prior
Crystalloid. Substance which, in solution, may pass deflation of the cuff. Uncuffed tracheal tubes are tradi-
through a semipermeable membrane (cf. colloid). Saline tionally used for paediatric anaesthesia.
solutions, dextrose solutions and Hartmanns solution Similar considerations apply to bronchial cuffs of
are commonly used clinically as iv fluids. endobronchial tubes; bronchial rupture may follow
See also, Colloid/crystalloid controversy excessive inflation.
Longitudinal wrinkles in the cuff may allow passage
CSE, see Combined spinalepidural anaesthesia of secretions from the pharynx into the tracheobronchial
tree; new cuffs have thus been designed in which wrin-
CSF, see Cerebrospinal fluid kles do not form, thereby reducing the risk of aspiration
pneumonia in patients requiring chronic ventilatory
CSF filtration. Therapeutic removal of cellular and support.
soluble components known to be involved in the patho- Filling the cuff with lidocaine (410%) has been
physiology certain of diseases. First used in 1991 in reported to reduce coughing on extubation.
severe GuillainBarr syndrome unresponsive to other See also, Tracheal tubes
therapies. CSF is removed through an intrathecal cath-
eter into a closed system via a syringe and pump and Cuirass ventilator, see Intermittent negative pressure
then reinjected through a filter with a pore size of 0.2 ventilation
m. Is now used in some cases of acute and chronic
inflammatory demyelinating polyneuropathies, multiple Curare. Dried plant extract used by South American
sclerosis, amyotrophic lateral sclerosis and bacterial Indians as arrow poison, containing tubocurarine and
meningitis. other alkaloids. Described in Raleighs writings in 1596.
Used experimentally by Waterton and Bernard, among
CSM, see Committee on Safety of Medicines others, from the early/mid-1800s onwards. Used to treat
166 CURB-65 score

tetanus and in psychiatric convulsive therapy. First used owing to secretion of melanocyte-stimulating
in anaesthesia by Lawen in 1912, but remained in short hormone).
supply for many years. Its use became more widespread medical treatment: metyrapone inhibits 11-
after Griffiths famous description in 1942; his supply hydroxylase and reduces cortisol production. May
was brought back from Ecuador by Gill. be used before surgery, to improve the patients
[Sir Walter Raleigh (15521618), English explorer; condition, or after irradiation.
Richard Cochran Gill (19011958), US explorer] [Don H Nelson, US endocrinologist]
Smith M, Hirsch NP (2000). Br J Anaesth; 85: 314
CURB-65 score, see Chest infection
Cushings reflex. Hypertension with compensatory bra-
Curling ulcers. Peptic ulcers occurring after severe dycardia occurring with acutely raised ICP. Due to the
burns. Most common in children. effect of local hypoxia and hypercapnia on the vasomo-
[Thomas Curling (18111888), English surgeon] tor centre as cerebral perfusion pressure falls.
Fodstad H, Kelly PJ, Buchfelder M (2006). Neurosur-
Current. Flow of electrical charge. Direct current gery; 59: 11327
describes flow of charge continuously in one direction, See also, Cushing, Harvey Williams
e.g. from a battery. Direction of flow alternates in an
alternating current, e.g. mains power supply. SI unit is Cushings syndrome. Clinical syndrome resulting from
the ampere. excessive endogenous or exogenous corticosteroid
levels.
Current density. Current per unit area. Important in Features:
electrocution and electrical burns as heat production is central obesity, i.e. limbs are spared. Buffalo hump
directly proportional to current density Thus there is no of fat behind the neck.
tissue damage at the site of a diathermy plate, but intense moon face, greasy skin, acne, hirsutism.
heat at the site of the probe or forceps, where area of skin atrophy and poor wound healing, with increased
contact is very small. Similarly, a small current delivered susceptibility to infection.
directly to the heart over a very small area may produce abdominal striae.
the same current density as a much larger current deliv- osteoporosis.
ered to the whole body, and may therefore be as danger- proximal muscle weakness.
ous (microshock). psychiatric disturbances.
hypertension.
Current-operated earth-leakage circuit breaker hypernatraemia and hypokalaemia.
(COELCB). Device containing equally sized coils of live diabetes mellitus.
and neutral wires, used in electrical circuits to prevent Caused by:
electrocution. The current in each wire induces magnetic Cushings disease (the most common non-iatrogenic
flux equal and opposite to that induced by the other, as cause).
long as each wire carries the same current. Imbalance adrenal tumours.
between the two currents, e.g. due to leakage of current other hormone-secreting tumours, e.g. bronchial
to earth, results in unequal magnetic fluxes which do not carcinoma secreting ACTH.
cancel each other out. Resultant magnetic flux induces corticosteroid therapy.
current in a third coil, causing rapid (within 5 ms) break- Investigation:
age of the circuit via a solenoid. raised urinary cortisol and 17-oxogenic corticoste-
roids (cortisol precursors).
Cushing, Harvey Williams (18691939). US neurosur- raised plasma cortisol levels; normally low at mid-
geon, professor of surgery at Harvard University. A night, and low the morning after dexamethasone
pioneer in neurosurgery, he developed many techniques, administration.
including the use of diathermy, and clips for cerebral ACTH levels are raised in Cushings disease and
vessels. Advocated record-keeping and monitoring ACTH-secreting tumours. Metyrapone decreases
during anaesthesia, and investigated many aspects of adrenal cortisol production, causing ACTH to
neurophysiology and neuropathology, several of which increase: this does not occur with adrenal tumours
bear his name. Won the Pulitzer Prize for his biography or ACTH-secreting tumours, but does occur in
of Osler, and published many books and articles. Cushings disease. The ACTH increase is measured
[Joseph Pulitzer (18471911), Hungarian-born US jour- directly, or cortisol precursors (17-oxogenic cortico-
nalist; Sir William Osler (18491919), Canadian-born US steroids) are measured in the urine.
and English physician] Hypertension and cardiac failure, hypernatraemia,
Hirsch NP, Smith GB (1986). Anesth Analg; 65: 28893 hypokalaemia and diabetes, although not always present,
may cause problems during anaesthesia. Steroid cover is
Cushings disease. Cushings syndrome is caused by required, as in corticosteroid therapy. Fragile skin and
ACTH-secreting adenoma of the pituitary gland. Inci- veins may be easily damaged. Postoperative fluid and
dence is 24 per million population; 80% occur in electrolyte balance is particularly important.
women. Newell-Price J, Bertagna X, Grossman A, Nieman L
Treatment: (2006). Lancet; 367: 160517
pituitary surgery (effective in up to 80% of See also, Cushing, Harvey Williams
cases).
irradiation of the pituitary gland. Cushings ulcers. Peptic ulcers occurring after head
bilateral adrenalectomy in resistant cases (carries injury, associated with increased gastric acid secretion.
the risk of Nelsons syndrome: hyperpigmentation See also, Cushing, Harvey Williams
 Cyclophosphamide 167

Cut-off effect. Reduced anaesthetic potency of larger cyanosis, typically affecting the tongue, may result from
molecules in a homologous series, despite increasing heart or lung disease, including right-to-left shunts.
lipid solubility. Methaemoglobinaemia and sulphaemoglobinaemia may
See also, Anaesthesia, mechanism of also cause bluish discoloration. Cyanosis may be further
mimicked by grey or blue discoloration of skin caused
CVA, see Cerebrovascular accident by heavy metals (e.g. iron, gold and lead) or drugs (e.g.
amiodarone and phenothiazines).
CVVH, Continuous venovenous haemofiltration, see
Haemofiltration Cyclic AMP, see Adenosine monophosphate, cyclic

CVVHD, Continuous venovenous haemodiafiltration, Cycling of ventilators, see Ventilators

see Haemodiafiltration
Cyclizine hydrochloride/tartrate/lactate. Antiemetic
Cyanide poisoning. May result from industrial acci-
drug, with antihistamine and anticholinergic actions.
dents, self-administration, smoke inhalation, prolonged
Available alone or combined with opioid analgesic drugs
use of sodium nitroprusside or use as a chemical weapon.
and ergotamine. Half-life is about 8h.
Absorption may occur via stomach, skin and lungs (the Dosage: 50mg orally/im/iv qds.
latter may be rapidly fatal). Causes inhibition of the Side effects include drowsiness and blurred vision.
cytochrome oxidase system and other enzymes, inter-
Painful if given iv/im. Rapid injection may cause
rupting cellular respiration. Tissues are thus unable to
tachycardia.
utilise delivered O2 (histotoxic hypoxia). Cyanide is
slowly converted to thiocyanate in the liver by the
enzyme rhodanese; a small amount binds to methaemo- Cyclodextrins. Cyclic oligosaccharides, studied for their
globin and a small amount to hydroxocobalamin. ability to encapsulate lipophilic molecules. Sugammadex
Features: is a cyclodextrin with optimal affinity for rocuronium,
non-specific: dizziness, headache, confusion. Apnoea
and has been shown to reverse the neuromuscular block-
may follow initial tachypnoea. ade produced by the latter, even if given within a few
reduced arteriovenous O2 difference, due to reduced
minutes of paralysis. Cyclodextrins have also been
uptake of O2 by tissues. Metabolic acidosis with studied as vehicles for drugs (e.g. propofol) in an attempt
increased lactate results from tissue hypoxia. to avoid the use of emulsifiers and other carriers.
convulsions and cardiorespiratory collapse may
Booij LHD (2009). Anaesthesia; 64 (Suppl. 1): 317
occur.
chronic poisoning causes peripheral neuropathy, Cyclo-oxygenase (COX). Enzyme acting on arachi-
ataxia and optic atrophy. donic acid to produce prostaglandin H2, from which
Measurement of plasma levels is technically difficult and other prostaglandins, prostacyclin and thromboxanes
may be unreliable unless performed rapidly. are formed. Exists in two forms:
Treatment: COX-1 (constitutive): present in many tissues and

general measures as for poisoning and overdoses. responsible for the maintenance of normal physio-
O2 therapy is particularly important. Staff must logical functions of prostaglandins, e.g. renal blood
avoid self-contamination. flow, gastric mucosal protection.
gastric lavage may be helpful. COX-2 (inducible): found in few resting cells

dicobalt edetate 300mg iv over 1min, repeated if (including brain, kidney, gravid uterus); induced
necessary. Combines with cyanide to form inert during inflammation.
compounds. May itself cause vomiting, hyperten- Most NSAIDs inhibit COX-1 more than (e.g. aspirin,
sion and tachycardia; reservation for severe cases indometacin, naproxen, piroxicam) or the same as (e.g.
has been suggested. Given with 50% glucose (50ml ibuprofen, diclofenac) COX-2. NSAIDs that preferen-
per dose). tially inhibit COX-2 (e.g. parecoxib, celecoxib) have
sodium thiosulphate 50%, 25ml iv over 10min. been developed in an attempt to minimise their side
Converts cyanide to thiocyanate. Used together effects (e.g. upper GI bleeding). The selective COX-2
with: inhibitor rofecoxib was withdrawn in 2004 because it was
- sodium nitrite 3%, 10ml iv over 3min. Converts associated with an increased incidence of MI, attributed
haemoglobin to methaemoglobin, which binds in early studies to a cardioprotective effect of naproxen
cyanide. More efficacious than inhaled amyl in the control group. The mechanism is thought to be
nitrite. Methaemoglobin together with carboxy- unequal inhibition of prostacyclin and thromboxane
haemoglobin if present should not exceed 40% synthesis.
total haemoglobin. Kam P (2000). Anaesthesia; 55: 4429
- hydroxocobalamin 70mg/kg iv over 20min.
Forms cyanocobalamin with cyanide. Has been Cyclophosphamide. Immunosuppressive and cytotoxic
used in cyanide poisoning and to reduce nitro- drug used in organ transplantation (especially bone
prusside toxicity, but not widely used in the UK. marrow transplantation), autoimmune disease and
malignancy. An alkylating agent, it binds to DNA and
Cyanosis. Blue discoloration of tissues due to increased is toxic to both resting and dividing cells. Exerts its great-
concentration of reduced haemoglobin in the blood. est effect on B lymphocytes, thus inhibiting antibody
Clinically detectable at less than 5g/dl reduced haemo- production. Also suppresses delayed hypersensitivity
globin, although this value is often quoted as the reactions. Bioavailability is 90% after oral dosage, with
minimum. Peripheral cyanosis, e.g. of fingernails, may peak levels at 1h. Metabolised in the liver with a half-
result from impaired peripheral perfusion. Central life of 6h.
168 Cyclopropane

Table 17 Colour-coding of cylinders

UK Recommended international system

Gas Shoulder Body USA Shoulder Body*

O2 White Black Green White White

N2O Blue Blue Blue Blue White
CO2 Grey Grey Grey Grey White
Entonox Blue/white quarters Blue White/blue quarters White
Helium Brown Brown Brown Brown White
O2 21%/helium Brown/white quarters Black Brown/yellow Brown/white quarters White
Air Black/white quarters Grey Yellow Black/white quarters White

*Use of white body agreed within Europe.

Dosage: 100300mg/day orally or 80300mg/m2/ - pressure of the last hydraulic test.

day iv. - symbol of the contained gas.
Side effects: nausea, vomiting, hair loss, dose-related the valve is opened by turning a longitudinal spindle,
cardiac toxicity, haemorrhagic cystitis (caused by a set within a gland screwed tightly into the valve
metabolite, acrolein), increased risk of infection and block. Compression of a nylon ring around the
malignancy. Levels are increased by concurrent spindle prevents leakage of gas along the spindle
administration of allopurinol and cimetidine. May shaft.
prolong suxamethoniums duration of action by bears the pin index system on the same face as the
decreasing cholinesterase activity. gas outlet.
a safety outlet is fitted to the valve block (USA) or
between the block and cylinder neck (UK); it melts
Cyclopropane (CH2)3. Inhalational anaesthetic agent,
at low temperatures, allowing escape of gas in case
first used in the early 1930s. No longer available in the
of fire.
UK and many other countries.
a testing collar is attached (see below).
Its main advantages were very rapid onset of anaes-
Colour-coding (UK): shoulder colour(s) represent
thesia (blood/gas partition coefficient 0.45) and mainte-
the predominant gas(es) in the cylinder. US colour-
nance of BP and cardiac output (largely due to
coding is different. An international colouring system
sympathetic activity) despite direct myocardial depres-
has been recommended, taking one of the colours
sion. Extremely flammable (explosive in O2 at 2.560%
from the UK system (Table 17). European standards
and in air at 2.510%), it also caused marked respiratory
initially followed this scheme but only applied to the
depression and reduced renal and hepatic blood flow.
cylinders shoulders, the suppliers being able to paint
Commonly used for paediatric induction using 50% in
the body as they chose. In 2000 it was suggested that
O2 (MAC of 9.2%). Supplied in orange size-B cylinders
all medical gas cylinders should be identified by
(containing 180 litres, partly as liquid) at a pressure of
having white bodies, and this was agreed within most
5 bar.
of Europe over the next decade (including the UK, in
2010, with all cylinders complying with the new colour
Cycloserine. Antibacterial and antituberculous drug, scheme by 2025).
used in TB resistant to first-line drugs. Contraindicated Bodies are labelled with:
in renal impairment, epilepsy and porphyria. name and symbol of the gas.
Dosage: 250500mg orally bd. volume and pressure of contained gas.
Side effects: rash, headache, dizziness, seizures, psy- information and warnings about explosions
chological changes, hepatic impairment. and flammability where appropriate. When the gas
supply is turned on suddenly, compression of the gas
within the valves and pipes causes a rise in tempera-
Cyclosporin, see Ciclosporin
ture. Oil or grease in the system may ignite, hence
the warning against these lubricants.
Cylinders. Traditionally made of molybdenum or chro- Testing:
mium steel; newer cylinders are made of aluminium every hundredth cylinder is cut into strips and
alloy and are much lighter. Composite cylinders usually tested at manufacture.
comprise a metal liner to prevent leakage of gas, with a each cylinder is tested 5-yearly to withstand high
carbon or glass fibre overwrap to provide extra strength. hydraulic pressures (about 200250 bar). Cylinders
Provide medical gases either directly to an output are filled with water under pressure, within a water
(e.g. attached to an anaesthetic machine) or from a bank jacket. Expansion and elastic recoil of the metal are
of cylinders (manifold) via pipelines. then measured.
The valve block screws into the open end of the cyl- internal inspection with an endoscope.
inder and has the following features: a plastic disc is placed around the valve block neck;
marked with: its colour and shape are coded for the date of the
- serial number. last test. The year in which testing is due is stamped
- tare (weight of the empty cylinder and valve on the disc, and a hole punched to indicate the
block; used for calculation of contents by weight). quarter of the year.
 Cytokines 169

Cylinder pressures: inhalational induction is prolonged because of

O2: 137 bar. V /Q
 mismatch. Ketamine increases bronchial
N2O: 40 bar. secretions.
CO2: 50 bar. usual technique: tracheal intubation and IPPV,
air: with tracheobronchial suction as required. Bron-
O2/helium: 137 bar. choalveolar lavage may be beneficial. Extubation is
O2/N2O: performed awake. Humidification of gases is
(maximal values at 15C, as marked on the important.
cylinders). careful fluid balance to avoid dehydration.
Modern pressure gauges are marked in kPa 100 (1 bar postoperative observation, physiotherapy, analgesia
= 100 kPa). and humidified O2 administration are important.
N2O and CO2 cylinders contain liquid; as such a cyl- Huffmyer JL, Littlewood KE, Nemergut EC (2009)
inder empties, pressure is maintained by evaporation of Anesth Analg; 109: 1949-61.
liquid (although a slight drop in pressure does occur as
temperature falls) until the liquid is depleted. Pressure Cystic hygroma. Congenital multiloculated cystic mass
then falls rapidly with further emptying. Gas-filled cylin- arising from the jugular lymph sac, the embryonic pre-
ders (e.g. containing O2) provide gas whose pressure is cursor of part of the thoracic duct. Contains lymph; char-
proportional to cylinder contents. acteristically transilluminates very well. Usually presents
Large Entonox cylinders contain connecting tubes soon after birth. Sometimes sclerosant treatment is
from the valve block to the lower part of the cylinder, to used; surgery is difficult because of widespread cystic
reduce risk of hypoxic gas delivery if separation of gases tissue throughout neck. The tongue and pharynx may be
occurs below the pseudocritical temperature. involved. Main anaesthetic problems are related to
Sizes of cylinders are denoted by capital letters, E airway obstruction and difficult intubation. Manual
being the usual size on anaesthetic machines: IPPV via a facemask may be impossible; therefore spon-
O2: C (gas content = 170 l), D (340 l), E (680 l). taneous ventilation is usually maintained until intuba-
N2O: C (450 l), D (900 l), E (1800 l). tion is achieved.
See also, Filling ratio; Piped gas supply See also, Intubation, difficult

Cystic fibrosis. Autosomal recessive genetic disease; Cytochrome oxidase system. Series of iron-containing
the commonest lethal inherited illness in Caucasians, enzymes within mitochondrial inner membranes.
affecting 1 in 1500 live births. Causes impaired produc- Electron transport from oxidised nicotinamide ade-
tion of cystic fibrosis transmembrane conductance regu- nine dinucleotide (NADH) or succinate proceeds via
lator (CFTR) protein, a complex channel that regulates sequential cytochromes, the iron component becoming
passage of water and ions across cell membranes. Pri- alternately reduced and oxidised as the electron is
marily affects exocrine gland function resulting in abnor- passed to the next in line. Their structure and arrange-
mally viscous secretions. ment within the membrane are thought to be crucial to
Features: their function. Electron flow is coupled to ATP forma-
repeated respiratory infection, usually by staphylo- tion; 3 molecules of ATP are formed per NADH and 2
coccus and pseudomonas, leading to bronchiectasis, ATP per succinate molecule. Cytochrome oxidase itself
pulmonary fibrosis and eventually pulmonary is the cytochrome binding to molecular O2 to form
hypertension and cor pulmonale. Nasal polyps are water, and is inhibited in cyanide poisoning and carbon
common. Pneumothorax may occur. V/Q mismatch, monoxide poisoning.
restrictive and obstructive defects and increased Similar enzymes exist in other membranes, e.g. cyto-
residual capacity often result in hypoxaemia. Arte- chrome P450 isoenzymes (P for pigment, 450nm for
rial PCO2 is usually reduced unless lung disease is enzymes absorption peak), found in smooth endoplas-
severe. Laryngospasm and coughing are common mic reticulum; these are responsible for phase I metabo-
during anaesthesia. lism of many drugs. Genetic polymorphism of the various
pancreatic insufficiency with malabsorption, intesti- enzymes partly explains interindividual variability in
nal obstruction (e.g. meconium ileus in the newborn) drug metabolism.
and diabetes mellitus. Obstructive jaundice may
occur. Cytokines. Protein mediators released by many cells,
renal impairment and amyloidosis may occur. Sur- including monocytes, lymphocytes, macrophages, mast
vival beyond the second and third decade is now cells and endothelial cells. Involved in regulating the
common with intensive physiotherapy, antibiotic activity, growth and differentiation of many different
therapy and pancreatic supplementation. Heart cells of the immune and haemopoietic systems. The cyto-
lung and lung transplantation is increasingly being kines tumour necrosis factor- (TNF; cachectin), inter-
performed since the disease seems not to recur in leukin (IL)-1 and IL-6 are thought to be central to the
transplanted lungs. pathophysiology of SIRS and sepsis; TNF and IL-1
Anaesthetic management: produce the systemic and metabolic features of SIRS,
careful preoperative assessment and continu- whilst IL-6 causes the acute-phase protein response. All
ation of physiotherapy. Coagulation may be three are released in response to endotoxin and other
impaired. Opioid premedication is usually avoided. stimuli. In sepsis, high blood concentrations of IL-6 espe-
Anticholinergic drugs may increase secretion vis- cially have been associated with poor outcome. Thera-
cosity but are commonly used to reduce the inci- pies for sepsis have been developed directed against the
dence of bradycardia; they may be given on actions of IL-1 and TNF (e.g. using antibodies or antag-
induction. onists), although encouraging results in animal experi-
regional techniques, where appropriate. ments have generally not been reproduced in humans.
170 Cytomegalovirus

Anti-TNF therapies are now established in rheumatoid prolong the effect of suxamethonium; busulfan may
arthritis. cause pulmonary fibrosis. Chlorambucil may rarely
Other cytokines include additional interleukins, and cause severe skin reactions.
interferons. Interferon- interacts with other cytokines cytotoxic antibiotics: doxorubicin may cause
and has been investigated as a target for the treatment cardiomyopathy; bleomycin may cause pulmonary
of sepsis. fibrosis.
antimetabolites: methotrexate may cause
Cytomegalovirus (CMV). Herpes group virus usually pneumonitis.
acquired subclinically during childhood; by 50 years vinca alkaloids: vincristine and vinblastine may
of age, 50% of individuals have anti-CMV antibodies. cause autonomic and peripheral neuropathy.
May be transmitted by blood transfusion, hence the others: cisplatin may cause nephrotoxicity, ototoxic-
requirement for screening before transfusion to at-risk ity and peripheral neuropathy; procarbazine has
groups. May cause major morbidity and mortality during monoamine oxidase inhibitor effects; azathioprine
pregnancy (resulting in cytomegalic inclusion disease: may cause hepatic impairment, nephritis and rarely
small infant with jaundice, hepatosplenomegaly, micro- pneumonitis.
cephaly, mental retardation) and in patients with immu- O2 therapy has been implicated in exacerbating the pul-
nodeficiency (clinical features include fever, interstitial monary fibrosis caused by cytotoxic drugs.
pneumonia, enteritis, hepatitis, carditis, chorioretinitis, Specific guidelines (issued by the Committee on the
leucopenia and thrombocytopenia). Treatment includes Review of Medicines) exist for the handling of cytotoxic
antiviral drugs such as ganciclovir or foscarnet sodium. drugs. These include the necessity for trained staff to
administer drugs, designated areas for drug reconstitu-
Cytotoxic drugs. Used in the treatment of malignancy tion, protective clothing, eye protection, safe disposal of
and as immunosuppressive drugs. All may cause nausea waste material and avoidance of handling cytotoxics by
and vomiting and bone marrow suppression; most are pregnant staff.
teratogenic and require careful preparation by trained Accidental intrathecal (instead of intravenous) injec-
personnel. Extravasation of iv drugs may cause severe tion of vincristine during combination chemotherapy
tissue necrosis. Some have side effects of particular almost inevitably results in death; in the UK, anaesthe-
anaesthetic/ICU relevance: tists have been involved in such errors. Totally incom
alkylating agents (act by damaging DNA and patible intrathecal/intravenous connections have been
impairing cell division): cyclophosphamide may developed as a result.
 D
wave, see WolffParkinsonWhite syndrome Dalfopristin, see Quinupristin

DA examination (Diploma in Anaesthetics). First spe- Dalteparin sodium, see Heparin

cialist examination in anaesthetics; first held in 1935 in
London. Originally intended for anaesthetists with at Daltons law. The pressure exerted by a fixed amount of
least 2 years experience and 2000 anaesthetics, later a gas in a mixture equals the pressure it would exert
reduced to 1 years residence in an approved hospital. A if alone; thus the pressure exerted by a mixture of
two-part examination was introduced in 1947, becoming gases equals the sum of the partial pressures exerted by
the FFARCS examination in 1953; the single-part DA each gas.
remained separate until 1984, when the DA (UK) [John Dalton (17661844), English chemist]
became the first part of the new three-part FFARCS.
Replaced by the new FRCA examination in 1996. Damage control resuscitation. Approach to major
trauma, developed in modern military settings. Aims to
Dabigatran etexilate. Direct thrombin inhibitor, pre- reduce the incidence and severity of the combination of
venting the conversion of fibrinogen to fibrin; thus acute coagulopathy, hypothermia and metabolic acidosis
impairs coagulation and platelet activation. Prolongs that commonly accompany major haemorrhage. Con-
the activated partial thromboplastin time (APTT). A sists of:
prodrug, rapidly metabolised to active metabolite (dabi- permissive hypotension: restricted fluid resuscita-
gatran) by non-specific esterases; oral bioavailability is tion to maintain a radial pulse rather than a normal
6.5%. Onset of action is 0.52h, with steady state or near-normal BP, accepting a period of organ
achieved within 3 days. 80% of drug is renally excreted hypoperfusion (except in head injury, where main-
unchanged; half-life is 814h, increased to > 24h in tenance of cerebral perfusion pressure is thought to
severe renal failure. Also metabolised by the liver and be vital).
excreted in the bile. haemostatic resuscitation: early use of blood prod-
Licensed for DVT prophylaxis in adults undergoing ucts to prevent/treat acute coagulopathy, including
total knee or hip replacement surgery, and for preven- platelets (in a 1:1 ratio with packed red cells [1 pool
tion of CVA in patients with AF with certain risk factors. of platelets for every 5 units of red cells]), fresh
Under investigation for the treatment of DVT and acute frozen plasma (in a 1:1 ratio) and cryoprecipitate;
coronary syndrome. Developed as an alternative to war- tranexamic acid, eptacog alfa and calcium have also
farin, over which it has several advantages: been advocated. Use of more recently donated
no therapeutic monitoring required. packed red cells rather than older units may be
fixed dosage (modified according to age, indication, beneficial.
renal function and drug interactions). aggressive warming to reduce hypothermia.
faster onset and shorter duration of action. damage-control surgery: restriction of early
stable, predictable pharmacokinetics, with fewer surgery to the minimum possible, e.g. clamping/
drug interactions. packing/suturing major defects, rather than pro-
lower incidence of major bleeding complications. longed, definitive procedures.
Disadvantages include: higher cost; no specific antidote Jansen JO, Thomas R, Loudon MA, Brooks A (2009). Br
in case of overdose (although can be removed by dialy- Med J; 338: b1778
sis); unsuitable for patients with severe renal impairment
(GFR < 30ml/min). Damping. Progressive diminution of amplitude of oscil-
Dosage: lations in a resonant system, caused by dissipation of
DVT prophylaxis in adults undergoing knee/hip stored energy. Important in recording systems such as
replacement: 110mg orally 14h after surgery fol- direct arterial BP measurement. In this context, damping
lowed by 220mg daily, reduced to 75mg followed mainly arises from viscous drag of fluid in the cannula
by 150mg daily in renal impairment and the elderly. and connecting tubing, compression of entrapped air
CVA prophylaxis in patients with AF: 150mg orally bubbles, blood clots within the system and kinking.
bd, reduced to 75mg in renal impairment. Excess damping causes a flattened trace which may be
Drug interactions: potentiated by concomitant vera- distorted (phase shift). The degree of damping is
pamil and amiodarone; reduced dosing regimen is described by the damping factor (D); if a sudden change
used. Inhibited by rifampicin, ketoconazole and is imposed on a system, D = 1 if no overshoot of the
quinidine. trace occurs (critical damping; Fig. 49a). A marked over-
Main side effect is bleeding; risk is similar or lower than shoot followed by many oscillations occurs if D << 1 (Fig.
equivalent treatment with warfarin. 49b), and an excessively delayed response occurs if D >>
Hankey GJ, Eikelboom JW (2011). Circulation; 123: 1 (Fig. 49c). Optimal damping is 0.60.7 of critical
143650 damping, and produces the fastest response without

171
172 Danaparoid sodium

(a) (b) (c)

Sudden change Sudden change Sudden change
Recorded variable

Recorded variable

Recorded variable
Time Time Time

Fig. 49 Damping: (a) D = 1; (b) D << 1; (c) D >> 1

excessive oscillations. D depends on the properties of the Data. In statistics, a series of observations or
liquid within the system and the dimensions of the measurements.
cannula and tubing. Data may be:
continuous: e.g. length in metres; the difference
Danaparoid sodium. Heparinoid mixture, containing between 2 and 3m is the same as that between 35
no heparin, used for the prophylaxis of deep vein throm- and 36m. Although they may be treated in the same
bosis. Useful as a heparin alternative in cases of heparin- way, there are two types of continuous data:
induced thrombocytopenia. - ratio: includes zero value, e.g. plasma drug con-
Dosage: centration. 10mmol/l is half of 20mmol/l (i.e. the
prophylaxis: 750 units sc bd for 710 days. ratio of two measurements holds meaning).
parenteral anticoagulation: 12503750 units - interval: does not include zero, e.g. Celsius tem-
(depending on body weight) iv, followed by 800 perature scale (the zero is an arbitrary point in
units over 2h, 600 units over 2h, then 200 units/h the scale; thus 10C does not represent half as
for 5 days. much heat as 20C). The Kelvin scale is a ratio
Side effects: as for heparin. Contains sulphite, which scale since 0 K does represent absence of heat and
may trigger bronchospasm and hypotension in sus- thus 10 K represents half as much heat as 20 K.
ceptible patients. Anti-Xa activity should be moni- If they have a normal distribution, continuous data
tored in renal impairment or obese patients. may be described by the mean and standard devia-
tion as indicators of central tendency and scatter
DandyWalker syndrome, see Hydrocephalus respectively (described as for ordinal data if not
normally distributed).
Dantrolene sodium. Hydantoin skeletal muscle relax- categorical (non-continuous):
ant that acts by binding to the ryanodine receptor and - ordinal, e.g. ASA physical status. The difference
limits entry of calcium into myocytes. Used to treat spas- between scores of 2 and 3 does not equal that
ticity, neuroleptic malignant syndrome and MH. between scores of 4 and 5, and a score of 4 is not
Dosage: twice as unfit as a score of 2. Ordinal data are
25400mg orally od for muscle spasm. described by the median and percentiles (plus
1mg/kg iv for treatment of MH, repeated up to range).
10mg/kg. The solution is irritant with pH 910, and - nominal, e.g. diagnosis, hair colour. May be
is best infused into a large vein. Presented in bottles dichotomous, e.g. male/female; alive/dead.
of 20mg orange powder with 3g mannitol and Nominal data are described by the mode and a
sodium hydroxide, each requiring mixing with 60ml list of possible categories.
water. Preparation of a therapeutic dose is there- Different kinds of data require different statistical tests
fore time-consuming. Once prepared, the solution for correct analyses and comparisons: parametric tests
lasts 6h at 1530C. Dry powder has a shelf-life of for normally distributed data (most continuous data)
9 months. and non-parametric tests for non-normally distributed
Side effects: hepatotoxicity may occur after prolonged data (categorical and some continuous data). The latter
oral use; muscle weakness and sedation may follow iv may often be normalised by mathematical transforma-
injection. The high pH of the iv solution may cause tion, allowing application of the more sensitive paramet-
venous thrombosis following prolonged infusion, and ric tests.
tissue necrosis following extravasation. See also, Clinical trials; Statistical frequency
Krause T, Gerbershagen MU, Fiege M, et al (2004). distributions
Anaesthesia; 59: 36473
Davenport diagram. Graph of plasma bicarbonate con-
Darrows solution. Hypotonic solution designed for iv centration against pH, useful in interpreting and explain-
fluid replacement in children suffering from gastroen- ing disturbances of acidbase balance. Different lines
teritis. Composed of sodium 122mmol/l, chloride may be drawn for different arterial PCO2 values, but for
104mmol/l, lactate 53mmol/l and potassium 35mmol/l. each line, bicarbonate falls as pH falls and increases as
[Daniel Darrow (18951965), US paediatrician] pH increases (Fig. 50).
 D-dimer 173

Standards of anaesthetic and surgical care and equip-

Pco2 8 kPa (60 mmHg) ment (including preoperative preparation, monitoring
40
C Pco2 5.3 kPa (40 mmHg) and recovery facilities) are as for inpatient surgery.
Pco2 2.6 kPa (20 mmHg) Patients may be managed within:
G
[HCO3] (mmol/I)

B separate dedicated day-case units within hospitals:

30
A provide geographical, staffing and some administra-
D
tive independence from the main hospital, but allow
20 access to hospital facilities if needed, e.g. X-ray,
F
E laboratories, wards, ICU.
traditional inpatient lists.
10
completely separate units.
Patient selection: traditional rigid criteria (e.g.
0 relating to age, ASA physical status, BMI) are now
0 7.0 7.2 7.4 7.6 7.8 generally considered unnecessary, three main criteria
pH being:
social situation, e.g. willing patient, access to a tele-
Fig. 50 Davenport diagram (see text) phone, responsible adult to collect the patient and
stay at home for 24h.
medical condition: patient should be fit or any
chronic disease should be stable/controlled.
planned procedure: low risk of complications, which
Can be used to demonstrate what happens in various should be mild; mild expected pain/PONV. Opera-
acidbase disorders: tions expected to last less than 60min are prefera-
line BAD represents part of the titration curve for ble. Operations previously considered unsuitable
blood. are increasingly performed on an outpatient basis,
point A represents normal plasma. e.g. tonsillectomy, laparoscopic cholecystectomy.
point B represents respiratory acidosis; i.e. a rise Patients must be informed of the requirements for
in arterial PCO2, reducing pH and increasing fasting and home arrangements; information leaflets are
bicarbonate. In order to return pH towards normal, widely used for this purpose.
compensatory mechanisms (e.g. increased renal Anaesthetic technique:
reabsorption) increase bicarbonate; i.e. move patients are fully assessed preoperatively (often
towards point C. using a questionnaire). Anaesthetic outpatient
point D represents respiratory alkalosis; compensa- clinics are widely used.
tion (increased renal bicarbonate excretion) results premedication is usually omitted, although short-
in a move towards point E. acting drugs (e.g. temazepam) are sometimes used.
point F represents metabolic acidosis; respiratory general principles are as for any anaesthetic, but
compensation (hyperventilation with a fall in arte- rapid recovery is particularly desirable. Thus short-
rial PCO2) causes a move towards point E. acting drugs are usually used, e.g. propofol, fentanyl,
point G represents metabolic alkalosis; com alfentanil. Sevoflurane and desflurane are com-
pensatory hypoventilation causes a move towards monly selected volatile agents because of their low
point C. blood gas solubility and rapid recovery. Tracheal
The same relationship may be displayed in different intubation is acceptable but is usually avoided if
ways, e.g. the Siggaard-Andersen nomogram, which con- possible. Suxamethonium is often avoided as muscle
tains more information and is more useful clinically. pains are more common in ambulant patients.
[Horace W Davenport (19122005), US physiologist] regional techniques may be suitable (often com-
bined with general anaesthesia to provide postop-
erative analgesia).
Davy, Sir Humphrey (17781829). Cornish-born scien-
facilities for admission to an inpatient ward must be
tist, inventor of the miners safety lamp. Discovered
available in case of excessive bleeding or other com-
sodium, potassium, calcium and barium. Suggested the
plications (occur in < 5% of cases).
use of N2O (which he named laughing gas) for analge- Postoperative assessment must be performed before
sia in 1799, whilst director of the Medical Pneumatic
discharge; the following are usually required:
Institution in Bristol. Later became President of the
full orientation and responsiveness.
Royal Society.
ability to walk, dress, drink and pass urine.
Riegels N, Richards MJBM (2011). Anesthesiology; 114:
adequately controlled pain.
12828
controlled bleeding and swelling.
stable vital signs.
Day-case surgery. Surgery in which the patient presents Written and verbal instructions are given to the patient
to hospital and returns home on the day of operation. not to take sedative drugs or alcohol, or participate in
Increasingly performed, as it has many advantages over potentially dangerous activities (e.g. operating machin-
inpatient surgery: ery, driving, frying food), usually for 2448h.
reduced psychological upheaval for patients, espe- AAGBI, BADS (2011). Anaesthesia; 66: 41734
cially children.
reduced requirement for nursing care and hospital DDAVP, D-Amino-8-D-arginine-vasopressin, see Des-
services, and thus cheaper. mopressin
allows larger numbers of patients to be treated.
reduced risk of hospital-acquired infection. D-dimer, see Fibrin degradation products
174 Dead space

Dead space. Volume of inspired air that takes no part - counselling of staff after a patients death, espe-
in gas exchange. Divided into: cially when unexpected.
anatomical dead space: mouth, nose, pharynx and - organisational/educational: audit; surveys of ICU
large airways not lined with respiratory epithelium. and anaesthetic morbidity and mortality; risk
Measured by Fowlers method. management.
alveolar dead space: ventilated lung normally con- See also, Ethics; Medicolegal aspects of anaesthesia
tributing to gas exchange, but not doing so because
of impaired perfusion. Thus represents one extreme Debrisoquine sulphate. Antihypertensive drug, acting
of V/Q mismatch. by preventing noradrenaline release from postgangli-
Physiological dead space equals anatomical plus alveo- onic adrenergic neurones. Similar in effects to guanethi-
lar dead space. It is calculated using the Bohr equation. dine, but does not deplete noradrenaline stores. No
Assessment may be useful in monitoring V /Q  mismatch longer available in UK.
in patients with extensive respiratory disease, especially
when combined with estimation of shunt fraction. Decamethonium dibromide/diiodide. Depolarising
Normally equals 23ml/kg; i.e. 30% of normal tidal neuromuscular blocking drug, introduced in 1948. Block-
volume. In rapid shallow breathing, alveolar ventilation ade lasts 1520min. No longer in use in the UK.
is reduced despite a normal minute ventilation, because
a greater proportion of tidal volume is dead space. Decerebrate posture. Abnormal posture resulting
Increased by: from bilateral midbrain or pontine lesions (below the
increased lung volumes. level of the red nucleus). Composed of internal rotation
bronchodilatation. and hyperextension of all limbs, with hyperextension of
neck extension. neck and spine, and absent righting reflexes. Similar pos-
PE/air embolism. turing may be seen in severe structural brain damage or
old age. coning.
hypotension. See also, Decorticate posture
haemorrhage.
pulmonary disease. Declamping syndrome, see Aortic aneurysm,
general anaesthesia and IPPV. abdominal
atropine and hyoscine.
apparatus (see below). Decompression sickness (Caisson disease). Syndrome
Decreased by: following rapid passage from a high atmospheric pres-
tracheal intubation and tracheostomy. sure environment to one of lower atmospheric pressure
supine position. (e.g. surfacing after underwater diving), especially if fol-
Apparatus dead space represents wasted fresh gas lowed by air transport at high altitude. Caused by forma-
within anaesthetic equipment. Minimal lengths of tubing tion of nitrogen bubbles as the gas comes out of solution,
should lie between the fresh gas inlet of a T-piece and which it does readily because of its low solubility. Bubbles
the patient, especially in children, whose tidal volumes may embolise to or form in various tissues, giving rise to
are small. Facemasks and their connections may consid- widespread symptoms in: the joints (the bends); the
erably increase dead space. CNS (the staggers); the skin (the creeps); the lungs
(the chokes). Treated by immediate recompression fol-
lowed by slow, controlled depressurisation.
Death. Defined as the irreversible loss of the capacity [Caisson: pressurised watertight chamber used for con-
for consciousness and the capacity to breathe. Anaesthe- struction work in deep water]
tists and intensivists may face a number of issues sur- Vann RD, Butler FK, Mitchell SJ. Moon RE (2011).
rounding the death of patients: Lancet; 377: 15364
practical:
- mortality/survival prediction and allocation of Decontamination of anaesthetic equipment, see Con-
resources; triage. tamination of anaesthetic equipment
- relief of symptoms, e.g. pain management, pallia-
tive care. Decorticate posture. Abnormal posture resulting from
- CPR. lesions of the cerebral cortex, internal capsule and thala-
- diagnosis of brainstem death. mus with preservation of basal ganglia and brainstem
- organ donation. function. Composed of leg extension, internal rotation
ethical: and plantar flexion, with moderate arm flexion. Passive
- informed consent before treatments (i.e. the risk rotation of the head to one side causes extension of the
of death). ipsilateral arm, with full flexion of the contralateral arm,
- withdrawing treatment or resisting aggressive due to intact tonic neck reflexes. The contralateral leg
interventions when they are likely to be futile. may flex. Occurs in severe structural brain damage.
- advance decisions. See also, Decerebrate posture
- do not attempt resuscitation orders.
- euthanasia. Decrement, see Fade
medicolegal:
- reporting of deaths to the coroner. Decubitus ulcers (Pressure sores). May result from a
- claims of negligence or manslaughter. number of factors:
psychological: inadequate peripheral perfusion, e.g. peripheral
- adequate preparation and support of patients, vascular disease, use of vasopressor drugs,
relatives and staff. hypotension.
 Defibrillation 175

malnutrition, including mineral deficiency. discontinued when a prothrombin time of 23 times

predisposing conditions, e.g. diabetes mellitus, normal is achieved. Long-term interruption of leg blood
immunodeficiency. flow may not be prevented, and prevention of PE has
reduced sensation. never been proven. Initial bed rest, leg elevation and
diarrhoea or urinary incontinence. analgesia are also prescribed, although there is no evi-
poor support of limbs, with infrequent turning. dence that these measures affect outcome. Optimal
All may coexist in critically ill patients. May cause pain duration of warfarin therapy is controversial but the
or be a source of infection. Prevention includes: identi- usual duration ranges from 6 weeks to 6 months, depend-
fication of patients at risk (e.g. with the Waterlow pres- ing on underlying risk factors. Surgical removal of
sure sore assessment tool); regular inspection of pressure thrombus has been performed, but reaccumulation
points and turning; support of pressure points to spread usually occurs, possibly due to vessel wall damage. Use
the weight of the body over a wider area; attention to of fibrinolytic drugs is controversial.
nutrition; and use of devices such as air mattresses which Prophylaxis should be considered for all but minor
vary the pressure points continuously. Once present, surgery, and in all immobile patients. Methods used:
ulcers are managed by raising the affected limb/area, reduction of stasis:
regular dressings and cleaning, and negative-pressure - heel cushion to prevent pressure on calf veins and
dressings (vac dressings) where indicated. Erosions a cushion under the knees to prevent hyperexten-
may also occur if tubes and other equipment are allowed sion, leading to popliteal vein occlusion.
to exert undue pressure, e.g. around the mouth/nose. - elevation of legs.
[Judy Waterlow, British nurse] - intermittent pneumatic compression of the calves
Keller BP, Wille J, van Ramshorst B, van der Werken C peri- and postoperatively.
(2002). Intensive Care Med; 28: 137988 - graduated compression stockings.
- encouragement of postoperative leg exercises and
Deep vein thrombosis (DVT). Thrombus formation in early mobilisation.
the deep veins, usually of the leg and pelvis. A common reduction of intravascular coagulation:
postoperative complication, especially following major - fibrinolytic drugs: not shown to prevent DVT.
joint replacement, colorectal surgery and surgery for - antiplatelet drugs: have been shown to prevent
cancer. The true incidence is unknown but may exceed DVT and PE.
50% in high-risk patients. Carries high risk of PE. May - heparin and warfarin anticoagulation: effective
rarely cause systemic embolisation via a patent foramen but with risk of haemorrhage. Low-dose heparin
ovale (present in 30% of the population at autopsy). is widely used (5000 units sc 2h preoperatively
Triad of predisposing factors described by Virchow then bd/tds) and has been shown to be effective
in 1856: in reducing DVT and fatal PE. Low-molecular-
venous stasis, e.g. low cardiac output (e.g. cardiac weight heparin reduces DVT with reduced haem-
failure, MI, dehydration), pelvic venous obstruc- orrhagic side effects (for doses, see Heparin).
tion, prolonged immobility. Dihydroergotamine has been used together with
vessel wall damage, e.g. direct trauma, inflamma- heparin, and is thought to reduce the incidence
tion, varicosities, infiltration. further, possibly via venous vasoconstriction.
increased blood coagulability, e.g. trauma, malig- - discontinuation of oral contraceptives
nancy, pregnancy, oestrogen or antifibrinolytic preoperatively.
administration, hereditary hypercoagulability, - epidural/spinal anaesthesia is thought to be asso-
smoking (see Coagulation disorders). ciated with increased fibrinolysis and reduced risk
More common in old age, sepsis and obesity. Increased of DVT.
risk after surgery is thought to be related to increased - statins reduce the incidence of DVT.
platelet adhesiveness and activation of the coagulation Low-molecular-weight heparin and compression
cascade caused by tissue trauma, exacerbated by possi- stockings are most commonly used.
ble venous damage and immobility. [Rudolph LW Virchow (18211902), German patholo-
Clinical diagnosis is unreliable but suggested by ten- gist; John Homans (18771954), US surgeon]
derness, swelling and increased temperature of the calf, Kyrle PA, Eichinger S (2005). Lancet: 365: 116374
and pain on passive dorsiflexion of the foot (Homans See also, Coagulation studies
sign). The upper leg may also be involved. Accom
panying superficial thrombophlebitis may be absent. Defibrillation. Application of an electric current across
Investigations include: Doppler ultrasound; impedance the heart, to convert (ventricular) fibrillation to sinus
plethysmography; thermography; uptake of radiola- rhythm. Use of electricity was described in the late
belled fibrinogen or platelets; and venography (the gold 1700s/early 1800s (e.g. by Kite), but modern use arose
standard test). Measurement of FDPs (e.g. D-dimer) is from experiments in the 1930s1950s, largely by
also used, a normal level excluding DVT. Kouwenhoven. The first successful resuscitation of a
Treated by systemic anticoagulation with unfraction- patient from VF was by Claude Beck in 1947. Direct
ated or low-molecular-weight heparin; the latter are current is more effective and less damaging than alter-
more commonly used since they can be given sc once a nating current.
day in fixed doses based on the patients weight, without Modern defibrillators contain a capacitor, with poten-
needing laboratory monitoring. This tends to offset tial difference between its plates of 50008000V (Fig.
the increased drug cost. In addition, haemorrhagic com- 51a). Stored charge is released during discharge; the
plications are less frequent than with unfractionated energy released is proportional to the potential differ-
heparin. Low-molecular-weight heparins are thus used ence. An inductor controls the shape and duration of
to treat DVT without admission to hospital in selected the delivered electrical pulse. With traditional mono
patients. Warfarin is administered orally, and heparin phasic defibrillation up to 400J is used for external
176 Defibrillators, implantable cardioverter

(a) PD Table 18 North American Society of Pacing and

Electrophysiology/British Pacing and Electrophysiology
Group generic implantable defibrillator code

S1 Position 1: Position 2: Position 4:

C chamber chamber Position 3: monitoring anti-bradycardic
shocked paced modality chamber paced

0 = None 0 = None E = ECG 0 = None

A = Atrium A = Atrium H = Haemodynamic A = Atrium
V = Ventricle V = Ventricle V = Ventricle
I D = Dual D = Dual D = Dual

Patient

is used. Lower energy levels and R-wave synchronisa-

S2
tion are used in cardioversion. Repeated shocks may
result in myocardial damage.
Hazards include electrocution of members of
(b) the resuscitation team and fire. Standing clear of the
patient and disconnection of the patients oxygen supply
(moving it 1m from his/her chest) during defibrillation
is mandatory.
Automatic external defibrillators (AEDs) identify
life-threatening arrhythmias, prompt medical personnel
on how to proceed, and deliver shocks with the opera-
tors approval. They are increasingly available in public
Current

areas for use by non-medical staff.

Implantable cardioverter defibrillators (ICDs) are
used for recurrent VF/VT or predisposing conditions
(see Defibrillators, implantable cardioverter).
[William Kouwenhoven (18861975), US engineer;
Claude S Beck (18941971) US thoracic surgeon]
See also, individual arrhythmias; Cardiac pacing; Cardio-
pulmonary resuscitation
Time
Defibrillators, implantable cardioverter (ICD).
Fig. 51 Defibrillator. (a) Circuit diagram for basic model. PD, potential Specialised pacemakers designed to detect and treat
difference (50008000V); C, capacitor; S1 and S2, switches; I, inductor. potentially life-threatening arrhythmias. Have similar
(b) Comparison of currents delivered by monophasic (solid) and principles to pacemakers but are described by a different
biphasic (dashed) types (N.B. the latter varies in current strength and coding system (Table 18). Depending on the patients
duration according to settings and/or measured transthoracic arrhythmia, they may respond with anti-tachycardia
impedance) pacing, anti-bradycardia pacing, a low-energy synchro-
nised shock (< 5J) or a high-energy unsynchronised
shock. A particular concern during surgery is the poten-
tial for electromagnetic interference (e.g. from surgical
defibrillation (360J actually delivered to the patient diathermy) to be misinterpreted as VF or VT, causing
because of energy losses), and 2050J for internal defi- inappropriate discharge of the defibrillator. Defibrillator
brillation. The current pulse (up to 30 A) causes synchro- function may be disabled either by preoperative repro-
nous contraction of the heart muscle followed by a gramming of the ICD or intraoperative application of a
refractory period, thus allowing sinus rhythm to occur. magnet. The latter may have unpredictable effects on the
Modern devices deliver lower-energy biphasic wave- ICD and this should be confirmed with the ICD manu-
forms, which are more effective at terminating VF; facturer before use.
current is delivered in one direction followed immedi- Anaesthetic management for insertion is similar to
ately by a second current in the opposite direction (Fig. that for pacemakers.
51b). More sophisticated developments include the Joshi GP (2009). Curr Opin Anaesthesiol; 22: 7014
ability to measure and correct for the transthoracic
impedance by varying the shock delivered. Deflation reflex. Stimulation of inspiration by lung
Firm application of paddles (one to the right of the deflation, initiated by pulmonary stretch receptors. Of
sternum, the other over the apex of the heart taking uncertain significance in humans.
care to avoid any implanted devices) using conductive See also, HeringBreuer reflex
jelly increases efficiency, although self-adhesive pads are
now preferred. They may also be placed on the front and Degrees of freedom. In statistics, the number of obser-
back of the chest. Thoracic impedance is reduced by the vations in a sample that can vary independently of other
first shock, so a second discharge at the same setting will observations. For n observations, each observation may
deliver greater energy to the heart. For children, 4J/kg be compared with n 1 others; i.e. degrees of freedom
 Demyelinating diseases 177

= n 1. For chi-squared analysis, it equals the product of intermittent-flow anaesthetic machines, or be used to
(number of rows 1) and (number of columns 1). administer Entonox. The standard Entonox valve was
developed from underwater breathing apparatus, and
Dehydration. Reflects loss of water from ECF, alone or contains a two-stage pressure regulator within one unit
with intracellular fluid (ICF) depletion. Sodium is usually that fits directly to the cylinder. The first-stage regulator
lost concurrently, giving rise to hypernatraemia or hypo- is similar to those on anaesthetic machines. At the second
natraemia, depending on the relative degrees of loss. If stage, gas flow is prevented by a rod which seals the
ECF osmolality rises, water passes from ICF into ECF valve. The patients inspiratory effort moves a sensing
by osmosis. A predominant water loss is shared by both diaphragm and tilts the rod, opening the valve. Very
ICF and ECF; water and sodium loss is borne mainly by small negative pressures are required to produce gas
ECF if osmolality is not greatly affected. Thus fever, lack flow of up to 300 l/min. The mouthpiece/mask elbow
of intake, diabetes insipidus and osmotic diuresis (mainly piece incorporates an expiratory valve and a safety
water loss) may be tolerated for longer periods than (overpressure) valve. Other demand valves for use with
severe vomiting, diarrhoea, intestinal obstruction and Entonox have the second-stage (demand) regulator
diuretic therapy (water and sodium loss), although attached to the patients mask.
reduced water intake often accompanies the latter
conditions. Demeclocycline hydrochloride. Tetracycline, used
The physiological response to dehydration includes as an antibacterial drug and to treat the syndrome of
increased thirst, vasopressin secretion and renin/ inappropriate ADH secretion (SIADH), possibly by
angiotensin system activation, and CVS compensation blocking the renal action of vasopressin.
for hypovolaemia via osmoreceptor and baroreceptor Dosage:
mechanisms. infection: 150mg qds or 300mg bd orally.
Children are particularly prone to dehydration, SIADH: 6001200mg/day in divided doses, orally.
as they exchange a greater proportion of body water Side effects: as for tetracycline.
each day.
Clinical features are related to the extent of water Demyelinating diseases. Non-specific group of disor-
loss: ders, with abnormality of the axonal myelin sheath as the
5% of body weight: thirst, dry mouth. predominant feature. Defective myelin may be present
510% of body weight: decreased intraocular pres- at birth (dysmyelinating) or may arise in areas of previ-
sure, peripheral perfusion and skin turgor, oliguria, ously normal myelin (demyelinating). Multiple (dissemi-
orthostatic hypotension. JVP/CVP are reduced. nated) sclerosis (MS) is the commonest of the latter and
1015%: shock, coma. is considered below; others include post-immunisation
Blood urea and haematocrit are increased, and urine has or parainfectious encephalomyelitis.
high osmolality (over 300 mosmol/kg) and low sodium Aetiology of MS is unknown but it is considered an
content (under 10mmol/l), assuming normal renal autoimmune disease, possibly involving climatic, geo-
function. graphical, genetic and viral factors. Plaques of demyelin-
Treatment includes oral and iv fluid administration; ation occur throughout the CNS, with preservation of
in the latter, dextrose solutions are favoured for combi- axon continuity. Optic nerve, brainstem and spinal cord
nations of ICF and ECF losses and electrolyte solutions are particularly affected, with sparing of peripheral
for ECF losses alone. Dehydration should be corrected nerves. Neurological lesions are separated temporally
preoperatively. and spatially, producing a variable clinical picture.
See also, Fluid balance; Fluids, body Common presentations include limb weakness, spastic-
ity, hyperreflexia, visual disturbances, paraesthesia and
Delirium tremens (DTs). Alcohol withdrawal syn- incoordination. Progression is variable with relapses
drome seen in chronic heavy drinkers. Occurs in about associated with trauma, infection, stress and rise in body
5% of cases. Thought to be caused by reduction in both temperature.
inhibitory GABAA activity and presynaptic sympathetic Diagnosed clinically, supported by gadolinium-
inhibition; hypomagnesaemia and hypocalcaemia may enhanced MRI findings and the presence of oligoclonal
contribute to CNS hyperexcitability. Characterised by: IgG bands in the CSF. Evoked potential testing may
tremor, agitation. support the diagnosis.
confusion, disorientation, hallucinations (usually Treatment is supportive, but may include corticoste-
visual). roids. Interferon beta has been shown to decrease
sweating, tachycardia, hypertension. the relapse rate in relapsing remitting MS. Hyperbaric
dehydration. O2 therapy has been advocated but results are
Usually occurs 23 days after withdrawal of alcohol, and disappointing.
lasts 34 days. May thus occur perioperatively. Anaesthetic implications are unclear, since effects
Treatment includes: rehydration; correction of of stress, surgery and anaesthesia cannot be separated
hypoglycaemia and electrolyte imbalance; and sedation. from the spontaneity of new lesion formation. Thus case
Benzodiazepines are the agents of choice, although car- reports are often conflicting in their conclusions.
bamazepine and phenobarbital have also been used. Increases in body temperature should be avoided; avoid-
Prevention is important and is achieved with the same ance of anticholinergic drugs has been suggested. An
drugs. abnormal response to neuromuscular blocking drugs,
Kosten TR, OConnor PG (2003). N Engl J Med; 348: including hyperkalaemia following suxamethonium, has
178695 been suggested but without direct evidence. Prolonged
muscle spasms may occur, but epilepsy is rare. Increased
Demand valves. Valves that allow self-administration of tendency to DVT has been suggested. Impairment of
inhalational anaesthetic agents; they may form part of respiratory and autonomic control has been reported.
178 Denervation hypersensitivity

Although not contraindicated, epidural or spinal anaes- arrhythmias may arise from use of adrenaline solu-
thesia has sometimes been avoided for medicolegal tions, stimulation of the trigeminal nerve, anxiety
reasons, although it is increasingly used as the preferred and hypercapnia.
method of obstetric analgesia and anaesthesia. Mouth packs may be employed to prevent airway
soiling. They should be placed under the tongue, pushing
Denervation hypersensitivity. Increased sensitivity of the tongue back to seal the mouth from the airway.
denervated skeletal muscle to acetylcholine. Develops Mouth gags or props are often used to hold the mouth
approximately 45 days after denervation, and is due to open.
proliferation of extrajunctional acetylcholine receptors Dental surgery is performed on an inpatient surgery
over the entire muscle membrane, instead of being basis if airway obstruction, cardiac or respiratory disease,
restricted to the neuromuscular junction. Thought to be coagulation disorders or extreme obesity is present.
the mechanism underlying the exaggerated hyperkalae- Nasotracheal intubation is usually performed, and a
mic response to suxamethonium seen after peripheral throat pack placed. Use of concentrated adrenaline solu-
nerve injuries. Its cause is unclear. Also occurs in smooth tions by dentists is still common, e.g. 1:80 000, despite
muscle. anaesthetists objections.

Density. For a substance, defined as its mass per unit Depolarising neuromuscular blockade (Phase I
volume. Relative density (specific gravity) is the mass of block). Follows depolarisation of the postsynaptic mem-
any volume of substance divided by the mass of the same brane of the neuromuscular junction via activation of
volume of water. acetylcholine receptors, but with only slow repolarisa-
tion. Effect of depolarisation of presynaptic receptors is
Dental injury, see Teeth unclear, but may be partially responsible for the fascicu-
lation seen. Suxamethonium is the most commonly used
Dental nerve blocks, see Mandibular nerve blocks; and widely available drug; previously used drugs include
Maxillary nerve blocks decamethonium and suxethonium.
Features of depolarising blockade:
Dental surgery. Anaesthesia may be required for tooth may be preceded by fasciculation.
extraction, conservative dental surgery or maxillofacial does not exhibit fade or post-tetanic potentiation.
surgery. increased by acetylcholinesterase inhibitors.
For outpatient ambulatory surgery, the following may potentiated by respiratory alkalosis, hypothermia,
be used: hyperkalaemia and hypermagnesaemia.
mandibular and maxillary nerve blocks. antagonised by non-depolarising neuromuscular
relative analgesia. blocking drugs.
iv sedation, e.g. Jorgensen technique and variants. development of dual block with excessive dosage of
inhalational anaesthetic agents, including N2O and/ drug.
or volatile agents. Traditionally administered from See also, Neuromuscular blockade monitoring; Non-
intermittent-flow anaesthetic machines, using nasal depolarising neuromuscular blockade
inhalers, although continuous-flow machines are
increasingly used. Quantiflex apparatus is also used. Dermatomes. Lateral walls of somites (segmental units
Occupational exposure to N2O is a hazard, espe- appearing longitudinally early in embryonic develop-
cially in small dental surgeries. ment), which form the skin and subcutaneous tissues.
iv anaesthetic agents. Cutaneous sensation retains the somatic distribution,
The use of general anaesthesia for dental surgery is corresponding to segmental spinal levels. Thus areas of
declining, with local anaesthetic techniques becoming skin are supplied by particular spinal nerves; useful in
more common, especially for conservative dentistry. determining the extent of regional anaesthetic blocks
General anaesthesia is usually reserved for patients who and localising neurological lesions (Fig. 52).
have learning difficulties or are extremely nervous, chil- See also, Myotomes
dren, those undergoing multiple extractions and those
with local infection (infiltration is less effective, and may Dermatomyositis, see Polymyositis
spread infection). Because of safety concerns, general
anaesthesia is now provided by anaesthetists within hos- Desensitisation block, see Dual block
pitals, in the UK.
General anaesthetic principles are as for day-case Desferrioxamine mesylate. Chelating agent used in
surgery; main problems: the treatment of aluminium and iron poisoning.
high proportion of children, usually anxious and Dosage: 15mg/kg/h iv to a maximum of 80mg/
unpremedicated. kg/24h. Also given by sc infusion in chronic iron
shared airway as for ENT surgery. Airway obstruc- overload, e.g. associated with haemochromatosis or
tion, mouth breathing during nasally administered repeated blood transfusions: 2050mg/kg/day given
anaesthesia, airway soiling and breath-holding may over 812h, 37 times per week.
occur. For these reasons the traditional nasal inhaler Side effects: anaphylaxis, hypotension, tachycardia,
(mask-like device held over the nose from behind thrombocytopenia, visual and hearing loss.
the patients head) is now rarely used by hospital
anaesthetists. Desflurane. 1-Fluoro-2,2,2-trifluoroethyl difluorometh-
the risk of hypotension in the sitting position must yl ether. Inhalational anaesthetic agent, synthesised in
be weighed against that of airway soiling if supine; the 1960s but only introduced in the UK in 1994. Chemi-
the semi-sitting position with the legs raised is often cal structure is the same as isoflurane, but with the
used as a compromise. chlorine atom replaced by fluorine (Fig. 53).
 Desmopressin 179

requires the use of an electrically powered vapo-

riser due to its low boiling point.
V1 Effects:
C2
CNS:
V2
- rapid induction (although limited by its irritant
V3 properties) and recovery.
C3 - EEG changes as for isoflurane.
C4 - may increase cerebral blood flow, although the
C5 T2 response of cerebral vessels to CO2 is preserved.
- ICP may increase due to imbalance between the
production and absorption of CSF.
T4 - reduces CMRO2 as for isoflurane.
- has poor analgesic properties.
T1 RS:
- causes airway irritation; not recommended for
induction of anaesthesia since respiratory compli-
cations (e.g. laryngospasm, breath-holding, cough,
C6 T10 apnoea) are common and may be severe.
L1 - respiratory depressant, with increased rate and
C7
T12 decreased tidal volume.
L1 S4 CVS:
C8
S3 - vasodilatation and hypotension may occur, similar
S5 to that with isoflurane. May cause tachycardia
L2 L3 L2 and hypertension via sympathetic stimulation,
especially if high concentrations are introduced
rapidly.
- myocardial ischaemia may occur if sympathetic
stimulation is excessive.
L3
- arrhythmias uncommon, as for isoflurane. Little
S2
myocardial sensitisation to catecholamines.
- renal and hepatic blood flow generally
preserved.
L4 other:
L4
L5 - dose-dependent uterine relaxation (although less
than isoflurane and sevoflurane).
- skeletal muscle relaxation; non-depolarising neu-
L5 romuscular blockade may be potentiated.
S1 - may precipitate MH.
S1 Only 0.02% metabolised.
26% is usually adequate for maintenance of anaes-
thesia, with higher concentrations for induction. Uptake
Fig. 52 Dermatomal nerve supply and excretion are rapid because of its low blood gas
solubility; thus it has been suggested as the agent of
choice in day-case surgery, although this is controversial.
Although more expensive than isoflurane, less drug is
F H F required to maintain anaesthesia once equilibrium is
reached, and equilibrium is reached much more quickly;
F C C O C H it may therefore be more economical for use during
longer procedures.
F F F
Desmopressin (1-desamino-8-D-argininevasopressin;
Fig. 53 Structure of desflurane DDAVP). Analogue of vasopressin, with a longer-lasting
antidiuretic effect but minimal vasoconstrictor actions.
Used to diagnose and treat non-nephrogenic diabetes
Properties: insipidus. May also be used to increase factor VIII and
colourless liquid with slightly pungent vapour. von Willebrand factor levels by 24 times in mild hae-
mw 168. mophilia or von Willebrands disease. Has also been
boiling point 23C. used to improve platelet function in renal failure and to
SVP at 20C 88kPa (673mmHg). reduce blood loss in cardiac surgery.
partition coefficients: Dosage:
- blood/gas 0.42. diabetes insipidus: 1020 g od/bd, intranasally;
- oil/gas 19. 100200 g orally tds; or 14 g/day iv/sc/im.
MAC 57% in adults; 7.210.7% in children. to increase factor VIII levels: 0.4 g/kg in 50ml
non-flammable, non-corrosive. saline iv 1h preoperatively, repeated at 4 and 24h.
supplied in liquid form with no additive. Side effects: fluid retention, hyponatraemia, pallor,
may react with dry soda lime to produce carbon abdominal cramps, and angina in susceptible
monoxide (see Circle systems). patients.
180 Dew point

Dew point. Temperature at which ambient air is satu- used in hypovolaemia; concurrent water and elec-
rated with water vapour. As air containing water vapour trolyte administration should be provided.
cools (e.g. when it is in contact with a cold surface) con- anaphylaxis: thought to result from previous cross-
densation occurs when the dew point is reached (e.g. immunisation against bacterial antigens. Its inci-
misting on the surface of spectacles on entering a warm dence is reduced from 1:4500 to 1:84000 by
room from the cold). This process may be used to pretreatment with 3g dextran 1 (mw 1000), to
measure humidity. occupy and block antigen binding sites of circulat-
ing antibodies to dextran.
Dexamethasone. Corticosteroid with high glucocorti- interference with blood compatibility testing.
coid but minimal mineralocorticoid activity and long bleeding tendency. Initial administration should be
duration of action, thus used where sustained activity is limited to 5001000ml, and the total amount
required but when water retention would be harmful, administered restricted to 10 (dextran 40) and 20
e.g. cerebral oedema. Also used in congenital adrenal (dextran 70) ml/kg/day.
hyperplasia, to reduce oedema following ENT surgery, osmotic diuresis.
and in the diagnosis of Cushings disease. Other uses See also, Colloids
include prevention and treatment of PONV, and stimu-
lation of fetal lung maturation in premature labour. Dextromoramide tartrate. Opioid analgesic drug,
Dosage:
related to methadone. Introduced in 1956. Less sedating,
0.510mg orally od.
and shorter acting (duration 23h) than morphine, but
0.520mg iv (10mg followed by 4mg qds in cere-
with similar effects. No longer available in the UK.
bral oedema; 4mg to prevent PONV).
Side effects: as for corticosteroids.
Dextropropoxyphene hydrochloride/napsilate. Opi-
Dexmedetomidine hydrochloride. Selective - oid analgesic drug, related to methadone. Prepared in
adrenergic receptor agonist, with about 13001600 times 1953. Poorly effective alone, but effective when com-
the affinity for 2-receptors as for 1. Rapidly distributed bined with paracetamol (as co-proxamol). Overdose of
after iv injection (half-life about 6min) with an elimina- this combination is particularly dangerous; initial respi-
tion half-life of 22.5h. Volume of distribution is about ratory depression and coma (due to dextropropoxy-
1.3 l/kg. 94% protein-bound. Inactivated mainly to gluc- phene) may be treated correctly but later liver failure
uronides with 8090% excreted in the urine. Has similar (due to paracetamol poisoning) may occur if appropriate
effects to clonidine but more predictable and easier to prophylaxis is not given. Safety concerns, even at or just
titrate, e.g. for sedation in ICU. above normal doses, led to co-proxamols phased with-
Dosage: 1 g/kg iv over 1015min, then 0.21.4 g/ drawal from the UK in 2005.
kg/min.
Side effects: as for clonidine. May cause hypertension Dextrose solutions. IV fluids available as 5, 10, 20, 25
at high doses via peripheral vasoconstriction. May and 50% solutions in water (50, 100, 200, 250 and 500g/l
also reduce renal blood flow. Has little direct effect respectively). Once administered, the glucose is rapidly
on respiration. metabolised and the water distributed to all body fluid
compartments. Thus used in hypoglycaemia, and to
Dextrans. Group of branched polysaccharides of replace water losses. Also used with insulin to treat acute
200000 glucose units, derived from the action of bacte- hyperkalaemia.
ria (Leuconostoc mesenteroides) on sucrose. Partial Excess administration may result in hyponatraemia.
hydrolysis produces molecules of average mw 40kDa, Solutions of higher concentrations are increasingly
70kDa and 110kDa (dextrans 40, 70 and 110 respec- hypertonic, acidic and viscous; they may cause thrombo-
tively). Dextran 40 is used to promote peripheral blood phlebitis if infused peripherally. Osmolality of 5% dex-
flow, e.g. in arterial insufficiency and in prophylaxis of trose solution is 278 mosmol/kg; of 10% solution 523
DVT. Dextrans 70 and 110 are used mainly for plasma mosmol/kg. pH of 5% solution is approximately 4.0. May
expansion; the latter is now rarely used and is unavail- cause haemolysis of stored erythrocytes when infused iv
able in the UK. Dextrans increase peripheral blood immediately before stored blood without first flushing
flow by reducing viscosity, and may coat both endothe- the line with saline, presumably because the dextrose is
lium and cellular elements of blood, reducing their taken up and metabolised by the cells to leave a hypo-
interaction. They reduce platelet adhesiveness, possibly osmotic solution.
impair factor VIII activity and may have anti- See also, Fluids, body; Intravenous fluid administration
inflammatory properties.
Size of dextran molecules is directly proportional to
the degree of plasma expansion produced and the mol- Dezocine. Synthetic opioid analgesic drug, related
ecules circulation time. Half-life ranges from 15min for to pentazocine; available in the USA but not in the
small molecules to several days for larger ones. Major UK. Comparable in potency, onset and duration of
route of excretion is via the kidneys. action to morphine. Has some opioid receptor antago-
Supplied in 5% dextrose or 0.9% saline, as 6% (dex- nist activity, less than that of nalorphine but greater than
trans 70 and 110) or 10% (dextran 40) solutions. Dextran that of pentazocine. Administered im or iv in doses of
70 is also supplied as a 6% solution in hypertonic saline 2.520mg.
(7.5%); 250ml given over 25min should be followed
immediately by isotonic fluids. Diabetes insipidus. Polyuria and polydipsia associated
Side effects: with reduced vasopressin activity, either because secre-
renal failure caused by tubular obstruction by tion by the pituitary gland is reduced (cranial/neurogenic)
dextran casts; mainly occurs with dextran 40 when or the kidneys are unresponsive (nephrogenic):
 Diabetes mellitus 181

cranial: occurs in head injury, neurosurgery (espe- Complications:

cially post-pituitary surgery), intracranial tumours. renal impairment, caused by glomerulosclerosis, vas-
Rarely familial. cular insufficiency, infection and papillary necrosis.
nephrogenic: caused by drugs, e.g. lithium, demeclo- arteriosclerosis causing ischaemic heart disease,
cycline and gentamicin; a rare X-linked recessive peripheral vascular insufficiency and CVA. Micro-
form may also occur. vascular involvement may cause cardiac failure and
Characterised by inappropriate production of large impaired ventricular function. Hypertension is
volumes of dilute urine, with raised plasma osmolality. more common than in non-diabetic subjects.
Patients cannot concentrate their urine in response to autonomic and peripheral neuropathy, the latter
water deprivation. The two types are distinguished by sensory or motor. Single nerves may also be affected,
their response to administered vasopressin. including cranial nerves.
Treatment: retinopathy and cataract formation.
cranial: desmopressin (synthetic vasopressin ana- skin: collagen thickening, blisters, necrobiosis
logue) 1020 g od/bd intranasally; 100200 g lipoidica.
orally tds; or 14 g/day iv/sc/im. increased susceptibility to infection and delayed
nephrogenic: thiazide diuretics. wound healing.
Anaesthetic considerations are related to impaired fluid diabetic coma.
balance with hypovolaemia, dehydration, hypernatrae- syndrome of stiff joints may occur: suggested by the
mia and other electrolyte imbalance. Careful attention prayer sign (inability to press the palmar surfaces
to fluid balance, with monitoring of urine and plasma of the index fingers fully flat against one another
osmolality and electrolytes, is required. when pressing the palms together). Has been associ-
ated with difficult tracheal intubation and reduced
Diabetes mellitus. Disorder of glucose metabolism compliance of the epidural space.
characterised by relative or total lack of insulin Anaesthetic management is related to the above
or insulin resistance. This results in lipolysis, gluconeo- complications and to the perioperative control of
genesis and glycogenolysis, with hepatic conversion of blood sugar. Mortality and morbidity are increased
fatty acids to ketone bodies, and hyperglycaemia. The when compared with non-diabetic patients.
resultant glycosuria causes an osmotic diuresis, with Patients should be assessed for fitness and diabetic
polyuria, polydipsia and excessive sodium and potas- control, and scheduled for surgery at the beginning
sium loss. of the operating list. The aim is to avoid hyper
Affects 4.5% of the UK population; over 80% glycaemia, ketoacidosis, hypoglycaemia and electro-
are over 80 years old and 50% are likely to require lyte imbalance:
surgery. NIDDM patients: for minor surgery, monitoring of
May be: blood sugar levels is usually all that is required.
primary: thought to be related to genetic, infective Chlorpropamide is withheld for 48h before surgery;
and immunological factors, but the aetiology is shorter-acting sulphonylureas and biguanides are
unclear. withheld on the morning of surgery. A glucose level
secondary: < 12mmol/l is traditionally thought to be accept-
- pancreatic disease, e.g. pancreatitis, malignancy. able, although tighter control (aiming for the same
- insulin antagonism, e.g. corticosteroids, Cushings levels as in IDDM) has been suggested. Patients are
syndrome, acromegaly, phaeochromocytoma. treated as for IDDM when undergoing major
- drugs, e.g. thiazide diuretics. surgery. Oral medication is restarted when oral
Classically divided into type 1 (insulin-dependent; calorie intake is resumed postoperatively.
IDDM), presenting in children or young adults, and IDDM: patients are starved preoperatively, with
type 2 (non-insulin-dependent; NIDDM), presenting morning insulin omitted. They should receive
in adults (and occasionally children) who are usually insulin and dextrose iv throughout the periopera-
obese. Type 1 DM is an autoimmune disease, with 85% tive period, to avoid hyper- and hypoglycaemia and
of patients having antibodies against pancreatic islet maintain plasma glucose between 6 and 10mmol/l.
cells, and results in low or absent circulating insulin; Dextrose and insulin infusions should be through
treatment is with exogenous insulin. Type 2 DM is due the same iv cannula, to reduce risk of accidental
to a relative lack of insulin and insulin resistance and is overdose of one infusion should the other infusion
caused by excessive calorie intake and obesity in geneti- cease running. Several regimens are used:
cally susceptible individuals; it is treated with diet - Alberti regimen: 1000ml 10% dextrose + 10 units
control, oral hypoglycaemic drugs (sulphonylureas, big- soluble insulin + 10mmol potassium infused at
uanides, acarbose, thiazolidinediones and meglitinides), 100ml/h. The infusion is changed to contain more
a combination of oral hypoglycaemic drugs and insulin, or less insulin according to regular testing with
or insulin alone. glucose reagent sticks. The preoperative insulin
The World Health Organization suggests the follow- regimen is restarted when the patient is drinking
ing diagnostic criteria: and eating normally.
symptoms + plasma glucose concentration > - the total daily insulin requirement is divided by
11.1mmol/l, four, adding the result to 500ml 5% dextrose +
or two fasting glucose concentrations > 510mmol potassium. The bag is infused at
7.0mmol/l, 100ml/h, with regular checking of blood glucose
or glucose concentration > 11.1mmol/l, 2h after levels.
ingestion of glucose in a glucose tolerance test. - 5% dextrose + 510mmol potassium is infused at
A random HbA1c measurement lacks sensitivity as a 100ml/h, with insulin infused via a syringe pump,
diagnostic marker. adjusted according to a sliding scale.
182 Diabetic coma

Since the symptoms of hypoglycaemia are masked by hourly for 2h, then 2-hourly, then 24-hourly.
general anaesthesia, regular perioperative monitoring of This is changed to 5% dextrose when blood
plasma glucose is required. Lactate-containing solutions glucose is 1015mmol/l (180270mg/dl). Hypo-
are usually avoided as they may increase plasma glucose tonic saline is used in hyperosmolar coma as
levels, although actual increases are small unless large below.
volumes are given. - potassium supplementation is required despite
Regional techniques are often preferred because they any initial hyperkalaemia, since the body potas-
interfere less with oral intake. Insulin requirements may sium deficit will be revealed once tissue uptake
be increased after major surgery as part of the stress is stimulated by insulin. Suitable starting
response to surgery. regimen: 1020mmol in the first litre of fluid;
Emergency surgery is particularly hazardous, 1040mmol thereafter, depending on the
especially if diabetes is poorly controlled. Adequate plasma potassium after 1h (repeated every few
resuscitation must be performed, with treatment of keto- hours).
acidosis if present. Hyperglycaemia may present with - insulin should be given iv. An initial bolus
abdominal pain, and abdominal surgery may reveal no of 0.15 units/kg is followed by 0.1 units/kg/h,
abnormality. producing a gradual correction of blood glucose
Pregnancy may precipitate or worsen diabetes, and levels.
close medical supervision is required. During labour, - bicarbonate therapy (guided by base excess) if
regimens usually involve iv infusions of 5% dextrose pH is under 7.07.1.
(e.g. 500ml/8h) with iv insulin rate adjusted accordingly. - hypophosphataemia may require replacement,
Epidural anaesthesia is usually suggested, since it reduces e.g. with potassium phosphate, 520mmol/h.
acidosis in labour and facilitates caesarean section if hyperosmolar non-ketotic coma: typically seen in
indicated. elderly patients with type 2 diabetes mellitus and
[K George MM Alberti, Newcastle physician] presents with slow onset with polyuria and progres-
Robertshaw HJ, Hall GM (2006). Anaesthesia; 61: sive dehydration. Focal neurological features may
118790 occur. Blood glucose levels and osmolality are very
high, with little or no ketonuria. Treatment includes
small doses of insulin and 0.45% saline adminis-
Diabetic coma. Coma in diabetes mellitus may be tered slowly iv. Cerebral oedema and convulsions
caused by: may occur if rehydration is too rapid.
hypoglycaemia: caused by overdose of hypoglycae- lactic acidosis: usually occurs in elderly patients
mic agent, excessive exertion or decreased food taking biguanides. Blood glucose may be normal,
intake. Treatment includes iv glucose; iv/im gluca- with little or no ketonuria.
gon may occasionally be useful in out-of-hospital Clinical distinction between different types of diabetic
situations. coma is unreliable. Features aiding the diagnosis are
ketoacidosis: more common in insulin-dependent shown in Table 19.
diabetics. Mortality is 610%, highest in old age.
Often precipitated by other illness (e.g. infection Diagnostic peritoneal lavage, see Peritoneal lavage
and MI), since insulin requirements are increased.
May develop insidiously. Dialysis. Artificial removal of water and solutes from the
- features: blood by selective diffusion across a semipermeable
- of dehydration, e.g. hypotension, tachycardia. membrane. Indications include renal failure and severe
- of acidosis, e.g. hyperventilation (Kussmaul cardiac failure unresponsive to diuretic therapy; may
breathing). also remove drugs from the circulation in poisoning and
- vomiting, diarrhoea, abdominal pain; the last overdoses, although only effective for smaller, non-
may simulate an acute surgical emergency, protein-bound, water-soluble molecules. Collectively
requiring careful review of the diagnosis. termed renal replacement therapy; many variants exist
- smell of acetone on the breath. but they may be classified into:
- diagnostic criteria include pH < 7.3, HCO3 peritoneal dialysis.
< 15mmol/l and blood glucose > 14mmol/l. intermittent haemodialysis.
However, glucose levels may be normal in those continuous haemodiafiltration.
who are chronically malnourished. All techniques rely on the diffusion of water and solutes
- management: across a semipermeable membrane; this passage may
- measurement of urea and electrolytes, glucose, be manipulated by altering the hydrostatic or osmotic
arterial blood gases, full blood count. Urine dip- gradients across the membrane to optimise removal. In
stick for ketones and nitrites. CXR and blood
cultures.
- general management: O2 and airway control if Table 19 Features of different types of diabetic coma
required, nasogastric tube (gastric dilatation is
common), urinary catheter, CVP measurement, Type Blood glucose (mmol/l) Dehydration Ketones
ECG and other standard monitoring. Antibiot-
ics are administered if infection is suspected. Hypoglycaemia <2 0 0
Prophylactic low-molecular-weight heparin is Ketoacidosis > 14 +++ ++
routinely given. Hyperosmolar > 14 +++ 0
- fluid therapy: guided by CVP measurement; up non-ketotic
to 68 litres may be required. Suitable starting Lactic acidosis Variable + 0 to +
regimen: 1 litre of 0.9% saline over 30min, then
 Diaphragmatic herniae 183

haemoperfusion, unwanted molecules (including lipid- - to the lower six ribs, costal cartilages and xiphi-
soluble protein-bound ones) are adsorbed on to acti- sternum anteriorly.
vated charcoal or an ion exchange resin, thus involving Has three main openings transmitting the following
a different principle from that of dialysis. Both dialysis structures:
and adsorption techniques have been used to remove inferior vena cava and right phrenic nerve at the
circulating toxins in hepatic failure, such techniques level of T8.
usually being termed liver dialysis. oesophagus, vagus and gastric nerves and branches
of the left gastric vessels at the level of T10.
Diamorphine hydrochloride (Diacetylmorphine; aorta, thoracic duct and azygos vein at the level
Heroin). Opioid analgesic drug, introduced in 1898; said of T12.
to cause less constipation, nausea and hypotension than The diaphragm is also pierced by the left phrenic
morphine, but more likely to cause addiction. Also sup- nerve and splanchnic nerves.
presses coughing to a greater extent. Inactive prodrug The sympathetic chain passes behind the medial
that is rapidly hydrolysed by plasma cholinesterase to lumbosacral arch.
6-monoacetylmorphine (responsible for the rapid onset Nerve supply: from C35 via the phrenic nerves, with
of action), which is then slowly metabolised to morphine some sensory supply to the periphery via the lower
in the liver. Unavailable in the USA, Australia and parts intercostal nerves.
of Europe (e.g. Germany) because of its reputation as a Development:
drug of addiction, although there is no evidence that originally in the neck; descends during develop-
medical use increases its abuse. ment, retaining its cervical nerve supply.
Dosage: 5mg is equivalent to 10mg morphine. It formed from:
may be given im, iv, sc, orally, epidurally (15mg) or - oesophageal mesentery dorsally.
intrathecally (100300 g); also effective given - right and left pleuroperitoneal membranes
intranasally. laterally.
See also, Spinal opioids - septum transversum anteriorly (forming the
central tendon).
Diaphragm. Fibromuscular sheet separating the thorax - small peripheral contribution from body wall.
from the abdomen. The main respiratory muscle, it flat- Defects in development may produce diaphragmatic
tens and descends vertically during inspiration, expand- herniae.
ing the thoracic cavity. During expiration, it relaxes; in See also, Hiatus hernia
forced expiration, contraction of the anterior abdominal
muscles pushes the diaphragm upwards. Diaphragmatic herniae. Herniation of abdominal
Consists of (Fig. 54): viscera through the diaphragm into the thorax. Congeni-
central tendon, attached to the pericardium above. tal herniae occur in approximately 1 in 4000 live births
peripheral muscular part. Attachments: (1 in 2500 of all births), are often familial and are caused
- posteriorly via the medial and lateral lumbosacral by failure of fusion of the various components of the
arches (arcuate ligaments), to fascia covering diaphragm, e.g.:
psoas and quadratus lumborum muscles respec- foramen of Bochdalek: through a defective pleuro-
tively. The right and left crura attach to vertebrae peritoneal membrane, usually left-sided. The most
L13 and L12 respectively; between them lies common form (80%).
the median lumbosacral arch (median arcuate foramen of Morgagni: between xiphoid and costal
ligament). origins; more common on the right side.
through the central tendon or oesophageal hiatus.
Usually diagnosed during routine antenatal ultrasound.
Other congenital defects may be present (e.g. cardiac
Inferior vena cava Central tendon Left phrenic nerve anomalies found in 50%).
Causes respiratory distress, cyanosis, scaphoid
abdomen and bowel sounds audible in the thorax. Diag-
nosed clinically and by X-ray. The lung on the affected
side is often hypoplastic, with decreased compliance and
increased pulmonary vascular resistance (PVR). Arterial
hypoxaemia reflects immature lung tissue and impaired
ventilation caused by presence of thoracic bowel,
Oesophagus and persistent fetal circulation caused by the raised
PVR. PVR is further increased by hypoxic pulmonary
Aorta vasoconstriction.
Immediate management includes gastric decompres-
sion, improving oxygenation and decreasing PVR. PVR
may be reduced by: avoiding hypocapnia and hypother-
Right crus
Quadratus mia; treating acidosis; use of inhaled nitric oxide and iv
lumborum muscle vasodilator drugs (e.g. sodium nitroprusside 12 g/kg/
min, prostacyclin 510ng/kg/min).
Medial lateral Psoas major muscle IPPV by face-piece may increase gastric distension
lumbrosacral arches and should be avoided. IPPV is best performed via a
(arcuate ligaments) Vertebral column tracheal tube, avoiding excessive inflation pressures
since pneumothorax and acute lung injury may easily
Fig. 54 Inferior aspect of diaphragm occur. Surgery is usually delayed until respiratory
184 Diarrhoea

stability is achieved. High-frequency ventilation and for coronary blood flow; used to calculate endocardial
extracorporeal membrane oxygenation have been used. viability ratio.
Mortality is high if pneumothorax occurs and lung com- See also, Cardiac cycle
pliance is low.
Anaesthesia for surgical correction is as for paediatric Diathermy (Bovie machine). Device used to coagulate
anaesthesia. N2O is avoided because of distension of blood vessels, and cut and destroy tissues during surgery,
thoracic bowel. Excessive inflation of the hypoplastic by the heating effect of an electric current passed
lung at the end of the procedure should be avoided, through them. Alternating current with a frequency
since pneumothorax may occur. Abdominal closure of 0.51MHz is used; a sine wave pattern is employed
may be difficult once the bowel is returned to the for cutting and a damped or pulsed sine wave pattern
abdomen; postoperative IPPV may be required. The for coagulation. Electrical stimulation of skeletal and
hypoplastic lung slowly re-expands, usually within a few cardiac muscle is negligible at these high frequencies.
days/weeks. The current density is kept high at the site of intended
Acquired acute herniae may follow blunt or penetrat- damage by using small electrodes at this site, e.g.
ing trauma or surgery. They may impair ventilation, or forceps tips.
only cause symptoms if strangulation or obstruction Diathermy may be:
occurs. Hiatus hernia is gradual in onset. unipolar (monopolar):
[Giovanni B Morgagni (16821771), Italian anatomist; - forceps or pencil-point, act as one electrode.
Victor A Bochdalek (18011883), Czech anatomist] - large plate strapped to the patients leg acts as the
Bsenberg AT, Brown RA (2008). Curr Opin Anesthe- other electrode, often at earth potential. Current
siol; 21: 32331 density at this site is low because of the large area
See also, Cardiopulmonary resuscitation, neonatal of tissue through which current passes, thus little
heating occurs.
Diarrhoea. Common problem in the ICU which contrib- bipolar: current is passed across tissue held between
utes to increased mortality; may result in dehydration the two tips of a pair of forceps. The power used is
and skin excoriation, and is upsetting to the patient and small and the current dispersal through other tissues
relatives. There are many causes, including: is negligible; thus used for more delicate surgery,
infection (e.g. norovirus, Clostridium difficile, sal- e.g. eye surgery and neurosurgery. No plate elec-
monella, campylobacter species). trode is required.
inflammatory bowel disease. Hazards:
malabsorption. interference with monitoring equipment.
bowel ischaemia. incorrect attachment of the plate may cause
drugs (e.g. antibacterial drugs). burns, e.g. if contact is only made over a small
enteral nutrition. surface area.
Spurious (over-flow) diarrhoea may occur in severe burns may occur if the surgeon activates the dia-
constipation. Non-infectious diarrhoea tends to occur thermy accidentally, or if the forceps are touching
without blood or mucus. Stools usually return to normal the patient or lying on wet drapes. When not used,
after the causal agent is removed. the forceps should be kept in a protective non-
Management includes appropriate investigation conducting holder. An audible buzzer warns that
(stool cultures and microscopy, sigmoidoscopy; more the device is operating.
invasive endoscopy or imaging may be required) and if the plate electrode is earthed, and connections
maintenance of fluid and electrolyte balance. Probiotic are faulty, current may take other routes to reach
agents may be useful. Specific causes are managed earth. Thus current may flow through any earthed
accordingly. Symptomatic treatment (e.g. with codeine metal conductor the patient touches (e.g. drip
or loperamide) may be indicated, although they are gen- stands, ECG leads), causing burns at the site of
erally avoided in children and in infective diarrhoea. contact. In addition, the mains (50Hz) current may
See also, Clostridial infections flow through the system. A capacitor within the
circuit will prevent the latter, whilst allowing the
Diastole, see Cardiac cycle; Diastolic interval diathermy current to flow. Risks from flow of
current to earth are reduced if the circuit is com-
Diastolic blood pressure. Lowest arterial BP during pletely isolated from earth (floating), since current
diastole. Contributes to MAP and represents the pres- will no longer take these other routes.
sure head for coronary blood flow. may act as an ignition source of flammable sub-
Diastolic BP has been used to guide therapy in hyper- stances, e.g. anaesthetic agents, bowel gases, alcohol
tension, treatment usually being advocated if it exceeds skin preps.
90mmHg, but this is controversial. may interfere with implantable cardioverter defi-
brillators and pacemaker function.
Diastolic interval. Duration of diastole. Shortened [William T Bovie (18821958), US biophysicist]
when heart rate is increased; e.g. equals about 0.62 s at See also, Cardiac pacing; Electrocution and electrical
65 beats/min, but only 0.14 s at 200 beats/min. burns; Explosions and fires
Short diastolic intervals reduce coronary blood flow
and ventricular filling. Diazepam. Benzodiazepine, widely used for sedation,
anxiolysis and as an anticonvulsant drug. Has been used
Diastolic pressure time index (DPTI). Area between for premedication, and to supplement or induce anaes-
tracings of left ventricular pressure and aortic root pres- thesia. Insoluble in water; original preparations caused
sure during diastole (see Fig. 61; Endocardial viability pain on injection and thrombophlebitis. These are rare
ratio). Represents the pressure head and time available with emulsions of diazepam in soya bean oil.
 Differential lung ventilation 185

May cause respiratory depression, especially in the used for musculoskeletal pain and renal colic. Exten-
elderly. Reduced cardiac output and vasodilatation sively (> 99%) protein-bound in plasma; half-life is
occur with large doses. Drowsiness and confusion, espe- 12h. 60% excreted via urine, the rest passing into
cially in the elderly, may persist for several hours. the faeces.
Absorption after im injection is unreliable and the Dosage:
injection is painful. 1mg/kg (up to 75mg) via deep im injection bd for
Half-life is 2070h, with formation of active metabo- up to 2 days.
lites (that are renally excreted) including nordiazepam 75mg iv qds for up to 2 days. Should be diluted
(half-life up to 120h), desmethyldiazepam, oxazepam immediately before use with 100500ml 0.9%
and temazepam. Thus repeated doses (e.g. in ICU) may saline or 5% glucose, which should then be buffered
lead to delayed recovery. with 0.5ml 8.4% or 1ml 4.2% sodium bicarbonate
Dosage: solution. A new preparation, able to be given
1030mg orally for premedication (0.5mg/kg in without buffering or diluting, was introduced in the
children, up to 10mg). UK in 2008 but was withdrawn 2 years later because
510mg iv for sedation or anticonvulsant effect, vials were found to contain particulate material.
repeated as necessary. Rectal administration is also 75150mg/day orally/pr in divided doses (13mg/
effective. kg in children). A case involving a misplaced diclo
fenac suppository inserted vaginally and subse-
Diazoxide. Vasodilator drug, used for emergency treat- quent claims of rape have led to recommendations
ment of severe hypertension. Acts directly on blood that all planned suppository insertions should be
vessel walls by activating potassium channels. Previously discussed beforehand with the patient.
indicated in hypertensive crisis, but the risk from sudden Side effects: as for NSAIDs. Should be used with

reduction in BP has resulted in its indication for iv use caution in renal impairment and asthma. Muscle
being restricted to severe hypertension associated with damage after im injection has been indicated by
renal disease. Increases blood glucose level by increasing increased plasma creatine kinase levels. Sterile
catecholamine levels and by reducing insulin release; abscesses have occurred after superficial injection.
may be used orally to treat chronic hypoglycaemia (e.g.
in insulinoma). Dicobalt edetate, see Cyanide poisoning
Dosage: 13mg/kg (up to 150mg) iv for hyperten-
sion, repeated after 515min if required. MI and Dicrotic notch, see Arterial waveform
CVA have followed larger doses. For hypoglycaemia,
5mg/kg/day orally. Diethyl ether. C2H5OC2H5. Inhalational anaesthetic
Side effects: tachycardia, hyperglycaemia, fluid agent, first prepared in 1540. Paracelsus described its
retention. effects on chickens in the same year. Produced by heating
concentrated sulphuric acid with ethanol. First used for
Dibucaine, see Cinchocaine anaesthesia in 1842 by Clarke and Long, who did not
publish their work until later. Introduced publicly by
Dibucaine number. Degree of inhibition of plasma cho- Morton in the USA in 1846; used in London by Boott
linesterase by dibucaine (cinchocaine). Sample plasma is and in Dumfries in the same year. Classically given
added to a benzoylcholine solution, and breakdown of by open-drop techniques, and more recently using a
the latter is observed using measurement of light absorp- draw-over technique (e.g. using the EMO vaporiser), or
tion. This is repeated using plasma pretreated with a 105 by standard plenum vaporiser. Inspired concentrations
molar solution of dibucaine; the percentage inhibition of of up to 20% may be required during induction of
benzoylcholine breakdown by the enzyme is the dibu- anaesthesia.
caine number. Abnormal variants of cholinesterase are No longer generally available in the UK, although
inhibited to lesser degrees, with dibucaine numbers less widely considered one of the safest inhalational agents,
than the normal 7585%. Thus useful in the analysis and largely because respiratory depression is late and pre-
typing of different abnormal variants, which may give cedes cardiovascular depression. Still used worldwide,
rise to prolonged paralysis following suxamethonium because of its safety and low cost.
administration. Its many disadvantages include flammability, high
Similar testing may be performed using inhibition by blood/gas partition coefficient resulting in slow uptake
fluoride, chloride, suxamethonium itself and other and recovery, respiratory irritation causing coughing and
compounds. laryngospasm, stimulation of salivary secretions, high
incidence of nausea and vomiting, and occurrence of
convulsions postoperatively, typically associated with
DIC, see Disseminated intravascular coagulation pyrexia and atropine administration. Sympathetic stimu-
lation maintains BP with low incidence of arrhythmias,
Dichloroacetate, see Sodium dichloroacetate but hyperglycaemia may occur.
Has been used in severe asthma because of its bron-
Dichlorphenamide. Carbonic anhydrase inhibitor, used chodilator properties.
to treat glaucoma but also to stimulate respiration, pos- 1015% metabolised to alcohol, acetaldehyde and
sibly by lowering CSF pH. Actions are similar to those acetic acid.
of acetazolamide, but longer lasting. Has been used to
assist weaning in ICU. Differential lung ventilation (DLV). Performed when
the requirements of each lung are so different that con-
Diclofenac sodium. NSAID, commonly used for post- ventional IPPV cannot maintain adequate gas exchange,
operative analgesia, reducing opioid requirements. Also e.g. because the poor compliance of one lung diverts the
186 Difficult intubation

delivered tidal volume to the other, more compliant, maintained if the gas is soluble in the liquid; i.e. rate of
lung. Thus reserved for when lung pathology is unilateral diffusion is proportional to solubility.
or much worse on one side, e.g. following aspiration
of gastric contents or irritant substances, unilateral pneu- Diffusion hypoxia, see Fink effect
monia, bronchopleural fistula. May be performed using
two conventional ventilators, each connected to one Digital nerve block. Each digit is supplied by two
lumen of a double-lumen endobronchial tube. The set- palmar and two dorsal digital nerves. A fine needle is
tings of each (including the ventilatory mode) are introduced from the dorsal side of the base of the digit,
adjusted independently in order to achieve adequate and 23ml local anaesthetic agent (without adrenaline)
lung expansion and gas exchange; synchronised inflation/ injected on each side, between bone and skin.
deflation is usually not necessary, although sideways
motion of the mediastinum (if one lung inflates just as Digoxin. Most widely used cardiac glycoside, used to
the other deflates) may cause haemodynamic distur- treat cardiac failure and supraventricular arrhythmias,
bance in susceptible patients. In some circumstances, it e.g. AF, atrial flutter and SVT. Described and investi-
may be possible to ventilate the better lung whilst apply- gated by Withering in 1785 in his Account of the Fox-
ing only CPAP to the diseased one. glove. Slows atrioventricular conduction and increases
myocardial contractility. Reduces hospitalisation rates
Difficult intubation, see Intubation, difficult and symptoms due to severe cardiac failure refractory
to first-line treatment, but has no effect on mortality.
Diffusing capacity (Transfer factor). Volume of a sub- Volume of distribution is large (700 litres) and half-life
stance (usually carbon monoxide [CO]) transferred long (36h); elimination is therefore lengthy after termi-
across the alveoli per minute per unit alveolar partial nation of treatment. Dosage must be reduced in renal
pressure. CO is used because it is rapidly taken up by impairment and in the elderly. Therapeutic plasma levels:
haemoglobin in the blood; thus its transfer from alveoli 12ng/ml (blood is taken 1h after an iv dose, 8h after
to blood is limited mainly by diffusion across the alveo- an oral dose).
lar membrane. Contraindicated in WolffParkinsonWhite syn-
Measurement: drome, since atrioventricular block may encourage
a single breath of gas containing 0.3% CO and 10% conduction through accessory pathways with resultant
helium is held for 1020 s. Initial alveolar partial arrhythmia.
Dosage:
pressure of CO is derived by measuring the dilution
of helium that has occurred. Expired partial pres- loading dose for rapid digitalisation:

sure of CO is measured. - 1.01.5mg orally in divided doses over 24h (250

continuous breathing of gas containing 0.3% CO, 500mg/day if less urgent).
for up to a minute. Rate of uptake of CO is mea- - 0.751.0mg iv over at least 2h. Fast injection may
sured when steady state is reached. cause vasoconstriction and coronary ischaemia.
Normal value: 1725ml/min/mmHg. maintenance: 62.5500 g daily (usual range 125

Reduction in pulmonary diseases (e.g. pulmonary fibro- 250 g).

Side effects and toxicity:
sis) has been traditionally attributed to increased alveo-
lar membrane thickness, although V/Q mismatch may more common in hypokalaemia, hypercalcaemia or

be more important. Also reduced when alveolar mem- hypomagnesaemia.

brane area is reduced, e.g. after pneumonectomy (cor- nausea, vomiting, diarrhoea.

rected for by calculation of diffusing coefficient: diffusing headache, malaise, confusion. Blurred or yellow

capacity per litre of available lung volume). discoloration of vision (xanthopsia) occurs early;
The term transfer factor is sometimes used because the presence of hyperkalaemia suggests severe
the measurement refers to overall measurement of gas toxicity.
transfer, which may be affected by ventilation, perfusion any cardiac arrhythmia may occur; bradycardia,

and diffusion defects distributed unevenly throughout heart block and ventricular ectopics, including bi-
the lung. Correlation with clinical examination is not and trigemini, are commonest.
always reliable for these reasons. ECG findings:

Jensen RL, Crapo RO (2003). Respir Care; 48: 77782 - prolonged PR interval and heart block.
- T wave inversion.
- ST segment depression (the reverse tick).
Diffusion. Movement of a substance from an area of
life-threatening arrhythmias and hyperkalaemia
high concentration to one of low concentration, resulting
should be treated promptly with digoxin-specific
from spontaneous random movement of its constituent
antibody fragments. Potassium replacement may
particles. May occur across membranes, e.g. from alveoli
also be required. Electrical cardioversion may result
to bloodstream.
Rate of diffusion across a membrane is propor-
in severe arrhythmias, and should be avoided. Mag-
nesium is the drug of choice for digoxin-induced
tional to:
ventricular arrhythmias.
available area of membrane.
[William Withering (17411799), English physician]
concentration gradient across the membrane (Ficks
law). Dihydrocodeine tartrate. Opioid analgesic drug, of
1 similar potency to codeine. Prepared in 1911. Causes
(Grahams law).
mw of the substance fewer side effects than morphine or pethidine at equiva-
For diffusion of a gas across a membrane into a liquid lent analgesic doses. Also has a marked antitussive
(e.g. across the alveolar membrane), concentration gra- effect. Commonly used in combination with paracetamol
dient is proportional to the pressure gradient, and is as co-dydramol (500mg/10mg per tablet).
 Diploma in Intensive Care Medicine 187

Dosage: 30mg orally or up to 50mg sc/im, 46-hourly; tubocurarine; introduced in 1948. More potent and
0.51mg/kg in children. longer-lasting (up to 2h) than tubocurarine, and with
less ganglion blockade and histamine release, i.e. more
Diltiazem hydrochloride. Class III calcium channel cardiostable. No longer used in the UK, although has
blocking drug and class IV antiarrhythmic drug, used to been popular in the USA as metocurine. Almost entirely
treat angina and hypertension, especially when - renally excreted.
adrenergic receptor antagonists are contraindicated or Intubating dose: 0.20.4mg/kg; acts within 35min.

ineffective. Causes vasodilatation and prolonged atrio-

ventricular nodal conduction. Causes less myocardial Dinoprost/dinoprostone, see Prostaglandins
depression than verapamil but may cause severe brady-
cardia. After single oral dosage, 90% absorbed but bio- 2,3-Diphosphoglycerate (2,3-DPG). Substance formed
availability is only 45% because of extensive first-pass within red blood cells from phosphoglyceraldehyde, pro-
metabolism. About 65% excreted via the GIT. An iv duced during glycolysis. Binds strongly to the chains
preparation is available in the USA for treatment of AF, of deoxygenated haemoglobin, reducing its affinity for
atrial flutter and SVT. O2 and shifting the oxyhaemoglobin dissociation curve
Dosage:
to the right, i.e. favours O2 liberation to the tissues. Binds
60120mg orally tds (90180mg bd, or 120360mg poorly to the chains of fetal haemoglobin.
od for sustained-release preparations). Levels are increased by:
0.25mg/kg iv over 2min, followed by 0.35mg/kg anaemia.
over 2min, then 515mg/h if required. alkalosis.
Side effects: bradycardia, hypotension, malaise, head-
chronic hypoxaemia, e.g. in cyanotic heart disease.
ache, GIT disturbances, rarely, impaired liver high altitude.
function. exercise.
pregnancy.
Dilution techniques. Used for measuring body com- hyperthyroidism.
partment volumes (e.g. blood, plasma, ECF and lung hyperphosphataemia.
volumes). A known quantity of tracer substance is intro- certain red cell enzyme abnormalities.
duced into the space to be measured, and its concentra- Levels are decreased by:
tion measured after complete mixing: acidosis, e.g. in stored blood; requires 1224h for

C1 V1 = C 2 (V1 + V2 ) levels to be restored.

hypophosphataemia.
where C1 = initial concentration of indicator hypothyroidism.
C2 = final concentration of indicator hypopituitarism.
V1 = volume of indicator
V2 = volume to be measured
Diphtheria. Infection caused by Corynebacterium diph-
Tracer substances include dyes and radioisotopes; the theriae, a Gram-positive rod. Now rare in the Western
latter may be injected as radioactive ions or attached to world due to immunisation, but formerly a major cause
proteins, red blood cells, etc. Gaseous markers may be of death, particularly in children.
used to study lung volumes, e.g. helium to measure FRC. Features:
The principle may be extended for cardiac output symptoms of upper respiratory infection.
measurement, where radioisotope, dye or cold crystal- increasing malaise and fever. Diphtheria toxin may
loid solution is injected as a bolus proximal to the right affect CNS, heart and other organs. Cranial nerve
ventricle, and its concentration measured distally, e.g. and peripheral nerve palsies, visual disturbances
radial or pulmonary artery. A concentrationtime curve and cardiac failure with conduction defects and
is plotted to enable calculation of cardiac output. A arrhythmias may occur.
double indicator dilution technique has been used to a thick exudative membrane may form across the
measure extravascular lung water. posterior pharynx/larynx, causing complete
obstruction.
Dimercaprol (BAL; British Anti-Lewisite). Chelating Treatment:

agent previously used in the treatment of heavy metal as for airway obstruction.
poisoning, especially antimony, arsenic, bismuth, mercury antitoxin administration.
and gold. Now superseded by newer agents. Following iv benzylpenicillin.
im injection, peak levels occur within 1h, with elimina-
tion in 4h. Contraindicated in liver disease and glucose Dipipanone hydrochloride. Opioid analgesic drug,
6-phosphate dehydrogenase deficiency. similar to methadone and dextromoramide. Prepared in
Dosage: 2.53.0mg/kg im 4-hourly for 2 days, bd/qds 1950. Available in the UK for oral use as tablets of 10mg
on day 3 and od/bd thereafter. combined with cyclizine 30mg.
Side effects: haemolytic anaemia, transient hyperten- Dosage: 13 tablets qds. Anticholinergic effects of
sion and tachycardia, agitation, paraesthesia, head- cyclizine may limit its use.
ache, tremor, nausea and vomiting, erythema and pain
on injection. Contains peanut oil as a solvent. Diploma in Intensive Care Medicine (DICM).
[Lewisite a potent arsenic-based chemical weapon Instituted in 1997/8 to permit identification of doctors
used in World War II] trained to an adequate standard to undertake a career
with a large commitment to intensive care medicine in
Dimethyl tubocurarine chloride/bromide. Non- the UK. Aims to test knowledge and its application, and
depolarising neuromuscular blocking drug, derived from the ability to communicate with medical and nursing
188 Dipyridamole

staff, patients and their relatives. Candidates for the capillary microthrombosis may cause multiple
Diploma must possess a postgraduate qualification organ failure.
in their primary specialty (e.g. FRCA, MRCP, FRCS), shock, acidosis and hypoxaemia may occur.
should have completed the stipulated periods of training Investigations may reveal: low titres of fibrinogen, coag-
(see Intensive care, training in), and must submit a dis- ulation factors, protein C and antithrombin III; throm-
sertation. Replaced in 2013 by the Fellowship of the bocytopenia; high titres of fibrin degradation products;
Faculty of Intensive Care Medicine exam (FFICM). and prolonged prothrombin, partial thromboplastin and
thrombin times.
Treatment:
Dipyridamole. Antiplatelet drug, used to prevent CVA
and as an adjunct to oral anticoagulation, e.g. in patients directed at underlying causes.

with prosthetic heart valves. Modifies platelet aggrega- supportive.

tion, adhesion and survival. Also given iv for stress administration of fresh frozen plasma, platelets

testing during diagnostic cardiac imaging; causes marked and cryoprecipitate. Antithrombin III concentrates
vasodilatation. May cause coronary steal. have been used.
Dosage: 100150mg orally tds/qds (slow-release: the role of heparin is still unclear, but it should be

200mg bd). considered if initial therapy does not improve the

Side effects: may be hazardous in severe coronary and patients condition. Heparin has been used mainly
aortic stenosis due to its vasodilating effects. Nausea, in the treatment of chronic DIC without major
vomiting and headache may also occur. coagulopathy.
eptacog alfa has been used (off-licence) in refrac-
tory life-threatening haemorrhage.
Disaster, major, see Incident, major Levi M, Schultz M (2010). Minerva Anesthesiol; 76:
8519
Disequilibrium syndrome. Syndrome comprising See also, Blood products; Coagulation disorders; Coagu-
nausea, vomiting, headache, restlessness, visual distur- lation studies
bances, tremor, coma and convulsions, associated with
dialysis. More common in patients with pre-existing Disseminated sclerosis, see Demyelinating diseases
intracranial pathology, severe acidosis or uraemia. The
cause is uncertain, although increased brain water is sug- Dissociation curves, see Carbon dioxide dissociation
gested by CT scanning. Rapid changes in osmolality or curve; Oxyhaemoglobin dissociation curve
CSF pH have been suggested. Reduced by gradual insti-
tution of dialysis, especially if plasma urea is very high, Dissociative anaesthesia, see Ketamine
and by careful management of sodium balance. Manage-
ment is supportive. Distigmine bromide. Acetylcholinesterase inhibitor,
used in urinary retention and intestinal atony, and, very
Disinfection of anaesthetic equipment, see Contami- rarely, myasthenia gravis (duration of action is up to
nation of anaesthetic equipment 24h; thus risk of accumulation and cholinergic crisis is
greater than with shorter-acting drugs).
Dosage: 520mg orally od.
Disodium pamidronate, see Bisphosphonates
Side effects: as for neostigmine.

Disopyramide phosphate. Class Ia antiarrhythmic Distribution curves, statistical, see Statistical frequency
drug, used to treat SVT and VT. Half-life is 7h. distributions
Dosage:
300800mg/day orally in divided doses.
Disulfiram. Drug used in the treatment of alcoholism;
2mg/kg up to 150mg iv over at least 5min, fol-
inhibits the metabolism of alcohol by alcohol dehydro-
lowed by 0.4mg/kg/h infusion or 200mg orally genase with increased production of acetaldehyde, the
tds; maximum 300mg in the first hour and latter causing unpleasant effects (flushing, headache, pal-
800mg/day. pitations, nausea and vomiting) when alcohol is ingested.
Side effects: myocardial depression, hypotension,
Arrhythmias and hypotension may follow large intakes
anticholinergic effects, e.g. urinary retention, atrio- of alcohol. Similar but lesser reactions may occur in
ventricular block. patients taking metronidazole who ingest alcohol.
Dosage: 200mg orally od initially, increased up to
Disseminated intravascular coagulation (DIC). Path- 500mg.
ological activation of coagulation by a disease process, Side effects: drowsiness, nausea, vomiting, psychosis,
leading to fibrin clot formation, consumption of platelets peripheral neuritis, hepatic impairment. Causes
and coagulation factors (I, II and XIII), and secondary enzyme inhibition, thus enhancing the actions of
fibrinolysis. May be precipitated by shock, sepsis, hae- many drugs, including tricyclic antidepressants, ben-
molysis, malignancy, trauma, burns, major surgery, PE, zodiazepines, warfarin, theophylline and phenytoin.
extracorporeal circulation and obstetric conditions, e.g.
pre-eclampsia, amniotic fluid embolism, intrauterine Diuresis, forced, see Forced diuresis
death and placental abruption.
Effects: Diuretics. Drugs increasing the rate of urine production
may occur chronically, with little clinical by the kidney.
abnormality. Divided into:
bruising, bleeding from wounds, venepuncture sites, thiazide diuretics: act at the proximal part of the
GIT, lung, urinary tract and uteroplacental bed. distal convoluted tubule of the nephron, and
 Dolls eye movements 189

also at the proximal tubule. Have low ceilings DNR orders, Do not resuscitate orders, see Do not
of action; i.e. maximal effects are produced by attempt resuscitation orders
small doses. May cause hypokalaemia, hypomag-
nesaemia, hyperuricaemia, hyperglycaemia and D O2, see Oxygen delivery
hypercholesterolaemia.
osmotic diuretics, e.g. mannitol: increase renal blood Do not attempt resuscitation orders (DNAR orders;
flow by plasma expansion, then draw water into the Do not resuscitate orders; DNR orders). Instructions in
renal tubules by osmosis. Other small molecules a patients records that CPR is not to be performed
which are filtered but not reabsorbed may have should cardiorespiratory arrest occur. Generally reserved
similar osmotic diuretic actions, e.g. glucose, urea for patients in whom quality of life is currently so poor,
and sucrose. or the likelihood of success so low, that active resuscita-
potassium-sparing diuretics, e.g. triamterene, tion is not indicated. Although previously often written
amiloride, spironolactone: act at the distal convo- without consultation with the patients or the patients
luted tubule, where most potassium is normally relatives, respect for patients autonomy and views, and
lost; spironolactone acts by aldosterone receptor those of their relatives, has led to full and open discus-
antagonism. May cause hyperkalaemia and sion being preferred. Surveys have shown that patients
hyponatraemia. are mostly appreciative of being included in these dis-
loop diuretics, e.g. furosemide, bumetanide, etha cussions. DNAR/DNR orders are often suspended peri-
crynic acid: act at the ascending loop of Henle. More operatively, since the fact that surgery is taking place
potent, with high ceilings of action. Immediate implies that active treatment is worthwhile; also the
benefit in fluid overload/cardiac failure is thought results of resuscitation during anaesthesia are often
to be due to vasodilatation. May cause hypokalae- better than those of CPR on the wards.
mia, hyperuricaemia, hypomagnesaemia and hyper- Any discussion and decision regarding DNAR/DNR
glycaemia. Ototoxicity may occur following rapid orders should be clearly documented and, more impor-
iv injection and with concurrent aminoglycoside tantly, all staff must be made aware of any changes in
therapy. DNAR/DNR status. The ASA has issued guidelines for
other substances causing diuresis: anaesthetic management of patients with DNAR/DNR
- carbonic anhydrase inhibitors, e.g. orders. Hospitals may offer specific forms to be signed
acetazolamide. by the patient or other legally responsible person. In the
- xanthines, e.g. aminophylline: reduce sodium UK, matters are less formalised.
excretion and increase GFR. See also, Advance decisions; Ethics
- dopamine: increases renal blood flow and GFR;
also reduces sodium absorption. Dobutamine hydrochloride. Synthetic catecholamine,
- water and ethanol: inhibit vasopressin secretion. used as an inotropic drug, e.g. in cardiac stress testing,
- acidifying salts, e.g. ammonium chloride: increase after cardiac surgery, and in septic or cardiogenic shock.
hydrogen ion and sodium excretion. Stimulates 1-adrenergic receptors, with weak stimula-
- demeclocycline: blocks the action of vasopressin tion of 2- and -receptors. Does not affect dopamine
on the distal tubule and collecting duct; used in receptors. Increases myocardial contractility, with less
the syndrome of inappropriate ADH secretion. increase in myocardial O2 consumption than other cat-
Anaesthesia for patients taking diuretics: hypovolaemia echolamines. Causes less tachycardia than dopamine or
and electrolyte disturbances are possible, especially in isoprenaline, probably because of a reduced effect on
the elderly. Hypokalaemia may represent severe body the sinoatrial node, and less activation of the barorecep-
potassium depletion; conversely, potassium supplements tor reflex. Reduces left ventricular end-diastolic pressure
and potassium-sparing diuretics may cause hyperkalae- if raised.
mia. Severe hyponatraemia may follow treatment with Plasma half-life is about 2min. Excreted via the
potassium-sparing diuretics. Combinations of different urine. Supplied as a solution for dilution with saline or
types of diuretic tend to be synergistic. 5% dextrose before use.
[Friedrich GJ Henle (18091885), German anatomist] Usual dosage: 2.510 g/kg/min by infusion; higher
rates may be required.
Side effects: hypotension (due to 2-receptor agonism),
Diving reflex. Decreased respiration, vagal bradycardia
tachycardia and ventricular arrhythmias at high
and splanchnic and muscle bed vasoconstriction follow-
doses.
ing immersion of the face in cold water. Cerebral and
cardiac circulations are preserved. Occurs in mammals,
Dog bites, see Bites and stings
birds and reptiles; it has been suggested that it may aid
survival in humans, e.g. in boating and skiing accidents.
Dolasetron mesilate. 5-HT3 receptor antagonist,
licensed as an antiemetic drug in chemotherapy-induced
Divinyl ether. Inhalational anaesthetic agent, intro- and PONV. Similar to ondansetron.
duced in 1933 and no longer used. Similar in potency and Dosage:
explosiveness to diethyl ether, but less irritant. Liver PONV: 50mg orally or 12.5mg iv.
damage resulted from prolonged use. Combined 1:4 with nausea/vomiting following chemotherapy: 200mg
ether as Vinesthene Anaesthetic Mixture. orally or 100mg iv 3060min before treatment, for
up to 4 days.
DLV, see Differential lung ventilation
Dolls eye movements (Oculocephalic reflex). Reflex
elicited in unconscious patients by quickly turning the
DNAR orders, see Do not attempt resuscitation orders patients head to one side and holding it there. The eyes
190 Domperidone maleate

move conjugately to the right when the head is turned to venoconstriction. Some 2-stimulation also
to the left, and vice versa; i.e. they continue to point in occurs.
the original position in relation to the body, as if fixed over 15 g/kg/min: stimulates 1-receptors, causing
on a distant object. They then move to the midposition. peripheral vasoconstriction.
The reflex involves bilateral vestibular apparatus and Rapidly taken up by tissues and metabolised by dopa-
nerves, brainstem and oculomotor nerves; it is therefore mine -hydroxylase and monoamine oxidase pathways,
absent in brainstem death or dysfunction. Normally with renal excretion of metabolites. Plasma half-life is
absent because of cerebral activity influencing eye about 1min. Dosage must be reduced if the patient is
movement; i.e. it becomes apparent if cerebral activity is taking monoamine oxidase inhibitors.
suppressed or interrupted. Side effects: tachycardia and ventricular arrhythmias
are common at higher doses. Severe tissue necrosis
Domperidone maleate. Antiemetic and prokinetic may follow peripheral extravasation; it should thus be
drug related to metoclopramide, and with similar actions. administered into a large vein (preferably central).
Less able to penetrate the bloodbrain barrier, thus less May cause gastric stasis and suppress release of oxy-
likely to cause sedation and dystonic reactions than tocin and other pituitary hormones. Has also been
other antiemetic drugs. No longer available for iv use, implicated in reducing T-cell responsiveness and
because of associated ventricular arrhythmias. reducing GIT oxygenation via shunting of blood at
Dosage: mucosal level.
1020mg tds/qds orally.
60mg bd pr. Dopamine receptors. Found peripherally and in the
CNS. Subdivided into:
Donepezil, see Acetylcholinesterase inhibitors central:
- D1 receptors: G protein-coupled receptor; stimu-
Donnan effect (GibbsDonnan effect). Effect of lation results in increased intracellular cAMP. D5
charged particles on one side of a membrane on the dopamine receptors are related.
distribution of other charged particles, when the former - D2 receptors: G protein-coupled receptor found
cannot diffuse through the membrane but the latter can. in pathways involving the basal ganglia and
For example, the cell membrane is largely impermeable hypothalamus, concerned with coordination of
to negatively charged intracellular proteins, whereas it is movement, behaviour and inhibition of prolactin
relatively permeable to K+ and Cl ions. The distribution release. Also present in the chemoreceptor trigger
of these ions on either side of the membrane is therefore zone where stimulation results in vomiting, and in
affected by the electrical gradient produced by the pro- the spinal cord. Butyrophenones are the classical
teins, as well as their own concentration gradients. There antagonists; others include phenothiazines and
is a fixed ratio between the concentration of diffusible metoclopramide. Bromocriptine is an agonist.
ions on one side of the membrane and the concentration - D3 receptors: present in the brain, especially
of those on the other. This ratio is the same for all the limbic system. Function is uncertain.
ions distributed about a particular membrane under the peripheral:
same conditions. - DA1 receptors: postsynaptic; thought to be
[Frederick Donnan (18701956), English chemist; Josiah analogous to central D1 receptors. Stimulation
Gibbs (18391903), US physicist] causes vasodilatation in renal and mesenteric
vascular beds.
Dopamine. Naturally occurring catecholamine and - DA2 receptors: presynaptic; stimulation inhibits
neurotransmitter, found in postganglionic sympathetic noradrenaline release via negative feedback. Inhi-
nerve endings and the adrenal medulla. A precursor of bition of cAMP formation may be involved. May
adrenaline and noradrenaline. Used as an inotropic also be present at cholinergic nerve endings.
drug, e.g. in cardiogenic or septic shock. Formerly Inhibited by butyrophenones, i.e. thought to be
used to provide renal protection in situations when analogous to central D2 receptors.
kidney function is compromised but no evidence exists Further subclasses of dopamine receptors may also exist.
for its efficacy and reports of bowel hypoperfusion have Girault J, Greengard P (2004). Arch Neurol; 61: 6414
led to diminishing use of low-dose (renal) dopamine
in ICU. Dopexamine hydrochloride. Synthetic analogue of
Supplied as the hydrochloride in a concentrated solu- dopamine, used as an inotropic drug in cardiac failure,
tion for dilution in saline or 5% dextrose, or as a ready- e.g. after cardiac surgery. Stimulates peripheral dopa-
made iv solution in dextrose. Inactivated by alkali. mine receptors and 2-adrenergic receptors, with indi-
Effects depend on the dose used: rect stimulation of 1-adrenergic receptors via inhibition
up to 5 g/kg/min: traditionally believed to stimu- of neuronal reuptake of catecholamines. Causes periph-
late dopamine receptors, causing renal and mesen- eral (including renal) vasodilatation with reduced BP
teric vasodilatation and increasing renal blood flow, and increased cardiac output. 40% bound to red blood
GFR, urine output and sodium excretion. However, cells. Half-life is 7min.
it is now thought that these so-called renal effects Dosage: 0.56.0 g/kg/min.
of dopamine are actually a non-specific response to Side effects include tachycardia (usually mild) and
increased cardiac output. arrhythmias, nausea, vomiting and tremor.
515 g/kg/min: stimulates 1-adrenergic receptors;
myocardial contractility, cardiac output, BP and O2 Doppler effect. Change in observed frequency of a
consumption are increased. Pulmonary capillary signal when the signal source moves relative to the
wedge pressure may paradoxically increase, possi- observer; increasing as the source approaches, decreas-
bly because of increased venous return secondary ing as it moves away. For example, the wavefronts in
 Downs syndrome 191

front of a moving car horn will be closer together than

when the horn is stationary, because when each wave-
front is emitted, the horn moves forward before emitting
another. Similarly, the wavefronts behind the horn are
further apart. To the observer, the tone of the horn

Response
changes from higher-pitched to lower-pitched as the A B A+D
horn approaches and passes, although the actual fre-
quency emitted has not changed.
The principle is used clinically to determine velocities
and flow rates of moving substances, e.g. in cardiac C A+E
output measurement. An ultrasound beam may be
directed along the path of flow; the sound waves reflect
from the surfaces of the blood cells as they approach or
Log dose
move away. Analysis of the reflected frequencies allows
determination of blood velocity. Doppler probes contain Fig. 55 Doseresponse curves (see text)
both emitter and detector in the probe tip.
May also be used to detect arterial wall movement in
arterial BP measurement; onset of movement occurs at
systolic pressure, and cessation at diastolic pressure, as Doseresponse curves. Curves describing the relation-
the cuff is deflated from high pressure. The ultrasonic ship between dose of a drug or physiological agent and
beam is directed across the artery. the resultant response. If a logarithmic scale is used for
[Christian Doppler (18031853), Austrian physicist] the abscissa the curve is sigmoid-shaped, with increasing
See also, Transcranial Doppler ultrasound response as dose is increased until a plateau is reached
(Fig. 55).
Dorsal column stimulation. Technique used in intrac- Different curves are characterised by their:
table pain management. Most effective in treatment of position on the abscissa (related to potency).
neuropathic pain, it increases concentrations of GABA maximal height (efficacy).
and 5-hydroxytryptamime in the dorsal horn of the slope (influenced by the number of receptors that
spinal cord and thus supports the gate control theory of must be activated before a drug has an effect).
pain. Has been performed percutaneously using a wire Drugs A and B are both agonists, but A is more potent.
electrode connected to an external power source, but an Drug C is less efficacious and is therefore a partial
implantable system is usually employed. Electrodes may agonist. Addition of a competitive antagonist, D, to A
be placed at open laminectomy, or inserted into the epi- shifts the curve to the right (i.e. reduced potency) but
dural space through a needle. The electrodes are placed without altering its height (i.e. same efficacy). A non-
above the highest level of the pain, and connected to a competitive antagonist, E, shifts the curve to the right,
subcutaneous inductance coil, usually on the abdominal reduces its height and alters its slope.
wall, by insulated wires. The patient applies an external The curves are affected by individual variability in
power source over the coil for pain relief. Implantable response, related to differences in pharmacokinetics and
power sources may be used. The term spinal cord stimu- pharmacodynamics. The dose of drug required to
lation has been suggested as being more appropriate produce a certain response in a given percentage of the
since the exact site of stimulation in a particular case is population (n%) is described as the effective dose, EDn.
not clear. See also, Receptor theory
Oakley JC, Prager JP (2002). Spine; 27: 257483
Dosulepin hydrochloride (Dothiepin). Tricyclic antide-
Dorsal root entry zone procedure (DREZ proce- pressant drug, similar to amitriptyline. Used in endoge-
dure). Production of destructive lesions in the DREZ; nous depression and in chronic pain management.
has been used for severe chronic pain states, including Dosage: 5075mg orally, increased up to 225mg/day.
postherpetic neuralgia, deafferentation pain (anaesthe- 2550mg is used in pain management.
sia dolorosa, pain associated with CVA and neurological Side effects: as for amitriptyline.
injury), facial trauma, atypical facial pain and migraine/
cluster headache; it has also been used in severe cancer Double-blind studies, see Clinical trials
pain. Thought to interrupt the site of integration of pain
pathways via the lateral spinothalamic and spinoreticu- Double-lumen tubes, see Endobronchial tubes
lothalamic tracts. A small electrode is inserted into the
spinal cord at each level of the pain and radiofrequency Downs syndrome. Syndrome resulting from presence
lesions induced in order to destroy the abnormally active of an extra chromosome 21 (trisomy 21). Usually due to
dorsal horn neurones. non-dysjunction of chromosomes during germ cell for-
mation, and rarely due to translocation in parental cells.
Dorsalis pedis artery. Continuation of the anterior Incidence is ~1:700 overall, increasing with maternal age.
tibial artery, itself a branch of the popliteal artery. Passes 45% of patients live to 60 years.
along the dorsum of the foot to the space between the Features:
first and second metatarsal bones, where it enters the round head and face, slanting eyes with prominent
sole of the foot to anastomose with the lateral plantar and wide epicanthic folds. Ears are low-set; the
artery. May be used as a site for arterial cannulation, mouth is small with a large tongue.
lateral to extensor hallucis longus tendon with the foot broad short hands, with a single transverse palmar
flexed. Cannulation may be difficult in peripheral vascu- crease; the gap between first and second toes is
lar disease. large.
192 Doxacurium chloride

respiratory involvement includes obstructive sleep Non-rebreathing

apnoea (in 60%), abnormal central respiratory valve
drive, tracheal stenosis and a tendency to develop
Air +/ O2
chest infections.
congenital heart disease is common, especially ASD
and VSD, Fallots tetralogy and patent ductus
arteriosus.
duodenal atresia and other congenital abnormali- Vaporiser
ties are common, as is gastro-oesophageal reflux.
acute myeloid leukaemia is common.
hypotonicity.
learning difficulties (IQ 2060); epilepsy (in
10%). Dementia is common, as is postoperative
agitation.
hypothyroidism and insulin-dependent diabetes
mellitus are common.
Anaesthetic problems: Bag or bellows
cardiac abnormalities as above.
Fig. 56 Draw-over systems
airway difficulties, including difficult tracheal intu-
bation due to macroglossia and subglottic stenosis;
obstructive sleep apnoea. Excessive secretions are 2,3-DPG, see 2,3-Diphosphoglycerate
common.
hypotonia. DPL, Diagnostic peritoneal lavage, see Peritoneal lavage
atlantoaxial subluxation and instability.
[John Down (18281896), English physician] Draw-over techniques. Anaesthesia in which the
patients inspiratory effort draws room air (with or
without added O2) over a volatile agent with each breath.
Doxacurium chloride. Non-depolarising neuromuscu- More sophisticated, but similar to, open-drop techniques.
lar blocking drug, introduced into the USA in 1991. Has There should be minimal resistance in the breathing
similar features to pancuronium, but without cardiovas- system and vaporiser. Incorporation of bellows or a self-
cular effects. Dose range: 2580 g/kg; intubation may inflating bag into the breathing system allows IPPV, and
be performed 46min after the initial dose. Effects last provides a reservoir if continuous flow of O2 is added.
13h, depending on dosage. Excreted unchanged via the Non-rebreathing valves prevent exhalation back into the
kidneys and liver. Causes histamine release only at much vaporiser; a unidirectional valve is necessary upstream
higher doses than required clinically. Has been suggested of the bellows or bag, if used, to allow IPPV (Fig. 56).
for prolonged surgery where cardiovascular stability is Uses:
required, e.g. neurosurgery or cardiac surgery. shortage of compressed gas supplies, e.g. battle-
fields, accident sites, developing countries.
Doxapram hydrochloride. Analeptic drug, used for its inhalational analgesia in obstetrics (no longer used).

respiratory stimulant properties. Acts on peripheral che-

moreceptors, increasing tidal volume more than respira- Dreaming, see Awareness
tory rate. Increases work of breathing and therefore
oxygen demand. May be administered by infusion for Dresslers syndrome, see Myocardial infarction
type 2 respiratory failure in patients with COPD, in an
attempt to avoid the need for IPPV; however, for this DREZ, see Dorsal root entry zone procedure
indication it has largely been superseded by non-invasive
positive pressure ventilation. Also used in postoperative Dronedarone, see Antiarrhythmic drugs
respiratory depression, without reversing opioid-induced
analgesia. Has been used routinely to reduce post Droperidol. Butyrophenone, discontinued in the UK in
operative pulmonary complications, especially in at-risk 2001 because of cases of prolonged QT interval; rein-
patients. Half-life is 24h. troduced in the UK in 2009 at a lower recommended
Dosage: dosage and licensed only for use as an antiemetic drug.
11.5mg/kg iv over 30 s; repeated hourly. A powerful dopamine antagonist, related to haloperidol
1.54mg/min by infusion, according to response. but of shorter duration of action (612h; cf. haloperidol
Steady-state plasma levels are produced by: 2448h). Typically caused apparent outward sedation
- 4mg/min for 15min, but internal distress.
- 3mg/min for 15min, Dosage: 0.6251.25mg iv 30min before end of
- 2mg/min for 30min, surgery, repeated up to qds.
- 1.5mg/min thereafter.
Side effects: hypertension, tachycardia (resulting Drotrecogin alfa (alpha), see Protein C
from vasomotor stimulation), restlessness, confusion,
dizziness, sweating, nausea, salivation. Convulsions Drowning, see Near-drowning
may occur with high doses.
Contraindicated in coronary artery disease, severe Drug absorption, distribution, metabolism and
hypertension, thyrotoxicosis, asthma and epilepsy. excretion, see Pharmacokinetics
Effects are said to be potentiated by monoamine oxidase
inhibitors. Drug addiction, see Substance abuse
 Dual block 193

Drug development. New drugs or indications for old costs of new drug development are considerable and
drugs may arise from: often prohibitive.
incidental observation, e.g. antiplatelet action of
aspirin. Drug interactions. Common cause of morbidity and
modification of the structure of known natural sub-
mortality, especially in hospital, although some interac-
stances, e.g. H2 receptor antagonists. tions are beneficial.
modification of existing drugs, e.g. opioid May be:
analgesics. pharmacokinetic:
screening of natural compounds.
- outside the body, e.g. precipitation of thiopental/
computer-assisted modelling of new molecules.
atracurium mixture.
Stages of development:
- at site of absorption, e.g. effect of opioids and
identification of the substance.
metoclopramide on gastric emptying, use of vaso-
in vitro studies.
constrictors to delay local anaesthetic drug
animal studies:
absorption, second gas effect.
- effects, interactions, pharmacokinetics, etc. - affecting distribution, e.g. displacement of warfa-
- toxicology: acute/chronic (usually up to 2 years) rin from protein-binding sites by salicylates.
effects, therapeutic index; use of different - affecting metabolism (e.g. concurrent administra-
animals, routes, doses. Includes histological/ tion of carbidopa inhibiting peripheral conversion
biochemical effects on organs, bacterial mutagen- of levodopa to dopamine), enzyme induction/
icity, teratogenicity, carcinogenicity, and effects inhibition, e.g. by cimetidine (inhibition) or barbi-
on fertility. turates (induction).
Doubts have been expressed over the ethics of - affecting elimination, e.g. decreased penicillin
animal experiments and problems caused by species excretion caused by probenecid.
differences (e.g. thalidomide was free of teratoge- pharmacodynamic:
nicity in mice and rats but had devastating effects - additive:
in humans). In the UK, undertaking animal studies - summation: net effect equals the sum of indi-
requires a Home Office licence. vidual drug effects.
chemical details, e.g. formulation, manufacture,
- synergism: net effect exceeds the sum of indi-
quality, storage. vidual effects.
human studies:
- potentiation: one drug increases the effect of
- phase I (clinical pharmacology): 2050 subjects, another. Examples: decreased requirement for
usually healthy volunteers. Pharmacokinetic and anaesthetic agents when opioids and other sed-
pharmacodynamic effects, safety, etc. atives are used, and the increase in non-
- phase II (clinical investigation): 50300 patients. depolarising neuromuscular blockade caused
Further information as above, plus effective dose by aminoglycosides and phenytoin.
ranges and regimens. - antagonism: may be competitive, physiological,
- phase III (formal clinical trials): 2501000+ etc.
patients. Comparison with other treatments. Fre- - indirect effects, e.g. hypokalaemia induced by
quent side effects are noted. diuretics increases digoxin toxicity; pethidine
- phase IV (postmarketing surveillance): 2000 interaction with monoamine oxidase inhibitors;
10 000+ patients. Rare side effects are noted, e.g. sensitisation of the myocardium to catechol-
oculomuco-cutaneous syndrome following oral amines by halothane.
practolol therapy. Techniques used: See also, Doseresponse curves
- cohort studies: large numbers are observed
over long periods, noting side effects when
they occur. May detect rare effects (less than Drug labels, see Syringe labels
1:500), but costly and difficult to organise. May
examine specific groups (e.g. the elderly) previ- Dual block (Phase II block). Phenomenon seen when
ously excluded. large doses of suxamethonium or related drugs are
- case-control studies: records of patients with a administered, in which features of non-depolarising neu-
suspected side effect are analysed for previous romuscular blockade gradually replace those of depola-
drug exposure. Easier and cheaper than cohort rising neuromuscular blockade. More commonly seen
studies, but less precise and more susceptible to with concurrent administration of acetylcholinesterase
bias. May detect side effects with frequency up inhibitors and in myasthenia gravis.
to 1:500. Prove association, not causation; give Typically, tachyphylaxis to suxamethonium develops
relative risk. after administration of 400500mg by infusion or
- voluntary reporting (yellow card system in UK). repeated doses, although individual variation is wide.
Specific anaesthetic cards are available. This is followed by non-depolarising neuromuscular
- general statistics, e.g. recording sudden changes blockade, which may be reversed by neostigmine,
in disease incidence. although reversal is inconsistent. In doubtful cases,
Statutory regulatory bodies are concerned with drug edrophonium 10mg has been suggested as a test; the
development from the animal study stage onwards: the block worsens if depolarising, reverses if non-
Committee on Safety of Medicines in the UK, the Food depolarising. Use of nerve stimulators has largely super-
and Drug Administration in the USA (the European seded this test.
Medicines Evaluation Agency coordinates such activi- Has also been termed desensitisation block, and
ties in Europe). A product licence is granted after phase sometimes subdivided into different phases. The mecha-
III trials, and reviewed every 5 years in the UK. Financial nism is unclear; depolarisation is thought not to persist
194 Ductus arteriosus, patent

despite continued presence of the drug. Pre- or postjunc- Predisposing factors:

tional receptor modulation may be involved. inexperienced operator.
See also, Neuromuscular blockade monitoring unfamiliar equipment, e.g. sharper or blunter
needles than one is used to.
Ductus arteriosus, patent (Arterial duct). Accounts for faulty equipment, e.g. blocked needles, sticking

1015% of congenital heart disease. The duct normally syringes.

closes within a few days of birth; bradykinin, prostaglan- use of air instead of saline for loss of resistance has

dins and a rise in PO2 are thought to be involved, although been implicated but there is no good evidence that
the precise mechanism is unclear. If it remains open, this is true.
Diagnosis is usually obvious since a stream of CSF
significant left-to-right shunt may occur.
Features: flows from the needle hub, although flow may be slow
neonates/infants: cardiac failure, respiratory failure. and lead to confusion if saline has been used. Testing
older patients: the fluid for pH (CSF > 7), temperature (CSF is
- may be symptomless; cardiac failure or bacterial warm), glucose and protein content (CSF contains
endocarditis may occur. both) will reliably distinguish saline from CSF.
Management options:
- signs: continuous murmur heard at the left sternal
edge, louder on expiration; may be systolic only, remove needle/catheter and abandon the
if the shunt is large. A pulmonary regurgitant procedure.
murmur may be present. convert the block into single-shot or continuous

- pulmonary plethora and cardiomegaly on CXR. spinal anaesthesia (the presence of a subarachnoid
pulmonary hypertension may develop when catheter has been suggested as causing inflamma-
older. tion of the dural edges, leading to more rapid
Treatment: healing and closure of the hole with a reduced inci-
medical (neonates): indometacin 200 g/kg iv, then dence of severe headache, although strong evidence
two doses of 100 g/kg (up to 8h old), 200 g/kg for this is lacking).
(27 days old) or 250 g/kg (over 7 days old) at resite the catheter in an adjacent interspace:

1224h intervals. - cautious administration of test dose and subse-

surgical: ligation/division of duct; left thoracotomy quent doses (fractionated injection may be safer,
is usually performed. Haemorrhage, recurrent as partial subarachnoid injection may occur).
laryngeal nerve or thoracic duct damage may occur. - 1 litre saline may be given over 1224h through
Postoperative IPPV may be required, especially in the catheter to reduce the incidence of post-dural
babies. puncture headache. 5060ml boluses of saline
Anaesthesia: as for congenital heart disease. over 1020min have also been used. Avoid dehy-
Prostaglandin E1 is used to prevent ductal closure in dration. Use of laxatives has been suggested as
babies with congenital heart disease awaiting surgery, a means of reducing straining; abdominal binders
e.g. permitting right-to-left shunting to allow perfusion have also been suggested as reducing the inci-
of the legs in severe aortic coarctation, or left-to-right dence of headache but neither method is com-
shunting to allow pulmonary perfusion in severe Fallots monly used.
tetralogy. - in obstetrics, instrumental delivery has been sug-
See also, Fetal circulation gested to avoid straining during the second stage
of labour, but this is controversial.
- prophylactic blood patch via the epidural catheter
Duloxetine Antidepressant drug acting via inhibition of
at the end of the case/labour is controversial since
uptake of 5-HT and noradrenaline. Licensed for major
it may be less successful than one performed later;
depression, generalised anxiety disorders and stress
it also exposes patients to a treatment that not all
incontinence in women. Also first-line treatment for
will require.
painful diabetic neuropathy.
inform the patient and nursing/midwifery staff.
Dosage: 30120mg orally per day in divided doses.
management of headache if it occurs (see Post-dural
Side effects: nausea, abdominal pain, insomnia, dry
puncture headache).
mouth, visual disturbances.
Post-dural puncture headache may rarely occur without
suspected dural puncture.
Dumping valve. Device preventing application of exces-
sive negative pressure to patients airways, used in scav- Durranss sign. Increased rate and depth of breathing
enging systems and some breathing attachments. Usually following rapid injection of solution into the epidural
opens at 0.5 cmH2O, allowing air to be drawn in. space. More common in unconscious patients.
[Sidney F Durrans, Dorset anaesthetist]
Dural tap. Accidental puncture of the dura whilst per- See also, Epidural anaesthesia
forming epidural anaesthesia; the term usually refers to
puncture by the epidural needle, although the epidural DVT, see Deep vein thrombosis
catheter may rarely enter the subarachnoid space, espe-
cially if there has been a partial dural tear during inser- Dye dilution cardiac output measurement, see
tion. Important because it may interfere with the planned Cardiac output measurement
anaesthetic technique and because of the risk of post-
dural puncture headache. Said to occur in 1% of cases Dynamic hyperinflation (DHI). Progressive accumula-
in UK hospitals, although most authorities believe this tion of gas (gas trapping) within the lung due to incom-
is too high, with an incidence of 0.5% or lower being plete exhalation of the inspired volume. Occurs in
attainable with good training. patients with increased airway resistance (e.g. in asthma
 Dystrophia myotonica 195

and COPD), when expiratory time is insufficient to Dyspnoea related to exercise tolerance is useful as a
allow the lungs to return to a normal FRC. Gas trapping means of assessing respiratory/cardiovascular function,
continues until a new equilibrium is reached; at this e.g. during preoperative assessment. Certain patterns
higher FRC, increased small airway diameter and elastic are characteristically associated with certain disease
recoil forces compensate for the airflow obstruction such processes, e.g. orthopnoea (left ventricular failure, also
that expired and inspired volumes equalise (this state is severe restrictive lung disease) or paroxysmal nocturnal
termed static hyperinflation). dyspnoea (left ventricular failure).
Pressure exerted by trapped gas at end-expiration Nishino T (2011). Br J Anaesth; 106: 46374
(termed intrinsic or auto-PEEP), combined with See also, Breathing, control of
increased lung volumes, may result in the following:
increased work of breathing and dyspnoea (in spon- Dyspnoeic index. Difference between maximal volun-
taneously breathing patients). tary ventilation and maximum minute ventilation
reduced venous return and increased pulmonary reached during exercise, as a percentage of maximal vol-
vascular resistance; this may impair cardiac output untary ventilation. Has been used to try to relate the
and cause significant hypotension. subjective feeling of breathlessness to an objective
patientventilator asynchrony and impaired measure of cardiorespiratory function.
pressure-contolled ventilation.
barotrauma (e.g. pneumothorax). Dysrhythmias, see Arrhythmias
Methods of assessing DHI include:
assessment of cardiac output with the ventilator dis- Dystonic reaction. Acute side effect of dopamine
connected; dramatic improvement suggests signifi- antagonist drugs, e.g. many antiemetic drugs. May follow
cant DHI. oral therapy, but particularly common after parenteral
measurement of the plateau airway pressure administration. More common after phenothiazine
(PPlateau; the airway pressure measured after tran- administration (e.g. prochlorperazine and perphenazine)
sient expiratory occlusion at end-inspiration). than after metoclopramide, but the latter is especially
measurement of intrinsic PEEP. likely to cause it in children and young women.
Modern ICU ventilators are usually able to perform the Consists of involuntary muscle contraction, espe-
last two measurements. DHI during mechanical ventila- cially involving the face. Oculogyric crisis (involuntary
tion may be mitigated by ensuring prolonged expiratory conjugate deviation of the eyes, usually upwards) may
times (> 4 s) and low tidal volumes (e.g. 57ml/kg). also occur.
Marini JJ (2011). Am J Respir Crit Care Med; 184: Treatment: diazepam 510mg iv; benzatropine
75662 12mg iv/im; procyclidine 510mg iv/im.

Dyne. Unit of force in the cgs system of units. 1 dyne Dystrophia myotonica. Most common of the myotonic
is the force required to accelerate a mass of 1 gram syndromes, with prevalence of 1 in 20 000. Multisystem
by 1 centimetre per second per second. 1 newton = disease with autosomal dominant inheritance; patients
100 000 dyne. present at 1535 years old.
Features:
Dynorphins. Endogenous opioid peptides; dynorphin myotonia (increase in muscle tone following con-
18 (8 amino acids) is found in the CNS, especially hypo- traction). Exacerbated by cold.
thalamus and posterior pituitary; dynorphin 117 (17 cardiomyopathy and conduction defects.
amino acids) is found in the duodenum. Thought to act respiratory muscle weakness and poor central
as neurotransmitters in pain pathways; more active at control of respiration; may lead to respiratory
than at opioid receptors. failure.
central and obstructive sleep apnoea.
Dysaesthesia. Abnormal unpleasant sensation, whether cognitive defects.
spontaneous or evoked; e.g. hyperalgesia, allodynia. cataracts, frontal balding, sternomastoid and tempo-
ral muscle wasting, ptosis.
Dysequilibrium syndrome, see Disequilibrium weakness of forearm and calf muscles.
syndrome testicular atrophy.
thyroid and adrenal impairment.
Dyspnoea. Feeling of breathlessness, with sensory and poor bulbar function and delayed gastric
affective components. Mechanism is unclear, but may emptying.
involve neuromechanical dissociation a mismatch Anaesthetic problems:
between central ventilatory drive and the magnitude of related to poor cardiorespiratory reserve.
ventilation produced (as reflected by ongoing sensory increased risk of aspiration of gastric contents.
afferent signalling). Sensory afferents originate in chest increased sensitivity to iv anaesthetic agents,
wall stretch receptors, pulmonary vagal receptors and opioids and non-depolarising neuromuscular block-
chemoreceptors. ing drugs.
May occur in: suxamethonium and acetylcholinesterase inhibitors
increased respiratory drive, e.g. due to hypoxaemia, may cause prolonged muscle contraction which may
hypercapnia, acidosis, pulmonary receptor activity. hinder laryngoscopy and ventilation.
increased work of breathing. Russell SH, Hirsch NP (1994). Br J Anaesth; 72:
impaired neuromuscular function of respiratory 21016
muscles. See also, Myotonia congenita
 E
Ear, nose and throat surgery (ENT surgery). Proce- - access to the airway during surgery is restricted,
dures vary from minor day-case surgery (e.g. myringot- therefore monitoring is particularly important.
omy) to major head and neck dissections. Anaesthetic Obstruction of the airway is possible, especially
considerations: during tonsillectomy if a mouth gag is used.
preoperatively: - N2O is usually avoided in middle ear surgery,
- airway obstruction may be present (often because of expansion of gas-filled cavities.
worse on lying flat), particularly in adults present- - surgery involving the face and neck may damage
ing with known or suspected tumours. Flexible the facial and laryngeal nerves respectively (see
nasendoscopy performed in clinic can be a useful Hyperthryoidism). Absence of neuromuscular
source of information regarding the patients blockade may be requested by the surgeon in
upper airway anatomy. Potential difficulty with order to allow identification of nerves by electri-
intubation/mask ventilation should be assessed. cal stimulation. Spontaneous ventilation, or IPPV
- obstructive sleep apnoea (with features of chronic using opioids (e.g. remifentanil), a volatile agent
hypoxaemia) may be present. and induced hypocapnia, may be employed.
- specific emergencies include bleeding tonsil, - hypotensive anaesthesia is sometimes used, espe-
inhaled foreign body, epiglottitis and peritonsillar cially for major reconstructive surgery, laryngec-
abscess. tomy, mastoidectomy and middle ear surgery.
- good communication with the surgeon allows - thoracotomy is occasionally required, e.g. mobili-
selection of airway techniques that are both safe sation of the stomach for anastomosis.
and provide adequate surgical access. - laser surgery is common, especially for laryngeal
- anxiolytic, analgesic or antisialagogue premedica- surgery.
tion may be useful depending on the clinical - adrenaline solutions are often used by the surgeon.
context and intended anaesthetic technique. - if used, the throat pack must be removed before
perioperatively: the patient wakes. The pharynx may be inspected
- induction appropriate to the patients age, and suctioned to ensure absence of bleeding and
co-morbidities, anticipated airway difficulty, etc. blood clot, especially behind the soft palate (cor-
- techniques for securing the airway in potentially oners clot).
difficult cases include: - tracheal extubation is performed with the patient
- direct laryngoscopy under deep inhalational deeply anaesthetised or awake (but not in
anaesthesia. between, because of the risk of laryngospasm)
- fibreoptic intubation (awake or anaesthe- and in the head-down, lateral position to reduce
tised). airway soiling.
- videolaryngoscopy. postoperatively: as for any surgery. Major proce-
- tracheostomy or cricothyrotomy performed dures may require ICU/IPPV postoperatively.
under local anaesthesia. See also, Intubation, difficult; Mandibular nerve blocks;
- options for airway maintenance: Maxillary nerve blocks
- tracheal tube: traditionally used for most
procedures, with a throat pack if bleeding or Early warning scores. Simple scoring systems used to
debris is anticipated. Preformed tubes are aid identification of critically ill patients or those at risk
useful. Oral intubation is suitable for many of further clinical deterioration. Several different systems
procedures, including laryngectomy and tonsil- have been described, employing different groups of
lectomy. Nasal intubation provides better sur physiological parameters (e.g. systolic BP, heart rate,
gical access to the oral cavity; topical local respiratory rate, temperature, neurological status and
anaesthetic agents and vasopressor drugs (e.g. urine output) that are weighted on the basis of their
cocaine) are used to reduce nasal bleeding deviation from a normal range. Early warning schemes
(see Nose). A small-diameter (5mm) tube, may be used to trigger calls for assistance from the
passed orally or nasally, is usually suitable for patients primary team, a medical emergency team, an
microlaryngoscopy. outreach team or others. In the UK, the modified early
- LMA (flexible/reinforced): avoids problems warning score is most commonly used.
associated with intubation/extubation but may Cuthbertson BH, Smith GB (2007). Br J Anaesth; 98:
impair surgical access and be more prone to 7046
displacement. See also, Acute life-threatening events recognition and
- facemask anaesthesia: suitable for minor ear treatment
operations (e.g. myringotomy/grommets).
- injector techniques: often used for bronchos- Earth-leakage circuit-breaker, see Current-operated
copy, laryngoscopy, tracheal surgery. earth-leakage circuit-breaker

197
198 EastFreeman automatic vent

EastFreeman automatic vent, see Ventilators aspiration of gastric contents, cardiac failure, pul-
monary oedema.
EatonLambert syndrome, see Myasthenic syndrome fetal death.
Incidence is 23 cases per 10000 births in the UK. Occurs
Ebsteins anomaly. Congenital heart defect character- antepartum in 45% of cases, intrapartum in 20% and
ised by apical displacement of the posterior and septal postpartum in 35% (usually under 24 days postpartum
leaflets of the tricuspid valve, causing atrialisation of but eclampsia has been reported up to 23 weeks after-
the right ventricle. Results in: wards). Only 40% of cases have hypertension and
right heart failure and cyanosis (due to right-to-left proteinuria in the preceding week, and in many cases
shunting). premonitory signs of headache, photophobia and hyper-
tricuspid valve regurgitation. reflexia do not precede convulsions, which may recur if
ASD is often present. untreated. Mortality is almost 2% in the UK, usually
May lead to arrhythmias, conduction defects (especially from CVA; perinatal mortality is 56%. Maternal mor-
the WolffParkinsonWhite syndrome) and sudden tality is up to 25% mortality in developing countries.
Treatment:
death. Surgery may be indicated in severe cases.
[Wilhelm Ebstein (18361912), German physician] O2 administration. Tracheal intubation and IPPV

Paranon S, Acar P (2008). Heart; 97: 23743 may be required; the former may be difficult because
See also, Congenital heart disease; Tricuspid valve lesions of airway oedema.
anticonvulsant drugs; magnesium sulphate is the

ECCO2R, see Extracorporeal carbon dioxide removal drug of choice for treating eclamptic seizures, super-
seding diazepam and phenytoin that were tradition-
ally used in the UK; it reduces the incidence of
ECF, see Extracellular fluid recurrent convulsions and of fetal/maternal compli-
cations. Thiopental is suitable in resistant cases; tra-
ECG, see Electrocardiography cheal intubation is required.
head-down, left lateral position, if the trachea is
Echocardiography. Cardiac imaging using reflection of unprotected.
ultrasound pulses from interfaces between tissue planes. lowering of BP as for pre-eclampsia.
A single beam may be studied as it passes through the delivery of the fetus.
heart, displaying movement of tissue planes over time, admission to ICU may be required.
usually recorded on moving paper (M mode). Alterna- Sibai BM (2005). Obstet Gynecol; 105: 40210
tively, beams are directed in different directions from the
same point, covering a sector of tissue; a moving cross- ECMO, see Extracorporeal membrane oxygenation
section may then be displayed on a screen. Analysis of
the frequencies of reflected pulses may provide informa- Ecothiopate iodide. Organophosphorus compound,
tion about the velocity of moving structures and blood used as eye drops to treat severe glaucoma. Plasma cho-
flow (Doppler effect); flow characteristics may be colour- linesterase levels may be reduced for 34 weeks follow-
coded and superimposed on sector images. The passage ing its use, prolonging the action of suxamethonium.
of injected saline may be studied as it travels through
the heart, probably due to entrainment of small air Ecstasy, see Methylenedioxymethylamphetamine
bubbles.
Useful in diagnosing and quantifying valvular heart ECT, see Electroconvulsive therapy
disease, congenital heart disease, patent foramen ovale,
myocardial and pericardial disease, and in assessing Ectopic beats, see Atrial ectopic beats; Junctional
myocardial function. Techniques for the latter involve arrhythmias; Ventricular ectopic beats
measurement of left ventricular dimensions and provide
information about ejection fraction and cardiac output. ED50, see Therapeutic ratio/index
Doppler techniques may be used to estimate pressure
gradients across valves, as the gradient is related to Edema, see Oedema
the difference in velocities across the stenosis. Abnor-
malities of ventricular wall movement may occur in Edetate, see Cyanide poisoning; Sodium calcium edetate
the early stages of myocardial ischaemia, before ECG
changes occur. EDRF, Endothelium-derived relaxing factor, see Nitric
Focused echocardiography consists of an abbre- oxide
viated examination using limited views; increasingly
performed by non-cardiologists to guide immediate man- Edrophonium chloride. Acetylcholinesterase inhibitor,
agement in emergency or critical care environments. used to reverse non-depolarising neuromuscular block-
Transoesophageal echocardiography gives a good ade, and in the diagnosis of myasthenia gravis and dual
view of much of the heart, and has been used periopera- block. Has also been used to treat SVT. Binds reversibly
tively and in ICU. to acetylcholinesterase, with onset of action 30s and
duration of about 5min. Of faster onset than neostig-
Eclampsia. Convulsions caused by hypertensive disease mine, and with fewer muscarinic side effects.
of pregnancy (pre-eclampsia). Dosage:
Carries risk of: reversal of neuromuscular blockade: 0.50.7mg/kg
complications of pre-eclampsia, especially iv with atropine.
coagulopathy. diagnosis of myasthenia gravis: 2mg iv, followed
cerebral oedema/haemorrhage, coma, death. by 8mg iv, if no adverse reaction has occurred.
 Elbow, nerve blocks 199

Improvement in muscle strength occurs in myasthe- end-diastolic end-systolic

nia gravis. Test has low sensitivity and specificity.
volume volume
differentiation between myasthenic and choliner- equals: 100%
end-diastolic volume
gic crises: 2mg iv, 1h after the last dose of cholin-
ergic drug. Increased muscle strength occurs in Useful as an indication of the hearts ability to eject
myasthenic crisis; worsening of weakness in cholin- stroke volume. Measured using nuclear cardiology,
ergic crisis. echocardiography, pulmonary artery catheterisation or
diagnosis of dual block: 10mg iv; causes transient contrast angiography. Normally greater than 60%. May
improvement in muscle power. also be determined for the right ventricle.
treatment of SVT: 520mg iv.
Side effects: bradycardia, hypotension, nausea, Ejector flowmeter. Device used for scavenging from
vomiting, diarrhoea, abdominal cramps, increased anaesthetic breathing systems. O2 or air passing through
salivation, muscle fasciculation. Convulsions and the ejector causes entrainment of waste gases by the
bronchospasm may also occur. The ECG should Venturi principle. The rate of removal is adjusted using
always be monitored when edrophonium is adminis- a flowmeter until it equals the rate of fresh gas supply.
tered, and atropine must always be available. Several litres of driving gas may be required per minute,
at a pressure of at least 1 bar.
EEG, see Electroencephalography
EKG, see Electrocardiography
Efficacy. Maximal effect attainable by a drug; e.g. mor- Elastance. Reciprocal of compliance. Total elastance for
phine is more efficacious than codeine. A pure antago- lungs + chest wall is approximately 10 cmH2O/l.
nist has an efficacy of zero.
See also, Doseresponse curves; Potency Elbow, nerve blocks. Used for surgery to the hand and
wrist; useful for supplementation of a brachial plexus
EGTA, Esophageal gastric tube airway, see Oesophageal block. May be performed using surface anatomy land-
obturators and airways marks, a peripheral nerve stimulator and/or ultrasound
guidance.
The following nerves are blocked (Fig. 57):
Eicosanoids. Collective term used for products of ara-
median (C5T1): lies immediately medial to the
chidonic acid metabolism involved in inflammation,
immunity and cell signalling. Include: brachial artery in the antecubital fossa. A needle is
prostanoids: produced by the cyclo-oxygenase
inserted with the elbow extended, level with the
pathway, i.e. prostaglandins, prostacyclin and epicondyles, to approximately 5mm, and 5ml local
thromboxanes. anaesthetic agent injected. Subcutaneous infiltra-
leukotrienes produced by the lipoxygenase tion blocks cutaneous branches.
radial (C5T1): lies in the antecubital fossa in the
pathways.
groove between biceps tendon medially and bra-
chioradialis muscle laterally. A needle is inserted
Eisenmengers syndrome. Right-to-left cardiac shunt level with the epicondyles with the elbow extended,
developing after long-standing left-to-right shunt; shunt and directed proximally and laterally to contact
reversal occurs because increased pulmonary blood flow the lateral epicondyle. 24ml solution is injected,
results in increased pulmonary vascular resistance and and a further 5ml during withdrawal to skin.
pulmonary hypertension. Prognosis is poor, since pulmo- This is repeated with the needle directed more
nary hypertension is not affected by surgical correction proximally.
of the shunt. May follow any left-to-right shunt, although
the original description referred to VSD. May occur late
in ASD and patent ductus arteriosus.
(a) (b)
Features:
dyspnoea, effort syncope, angina, haemoptysis.
supraventricular arrhythmias, right ventricular
failure, features of pulmonary hypertension.
Anaesthesia is tolerated poorly; reduction in peripheral
resistance increases the shunt with worsening hypoxae-
mia, that in turn further increases pulmonary vascular Lateral cutaneous
resistance. Factors that decrease pulmonary blood flow nerve of forearm
also exacerbate the right-to-left shunt, e.g. IPPV. Risk
of systemic air embolism following iv injection of bubbles
is high.
Pregnancy is also tolerated badly; maternal mortality Radial nerve
is 3050%. Very cautious epidural anaesthesia has been Ulnar nerve
suggested if pregnancy progresses to term.
Heartlung transplantation is the only definitive
treatment.
[Victor Eisenmenger (18641932), German physician] Median nerve

Ejection fraction. Left ventricular stroke volume as a Fig. 57 Cutaneous distribution of nerves blocked at the elbow:
fraction of end-diastolic volume. (a) anterior; (b) posterior
200 Elderly, anaesthesia for

lateral cutaneous nerve of the forearm (C57): lies - widespread atherosclerosis with a less compliant
alongside the radial nerve. It is a continuation of the arterial system. Hypertension is common.
musculoskeletal nerve of the brachial plexus. May - veins are more tortuous, thickened and fragile.
be blocked by subcutaneous infiltration between - DVT is more common.
biceps and brachioradialis, using the same puncture RS:
site as for the radial nerve. - decreased lung compliance and alveolar surface
ulnar (C6T1): passes through the ulnar groove area.
behind the medial humeral epicondyle. With the - increased closing capacity, therefore more airway
elbow flexed to 90, a fine needle is inserted 12cm collapse with resultant increase in alveolar
proximal to the groove, pointing distally. At 12cm arterial O2 difference. Normal alveolar PO2 is
depth, 25ml solution is injected. Neuritis may approximately:
follow injection into the nerve, or block within the age age
ulnar groove. 13.3 kPa 100 mmHg
30 4
See also, Brachial plexus block; Wrist, nerve blocks
- decreased response to hypercapnia and
Elderly, anaesthesia for. Increasingly common as the hypoxaemia.
population ages. Mortality and morbidity are higher in - higher incidence of postoperative atelectasis, PE
older patients. and chest infection.
Anaesthetic considerations, compared with younger pharmacology:
patients: - increased sensitivity to many drugs, especially
CVS: CNS depressants.
- ischaemic heart disease is more likely, with - drug distribution, metabolism and elimination are
reduced ventricular compliance and contractility, altered. A greater proportion of body weight is
and cardiac output. fat, due to a decrease in total body water. Plasma
- decreased blood flow to vital organs. proteins are reduced with altered drug binding.
- cerebrovascular insufficiency is common. - half-lives of many drugs are increased.

Components of electrical circuits Symbols on electrical equipment

Attention, read the

Battery
instructions before use
Class II Double insulated
Alternating current
Earth
Direct current

No patient connection Both direct and alternating

Resistor
Type B or non-isolated patient current
connection
Variable resistor Protective earth

Capacitor Fully isolated floating Equipotential earth point

Type BF
patient connection
Neutral conductor
Inductor
As for type BF but
High voltage
lower leakage currents.
Diode Type CF
Suitable for intracardiac
application Non-ionising radiation
Amplifier
Constructed to prevent Drip proof
Anaesthetic ignition of flammable
Transformer proof anaesthetic mixture Splash proof
with air

Measuring device Watertight

e.g. galvanometer Constructed to prevent
Anaesthetic Off
ignition with oxygen or
proof class G
Switch nitrous oxide
On

Fig. 58 Electrical symbols

 Electrocardiography 201

metabolic: lead refers to the recorded voltage difference between

- metabolic rate is lower. two electrodes; one acts as the positive electrode,
- impaired renal function, thought to be due to the other as the negative (or reference) electrode.
decreased renal blood flow and decreased number The limb leads (IIII, aVR, aVL, aVF) record in the
of glomeruli; suggested decrease in GFR is 1% frontal plane, the chest leads (V16) in the transverse
per year over 20. plane. The leads may be represented on the chest and
- fluid balance is more critical with reduction in heart as in Figure 59a. Thus abnormalities of the inferior
total body water; dehydration is common follow- portion of the heart will be demonstrated in the inferior
ing trauma and illness. leads (i.e. aVF, II and III), and abnormalities of the
- diabetes mellitus and malnutrition are more anterolateral heart in aVL, I, II, etc. V12 demonstrate
common. electrical activity from the right side of the heart, V34
nervous system: from the septum and front, and V56 from the left side.
- cerebrovascular disease is common. Depolarisation towards a positive electrode (or repolari-
- confusion and postoperative cognitive dysfunc- sation away) results in a positive deflection; depolarisa-
tion are more likely, and may be caused by tion away (or repolarisation towards) causes negative
hypoxia, hyperventilation, drugs, hospitalisation deflection.
and any illness. standard bipolar limb leads:
- autonomic nervous system dysfunction is - I: between left arm (positive electrode) and right
common. arm (negative).
- impaired hearing, vision and memory loss are - II: between left leg (positive electrode) and right
common. arm (negative).
other considerations: - III: between left leg (positive electrode) and
- heat loss during anaesthesia is more likely due to left arm.
impairment of both central control and compen- Einthovens triangle is the imaginary inverted equi-
satory mechanisms. lateral triangle centred on the heart, whose sides are
- hiatus hernia is more common, with risk of regur- formed by the axes of the standard limb leads.
gitation and aspiration. augmented unipolar limb leads: combinations of
- systemic diseases and multiple drug therapy are reference electrodes are used that augment the
more common. signal along the desired vector:
- cervical spondylosis is common, with reduced - aVR: right arm.
neck movement. Pain from arthritis may cause - aVL: left arm.
great discomfort, e.g. during local anaesthetic - aVF: left leg.
techniques. Ligaments are often calcified and electrode placement for unipolar chest leads
tough. (reference electrode is formed by the combined
In general, patients are frailer, with greater likelihood of limb leads, such that the reference point is
perioperative complications and slower healing. Atten- mid-chest):
tion to detail (e.g. fluid balance) is more important than - V1: fourth intercostal space, right sternal edge.
with younger patients, since physiological reserves are - V2: fourth intercostal space, left sternal edge.
less. Smaller doses of most agents are required, and arm - V3: midway between V2 and V4.
brain circulation time is prolonged. - V4: fifth intercostal space, left midclavicular line.
Warming blankets, adequate humidification and - V5: fifth intercostal space, left anterior axillary
appropriate monitoring (e.g. of urine output) should be line.
provided. Postoperative O2 therapy should be instituted - V6: fifth intercostal space, left midaxillary line.
immediately and possibly continued for 13 days, since Output is displayed on an oscilloscope or recorded on
hypoxia may readily occur. moving paper. Frequency range is 0.580Hz. Magnitude
The physiological age of the patient is usually more of deflection is proportional to the amount of heart
relevant than the chronological age: e.g. fit 90-year-olds muscle, but reduced by passage through the chest. Skin
may present less risk than frail 70-year-olds. resistance is reduced by cleaning with alcohol and skin
abrasion. Electrodes are usually silver/silver chloride
Electrical symbols. Used to denote components of elec- with chloride conducting gel, to reduce generation of
trical circuits. Specific symbols are also used on electrical potentials in the electrode by the recorded potential, and
equipment to indicate the safety features or other char- reduce impedance variability. Electrodes of differing
acteristics or instructions (Fig. 58). compounds may generate potential by a battery-like
See also, Electrocution and electrical burns effect. Interference may result from muscle activity,
radiofrequency waves from diathermy and other equip-
ment and inductance by electrical equipment. Differen-
Electroacupuncture, see Acupuncture tial amplifiers with common-mode rejection (elimination
of signals affecting both input terminals of a recording
Electrocardiography (ECG). Recording and display of system) are used to reduce interference.
cardiac electrical activity. First performed through the Plan for the interpretation of standard ECG, with
intact chest in 1887 by Waller. Used for investigation of normal values (Fig. 59b):
cardiac disease, particularly ischaemic heart disease and patients name, clinical context, date.
arrhythmias, also for monitoring cardiac rhythm. usual speed of recording is 25mm/s; usual calibra-
Standard modern ECG recordings are obtained from tion is 1 mV/cm (usually confirmed on each record-
different combinations of chest and limb electrodes, ing with a calibration mark).
each set recording along a different vector, thus provid- rate: heart rate in beats/min is calculated by dividing
ing information about a different part of the heart. A the number of 5mm squares between successive
202 Electrocardiography

(a) (b) (c)

aVR aVL

R
aVR 90 aVL

1 2 P T
U 180 0
3 I I

4 Q
5 V leads S
6
PR ST III +90 II
QRS
aVF
QT

III II
aVF
Fig. 59The ECG: (a) arrangement of leads; (b) normal ECG; (c) electric axis

QRS complexes into 300, assuming a recording increase in height from V1 to V4; either increases
speed of 25mm/s. or decreases in V56.
rhythm: - duration is 0.040.12s (13mm squares).
- regular or irregular. An irregular rhythm may - amplitude in I + II + III > 5mm. Left ventricular
be regularly (e.g. missing every third QRS) or hypertrophy exists if the R wave in V6 + S wave
irregularly irregular (e.g. completely random in V1 > 35mm. In right ventricular hypertrophy
in AF). the R:S ratio > 1 in V12.
- presence/absence of P waves, flutter waves in - shape; presence of Q waves.
atrial flutter, ventricular ectopic beats, pacing - abnormal waves, e.g. J and waves in hypo
spikes, etc. thermia and WolffParkinsonWhite syndrome
axis: summation of electrical potentials from the respectively.
standard and aV leads, plotted as vectors. The ST segment:
normal axis lies between 30 and +90 (Fig. 59c). - level within 1mm of baseline.
Simple method of determination: since leads I and - shape.
aVF are at right angles to each other, they can be T wave (ventricular repolarisation):
used alone; e.g. if the QRS deflection is positive in - orientation as for QRS complexes.
both, the axis lies between 0 and 90. If I is positive - height < 5mm.
and aVF negative, the axis lies between 0 and - shape.
90.
Left axis deviation (< 30) may occur in: Q -T interval : corrected QT
- normal subjects (especially if pregnant), ascites,
measured Q T
etc. = Normal range 0.35 0.43 s
- left bundle branch block, left anterior cycle length
hemiblock.
- left ventricular hypertrophy. U wave.
Right axis deviation (> 90) may occur in: During anaesthesia/intensive care, a three-electrode
- normal subjects. system (allowing recording of the three standard limb
- right ventricular hypertrophy. leads) is often used and lead II is selected for continuous
- right bundle branch block, left posterior rhythm monitoring. A five-electrode system incorporat-
hemiblock. ing a right leg and precordial electrode (in addition to
P wave (atrial depolarisation): the right arm/left arm/left leg electrodes) enables record-
- positive in I, II, and V46; negative in aVR, since ing of an anterior chest lead; useful when monitoring left
depolarisation moves downwards and to the left. ventricular myocardial ischaemia. The CM5 lead configu-
- height < 2.5mm. ration (central manubrium V5) also looks at the left
- width < 3mm. ventricle:
- shape. right arm electrode in suprasternal notch.
PR interval: normally 0.120.2s (35mm squares). left arm electrode over apex of heart (V5 position).
QRS complex (ventricular depolarisation): left leg electrode on left shoulder or leg serves as
- usually positive in I, II and V46; negative in aVR ground.
and V12, since most left ventricular depolarisation Other lead configurations are also used, e.g. CH5, CC5
moves downwards and to the left. Progresses and CS5, with right arm electrode on the patients head,
smoothly across the chest leads, e.g. stepwise right side of chest and subscapular regions respectively.
 Electrocution and electrical burns 203

The CB5 configuration with electrode over the right infusion devices may cause sudden cardiac arrest
scapula is better for demonstrating arrhythmias. or burns.
24-hour ambulatory ECG monitoring is performed Current flows between opposite poles for direct
for assessing arrhythmias and their therapy, and detect- current, or from live wire to earth for alternating current,
ing myocardial ischaemia. Some devices run continu- e.g. mains power. Mains voltage is 240 V at 50Hz in the
ously whilst others are activated by the patient when UK and 110 V at 60Hz in the USA. Current flows via
he or she experiences symptoms. 24-hour tapes have the path of least resistance; if this path includes a person,
been used to investigate arrhythmias and ischaemia e.g. patient or doctor via earthed equipment, ECG lead
perioperatively. or floor, electrocution occurs.
[Augustus Desir Waller (18561922), French-born Effects:
British physiologist; Willem Einthoven (18601927), heat production due to high resistance of tissues.
Dutch physician and physiologist] Amount of heat is related to current density. May
See also, Cardiac cycle; Heart block: His bundle electrog- produce burns at sites of current entry/departure.
raphy; Myocardial infarction nerve and muscle stimulation; e.g. effect of current
across chest (approximate values):
Electroconvulsive therapy (ECT). Passage of electric - 1mA: tingling.
current, usually alternating, across the skull to produce - 5mA: pain.
convulsions; used to treat severe depressive psychosis. - 15mA: tonic muscle contraction, i.e. cant let go
3045 J is usually given over 0.51.5s; it may also be threshold.
given as repeated ultra-short bursts. Usually given in - 50mA: respiratory arrest.
courses over a few weeks. First used in the late 1930s. - 100mA: VF.
Brief general anaesthesia is required; partial muscle - > 5 A: tonic contraction of the myocardium
relaxation is usually provided, to allow assessment of (utilised in defibrillation).
resultant convulsions whilst reducing the risk of verte- Magnitude of current depends on the resistance to
bral fractures and other trauma. flow, which is reduced if contacts are wet or have
Anaesthetic considerations: large surface area. Current density at the myocar-
preoperatively: dium is important; thus 100 A is sufficient to cause
- patients should be prepared, starved and investi- VF if delivered directly to the heart (microshock).
gated as for any anaesthetic procedure. Particular Other important factors include:
care is required if cardiovascular disease or intra- - frequency of alternating current: 5060Hz is par-
cranial pathology coexists. ticularly dangerous but cheap to provide.
- concurrent drug therapy may include antidepres- - timing of shock (e.g. R on T phenomenon).
sant drugs, including monoamine oxidase inhibi- Methods of protection:
tors, lithium. regular checking and maintenance of electrical
- premedication is usually omitted. equipment.
perioperatively: use of batteries only (impractical).
- monitoring is required as for any procedure. connection of equipment casing to earth (defined as
- a single induction dose of iv agent is usually given. class I equipment). Accidental contact between the
Methohexital was traditionally used because of its live wire and casing then causes a large current to
short action and pro-convulsant properties. Pro- flow to earth, with melting of protective fuses and
pofol (at 1mg/kg) provides greater haemody- breakage of the circuit. Fuses are made of thin wire
namic stability and more rapid post-ictal recovery that melts at certain current loads; they serve to
whilst having the same therapeutic benefit as protect equipment in case of faults, but do not melt
methohexital and has become the induction agent quickly enough to prevent dangerous currents
of choice. flowing. Fuses are usually placed in live and neutral
- suxamethonium 0.5mg/kg is commonly given, wires and mains plugs.
although smaller doses have been used. double insulation of all conducting wires within
- a soft mouth guard is inserted to protect the teeth equipment (class II).
and gums. use of isolated circuits, e.g. in diathermy, ECG:
- the lungs are ventilated with O2 by facemask after patients are not connected directly to earth via
induction of anaesthesia, since seizure threshold plates and electrodes, but via transformers within
is reduced by hypocapnia. Oxygenation is usually each piece of apparatus. Current thus cannot reach
continued during and after the convulsions, earth through the patient if contact with a live
although the need for the former has been supply occurs. Class III equipment uses internal
questioned. transformers to reduce voltage, e.g. to under 24 V.
- intense parasympathetic discharge may follow Internal transformers are cheaper and more practi-
passage of current, and may be followed by cal than large external transformers, e.g. one for an
increased sympathetic activity. Atropine should operating suite.
always be available; routine administration has reduction of stray leakage currents, e.g. due to
been suggested. drops in potential along the length of conductors,
recovery facilities: as normal. Confusion may caused by capacitance between casing and innards
follow. or inductance. Leakage currents may be sufficient
Ding Z, White PF (2002). Anesth Analg; 94: 135164 to produce microshock. Earth conductors are
connected to each other to reduce differences
Electrocution and electrical burns. Hazard of using between them. Current-operated earth-leakage
electrical equipment; during anaesthesia, malfunction or circuit breakers may be used. Standards for leakage
improper use of diathermy, monitoring equipment or currents are defined, e.g. 10 A maximum from the
204 Electroencephalography

casing or delivered to the patient for intracardiac field and current is described by Flemings right-hand
equipment; 100500 A for other equipment, rule, with thumb, forefinger and middle finger of the
depending on usage. right hand extended at mutual right angles (e.g. forefin-
reduction of the risk of microshock by avoiding con- ger pointing forward, thumb upward and middle finger
ducting solutions, e.g. saline in intracardiac lines medially). If the forefinger points in the direction of the
such as CVP manometers. Needle electrodes are field, and thumb in the direction of movement, the
also avoided, since their resistance is low. middle finger will point in the direction of the induced
electrical equipment, plugs, etc., should not be placed current.
on the floor where solutions may fall on them. Electromagnets within a semicircular probe are
Medical electrical equipment is marked with the appro- placed around an artery, and the moving blood is the
priate electrical symbols to indicate its level of safety conductor. The potential difference between the walls of
features (see Fig. 58). the vessel is measured and average velocity of blood flow
determined. Alternating current is used for magnetic
Electroencephalography (EEG). Recording of electri- field generation, to avoid the effect of induction of
cal activity of the brain. Signals from different combina- current in the detector electrode circuit.
tions of 2022 scalp electrodes are presented as 16 [Michael Faraday (17911867), English chemist; Sir John
continuous traces on paper sheets. Shape, distribution, Fleming (18491945), English electrical engineer]
incidence and symmetry of waves are analysed to give
information about underlying brain activity, in conjunc- Electromechanical dissociation (EMD). Term used to
tion with clinical details. Concealed abnormalities may describe a cardiac state in which organised electrical
be revealed during voluntary hyperventilation. depolarisation occurs throughout the myocardium, but
Different rhythms: there is no synchronous shortening of the myocardial
alpha: normal 813Hz waves. Prominent at the fibres and mechanical contractions are absent. Part of
parieto-occipital area during the awake but resting the spectrum of pulseless electrical activity, though the
state, with the eyes closed. latter also includes mechanical contractions too weak to
beta: normal 1330Hz waves. Prominent over the produce a detectable cardiac output.
frontal area during the awake and active state. See also, Cardiac arrest
delta: < 4Hz waves; normal during adult slow-wave
sleep. Electromyography (EMG). Recording of spontaneous
theta: 48Hz waves; present during the transition
or evoked electrical activity from skeletal muscle; usually
between wakefulness and sleep, and during medita- combined with nerve conduction studies that measure
tive states. the velocity of nerve conduction following stimulation
As age increases, infantile beta activity is slowly replaced at different sites along a nerve pathway. Thus useful
by adult alpha activity. Characteristic patterns occur in distinguishing between disorders of muscle, isolated
in normal sleep. During anaesthesia, alpha rhythms or generalised nerve disease or lesions, and disorders
become depressed, and are replaced by theta and delta affecting the neuromuscular junction.
rhythms. Slow rhythms may reappear at deeper levels of In anaesthesia, it has been used to determine fronta-
anaesthesia, followed by periods of little or no activity lis muscle tone to monitor depth of anaesthesia. Also
separated by bursts of activity (burst suppression). The used in neuromuscular blockade monitoring; nerve
pattern differs with different agents used. Perioperative stimulation and muscle action potential recording are
use is limited by electrical interference, difficult inter achieved using surface skin electrodes, although needle
pretation and production of large amounts of paper. electrodes have been used. Less convenient than devices
Modified forms of EEG have therefore been developed, measuring mechanical muscle response, it may detect
e.g. cerebral function monitor, cerebral function analys- electrical activity when mechanical contraction is
ing monitor, power spectral analysis, bispectral index undetectable.
monitor. Used to investigate intracranial activity in, e.g., Is also used to investigate critical illness polyneuropa-
head injury, epilepsy, cerebrovascular disease, coma, thy and the neuromuscular function of the eye, bladder,
encephalopathies, surgery. Similar principles are involved GIT, etc.
in measuring evoked potentials. See also, Anaesthesia, depth of
See also, Anaesthesia, depth of

Electrolyte. Compound that dissociates in solution to Electron capture detector. Device used in the analysis
produce ions, allowing conduction of electricity; also of gas mixtures that have been separated by, for example,
refers to the ions themselves. Sodium, potassium, gas chromatography; particularly useful in detecting
calcium, magnesium and hydrogen ions are the most halogenated compounds. Electrons within an ionisation
important cations in the body; chloride and bicarbonate chamber pass from cathode to anode, but are captured
ions the most important anions. by the halogenated substance blown through the
See also, Fluids, body; Intravenous fluids chamber. The current passing across the chamber is
therefore reduced, depending on how many electrons
Electrolyte imbalance, see individual disorders are captured. Used to quantify the amount of known
substances, not to identify unknown ones.
Electrolyte solutions, see Intravenous fluids See also, Gas analysis

Electromagnetic flow measurement. Relies on the Embryo, see Environmental safety of anaesthetists; Fetus,
principle that a moving conductor within a magnetic effect of anaesthetic agents on
field induces current that is proportional to the rate of
movement (Faradays law). Relationship of movement, EMD, see Electromechanical dissociation
 Encephalitis 205

Emergence phenomena. Usually consist of agitation 2.5% as an oilwater emulsion. The melting point of
and confusion, with laryngospasm, breath-holding, etc.; each local anaesthetic agent is lowered by the presence
may be equivalent to the second stage of anaesthesia of the other; the resultant mixture has a melting point of
seen on induction, or be due to other causes of confu- 18C and is effective in providing analgesia of the skin
sion, including the central anticholinergic syndrome 6090min after topical application and covering with an
and dystonic reactions. Hallucinations and frightening occlusive dressing. May continue to be released from
dreams are common after ketamine. skin depots even after removal of surface cream. Particu-
larly useful in children. May produce blanching of the
Emergency surgery. Usually refers to surgery occur- skin; increases in methaemoglobin have been reported
ring within 24h of admission or diagnosis; i.e. includes several hours after application.
those cases where surgery follows resuscitation, and Uses described include analgesia for venepuncture,
those where surgery and resuscitation proceed simulta- venous and arterial cannulation, lumbar puncture,
neously (e.g. ruptured aortic aneurysm). epidural injection, superficial skin surgery and relief of
Problems may be related to: tourniquet pain during IVRA.
inadequate preparation of patients for surgery:
full stomach, i.e. risk of aspiration of gastric EMMV, Extended mandatory minute ventilation, see
contents. Mandatory minute ventilation
untreated pre-existing disease, electrolyte imbal-
ance, etc. EMO inhaler, see Vaporisers
appropriate investigations and cross-matching of
blood not performed or not ready. Emphysema, see Chronic obstructive pulmonary disease
the presenting complaint:
- haemorrhage and hypovolaemia. Emphysema, subcutaneous. Presence of gas in subcu-
- intestinal obstruction/intra-abdominal pathology: taneous tissues.
dehydration and hypovolaemia, electrolyte imbal- May be caused by:
ance, etc. Further risk of aspiration due to delayed trauma, including surgery (hence the term surgical
gastric emptying and vomiting/haematemesis. emphysema); gas arises from the atmosphere,
- trauma: haemorrhage, head injury, chest trauma, viscera or air sinuses.
etc. pneumothorax or rupture of a viscus, e.g.
- airway obstruction/inhaled foreign body. oesophagus.
- related to specialist surgery, e.g. cardiac surgery, barotrauma.
neurosurgery. infection with gas-producing organisms, e.g. gas
The balance between the need for preoperative treat- gangrene.
ment and urgency of surgery is sometimes difficult, but rarely, deliberate self-injection of subcutaneous air
inadequate preoperative correction of fluid and electro- in disordered mental states.
lyte disturbance is consistently associated with increased Often palpable under the skin, and may be visible on
perioperative mortality. Treatment of cardiac failure is X-ray. The gas is slowly absorbed once the cause is
also important whenever possible. Careful preoperative treated. Multiple skin puncture has been performed to
assessment and discussion with the surgeon are vital. allow escape of gas, and high FIO2 suggested to increase
Anaesthetic management is as for routine surgery but absorption (O2 being more soluble than nitrogen), but
with the above considerations. Thus smaller doses of the value of these measures is unknown.
drugs than usual are given initially. Rapid sequence
induction is usually employed. Measures against heat Empyema. Collection of pus within the pleural cavity.
loss are important. Invasive monitoring and postopera- A complication of chest trauma (especially if haemotho-
tive HDU/ICU and IPPV should be considered. rax was present), pneumonia, chest drainage, thoracic
Regional techniques are particularly useful for limb surgery and subdiaphragmatic abscess. Clinical features
surgery, but epidural/spinal anaesthesia is hazardous if include pyrexia, chest pain and productive cough. CXR
hypovolaemia is present. features are those of a pleural effusion; if encapsulated
Special Issue (2013). Anaesthesia; 68 s1: 1124 it may resemble a pulmonary cyst. Diagnosis is confirmed
See also, specific procedures; Anaesthetic morbidity and by imaging and aspiration of pus. Treatment depends on
mortality aetiology but includes antibacterial drugs, chest drainage
(sometimes requiring ultrasound or CT scan guidance)
Emesis, see Vomiting and surgery. May rarely lead to bronchopleural fistula.

Emetic drugs. Given to empty the stomach, e.g. follow- Enalapril maleate. Angiotensin converting enzyme
ing poisoning, or preoperatively to reduce risk of aspira- inhibitor, used to treat hypertension and cardiac failure
tion pneumonitis. Now rarely used, because of poor (including following MI). A prodrug, it is converted to
efficacy and the risk of causing aspiration; particularly enalaprilat by hepatic metabolism. Longer acting than
dangerous after ingestion of corrosive or petroleum captopril, with onset of action within 2h; half-life is up
derivatives, or in unconscious patients. Include apomor- to 35h via active metabolites.
phine and ipecacuanha; copper sulphate and sodium Dosage: 2.540mg orally od.
chloride are no longer used. Side effects: hypotension following the first dose or
following induction of anaesthesia, cough, dizziness,
EMG, see Electromyography weakness, nausea, diarrhoea, rash, renal impairment.

EMLA cream (Eutectic mixture of local anaesthetics). Encephalitis. Acute infection of the brain parenchyma,
Mixture of prilocaine base 2.5% and lidocaine base usually caused by a virus, that results in diffuse
206 Encephalopathy

inflammation affecting the meninges. Usually presents

with the triad of fever, headache and altered mental
status. Other clinical features include neck stiffness,
lethargy, confusion, coma, encephalopathy, focal neuro-
logical signs and epilepsy.
Causes:
viral infection: viruses gain entry to the CNS via
the haematological route or retrograde neuronal
spread. Viruses include herpes simplex (most com- (a)
monly), varicella zoster, cytomegalovirus and
EpsteinBarr virus.
immunologically mediated parainfectious pheno
menon following a variety of infections or
vaccinations.
autoimmune encephalitis (including anti-NMDA
receptor encephalitis and anti-voltage-gated potas-
sium channel encephalitis) is being increasingly
recognised; presents with psychiatric, epileptic and
movement disorder features.
neoplastic or paraneoplastic encephalitis.
Differential diagnosis includes meningitis and cerebral
abscess. Investigations include CSF examination (mild
increase in protein, lymphocytosis, normal glucose in
viral encephalitis), CT and MRI scanning, EEG and
viral titres/cultures from blood and CSF. Treatment is
largely supportive, with tracheal intubation and IPPV
for patients with depressed consciousness. Aciclovir
(b)
should be given to all cases of suspected viral encepha-
litis whilst a definitive diagnosis is sought.
Long SS (2011). Adv Exp Med Biol; 697; 15373

Encephalopathy. Diffuse disorder of cerebral function

with or without focal neurological deficit. Usually results
in delirium, stupor and coma. Aetiology is as for coma.

Fig. 60 Double-lumen endobronchial tubes: (a) right-sided;

Endobronchial blockers (Bronchial blockers). Used in (b) left-sided
thoracic surgery to isolate a portion of lung, e.g. to avoid
air leaks during IPPV or prevent contamination of
normal lung with secretions, pus or blood. Less often
used now, except for paediatric surgery, endobronchial
tubes being more popular and versatile. Previous ver- cuffed endobronchial portion, curved to the left or
sions were made of red rubber; modern versions are right as appropriate (the latters cuff is deflected
thin plastic catheters with an inflatable distal cuff, usually around a slot for the right upper bronchus). The
inserted under direct vision via a bronchoscope, either bronchial cuff and inflation port on single-use tubes
before tracheal intubation with a standard tracheal are blue by convention.
tube or after intubation with a specific tubeblocker cuffed tracheal portion.
combination. oropharyngeal portion, concave anteriorly.
The main problem of right-sided tubes is related to
Endobronchial tubes. Used in thoracic surgery to allow the short length of the right main bronchus before
sleeve resection of the bronchus, or to isolate infected giving off the upper lobe bronchus. Hence left-sided
lung or potential air leak, e.g. in bronchopleural fistula tubes are usually preferred, even for right-sided
or emphysematous lung cysts. Other pulmonary surgery surgery, because of the risk of inadequate ventilation
(e.g. pneumonectomy/lobectomy, pleural, aortic, oesoph- of the right upper lobe if incorrectly positioned.
ageal and mediastinal surgery) is possible with conven- Right-sided tubes are often preferred if the left main
tional tracheal tubes, although surgery may be made bronchus is compressed by aortic aneurysm, to
easier by collapsing one lung. Also used in ICU in prevent traumatic haemorrhage.
patients with severe, unilateral lung injury or broncho- Insertion:
pleural fistula. Risks of one-lung anaesthesia should be as for tracheal tubes initially, with the bronchial
considered before use. curve concave anteriorly to aid passage through the
Different tubes, usually made of red rubber, were pharynx.
developed in the 1930s1950s, and included single-lumen rotated 90 when the tip is through the larynx, to
and double-lumen designs, for insertion into the left direct the endobronchial part to the appropriate
(most commonly) or right main bronchus. Modern side.
double-lumen tubes are usually plastic, with thinner connected to the breathing system via a double
walls and low-pressure cuffs, and have the following fea- catheter mount, each lumen connected via a capped
tures (Fig. 60): connector and compressible tubing. Cuff inflation:
 Endorphins 207

- the tracheal cuff is inflated until the air leak with systemic embolisation. Systemic immune complex
stops; both sides of the chest are checked for deposition may also occur. Overall mortality is ~40%.
ventilation. Traditionally divided into acute and subacute,
- the catheter mount to the tracheal lumen is although definitions are imprecise:
clamped, and the tracheal lumen opened to air. acute:
- the lung is inflated via the bronchial lumen only, - usually due to virulent organisms, e.g. Streptococ-
inflating the bronchial cuff until no air leak is cus pneumoniae, Staphylococcus aureus.
heard from the tracheal lumen. Only the selected - often affects normal valves
side of the chest should now move. - presents early with rapid progression to death
- the tracheal lumen is reconnected and both sides unless early aggressive treatment is instituted.
of the chest are checked as before. subacute:
- both lungs should now be able to be ventilated - usually due to Streptococcus viridans or
separately, by inflating via one lumen only and enterococci.
opening the other to air. - underlying structural heart disease or presence of
Fibreoptic endoscopy is the best way of checking prosthetic valves is usual.
correct positioning, since clinical assessment may - chronic malaise and slow course of disease are
not be reliable; it is especially useful with right- typical.
sided tubes. It may also be used to check for cuff Infection with atypical organisms, e.g. fungi and
herniation causing tube or bronchial obstruction. staphylococci, is more common in iv drug abusers and
Complications are as for tracheal intubation (see Intuba- in this group affects the tricuspid valve in 50%.
tion, complications of). Bronchial rupture may occur if Features:
excessive volumes are used for cuff inflation. Incorrect fever (90%), malaise, weight loss, night sweats,
positioning, or movement during positioning of the anaemia.
patient, may result in uneven ventilation and impaired heart murmurs (85%), cardiac failure, valve lesions.
gas exchange. peripheral embolisation/vasculitic phenomena,
See also, Tracheobronchial tree e.g. splinter haemorrhages in nail beds, conjuncti-
vae and retina (Roth spots), painful fingertip
Endocardial viability ratio (EVR). Ratio of diastolic swellings (Oslers nodes), painless haemorrhagic
pressure time index to tension time index, obtained by lesions on palms and soles (Janeway lesions),
recording left ventricular and aortic root pressure trac- kidneys (causing haematuria), CNS (causing
ings (Fig. 61). May indicate myocardial O2 supply/ CVA). Splenomegaly and clubbing may occur.
demand ratio and likelihood of myocardial ischaemia Diagnosis:
(thought to be likely when the ratio is under 0.7). blood cultures (positive in 90% of cases); two sets
should be taken 12h apart. Positive cultures with
Endocarditis, infective. Infective inflammation of the typical organisms are highly suggestive of the condi-
endocardial lining of the heart and valves, most com- tion. Can be taken even when temperature is normal
monly the aortic valve (previously the mitral valve). since the bacteraemia is constant.
Commonly associated with abnormal valves (e.g. rheu- echocardiography (initially transthoracic then
matic, degenerative or prosthetic valves) or congenital transoesophageal if the former is negative).
heart disease, but approximately 50% of cases involve serological testing is performed if cultures are nega-
normal valves. Men are twice as commonly affected. tive (e.g. if the patient is already on antibiotics).
Nosocomial endocarditis may result from catheter- tissue culture of skin lesions may be helpful.
related sepsis or invasive procedures (e.g. endoscopy, Treatment is supportive with antimicrobial therapy
dental extractions). Results in tissue destruction and depending on the infecting organism. Treatment usually
vegetations of platelets, macrophages and organisms, lasts 46 weeks. Cardiac valve replacement is necessary
in ~50%; indications include CVS instability associated
with valve destruction, persistent fever despite pro-
longed antimicrobial therapy, presence of highly resis-
tant organisms, prosthetic valve involvement and large
vegetations with embolic potential. Prophylaxis in
Diastole Systole structural disease is as for congenital heart disease.
[Moritz Roth (18491914), Swiss physician; Sir William
Osler (18491919), Canadian-born US and English phy-
sician; Theodore Caldwell Janeway (18721917), US
physician]
Aortic root European Society of Cardiology Task Force (2009). Eur
Heart J; 30: 2369413

Endocrine disorders, see individual diseases

Left ventricle
Endomorphins. Endogenous opioid peptides for
opioid receptors. Produce spinal and supraspinal analge-
sia experimentally; have been found in the human brain,
Diastole pressure Tension although their role is uncertain.
time index time index
Endorphins. Endogenous opioid peptides derived
Fig. 61 Left ventricular and aortic root pressure tracings from -lipotropin, secreted by the anterior pituitary and
208 Endothelin

hypothalamus. -Endorphin (31 amino acids) is the most End-tidal gas sampling. Gives the approximate compo-
potent endogenous opioid, active mainly at and sition of alveolar gas, unless major V/Q mismatch
opioid receptors. Also inhibits GABA and promotes exists or tidal volume is very small. Useful for estimating
dopamine secretion. Derived from pro-opiomelanocortin alveolar and hence arterial PCO2, e.g. for monitoring
(99 amino acids), from which ACTH is derived. Thought adequacy of ventilation. Alveolar concentrations of
to be involved in central pain pathways, emotion, etc. inhalational anaesthetic agents may also be monitored.
May also be involved in haemorrhagic and septic shock; May also indicate extent and rate of uptake of inhala-
thought to reduce SVR, cardiac output and BP, while tional agents, if expired and inspired concentrations are
decreasing GIT motility and sympathetic activity and compared, and the state of O2 supply/demand. On-line
enhancing parasympathetic activity. This may explain multiple gas monitors are now routine, providing breath-
why naloxone sometimes improves cardiovascular vari- by-breath measurements. Since the gas sampled by these
ables in shock. is not strictly end-tidal, the sampling line being placed
some distance away from the patients airway, the term
Endothelin. Vasoconstrictor peptide derived from vas- end-expiratory is more accurately applied. Mixing of
cular endothelium, involved in regulation of basal vas- end-expiratory gas with fresh gas may lead to inaccuracy,
cular tone and BP. Produced from an inactive precursor, especially if samples are taken between the breathing
it acts at specific endothelin receptors to cause vasocon- system filter and the anaesthetic machine.
striction (type A receptors). Type B receptor activation See also, Carbon dioxide, end-tidal; Gas analysis
may also result in production of nitric oxide and prosta-
cyclin. May be involved in local blood flow and in various Energy. Capacity to perform work, whether mechanical,
cardiovascular disorders, notably cardiac failure and pul- chemical or electrical. Kinetic energy is the energy of a
monary hypertension. Endothelin receptor antagonists body due to its motion; potential energy is the energy of
such as bosentan (which antagonises both A and B a body due to its state or position. Thus a body on a table
receptors) have been investigated as possible treatments has potential energy due to the effect of gravity; when it
for these. falls, this is converted to kinetic energy. Similarly, the
potential energy of a stretched spring is converted to
Endothelium-derived relaxing factor, see Nitric kinetic energy as it recoils. The law of conservation of
oxide energy states that energy cannot be destroyed or created,
but only converted to other forms of energy, e.g. heat,
Endotoxins. Lipopolysaccharides (LPS) present on the light, sound. Molecules within a body have potential
surface of Gram-negative bacteria. LPS consist of: a lipid energy due to their chemical composition and forces
chain (lipid A), responsible for the biological effects; a between them, and kinetic energy due to their move-
core polysaccharide; and oligosaccharide side chains ment. SI unit is the joule, although the Calorie (Cal;
specific to each strain. Released when the bacteria die, equals 1000 cal) is widely used for dietary energy
and extremely toxic, probably via release and activation estimations.
of many inflammatory substances, including cytokines. Energy is liberated in the body by breakdown of
Endotoxaemia may be involved in the aetiology of metabolic substrates, e.g. approximately 4 Cal/g carbo-
sepsis, although it may occur in the absence of infection, hydrate and protein, 9 Cal/g fat, 7 Cal/g alcohol. It may
and proven Gram-negative sepsis may not be accompa- be stored in high phosphate bonds, e.g. in ATP, and in
nied by endotoxaemia. Translocation of GIT organisms other compounds, e.g. glycogen.
or their endotoxins into the bloodstream across the gut See also, Basal metabolic rate; Energy balance;
wall has been suggested to occur in critical illness. Metabolism
Attempts have been made to prevent endotoxaemia by
killing GIT organisms (selective decontamination of the
digestive tract), and to treat established endotoxaemia Energy balance. Difference between Calorie intake and
with anti-endotoxin antibodies. energy output. If intake is less than expenditure, energy
Wendel M, Paul R, Heller AR (2007). Intensive Care balance is negative and endogenous energy stores are
Med; 33: 2535 utilised; if it is greater, balance is positive and the indi-
See also, Bacterial translocation vidual gains weight. Many critically ill patients (e.g. those
with trauma, sepsis) have increased catabolism and gly-
Endotracheal tubes, see Tracheal tubes cogenolysis, insulin resistance with resultant lipolysis
and increased basal metabolic rate. In order to provide
End-plate potentials. Depolarisation potentials pro- adequate nutrition in these patients, it is possible to esti-
duced at the postsynaptic motor end-plate of the neu mate energy expenditure, e.g. with indirect calorimetry
romuscular junction by binding of acetylcholine (ACh) using bedside devices (metabolic carts). This allows
to receptors. Their size and duration depend on the measurement of O2 and CO2 exchange and thus respira-
amount of ACh released, the number of ACh receptors tory exchange ratio; however such techniques are not
free and the activity of acetylcholinesterase. Miniature widely used because of inaccuracies related to gas leaks
end-plate potentials (under 1 mV) are thought to be from the patient/ventilator circuit and the effect of water
produced by random release of ACh from single vesicles vapour.
(quantal theory), and are too small to initiate muscle Normal subjects require about 25 Cal/kg/day; most
contraction. Simultaneous release of ACh from many critically ill patients require about 2540 Cal/kg/day.
vesicles follows depolarisation of the pre-synaptic See also, Nitrogen balance
membrane; the resultant large end-plate potential
causes depolarisation of adjacent muscle membrane, Enflurane. 2-Chloro-1,1,2-trifluoroethyl difluoromethyl
and muscle contraction. ether (Fig. 62). Inhalational anaesthetic agent, intro-
See also, Neuromuscular transmission duced in 1966.
 Entonox 209

Inspired concentrations of 13% are usually ade-

CI F F
quate for anaesthesia, with higher concentrations for
H C C O C H
induction.

F F F Enkephalins. Endogenous opioid peptides found in the

CNS, especially:
Fig. 62 Structure of enflurane periaqueductal grey matter.
periventricular grey matter.
limbic system.
medullary raphe nucleus.
Properties: spinal cord, especially laminae II and III (substantia
colourless volatile liquid with ether-like smell; gelatinosa) of the dorsal horn.
vapour is 7.5 times denser than air. Methionine enkephalin and leucine enkephalin (each 5
mw 184.5. amino acids) are derived from proenkephalin; they are
boiling point 56.5C. thought to be involved in the modulation of pain path-
SVP at 20C 24 kPa (175mmHg). ways, e.g. gate control theory of pain. Active mainly at
partition coefficients: opioid receptors.
- blood/gas 1.9. See also, Endorphins
- oil/gas 98.
MAC 1.7% (middle age); 1.9% (young adults); 2.4 Enoxaparin, see Heparin
2.5% in children/teenagers.
non-flammable and non-corrosive. Stable without Enoximone. Selective (PDE III) phosphodiesterase
additives and unaffected by light. inhibitor unrelated to catecholamines or cardiac glyco-
Effects: sides. Used as an inotropic drug, particularly in cardio-
CNS: genic or other types of shock, in which there is an
- smooth and rapid induction and recovery. element of heart failure (e.g. after cardiac surgery, and
- epileptiform EEG activity may occur (typically in patients awaiting heart transplants). Increases cardiac
a three per second spike and wave pattern), espe- contractility and stroke volume with minimal tachycar-
cially at doses > 2 MAC with coexisting hypocap- dia, and without increasing myocardial O2 demand. Also
nia. Convulsions may occur postoperatively. causes vasodilatation (reducing both preload and after-
- increased cerebral blood flow but reduced intra- load), thereby decreasing ventricular filling pressures.
ocular pressure. BP may fall.
- weak analgesic properties. Acts directly on cardiac muscle rather than adrener-
RS: gic (or other) receptors.
- depresses airway reflexes less than halothane and Preparation contains alcohol, propylene glycol and
therefore tracheal intubation is more difficult sodium hydroxide (pH 12). Crystal formation may occur
when the patient is breathing spontaneously. with glass syringes, etc., and if mixed with other drugs
- causes greater respiratory depression than halo- and dextrose solutions.
thane or isoflurane; an increased respiratory rate Undergoes hepatic metabolism to partially active
is common, with decreased tidal volume. metabolites, excreted renally.
- bronchodilatation. Dosage: 90g/kg/min over 1030min iv, followed by
CVS: continuous or intermittent infusion of 520g/kg/
- causes greater myocardial depression than halo- min, up to 24mg/kg/day.
thane. SVR is reduced, with compensatory tachy- Side effects: hypotension, nausea and vomiting,
cardia. Hypotension is common. insomnia, headache.
- causes fewer arrhythmias than halothane, and
less sensitisation of the myocardium to ENT surgery, see Ear, nose and throat surgery
catecholamines.
other: Enteral nutrition, see Nutrition, enteral
- dose-dependent uterine relaxation.
- nausea and vomiting are uncommon. Entonox. Trade name for gaseous N2O/O2 50:50 mixture,
- muscle relaxation and potentiation of non- supplied in cylinders at a pressure of 137 bar. Invented
depolarising neuromuscular blocking drugs is by Tunstall in 1962. Cylinders are coloured blue with
greater than that seen with halothane or blue/white quartered shoulders. May also be supplied by
isoflurane. pipeline. Formed by bubbling O2 through liquid N2O
- may precipitate MH. (Poynting effect).
About 2% metabolised, the rest excreted via the Cylinders must be kept above 7C (pseudocritical
lungs. Although fluoride ions may be produced by temperature) to prevent liquefaction of the N2O (a
metabolism, toxic levels are usually not reached, although process called lamination). If this occurs and gas is
they have been reported in obese patients after pro- drawn from the top of the cylinder, O2 will be delivered
longed anaesthesia. Patients with pre-existing renal first, followed by almost pure N2O. In the large cylinders
impairment or receiving other nephrotoxic drugs or used for connection to a pipeline system via a manifold,
enzyme-inducing drugs, e.g. isoniazid, are also thought to gas is therefore drawn first from the bottom of the cyl-
be at risk. inder by a tube; should liquefaction of N2O now occur,
Hepatitis has been reported following enflurane; N2O containing about 20% O2 is delivered first. Warming
cross-sensitivity with halothane has been suggested, but and repeated inversion of the cylinders will reconstitute
this is disputed. the gaseous mixture.
210 Envenomation

Widely used for inhalational analgesia for trauma and by subsequent studies, and effects of breathing
minor procedures, e.g. physiotherapy or change of dress- small amounts of volatile agents are thought to be
ings; most commonly used with a demand valve for self- minimal, if any. Effects of N2O are now considered
administration. Onset of analgesia is rapid, with minimal potentially more harmful; increased incidence of
cardiovascular, respiratory or neurological side effects. spontaneous abortion and possibly congenital mal-
Should sedation occur, the patient reduces the intake formation in theatre workers or their spouses is
and recovery rapidly occurs. Caution is required if the suspected but has never been conclusively proven.
patient has an undrained pneumothorax, as N2O may This may be via methionine synthase inhibition.
increase its size. Effect on performance is controversial; there is no
Also widely used in the UK for inhalational analgesia conclusive evidence that the low atmospheric con-
during labour, although there is little evidence that pain centrations measured are deleterious. Any risks are
scores are reduced. reduced by scavenging, avoiding spillage, monitor-
Continuous use (e.g. in ICU) has declined because of ing contamination levels and testing apparatus for
interaction of N2O with the methionine synthase system. leaks. Workplace exposure limits set out in COSHH
[Michael Tunstall (19282011), Scottish anaesthetist] regulations for Great Britain and Northern Ireland
See also, Obstetric analgesia and anaesthesia are 100ppm N2O, 50ppm enflurane/isoflurane and
10ppm halothane (each over an 8-h period). In the
Envenomation, see Bites and stings USA, the National Institute for Occupational Safety
and Health has recommended an 8-h time-weighted
Environmental impact of anaesthesia. Has attracted average limit of 2ppm for halogenated anaesthetic
increasing attention through two main areas: agents in general (0.5ppm together with exposure
direct effects of inhalational agents: to N2O).
- reaction of chlorine and bromine atoms from infection, e.g. with hepatitis or HIV infection. Risks
atmospheric volatile agents, released by the action are reduced by immunisation against hepatitis B,
of ultraviolet radiation, with ozone, depleting wearing of gloves and goggles, avoidance of needles
the latter. wherever possible, and careful disposal of any con-
- acting as greenhouse gases, preventing the escape taminated equipment. Needles should never be
of infrared radiation from the earth. N2O is less resheathed by holding their cover in ones hand.
potent in this regard than sevoflurane (which is Devices for safe handling of used needles (e.g. non-
less potent than isoflurane and especially desflu- removable caps or cannulae/syringes with self-
rane), but lasts longer in the atmosphere so is retracting needles) became mandatory in the USA
thought to have a greater overall effect. In addi- in 2001, with European legislation introduced in
tion, it is used in much higher concentrations, thus 2006. In case of accidental needlestick injuries:
thought to account overall for > 99% of the climate - wash with soap and water.
impact potential of anaesthetic gases (with medical - encourage bleeding.- the source patient should be
N2O accounting for ~1% of atmospheric N2O). risk-assessed (ideally by a doctor other than the
increasing use of disposable equipment that must person who sustained the injury), with a view to
be incinerated at high temperature, generating considering post-exposure prophylaxis (PEP) for
further CO2 and releasing toxins (e.g. dioxins, plas- HIV infection.
ticisers) into the atmosphere, as well as generation - testing for HIV and hepatitis infection requires
of large amounts of waste from packaging. informed patient consent and counselling, a cause
Suggested measures to minimise the above include: of much controversy should a healthcare worker
reduction in generation of waste, e.g. reduced pack- suffer a needlestick injury from an unconscious
aging, re-use where possible, dilution of drugs from patient. If considered necessary, PEP with 23
iv fluid bags already in use rather than fresh saline/ antiretroviral agents (including zidovudine)
water ampoules. started within 72h after exposure and continued
increased recycling, including glass from ampoules. for 28 days is recommended. PEP reduces the risk
incineration only for contaminated material, and of infection by 80%. Follow-up HIV serology
high-temperature incineration only for truly sharp testing should be performed at 1, 3 and 6 months.
objects. Risk of infection after accidental exposure of
power-saving strategies, e.g. turning off equipment healthcare workers is estimated at 0.3% for HIV
not in use. (needlestick; higher risk after conjunctival inocu-
avoidance of N2O, use of low-flow systems. lation), 3% for hepatitis C and up to 30% for
consideration of transportation costs when ordering hepatitis B. Risk is affected by the number of viral
equipment/drugs. particles inoculated and the route. Other more
Sneyd JR, Montgomery H, Pencheon D (2010). Anaes- contagious infections: deaths were reported fol-
thesia; 65; 4357 lowing exposure to patients infected with severe
acute respiratory syndrome.
Environmental safety of anaesthetists. Hazards faced risk of electrocution and burns, explosions and fires,
may be due to: radiation exposure, back injury, stress and fatigue.
inhalational agents: fears were expressed, especially Access to addictive drugs makes abuse of anaes-
in the 1960s, because of reported high incidence of thetic agents easier. Alcohol abuse is common
lymphoid tumours in anaesthetists. Chronic expo- among doctors. Increased risk of suicide is sus-
sure to low concentrations of volatile agent was pected, but not proven.
thought to be responsible, hence attempts to remove personal injury during interhospital transfer of
it from the immediate atmosphere by adsorption or patients.
scavenging. Such an association was not supported Similar concerns exist for staff on the ICU.
 Epidural anaesthesia 211

Andersen MP, Nielsen OJ, Wallington TJ (2012). Anesth Actions:

Analg; 114: 10815 directly stimulates - and -adrenergic receptors.
See also, Contamination of anaesthetic equipment; releases noradrenaline from nerve endings.
COSHH regulations inhibits monoamine oxidase.
Effects:
Enzyme. Protein accelerating a specific chemical reac- increased heart rate, myocardial contractility and
tion, i.e. a biological catalyst. Sensitive to pH and BP.
temperature. vasoconstriction.
Classified according to the reaction catalysed: bronchodilatation.
oxidoreductases: oxidation/reduction, e.g. metabo- CNS arousal and pupillary dilatation.
lism of many drugs. increased sphincter tone.
transferases: transfer of groups between molecules, placental and uterine blood flow is maintained; thus
e.g. transaminases. it has been traditionally considered the agent of
hydrolases: hydrolytic cleavage or reverse, e.g. choice in obstetric regional anaesthesia.
acetylcholinesterase. Dosage:
lysases: cleavage of CC, CN, etc., without oxida- 36mg repeated as required up to 30mg.
tion, reduction or hydrolysis, e.g. decarboxylases. 1560mg orally/im tds.
isomerases: intramolecular rearrangements, e.g. Tachyphylaxis occurs with repeated administration. May
mutases. cause restlessness and palpitations in overdose.
ligases: reactions involving high-energy bonds, e.g.
ATP, and formation of CC, CN, etc. Epidural anaesthesia. Introduction of local anaesthetic
Reactions involve formation of intermediate structures, agent into the epidural space in order to induce loss of
with formation of reaction products and reformation of sensation adequate for surgery (the term epidural anal-
enzyme. gesia refers to provision of pain relief, e.g. during
See also, Enzyme induction/inhibition; MichaelisMenten labour). Can be divided anatomically into cervical, tho-
kinetics racic, lumbar and caudal. Caudal analgesia was first per-
formed in 1901; lumbar blockade was performed by
Enzyme induction/inhibition. Certain drugs may alter Pages in 1921 and popularised by Dogliotti in the 1920s
the activity of enzymes involved in their metabolism, 1930s, although it was probably introduced by Corning
most importantly, in the liver. Induction is an increase in following his initial experiments. Continuous catheter
the amount of enzyme, caused by increased synthesis or techniques were introduced in the late 1940s.
decreased breakdown. It is usually related to the dura- Following injection, local anaesthetic may act at
tion and extent of drug exposure. The cytochrome P450 epidural, paravertebral or subarachnoid nerve roots,
system is often involved. Inhibition is a reduction in the or directly at the spinal cord. Systemic effects may
amount of enzyme or impairment of its activity. also occur.
May affect metabolism of the original drug and other Indications are as for spinal anaesthesia; main
drugs, leading to drug interactions, e.g.: advantages are avoidance of dural puncture, and those
enzyme induction: related to catheter technique, i.e. allows control over
- barbiturates increase metabolism of warfarin, onset, extent and duration of blockade. Thus used for
phenytoin and chlorpromazine. peri- and postoperative analgesia, analgesia following
- phenytoin increases metabolism of digitoxin, thy- chest trauma, obstetric analgesia and anaesthesia, and
roxine, vecuronium, pancuronium and tricyclic treatment of chronic pain. However, blockade is less
antidepressants. intense than spinal anaesthesia, with greater chance of
- alcohol increases metabolism of warfarin, barbi- missed segments, and the dose of drug injected is poten-
turates and phenytoin. tially dangerous if incorrectly placed.
- smoking increases metabolism of vecuronium, Opioid analgesic drugs may be injected into the epi-
pancuronium, morphine, aminophylline, chlor- dural space to provide analgesia.
promazine and phenobarbital. (For anatomy, path taken by needle, etc., see Epidural
enzyme inhibition: space.)
- ecothiopate reduces metabolism of suxa Technique (lumbar block):
methonium. performed with the patient in the lateral or sitting
- metronidazole reduces metabolism of acetalde- position. Preparation of patient is as for spinal
hyde produced by alcohol metabolism. anaesthesia. Full aseptic technique, including sterile
- cimetidine reduces metabolism of lidocaine, mor- gown, is usual in the UK, especially when a catheter
phine, pethidine, labetalol, propranolol and is inserted.
nifedipine. median/paramedian approaches are used as for
Sweeney BP, Bromilow J (2006). Anaesthesia; 61: spinal anaesthesia. Easier catheter insertion, with
15977 less risk of dural or vascular puncture, is claimed for
the latter approach. It may also be easier in the
EOA, Esophageal obturator airway, see Oesophageal elderly, particularly if back flexion is difficult or the
obturators and airways ligaments are calcified.
deep and superficial infiltration with local anaes-
Ephedrine hydrochloride. Sympathomimetic and vaso- thetic is performed.
pressor drug, mainly used to treat hypotension (espe- 1619 G Tuohy needles are usually employed, espe-
cially in spinal and epidural anaesthesia). Sometimes cially for catheter insertion. The curved blunt tip
used in the treatment of bronchospasm and autonomic reduces the risk of dural puncture and facilitates
neuropathy. catheter direction (Fig. 63). The needle is usually
212 Epidural anaesthesia

(a) More recently, syringe devices with spring-loaded

plungers have been described; when the epidural
space is entered the plunger automatically moves
within the barrel.
injection of a test dose through the needle is
controversial and rarely performed, especially if a
catheter is to be inserted.
injection through the needle may be single shot or

(b) fractionated; faster onset and higher block are

claimed for the former but better control and safety
claimed for the latter.
catheter technique:
- a 1618 G catheter is inserted through the needle
Fig. 63 (a) Winged Tuohy needle. (b) Detail of tip
and directed usually upwards within the epidural
space. Incidence of bloody tap is thought to be
reduced if saline is injected before the catheter
marked at 1cm intervals (Lee markings), and may is inserted. If insertion is difficult, injection of
be winged. The Crawford needle (straight-tipped 510ml saline or slight straightening of the legs
with an oblique bevel) is sometimes used. The stylet may help. The catheter should never be pulled
is removed when the needle tip is gripped by the back through the needle, as its tip may be sheared
interspinous ligament (see Vertebral ligaments). off. Smaller needles are available for children.
Less damage to the longitudinal ligamentous fibres - the needle is removed over the catheter. 35cm
has been claimed if the needle is inserted with the of the latter is usually left in the space; too little
bevel facing laterally; the needle may then be may increase the risk of falling out; too much may
rotated 90 once the space is entered. However, increase the risk of inadequate block, e.g. by
insertion with the bevel facing cranially is usually passing through an intervertebral foramen. After
advocated, since this avoids the risk of dural punc- aspiration and confirmation of the absence of
ture during rotation of the needle. CSF or blood in the catheter, it is fixed to the
the epidural space is identified by exploiting the patients back.
negative pressure that is usually present within it. - catheter types:
Methods include: the hanging drop technique; a - single end hole: thought to be more likely
bubble indicator placed at the needle hub; collaps- to obstruct, and to produce incomplete block-
ing drums or balloons (e.g. Macintoshs); and the ade, e.g. if the tip is near an intervertebral
loss of resistance technique: foramen.
- a low-resistance syringe is attached to the needle - closed end with (usually three) side holes: the
(after checking first to ensure a smooth action). It most common type in the UK. May account for
may be filled with: development of extensive blockade, e.g. if
- saline: minimal give when compressed, thus the distal hole is located in the subarachnoid
easier to judge resistance to injection. May be space and the proximal hole is in the epidural
confused with CSF if dural puncture occurs (dif- space. Solution injected slowly is thought to
ferentiated by detection of glucose/protein in leave via the proximal hole with epidural block
CSF but not in saline, using reagent strips). as expected; rapid injection may produce sub-
- air: avoids confusion with CSF but compressible arachnoid injection. Similar events may occur
in the syringe, i.e. bounces; judgement of with iv placement of the tip.
loss of resistance is therefore harder. Neckache - a 0.2 m filter is attached to the proximal end of
is common and thought to be caused by small the catheter to reduce bacterial contamination
air emboli (may be detected by sensitive and injection of fragments from ampoules.
Doppler ultrasound). Pneumocephalus has - test doses of 23ml local anaesthetic (or bigger
been reported. volumes if low concentrations are used) are com-
- local anaesthetic: may be less painful during monly used to detect accidental subarachnoid or
insertion, but risks iv or subarachnoid intravascular placement of the catheter, although
injection. their use is controversial.
- continuous pressure is applied to the plunger as - single or fractionated injections are controversial,
the needle is advanced, until a sudden give is felt. as above.
Alternatively, pressure is applied intermittently - assessment and management of blockade: as for
after each (small) advance of the needle. The spinal anaesthesia.
former technique is thought to be more likely to Thoracic block:
push the dura away from the needle when the especially useful for postoperative analgesia and
epidural space is entered. In either case, the oper- pain relief following trauma. Allows selective block-
ators other hand controls advancement, e.g. by ade of required thoracic segments with sparing of
placing the back of the hand against the patients lower segments.
back and gripping the needle firmly between general principles are as above. The paramedian
thumb and fingers. approach is usually employed as thoracic spinous
- high resistance to injection is encountered whilst processes are angled more steeply caudally, making
the needle tip is in the ligamentum flavum; sudden the median approach difficult. The negative pres-
loss of resistance with easy injection occurs when sure is of greatest magnitude in the thoracic region;
the epidural space is entered. this may aid identification of the epidural space.
 Epidural anaesthesia 213

the needle is inserted lateral to the interspace below injection of local anaesthetic is performed with
that to be blocked, and directed slightly medially to care in case the catheter still lies (at least par-
encounter the lamina. It is then walked off cranially tially) within a vein.
to enter the ligamentum flavum. - epidural haematoma: as for spinal anaesthesia.
a catheter technique is almost always used. Recommendations for patients receiving low-
Cervical block: has been performed for pain therapy, molecular-weight heparin (LMWH): in fully anti-
and for carotid artery, thyroid and arm surgery. coagulated patients an interval of 24h should be
General principles are as above. allowed between the last dose and insertion/
Solutions used: removal of an epidural catheter; this is reduced to
bupivacaine, levobupivacaine or ropivacaine 0.25 12h in those receiving lower-dose LMWH for
0.75%, and lidocaine 12%, are most commonly DVT prophylaxis. The first dose of LMWH may
used in the UK. Onset with bupivacaine is about be given 24h after removal of the catheter (e.g.
1530min; effects last about 1.52.5h. Lower con- immediately postoperatively).
centrations of bupivacaine ( 0.1%), especially - dural tap: usually obvious if caused by the epidu-
combined with opioids, e.g. fentanyl 24g/ml, ral needle, as CSF flows back. Puncture by the
are commonly used to provide analgesia whilst epidural catheter may be harder to detect; flow of
allowing mobility, particularly in obstetrics and for CSF may not be obvious, especially if saline was
postoperative analgesia (see Spinal opioids). Infu- used to identify the epidural space.
sions ( 1520ml/h) or boluses ( 20ml) may be - shearing of the catheter tip: should be docu-
used; the former are especially common postopera- mented and the patient informed. Thought not to
tively since the duration of action is shorter than have adverse effects.
with concentrated solutions. Onset with lidocaine - knotting of the catheter is possible if excessive
is about 515min; effects last about 11.5h if 1: lengths are inserted.
200000 adrenaline is added. Higher concentrations following injection of drug:
are used if muscle relaxation is required. Alkalin- - hypotension as for spinal anaesthesia.
ised solutions produce faster onset of denser - local anaesthetic toxicity due to systemic absorp-
blockade. tion or iv injection.
lumbar blockade: 1030ml is usually adequate. - extensive blockade:
Rough guide: 1.5ml/segment to be blocked, - accidental spinal blockade (subarachnoid):
including sacral segments; 1.0ml/segment if over onset is usually within a few minutes. May lead
50 years or in pregnancy; 0.75ml/segment if over to total spinal block if a large amount of drug is
80 years. injected, with rapidly ascending motor and
Reduction of requirement with age is thought to be sensory blockade, respiratory paralysis and
due to decreased leakage, e.g. through interverte- central apnoea, cranial nerve involvement with
bral foramina. The above scheme does not take into fixed dilated pupils and loss of consciousness.
account body size or site of injection/catheter Management includes oxygenation with tra-
insertion. cheal intubation and IPPV, and cardiovascular
Effect of gravity: the dependent side tends to support. Recovery without adverse effects is
experience faster and denser block. usual if hypoxaemia and hypotension are
thoracic block: 35ml is used to block 24 segments avoided.
at the required level. - subdural blockade: piercing by the catheter of
cervical block: 68ml is usually used. the dura but not arachnoid. Onset is typically
tachyphylaxis is common; it may be related to local within 2030min; blockade may be unilateral
pH changes but the precise mechanism is unclear. and include cranial nerve lesions. The arachnoid
Effects: similar to spinal anaesthesia, but block (and may rupture if large volumes are injected,
hypotension) are slower in onset. Density of block leading to high or total spinal block.
and muscle relaxation are less, with greater incidence - unexplained, with correct epidural placement of
of incomplete block. Motor block may be assessed the catheter. Partial subarachnoid or subdural
using the Bromage scale. catheter placement is thought to be responsible
Contraindications: as for spinal anaesthesia. for the many patchy blocks encountered in
Complications: practice. Catheter migration may occur during
related to insertion of needle/catheter: prolonged blockade, e.g. in obstetrics.
- trauma: - isolated cranial nerve palsies, e.g. fifth and
- local bruising/pain. sixth, and Horners syndrome, have been
- neurological damage is rare, although restric- reported.
tion of the technique to awake patients has been Extensive blocks may develop after top-up injec-
suggested, especially for thoracic or cervical tions during apparently normal epidural blocks.
block. This suggestion is controversial. - incomplete blockade: missed segments/unilateral
- bloody tap: if bleeding occurs through the needle, block. Management: as for obstetric analgesia and
it should be withdrawn and a different space used. anaesthesia.
If blood is obtained through the catheter (vigor- - nerve damage due to injection of incorrect drugs/
ous aspiration is avoided as it may collapse the solutions. In addition, preservatives in certain
veins), withdrawal of the catheter 1cm following preparations of local anaesthetics are suspected
saline flushing may be performed. If blood is still to be neurotoxic, as are skin cleansing solutions.
obtained, the catheter should be removed and a - shivering.
different space used. If no further flow of blood - prolonged blockade: uncommon; has lasted up to
occurs, the catheter may be fixed. Subsequent 812h after the last injection.
214 Epidural opioids

- anterior spinal artery syndrome: thought to be 5: ligamentum flavum (between laminae of adjacent
related to severe hypotension, not to the tech- vertebrae).
nique itself. 6: epidural space.
- adverse drug reactions to agents used: rare. The normal distance between the skin and the epidural
late: space varies between 2 and 9cm.
- arachnoiditis, cauda equina syndrome. For the lateral approach: 1, 2, 5, 6.
- abscess formation/meningitis: thought to be rare See also, Epidural anaesthesia; Vertebrae; Vertebral
if aseptic techniques are used. ligaments
[Fidel Pages (18861923), Spanish surgeon; Achilles
Dogliotti (18971966), Italian surgeon; Edward B Tuohy Epidural volume expansion, see Combined spinal
(19081959), US anaesthetist; John Alfred Lee (1906 epidural anaesthesia
1989), Southend anaesthetist; Oral B Crawford, US
anaesthetist] Epiglottis, see Larynx

Epiglottitis. Infective inflammation of the epiglottis,

Epidural opioids, see Spinal opioids often resulting in upper airway obstruction. Caused by
Haemophilus influenzae type b in over 50% of cases.
Most common in children aged 25 years but may also
Epidural space. Continuous space within the vertebral occur in adults (usually aged 2040 years); the incidence
column, extending from the foramen magnum to the in the UK has fallen since a specific vaccine was intro-
sacrococcygeal membrane of the sacral canal. The verte- duced. Classically follows an acute course, with fever,
bral canal becomes triangular in cross-section in the marked systemic upset, stridor and adoption of the
lumbar region, its base anterior; the epidural space is sitting position with the jaw thrust forward and an open
that part external to the spinal dura. It is very narrow drooling mouth. These features, plus absence of cough,
anteriorly, and up to 5mm wide posteriorly. help distinguish it from croup. Epiglottitis may progress
Boundaries: to complete airway obstruction, which may be provoked
internal: dura mater of the spinal cord (at the by pharyngeal examination and anxiety (e.g. due to iv
foramen magnum, reflected back as the periosteal cannulation). Although lateral X-rays of the neck may
lining of the vertebral canal). reveal epiglottic enlargement, they may also provoke
external: obstruction, and clinical assessment is sufficient in
- posteriorly: ligamenta flava, and periosteum lining severe cases. Pulmonary oedema may occur if obstruc-
the vertebral laminae. tion is severe.
- anteriorly: posterior longitudinal ligament. Management:
- laterally: intervertebral foramina, and periosteum assessment:
lining the vertebral pedicles. The space may - general state: exhaustion, toxaemia, etc.
extend through the intervertebral foramina into - respiratory distress: stridor, use of accessory respi-
the paravertebral spaces. ratory muscles, including flaring of the nostrils,
Contains epidural fat, epidural veins (Batsons plexus), intercostal and suprasternal recession, tachy-
lymphatics and spinal nerve roots. Connective tissue pnoea, cyanosis.
layers have been demonstrated by radiology and endos- experienced anaesthetic, paediatric and ENT help
copy within the epidural space, in some cases (rarely) should be sought.
dividing it into right and left portions. humidified O2 administration.
Pressure in the epidural space is found to be negative nebulised adrenaline (0.4ml/kg [400g/kg] of a
in most cases, occasionally positive. Postulated expla- 1:1000 racemic solution to a maximum of 5ml
nations include: [5mg]).
artefactual or transient negative pressure: iv fluids and antibacterial drugs are required,
- anterior dimpling of the dura by the needle. although iv cannulation should not be attempted
- anterior indentation of the ligamentum flavum by before relief of the airway obstruction. Third-
the needle, followed by its sudden posterior recoil generation cephalosporins are the drugs of choice
when punctured. because of increasing resistance to the traditionally
- back flexion causing stretching of the dural sac, used chloramphenicol or ampicillin.
and/or squeezing out of CSF. anaesthesia is as for airway obstruction; commonly
true negative pressure: inhalational induction using sevoflurane in O2 with
- transmitted negative intrapleural pressure via the patient sitting until tracheal intubation is pos-
thoracic paravertebral spaces. sible. Induction is usually slow. Apparatus for diffi-
- relative overgrowth of the vertebral canal com- cult intubation plus facilities for urgent tracheostomy
pared with the dural sac. must be available. Atropine may be given once an
- true positive pressure: bulging of dura due to iv cannula is sited. An oral tracheal tube is passed
pressure of CSF. initially, and is changed for a nasal tube to allow
Passage taken by an epidural needle when entering better fixation and comfort.
the epidural space (median approach): intubation is usually required for less than 24h.
1: skin. Spontaneous ventilation is usually acceptable.
2: subcutaneous tissues. Humidification is essential. Sedation may not be
3: supraspinous ligament (along the tips of spinous required, but care must be taken to avoid accidental
processes from C7 to sacrum). extubation.
4: interspinous ligament (between spinous processes extubation is performed when the clinical condition
of adjacent vertebrae). has improved, and a leak is present around the tube.
 Erg 215

members of the patients household should receive Epistaxis. Nasal bleeding. May occur from:
prophylactic antibacterial agents. veins of the nasal septum (younger patients).
See also, Paediatric anaesthesia arterial anastomoses of the lower part of the nasal
septum (Littles area), especially in older patients.
May be associated with hypertension.
Epilepsy. Tendency to epileptic seizures, associated with
Usually follows trauma, but predisposing conditions
abnormal or excessive hypersynchronous neuronal
include bleeding disorders, hereditary telangiectasia and
activity within the brain.
Traditionally classified into:
raised venous pressure. Bleeding may be caused by nasal
intubation or passage of a nasal airway, especially if a
generalised:
vasoconstrictor (e.g. cocaine) is not used first.
- grand mal (tonicclonic convulsions): tonic (sus-
Usually managed by nasal packing but may require
tained muscle contraction) followed by clonic
ligation of the maxillary or anterior ethmoidal arteries,
(jerking) phases lasting about 30s each, with loss
the former via the neck or oral route, the latter from the
of consciousness. May be preceded by prodromal
front of the nose.
symptoms hours or days before, and an aura
Anaesthetic management is similar to that of the
minutes before.
bleeding tonsil (see Tonsil, bleeding).
- petit mal (absence seizures): characterised by
[James L Little (18361885), US surgeon]
3Hz synchronised spikes on the EEG. May
present as inattentive staring or head-banging;
EPLS, see European Paediatric Life Support
despite appearances, the patient is not conscious
during these seizures.
Epoprostenol, see Prostacyclin
- other types of generalised seizures include atonic
and myoclonic.
EPSP, Excitatory postsynaptic potential, see Synaptic
partial (focal):
transmission
- may occur with (complex partial) or without
(simple partial) derangement of consciousness.
Eptacog alfa. Recombinant activated coagulation factor
- classic presentations:
VIIa. Prohaemostatic agent that activates the coagula-
- temporal: associated with auditory, visual or
tion cascade mainly via factors IX and X. Used for
olfactory hallucinations and emotional or mood
patients with complicated coagulation disorders, both
changes.
pre-existing (e.g. certain types of haemophilia) and
- Jacksonian: clonic movements spreading from
acquired, e.g. after major surgery or trauma. Because of
an extremity, e.g. single digit, to involve the
the difficulty studying the latter group, most experience
whole body.
is limited to case series and anecdotal reports and this,
Definition of disease is difficult because certain stimuli
along with the high cost of the preparation (~500 per
will induce convulsions in normal subjects, e.g. hypoxia,
mg), makes its use controversial. Associated with a 12%
hypo/hyperglycaemia. Usually idiopathic, especially
incidence of thrombotic complications, adding to the
in childhood; intracranial lesions and infections (e.g.
controversy. Requires functioning platelets and normal
encephalitis) must be excluded in adults presenting with
fibrinogen levels for maximal clinical effect.
a single seizure. Pyrexia is a common cause in children; Dosage: 90120g/kg iv over 35min, repeated 2
other causes are as for convulsions.
6-hourly (N.B. not currently licensed for use in coagu-
Treatment is with anticonvulsant drugs, and is directed
lopathy related to trauma/surgery).
at any underlying cause. Side effects: hypersensitivity, arterial and venous
Anaesthetic considerations:
thrombosis.
preoperative assessment: frequency of seizures, date
Levi M, Peters M, Buller HR (2005). Crit Care Med; 33:
of last seizure, drug therapy (including measure-
88390
ment of blood levels where appropriate). Identifica-
tion of cause if known.
Eptifibatide. Antiplatelet drug, used in some acute coro-
therapy is continued throughout the perioperative
nary syndromes. Acts by reversibly inhibiting activation
period; benzodiazepines are often used for premed-
of the glycoprotein IIb/IIIa complex on the surface of
ication because of their anticonvulsant activity.
platelets.
anaesthetic drugs associated with convulsions are
Dosage: 180g/kg iv followed by 2g/kg/min for up
avoided, e.g. enflurane, ketamine. Although propo-
to 72h (96h if percutaneous coronary intervention
fol may activate the EEG at low concentrations and
performed).
may cause myoclonic jerks, it is used successfully to Side effects are related to increased bleeding. Platelet
treat status epilepticus. Thiopental, halothane and
function takes up to 24h to return to normal after
isoflurane have anticonvulsant properties and are
discontinuation of therapy.
therefore the traditional drugs of choice. Doxa-
pram, naloxone and tramadol are avoided. Hypo-
Equivalence. Amount of a substance divided by its
capnia lowers the seizure threshold.
valence. Equivalent weight (gram equivalent) is the
anticonvulsant therapy is restarted as soon as pos-
weight of substance combining with or chemically equiv-
sible postoperatively.
alent to 8g O2, or 1g hydrogen.
[John Hughlings Jackson (18351911), English
Electrical equivalence is the number of moles of
neurologist]
ionised substance divided by valence.
Perks A, Cheema S, Mohanraj R (2012). Br J Anaesth;
108: 56271
Erg. Unit of work in the cgs system. 1 erg = work done
by a force of 1 dyne acting through a distance of 1
Epinephrine, see Adrenaline centimetre.
216 Ergometrine maleate

Ergometrine maleate. Smooth muscle constrictor, with reticulocyte count: < 2% of red cells. Increased in
potent effects on uterine and vascular tone; used to red cell loss from haemolysis or haemorrhage, sig-
reduce postpartum or post-termination uterine bleeding. nifying a normal bone marrow response. Also
Uterine contraction occurs 5min after im injection and increased in treatment of deficiency anaemias.
1min after iv injection; it lasts up to an hour. Slowly mean corpuscle volume (MCV): 80100fl.
being replaced by synthetic oxytocin because of its Decreased in iron deficiency or defective haemo-
adverse effects (nausea, vomiting and vasoconstriction globin synthesis. Increased when reticulocyte count
causing a marked rise in BP and CVP; the latter is exac- is increased, or due to megaloblastic cell formation
erbated by autotransfusion of blood from the uterus, and (e.g. vitamin B12/folate deficiency). Also increased
lasts up to several hours). Therefore hazardous in in alcoholism.
patients with cardiovascular disease, particularly pre- mean corpuscle haemoglobin (MCH): 2634pg.
eclampsia. Despite this, it is often given routinely com- mean corpuscle haemoglobin concentration
bined with oxytocin at the end of the second stage of (MCHC): 3236g/dl. Decreased in iron deficiency
labour. An aggravating role of ergometrine-induced or defective haemoglobin synthesis.
vasoconstriction has been suggested in aspiration pneu- erythrocyte sedimentation rate (ESR): < 10mm/h.
monitis. Has been used as a vasopressor, e.g. in spinal Measure of the rate at which red cells settle when
anaesthesia. a column of blood is left for 1h. High values indi-
Dosage: 0.10.5mg im/iv; 0.51.0mg orally. cate reduced settling. Increased in many inflamma-
See also, Uterus tory, autoimmune and infective diseases, malignancy,
old age and pregnancy.
Error, fixation, see Fixation error Examination of the peripheral blood film gives infor
mation about haematological disease, e.g. abnormally
shaped erythrocytes (sickle cell anaemia, hereditary
Errors, statistical. In statistics, may lead to incorrect
spherocytosis, target cells in impaired haemoglobin
conclusions because of inadequate test design and analy-
production or liver disease).
sis, too small a sample size or inaccurate data collection.
See also, Erythropoiesis
Include:
type I (; false positive): acceptance of a result as
Erythromycin. Macrolide-type antibacterial drug with
not due to chance when it is (i.e. false rejection of
similar spectrum to penicillin; thus a useful alternative
the null hypothesis). Represented by the P value
in penicillin allergy. Especially useful in respiratory
(probability); a value of 0.05 is usually accepted as
infections (including Legionnaires disease and Myco-
the maximum acceptable.
plasma infections) and staphylococcal infections. Also
type II (; false negative): rejection of a result as
promotes GIT activity via stimulation of GIT motilin
due to chance when it is not (i.e. false acceptance of
receptors; used as a prokinetic drug in ileus (given iv or
the null hypothesis). A value of 0.2 is usually con-
via nasogastric tube).
sidered the maximum acceptable. Dosage:
It is thus easier to demonstrate a non-significant
250mg1g orally qds.
result than a significant one. As the required P value
50mg/kg/day by iv infusion or in divided doses.
is made smaller, the risk of rejecting a real result Side effects: nausea, vomiting, abdominal pain, diar-
(i.e. type II error) increases (assuming a constant
rhoea, rash, reversible hearing loss, arrhythmias, pain
sample size). Errors may limit the usefulness of an inves-
on iv injection.
tigation described by its sensitivity, specificity and pre-
dictive value.
Erythropoiesis. Formation of erythrocytes, usually
restricted to the vertebrae, sternum, ribs, upper long
Ertapenem. Broad-spectum carbapenem and antibacte- bones and iliac crests in adults. Requires iron, vitamin
rial drug, active against Gram-positive organisms and B12 and folate, and possibly other vitamins and minerals.
anaerobes, but not against pseudomonas or acineto- Stepwise differentiation from stem cells includes haemo-
bacter species, unlike imipenem or meropenem. globin synthesis and nuclear extrusion to form reticulo-
Dosage: 1g iv od.
cytes, taking about 7 days. Regulated by erythropoietin.
Side effects: as for imipenem.

Erythropoietin. Glycoprotein hormone secreted mainly

Erythrocytes (Red blood cells). Biconcave discs, about by the kidneys, but also by the liver. Secretion is increased
2 m thick and 8 m in diameter and without nuclei. by haemorrhage and hypoxia (possibly via prostaglandin
Produced by red bone marrow. Contain haemoglobin, synthesis), and inhibited by increased numbers of circu-
maintained in an appropriate state for O2 transport (i.e. lating erythrocytes. Causes increased erythropoiesis.
containing iron in the reduced state, in the presence of Erythropoietin receptors are present in erythrocytes,
2,3-DPG). Also have an integral role in carbon dioxide bone marrow and on central and peripheral neurones;
transport. Maintenance of structural integrity and the latter are involved in neuronal development and
osmotic stability is via membrane pumps; the main repair. Infusion of erythropoietin produced by recombi-
energy source is aerobic glycolysis. nant genetic engineering has been used to treat anaemia
Circulating lifespan is about 120 days; they are in renal failure, but treatment is very expensive. It has
removed by the reticuloendothelial system and broken also been used to increase the yield of blood collected
down, with salvage and reuse of iron and amino acids for autologous blood transfusion, e.g. 300U/kg thrice
from haemoglobin. weekly, reducing to 100U/kg after 2 weeks. The first
Normal laboratory findings (adult): dose given iv produces higher levels; subsequent sc
red cell count (RBC): 4.56.0 10 /l blood (male);
12
dosage produces a more sustained effect. Red cell aplasia
4.05.2 1012/l blood (female). has been reported following its sc use in renal failure.
 Ethyl alcohol 217

Escape beats. On the ECG, complexes arising from sites justice: the right to receive what is deserved.
other than the sinoatrial node, when the latter does not Although easy in certain circumstances (e.g. require-
discharge (i.e. sinus arrest or severe bradycardia). Dis- ment for dialysis in acute kidney injury), other
tinct from ectopic beats, which arise prematurely in the situations may be less clear (e.g. liver transplanta-
cardiac cycle. tion in chronic alcoholism). Overlaps with equity
(fairness), manifested in arguments over rationing
Esmolol hydrochloride. Cardioselective -adrenergic of healthcare.
receptor antagonist, with no intrinsic sympathomimetic The principles underlying ethical practice are not mutu-
activity. Hydrolysed by red blood and other esterases, ally exclusive and may even oppose one another, e.g.
with a half-life of 9min. Used to treat AF, atrial flutter withholding blood from a Jehovahs Witness respects
and SVT, and during anaesthesia to prevent/treat tachy- his/her autonomy whilst not practising beneficence/
cardia and hypertension, e.g. associated with tracheal non-maleficence.
intubation. Has been used in hypotensive anaesthesia. The above approach (principlism) is favoured by
Dosage: many because it is relatively simple and easy to under-
SVT, etc.: 500g/kg/min loading dose iv for 1min, stand, though there are many other systems for judging
then 50150g/kg/min maintenance titrated to the moral value of medical decisions, such as consequen-
effect. tialism (judgement according to the outcomes of deci-
perioperative use: 0.51.0mg/kg iv over 1530s, fol- sions) and rights-based approaches.
lowed by 50300g/kg/min infusion. Anaesthetic/ICU implications include:
Side effects: bradycardia, hypotension, sweating, informed consent.
nausea, confusion, thrombophlebitis, pain on injec- patients rights to confidentiality, including non-
tion. Bronchospasm may occur in susceptible patients. disclosure of records without permission, although
the doctor has statutory duties that may override
Esophagus, see Oesophagus this (e.g. reporting of notifiable diseases, births and
deaths).
ESR, Erythrocyte sedimentation rate, see Erythrocytes HIV infection: there is a moral duty to treat infected
patients as well as taking steps to protect oneself. A
Etamsylate (Ethamsylate). Haemostatic drug, thought doctor who has reason to believe that he/she is
to reduce bleeding by correcting abnormal platelet infected has a duty to seek advice and testing.
adhesion. Does not affect fibrinolysis. Has been used to the duty to seek Research Ethics Committee
prevent and treat periventricular haemorrhage in pre- approval and informed consent for research.
mature babies (12.5mg/kg im/iv qds). the duty to protect patients from sick and incompe-
tent medical colleagues (see Sick Doctor Scheme).
Ethambutol hydrochloride. Antituberculous drug do not attempt resuscitation orders and advance
added to triple therapy (isoniazid, rifampicin, pyrazin- decisions.
amide) if resistance is suspected. admission criteria for, and rationing of, intensive
Dosage: 25mg/kg orally od for 2 months, then 15mg/ care.
kg daily for 6 months. withholding or withdrawal of treatment (including
Side effects: visual disturbances, peripheral neuritis, surgery) in cases of medical futility.
rash, thrombocytopenia. Requires monitoring of management of terminal and palliative care.
plasma levels (peak 26mg/l; trough < 1mg/l). euthanasia.
Waisel DB, Truog RD (1997). Anesthesiology; 87:
Ethamsylate, see Etamsylate 41117

Ethanol, see Alcohols Ethmoidal nerve block, anterior, see Ophthalmic nerve
blocks
Ethanol poisoning, see Alcohol poisoning
Ethoheptazine citrate. Analgesic drug, used for mild/
Ether, see Diethyl ether
moderate pain. Combined with meprobamate, a sedative
muscular antispasmodic, and aspirin. Not available in the
Ethics. Principles of moral behaviour; often translated
UK.
into medical practice by reference to four basic Dosage: 75150mg orally tds.
concepts: Side effects are largely related to meprobamate and
autonomy: the right of a fully informed individual
include drowsiness and hypersensitivity.
to choose a course of action (or inaction).
beneficence: the obligation to do good; may not nec-
essarily lie in preserving life if that life is of such Ethosuximide. Anticonvulsant drug used in petit mal
poor quality (e.g. because of pain or severe disabil- epilepsy and myoclonic seizures. Thought to block T-type
ity) that it is considered less beneficial for the calcium channels in thalamic neurones.
Dosage: 500mg1.5g orally daily. Therapeutic plasma
patient than death.
non-maleficence: the obligation to avoid doing concentration 40100mg/l.
Side effects: GIT disturbance, drowsiness, psychiatric
harm (primum non nocere). Difficulties may arise
if beneficial medical interventions also cause disturbance, rash, hepatic and renal impairment,
harm (recognised in the doctrine of double effect), blood dyscrasias.
e.g. administration of morphine to a terminally
ill patient to relieve pain, even though it may Ethyl alcohol, see Alcohol poisoning; Alcohol with-
hasten death. drawal syndromes; Alcoholism; Alcohols
218 Ethyl chloride

Ethyl chloride. Inhalational anaesthetic agent, first - reduces cerebral blood flow and intraocular
described in 1848; popular in the 1920s particularly for pressure.
induction of anaesthesia because of its rapid action. other:
Extremely volatile (boiling point 13C) and difficult to - increases the incidence of PONV.
control; also inflammable. Now used solely for its cooling - does not cause histamine release.
action when sprayed on to skin, to cause anaesthesia Metabolism:
before minor procedures or to test the extent of regional rapidly metabolised by plasma esterases and liver
blockade. enzymes; elimination half-life is about 70min.
Largely excreted via the urine. Not cumulative.
Ethylene. Inhalational anaesthetic agent, used clinically interferes with adrenal corticosteroid synthesis by
in 1923. A gas of similar blood/gas solubility to N2O, but inhibiting 11--hydroxylase and 17--hydroxylase.
more potent. Also extremely explosive and unpleasant IV infusion for sedation on ICU increases mortality;
to inhale. Cylinder body and shoulder are coloured it is now contraindicated for this purpose. Following
violet. a single induction dose, the rise in plasma cortisol
normally seen after surgery is delayed for up to 6h.
Ethylene glycol poisoning, see Alcohol poisoning The significance of this is disputed.
Dose: 0.20.3mg/kg.
Ethylene oxide, see Contamination of anaesthetic
equipment Etorphine hydrochloride. Analogue of thebaine, a nat-
urally occurring opioid. 10003000 times as potent as
Etidocaine hydrochloride. Local anaesthetic agent morphine. Used to immobilise large animals.
introduced in 1972, derived from lidocaine. Onset is
rapid, and duration of action is similar to that of bupiva- European Academy of Anaesthesiology (EAA).
caine. Produces motor blockade that may exceed sensory Founded in 1978 to improve standards, training and
blockade. Used in 11.5% solutions. Maximal safe dose research in anaesthesia. Organises the European
is 2mg/kg. Not available in the UK. Diploma in Anaesthesiology and Intensive Care. Amal-
gamated with the European Society of Anaesthesiolo-
Etomidate. IV anaesthetic agent, introduced in 1973. gists and the Confederation of European National
A carboxylated imidazole (five-membered ring contain- Societies of Anaesthesiologists to form the European
ing three carbon atoms and two nitrogen atoms) com- Society of Anaesthesiology in 2005.
pound (Fig. 64), presented in 35% propylene glycol; pH Thomson D (1995). Acta Anaesth Scand; 39: 4424
is 8.1. 75% bound to plasma proteins after injection. See also, European Federation of Anaesthesiologists
Methoxycarbonyl-etomidate (MOC-etomidate) is a new
etomidate analogue that is rapidly metabolised and does European Board of Anaesthesiology (EBA). Govern-
not cause adrenocortical suppression (see below). ing body for specialist anaesthetic training within the
Effects: European Union, under the auspices of the European
induction: Union of Medical Specialties, which was founded in
- rapid onset of anaesthesia, lasting up to 8min 1958. Works with the various anaesthetic bodies in
after a single dose. member states.
- muscle contractions are common; reduced by use Scherpereel P (1995). Acta Anaesth Scand; 39: 4389
of opioids.
- pain is common when injected into small veins; European Diploma in Intensive Care Medicine
reduced by mixing with 12ml 1% lidocaine. (EDIC). Organised by the European Society of
Thrombosis is rare. Intensive Care Medicine since 1989. Consists of an
CVS/RS: English written (multiple choice) examination and an
- causes less hypotension than propofol and thio- oral/clinical one (usually in the country and language of
pental; thus often used in shocked patients, the the examinee), together with a requirement for a basic
elderly and those with cardiovascular disease. medical specialty and 2 years intensive care medicine
- respiratory depression is less than with training.
thiopental.
CNS: European Diploma in Anaesthesiology and Intensive
- not analgesic. Care (EDAIC). Examination held since 2005 by the
- not associated with epileptiform discharges. European Society of Anaesthesiology, having taken
over this function from the European Academy of
Anaesthesiology, which ran it from 1984. Available in
multiple languages; consists of two parts (written and
O oral), each covering basic science and clinical topics. Pass
N rates are in the order of 60% and 80% respectively.
CH3 CH2 O C C
There is also an optional in-training assessment part.
N Zorab JSM (1995). Acta Anaesth Scand; 39: 57981
CH3 C H
European Federation of Anaesthesiologists (EFA).
Umbrella organisation formed in 2001 to coordinate
the activities of and encourage cooperation between
the European Academy of Anaesthesiology, European
Society of Anaesthesiologists and Confederation of
Fig. 64 Structure of etomidate European National Societies of Anaesthesiology.
 Evoked potentials 219

Adopted the European Journal of Anaesthesiology as programme PACT. Intensive Care Medicine is its
its official journal. official journal.

European Journal of Anaesthesiology. Established in European Society of Paediatric and Neonatal Inten-
1984. The official journal of the European Society of sive Care (ESPNIC). Founded and based in Brussels to
Anaesthesiology, having been the official journal of the advance and promote paediatric and neonatal intensive
European Academy of Anaesthesiology, the European care. Has medical and nursing branches. Holds an annual
Society of Anaesthesiologists, the Confederation of congress and has Intensive Care Medicine as its official
European National Societies of Anaesthesiology, Fon- journal.
dation Europenne dEnseignement en Anaesthsiolo-
gie and European Union of Medical Specialties (since European Union of Medical Specialties (Union
1999) and the European Federation of Anaesthesiolo- Europenne des Mdecins Spcialistes; UEMS), see
gists (since 2001). European Board of Anaesthesiology

European Medicines Evaluation Agency (EMEA). Euthanasia. Intentional ending of a patients life for his
Body established in 1995 to regulate the introduction or her benefit, e.g. to relieve intolerable and incurable
and investigation of new drugs throughout Europe, and suffering. May be voluntary if administered to a compe-
to ease communication between the various national tent person in response to his or her informed request,
regulatory bodies. Thus acts as a link between the Com- or non-voluntary if administered to an incompetent
mittee on Safety of Medicines in the UK and similar person. Distinction is also made between active eutha-
bodies in other countries. nasia, in which medical intervention hastens death, and
Herxheimer A (1996). Br Med J; 312: 394 passive euthanasia, in which life-sustaining treatment is
withheld or withdrawn (e.g. enteral feeding). Assisted
suicide differs in that the physician provides the mecha-
European Paediatric Life Support (EPLS). Collabora-
nism for death but the patient administers the lethal
tion between the European Resuscitation Council and
agent. Euthanasia remains illegal throughout the world
the Resuscitation Council (UK). The EPLS course pro-
except in the Netherlands, where it was legalised in 2000,
vides training for healthcare professionals in the early
Belgium (2002) and Luxembourg (2009), all with formal
recognition of the child in respiratory or circulatory
guidelines laid down for its use. Assisted suicide is legal
failure and the prevention of respiratory or cardiorespi-
in Switzerland (since 1941) and the states of Montana,
ratory arrest.
Oregon and Washington in the USA.
Emanuel EJ (2002). Arch Intern Med; 162: 14252
European Resuscitation Council (ERC). Formed in
1989 with a mandate to produce guidelines and recom- EVE, Epidural volume expansion, see Combined spinal
mendations appropriate to Europe for the practice of epidural anaesthesia
basic and advanced cardiopulmonary and cerebral
resuscitation. Composed of elected representatives from Evoked potentials (EPs). Electrical activity recorded
the participating European countries. Held its first major from the CNS or peripherally following peripheral or
international conference in 1992. Regularly produces central stimulation. Used to investigate demyelinating
guidelines regarding basic and advanced CPR. Resusci- disease, neuropathies and brain tumours, and in moni-
tation is its official journal. toring of head injury and coma. Also used to monitor
See also, Resuscitation Council (UK); International and investigate depth of anaesthesia or CNS integrity
Liaison Committee on Resuscitation during surgery.
Requires complex equipment to increase recording
European Society of Anaesthesiology (ESA). Formed sensitivity and reduce interference. Recorded potentials
in 2005 by the amalgamation of the European Society of are small (usually 12 V) compared with background
Anaesthesiologists, the European Academy of Anaes- electrical activity (over 100 V); the signal is amplified
thesiology and the Confederation of European National and (random) background activity averaged out using
Societies of Anaesthesiologists. Seeks to provide all the computer averaging. Filters reduce noise. Displayed as a
educational and regulatory activities of the three com- plot of voltage against time; a stimulation spike occurs
ponent organisations. Adopted the European Journal of within 1 ms, followed by a composite pattern represent-
Anaesthesiology as its official journal. Representation of ing potentials from near and distant structures along the
different nationalities within the organisation is via indi- conduction pathway, depending on the sites of stimula-
vidual members (who are all eligible to join the ESAs tion and recording. Upward peaks represent negative
various committees) and the National Anaesthesia Soci- potentials by convention. Latency is the time between
eties Committee (NASC). the stimulation spike and the first major peak; amplitude
Priebe HJ (2005). Eur J Anaesth; 22: 13 is the height from this peak to the following trough.
Different types:
European Society of Intensive Care Medicine sensory EPs:
(ESICM). Founded in 1982 in Geneva to advance knowl- - somatosensory (SEPs):
edge, research and education in intensive care medicine, - supramaximal stimulation of the posterior tibial
and subsequently to improve facilities for intensive care or median nerves. Direct spinal cord stimulation
medicine in Europe. Holds an annual congress, organises may be performed to monitor cord integrity
the European Diploma in Intensive Care Medicine and during spinal surgery.
administers several multicentre and multinational - recording from:
surveys, e.g. the European Consortium for Intensive - scalp EEG electrodes, e.g. one over the
Care Data (ECICD). Also administers the educational sensory area appropriate to the site of
220 Exercise

stimulus plus a reference electrode else- Exercise. Produces physiological changes that increase
where. May also examine transmission oxygen flux and removal of waste products from active
between different sites along the conduction tissues:
pathway, e.g. central conduction time (CCT) cardiovascular:
between activity at the level of C5 to cortical - increased cardiac output mainly due to increased
activity. heart rate (to a maximum rate of about 195 beats/
In general, most anaesthetic agents increase min in adults). Stroke volume increases slightly in
latency and decrease amplitude (etomidate normal individuals, although it can double in
consistently increases amplitude) in a dose- trained athletes. The increase in cardiac output
related manner. Amplitude increases follow- starts before exercise due to cortical activation of
ing tracheal intubation or skin incision, the sympathetic nervous system. Following initia-
suggesting SEPs represent magnitude of stim- tion of exercise, CVS reflexes are activated fol-
ulus rather than anaesthetic depth. The tech- lowing stimulation of muscle mechanoreceptors,
nique has also been used to monitor function baroreceptors and joint receptors.
during craniotomy, e.g. measuring CCT: - BP increases (systolic > diastolic), reflecting
impaired conduction may represent physical increased cardiac output despite decreased SVR
damage, hypoxia or ischaemia. due to vasodilatation in exercising muscles.
- epidural space in spinal surgery; e.g. bipolar - increased venous return due to increased skeletal
electrodes placed via an epidural needle at muscle pump activity and thoracic pump action.
the lower cervical level. Electrodes may also - blood flow is diverted to skin and actively con-
be placed in the subdural space if the dura is tracting muscles at the expense of renal and
opened. Skin/vertebral recording is less splanchnic blood flow. Muscle blood flow may
reliable. increase 30-fold as a result of accumulation of
Anaesthetic agents have minimal effects local metabolites (e.g. K+, lactic acid), a decrease
on spinal evoked potentials; the technique is in arterial PO2 and an increase in PCO2. Arterio-
useful for investigating spinal conduction at venous O2 difference may increase threefold due
any anaesthetic depth. Each side is tested to a shift of the oxyhaemoglobin dissociation
individually; amplitude reduction greater than curve to the right secondary to the acidosis, raised
50% during surgery is likely to indicate post- temperature in muscles and raised 2,3-DPG levels
operative neurological deficit. Used for found during exercise.
surgery for kyphoscoliosis, tumours, vascular - coronary blood flow may increase to up to five
lesions, etc., also for surgery to the brachial times the resting level.
plexus, aortic arch, etc. respiratory:
- auditory (AEPs): - increased minute ventilation due to increase in
- stimulation of the eighth cranial nerves with respiratory rate and tidal volume. The increase is
audible clicks, usually at 610Hz. proportional to the rise in oxygen demand and is
- recording from scalp electrodes (e.g. vertex/ due to cortical stimulation and afferent impulses
mastoid), and reference on the forehead. from proprioceptors in muscles, tendons and
- recorded pattern represents brainstem, and joints.
early and late cortical responses. Brainstem - pulmonary blood flow increases up to sixfold.
EPs are little affected by anaesthetics; early Thus oxygen uptake by the lungs can reach
cortical EPs are most consistently affected as 4000ml/min, which exceeds cardiac oxygen deliv-
for SEPs. ery capacity.
- visual (VEPs): - CO2 excretion can reach 8000ml/min.
- stimulation of optic nerves using swimming temperature regulation: the heat produced is dissi-
goggles incorporating light-emitting diodes; pated by increased sweating, skin vasodilation and
2Hz is usually employed. heat loss through expired air.
- recording from the occiput. If extreme exercise continues, exhaustion follows; BP
- thought to be less reliable than SEPs or falls, cutaneous vasoconstriction occurs, body tempera-
AEPs, but have been used to monitor func- ture rises and accumulation of lactic acid and CO2 results
tion during surgery for lesions involving in increasing acidosis. Muscle cramps and fatigue occur.
the optic nerve and chiasma, and pituitary Exertional myoglobinuria may be seen.
gland.
motor EPs: Exercise testing. Most commonly, involves ECG record-
- stimulation of the scalp using large voltages, or ing while performing exercise, e.g. using a treadmill or
the motor cortex directly. Induction of potential bicycle, with workload increased in steps.
using magnetic fields has been used. Testing is used to help diagnose chest pain or breath-
- recording from the median or posterior tibial lessness, and to indicate prognosis in ischaemic heart
nerve, or EMG of limb muscles. Very sensitive disease, especially following MI. ST depression is the
to anaesthetic agents, thus less suitable for most significant sign during exercise, but other changes,
monitoring anaesthetic depth. Recording from e.g. ST elevation, Q waves, may occur. Chest pain, hypo-
the epidural space is thought to be less affected tension and arrhythmias may also be provoked. Testing
by anaesthetics, and has been used for spinal may be combined with other measurements, e.g. arterial
surgery. BP, respiratory rate, tidal volume, O2 consumption, CO2
Kumar A, Bhattacharya A, Makhija N (2000). Anaesthe- output, arterial blood gases and cardiac output. Reduced
sia; 55: 22541 ejection fraction (e.g. demonstrated by echocardiogra-
See also, Anaesthesia, depth of phy) or cardiac output may suggest reversible ischaemia
 Explosions and fires 221

that may persist after cessation of exercise (myocardial Regurgitation of gastric contents may occur during
stunning). expired air ventilation; this may be reduced by applica-
Inotropic drugs, e.g. dobutamine, may also be used to tion of cricoid pressure if another person is available.
provoke similar changes to those caused by exercise Various devices, some with valves, are available
(dobutamine stress test). for avoidance of direct mouth-to-mouth contact, to
Traditionally, the patients own exercise tolerance improve aesthetic acceptability and reduce risk of cross-
(e.g. maximum walking distance or stairs climbed) has contamination; most hinder efficient ventilation. An
been used as a general indicator of cardiorespiratory anaesthetic facemask is suitable. Expired air ventilation
function. More recently, formal cardiopulmonary exer- may be performed through a correctly placed tracheal
cise testing has been used to predict outcomes after tube or LMA.
major surgery, using the work at which maximal O2 con-
sumption is reached, or the work at which anaerobic Explosions, see Burns; Chest trauma; Explosions and
energy metabolism (anaerobic threshold) starts, as fires; Incident, major; Smoke inhalation; Trauma
markers of cardiopulmonary reserve.
Albouaini K, Egred M, Alahmar A, Wright DJ (2007). Explosions and fires. Occur when a substance combines
Heart; 93: 128592 with O2 or another oxidising agent, with release of
energy. Activation energy is required to start the process,
Exomphalos, see Gastroschisis and exomphalos with utilisation of energy produced to maintain combus-
tion. If the reaction proceeds very fast, large amounts of
Exotoxins. High-molecular-weight, heat-labile and anti- heat, light and sound are given out, i.e. an explosion
genic proteins produced by micro-organisms. Although occurs. Speed of reaction is greatest for stoichiometric
some bacteria produce only one significant kind of exo- mixtures.
toxin (e.g. clostridia), others produce several (e.g. strep- The following are required for explosions to occur:
tococci and staphylococci). Exotoxins and endotoxins combustible substance (fuel):
contribute to the pathogenesis of SIRS. Some are used - anaesthetic agents, e.g. cyclopropane, diethyl
clinically, e.g. botulinum toxins. ether. CC bonds are susceptible to breakdown;
CF bonds are resistant, hence the non-
Expert systems. Computerised systems consisting of flammability of modern inhalation anaesthetic
databases of knowledge and rules that are connected to agents.
the user via an interface. The latter takes data from the - alcohol used to clean skin.
database and delivers inferences to the user. A facility - gases, e.g. methane and hydrogen in the patients
for adding knowledge to the database allows the system GIT.
to learn continually. Expert systems may be: - grease/oil in anaesthetic pressure gauges (see
diagnostic, e.g. for interpretation of arterial blood Adiabatic change).
gases, ECG. gas to support combustion: O2 is standard in most
therapeutic, e.g. for providing optimal ventilator anaesthetic techniques. N2O breaks down to O2 and
settings. nitrogen with heat, producing further energy; thus
reactions may be more vigorous with N2O than with
Expiratory flow rate, see Forced expiratory flow rate O2 alone.
energy source: About 1 J is required for most reac-
Expiratory pause, see Inspiratory: expiratory ratio tions with O2; about 100 J with air. Sources include:
- sparks from:
Expiratory reserve volume (ERV). FRC minus resid- - build-up of static electricity.
ual volume. Normally 11.2 litres. Reduced ERV is - electrical equipment, e.g. diathermy, monitors,
usually the cause of reduced FRC. See also, Lung switches.
volumes - naked flames, cigarettes, hot wires, diathermy,
light sources.
Expiratory valve, see Adjustable pressure-limiting - lasers (see Laser surgery).
valve May result in burns, direct trauma and smoke inhalation.
Although uncommon now with modern techniques,
Expired air ventilation. Component of CPR said to be explosions and fires continue to be reported.
referred to in the Bible (2 Kings 4: 345). Reported in Precautions during anaesthesia include:
the 1700s and 1800s, but only became medically accepted avoidance of flammable agents. If used, a zone of
practice in the 1950s, following demonstration that it was risk (within which no potential source of ignition
effective in apnoea during anaesthesia. Adequate oxy- should be placed) has been defined, e.g. extending
genation may be maintained with expired air of O2 con- 25cm from any part of the apparatus or patients
centration 1516%. airways that contain the anaesthetic mixture.
Having cleared the airway of debris, and with the antistatic precautions, e.g. conductive rubber,
patient supine, the neck is extended and the jaw held floor.
forward. In adults, the nose is pinched closed and the checking and maintenance of all electrical equip-
operators mouth placed firmly over that of the patient ment. Use of spark-free switches.
(mouth-to-mouth respiration). Slow deep exhalations use of air instead of N2O.
are made whilst observing the patients chest for expan- use of circle systems.
sion. Exhalation is passive. May also be performed air conditioning and scavenging, to reduce levels of
through the patients nose (mouth-to-nose respiration). anaesthetic agents. Sparks are reduced by maintain-
In children, the operators mouth is placed over the ing relative humidity above 50%, and temperature
patients nose and mouth. above 20C.
222 Exponential process

(a) (b) (c) (d)

A A A A
A0

A/2
A x 37%

t1/2
Time Time Time Time

Fig. 65Types of exponential processes: (a) and (b) exponential decay; (c) exponential build-up; (d) positive exponential

Fire-fighting equipment should be present in every oper- Plotted on semi-logarithmic paper, exponential pro-
ating department. cesses assume straight lines, e.g. used in the analysis of
Non-combustion explosions may occur if cylinders washout curves.
are faulty or internal pressure excessively high.
Macdonald AG (1994). Br J Anaesth; 72: 71022; 73: Extended mandatory minute ventilation, see Manda-
84756 tory minute ventilation
See also, Ignition temperature
External jugular venous cannulation. The external
Exponential process. A process in which the rate of jugular vein passes posteriorly over the sternomastoid
change of a quantity at a given time is in constant pro- muscle from the angle of the jaw and joins the subclavian
portion to the amount of the quantity at that time. vein behind the midpoint of the clavicle (see Fig. 86;
Different types: Internal jugular venous cannulation). It is often visible
exponential decay (negative exponential), e.g. and thus easier to locate than the internal jugular vein,
passive lung deflation after a breath, radioactive although valves may hinder cannulation and misplace-
decay, washout curves (Fig. 65a). Similar curves are ment is common. In some individuals the vessel is not a
obtained in pharmacokinetics, in which several distinct structure but is replaced by a venous plexus. The
curves may be superimposed. For exponential decay: technique of cannulation involves placing the patient
A = A0 b kt slightly head down with the arms by the side and the
head turned to the contralateral side. After cleansing the
where A = value of variable at a given time skin, the skin is punctured well above the clavicle and
A0 = A at time zero the needle advanced immediately over the vein at
b = a particular base, usually e (2.718) about 20 to the frontal plane. A J-wire may help the
because mathematical manipulations catheter negotiate the valves at the junction with the
are easier subclavian vein.
k = a constant (the rate constant)
t = time
Extracellular fluid (ECF). Body fluid compartment;
The rate constant (k) is the constant of proportion-
volume is about 14 litres (20% of body weight). Consists
ality linking the rate of the change of the quantity
of interstitial fluid and plasma. Transcellular fluid
to its value (i.e. k = rate/quantity). Its reciprocal is
(approximately 1 litre, composed of CSF, synovial fluid,
the time constant (), and is also defined as the time
etc.) and fluid within dense connective tissue, bone, etc.,
required for completion of the process at the initial
are usually excluded from the definition since these
rate of change. Substituting for k (and e for b):
fluids are not readily exchangeable.
A = A0 e t/ Measurement by dilution techniques is difficult
At time : A = A0 e1 because of eventual exchange with the above compart-
Thus: ments, and because the substance used must remain
- at time = , A = e1 of its original value = 37% extracellular. Substances used include inulin labelled
(63% complete); with carbon-14, mannitol, sucrose, chloride-36 ions,
- at 2, A = e2 of its original value = 13.5% (86.5% bromide-82 ions, sulphate and thiosulphate. Slightly dif-
complete); ferent values are obtained for each.
- at 3, A = e3 of its original value = 5% (95% Compositions of plasma and interstitial fluid are dif-
complete). ferent (see Fluids, body).
The duration of the process is also indicated by See also, Dehydration; Fluid balance
half-life (time taken for original value to fall by half;
Fig. 65b). Extracorporeal carbon dioxide removal (ECCO2R).
build-up exponential (wash-in curve), e.g. lung Method of respiratory support in which CO2 is removed
inflation with a constant-pressure generator ventila- via a venovenous extracorporeal circuit and oxygenation
tor, or uptake of inhalational anaesthetic agents is maintained by either apnoeic oxygenation or IPPV at
(Fig. 65c). very slow rates (14 breaths/min). Facilitates lung-
positive exponential (breakaway function), e.g. protective ventilation strategies by preventing respira-
growth of bacteria (Fig. 65d). tory acidosis. The extracorporeal circuit runs at only
 Extubation, tracheal 223

12 l/min; thus lung ischaemia is less likely than with Extraction ratio (ER). Measure of the amount of
extracorporeal membrane oxygenation. Initial human removal of drug by an organ, e.g. liver:
studies showed improved survival rates compared with C i Co
conventional IPPV. ER =
Practical considerations and complications are as for Ci
cardiopulmonary bypass. where Ci = drug concentration in blood entering the
organ,
Extracorporeal circulation, see Cardiopulmonary Co = drug concentration in blood leaving the
bypass; Extracorporeal carbon dioxide removal; Extra- organ.
corporeal membrane oxygenation; Haemodiafiltration; Factors affecting ER include enzyme activity and drug
Haemodialysis; Haemofiltration; Haemoperfusion; Plas- protein-binding.
mapheresis; Ultrafiltration Drugs with high ER (e.g. lidocaine and propranolol)
undergo significant first-pass metabolism in the liver
Extracorporeal membrane oxygenation (ECMO). after oral administration. The rate of elimination is thus
Method of respiratory support for extremely hypoxae- more dependent on hepatic blood flow than hepatic
mic patients despite optimum mechanical ventilation. function; clearance of drugs with a low ER is more sensi-
An arteriovenous extracorporeal circuit provides oxy- tive to changes in hepatic function (e.g. enzyme induction/
genation and removal of CO2 from anticoagulated inhibition) than blood flow.
blood. Very successful in neonates (e.g. with respiratory Drugs with low ER include diazepam, digoxin and
distress syndrome) but results are less clear in adults, in phenytoin.
whom it is used mainly for temporary support before
lung transplantation. Removal of a large proportion of Extradural (epidural) haemorrhage. Haemorrhage
the cardiac output by the arteriovenous circuit may between the periosteum and dura.
May be:
exacerbate lung ischaemia. Simpler external oxygen-
intracranial: may occur from meningeal vessels
ators include the Novolung interventional lung assist
device, a pumpless alternative that uses an arteriove- (classically the middle meningeal artery), dural
nous shunt. sinuses or fractured bone. Features are as for head
Practical considerations and complications are as for injury; typically depressed consciousness, contralat-
cardiopulmonary bypass. eral hemiparesis and ipsilateral pupillary dilatation
Brodie D, Bacchetta M (2011). N Engl J Med; 365: follow a lucid interval of a few hours after recovery
190514 from relatively minor trauma. CT shows a typical
biconvex hyperintense lesion. Management: as for
head injury, with urgent evacuation of the clot.
Extracorporeal shock wave lithotripsy. Non-invasive spinal: may occur spontaneously in patients with
treatment of renal and biliary calculi using an acoustic impaired coagulation, or following lumbar punc-
pulse. Shock waves generated by the underwater dis- ture, and spinal or epidural anaesthesia. Marked
charge of a spark plug (1824000 V) are focused on the haemorrhage with haematoma formation may
calculus by a computer-controlled reflector, with the cause spinal cord/nerve compression, that may be
patient suspended in a water bath on a hydraulic sup- masked by regional blockade.
portive cradle. At the interface between tissue fluid and
calculus, energy released from the shock wave fragments Extravascular lung water (EVLW). Volume of water
the stone. Approximately 10002000 shocks are required contained within the pulmonary interstitium and alveo-
to disintegrate an average stone, taking about 3060min. lar space. Usually 45ml/kg. Measurement of EVLW has
Shocks are triggered by the ECG R wave to avoid attracted attention as a possible means of detecting pul-
arrhythmias. Contraindications include cardiac pace- monary oedema before it becomes apparent, although
makers unless reprogrammed (timing may be modified), its usefulness in clinical practice is controversial. Deter-
aortic calcification, pregnancy and presence of orthopae- mined by Starling forces and integrity of the pulmonary
dic prostheses. capillary and alveolar epithelium. Disruption of the
Energy may be released at any interface and cause former (e.g. by left ventricular failure) or the latter (e.g.
pain, e.g. at water/skin interfaces; therefore anaesthesia in acute lung injury) may result in increased EVLW.
is required. General and regional techniques have Measured by the double indicator dilution technique
been used. High-frequency ventilation has been used, in which cold indocyanine dye is injected into the right
since diaphragmatic movement is reduced. Other anaes- atrium. The dye is contained within the intravascular
thetic considerations are related to positioning, tem- space and its dilution curve allows calculation of the
perature control, inaccessibility of the patient and intravascular compartment. In contrast, the heat (mea-
monitoring, effects of immersion (increased CVP and sured by a thermistor placed in the aorta) from the solu-
pulmonary artery pressure) and requests for pharma- tion is dissipated into the surrounding lung tissue and its
cological intervention to increase heart rate and thus dilution curve represents the sum of the intravascular
rate of discharge. IV fluid administration is usually and extravascular compartments. Subtraction of the
required to produce a good diuresis, to wash away curves allows calculation of the EVLW. Other methods
calculi fragments. Renal bleeding may occur if coagula- of assessing EVLW include CXR, CT and MRI scanning
tion is impaired. and positron emission tomography techniques.
Plasma lactate dehydrogenase concentrations may be See also, Cardiac output measurement; Dilution
increased postoperatively. PONV is common. techniques
The newest lithotriptors do not require immersion of
the patient in water; the pain produced is less and seda- Extubation, tracheal. Problems that may occur include
tion local anaesthesia may be suitable. the following:
224 Eye, anatomy

cardiovascular response: similar to that on tracheal involving the head and neck and in patients in the
intubation but usually of reduced magnitude. prone position. For the latter, the use of a mirrored
coughing and laryngospasm: the latter is especially headrest allows observation of head position.
likely to occur at light planes of anaesthesia and in inhalational agents may be irritant to the cornea.
children. tear production is impaired by anaesthesia, espe-
regurgitation and aspiration of gastric contents. cially after 12h duration; resultant drying out may
airway obstruction. lead to corneal abrasion.
laryngeal trauma caused by the cuff if still inflated. lasers are increasingly used in surgery, especially
At the end of anaesthesia, tracheal extubation is per- around the head and neck.
formed with the patient either deeply anaesthetised or Paraffin-based ointments reduce the incidence of abra-
awake. Whilst the former avoids complications such as sions but may impair vision for up to several hours.
coughing and hypertension, the latter option allows Methylcellulose or saline drops may also be efficacious
return of the patients respiratory and laryngeal reflexes but require regular administration (e.g. hourly). Routine
and is therefore recommended in patients particularly at taping of the eyes is the simplest method of preventing
risk of complications. These include those in whom corneal abrasions.
access to the airway is impaired and those at risk of Suresh P, Mercieca F, Morton A, Tullo AB (2000). Inten-
airway obstruction or aspiration (in whom extubation sive Care Med; 26: 1626
may be performed in the lateral position).
In patients in whom deep extubation is unsuitable but Eye, penetrating injury. Anaesthetic considerations:
when smooth emergence from anaesthesia is particu- as for any intraocular ophthalmic surgery.
larly important (e.g. neurosurgery, maxillofacial surgery), risk of expulsion of intraocular contents should
alternative techniques include exchanging the tracheal intraocular pressure (IOP) rise.
tube for an LMA, or use of a remifentanil infusion. may present as an acute emergency following
Extubation should be preceded by suction to the trauma, for eye or other surgery, i.e. with risk of
pharynx and larynx, preferably under direct vision, to aspiration of gastric contents.
remove secretions and blood that might otherwise be Management:
inhaled. Secretions are particularly marked in unpre- preoperatively:
medicated patients and following neostigmine. Inflation - general assessment, particularly of airway and
of the lungs with O2 immediately before and during risk of difficult intubation.
extubation provides an O2 reserve in case of laryngo- - delaying surgery should be considered if possible,
spasm and helps expel sputum from the upper airway. to allow gastric emptying. Risk of aspiration
Facilities for reintubation should be available. pneumonitis may be reduced by metoclopramide,
In patients in whom reintubation is predicted to be H2 receptor antagonists, etc.
difficult, a bougie, fibrescope or airway exchange cathe- perioperatively: choice to be made, if surgery cannot
ter may be placed into the trachea before extubation. In wait:
this group of patients high-dose corticosteroids may be - to risk the rise in IOP caused by suxamethonium
considered to prevent post-extubation laryngeal oedema. whilst performing rapid sequence induction. Risks
After extubation, adequate ventilation should be con- may be reduced by:
firmed and supplemental oxygen administered during - methods used to reduce the rise in IOP, although
transfer to a recovery room. not always reliable:
Similar considerations apply to patients in ICU after - generous dose of induction agent, or a sup-
successful weaning from ventilators. plementary dose before intubation, especially
Popat M, Mitchell V, Dravid R, etal (2012). Anaesthesia; using propofol.
67: 31840 - iv -adrenergic receptor antagonists, lido-
caine, opioids, acetazolamide, and non-
Eye, anatomy, see Cranial nerves; Orbit; Skull depolarising neuromuscular blocking drug
pretreatment have been studied, with mixed
Eye care. Important during both anaesthesia and inten- results.
sive care since the eye is at risk for a number of reasons: Some centres have reported that use of suxame-
the cornea is susceptible to hypoxia since it is thonium need not result in loss of intraocular
usually covered by the eyelid when unconscious, contents.
thus preventing diffusion of O2 from the atmo- - to use alternative means of achieving tracheal
sphere. Hypoxaemia may thus lead to corneal intubation (although laryngoscopy and intubation
oedema that in turn may cause sloughing and themselves raise IOP):
corneal abrasion. - rapid sequence induction using high-dose
rarely, postoperative blindness (in one or both eyes) rocuronium.
has been reported in patients with normal preop- - inhalational induction/awake intubation: how-
erative vision. Ischaemic optic neuropathy associ- ever, coughing and straining increase IOP.
ated with perioperative hypotension, anaemia, - the above may be combined with measures to
facial oedema and direct or indirect pressure on the reduce risk from aspiration.
eyes has been suggested as a cause. The individual patients medical condition and
normal protective mechanisms (blink reflex, and severity of injury, and the skill of the anaesthetist,
the upturning of the eye and complete closure of should be carefully considered before deciding on
the lids during normal sleep) are obtunded by the most appropriate technique. Ultimately, safe
anaesthesia. tracheal intubation must take precedence over pro-
direct damage may be caused by anaesthetic and tection of the eye. Other drugs known to increase
surgical equipment, especially during procedures IOP, e.g. ketamine, should be avoided.
 F
F wave, see Atrial flutter. Common conditions:
cleft lip and palate: incidence is about 1 in 600; it
Facemasks. The traditional black antistatic rubber may involve the lip (right, left or bilateral), palate,
anaesthetic masks, with soft edges or inflatable rims, or combinations thereof. Other abnormalities are
have largely been replaced by clear, disposable, plastic present in up to 15% of cases. Swallowing abnor-
masks. Ideally, they should have minimal dead space and malities may be present, with risk of aspiration
make an airtight seal with the patients face. Some are pneumonitis. Surgery for cleft lip is usually per-
malleable to improve fit. Damage may be caused to eyes, formed at 36 months, for cleft palate at 612
nose and face if excessive pressure is used. Dead space months.
may be measured using water, and may be up to 200ml Induction of anaesthesia is as for standard paediat-
if the elbow attachment is included. Paediatric face- ric anaesthesia, but tracheal intubation may be dif-
masks may be small versions of adult ones or specially ficult if the laryngoscope blade slips into the cleft.
designed to minimise dead space, e.g. Rendell-Bakers To prevent this the cleft may be packed with gauze
(anatomically moulded to fit the face). Others are spe- or the Oxford blade used. Preformed or rigid tra-
cifically designed for delivery of CPAP or non-invasive cheal tubes are usually employed, with a throat
ventilation. pack. Further surgery may be required in later
[Leslie Rendell-Baker (19172008), British-born US years.
anaesthetist] mandibular hypoplasia: e.g. in Pierre Robin syn-
See also, Open-drop techniques drome (macroglossia, cleft palate and cardiac
defects) and Treacher Collins syndrome (choanal
Facet joint injection. Injection of the posterior facets atresia, downwards sloping eyes, deafness, low-set
of the intervertebral joints, performed in patients with ears and cardiac defects). The small mandible leaves
mechanical low back pain not associated with leg symp- little room for the tongue, the larynx appearing
toms or signs of root irritation/compression. The poste- anterior. Intubation may be extremely difficult;
rior primary ramus of each spinal nerve divides into deep inhalational anaesthesia, awake or blind nasal
lateral and medial branches; the latter supplies the lower intubation, cricothyrotomy and tracheostomy have
portion of the facet joint capsule at that spinal level and been employed.
the upper portion of the capsule below. Thus two poste- hypertelorism (increased distance between the
rior primary rami must be blocked to anaesthetise one eyes): associated with many other abnormalities or
facet joint. syndromes, including airway abnormalities. Correc-
With the patient prone, the joint is located using tive surgery may include mandibular or maxillary
image intensification radiography, and a needle inserted osteotomies, craniotomy and multiple rib grafts; it
under local anaesthesia. It is walked medially and supe- is often prolonged with significant haemorrhage.
riorly off the transverse process of the vertebra to reach other deformities that may produce airway prob-
the angle where the lateral edge of the facet joint meets lems include macroglossia, cystic hygroma and
the superomedial aspect of the transverse process. Local branchial cyst. Raised ICP may occur with hydro-
anaesthetic agent may be injected, or longer-lasting cephalus and craniosynostosis (premature closure
relief obtained by destroying the facet joint nerve using of the cranial sutures).
radiofrequency rhizolysis. [Edward Treacher Collins (18621919), English
Cohen SP, Raja SN (2007). Anesthesiology; 106: ophthalmologist; Pierre Robin (18671950), French
591614 paediatrician]
Nargozian C (2004). Pediatr Anaesth; 14: 539
Facial deformities, congenital. Patients may present See also, Intubation, difficult
for radiological assessment and corrective cosmetic
surgery. Facial nerve block. Performed to prevent blepharo-
Anaesthetic considerations are usually related to: spasm during ophthalmic surgery, e.g. with retrobulbar
airway difficulties, including difficult intubation. block.
other congenital abnormalities, e.g. CVS, renal, Methods:
CNS. local anaesthetic infiltration between muscle and
general problems of paediatric anaesthesia and bone along the lateral and inferior margins of the
plastic surgery, e.g. fluid balance, heat and blood orbit.
loss during prolonged procedures. Topical vasocon- injection of 5ml solution over the condyloid process
strictors may be used to reduce bleeding. of the mandible, just anterior to the ear and below
repeat anaesthetics. the zygoma.

225
226 Facial trauma

Facial trauma. Anaesthetic and resuscitative consider- academic side of anaesthesia whilst the latter body con-
ations include: possible airway obstruction and difficult centrated on general and political aspects. Administered
tracheal intubation; risk of aspiration of gastric contents; and regulated the FFARCS examination and training
postoperative management of the airway; and the pres- of junior anaesthetists, until it became the College of
ence of other trauma (especially to head, eyes, chest Anaesthetists in 1988 and thence the Royal College
and neck). of Anaesthetists in 1992. The corresponding Faculty
Classification of facial injuries: in Ireland was founded in 1959, becoming a College
maxillary fractures: often more serious, and associ- in 1998.
ated with significant head injury. Classified by Le
Fort after dropping heavy objects on to the faces of Faculty of Intensive Care Medicine, Royal College
cadavers: of Anaesthetists. Established in 2010 by seven parent
- I: transverse fractures of mid-lower maxilla. Colleges, its remit is to define and promote standards
- II: triangular fracture from top of the nose to base of education and training in critical care. Replaces the
of the maxilla. Intercollegiate Board for Training in Intensive Care
- III: severe fractures involving the orbit, with dis- Medicine. Responsible for developing a primary spe-
ruption of facial bones from the skull. Cribriform cialty training programme for intensive care medicine.
plate disruption and CSF leak are common.
zygomatic fractures: may hinder mouth opening. Faculty of Pain Medicine, Royal College of Anaesthe-
nasal fractures: may require reduction under anaes- tists. Established in 2007, to promote education, training
thesia; tracheal intubation and insertion of a throat and excellence in the delivery and management of pain
pack may be required if epistaxis occurs. If the latter medicine.
is severe, a nasal compression device may be
necessary. Factor VIIa, recombinant, see Eptacog alfa
Anaesthetic management:
preoperatively: Fade. Progressive reduction in strength of muscle con-
- assessment for the above factors. Airway obstruc- traction during tetanic or intermittent stimulation (e.g.
tion and major haemorrhage are more likely with train-of-four), exaggerated in non-depolarising neuro-
bilateral fractures. muscular blockade. Thought to be caused partly by
- gastric contents, including swallowed blood. inadequate mobilisation of acetylcholine in presynaptic
Fractures rarely require immediate surgery; pre- nerve endings at the neuromuscular junction compared
operative fasting is usually possible. with the rate of release. Block of prejunctional acetyl-
- the patient should be warned about postoperative choline receptors, which normally increase mobilisation
inability to open the mouth if the jaw is wired. by a positive feedback mechanism, is thought to be
perioperatively: involved during neuromuscular blockade. Thus patterns
- rapid sequence induction may be necessary. Other of fade vary between blocking drugs, reflecting their dif-
techniques may be required if airway obstruction fering affinities for prejunctional receptors (e.g. greater
or cervical instability is present (e.g. awake fibre- with tubocurarine than with pancuronium).
optic tracheal intubation, tracheostomy). Feldman S (1993). Anaesthesia; 48: 12
- nasal tracheal intubation is usually required. Oral
intubation may be performed first to secure the Failed intubation, see Intubation, failed
airway.
- procedures often involve wiring of jaw segments Fallots tetralogy. Commonest cause of cyanotic heart
together, and splinting of the mandible to the disease (65%), accounting for 510% of congenital heart
upper jaw. Silk threads are sometimes used. Plates disease.
may be applied, with wiring 12 days later. Consists of:
postoperatively: VSD.
- tracheal extubation should be performed when pulmonary stenosis (ranges from subvalvular steno-
the patient is awake and in the lateral position. If sis to pulmonary atresia).
severe oedema is anticipated, the tracheal tube is overriding aorta.
left in place postoperatively until it has subsided. right ventricular hypertrophy.
Oral suction may be impossible. Dexamethasone Blood flow from right ventricle to pulmonary artery is
is often given intraoperatively to reduce oedema. reduced, with shunting through the VSD and aortopul-
- the tracheal tube may be withdrawn into the monary collaterals.
pharynx to act as a nasal airway or an airway Features:
exchange catheter placed. hypoxaemia and cyanosis, usually from birth, with
- postoperative care should be on HDU/ICU, since secondary polycythaemia. Dyspnoea occurs on
the airway must be closely monitored. Wire effort.
cutters should be next to the patient at all times. acute exacerbations of shunt are attributed to infun-
[Ren Le Fort (18291893), French surgeon] dibular spasm and increased pulmonary vascular
See also, Dental surgery; Maxillofacial surgery; Induc- resistance secondary to hypoxia. Features include
tion, rapid sequence; Intubation, difficult worsening cyanosis, syncope and metabolic acidosis.
Symptoms are relieved by squatting; thought to
Facilitation, post-tetanic, see Post-tetanic potentiation increase SVR and encourage pulmonary blood flow.
supraventricular arrhythmias; right heart failure in
Faculty of Anaesthetists, Royal College of Surgeons adults.
of England. Founded in 1948 at the request of the a loud pulmonary murmur suggests mild stenosis. A
Association of Anaesthetists, in order to manage the large VSD may be unaccompanied by a murmur.
 Fat embolism 227

Corrective surgery is usually performed within the first Dalens B, Vanneuville G, Tanguy A (1989). Anesth
year of life. The VSD and right ventricular outflow are Analg; 69: 70513
repaired with patches; right ventricular pressure mea- See also, individual nerve blocks
surement indicates whether there has been adequate
relief of obstruction. Shunt procedures are performed Fascicular block, see Bundle branch block
for palliation if marked polycythaemia or pulmonary
arterial hypoplasia is present.
Anaesthetic management: Fasciculation. Visible contraction of skeletal muscle
as for congenital heart disease, VSD, cardiac surgery, fibre fasciculi, seen following use of suxamethonium
paediatric anaesthesia. and other depolarising neuromuscular blocking drugs.
infundibular spasm is provoked by fear and anxiety, Possible damage to fibres is suggested by increased
and may be treated with -adrenergic receptor serum myoglobin and creatine kinase following suxame-
antagonists. Sedative premedication is often given. thonium; it may also be partly responsible for the
avoidance of air bubbles in iv injectate, because of raised potassium that occurs. May be related to post-
the risk of systemic embolisation. suxamethonium myalgia, since measures to reduce the
peripheral vasodilatation worsens shunt and cyano- latter often reduce visible fasciculation.
sis. Vasopressor drugs (e.g. phenylephrine) may be Also occurs in motor neurone disease, spinal motor
used to increase SVR and pulmonary blood flow. neurone lesions, and rarely in myopathies. Muscle fibre
[Etienne-Louis Fallot (18501911), French physician] fibrillation (e.g. occurring after denervation injury) is
invisible.
False negative/false positive, see Errors
Fasciitis, necrotising, see Necrotising fasciitis
Familial periodic paralysis. Rare group of autosomal
dominant myopathies due to defects in ion channels in
skeletal muscle; characterised by episodes of severe Fat, brown, see Brown fat
weakness, often precipitated by extremes of tempera-
ture, physical activity, stress and large carbohydrate Fat embolism. Dispersion of fat droplets into the circu-
loads. Although traditionally classified into hypo- or lation, usually following major trauma. Also occurs in
hyperkalaemic variants, the condition may be associated acute pancreatitis, burns, diabetes mellitus, joint recon-
with normal plasma potassium levels. Diagnosis may be struction (possibly related to use of methylmethacrylate
difficult, but exercise EMG has a high level of sensitivity; cement), cardiopulmonary bypass, liposuction, bone
detection of known gene mutations can be helpful. marrow harvest/bone marrow transplantation and par-
Treatment depends on type of disease but includes the enteral infusion of lipids. Post-mortem evidence of fat
use of carbonic anhydrase inhibitors (e.g. acetazol- embolism is found in 90% of fatal trauma cases. The
amide), oral potassium supplements (for hypokalaemic mechanical (infloating) theory proposes that fat liber-
variant) and thiazide diuretics (for hyperkalaemic ated from fractured bone enters the venous system and
variant). impacts in pulmonary capillaries, resulting in pulmonary
Careful use of neuromuscular blocking drugs dysfunction. Systemic embolism may occur via pulmo-
is required, with close monitoring of perioperative nary arteriovenous shunts or a patent foramen ovale.
potassium levels. Arrhythmias may accompany potas- The biochemical theory suggests that free fatty acids
sium changes. Glucose-containing intravenous fluids released following trauma induce an inflammatory
should be avoided in the hyperkalaemic form of the response that causes pulmonary dysfunction, possibly
disease. Increased susceptibility to MH is thought to be mediated via an increase in plasma lipase. Both pro-
unlikely. cesses may occur.
Finsterer J (2008). Acta Neurol Scand; 117: 14558 The fat embolism syndrome occurs after less than
10% of trauma cases, typically 1236h after long bone
Fascia iliaca compartment block. Injection of local fractures. Early fixation of fractures may reduce its
anaesthetic solution deep to the fascia iliaca into a incidence.
compartment between the iliacus and psoas muscles, Features:
through which run the femoral, lateral cutaneous, geni- confusion, restlessness, coma, convulsions, cerebral
tofemoral and obturator nerves. Primarily used to infarction.
provide analgesia for surgery to the hip, anterior thigh dyspnoea, cough, haemoptysis. Hypoxaemia is
and knee; increasingly performed in emergency depart- almost inevitable. Pulmonary hypertension and pul-
ments by non-anaesthetists to provide analgesia for hip monary oedema may occur. Typically, gives a snow-
fractures. storm appearance on the CXR, but radiography
A needle is inserted 0.5cm caudal to the junction of may be normal. May contribute to development of
the lateral third of the inguinal ligament with the medial ARDS.
two-thirds. A click or give (the latter if continuous pres- petechial rash, typically affecting the trunk, pharynx,
sure is applied to the plunger of the syringe) is felt as axillae and conjunctivae.
the needle passes through the fascia lata, followed by tachycardia, hypotension, pyrexia.
a second click as the fascia iliaca is pierced. An platelets are reduced in 50%; hypocalcaemia is also
ultrasound-guided in-plane approach may also be used. common. Coagulation disorders may occur.
3040ml local anaesthetic agent (e.g. 0.25% bupiva- fat droplets are detected in cells obtained by bron-
caine) is then injected. Distal pressure is advocated to chopulmonary lavage in 70% of cases. The presence
encourage cranial extension of the solution. A catheter of fat droplets in the urine is a non-specific finding
may be inserted to allow continuous infusion of local following trauma. Retinal examination may reveal
anaesthetic. intravascular fat globules.
228 Fats

Management: fish oils and plant oils) has been suggested as

O2 therapy; IPPV may be required. reducing production of inflammatory mediators
supportive therapy. Fluid restriction has been advo- and thereby various cardiovascular and inflamma-
cated for reducing lung water. tory disorders.
corticosteroids have been shown to reduce mortal- - esterified with triglycerides, cholesterol or phos-
ity in several small studies, but optimum dosage, pholipids, or bound to circulating albumin as
timing and patient selection remain unclear. FFAs.
heparin, aprotinin, aspirin, clofibrate, prostacyclin, - FFAs are used as an energy source by most tissues.
dextran and alcohol infusion have all been tried, Lipoproteins are classified according to their size: chylo-
without conclusive benefit. microns 80500nm; VLDLs 3080nm; IDLs 2540nm;
Prognosis is variable and unrelated to initial severity. LDLs 20nm; HDLs 7.510nm. LDLs and IDLs are
Mortality is 1020%. formed from VLDLs; HDLs are formed in the liver.
Akhtar S (2009). Anesthesiol Clin; 27: 53350 High levels of cholesterol, LDLs and VLDLs are associ-
ated with ischaemic heart disease, although the role of
Fats (Lipids). Four main classes are present in plasma each is controversial. HDLs may be protective.
and cells:
triglycerides: Fazadinium bromide. Obsolete non-depolarising neu-
- composed of glycerol and fatty acids. Formed in romuscular blocking drug, introduced in 1972. Acts
the GIT, liver and adipose tissue. within 60s and marketed as an alternative to suxame-
- the main source of dietary fat; digested in the thonium. Withdrawn because of marked cardiovascular
small bowel. Initially emulsified by bile salts effects due to ganglion and vagal blockade.
and broken down to monoglycerides, free fatty
acids (FFAs) and glycerol by lipases within the FDA, see Food and Drug Administration
GIT. Undigested triglycerides are only minimally
absorbed but glycerol and FFAs are taken up FDPs, see Fibrin degradation products
readily. Short-chain fatty acids pass directly into
the portal vein and circulate as FFAs; long-chain FEEA, see Fondation Europenne dEnseignement en
FFAs (over 1012 carbon atoms) are reconsti- Anaesthsiologie
tuted with glycerol to reform triglycerides before
incorporation into chylomicrons. Felypressin. Synthetic analogue of vasopressin, used as
- endogenous triglycerides are synthesised in the a locally acting vasoconstrictor. Has minimal effects on
liver and secreted as very low-density lipoproteins the myocardium, therefore safer than adrenaline during
(VLDLs). These are hydrolysed in the blood by anaesthesia with halothane. Available in combination
lipoprotein lipase; the FFAs released are taken with prilocaine for local infiltration.
up by tissues for resynthesis of triglycerides or
remain free in the plasma. During starvation, Femoral artery. Continuation of the external iliac
intracellular hormone-sensitive lipase breaks artery; enters the thigh below the inguinal ligament
down adipose triglycerides to FFAs and glycerol midway between the anterior superior iliac spine and
(increased by -adrenergic stimulation; decreased symphysis pubis, where it lies between the femoral vein
by insulin). medially and femoral nerve laterally. Descends through
sterols: the femoral triangle and enters (and runs in) the subsar-
- include corticosteroids, bile salts and cholesterol torial canal. Ends by piercing adductor magnus 10cm
(from which the former two are derived). above the knee joint where it becomes the popliteal
- plasma cholesterol is esterified with fatty acids, or artery.
circulates within low-density, high-density and May be cannulated for arterial BP measurement,
intermediate-density lipoproteins (LDLs, HDLs dialysis and use of the intra-aortic counter-pulsation
and IDLs respectively) and VLDLs, especially the balloon pump as well as providing access for
first. Unesterified cholesterol forms a major com- angiography.
ponent of cell membranes.
- cholesterol is either synthesised, mainly in the Femoral nerve block. Useful as an adjunct to general
liver, or absorbed from the GIT and delivered to anaesthesia for operations involving the anterior thigh,
the liver in chylomicrons. hip, knee and medial lower leg. May be combined with
phospholipids: sciatic nerve block and/or obturator nerve block for
- mainly synthesised in the liver and small intestine more extensive surgery to the lower limb. Also used for
mucosa. analgesia in leg and thigh fractures.
- circulate in the plasma in lipoproteins and consti- Anatomy:
tute important cellular components, but not part the femoral nerve (L24) arises from the lumbar
of the depot fats. Present in myelin and cell plexus, passing under the inguinal ligament to enter
membranes. the femoral triangle lateral to the femoral artery.
fatty acids: Divides into terminal branches within 36cm.
- may be saturated (no double bonds between supplies hip and knee joints and muscles of the
carbon atoms) or unsaturated (variable number anterior thigh. Also supplies skin of the anterior
of double bonds). Deficiency of certain polyun- thigh and knee, and medial lower leg and foot via
saturated fatty acids may impair capillary, hepatic, the saphenous branch (Fig. 66).
immune and GIT function, hence they are termed Block:
essential. A change in intake from omega-6 to the femoral artery is palpated below the mid ingui-
omega-3 essential fatty acids (the latter found in nal point (i.e. halfway between the superior anterior
 Femoral venous cannulation 229

iliac spine and pubic tubercle); the femoral vein lies Femoral triangle. Compartment of the anterior upper
medially and the nerve laterally. thigh; its borders are the inguinal ligament supero
a needle is introduced through a wheal 12cm medially, the medial border of adductor longus medially
lateral to the pulsation, and directed slightly crani- and the medial border of sartorius laterally (Fig. 67). Its
ally, to a depth of 34cm. A nerve stimulator may floor is formed by adductor longus, pectineus, psoas and
be used to aid location of the nerve, looking for iliacus muscles, and its roof by the fascia lata of the thigh.
contraction of the quadriceps muscle. Ultrasound- Contains the femoral artery, vein and canal within the
guided techniques (in- or out-of-plane) may also aid femoral sheath; the femoral nerve and lateral cutaneous
needle placement. nerve of the thigh lie laterally.
after aspiration to exclude vascular puncture, 10
15ml local anaesthetic agent is injected. A further Femoral venous cannulation. The femoral vein is the
510ml is injected in a fan laterally as the needle is continuation of the popliteal vein and accompanies the
withdrawn, in case cutaneous branches arise higher femoral artery in the femoral triangle, ending medial
than normal. to the latter at the inguinal ligament, where it becomes
injection of 3040ml solution at the initial site, with the external iliac vein. Following skin cleansing, the
distal compression, has been claimed to force solu- patients leg is extended and slightly abducted at the hip.
tion cranially to the lumbar plexus, lying between The femoral vein lies 11.5cm medial to the femoral
psoas and quadratus lumborum muscles (three-in- artery, 23cm below the inguinal ligament. The needle
one block). In fact, a continuous femoral sheath is inserted here and advanced at an angle of 4560 to
probably does not exist as a separate entity; the the frontal plane. When venous blood is aspirated, the
three-in-one block is thought to represent com- syringe is lowered to lie flat on the skin. A Seldinger
bined femoral and lateral cutaneous nerve blocks technique is usually employed thereafter. Ultrasound
below the inguinal ligament as a result of non- guidance may be useful.
specific spread. Fascia iliaca compartment block is May be performed for central venous cannulation;
a more reliable and anatomically sound method of traditionally avoided if other routes are available
producing block of the three nerves. because of (probably unfounded) fears of infection
or thrombosis. May be useful in superior vena caval
obstruction.

Anterior Posterior

Anterior superior Lateral cutaneous nerve of thigh

iliac spine
Iliacus muscle Psoas major muscle
Femoral nerve
Lateral cutaneous n Inguinal Femoral artery
of thigh ligament Pubic tubercle

Femoral canal Femoral vein

Femoral n
Pectineus muscle

Posterior cutaneous n Adductor longus

of thigh muscle

Obturator n Sartorius muscle

Saphenous n

Common peroneal n
cutaneous branch

Patella

Fig. 67 Right femoral triangle (N.B. The spermatic cord emerging

Fig. 66 Nerve supply of leg (for nerve supply of ankle and foot, see through the external inguinal ring superolateral to the pubic tubercle
Fig. 11 Ankle, nerve blocks) is not shown)
230 Fenoldopam mesylate

Fenoldopam mesylate. Selective D1-dopamine recep- from the origin of the carotid arteries. Thus relatively
tor partial agonist, introduced in the USA in 1998 as an O2-rich blood is conserved for the brain, and the rest of
iv vasodilator drug. Also has mild 2-adrenergic agonist the body is perfused with the less oxygenated blood.
properties. Causes increased renal blood flow, diuresis Deoxygenated blood reaches the placenta via the two
and sodium excretion. Given as an infusion for hyper- umbilical arteries, arising from the internal iliac arteries;
tensive crisis, its short half-life of 5min results in rapid they receive about 60% of cardiac output.
offset of action. Metabolised in the liver to inactive Approximate values:
compounds. umbilical vein:
- PO2 4kPa (30mmHg).
Fenoterol hydrobromide. -Adrenergic receptor - PCO2 6kPa (45mmHg).
agonist, used as a bronchodilator drug. Similar in action - pH 7.2
to salbutamol and terbutaline but less 2-selective. Now umbilical artery:
only available in the UK as part of a compound aerosol - PO2 2kPa (15mmHg).
formulation. - PCO2 7kPa (53mmHg).
Dosage: 200400g by aerosol inhalation tds as At birth, placental blood flow ceases, and peripheral
required. resistance increases. Lung expansion lowers pulmonary
Side effects: as for salbutamol. vascular resistance, both directly and via reduction of
hypoxic pulmonary vasoconstriction. Thus pulmonary
Fentanyl citrate. Synthetic opioid analgesic drug, and right heart pressures fall, and aortic and left heart
derived from pethidine. Developed in 1960. 100 times as pressures rise. Pulmonary blood flow increases and flow
potent as morphine. Widely used perioperatively as an through the ductus arteriosus and foramen ovale ceases.
analgesic, for sedation (e.g. on ICU) and in chronic pain. The ductus arteriosus usually closes within 48h due to
Onset of action is within 12min after iv injection; peak the high PO2. Pulmonary artery pressure, pulmonary vas-
effect is within 45min. Duration of action is about cular resistance and pulmonary blood flow approach
20min, terminated by redistribution initially as plasma adult values by 46 weeks.
clearance is less than for morphine. Postoperative respi-
ratory depression is possible if large doses are used,
especially in combination with opioid premedication
and other depressant drugs. Causes minimal histamine
release or cardiovascular changes, although may cause Aorta
bradycardia. Superior vena cava 60
Dosage:
to obtund the pressor response to laryngoscopy:
710g/kg iv. 50 Ductus
as a co-induction agent/during anaesthesia: 13g/ arterious
kg iv with spontaneous ventilation; 510g/kg with
IPPV. Up to 100g/kg is used for cardiac surgery. 30
Muscular rigidity and hypotension are more Ductus Pulmonary
common after high dosage. Has been used in venosus artery
neuroleptanaesthesia.
by infusion: 15g/kg/h, e.g. for sedation. For
65
patient-controlled analgesia: 20100g bolus with
35min lockout. 80
25, 50, 75 or 100g/h transdermal patch placed on From
the chest or upper arm and replaced (using a differ- placenta
ent site) every 72h. A patch employing iontopho-
resis has been developed for postoperative 25
patient-controlled analgesia but is not currently
Right ventricle Left ventricle
marketed.
100800g sublingual lozenges for breakthrough
cancer pain or short painful procedures (e.g. burns Inferior vena cava
dressing change).
Commonly used for epidural and spinal anaesthesia (see
Spinal opioids). Aorta

Fetal circulation. Oxygenated blood from the placenta 55

passes through the single umbilical vein and enters the
inferior vena cava, about 50% bypassing the liver via To placenta
the ductus venosus. Most of it is diverted through the
foramen ovale into the left atrium, passing to the brain
via the carotid arteries (Fig. 68). Deoxygenated blood
from the brain enters the right atrium via the superior
vena cava, and passes through the tricuspid valve to the
right ventricle. Because the resistance of the pulmonary
vessels within the collapsed lungs is high, the blood
passes from the pulmonary artery trunk through the Fig. 68 Diagram of fetal circulation, Arrows denote flow of blood.
ductus arteriosus to enter the aortic arch downstream Figures refer to the approximate oxygen saturation
 Fetus, effects of anaesthetic drugs on 231

Neonates may revert to persistent fetal circulation, - late (type II), i.e. after contractions: represent
with decreased pulmonary blood flow and right-to-left hypoxia, although not always with acidosis.
shunt through the ductus arteriosus, foramen ovale, or - variable: usually due to cord compression; they
both. This may occur if pulmonary vascular resistance is may indicate compromise if severe.
increased, e.g. by hypoxia, hypothermia, hypercapnia, Prolonged decelerations are more sinister, and
acidosis or polycythaemia. It may occur during surgery may represent severe fetal compromise.
if anaesthesia is too light or if the patient strains on the Recent NICE guidelines classify the CTG according to
tracheal tube. Right-to-left shunt increases with worsen- the baseline rate, variability, accelerations and decelera-
ing hypoxia and further reflex vasoconstriction. Ductal tions as being normal (all four criteria are normal),
shunting may be demonstrated clinically by measuring suspicious (one of the four is non-reassuring) or path-
O2 saturation (e.g. by pulse oximetry) in the arm and ological (two or more of the four are non-reassuring
leg simultaneously; a large difference (higher saturation or one is abnormal). Predictive value of cardiotocogra-
in the arm) represents significant ductal blood flow phy is poor in low-risk patients, hence its routine use is
(i.e. pulmonary artery pressure exceeds aortic pressure). controversial. Combination with fetal electrocardiogra-
If the right ventricle fails, right atrial pressure exceeds phy (ST waveform analysis) is thought to increase its
left atrial pressure, increasing shunt through the sensitivity.
foramen ovale. Signs of fetal compromise may be related to treatable
Treatment of persistent fetal circulation includes: O2 conditions, e.g. uterine hypertonicity associated with
therapy; correction of acidosis, hypercapnia and hypo- excessive oxytocin administration, maternal hypo
thermia; and inotropes and fluid administration. Drugs tension. Aortocaval compression should always be
that lower pulmonary vascular resistance (e.g. tolazoline, considered, especially if regional analgesia has been
isoprenaline) may be given. Extracorporeal membrane provided.
oxygenation has been used. fetal blood sample: pH under 7.2 represents severe
See also, Ductus arteriosus, patent acidosis. May be measured serially to observe
trends.
fetal scalp oximetry, EEG, ECG and continuous pH
Fetal haemoglobin. Consists of two chains and two
measurement have been investigated but are not
chains, the latter differing from chains by 37 amino
routinely available.
acids. Binds 2,3-DPG less avidly than haemoglobin A
Post-delivery, cord blood gas interpretation (pH repre-
(adult), thus shifting the oxyhaemoglobin dissociation
sents degree of acidosis at time of delivery), Apgar
curve to the left (P50 is 2.4kPa [18mmHg]) and favour-
scoring, time to sustained respiration and neurobehav-
ing O2 transfer from mother to fetus. At the low fetal
ioural testing of neonates may be assessed; these may be
PO2, it gives up more O2 to the tissues than adult hae-
useful prognostically.
moglobin would, because its dissociation curve is steeper
[Adolphe Pinard (18441934), French obstetrician]
in this part. Forms 80% of circulating haemoglobin at
Stout MJ, Cahill AG (2011). Clin Perinatol; 38: 12742
birth; replaced by haemoglobin A normally within 35
months. May persist in the haemoglobinopathies. Reac-
Fetus, effects of anaesthetic drugs on. The fetus
tivation of production of fetal haemoglobin using
is usually defined as such from the ninth week of gesta-
hydroxyurea has been used in the treatment of sickle
tion. Most major organ structures develop earlier
cell anaemia.
than this.
A variety of embryonic haemoglobins are present up Main anaesthetic considerations:
to 23 months of gestation.
effect of anaesthetic drugs on fetal development
and spontaneous abortion:
Fetal monitoring. Methods include: - animal studies suggest increased fetal loss and
presence of meconium in amniotic fluid: usually abnormalities following prolonged exposure to
represents fetal compromise, and presents risk of high concentrations of volatile agents and N2O.
meconium aspiration on delivery. - human studies have produced conflicting results.
heart rate, especially related to uterine contrac- It is generally accepted that general anaesthesia
tions. May be performed intermittently using a should be avoided where possible during preg-
trumpet-shaped stethoscope (Pinard) or portable nancy, particularly during the first trimester.
ultrasound machine, or continuously using a car- - N2O has been implicated (but not proven) as
diotocograph (CTG), a device that measures heart increasing the incidence of spontaneous abortion
rate by external ultrasonography or fetal scalp in health workers chronically exposed; current
electrode, and contractions by external transducer opinion holds that its use is not contraindicated in
or intrauterine probe: pregnant patients.
- normal baseline heart rate is 110160 beats/min, - new drugs should be avoided during early preg-
with beat-to-beat variability of 525 beats/min, nancy, until more information becomes
related to autonomic activity. Increased baseline available.
and reduced variability may indicate compromise, effect of anaesthetic drugs given during labour on
although they may also be caused by administra- the neonate:
tion of depressant drugs to the mother or mater- - indirect effects:
nal pyrexia. - reduced uteroplacental blood flow (e.g. due to
- accelerations usually indicate reactivity and oxytocin) or hypotension following regional
well-being. blockade or general anaesthesia.
- decelerations; usual significance: - maternal hypoxia (e.g. due to drug-induced
- early (type I), i.e. with contractions: vagally respiratory depression, total spinal block,
mediated, due to head compression. convulsions).
232 FEV1

- increased maternal catecholamine levels during drugs; e.g. umbilical vein/maternal blood
inadequate general anaesthesia with awareness; levels:
uteroplacental vasoconstriction and fetal acido- - prilocaine: > 1.
sis may result. Levels are reduced in labour fol- - lidocaine: 0.5.
lowing epidural block; this may reduce fetal - bupivacaine: 0.3.
acidosis. - etidocaine: 0.2.
- direct effects related to fetal plasma levels, - subtle neurobehavioural effects have been
affected by: shown; initial fears about adverse effects of
- uteroplacental blood flow. lidocaine compared with bupivacaine are now
- placental, maternal and fetal protein concentra- thought to be unfounded.
tions and drug binding. For example, diazepam - fetal methaemoglobinaemia may follow
binds to albumin and is extensively transferred excessive doses of prilocaine.
to the fetus; bupivacaine binds to 1-acid glyco- - procaine and 2-chloroprocaine are metabo-
protein (present in lower concentrations in the lised by esterases in maternal and fetal plasma.
fetus) and is transferred to a lesser extent. - others, e.g. benzodiazepines, phenothiazines:
- peak maternal plasma drug levels and their - all cross the placenta to some extent.
duration. - diazepam is more strongly bound to fetal than
- diffusion of drug across the placenta, depending to maternal protein, and has been associated
on membrane thickness, molecular size and with neonatal hypotonia and hypothermia.
shape, degree of ionisation and lipid solubility. Umbilical vein/maternal blood ratio is 2.0.
- reduced fetal hepatic and renal function. Most - all drugs that significantly cross the blood
drugs bypass the fetal liver via the ductus brain barrier may cross the placenta to similar
venosus. extents, e.g. atropine, propranolol.
- umbilical vein drug levels: reduced by dilution Littleford J (2004). Can J Anesth; 51: 586609
with blood from the rest of the body. Thus See also, Environmental safety of anaesthetists; Fetal
umbilical vein levels may not reflect fetal monitoring; Neurobehavioural testing of neonates
levels.
- fetal hypoxia and acidosis: cause trapping of FEV1, see Forced expiratory volume
basic drugs, e.g. opioids and local anaesthetic
agents, and increase blood flow to vital centres, Fever, see Pyrexia
e.g. brain. Thus brain levels may be increased.
specific drugs: FFARCS examination (Fellowship of the Faculty of
- opioid analgesic drugs: Anaesthetists at the Royal College of Surgeons of
- fetal respiratory and CNS depression are well England). First held in 1953; became the FCAnaes exam-
recognised. ination in 1989 following the founding of the College of
- fetal opioid levels are increased by acidosis. Anaesthetists and the FRCA examination upon granting
Peak levels occur 25h after im pethidine, of a royal charter to the College in 1992. The Irish equiva-
6min after iv injection. lent exam (FFARCSI) was first held in 1961.
- half-life in the fetus is prolonged; e.g.
pethidine: up to 20h; that of norpethidine is FFP, Fresh frozen plasma, see Blood products
longer.
- naloxone crosses the placenta easily, but its Fibreoptic instruments. First use of a fibreoptic instru-
administration is usually reserved for the ment (choledochoscope) for tracheal intubation was in
fetus. 1967 by Murphy. Fibreoptic bronchoscopes were intro-
- iv anaesthetic agents: duced in 1968. Flexible fibreoptic intubating broncho-
- all cross the placenta rapidly, but have usually scopes as thin as 34mm diameter are now widely
redistributed by the time of delivery. Thiopen- available.
tal selectively accumulates in fetal liver. Features:
- neurobehavioural depression has been shown rely on total internal reflection of light within
following their use, although the effect is bundles of glass fibres about 20m diameter.
small. each fibre is encased in glass of different refractive
- inhalational anaesthetic agents: index, the interface acting as the reflective
- at low inspired concentrations, any effect is surface.
small. fibres are lubricated and flexible; the instruments
- benefits of their use include uteroplacental tip can be flexed using controls at the proximal end.
vasodilatation and prevention of maternal each instrument contains bundles for passage of
awareness. light for illumination, and bundles for passage of the
- neuromuscular blocking drugs: image back to the proximal end. The arrangement
- very little transfer follows normal use. of the image-bearing bundles is identical at each
- gallamine and alcuronium cross the placenta end of the instrument (coherent), allowing accurate
to a slightly greater extent than the others. spatial representation of the object.
- local anaesthetic agents: a lens at each end allows focusing. A camera may
- transfer varies according to dose, site of be attached to the eyepiece at the proximal end,
injection (e.g. high fetal levels following allowing the operator and others to observe the
paracervical block), use of vasoconstrictors view on a screen. With improved miniaturisation it
and different plasma protein-binding charac- is now possible to place a small video chip directly
teristics of the fetus and mother for certain at the distal end of the instrument, so that there is
 Fick principle 233

no need for fragile optical bundles to be contained Fibrinolysis. Dissolution of fibrin; occurs following clot
within its shaft (which now contains electrical wires formation, allowing blood vessel remodelling, and also
carrying the digital image instead). after wound healing. Fibrinolytic and coagulation path-
may contain channels for suction, passage of gas, ways are in equilibrium normally, each composed of a
liquid and forceps. series of plasma precursor molecules.
very delicate instruments; easily damaged, e.g. by Plasminogen, a globulin, is activated to form plasmin,
teeth. Careful cleaning is required; passage of disin- a fibrinolytic enzyme. Activation involves clotting factors
fectant into the scope may disrupt lubrication XII and XI, kallikrein and kinins, and leucocyte prod-
between fibres. ucts. Activation of tissue plasminogen is caused by prod-
Apart from diagnosis (e.g. biopsy) and therapy (e.g. ucts released by endothelial cells. Plasminogen activators
removal of secretions and foreign bodies), they have and plasminogen itself bind to fibrin, with plasmin for-
been used for: mation thus localised to the site of fibrin formation.
tracheal intubation, with the patient awake or Fibrin is degraded to fibrin degradation products, with
anaesthetised. Especially useful in cases of known complement and platelet activation. Fibrinolysis may be
difficult intubation. The endoscope may be passed decreased by stress, including surgery; effects are great-
through a tracheal tube, and then guided via the est 23 days postoperatively. It may be increased by
mouth or nose into the larynx. Lidocaine may be fibrinolytic drugs, and following DIC as a response to
sprayed through a side port. The tube is passed over the large amount of fibrin formed. Also increased by
the scope into the trachea. May also be guided venous occlusion, catecholamines, and possibly epidural
through various airways that act as conduits. Has and spinal anaesthesia. Primary fibrinolysis may occur in
been used to place endobronchial tubes. certain malignancies.
checking the position of tracheal or endobronchial
tubes. Also used to aid placement of percutaneous Fibrinolytic drugs. Drugs causing fibrinolysis by acti-
tracheostomy. May be passed through special con- vating plasminogen. Used iv and intra-arterially to
nectors with rubber ports, thus allowing undisturbed prevent thrombosis, and to break up established
delivery of O2 and anaesthetic gases. thrombi, e.g. PE. Reduce mortality in acute MI when
assessment/diagnosis, sputum clearance and lavage, given iv within 12h. Also reduce morbidity when given
e.g. during/after thoracic surgery or in ICU. within 4.5h after acute ischaemic CVA. Streptokinase
Considerable practice is required to achieve adequate acts by binding to plasminogen, the resultant complex
skill in their use, which has been suggested as being activating other plasminogen molecules. Allergic reac-
desirable during all anaesthetists training but widely tions are common. Urokinase cleaves a specific peptide
acknowledged as being too difficult for most UK units bond in plasminogen, converting it to plasmin; it is used
to achieve. mainly for thrombolysis in the eye and arteriovenous
Rigid laryngoscopes incorporating fibreoptic chan- shunts. Tissue-type plasminogen activator (alteplase),
nels may also be used for tracheal intubation. reteplase and tenecteplase bind to fibrin and activate
Fibreoptic sensors have also been used for clinical plasminogen, converting it to plasmin; like streptoki-
measurement of e.g. pressure, flow and chemical nase, they are used as thrombolytics in MI. The major
concentrations. side effect is haemorrhage; nausea, vomiting and back
[Peter Murphy, US anaesthetist] pain may also occur.
See also, Intubation, awake; Intubation, difficult; Intuba-
tion, endobronchial; Intubation, tracheal Fibrocystic disease, see Cystic fibrosis

Fibrin degradation products (FDPs). Products of fibrin Fibronectin. Glycoprotein, involved in the removal of
breakdown by plasmin; thus blood levels reflect the rate intravascular debris and foreign substances via interac-
of fibrinolysis (e.g. increased levels occur in DIC). Half- tion with circulating leucocytes, enabling the opsonisa-
life is about 9h. May inhibit clot formation by competing tion process. May become depleted in critical illness,
for fibrin polymerisation sites. Also interfere with plate- especially trauma and sepsis; resultant impairment of
let function and thrombin; thus excess fibrinolysis may opsonisation is thought to contribute to organ hypoper-
impair further coagulation. May possibly damage vascu- fusion and MODS. Fibronectin level has been suggested
lar endothelium. as an additional indicator of disease progression in criti-
Non-specific testing for FDPs has been replaced in cal illness. Present in cryoprecipitate; replacement has
many centres by testing for the D-dimer portion of been used therapeutically but with conflicting results.
fibrin, which is released only during fibrinolysis and is
not present on fibrinogen or released during the latters Fick principle. Blood flow to an organ in unit time =
breakdown. amount of a marker substance taken
Measurement of FDPs (especially D-dimer) has been up by the organ in that time
used to aid diagnosis of DVT, a normal value excluding
thrombosis; however, levels may also be raised in many concentration difference of the substance in
other conditions (e.g. trauma, malignancy, pregnancy, the vesseels supplying and draining the organ
recent surgery and chronic inflammatory diseases). Thus The amount of a substance given up by an organ can also
D-dimer testing for thrombotic events has a sensitivity be used, e.g. CO2 (see below).
of about 90% and a specificity of 50%. May be used to determine blood flow to individual
Normal levels: < 10mg/l (FDPs); < 500ng/ml (D- organs, e.g. cerebral blood flow (KetySchmidt tech-
dimer). nique) or renal blood flow.
See also, Coagulation studies May also be used to determine cardiac output, using
O2 or CO2 as the substance measured, and the whole
Fibrinogen, see Coagulation body as the organ concerned:
234 Ficks law of diffusion

Using O2: cardiac output Can be placed anywhere in the breathing system,
O2 consumption (ml/min) although most commonly placed between the patient
= and the breathing system; require changing between
arterial mixed venous O2 concentration (ml/l) cases. All devices increase dead space and resistance to
substituting normal values: spontaneous ventilation, and are vulnerable to blockage
250 ml/min with fluid.
= Wilkes AR (2011). Anaesthesia; 66: 3139, 4051
200 150 ml/l
= 5 l/min Filtration fraction. Ratio of GFR to renal plasma flow
Using CO2: cardiac output (RPF). As RPF falls, GFR remains fairly constant
because of efferent arteriolar constriction, causing filtra-
CO2 output (ml/min) tion fraction to rise. Normally 0.160.2.
=
mixed venous arterial CO 2 concentration (ml/l)
substituting normal values: Fink effect. Reduced alveolar concentration of a gas
resulting from its dilution by another gas leaving the
200 bloodstream and entering the alveoli. Analogous but
=
540 500 ml/l opposite to the second gas effect. Originally described
= 5 l/min (as diffusion anoxia) in 1955 as the underlying cause of
hypoxaemia seen at the end of anaesthesia, when N2O
[Adolf Fick (18291901), German physiologist] leaving the bloodstream dilutes alveolar O2. Since recog-
nised as having little clinical importance, the effect of
Ficks law of diffusion. Rate of diffusion across a mem- hypoventilation and V/Q mismatch being much more
brane is proportional to the concentration gradient important.
across that membrane. [Bernard Raymond Fink (19142000), Seattle
See also, Fick principle anaesthetist]

Filgrastim, see Granulocyte colony-stimulating factor FIO2. Fractional inspired concentration of O2. By conven-
tion, expressed as a decimalised fraction, e.g. 0.21, 0.5,
although commonly still expressed as a percentage.
Filling ratio. Describes the extent to which cylinders
containing liquefied gases (e.g. N2O and CO2) are filled; First-pass metabolism. Metabolism of a substance
defined as the weight of substance contained in the cyl- once absorbed, occurring before it reaches the systemic
inder, divided by the maximum weight of water it could circulation. Active metabolites may be formed. Most
contain. The presence of gas above the liquid reduces the commonly refers to metabolism by the liver following
pressure increase caused by any temperature rise, reduc- oral administration of drugs, e.g. propranolol, morphine,
ing the risk of pressure build-up and rupture. lidocaine and GTN (i.e. drugs with a high extraction
Applicable to substances at temperatures below their
ratio). Drugs may be given by alternative routes to
critical temperatures, e.g.: bypass the liver, e.g. parenterally, sublingually or rectally.
N2O:
May also occur in the intestinal mucosa following oral
- 0.75 (temperate climate). administration (e.g. methyldopa, chlorpromazine, mid-
- 0.67 (tropical climate). azolam), and in the bronchial mucosa following inhala-
CO2: as for N2O.
tion (e.g. isoprenaline).
cyclopropane:
- 0.51 (temperate climate). Fixation error. Form of disordered situation awareness
- 0.48 (tropical climate). in which individuals distort available information so that
it fits with their notion of what is happening, rather than
Filters, breathing system. Devices routinely used for revise their assessment. Typically divided into: not appre-
reducing contamination of anaesthetic equipment. Two ciating the problem or its solution despite evidence to
main types of filter exist: the contrary (everything but that); persisting with one
pleated: resin-bonded ceramic or glass fibres in a diagnosis or plan despite evidence that it is wrong (this
densely packed, pleated sheet. Also known as and only this); or continuing to believe that there is no
hydrophobic filters as they do not absorb water. problem despite a worsening situation (everything is all
electrostatic: flat layer of electrostatically charged right). Anaesthetic examples include: repeated topping
material, with lower fibre density than pleated up of an epidural during labour that has ceased to func-
filters. tion, not accepting that it might have become dislodged;
In vitro evidence suggests that pleated filters are more giving repeated doses of sedation to an agitated patient
effective at preventing transmission of water-borne without appreciating that the cause is urinary retention;
pathogens (e.g. hepatitis C); since circle systems often and dealing with a worsening pulse oximeter reading by
contain condensation their use with electrostatic filters repeatedly cleaning and repositioning the probe instead
is not recommended. Filtration efficiency varies non- of addressing the hypoxaemia. Typically, a fresh practi-
linearly with particle size; most modern filters are mini- tioner can rapidly diagnose the fixation when introduced
mally efficient at particle sizes < 0.3m in diameter. to the scene, highlighting the value of involving col-
Testing involves challenging the filter with an aerosol leagues early when crises occur.
of sodium chloride particles at the most penetrating
particle size, using gas flow of 30l/min for adult filters Flail chest. Disruption of chest wall integrity, where a
(15l/min for paediatric). Modern filters usually incorpo- portion of the thoracic cage becomes detached from the
rate a heat-moisture exchanger. bony structure of the rest. The flail segment no longer
 Flow 235

moves outwards on inspiration, but is free to be drawn stoichiometric mixture lies within the explosive range.
inwards by negative intrathoracic pressure; it is pushed Flammability is greater in N2O than in O2, because the
out during expiration whilst the rest of the thorax con- former decomposes to produce O2 with release of energy.
tracts. Occurs in severe chest trauma with multiple frac- Addition of water vapour reduces flammability.
tures involving several ribs. May also result from surgery. Modern, non-flammable agents will ignite only at
Features: higher concentrations than occur during anaesthesia,
hypoventilation, with reduced tidal volume and and require much greater amounts of energy to initiate
vital capacity. Pendelluft is now thought not to ignition (activation energy).
occur; mediastinal shift results in air entry to both See also, Explosions and fires
lungs, although overall hypoventilation may be
severe. Hypoventilation is further exacerbated by
pain. Ability to cough is reduced due to mechanical Flash-point. Lowest temperature at which a saturated
impairment and pain. vapour of a liquid ignites when exposed to a flame, in
underlying lung contusion/atelectasis/pneumo the presence of one or more other gas(es).
thorax with resultant shunt and V/Q mismatch;
thought to be more important than hypoventilation.
Flecainide acetate. Class Ic antiarrhythmic drug. Slows
associated injuries, e.g. to mediastinum, head,
impulse conduction by blocking sodium channels, thus
abdomen.
prolonging phase 0 of the cardiac action potential (in
mediastinal shift may affect cardiac output.
Management is as for chest trauma, i.e.:
both the conducting system and myocardial cells). Used
for severe VT and extra-systoles, and SVT, especially
O2 administration.
those involving accessory pathways (e.g. Wolff
analgesia (e.g. systemic opioids/intercostal nerve
ParkinsonWhite syndrome).
block/epidural analgesia). Dosage:
treatment of hypovolaemia and associated injuries.
2mg/kg up to 150mg, over 1030min iv (with ECG
chest drainage if required.
monitoring).
physiotherapy.
by infusion: 1.5mg/kg/h for 1h; 0.10.25mg/kg/h
nasogastric drainage helps prevent gastric
thereafter.
dilatation.
100mg orally bd for VT (50mg for SVT).
if arterial blood gases are acceptable, no further
Side effects:
treatment may be required. Improved oxygen-
dizziness, visual disturbances, corneal deposits.
ation and chest wall splinting may be achieved
myocardial depression (minor), proarrhythmias.
by CPAP.
resistance to endocardial pacing.
tracheal intubation and IPPV. May be continued
increased plasma levels in hepatic/renal failure
until the underlying lung improves or surgical fixa-
(levels should be monitored).
tion of the flail segment (i.e. up to several weeks).
has been associated with increased risk of cardiac
IMV has been used.
arrest after MI, therefore reserved for life-
early fixation of rib fractures is preferred by some
threatening arrhythmias.
surgeons.
Pettiford BL, Luketich JD, Landreneau RJ (2007).
Thorac Surg Clin; 17: 2533 Flow. Volume of fluid moving per unit time. Flow
through a tube may be:
Flame ionisation detector. Device used in analysis of laminar: flow is smooth and without eddies.
gas mixtures, separated, e.g. by gas chromatography. A Flow velocity reduces towards the tubes sides
potential difference is applied across a flame of hydro- (approaching zero at the edge); flow at the centre is
gen gas burning in air. Addition of organic vapour to the greatest, at approximately twice the mean (Fig. 69a).
gas stream causes a change in current flow across the Described by:
flame, the amount of change proportional to the amount
of substance present. Used only to quantify the amount laminar flow
of a known substance, not to identify unknown ones. pressure gradient along tube radius4
See also, Gas analysis =
tube length viscosity of fluid 8
Flammability. Ability to support combustion. Depen- (HagenPoiseuille equation).

turbulent (Fig. 69b): caused when the tube is
dent on molecular structure; e.g. CC bonds readily
break down with heat and O2 to form carbon monoxide/ unevenly shaped, or when the fluid flows through
dioxide, whereas CF bonds are resistant. Flammability an orifice or around sharp edges. Also occurs from
limits refer to concentrations of a substance that will laminar flow when flow velocity is high, exceeding
support combustion; e.g.: the critical velocity. Reynolds number describes
cyclopropane:
the relationship between tube and fluid character-
- 2.560% in O2. istics and velocity at which turbulent flow occurs.
- 2.510% in air. Turbulent flow is proportional to:
- 1.530% in N2O. - radius2.
diethyl ether: - pressure gradient .
- 282% in O2. - 1/length.
- 235% in air. - 1/density of fluid.
- 1.524% in N2O. Flow in the airways and blood vessels is a mixture of
Ranges for explosive mixtures occur within these laminar and turbulent, but behaves approximately
limits, especially with high O2 concentration. The according to the above principles.
236 Flow-directed balloon-tipped pulmonary artery catheters

the number of holes below the bobbin, i.e. the

(a) bobbins height.
- Heidbrink flowmeter. The bobbin is extended
vertically to form a rod; its bottom end sits in a
tapered tube whilst its top end lies opposite a
linear scale above the tapered part. It functions in
a similar way to the rotameter, but without
rotating.
Velocity - peak-flow meters.
variable pressure, variable orifice. In the watersight
flowmeter, gas passes through a tube with holes
(b) along its length, immersed into water. At low gas
flows, gas bubbles from the upper holes only; at
higher flow rates, from the lower holes as well. The
holes are marked with according flow rates. Orifice
variability results from the different number of
holes through which gas may pass; pressure vari-
ability arises because pressure is higher at greater
depth of water.
Velocity constant pressure, constant orifice. Bubble flowme-
ters may be used for calibration at low flow rates.
Fig. 69 Flow profiles: (a) laminar with parabolic profile; (b) turbulent Gas passes along a uniform tube, carrying a thin
with flat profile
soap film with it. Flow is deduced by measuring the
velocity of the film along the tube using a timer.
Other flowmeters include:
Measurement: thermistor flowmeter: the cooling effect of a gas
gas: flowmeters. stream on a thermistor varies with flow rate.
liquid: dilution techniques, electromagnetic flow ultrasonic flowmeter: turbulent eddies are formed
measurement, Fick principle. Similar flowmeters to around a rod in the gas path. The frequency of oscil-
those used for gases may also be used. lation of the eddies, measured by Doppler probe, is
measurement of volume over a certain time. proportional to flow rate. Alternatively, ultrasound
beams may be projected diagonally across the gas,
Flow-directed balloon-tipped pulmonary artery and transit time measured.
catheters, see Pulmonary artery catheterisation Flow can also be determined by measuring the volume
of gas per unit time, e.g. using a respirometer.
Flow generators, see Ventilators [Jay A Heidbrink (18751957), US anaesthetist]

Flowmeters. Devices for measuring flow, usually refer- Flowvolume loops. Curves resulting from simultane-
ring to gas flow, e.g. from cylinders and anaesthetic ous measurement and plotting of air flow and lung
machines, or in breathing systems. volume during a maximal forced expiration. If residual
May be:
volume is known, lung volume may be determined by
constant orifice, variable pressure. Since flow
measuring expired volume. Characteristic loops are
through an orifice is proportional to the pressure obtained in certain conditions, although the loops
difference across it, flow may be deduced by mea- obtained in practice are rarely as easily distinguishable
suring the pressure difference across a fixed orifice. (Fig. 70). Also useful for assessing the efficacy of bron-
In the first two examples, only the downstream pres- chodilator therapy in COPD.
sure is measured, since the pressure upstream of Much of the information from studying forced expira-
the orifice is constant: tion may be obtained from flowvolume loops, e.g.
- simple pressure gauge downstream from the forced expiratory flow rate, forced expiratory volume
outlet of an O2 cylinder. The gauge may be and peak expiratory flow rate.
calibrated directly for flow, e.g. litres/min. See also, Lung function tests
- water depression flowmeter. The pressure is
measured with a simple water manometer.
- pneumotachograph. Pressure is measured elec- Flucloxacillin. Penicillinase-resistant penicillin used
tronically using transducers. to treat staphylococcal infections. Peak levels occur
constant pressure, variable orifice. If the pressure
within an hour of administration. 90% protein-bound;
across a variable orifice remains constant, the size although metabolised in the liver, 50% appears
of the orifice depends on the gas flow. Examples: unchanged in the urine.
Dosage:
- rotameter, simple ball flowmeter and dry bobbin
250500mg orally/im qds.
flowmeter. The size of the orifice is determined by
250mg2.0g slowly iv qds.
the height of the bobbin in its tube: the greater
Side effects: as for benzylpenicillin. Acute cholestatic
the height, the larger the orifice. In the rotameter
and ball flowmeter, the tube is of tapered bore, jaundice may occur even after stopping therapy.
being wider at the top than at the bottom. The dry
bobbin flowmeter tube is of uniform diameter, Fluconazole. Triazole antifungal drug used to treat local
with small holes arranged longitudinally. The vari- and systemic candidiasis and cryptococcal infection
ability of the effective orifice size is provided by (including meningitis), especially associated with HIV
 Fluid balance 237

infection. Well absorbed orally, with peak levels within

(a) 6h. Elimination half-life 30h.
Dosage: 50400mg orally/iv daily.
Side effects: nausea, vomiting, rashes, allergic reac-
tions, toxic epidermal necrolysis, hepatic impairment.
May increase blood levels of the antihistamines terf-
Flow

enadine and astemizole, resulting in prolonged QT

syndrome and fatal ventricular arrhythmias, including
torsade de pointes.
0
TLC RV Flucytosine. Intravenous antifungal drug used in
systemic yeast infections; often used together with
amphotericin, with which it is synergistic. Resistance
may occur.
Dosage: 50mg/kg qds iv over 2040min, usually for
no more than 7 days (prolonged therapy needed for
cryptococcal infection). Trough plasma levels of 25
(b)
50mg/l (200400mol/l) are optimal.
Side effects: nausea, vomiting, diarrhoea, rashes, con-
fusion, hepatitis, blood dyscrasias. Weekly blood
counts are required in prolonged treatment.
Flow

Fludrocortisone acetate. Mineralocorticoid used for

replacement therapy in adrenocortical insufficiency,
congenital adrenal hyperplasia and postural hypoten-
0 sion associated with autonomic neuropathy. Has similar
TLC RV actions to aldosterone; also has mild hydrocortisone-like
actions.
Dosage: 50300g od orally.
Side effects: hypertension, sodium and water reten-
tion, hypokalaemia. May also produce glucocorticoid
effects.
(c)
Fluid. Form of matter that continuously deforms when
subjected to a shearing force, i.e. gas or liquid. Continu-
ous shearing force results in flow; resistance to flow is
proportional to viscosity. For a Newtonian fluid (e.g.
Flow

water) viscosity is constant for different shear rates and

flows; for a non-Newtonian fluid (e.g. blood), it varies
with shear rates and flows.
[Sir Isaac Newton (16421727), English scientist]
0
See also, Fluidics
TLC RV
Fluid balance. Normal approximate daily fluid intake of
a 70-kg adult:
1500ml liquid
750ml in food
(d) 250ml from metabolism within the body.
total: 2500ml
Normal output:
1500ml urine
100ml in faeces
Flow

900ml insensible water loss.

total: 2500ml
Loss in sweat is normally negligible but may exceed
0 several litres in hot environments. Insensible losses
TLC RV
are also increased in high temperatures. About 5% of
body water is exchanged per day in adults, 15% in
infants; hence the increased risk of dehydration in
the latter.
Balance is normally regulated to maintain ECF
TLC, total lung capacity
volume and osmolality; changes are detected by barore-
RV, residual volume
ceptors and osmoreceptors, with resultant compensatory
Fig. 70 Characteristic flowvolume loops: (a) normal; (b) obstructive mechanisms:
lung disease; (c) restrictive lung disease; (d) tracheal/laryngeal water intake is regulated by thirst; increased by
obstruction hypovolaemia and hyperosmolality.
cardiovascular compensation for hypovolaemia.
238 Fluid therapy

urinary output is regulated by vasopressin, atrial Fluids, body. Approximately 60% of male body weight
natriuretic peptide and the renin/angiotensin is water; 5055% in females (greater proportion of fat).
system. Total body water may be measured using a dilution
Fluid balance may be disturbed in patients presenting technique with deuterium oxide (heavy water). Its main
for anaesthesia, perioperatively and in ICU: constituent compartments are intracellular fluid (ICF),
reduced intake, e.g. coma, dysphagia, nausea, fasting ECF, plasma and interstitial fluid (Fig. 71). Approxi-
instructions. mately 1 litre is contained within the GIT and CSF
increased intake, e.g. excessive iv administration. (transcellular fluid).
redistribution, e.g. to third space. In neonates, ECF exceeds 30% (but plasma is still
reduced output, e.g. syndrome of inappropriate 5%), and ICF is less than 40%. These differences are
antidiuretic hormone secretion. greatest in premature babies, when ECF exceeds ICF.
increased output, e.g. sweating, polyuria, vomiting, During childhood, the adult situation slowly develops.
diarrhoea. Composition of fluid compartments is shown in
Administration of iv fluids perioperatively is now Table 20.
routine, though; excessive dextrose administration may Modes of movement of ions and molecules between
lead to hyperglycaemia and hyponatraemia, whilst compartments:
excessive salt solution administration may cause periph- diffusion.
eral and pulmonary oedema. Improved recovery with facilitated diffusion: carrier molecules transport
reduced PONV has been claimed following fluid admin- substances from high to low concentrations, requir-
istration (especially containing dextrose) during minor ing no energy.
surgery compared with no fluids. active transport.
IV fluid administration should be guided by the filtration.
following: Movement of substances is also affected by other sub-
maintenance requirements: 40ml/kg/day (1.6ml/ stances, e.g. Donnan effect.
kg/h). Requirements are greater in paediatric Water moves across membranes from solutions of
anaesthesia. low concentrations to those of high concentrations
replacement of blood loss (see Haemorrhage). (osmosis). Depending on their constitution, different iv
third-space losses: with perioperative evaporative fluids will fill certain compartments more than others.
losses, approximately 1015ml/kg/h during major See also, Blood volume; Fluid balance
abdominal surgery.
other losses, e.g. nasogastric aspirate. Flumazenil. Benzodiazepine antagonist, structurally
Careful attention to fluid balance is required in all peri- related to midazolam and introduced in 1987. A com-
operative and critically ill patients to prevent complica- petitive inhibitor of benzodiazepines at the central
tions, e.g. hypernatraemia, hyponatraemia, dehydration, GABAA/benzodiazepine receptor complex. Used to
renal failure. Therapy is guided by CVP, urine output, reverse excessive sedation due to benzodiazepines,
BP, pulse and electrolyte balance. Body weight is a useful e.g. following attempted suicide, prolonged sedation
supplement to fluid intake/output charts. with benzodiazepines in ICU and iatrogenic over-
See also, Colloid/crystalloid controversy; Fluids, body dose. Benzodiazepine metabolism is unaffected. 50%
protein-bound.
Fluid therapy, see Intravenous fluids

Fluidics. Technology of operating control systems by

utilising flow characteristics of gases or liquids. Has
been used in control mechanisms of ventilators, e.g.
Total body water Intracellular fluid (ICF)
employing the Coanda effect. The direction of a jet of
42 l (60%) 28 l (40%)
gas in a valve may be switched by signal jets of driving
gas across the main jet. Combinations of signal jets allow
complex manipulation of the valve output, without Extracellular fluid (ECF) Transcellular fluid
moving parts. 14 l (20%) 1 l (1.5%)
Pneumatic spool valves may contain moving shuttles,
driven by gas from either end. The valve chamber is
divided into segments by seals through which the shuttle Interstitial fluid Plasma
passes; the valve output depends on the lining up of 9.5 l (14%) 3.5 l (5%)
ports and channels in the shuttle and valve wall. The
output may be used to drive cylinders that may be driven Fig. 71 Composition of body fluids, with volumes for an average
from either end. 70-kg man (% body weight)

Table 20 Approximate composition of body fluid compartments (mmol/l)

Compartment Na+ K+ HCO3 Cl Ca2+ Mg2+ SO42 HPO42 + PO43

Intracellular fluid 10 150 10 3 3 30 20 100

Interstitial fluid 140 5 30 110 5 3 1 2
Plasma 140 5 28 110 5 3 1 2
 Food and Drug Administration 239

Dosage: 0.20.3mg iv, repeated as necessary up of facilities, requirement for portable equipment and
to 12mg. May also be given by infusion lack of patient preparation. Commonest emergency is
(0.10.4mg/h). postpartum haemorrhage caused by retained placenta.
Side effects: nausea, vomiting, dizziness, headache, Use of a flying squad has declined as the number of
confusion, pulmonary oedema. Has caused excessive home deliveries has decreased. The above problems
excitement and convulsions, especially in patients have led many units to withdraw anaesthetic cover from
maintained on long-term benzodiazepines, e.g. for such squads, with emphasis on rapid transfer of the
epilepsy. Because of its short half-life (less than 1h), patient to hospital.
its effects may wear off with recurrence of sedation. See also, Cardiopulmonary resuscitation, neonatal;
Obstetric analgesia and anaesthesia
Fluoride ions. Nephrotoxic ions implicated in the high-
output renal failure seen following methoxyflurane Foetal, see Fetal
administration. Evidence for their role:
degree of renal impairment is proportional to
plasma concentration: Fomepizole (4-Methylpyrazole). Competitive inhibitor
- subclinical evidence of renal impairment occurs of alcohol dehydrogenase, available on a named-patient
above 50mol/l. basis for methanol or ethylene glycol poisoning. A
- polyuria, decreased urinary osmolality and loading dose of 15mg/kg iv over 30min is followed by
increased plasma sodium and osmolality occur 10mg/kg every 12h for four doses, then 15mg/kg every
above 80100mol/l. 12h until methanol or ethylene glycol concentrations
infusion of fluoride ions into rats produces similar are < 46mmol/l, and the patient is asymptomatic with
renal effects. normal pH. Undergoes hepatic metabolism and excreted
Mechanism of renal damage is unclear but may in the urine.
involve impairment of both renal Na/K/ATPase See also, Alcohol poisoning
systems and vasopressin action.
Levels are highest after methoxyflurane, but may be Fondaparinux sodium. Synthetic factor Xa inhibitor;
raised after other halogenated volatile agents: sulphated pentasaccharide derived from the factor
methoxyflurane: 5060mol/l after 2.5 MAC hours; Xa-binding moiety of unfractionated heparin. Licensed
90120mol/l after 5 MAC hours. for treatment of acute coronary syndromes and prophy-
enflurane: up to 30mol/l after prolonged use (over laxis and treatment of venous thromboembolism in
9h). Plasma levels are highest in obese patients. adults.
Enzyme induction with isoniazid is thought to Dosage:
increase levels. treatment of unstable angina/non-S-T segment ele-
isoflurane: under 5mol/l even after prolonged vation MI and DVT prophylaxis in immobilised
surgery. Levels of up to 90mol/l have been patients: 2.5mg sc od (in surgical patients, first dose
reported after several days use for sedation in ICU. 6h after skin closure).
halothane: minimal production of fluoride ions. treatment of DVT and PE: 5, 7.5 or 10mg sc od (for
sevoflurane: up to 40mol/l after prolonged surgery body weight < 50kg, 50100kg and > 100kg respec-
(unaffected by obesity). tively) until oral anticoagulation established.
desflurane: minimal production of fluoride ions. treatment of S-T segment elevation MI: 2.5mg iv,
followed by 2.5mg sc od.
Fluotec vaporiser, see Vaporisers Side effects: haemorrhage, purpura, thrombocytope-
nia, GI upset, rash.
Flupirtine maleate. Non-opioid, non-NSAID centrally
acting analgesic drug, recently investigated. Thought to
block NMDA receptors, although the precise mecha- Fondation Europenne dEnseignement en Anaes-
nism of action is unclear. Also causes muscular relax- thsiologie (Foundation for European Education in
ation via enhancement of GABA-mediated spinal Anaesthesiology; FEEA). Organisation founded in 1986
inhibition. Not available in the UK. (with financial support from the European Union) to
provide continuous medical education in anaesthesiol-
Flurbiprofen. NSAID available for oral and pr admin- ogy throughout Europe. Acts in agreement with national
istration; has been used for postoperative analgesia. anaesthetic societies and organises courses throughout
Dosage: 50100mg 46-hourly up to 300mg/day Europe and, more recently, South America.
(100mg suppositories available).
Side effects: as for NSAIDs. Food and Drug Administration (FDA). US organisa-
tion, involved in testing new drugs and reviewing test
Fluroxene (Trifluoroethyl vinyl ether). Obsolete inhala- results. Also controls imports, and regulates foods and
tional anaesthetic agent, introduced in 1954. The first cosmetics. Companies must apply to the FDA before
fluorine-containing volatile agent. Explosive, possibly initiating clinical trials. Evolved after World War II from
mutagenic, and toxic to experimental animals due to the 1938 Food, Drug and Cosmetics Act, restricting
biotransformation to trifluoroethanol. labelling and advertising of drugs; amended in 1968 to
require that drugs be shown to be efficacious as well as
Flying squad, obstetric. Mobile team including anaes- safe. Thus enforces laws enacted by US Congress. Previ-
thetist, obstetrician and midwife; first suggested in 1929, ously, the Pure Food and Drugs Act of 1906 and subse-
and organised in Glasgow in 1933. The usual problems quent amendments attempted to prevent improper
of obstetric anaesthesia and neonatal resuscitation are labelling and fraudulent claims by manufacturers.
compounded by the unfamiliar environment, limitation See also, Committee on Safety of Medicines
240 Foot, nerve blocks

Foot, nerve blocks, see Ankle, nerve blocks; Digital

nerve block (a)

Force. That which changes a bodys shape or state of FVC

motion. Derived SI unit of force is the newton; in base

Expired volume
units this is equivalent to mkg/s2. FEV1

Forced diuresis. Method of increasing renal excretion

of certain drugs using iv fluids or diuretics to increase
urinary volume. Sometimes used in poisoning and over-
doses. Further drug removal is achieved by manipulating
urinary pH, thereby trapping the ionised fraction of the
drug and preventing its diffusion back into the blood-
stream, since charged molecules diffuse poorly across 0 1
biological membranes. Time (s)
Forced alkaline diuresis:
(b)
used in poisoning with acid drugs, e.g. salicylates
and barbiturates.
500ml/h of the following fluids are administered in
FVC
rotation:
75% FVC

Expired volume
- 500ml 1.26% sodium bicarbonate.
- 500ml 5% dextrose.
- 500ml 0.9% saline.
a
CVP, urine output and pH, blood gases and plasma FEF 2575% = a/b
electrolytes (especially potassium) must be closely
monitored. Infusion rate is reduced in the elderly. 25% FVC
Forced acid diuresis:
used in poisoning with alkaline drugs, e.g. amfet-
amines, phencyclidines. 0 b
1000ml/h of the following fluids are administered Time (s)
in rotation:
(c)
- 500ml 5% dextrose + 1.5g ammonium chloride.
- 500ml 5% dextrose.
- 500ml 0.9% saline.
Expired volume

monitoring as above.
Severe metabolic upset and circulatory overload may FVC
occur. The technique is rarely used now, since it has been
superseded by haemodialysis and haemofiltration.
FEV1
Forced expiration. Means of investigating lung func-
tion, from which may be measured: forced expiratory
flow rate (FEF2575%), FEV, FVC and peak expiratory 0 1
flow rate. Other suggested measurements exclude the Time (s)
first 200ml of expiration, or analyse the flow rate at 50%
(d)
of vital capacity.
Flowvolume loops and data from spirometers (e.g.
the Vitalograph) may be analysed (Fig. 72). Repetition
Expired volume

following bronchodilator therapy may indicate the FVC

extent of reversible airway obstruction. FEV1
At lung volumes of up to 60% of vital capacity,
maximal expiratory flow rate is independent of effort;
increasing effort raises intrathoracic pressure, increasing
the pressure difference across the airways and leading
to airway collapse.
See also, Lung function tests 0 1
Time (s)
Forced expiratory flow rate (FEF2575%). Average flow
rate measured at between 25% and 75% of forced Fig. 72Typical forced expiratory patterns: (a) normal; (b) showing
maximal expired volume (Fig. 72). Usually changes with calculation of FEF (2575%); (c) obstructive lung disease; (d) restrictive
forced expiratory volume, but has wider spread of lung disease
normal values.
See also, Forced expiration; Lung function tests; Peak
expiratory flow rate
80% of FVC, which may be measured at the same time
Forced expiratory volume (FEV). Volume of gas forc- using a spirometer. Reduced in obstructive lung disease,
ibly exhaled from full inspiration, in a set period of time as is the FEV1/FVC ratio. In restrictive disease, FEV1
(normally 1s; the volume is then called FEV1). Normally may be normal, but FVC is reduced.
 Foreign body, inhaled 241

Easier and more comfortable to measure than

maximal voluntary ventilation. (a)
See also, Forced expiration; Lung function tests

Forced vital capacity (FVC). Vital capacity measured

when expiration is forced. Closure of some airways may
occur when intrathoracic pressure is high, causing air-
trapping. FVC thus may be less than true vital capacity.
Reduced in restrictive disease, the supine position, the
elderly, muscle weakness, abdominal swelling, pain, and
when premature airway closing occurs during forced
expiration, e.g. emphysema.
See also, Forced expiration; Lung function tests; Lung
volumes

Forceps. Many varieties may be used by anaesthetists, (b)

e.g. (Fig. 73):
Magills forceps: introduced in 1920 to assist place-
ment of gum-elastic bougies for insufflation anaes-
thesia. Used to guide tracheal tubes into the larynx,
or nasogastric tubes into the oesophagus, under
direct vision. May damage the tracheal tube cuff if
grasped. Also used to place pharyngeal packs or
to remove foreign bodies. The operators hand is
held out of the line of vision by the angled handles.
Adult and paediatric sizes are available, as are (c)
single-use versions. Many modifications have been
described.
Krauses forceps: used to hold local anaesthetic-
soaked pledgets in the piriform fossae for blocking
the superior laryngeal nerves for awake intubation.
They bear a spring catch and spiked jaws.
several tongue forceps exist; formerly used to pull
the tongue forward to relieve airway obstruction,
but now more likely to be used for fixing tubing
and drapes.
[Herman Krause (18481921), German laryngologist;
Berkley GA Moynihan (18651936), English surgeon] Fig. 73Types of forceps used in anaesthesia: (a) Magill; (b) Krause;
See also, Mouth gags (c) Moynihan tongue forceps

Foreign body, inhaled. Leading cause of accidental perioperatively:

death in children less than 4 years old. May obstruct - an experienced anaesthetists presence is manda-
upper or lower airways. Should be considered in any tory, as is good communication with the surgeon.
child with stridor or persistent cough and chest infec- - classic technique is inhalational induction of
tions. Diagnosis is based on history, clinical findings and anaesthesia; sevoflurane is usually the modern
imaging (although only 11% of aspirated objects are drug of choice (replacing halothane). N2O is
radio-opaque). Most small objects lodge in the right avoided in case of distal air-trapping, and to raise
main bronchus, because of its more vertical angle of FIO2. Induction may be slow.
origin and greater width. Organic matter (e.g. peanuts) - cautious intravenous induction whilst attempting
may cause intense bronchial inflammatory reactions to maintain spontaneous ventilation is an
within a few hours, with oedema and possibly bronchial alternative.
obstruction. Bronchiectasis may be a late complication. - lidocaine spray to the vocal cords may reduce risk
Other features may include: of perioperative laryngospasm.
distal atelectasis. - intraoperatively, both spontaneous and controlled
distal air-trapping if the object acts as a ball-valve. ventilation can be used, although IPPV is often
CXR at end-expiration may reveal unilateral avoided because of the risk of blowing the object
hyperinflation. distally. Adequate depth of anaesthesia and oxy-
features of airway obstruction. genation may be difficult to maintain with an
infection. inhalational agent and spontaneous ventilation,
Removal is via bronchoscopy (rigid most commonly). without excessive hypercapnia. TIVA (e.g. with
Anaesthetic management: remifentanil and propofol) may provide more
preoperatively: reliable and constant depth of anaesthesia, and
- assessment for: type of object aspirated; timing of can be titrated to allow spontaneous ventilation.
aspiration; and severity of airway obstruction. postoperatively:
Preoperative fasting is appropriate if possible. - close monitoring is required in case of broncho-
- premedication with atropine. Anxiolytic drugs spasm or laryngospasm.
may be helpful. - humidified O2 administration by mask.
242 Forward failure

Major complications occur in 1% of cases, and include

cardiorespiratory arrest (most commonly due to hypox-

Nitrogen concentration
aemia), bronchial rupture, pneumothorax or pneumo-
mediastinum, laryngeal oedema and failed bronchoscopy
requiring thoracotomy.
Fidowski CD, Zheng H, Firth PG (2010). Anesth Analg;
111: 101625 1 2 3 4

Forward failure, see Cardiac failure

Foscarnet sodium. Antiviral drug, reserved for treat- 0 Closing capacity Residual volume
ment of cytomegalovirus retinitis in AIDS (when ganci-
Volume
clovir is contraindicated) or for herpes simplex virus
infections that are unresponsive to aciclovir. Fig. 74 Fowlers method of estimating anatomical dead space and
Dosage: 60mg/kg iv tds, reduced to 60mg/kg od after
closing capacity (see text)
23 weeks. For resistant herpes simplex virus infec-
tions, 40mg/kg iv tds for 23 weeks.
Side effects: nausea, renal failure, GIT upset, hypocal-
caemia, convulsions.
Fowlers method (Single-breath nitrogen washout).
Method of investigation of lung volumes, described in
Fosphenytoin sodium. Water-soluble prodrug, com-
1948. The subject breathes air normally, and takes a
pletely converted to phenytoin after parenteral admin-
maximal breath of O2 (i.e. to vital capacity) from the end
istration, with a conversion half-life of 15min. Useful in
of normal expiration (i.e. FRC). Exhaled nitrogen con-
treating acute partial and generalised tonicclonic sei-
centration is measured during maximal slow expiration
zures. Particularly appropriate in management of status
(i.e. to residual volume), and plotted against volume of
epilepticus. 1.5mg of fosphenytoin is equivalent to 1mg
expired gas. A rapid-response nitrogen meter is required.
of phenytoin. Can be administered iv or im with good Four phases are described (Fig. 74):
absorption. Following its administration, monitoring of
phase 1: O2 from the conducting airways (anatomi-
phenytoin levels is not recommended until conversion
cal dead space), containing no nitrogen.
to phenytoin is complete (i.e. within 2h after iv infusion
phase 2: mixture of dead-space gas and alveolar gas.
and 4h after im injection).
phase 3: alveolar gas, containing the nitrogen
Side effects: paraesthesia, hypotension, nystagmus,
present in the alveoli before the O2 breath started.
ataxia, skin reactions, pruritus. Severe hypotension
There is a slight upward slope normally, increased
and arrhythmias, including heart block, VF and asys-
in lung disease.
tole have been described following its use; monitoring
phase 4: at closing capacity, lower alveoli and
of ECG, BP, pulse rate and respiratory function
airways collapse, thus the exhaled gas comes from
is recommended for 30min after the end of the
upper airways only. At the onset of the O2 inspira-
infusion.
tion, the upper airways were already considerably
expanded (with nitrogen-containing air) compared
Fospropofol. Water-soluble phosphorylated prodrug with lower ones, since most ventilation is of upper
of propofol; converted to the latter by plasma alkaline lung regions at normal tidal volume. Most of the
phosphatases within a few minutes of iv injection. inspired O2 therefore entered the lower alveoli,
Licensed in the USA for sedation in adults during endo- since they started off smaller. When they collapse,
scopic procedures (but not for general anaesthesia). nitrogen-rich gas from the upper alveoli is exhaled,
Presented as a clear, colourless solution of 3.5% concen- giving rise to phase 4.
tration. Initial iv bolus dose is 6.5mg/kg followed by Anatomical dead space is measured to the mid-point of
supplemental doses of 1.6mg/kg titrated to effect. Onset phase 2.
of action and recovery are slower than with propofol. CO2 measurement may be used in a similar way, using
Does not cause pain on injection but frequently (> 50% capnography.
incidence) causes unpleasant perineal paraesthesia (e.g. [Ward S Fowler, US physiologist]
burning, stinging) and pruritus. Other adverse effects
(e.g. hypotension, respiratory depression) are as for Fractional shortening, see Left ventricular fractional
propofol. shortening

Fourier analysis. Mathematical breakdown of wave- Frankenhausers plexus block, see Paracervical block
forms into simple sine wave constituents. Any complex
waveform consists of sine waves of different frequen- FRC, see Functional residual capacity
cies: the slowest (fundamental) frequency and harmon-
ics thereof. Used in analysis and reconstruction of FRCA examination (Fellowship of the Royal College
waveforms, e.g. transmission of electrical signals. The of Anaesthetists). Predated by the FFARCS examina-
higher the frequencies analysed, the more accurate the tion (195389) and the FCAnaes examination (198992).
reproduction. Since 1985 (as the FFARCS examination) it consisted of
[Baron Jean-Baptiste Fourier (17681830), French three parts: I, relating to the fundamentals of clinical
mathematician] anaesthesia; II, relating to the basic sciences; III, relating
to the practice of anaesthesia as a whole. Replaced in
Fourniers gangrene, see Necrotising fasciitis 1996 by a two-part examination: the Primary, relating to
 Functional residual capacity 243

basic sciences and clinical safety; and the Final, relating Fuel cell, see Oxygen measurement
to applied basic sciences and the practice of anaesthesia/
intensive care. Recent pass rates are in the order of Fullers earth. Soft, clay-like substance containing silica
4050% for each part. and clay minerals; found naturally in many parts of the
world. Used for pressing and cleaning cloths and fleeces
Free radicals. Atoms or molecules with unpaired elec- (fulling) and in the purification of oils. Used as an
trons, produced as intermediaries during certain biologi- adsorbent in paraquat poisoning.
cal reactions. For example, the reduction of molecular O2
to oxide ions produces oxygen-derived free radicals
including superoxide (O2), hydroxyl (OH) and hydro- Functional imaging. The study of changes in cerebral
peroxy (HO2) radicals, the latter two being particularly haemodynamic and metabolic status in response to
reactive. external stimuli. Techniques include positron emission
Involved in normal phagocyte function and host tomography, which provides maps of regional blood flow
defence; released into phagosomes to destroy bacteria. and oxygenation; functional MRI, which produces high-
May also be produced by radiation and certain chemi- resolution oxygenation maps; and near infrared spec-
cals, and increased production has been implicated in troscopy, which provides a continuous measure of tissue
many disease processes, e.g. pulmonary O2 toxicity, halo- oxygenation.
thane hepatitis, ARDS, paracetamol poisoning, burns,
carcinogenesis and bowel ischaemia. Defence mecha- Functional residual capacity (FRC). Lung volume,
nisms against normal free radical formation may be equivalent to the volume of gas present in the lung after
overwhelmed, resulting in oxidation of tissue compo- a normal expiration (the sum of residual volume and
nents. Reactions with free radicals may liberate further expiratory reserve volume). Normally 2.53.0 litres for
free radicals. an average male.
Defence mechanisms include the enzymes superox- Measurement:
ide dismutase (SOD) and catalase, and antioxidants helium dilution: breathing of air with a known con-
(free radical scavengers), e.g. glutathione and vitamin E. centration of helium from a spirometer, starting
Increasing these substances indirectly, or administering from the end of normal expiration. CO2 is absorbed
them directly, reduces tissue injury in some experimental using soda lime, and O2 replaced as it is used. The
models, but extrapolation to clinical use is unclear. helium distributes between spirometer, tubing and
the subjects lungs, with minimal uptake by the
Free water clearance, see Clearance, free water bloodstream. After equilibrium is reached, the new
concentration of helium is measured:
Freud, Sigmund (18561939). Austrian neurologist and total amount of helium in the system
psychiatrist, the inventor of psychoanalysis. Postulated = initial concentration volume of apparatus
that cocaine might be a treatment for morphine addic- = new concentration volume of (apparatus +
tion, and a stimulant for psychoneurotic patients. Inves- lungs)
tigated the drug with his friend Koller, who introduced nitrogen washout: the subject breathes 100% O2
it as the first local anaesthetic drug. Fled from Vienna to from end of normal expiration, and total volume of
London in 1938 to escape the Nazis. expired gas over several minutes is analysed for
nitrogen content. This amount of nitrogen was origi-
Friedreichs ataxia. Hereditary (autosomal recessive) nally contained in the FRC to give a concentration
condition consisting of progressive degeneration of spi- of 79%; thus FRC may be calculated.
nocerebellar and pyramidal tracts and dorsal root body plethysmograph.
ganglia, mainly affecting the legs. Onset is in childhood The helium dilution and nitrogen washout techniques
or teens. do not include collapsed portions of lung, or those
Features: with poor air entry (if not enough time is allowed
upper motor neurone weakness, with upgoing for equilibration). Measurements using the body
plantar reflexes (if present). plethysmograph include these areas, which may not
ataxia, dysarthria and nystagmus. participate in gas exchange. Comparison of the
impaired joint position, vibration and touch sense. tests may indicate the degree of airway collapse/
Reflexes may be absent. hypoventilation.
kyphoscoliosis and pes cavus. FRC is important because hypoxaemia may result if
diabetes mellitus occurs in 20% of patients. it is reduced:
cardiomyopathy in over 50% of patients, with risk if closing capacity (CC) exceeds FRC, airway
of cardiac failure and arrhythmias. closure occurs with quiet breathing, causing V/Q
Anaesthetic precautions: mismatch. Hypoxaemia of old age is thought to
preoperative assessment of neurological, cardiovas- result from this, since CC rises with age.
cular and respiratory systems. FRC serves as an O2 reserve; thus a reduced FRC
- cautious use of neuromuscular blocking drugs. holds less O2, e.g. if airway obstruction occurs. The
- risk of respiratory failure postoperatively; physio- FRC O2 store helps prevent large swings in arterial
therapy, O2 therapy and adequate analgesia are PO2 during respiration.
required. Reduced FRC may also reduce lung compliance and
[Nikolaus Friedreich (18251882), German neurologist] increase pulmonary vascular resistance.
Reduced by:
Frontal nerve block, see Ophthalmic nerve blocks supine position.
obesity.
Frusemide, see Furosemide pregnancy.
244 Fungal infection in the ICU

anaesthesia, even with IPPV (thought to involve Dosage:

decreased muscle tone and shift of thoracic and depends on renal function and response: 510mg
peripheral blood to the abdomen). may cause considerable diuresis given orally or iv
restrictive lung disease, e.g. pulmonary fibrosis; it (less than 4mg/min) to healthy patients. Up to
may also be reduced in pulmonary oedema, infec- 500mg may be given in severe renal impairment.
tion, atelectasis and ARDS. suitable starting dose in fluid retention or cardiac
Increased by: failure: 0.51.0mg/kg.
PEEP and CPAP. often given as an infusion, e.g. on ICU: 14mg/h,
increased airway resistance, e.g. asthma. although recent evidence suggests that renal failure
exercise due to sustained inspiratory muscle tone. is not prevented by this strategy.
Side effects:
ototoxicity, especially after rapid iv injection.
Fungal infection in the ICU. The incidence of nosoco- hypokalaemia.
mial infection involving fungi is increasing in ICU raised creatinine, urea and uric acid.
practice, related to increased use of antibiotics and rash, thrombocytopenia and leucopenia rarely.
immunodeficiency (either present before the present-
ing illness or acquired during it). Immunosuppressed Fusidic acid (Sodium fusidate). Steroidal antibacterial
patients may also present with fungal infection acquired drug, chemically related to the cephalosporins. Used to
outside hospital. treat penicillin-resistant staphylococcal infections, espe-
Candida species (mainly C. albicans) is responsible cially endocarditis and osteomyelitis (achieves high
for 10% of bloodstream infections in the ICU, and is the levels in bone). Well absorbed from the GIT and metab-
third most commonly isolated bloodstream pathogen. olised in the liver to inactive metabolites. Half-life 56h;
Other candida species, Torulopsis glabrata and other 98% protein-bound.
gut commensals may also be involved. Risk factors Dosage: 0.51.0g orally or iv tds.
for pathogenic colonisation include prolonged antibac- Side effects include nausea, vomiting, rashes, jaundice
terial therapy, critical illness, intravascular and urinary (with high doses).
catheters, TPN and immunosuppression. Diagnosis may
be difficult since blood cultures may be negative even Fuzzy logic. Method of describing and controlling
with severe fungal infection; however, isolation from systems in which various qualities are described in
multiple peripheral sites combined with clinical features terms of degrees, rather than absolutes, e.g. varying
of infection is thought to be sufficient for diagnosis. shades of grey instead of merely black and white.
Treatment is with antifungal drugs (e.g. amphotericin, Allows finer control than yes/no systems since, even if
fluconazole and flucytosine), often in combination for the latter are made more discerning by defining many
complex infections. Treatment of patients with fungal divisions (e.g. black, very dark grey, dark grey, medium
colonisation without clinical evidence of infection is grey), as there will always be a step between adjacent
controversial. categories. In fuzzy logic, each division (or shade) over-
Lipsett PA (2006). Crit Care Med; 34(Suppl): S21524 laps its neighbours, and thus any point may be defined
according to the extent to which it belongs to each
shade. Has been used in various systems, e.g. control of
Furosemide (Frusemide). Loop diuretic, derived from iv infusions.
sulphonamides. Decreases renal sodium and water reab- Grant P, Naesh O (2005). J R Soc Med; 98: 79
sorption, with potassium loss. IV injection causes vaso-
dilatation, with diuresis within 30min. FVC, see Forced vital capacity
 G
G protein-coupled receptors (GPCRs). Large family currently licensed): 300600mg preoperatively plus
of transmembrane receptors that bind a wide variety of 200300mg tds postoperatively.
ligands, including neurotransmitters and hormones. The Side effects include sedation, dizziness, ataxia, nystag-
target receptors of many drugs, including adrenergic, mus, tremor, diplopia, nausea, convulsions, cough.
dopamine, opioid, 5-HT and histamine agents. The Kong VKF, Irwin MG (2007). Br J Anaesth; 99: 77586
receptor consists of seven membrane-spanning helices
bound on the inner surface of the membrane to a G Gabexate mesilate. Synthetic serine protease inhibitor;
protein, so called because they bind guanine diphos- has been studied as a protective and therapeutic agent
phate (GDP) and triphosphate (GTP). G proteins in pancreatitis, as a neuroprotective agent in spinal
consist of three subunits: G, G and G. In the inactive
state, G has GDP on its binding site (Fig. 75a). Activa-
tion of the GPCR by a ligand causes an allosteric change
in the G subunit, resulting in the displacement of GDP
(a)
and replacement by GTP; the G and G subunits dis-
sociate from the complex (Fig. 75b). The activated G
subunit in turn activates an effector molecule, e.g. ade-
nylate cyclase (see Fig. 5; Adenylate cyclase). Activated
G is a GTPase that rapidly reconverts GTP to GDP,
thus restoring the G protein to its inactive state. Adenylate
Many types of G subunit exist, including: cyclase
Gs: stimulates adenylate cyclase, increasing levels
of cAMP in the cell, e.g. -adrenergic agonists and
glucagon are Gs-coupled.
Gi: inhibits adenylate cyclase, e.g. 2-adrenergic Gs
GDP
receptor agonists are Gi-coupled.
Gq: activates phospholipase C, generating inositol
G
triphosphate (IP3), e.g. 1-adrenergic receptor ago-
nists are Gq-coupled. GTP GY
In addition to their coupling to second messenger
systems, G proteins can also be directly coupled to ion
channels. They have been investigated as possible sites
(b)
for interaction with anaesthetic agents.
Hollmann MW, Danja Strumper D, Herroeder S, Durieux
ME (2005). Anesthesiology; 103: 106688 Ligand
See also, Receptor theory

G proteins, see G protein-coupled receptors

Adenylate
G6PD deficiency, see Glucose 6-phosphate dehydroge- cyclase
nase deficiency
ATP
GABA, see -Aminobutyric acid

GABA receptors, see -Aminobutyric acid receptors

CAMP

Gabapentin. Oral anticonvulsant drug, also used in

chronic pain management. In epilepsy, used mainly as GTP Gs
add-on therapy for partial seizures. Is also useful as an
adjunct for reducing postoperative pain and PONV.
GDP
Although structurally related to GABA, it is thought to
G
act by blocking voltage-gated calcium channels in the
CNS. Peak plasma levels occur within 23h of adminis- GY
tration, with half-life of 57h. Excreted renally.
Dosage: 300mg orally on the first day; bd then tds
on successive days, then titrated to response up to Fig. 75 G protein-coupled receptor in (a) inactive and (b) activated
800mg tds. For perioperative use (though not states (see text)

245
246 Gag reflex

cord injury, and as a treatment for DIC. Not available Ganglion blocking drugs. Nicotinic acetylcholine
in the UK. receptor antagonists acting at autonomic ganglia. The
first antihypertensive drugs, now rarely used because
Gag reflex. Elevation and constriction of the pharynx of widespread side effects caused by sympathetic block-
following stimulation of the posterior pharyngeal wall. ade (postural and exertional hypotension, decreased
The afferent pathway is via the glossopharyngeal nerve; sweating) and parasympathetic blockade (constipation,
the efferent is via the vagus. Elevation of the soft palate urinary retention, impotence, dry mouth, blurring of
when it is touched relies on afferent fibres in the maxil- vision). May first stimulate then block receptors (e.g.
lary division of the trigeminal nerve; often the two nicotine) or exhibit competitive antagonism (e.g. hexa-
reflexes are elicited together. The gag reflex is abolished methonium, pentolinium, trimetaphan). None is gener-
following local anaesthesia and lesions of the pharynx, ally available in the UK.
lesions involving the vagal nuclei in the medulla, and Because of the similarity between neuromuscular and
deep anaesthesia or coma. Absence of the gag reflex may ganglionic nicotinic receptors, ganglion blockers (e.g.
indicate that the airway is at risk, e.g. from aspiration of hexamethonium) may cause neuromuscular blockade,
vomit. The reflex is assessed as part of testing for brain- and neuromuscular blocking drugs (e.g. tubocurarine)
stem death. may cause ganglion blockade.

Gain, electrical. Ratio of output signal amplitude to Gangrene. Death and decay of body tissues; usually a
input signal amplitude. Thus a measure of amplification consequence of ischaemia bacterial decomposition but
of signal, e.g. in monitoring equipment. May be specified may be caused by micro-organisms in well-perfused
as voltage, current or power gain; expressed as a simple tissue (e.g. gas gangrene). Traditionally a clinical diagno-
ratio, or for power gain, also expressed as logarithm sis, thus described according to the causative insult and
(base 10) of the ratio (e.g. in bels or decibels). clinical appearances, even though some of the terms are
See also, Amplifiers now obsolete: traumatic gangrene (resulting from direct
[Alexander Bell (18471922), Scottish-born US injury); gas gangrene (associated with gas formation
inventor] within the tissues); Fourniers gangrene (affecting the
perineum); wet gangrene (associated with venous con-
Gallamine triethiodide, see Neuromuscular blocking gestion and oedema); dry gangrene (affected tissue is
drugs blackened and shrunken). Many terms have been super-
seded by more specific ones, e.g. necrotising fasciitis.
Galvanic skin response (Skin conductance response; [Jean A Fournier (18321914), Paris dermatologist]
Sympathogalvanic response). Measurement of the
skins electrical conductivity, which varies with its mois- Gas. Form of matter whose constituent molecules or
ture level. Test of sympathetic afferent, efferent and atoms are constantly moving, and whose mean positions
spinal interconnecting pathways, used to assess the are far apart. Tends to expand in all directions, and
effects of sympathetic nerve blocks. Has also been used diffuse and mix with other gases. Governed by the gas
to assess other regional blocks in which sympathetic laws under specified conditions. Formed when a liquid
blockade occurs, e.g. epidural anaesthesia, brachial exceeds its critical temperature. The constituent parti-
plexus block. cles are sufficiently far apart for the forces (e.g. Van der
Skin electrodes are placed on dorsal and ventral sur- Waals forces) between them to be almost negligible,
faces of the hand/foot, with a reference electrode else- unless the gas is compressed. Pressure exerted by a
where. Opposite sides of the body are normally gas is proportional to the number of collisions of
compared. The output is displayed on an oscilloscope atoms/molecules against the containers walls (which is
(e.g. ECG machine); a steady line results. With intact proportional to the number of gas molecules in the
sympathetic pathways, pinching the skin causes altered container).
skin conductance via changes in sweat gland secretion, See also, Boyles law; Charles law; Ideal gas law
displayed as a deflection lasting under 5s. Deflection is
abolished by successful blockade. The response may be Gas analysis. Possible methods:
diminished by use of atropine, repeated testing and in chemical:
the elderly. - gas reacts chemically with other substances to
Preblockade size of deflection has also been used to form non-gaseous compounds, with reduction of
assess suitability for subsequent sympathetic block. overall volume (e.g. Haldane apparatus) or pres-
Changes in skin potential may also be measured. sure (e.g. van Slyke apparatus). Alternatively, the
reaction results in emission of light that is mea-
Ganciclovir. Antiviral drug, related to aciclovir but sured by a photodetector, e.g. chemiluminescence
more active against cytomegalovirus and more toxic, nitric oxide analysis (NO + ozone producing O2 +
thus reserved for severe infections and to prevent NO2 + light).
infection during immunosuppression following organ - electrochemical: gas reacts with other substances,
transplantation. Valganciclovir, a prodrug, is available the number of electrons transferred during the
for oral use. reaction being proportional to the concentration
Dosage: 5mg/kg iv bd for 23 weeks (treatment) or of gas in the sample. Used in nitric oxide analysers
12 weeks (prophylaxis), followed by 5mg/kg daily. (NO being converted to NO2).
Side effects: many, including blood dyscrasias, rash, physical:
hepatorenal impairment, GIT upset, arrhythmias, - spectroscopy (e.g. infrared).
coma. Contraindicated in pregnancy. May cause - adsorption of vapours on to surfaces:
severe myelosuppression in combination with - rubber strips, e.g. in the Drger Narkotest.
zidovudine. Tension of the strips is reduced by volatile
 Gasserian ganglion block 247

agents; the extent is proportional to their con- bronchi.Turbulence is more likely at mid-inspiration/
centration. Temperature compensated using a expiration, when flow rate is highest (e.g. up to
bimetallic strip. Adjustable for use with differ- 50l/min).
ent agents and in the presence of N2O, to which Turbulence usually occurs in anaesthetic breathing
it is also sensitive. Has a slow response; now systems during peak flow, especially if sharp-angled
rarely used. bends are present, e.g. at connections between com-
- silicone polymer coating a vibrating quartz ponents. Turbulence is more likely with narrow
crystal, e.g. in the Engstrm Emma. Passing tubing and tubes.
alternating current through a crystal can cause other applications include the Venturi principle, flu-
it to vibrate at its resonant frequency (the piezo- idics, flowvolume loops and flowmeters.
electric effect); change in resonant frequency is See also, Airway resistance
proportional to the concentration of volatile
agent dissolved in the polymer coating. Gas gangrene. Infection due to clostridium species,
- interferometer: a light beam is split and passed usually C. perfringens, a spore-forming Gram-positive
through two chambers, one for reference and the anaerobic bacillus found in soil and faeces. Classically
other for samples. The beams are delayed to dif- associated with deep war wounds, especially those con-
ferent extents; thus the emergent beams are out taminated with dirt or foreign bodies, but may follow any
of phase. The resultant interference pattern is trauma, e.g. surgery. The incubation period is under 4
visualised through a telescope, and is displaced days, usually under 1 day.
when gas is drawn into the sample chamber. The organism produces gas within tissues, often
Degree of change is related to the sample concen- detectable clinically as subcutaneous emphysema. Local
tration. Used for calibration, e.g. of vaporisers, not spread is rapid, with oedema, pain and tissue necrosis;
for perioperative monitoring. endotoxin production often results in sepsis with MODS.
- mass spectrometry. Prevented and treated by wound debridement and
- gas chromatography and detectors, e.g. katharom- cleaning. Penicillin is an effective adjunct. Hyperbaric O2
eter, flame ionisation detector, electron capture therapy has been used to increase local tissue O2 content;
detector. antitoxin therapy is more controversial.
- fuel cell, and paramagnetic and polarographic See also, Clostridial infections; Oxygen, hyperbaric
analysers, used for O2 measurement.
- other methods (e.g. depending on different vis- Gas laws, see Avogadros hypothesis; Boyles law;
cosities of gases or velocity of sound through Charles law; Daltons law; Henrys law; Ideal gas law
gases) are rarely used now. Gas transport, see Carbon dioxide transport; Oxygen
[Heinrich Drger (18471917), German engineer; Carl- transport
Gunnar Engstrm (19121987), Swedish physician]
See also, Carbon dioxide measurement Gasp reflex. Production of a deep slow breath following
a large positive pressure inflation of the lungs. Originally
Gas chromatography. Technique used for gas analysis. described in cats and dogs, but may be seen in newborn
The sample mixture is injected into a stream of inert babies; during neonatal resuscitation, it may occur within
carrier gas (the mobile phase) that passes through a primary apnoea. A similar response may also be seen
column of silicaalumina particles coated in oil or wax after opioid administration in anaesthetised patients.
(the stationary phase). Separation of the sample compo- Heads paradoxical reflex, although similar, is pro-
nent gases occurs along the columns length, depending duced under different experimental circumstances.
on their relative solubilities in the two phases. Tempera- See also, Cardiopulmonary resuscitation, neonatal
ture of the column is carefully controlled. Liquids may
Gasserian ganglion block. Block of the trigeminal gan-
also be analysed. Suitable detectors (e.g. katharometer,
glion which lies medially in the middle cranial fossa
flame ionisation detector or electron capture detector)
within a dural reflection (Meckels cave), lateral to the
are required.
internal carotid artery and cavernous sinus. Results
in anaesthesia of the face, forehead and anterior scalp
Gas flow. Principles of flow are as for any fluid. Clinical (Fig. 76). Used mainly for treatment of trigeminal neu-
applications: ralgia, but also for surgery to the face. Performed using
flow is turbulent in the upper airway, trachea X-ray imaging to guide needle positioning.
and bronchi, especially during forceful breathing; Technique:
i.e. gas density is more important than viscosity. with the patient supine and looking straight ahead,
Thus in upper airway obstruction, flow is increased a 22G 10-cm needle is introduced 3cm lateral to
if low-density gas is used, e.g. heliumoxygen the angle of the mouth, level with the second upper
mixture. molar. Aiming at the pupil from the front, and the
flow is laminar in small bronchioles; i.e. viscosity is midpoint of the zygoma from the side, it is inserted
more important; although tube radius is very small, until it contacts bone (greater wing of sphenoid,
velocity is also very low. Helium has traditionally anterior to the foramen ovale). It is redirected
been considered of no use in improving gas flow in posteriorly 11.5cm deeper, passing through the
asthma, primarily a disease of small airways, but foramen. Correct positioning is confirmed by elec-
some evidence suggests that heliumoxygen may be trical stimulation of the needle, which elicits paraes-
useful in severe asthma, suggesting an element of thesia in the distribution of the appropriate branch
turbulent flow. of the trigeminal nerve.
flow may be mostly laminar during quiet breathing, after careful aspiration, 12ml solution, e.g.
with turbulence at branches in the trachea and 1% lidocaine, is injected. Alcohol injection or
248 Gastric contents

Gastric emptying. Normally results from peristaltic

waves of contraction passing through the cardia, antrum,
pylorus and duodenum, occurring up to three times/
Ophthalmic minute after a meal. Small amounts of liquid traverse the
pylorus, which closes as the contraction wave reaches it,
redirecting most of the propelled (solid) material back
C2 into the proximal stomach for further mixing. Thus
liquids transit faster than solids. Carbohydrates leave
faster than proteins and fats are slowest, due to inhibi-
tory feedback mechanisms involving duodenal hormone
secretion.
Slowed by:
Maxillary
lying down.
C3 increased sympathetic nervous system activity (e.g.
anxiety, fear, pain).
mechanical obstruction and duodenal distension.
Mandibular labour (little effect unless opioids given).
drugs, e.g. opioid analgesic drugs, anticholinergic
drugs, alcohol, dopamine.
Increased by:
gastric distension.
drugs, e.g. metoclopramide, domperidone (opioid-
induced gastric stasis is not reversed; cf. cisapride).
Rate of emptying is important because of the risks of
Fig. 76 Innervation of the face nausea, vomiting, regurgitation and aspiration of gastric
contents. Emptying also affects absorption of orally
administered drugs. A commonly used preoperative
starvation guideline is 6h for solid food/milk and 2h for
water in all but life-threatening emergencies; this is an
thermocoagulation may follow if ablative therapy estimate and gastric contents may be considerable even
is required. Accidental subarachnoid injection after fasting if gastric emptying is delayed. Small volumes
may occur. of water (150ml) given 23h preoperatively have been
Often painful; general anaesthesia or sedation may be shown to reduce the volume and acidity of gastric con-
employed, with waking up or reversal to confirm paraes- tents. Recent guidelines call for withholding of all solid
thesia, followed by resedation for ablation. Propofol or food on the day of surgery, unrestricted clear fluids up
a midazolam/flumazenil combination has been used. to 3h preoperatively and consideration of H2 receptor
Complications include anaesthesia dolorosa. antagonists for patients at risk.
[Johann Gasser (17231765), Austrian anatomist; Measurement:
Johann Meckel (17141774), German anatomist] measurement of plasma levels of orally adminis-
See also, Mandibular nerve block; Maxillary nerve block; tered substance, e.g. paracetamol (absorbed from
Ophthalmic nerve block the small intestine, not from the stomach).
serial nasogastric aspiration, with measurement of
Gastric contents. Anaesthetic importance: orally administered marker substance.
absorption of orally administered drugs; e.g. related measurement of impedance across the lower chest/
to gastric emptying, pH and drug interactions within upper abdomen; alters as composition of tissues, i.e.
the stomach. gastric contents, changes.
aspiration of gastric contents; severity of aspiration oral administration of radioisotope, with measure-
pneumonitis is related to the pH and volume of ment of radioactivity over the stomach.
aspirate, although the particulate nature of the aspi- ultrasound imaging.
rate is also important. X-ray imaging following oral contrast medium.
Gastric secretion is increased by: Emptying can be aided by naso- or orogastric aspiration.
presence of food in the mouth (vagal reflex). The latter is more effective, using a wide-bore tube with
anger, stress. multiple holes and lumina, but is unpleasant and rarely
presence of food in the stomach (local reflex). used except for emptying the stomach intraoperatively.
protein meal, via duodenal gastrin secretion. Emetic drugs are no longer used.
hypoglycaemia. Ng A, Smith G (2001). Anesth Analg; 93: 494513
alcohol, caffeine.
Gastric secretion and acidity are decreased by: Gastric intramucosal pH, see Gastric tonometry
vagotomy.
H2 receptor antagonists. Gastric lavage. Formerly performed following poison-
proton pump inhibitors. ing and overdose; now considered to have a very limited
drinking water. role, as evidence suggests risk of harm outweighs benefit
Gastric acidity is decreased by antacids. in the majority of cases.
Gastric volume is related to gastric emptying and Previously performed up to 4h after ingestion (longer
intake. Volume is reduced by H2 antagonists and protein if gastric emptying is delayed, e.g. by anticholinergic
pump inhibitors, but increased by antacids. drugs, aspirin), or at any time if the patient is uncon-
Ng A, Smith G (2001). Anesth Analg; 93: 494513 scious. Involves passage of a wide-bore orogastric tube,
 Gastroschisis and exomphalos 249

with aspiration to ensure the trachea has not been with adrenaline injection of bleeding points (0.5
entered inadvertently. 300600ml warm water is intro- 1.0ml of 1:10000). Other investigations may be
duced and allowed to drain under gravity; this is repeated useful, e.g. radionuclear imaging or conventional
until the aspirate is clear. Pulmonary aspiration may angiography (it may be possible to embolise bleed-
occur; the patient should be placed in the head-down ing vessels once identified).
lateral position with suction available. Tracheal intuba- specific management, e.g. oesophageal varices.
tion is required if laryngeal reflexes are absent. Lavage medical management as for peptic ulcer disease.
is contraindicated if petroleum derivatives have been surgery.
ingested, since pulmonary aspiration is particularly GIT haemorrhage associated with stress ulcers may
harmful. Oesophageal/gastric perforation is also likely if occur in critically ill patients on the ICU.
caustic substances have been ingested.
Gastro-oesophageal reflux. Normally prevented by the
Gastric tonometry. Indirect method of measuring lower oesophageal sphincter and anatomical arrange-
gastric intramucosal pH, which in turn is used as an ment of the oesophagus and stomach. Common in hiatus
indicator of gastric (and therefore GIT) mucosal O2 hernia and obesity. May cause burning retrosternal pain
balance. Intramucosal acidosis may indicate impaired and regurgitation of bitter fluid into the mouth, espe-
GIT O2 delivery or impaired utilisation, and has been cially on stooping/lying. Associated oesophagitis may
proposed as a useful indicator of poor splanchnic perfu- cause pain after meals. Medical treatment is as for peptic
sion and mortality; may be used to guide vasoactive drug ulcer disease/hiatus hernia, including weight loss and
therapy in the ICU and during major surgery. avoidance of the supine/head-down position. Anaes-
A tonometer incorporating a saline-filled balloon is thetic management is as for hiatus hernia.
placed via the oesophagus into the stomach, and luminal Ng A, Smith G (2001). Anesth Analg; 93: 494513
PCO2 (which approximates to intramucosal PCO2) deter-
mined by measuring PCO2 in the saline. A gas-filled Gastro-oesophageal sphincter, see Lower oesophageal
balloon has also been used, with recirculation of gas into sphincter
and out of the balloon with continuous measurement
of PCO2 at the distal end of the system. H2 receptor
Gastroschisis and exomphalos. Congenital malforma-
antagonists eliminate the effect of gastric acid, combin-
tions of the abdominal wall, associated with protrusion
ing with pancreatic bicarbonate to produce CO2. Direct
of abdominal contents:
measurement is also possible but involves mucosal
gastroschisis: abdominal wall defect, not associated
trauma and is less reliable. Arterial bicarbonate concen-
with the midline or umbilicus, causing herniation
tration is measured simultaneously and approximates to
of abdominal contents without a covering sac.
mucosal concentration, allowing calculation of intramu-
Incidence is 1:30000.
cosal pH (pHi).
exomphalos: midline defect, related to the umbili-
Although enthusiastically supported by some, gastric
cus. Bowel and other abdominal organs (with a
tonometry is not in widespread use due to cost, unfamil-
covering sac) fail to return to the abdominal
iarity with the technique and poor specificity.
cavity during fetal development. Incidence is
Kolkman JJ, Otte JA, Groeneveld ABJ (2000). Br J
1:500010000.
Anaesth; 84: 7486 Associated with:
prematurity.
Gastrointestinal haemorrhage. May arise from any other congenital abnormalities (e.g. cardiac defects,
part of the GIT, although most acute bleeds are caused other GIT malformations and genitourinary abnor-
by gastric or duodenal ulcers or erosions. May result in malities), especially with exomphalos.
the need for one or more of resuscitation, surgery or Initial problems:
ICU management. Mortality is 510% (higher in certain damage to exposed organs.
conditions, e.g. 30% in oesophageal varices). Features fluid and electrolyte balance.
range from obvious gross haematemesis to vomiting of heat loss.
small amounts of coffee grounds (blood altered by infection.
gastric acid) or the passage of melaena. Treatment:
Main considerations: the bowel is covered with a dry towel/plastic bag.
of the underlying cause, e.g. oesophageal varices primary surgical closure is preferable to delayed
associated with alcoholism; NSAID-induced ulcer- closure if possible.
ation associated with arthritic disease; the possibil- Anaesthetic considerations: as for paediatric anaes-
ity of coagulation disorders; systemic effects of thesia plus the above considerations. In addition:
malignancy. N2O diffuses into the bowel, increasing its size, and
haemorrhage and hypovolaemia. is avoided.
presence of a full stomach and the risk of aspiration abdominal closure may be difficult, with increased
of gastric contents. intra-abdominal pressure. Postoperative IPPV may
difficulty securing the airway whilst there is copious be necessary. Staged closure may be performed
haematemesis. using a Silastic pouch if adverse effects of primary
Management: closure (e.g. impaired lung compliance) are
O2, volume resuscitation, correction of coagulation excessive.
disorders. postoperative nutrition and prevention/treatment
endoscopy to identify the bleeding site; performed of infection are important.
as soon as the patient has been stabilised. It may be Raghavan M, Montgomerie J (2008). Paediat Anaesth;
possible to treat certain lesions via this route, e.g. 18: 7315
250 Gate control theory of pain

Table 21 Components of gelatin solutions

Sodium Chloride Calcium Potassium

A Solution Gelatin (g/l) (mmol/l) (mmol/l) (mmol/l) (mmol/l)

GABA Haemaccel 35 urea-linked 145 145 6.26 0.4

Gelofusine 40 succinylated 154 125 5.1 0.4
C SG
P
enk
5-HT

urinary catheters and which equals external circumfer-

ence in mm (approximately 3 external diameter).
[Joseph FB Charrire (18031876), Paris instrument-
A
maker]
Inhibitory synapse
Excitatory synapse Gay-Lussacs law, see Charles law
enk, enkephalin
P, substance P GCSF, see Granulocyte colony-stimulating factor
SG, substantia gelatinosa cell

Fig. 77 Gate control theory of pain

Gelatin solutions. Colloid solutions derived from
animal gelatin, a derivative of collagen. Commonly used
forms contain urea-linked (Haemaccel) or succinylated
(Gelofusine) gelatin components (Table 21); average
Gate control theory of pain. Proposed in 1965 by mw is about 35kDa. Used clinically as plasma substi-
Melzack and Wall to account for the influence of psycho- tutes, e.g. in haemorrhage and shock. Cheaper than
logical and physiological variables on pain transmission. albumin solutions and starch solutions, but with shorter
Suggests that impulses flow from periphery to brain half-life (about 4h). Only 1% metabolised with no accu-
through a gate at spinal level, the opening or closure of mulation in reticuloendothelial system. Allergic (ana-
which is influenced by other neural pathways. Pain is felt phylactoid) reactions have followed rapid infusion,
when impulse flow exceeds a certain critical level. The especially of Haemaccel (said to be reduced in its current
gate is closed by descending and large ascending (A) form); usually mild but occasionally severe. The inci-
fibres and opened by small ascending (C) fibres. It is dence of reactions is less than 0.15%.
thought to be located in the substantia gelatinosa (SG), Renal function and blood compatibility testing are
laminae II and III of the dorsal horn; interneurones unaffected. Gelatin solutions may interfere with platelet
project to target cells that then project cranially. The function and coagulation (via reduction in von Wille-
theory has since been modified to account for expanding brand factor activity) and restriction of their administra-
experimental and clinical evidence of neurotransmitter tion in major haemorrhage has been suggested, although
and receptor involvement (Fig. 77): this is controversial. The calcium in Haemaccel may
C fibres from deep receptors (e.g. chemical damage) coagulate stored blood if infused through the same
project to SG cells, probably via substance P (opens giving set without first flushing with saline.
gate). Cranial projection is via spinoreticular fibres.
A fibres (activated by e.g. high-frequency, Gelofusine, see Gelatin solutions
low-amplitude TENS) inhibit the above synapse
presynaptically; GABA is thought to be the neuro Gender differences and anaesthesia. Many factors
transmitter (closes gate). The A fibres also project may contribute to differences in responses to anaesthetic
cranially. and analgesic drugs between genders, for example:
A fibres from superficial receptors (e.g. tempera- pharmacokinetics:
ture, pinprick, acupuncture, low-frequency TENS) - absorption and drug binding: some differences
project cranially, via spinothalamic fibres. Cause but little evidence relating to anaesthetic drugs.
5-HT-mediated descending pathways to close the Alcohol is absorbed more rapidly in women
gate via enkephalin-secreting interneurones acting because it is broken down less in the gastric
on target cells. mucosa than in men.
Descending fibres are also affected by mood and - distribution: greater fat:water ratio in women;
emotion. thus volume of distribution of water-soluble drugs
A fibres also project directly on to interneurons, (e.g. vecuronium) is reduced, and of fat-soluble
inhibiting enkephalin secretion (i.e. open gate). drugs (e.g. diazepam) is increased. It has been
[Patrick D Wall (19252001), English neuroscientist; suggested that women recover more quickly after
Ronald Melzack, Montreal psychologist] propofol anaesthesia than men.
DMello R, Dickenson AH (2008). Br J Anaesth; 101: - metabolism: e.g. greater metabolism of morphine
816 to the active 6-glucuronide than the antagonistic
See also, Sensory pathways 3-glucuronide in women, compared to men. Other
differences may relate to sex-specific isoenzyme
Gauge. Measure of thickness/width; applied in medicine systems but experimental results are often
to cannulae, needles and catheters. Common systems conflicting.
include wire gauges used for needles and cannulae and - excretion: renal excretion is affected by body
the French gauge (Charrire), originally applied to weight and composition.
 Glasgow coma scale 251

pharmacodynamics: women are thought to be more other regulators, and may challenge outcomes of fitness
susceptible to the analgesic effects of opioid anal- to practise investigations.
gesic drugs and neuromuscular blocking drugs and,
although different pharmacokinetics may contrib- Genitofemoral nerve block, see Inguinal hernia field
ute, pharmacodynamic factors have also been sug- block
gested. Reduced sensitivity and earlier waking of
women after propofol may also be a pharmacody- Gentamicin. Broad-spectrum antibacterial drug of the
namic phenomenon. aminoglycosides group, especially active against Gram-
Further differences may result from cyclical changes in negative organisms, but poorly active against haemolytic
body fluid and hormonal status during the menstrual streptococci, haemophilus and anaerobes; thus often
cycle (e.g. PONV may be affected by phase of menstrual given with a penicillin metronidazole when given
cycle). There are also significant effects of pregnancy. empirically. <10% protein-bound and excreted renally,
Psychological factors and the reported greater incidence with plasma half-life of 23h with normal renal
of adverse effects in women may also contribute to function.
apparent differences between the sexes. Dosage: 35mg/kg daily in three divided doses slowly
Buchanan FF, Myles PS, Cicuttini F (2011). Br J Anaesth; iv or im. Less frequent administration is required in
106: 8239 renal impairment. One-hour (peak) plasma levels
should not exceed 10mg/l; trough levels should not
General Medical Council (GMC). Independent regula- exceed 2mg/l. A single iv dose of 57mg/kg over
tor for medical doctors in the UK, funded largely through 3060min provides an equally good response to tds
registration fees. Its remit is to promote and protect dosing, with fewer complications (including renal
patient safety by: fostering good practice; promoting and impairment). Monitoring is also easier.
regulating education and training; and dealing with Side effects: as for aminoglycosides.
doctors whose fitness to practise is in doubt. Sets stan-
dards of ethical and professional conduct through its Geriatric patient, see Elderly, anaesthesia for
guidance document, Good Medical Practice. Assumed
the role of the Postgraduate Medical Education and GFR, see Glomerular filtration rate
Training Board in 2010, and so sets and approves all
postgraduate medical curricula, assessment systems and GHBA, see -Hydroxybutyric acid
training programmes.
All practising doctors in the UK must be on the pub- Gland/gland nut, see Cylinders
licly available GMC List of Registered Practitioners.
Doctors referred to the GMC may undergo a fitness to Glasgow coma scale (GCS). Scoring system originally
practise assessment consisting of investigation and adju- devised in 1974 for assessment of patients with head
dication processes, which may result in acceptance of the injury but now widely applied to other causes of coma.
doctors actions; issuance of a warning; imposition of Validated as useful predictor of outcome after head
conditions on practice; or suspension/removal from the injury, intracranial haemorrhage, subarachnoid haemor-
register (striking off). rhage, poisonings and cardiac arrest. Originally described
Since 2003, the GMC has itself been accountable to for adults, it has been modified for use in infants. A
the Council for Healthcare Regulatory Excellence, (now maximum of 15 points may be scored (Table 22),
Professional Standards Authority for Health and Social expressed as a total or, more usefully, separated into the
Care) which audits the performance of the GMC and three categories (e.g. M3, V2, E2 gives more information

Table 22 Glasgow coma scale for adults and infants

Glasgow coma scale for adults Glasgow coma scale for infants

Activity Best response Scale Activity Best response Scale

Motor Obeys commands 6 Motor Obeys commands 6

Localises pain 5 Localises pain 5
Withdraws from pain 4 Withdraws from pain 4
Flexes in response to pain 3 Flexes in response to pain 3
Extends in response to pain 2 Extends in response to pain 2
No response 1 No response 1
Verbal Fully orientated 5 Verbal Coos or babbles 5
Confused 4 Irritable cries 4
Inappropriate words 3 Cries to painful stimuli 3
Incomprehensible sounds 2 Moans to painful stimuli 2
No response 1 None 1
Eye opening Eyes open spontaneously 4 Eye opening Spontaneous 4
Eyes open to command 3 To speech 3
Eyes open in response to pain 2 To pain 2
Eyes remain closed 1 None 1
252 Glaucoma

than GCS 7). Changes in scores over time are more cleared per minute then equals the volume filtered per
useful than single values. Despite its major limitation of minute, i.e.:
inability to assess patients unable to speak (e.g. aphasia, urine concentration urinary volume/min
intubation) because of its reliance on a verbal compo- GFR =
nent, it remains the most widely used coma scale and is plasma concentration
a component of the APACHE scoring system. Inulin, a carbohydrate derived from plant tubers, is
Kornbluth J, Bhardwaj A (2011). Neurocrit Care; 14: usually used. Radioactive chromium-labelled EDTA
13443 may also be used.
See also, Trauma scales Provides an indication of renal function, but is diffi-
cult to measure routinely. Creatinine clearance approxi-
mates to GFR, and is commonly measured instead.
Glaucoma. Damage to the eye associated with raised
Creatinine is actually secreted by the renal tubules to a
intraocular pressure (IOP).
Anaesthetic considerations:
small degree, but measurement of plasma levels overes-
timates by a small amount, tending to cancel any error.
related to IOP:
More recently, the MDRD equation (Modification of
- avoidance of drugs that raise IOP, e.g. ketamine.
Diet in Renal Disease Study Group) has been developed
Systemic atropine is safe; topical use may cause
that allows an estimated value (eGFR) to be calculated
mydriasis and obstruction of drainage of aqueous
from the serum creatinine concentration, adjusted for
humour.
sex (creatinine concentration lower in women), age (cre-
- IOP increases following tracheal intubation and
atinine concentration lower in older people) and race
extubation.
(creatinine concentration higher in African Americans
- avoidance of: trauma to the eye; steep head-down
than Caucasians). The eGFR is more accurate than a
position; coughing and straining.
24-h urine collection for creatinine clearance but is not
- IOP may be reduced by specific measures, e.g. iv
applicable to the extremes of age or body size, muscle
mannitol, acetazolamide.
disease, vegetarian diet or pregnancy.
related to concurrent drug therapy:
See also, Nephron; Renin/angiotensin system
- timolol drops and related drugs: systemic absorp-
tion and -blockade may occur.
Glomerulonephritis. Renal disease of usually unknown
- ecothiopate drops: may prolong suxamethoniums
aetiology, but often involving renal immune complex
action.
deposition or antibodies against glomerular basement
- pilocarpine and physostigmine drops: systemic
membrane. Histological classification is unrelated to
absorption and bradycardia may occur.
clinical presentation, which may include:
- acetazolamide: electrolyte imbalance may occur.
oliguria, salt and water retention, hypervolaemia
- cannabis may be used by patients with glaucoma,
and hypertension due to impaired glomerular filtra-
although evidence that it lowers IOP is scant.
tion (nephritic syndrome). Classically follows strep-
tococcal infection.
Glomerular filtration rate (GFR). Volume of plasma proteinuria, causing hypoproteinaemia and marked
filtered by the kidneys per unit time. Normally 120ml/ oedema if severe (nephrotic syndrome).
min (173 l/day). others: hypertension, haematuria, loin pain, renal
Depends on: failure (acute and chronic).
effective glomerular surface area: reduced by con- Anaesthetic considerations:
traction of mesangial cells within the glomerulus, impaired renal function.
e.g. in response to angiotensin II, vasopressin, nor- oedema and hypoproteinaemia.
adrenaline, leukotrienes, histamine and certain hypertension.
prostaglandins. Dopamine and atrial natriuretic drug therapy: may include antihypertensive drugs
peptide cause relaxation. and corticosteroids.
permeability of the capillary wall, basement mem- Segelmark M, Hellmark T (2010). Autoimmun Rev; 9:
brane and glomerular epithelium. Dependent on A36671
size (molecules under 48nm pass through rela- See also, Goodpastures syndrome
tively easily), protein-binding and charge (filtration
of cations is favoured over that of anions because Glomus tumours. Rare benign tumours arising from
of the negative charge of the glomerular wall). glomus bodies (arteriovenous anastomoses adjacent to
Increased in certain diseases. blood vessels, receiving rich sympathetic tone and
hydrostatic gradient across the capillary walls. involved in regulating local blood flow and skin tem-
Affected by: perature). More common in the limbs, but may arise
- renal blood flow and arteriolar tone (e.g. nor- from the glomus jugulare (tympanic body) in the upper
adrenaline constricts the afferent arterioles pre- jugular bulb. The latter may extend into the cerebellum
dominantly, whilst angiotensin II constricts the and brainstem, middle ear, internal jugular vein or later-
efferent arterioles). Autoregulation is thought to ally into the neck. Thus associated with neurological
involve afferent arteriolar vascular tone. lesions, including of lower cranial nerves. May rarely
- ureteric obstruction/renal oedema. secrete catecholamines or 5-HT. Anaesthetic concerns
osmotic gradient: rarely clinically important. include length of surgery and blood loss, and those of
Measured by iv infusion of a substance that is freely neurosurgery.
filtered and neither reabsorbed nor secreted by the renal Jensen NF (1994). Anesth Analg; 78: 11219
tubules. It must also be non-toxic, not metabolised and
have no effect on GFR. At steady state, the clearance Glossopharyngeal nerve block. Used to supplement
of the substance is calculated. The volume of plasma topical anaesthesia and/or superior laryngeal nerve
 Glucose 253

block, e.g. in awake intubation. Also used for tonsillec- receptors, causing changes in gene transcription, protein
tomy and glossopharyngeal neuralgia. Acute airway synthesis and cell function. Secretion is increased by
obstruction has followed its use for awake intubation ACTH.
and post-tonsillectomy analgesia. Actions:
Techniques: increased glycogen and protein breakdown, and
internal: glucose synthesis, with increased blood glucose
- posterior: having applied topical anaesthesia to levels.
the tongue, it is depressed and an angled needle required for normal effects of catecholamines on
inserted behind the middle of the posterior tonsil- metabolism, bronchi, CVS and fluid balance. This
lar pillar, to 1cm depth. After aspiration, 3ml may explain the hypotension seen in adrenocortical
local anaesthetic agent is injected. Blocks the insufficiency.
sensory pharyngeal, lingual and tonsillar branches, required for efficient muscle contraction and
and the motor branch to stylopharyngeus. Carotid nerve conduction; also involved in inflammatory/
puncture is more likely using this approach than immunological responses.
with the anterior. mild aldosterone-like activity.
- anterior: after topical anaesthesia, the tongue is Large doses of glucocorticoids suppress inflammation,
displaced away from the side to be blocked, and are used in many inflammatory and immunological
revealing a gutter between the tongue and the diseases.
teeth. A needle is inserted 0.250.5cm at the pos- See also, Adrenal gland; Corticosteroids
terior end of the gutter, and 2ml local anaesthetic
injected. Blocks the lingual branch primarily. Glucose. Carbohydrate, of central importance as an
external: 56ml solution is injected just behind and energy source within the body.
deep to the styloid process, found 24cm deep, Main metabolic pathways (Fig. 78):
midway between the tip of the mastoid process and production:
angle of the jaw. Internal carotid and jugular vessels - from breakdown of carbohydrate foodstuffs.
lie very close. - from glycogen, protein and fats via intermediate
steps in glucose metabolism; occurs in the liver
Glossopharyngeal neuralgia. Recurrent, sudden, stab- during starvation and exercise. Produces glucose
bing pain in the distribution of the glossopharyngeal 6-phosphate, which is converted by hepatic
nerve. May result from nerve compression by vertebral
or posterior inferior cerebellar arteries, local musculo
skeletal anomalies or trauma. May be relieved by topical
local anaesthetic to oropharyngeal trigger areas. Treat-
Carbohydrates etc
ment includes glossopharyngeal nerve block using local
anaesthetic at weekly intervals; alcohol injection or sur-
gical decompression of the glossopharyngeal nerve may 6C Glucose
be required.
Glucose 1-phosphate
Glottis, see Larynx
Glucose 6-phosphate Glycogen
Glucagon. Polypeptide hormone secreted by the A ()
Hexose/pentose
cells of pancreatic islets. Acts on the glucagon receptor
monophosphate pathway
(a G protein-coupled receptor), resulting in hepatic
+ energy via NADP
adenylate cyclase stimulation, leading to glycogen break-
down and release of glucose (hence its emergency use in
hypoglycaemia). Also increases hepatic gluconeogenesis Fructose 6-phosphate
from amino acids, and breakdown of fats to form ketone
bodies. Stimulates secretion of growth hormone, insulin Fructose 1,6-diphosphate
and somatostatin. Has inotropic and chronotropic
actions on the heart, unrelated to adrenergic receptors.
Thought to increase calcium transport into myocardial 3C Phosphoglyceraldehyde
cells, possibly via adenylate cyclase activation; used in
the treatment of -adrenergic receptor antagonist poi-
soning. Half-life is less than 10min. Phosphoglyceric acid
Secretion is increased by -adrenergic stimulation,
stress, exercise, amino acids, gastrin, cholecystokinin and
Phosphoenolpyruvic acid
starvation. It is decreased by hyperglycaemia, soma-
tostatin, ketone bodies, fatty acids, insulin and
-adrenergic stimulation. Lactic acid
Pyruvic acid
Dosage: + energy via ATP
hypoglycaemia: 0.51mg sc/im/iv.
-receptor antagonist overdose: 210mg iv (child:
50150g/kg).
Tricarboxylic acid cycle
Glucocorticoids. Hormones secreted by the adrenal + energy via ATP
cortex; consist mainly of cortisol and corticosterone.
Diffuse through cell membranes and act on intracellular Fig. 78 Main metabolic pathways of glucose
254 Glucoseinsulinpotassium infusion

glucose 6-phosphatase to glucose, which enters Chronic haemolysis is also associated with other
the bloodstream. Other tissues (e.g. muscle) lack inborn errors of metabolism, e.g. pyruvate kinase
this enzyme, and glucose 6-phosphate is catabo- deficiency.
lised directly via the glycolytic pathway. Cappellini MD, Fiorelli G (2008). Lancet; 371: 6474
uptake:
- from the GIT via carrier-assisted transport, i.e. as Glucose reagent sticks. Plastic strips bearing reagents,
part of an active transport mechanism for sodium used to measure glucose concentration, e.g. in blood or
ions. Thus indirectly utilises energy. urine. Glucose is converted by glucose oxidase to glu-
- from the bloodstream into cells by the action of conic acid and hydrogen peroxide, the latter oxidising a
insulin. dye to produce a colour change. Accuracy is increased
utilisation for energy production: via conversion by using reflectance colorimeters to quantify the colour
into glucose 6-phosphate and subsequent break- change, and may be reduced by use of alcohol swabs for
down (glycolysis). cleaning the skin. They are less accurate at lower (hypo-
conversion to glycogen via glucose 6-phosphate and glycaemic) glucose levels. Useful as a bedside test, and
glucose 1-phosphate. for home monitoring of glucose levels.
hexose/pentose monophosphate shunt: alterna-
tive energy-producing pathway from glucose Glucose tolerance test. Investigation used in the diag-
6-phosphate, with reduction of nicotinamide nosis of diabetes mellitus. Involves administration of
adenine dinucleotide phosphate (NADP). glucose either orally or iv, usually the former. 1.75g/kg
conversion to fats and proteins. is given orally up to 75g, in at least 250ml water. Blood
Fasting plasma levels are maintained at 46mmol/l (72 glucose normally rises from fasting levels to a peak at
108mg/dl) by the action of various hormones mainly on 1060min, declining thereafter. Fasting and 2-h levels
the liver; e.g. insulin decreases blood glucose, whilst glu- are used for diagnosis:
cagon, catecholamines, growth hormone, glucocorticoids venous plasma glucose under 7.8mmol/l (140mg/
and thyroid hormones increase it. dl) fasting and at 2h: normal.
Filtered and reabsorbed in the proximal tubules of venous plasma glucose over 11.1mmol/l (200mg/
the kidneys; renal capacity for reabsorption is exceeded dl) at 2h: diabetic.
above plasma levels of about 10mmol/l (180mg/dl). intermediate values: impaired glucose tolerance.
Congenital inability to reabsorb glucose results in renal Diabetes is usually diagnosed on random and fasting
glycosuria at normal plasma levels. The renal threshold blood sugar estimations alone. The tolerance test is
may also be reduced in pregnancy and tubular damage. mainly used to investigate diabetes in pregnancy,
See also, Catabolism; Diabetes mellitus; Metabolism; although there is disagreement about the definitions
Nutrition used.

Glucoseinsulinpotassium infusion. Infusion regimen -Glucosidase inhibitors. Saccharide hypoglycaemic

used in an attempt to reduce the size of MI, increase drugs that compete with saccharidases in the small intes-
cardiac output and reduce arrhythmias. First used in the tine, thus slowing the breakdown of poly- and disaccha-
1960s but abandoned because of doubts over its efficacy; rides to monosaccharides in the gut. Used alone or in
more recent evidence has suggested a reduction in mor- combination with other drugs to improve glycaemic
tality. Thought to reduce plasma free fatty acid levels, control, especially postprandial hyperglycaemia. Include
reducing myocardial energy and O2 requirements; it pos- acarbose, miglitol and voglibose.
sibly augments anaerobic metabolism by increasing ATP
supply. Regimens vary but most involve 2550 units Glue-sniffing, see Solvent abuse
insulin and 4050mmol potassium added to 500ml of
2550% glucose, infused iv at 100ml/h. Glucose/insulin Glutamate. Amino acid and major excitatory neu-
infusion has also been used in hyponatraemia due to the rotransmitter throughout the CNS, especially brain.
sick cell syndrome; it supposedly restores ionic balance. Released presynaptically, it activates various specific
receptors:
Glucose 6-phosphate dehydrogenase deficiency AMPA receptors (-amino-3-hydroxy-5-methyl-4-
(G6PD deficiency). X-linked recessive inherited disor- isoxazolepropionic acid receptors): involved in
der of red blood cell metabolism, common in Mediter- rapid neurotransmission.
ranean, African, Middle Eastern and South-East Asian kainate (a neurotoxin) receptors: similar effects to
populations. Impairs the hexose monophosphate shunt those of AMPA receptors.
of glucose metabolism, required for cell protection NMDA receptors: slower response; thought to be
against products of oxidation. Results in haemolysis, involved in long-term potentiation, including modu-
which may be chronic or associated with acute illness lation of pain and memory formation.
(especially typhoid and viral hepatitis infection), drugs others, linked to G protein-coupled receptors: less
(e.g. antimalarials, sulphonamides, aspirin and related clearly understood.
drugs, methylthioninium chloride [methylene blue]), and Manipulation of glutamate pathways is currently an
ingestion of broad beans (favism). Reduction of met active area of research since it is thought to be involved
haemoglobin is impaired, thus avoidance of prilocaine in pain perception, wakefulness and memory, post-injury
has been suggested. or ischaemic neurotoxicity (via glutamate-mediated
Classified according to degree of enzyme activity; intracellular calcium accumulation) and spinal cord neu-
Class 1 is severely deficient; Class 2 has 110% normal rotransmission. It may also have a role in anaesthesia
activity; Class 3 1060%; Classes 4 and 5 have increased itself, e.g. with ketamine.
activity. Provides some protection against falciparum
malaria. Glutamine, see Amino acids; Glutamate
 Glycopyrronium bromide 255

Glyceryl trinitrate (GTN; Nitroglycerin). Vasodilator type II: Pompes disease: glycogen is deposited in
drug, used to treat myocardial ischaemia and cardiac skeletal, cardiac and smooth muscle. Cardiac failure
failure, and to lower BP, e.g. in severe hypertension and and generalised muscle weakness are common. The
hypotensive anaesthesia. Acts via nitric oxide release to tongue may be enlarged. Enzyme replacement
affect vascular smooth muscle (mainly venous), lowering therapy is under investigation.
preload and reducing SVR and pulmonary vascular type V: McArdles disease: skeletal muscle phos-
resistance. Also increases coronary blood flow. A cuta- phorylase deficiency, impairing glycogenolysis.
neous slow-release patch may be applied preoperatively Muscle weakness and myoglobinuria may occur fol-
in patients with ischaemic heart disease, and these have lowing suxamethonium. Muscle atrophy may follow
also been applied to sites of iv fluid administration, use of tourniquets for surgery. Hypoglycaemia and
reducing infusion failure by up to 60%. Has also been acidosis are common.
used to reduce uterine contraction, e.g. in premature [Edgar von Gierke (18771945), German pathologist;
rupture of membranes (cutaneous patch) or as an acute Joannes C Pompe (19011945), Dutch pathologist; Brian
tocolytic drug (iv or sublingual). McArdle (19112002), English physician]
Dosage:
sublingually 0.31.0mg, repeated as required. Lasts
Glycolysis. Breakdown of glucose (six carbon atoms) to
about 2030min. Available as 0.3mg or 0.5mg
pyruvic acid or lactate (three carbon atoms). Each step
tablets; also as a 0.4mg/dose spray.
in the pathway (see Fig. 78) is catalysed by a specific
orally as slow-release tablets: 25mg tds.
enzyme. Energy released during the process is utilised
cutaneously: 510mg/day applied to the chest; 5mg
by production of ATP. The reactions occur anaerobi-
34-hourly to infusion sites.
cally, with a net gain of 2 moles of ATP per mole glucose.
iv: 0.25g/kg/min. Effects occur within 25min
Under aerobic conditions, pyruvic acid enters the tricar-
and last 510min after stopping the infusion. Some
boxylic acid cycle, with a net gain of 36 more moles of
preparations contain 3050% propylene glycol and
ATP. Anaerobic energy production is less efficient; for-
alcohol. GTN is adsorbed on to PVC; polyethylene
mation of lactate from pyruvate limits ATP production
and rigid plastic/glass infusion sets are acceptable.
Side effects: headache, flushing, hypotension, tachy-
to 2 moles per mole glucose. This may occur in exercising
muscle and red blood cells.
cardia. Tachyphylaxis is common.
Passage of glucose into muscle and fat cells is
increased by insulin, with increased glycolysis; most
Glycine. Amino acid, thought to be active as an inhibi- other cell membranes are relatively permeable to
tory neurotransmitter at spinal interneurones. Increases glucose. In the liver, glucose 6-phosphatase levels control
membrane chloride conductance, causing postsynaptic the rate of glycolysis; insulin causes increased levels and
hyperpolarisation. May also be involved in inhibitory starvation decreased levels.
pathways within the ascending reticular activating Other pathways may branch from the glycolytic
system. Also acts as a co-agonist at NMDA receptors. pathway, e.g. the hexose monophosphate shunt from
Used as an irrigating solution for TURP. Systemic glucose 6-phosphate in red blood cells. Protein and fat
absorption is thought possibly to be associated with CNS derivatives may enter the glycolytic chain and glycogen
symptoms, e.g. transient blindness, either via central may be broken down to glucose 6-phosphate via glucose
inhibitory pathways or conversion to ammonia. 1-phosphate.

Glycogen. Storage form of glucose; consists of glucose Glycopeptides. Group of antibacterial drugs; include
molecules linked together into a branched polymer. vancomycin and teicoplanin. Both are true antibiotics
Found mainly in liver and skeletal muscle, and formed since they are derived from micro-organisms. Have
from glucose 1-phosphate, derived from glucose bactericidal activity against aerobic and anaerobic
6-phosphate. Glycogenolysis provides glucose for gly- Gram-positive organisms, including meticillin-resistant
colysis, and is increased by adrenaline via liver Staphylococcus aureus.
-receptors (via cAMP) and -receptors (via intra
cellular calcium). Defects in the various storage and
breakdown pathways result in the glycogen storage Glycoprotein IIb/IIIa inhibitors, see Antiplatelet drugs
disorders.
Glycopyrronium bromide (Glycopyrrolate). Anticho-
Glycogen storage disorders. Inborn errors of metabo- linergic drug, used as premedication and pre- and peri-
lism affecting glycogen and glucose metabolism. All are operatively to prevent or treat bradycardia. Also used
rare, and almost all are autosomal recessive. Classified to prevent muscarinic effects of acetylcholinesterase
according to the deficient enzyme and the site of abnor- inhibitors used to reverse neuromuscular blockade. A
mal glycogen storage; 12 types have been described. quaternary ammonium compound, it does not cross the
Common to most are hypoglycaemia and acidosis with bloodbrain barrier and therefore has minimal central
hepatomegaly; cardiac, mental and renal impairment effects, as opposed to atropine and hyoscine. Also less
may also occur. likely to cause tachycardia, mydriasis and blurred vision,
The following are of particular concern: but markedly reduces production of sweat and saliva. Its
type I: von Gierkes disease: glucose 6-phosphatase action persists for longer than that of atropine, reducing
deficiency; i.e. cannot convert glucose to glycogen. postoperative bradycardia. Dry mouth may persist
Hypoglycaemia, acidosis, mental and growth retar- postoperatively.
dation, hepatomegaly, platelet dysfunction and Dosage:
renal impairment may occur, with death within 45g/kg im/iv.
early childhood. with acetylcholinesterase inhibitors: 1015g/kg.
256 Golden hour

Golden hour. Period following trauma in which active tissue transplants in which donor inflammatory cells
intervention is thought to be crucial in preventing the recognise host cells as being foreign and mount an
development of severe organ (especially brain) injury or inflammatory response against them. Particularly prob-
death. The concept has arisen from the observation that lematic and aggressive when the transplanted cells are
many trauma victims die shortly after the insult; many immunologically active, e.g. bone marrow transplanta-
of the survivors have evidence of persisting brain injury; tion. Acute GVHD typically occurs within 23 months
and experimental brain injury may be considerably of transplantation; affects mainly the skin, liver and GIT,
exacerbated by subsequent aggravating factors such as causing rash, hepatic impairment, diarrhoea with slough-
hypoxaemia and hypotension (and these two factors in ing of gut mucosa, and, in severe cases, death. A chronic
particular are common after severe trauma). Similar form may also occur, affecting the same organ systems.
considerations are likely to apply to other organs, Occurs to some extent in up to two-thirds of bone
although to less dramatic or significant extents. marrow recipients. Thought to be caused by transplanted
Recognition of the importance of the first hour or so T lymphocytes, GVHD may be prevented by various
after trauma has fuelled the debate on whether it is immunosuppressive drugs (and anti-T-cell antibodies)
better to resuscitate and stabilise victims at the scene of and removal of T cells from donor marrow preparations,
the accident before transfer to a hospital, or take them e.g. with radiation treatment. Activation of cytokines
at once (scoop and run). The former approach is now and other inflammatory mediators is also thought to be
generally accepted as being preferable in most cases for involved. Treatment is with immunosuppressive drugs
the above reasons, although controlled studies are rare (typically ciclosporin and prednisolone), although the
and there are situations in which scoop and run is response may be poor unless started early. If survived,
favoured, e.g. penetrating cardiac trauma. In practice, the GVHD may protect against subsequent relapse of leu-
emphasis is on maintenance of oxygenation, stabilisation kaemia. GVHD has also been described after intestinal,
of major fractures and control of external haemorrhage heartlung and liver transplantation. A form has also
before as rapid a transfer as possible. followed blood transfusion, especially in immunocom-
See also, Head injury; Transportation of critically ill promised recipients or when first-degree relatives donate
patients blood (involves close mismatch of leucocyte antigen
haplotypes). Typically occurs up to a month post-
Goldman cardiac risk index, see Cardiac risk index transfusion; features are similar to those above.
Bacigalupo A (2007). Br J Haematol; 137: 8798
Goldman constant-field equation. Equation used to
calculate the membrane potential of a cell. Similar in Grahams law. Rate of diffusion of a gas is inversely
concept to that of the Nernst equation, utilises the con- proportional to the square root of its mw.
centrations of sodium, potassium and chloride ions on [Thomas Graham (18051869), Scottish chemist]
either side of the membrane, and membrane permeabil-
ity to each: Gram-negative/positive bacteria, see Bacteria
RT PK+ [Ko + ] + PNa+ [Na o + ] + PCl [Cl i ]
V= ln Granisetron hydrochloride. 5-HT3 receptor antagonist,
F PK+ [K i + ] + PNa+ [Na i + ] + PCl [Cl o ]
licensed as an antiemetic drug in postoperative and
where V = membrane potential radio-/chemotherapy-induced nausea and vomiting.
R = gas constant Similar to ondansetron.
F = Faraday constant Dosage:
PK+ , PNa+ , PCl = permeability to potassium, PONV: 1mg slowly iv, repeated up to 2mg/day.
sodium and chloride respectively nausea/vomiting following radiotherapy or chemo-
[Ko+], [Nao+], [Clo] = outside concentration of ions therapy: 12mg orally, followed by 2mg/day in 12
[Ki+], [Nai+], [Cli] = inside concentration of ions doses, or 3mg iv (diluted in 15ml saline over 30s
[David E Goldman (19101998), US physiologist; or as iv infusion over 5min), repeated up to twice
Michael Faraday (17911867), English chemist] in 24h. A maximum of 9mg/day should be given by
any route.
Side effects: GI upset, headache, QT prolongation,
Goodpastures syndrome. Combination of glomerulo-
nephritis, rapidly progressive pulmonary haemorrhage arrhythmias.
and antibodies against glomerular basement membrane
(the first two may also occur without these antibodies, Granulocyte colony-stimulating factor (G-CSF).
e.g. in systemic vasculitides and connective tissue disease, Substance used to stimulate neutrophil production,
and strictly, do not constitute Goodpastures syndrome). especially in febrile neutropenic patients receiving che-
The antibodies react against a specific antigen present in motherapy. Has also been studied as a possible treat-
the basement membrane and also in the alveolar mem- ment of MODS, SIRS and sepsis. Various recombinant
brane, hence the association. Often follows an upper human preparations are available:
respiratory tract infection or exposure to certain chemi- filgrastim (unglycosylated G-CSF) and lenograstim

cals (e.g. following glue sniffing), presumably via forma- (glycosylated G-CSF): similar effects on neutro-
tion of new antigenic molecules, resulting in autoantibody phils. Side effects include musculoskeletal pain,
formation. Usually responds well to aggressive immuno- hypotension, allergic reactions, hepatosplenomeg-
suppressive therapy if treated early (i.e. before signifi- aly, hepatic impairment.
cant renal impairment). Plasmapheresis has been used. molgramostim (GM-CSF): stimulates production of

[Ernest W. Goodpasture (18861960), US pathologist] all granulocytes and macrophages. Has more side
effects than the above preparations.
Graft-versus-host disease (GVHD). Potentially life-
threatening condition affecting recipients of organ or Gravity suit, see Antigravity suit
 GuillainBarr syndrome 257

Greener, Hannah (18321848). Fifteen-year-old girl, many subjects, including tracheal tube cuffs, divinyl
traditionally accepted as being the first recorded death ether, cyclopropane, his pharyngeal airway (see Air-
under anaesthesia, although this is probably not the case ways) and a classic description of the stages of anaesthe-
(see below). She was having a toenail removed under sia. Received many honours and medals.
open chloroform anaesthesia in Newcastle in January Baskett TF (2004). Resuscitation; 63: 35
1848, when she suddenly collapsed and died, despite
attempted revival with brandy. GuillainBarr syndrome (Acute inflammatory/
A report published in England in March 1848 referred postinfectious polyneuropathy). Acute inflammatory
to the death in July 1847 of a 55-year-old man, Alexis polyneuropathy described in 1916, although previously
Montigny, in Auxerre, France. He died during removal reported by Landry in 1859. Commonest cause of acute
of a breast tumour under ether anaesthesia, possibly paralysis in the Western world. A number of variants are
because of airway obstruction aspiration or pulmonary described. 95% of cases have a demyelinating polyneu-
oedema. Other reports from 1847 described early post- ropathy; in the remainder the axon itself is affected.
operative deaths associated with ether anaesthesia, The Fisher variant is characterised by ophthalmoplegia,
although the causes are unclear. ataxia and areflexia. Incidence is 12 per 100000. 60%
Knight PR, Bacon D (2002). Anesthesiology; 96: of cases follow an infective process (usually an upper
12503 respiratory tract infection or diarrhoeal illness) within
the previous 6 weeks. Infectious agents implicated
Griffith, Harold Randall (18941985). Canadian anaes- include campylobacter, mycoplasma, cytomegalovirus
thetist in Montreal; famous for the use of curare in and HIV. May occasionally follow vaccination.
anaesthesia in 1942. None of the patients described Thought to be an autoimmune condition and,
apparently required respiratory assistance. Active in although no specific antibodies have been identified in
many other areas of anaesthetic research, including the the commonest demyelinating form, anti-ganglioside
properties of cyclopropane. Of world renown, he antibodies are associated with the axonal variant.
received many honours and medals. Features:
Seldon TH (1986). Anesth Analg; 65: 10513 weakness, usually bilateral and symmetrical; typi-
cally ascending from the legs but may affect any
Growth hormone. Polypeptide hormone released from region first. Cranial nerve involvement is common.
the anterior pituitary gland. Release is increased by: Weakness typically develops over 17 days and
hypoglycaemia, sleep and exercise. reaches a nadir in 4 weeks. Areflexia is invariable.
stress; i.e. produced as part of the stress response to 30% require mechanical ventilation. Recovery
surgery. takes from several weeks to months, and up to years
protein meal and glucagon. if axonal damage has occurred. 1015% are left with
dopamine receptor agonists. residual disability; 5% relapse.
Growth hormone-releasing and inhibiting hormones sensory disturbance: paraesthesia occurs in
(the latter is somatostatin) are released by the hypo- 50%, usually with glove and stocking distribution.
thalamus; growth hormone release is inhibited by growth Reduced touch, sensation and joint position sense
hormone itself. may also occur. Pain (e.g. in the calves and back) is
Effects: common and may be a presenting feature.
increased skeletal growth and cell division. features of autonomic disturbance include hypoten-
increased protein synthesis, lipolysis and gluconeo- sion or hypertension, tachy- and bradyarrhythmias,
genesis (anti-insulin effect). Oversecretion causes ileus and urinary retention.
gigantism before puberty, acromegaly thereafter. Diagnosed by history/clinical features. CSF protein
is raised (without an increase in white cell count) in
G-suit, see Antigravity suit > 90% of patients after a few days. Nerve conduction
studies help differentiate demyelination from axonal
GTN, see Glyceryl trinitrate damage.
Differential diagnosis is extensive and includes myas-
GTT, see Glucose tolerance test thenia gravis, poliomyelitis, porphyria, lead and solvent
poisoning, botulism and other causes of peripheral
Guanethidine monosulphate. Antihypertensive drug, neuropathy.
depleting adrenergic neurones of noradrenaline and Management:
preventing its release. Rarely used for hypertension now, supportive:
but sometimes useful in complex regional pain syn- - turning/nursing care/physiotherapy.
drome; e.g. 1025mg in 20ml saline injected iv into the - prophylaxis against DVT.
exsanguinated arm (3040mg in 40ml for leg), and the - adequate nutrition.
tourniquet kept inflated for 1020min. Close cardiovas- - prompt treatment of infection, e.g. urinary,
cular observation is required afterwards; hypotension respiratory.
may be delayed. A small amount of lidocaine is some- - appropriate treatment of haemodynamic
times added. The procedure may be repeated, e.g. on abnormalities.
alternate days for a number of weeks, often with long- - respiratory: close monitoring of vital capacity;
lasting results. 15ml/kg is usually taken as the minimum before
May cause diarrhoea and postural hypotension. IPPV is instituted, together with other features of
respiratory failure. However, earlier tracheal intu-
Guedel, Arthur Ernest (18831956). US anaesthetist, bation may be necessary if bulbar failure coexists.
practising in Indiana, then California. Considered a pio- Tracheostomy is often necessary since prolonged
neer of modern anaesthesia; published extensively on respiratory support may be required.
258 GVHD

immunoglobulin therapy (IVIg) is now the specific CSF filtration has been used occasionally in severe,
treatment of choice: 0.4g/kg/day iv over 35 days resistant cases.
(see Immunoglobulins, intravenous). [Georges Guillain (18761961), Jean A Barr (1880
plasmapheresis is equally effective as IVIg at speed- 1967) and Octave Landry (18261865), French neurolo-
ing recovery and is most beneficial if performed gists; Charles Miller Fisher, Canadian neurologist]
within the first 2 weeks, and before ventilatory Yuki N, Hartung HP (2012). N Engl J Med; 366:
support is required. Usually performed daily for 45 2294304
days. Combining plasmapheresis and IVIg has no
additional benefit.
corticosteroids have no role. GVHD, see Graft-versus-host disease
 H
H2 receptor antagonists. Competitive antagonists of H2 immediately after haemorrhage, since red cells and
histamine receptors. Used to reduce histamine-mediated plasma are lost together; compensatory mechanisms
gastric acid secretion in: peptic ulcer disease; gastro- restoring blood volume cause subsequent haemo
oesophageal reflux; those at risk of aspiration of gastric dilution. In prolonged severe irreversible shock,
contents; and to reduce gastric/duodenal bleeding in however, fluid shifts into the interstitium with resulting
patients in ICU. Their use in critically ill patients receiv- haemoconcentration.
ing enteral feeding is declining because they increase the
risk of nosocomial chest infections. Have also been used Haemodiafiltration. Modification of continuous arte-
with antihistamine drugs to reduce the severity of riovenous or venovenous haemofiltration (CAVHD or
adverse drug reactions and other allergic responses CVVHD respectively) in order to improve efficiency
involving histamine. and solute clearance rate. Circuitry and other aspects are
Drugs include: identical to those for haemofiltration except that 12l/h
cimetidine: introduced first. Cheapest, but with of dialysate fluid is allowed to run counter-current to the
more side effects. Inhibits hepatic microsomal blood flow on the filtrate side of the haemofilter (Fig.
enzymes. 79). Solute is cleared by a combination of diffusion and
ranitidine: fewer side effects than cimetidine and convection.
does not cause hepatic enzyme inhibition. Longer
duration of action. Haemodialysis. Dialytic technique for removal of
nizatidine: similar to ranitidine. solutes and water from blood by their passage across a
famotidine: similar to ranitidine. Available for oral semipermeable membrane into dialysis fluid (dialysate).
use only. Half-life is 23h and duration of action Indications include renal failure, fluid overload and pul-
about 10h. monary oedema, electrolyte disturbances, severe acido-
Marik PE, Vasu T, Hirani A, Pachinburavan M (2010). sis and some cases of drug poisoning and overdoses.
Crit Care Med; 38: 22228 Principles:
vascular access: usually via a: single needle single-
Haemaccel, see Gelatin solutions lumen catheter (through which blood is withdrawn
into the dialyser and then returned to the patient in
Haematocrit (Hct). Total red cell volume as a propor- an alternating cycle); double-lumen central venous
tion of blood volume. Slightly higher in venous than catheter (or two single ones); Silastic arteriovenous
arterial blood because of entry of chloride ions (chloride shunt connecting adjacent vessels, e.g. radial artery/
shift) into red cells with accompanying water entry. An cephalic vein (Scribner shunt); or permanent arte-
easily measured index of O2-carrying capacity of the riovenous fistula (see Shunt procedures).
passage of blood via an extracorporeal circuit to a
blood, assuming normal red cell haemoglobin concentra-
tion and function. Normal values: 0.40.54 (male); 0.37 semipermeable cellophane membrane or hollow
0.47 (female). Haemodilution to a Hct of 0.30.35 may fibre system. Traditional cellulose-based mem-
be beneficial for tissue O2 delivery (e.g. in critically ill branes may be associated with complement activa-
patients) because of reduced blood viscosity and tion and subsequent inflammatory cascade; thus
increased flow; a value below this level is thought to newer synthetic membranes (e.g. polyacrylonitrile,
compromise O2 delivery. polysulphone) are increasingly used, although more
Useful as a guide to adequate fluid replacement
expensive. Dialysate may be passed on the other
therapy, e.g.: side of the membrane, usually in a counter-current
blood loss: indicates relative need for red cells/
fashion. Blood flow is usually 150300ml/min. The
colloid. following are exchanged:
plasma loss, e.g. burns: plasma deficit may be
- solutes: pass by diffusion from blood to dialysate,
determined: depending on the concentration gradient, size
(mw) of solute, membrane porosity and duration
fall in plasma volume (%) of dialysis. Thus fluids of different composition
1 new Hct original Hct may be used to remove different amounts of
= 100 1
1 original Hct
solute as required. Most dialysis fluids contain
new Hct sodium, chloride, calcium, magnesium, acetate or
See also, Investigations, preoperative bicarbonate (as an alkali source; bicarbonate
itself cannot be added directly since it may pre-
Haemoconcentration. Increase in haematocrit and cipitate calcium and magnesium) and variable
haemoglobin concentration following dehydration or amounts of glucose and potassium. Solutes may
plasma loss. Degree of haemoconcentration may indi- also pass across the membrane by applying a
cate the extent of fluid deficiency. Does not occur hydrostatic pressure across the membrane,

259
260 Haemodilution

anticoagulation of the extracorporeal circuit is

(a) required, e.g. with heparin or prostacyclin infused
into the line upstream to the dialysis machine.
Artery Vein
Control of coagulation with infusion of protamine
to the downstream line has been used but may be
+ heparin + replacement fluid difficult.
return of blood to the patient.
Performed intermittently, e.g. for 46h daily/weekly as
Filter required.
Complications:
technical, e.g. related to vascular access and bleed-
ing, air embolism, clotting within the circuit. Modern
Drainage machines usually incorporate alarms and monitors
(b) for air bubbles.
hypotension: may be related to hypovolaemia, dis-
Vein Vein equilibrium syndrome or acetate in the dialysate
(thought to cause vasodilatation and cardiac depres-
sion; replacement with bicarbonate has been sug-
+ heparin + replacement fluid gested, although it is more complex to achieve).
hypoxaemia: mechanism is unclear.
Pump electrolyte and acidbase disturbances.
Filter increased rate of removal of many therapeutic
drugs including salicylates, phenobarbital, disopyra-
mide, methyldopa, lithium, theophylline, and many
Drainage antibacterial drugs.
[Belding H Scribner (19212003), Seattle nephrologist]
(c) Himmelfarb J, Ikizler TA (2010). N Engl J Med; 363:
183345
Artery Vein
See also, Dialysis; Haemodiafiltration; Haemofiltration

+ heparin + replacement fluid Haemodilution. Lowering of haematocrit and haemo-

globin concentration due to fluid shift, retention or
administration. May follow compensatory restoration of
Filter blood volume after haemorrhage, or iv fluid therapy with
only partial replacement of red cell losses. Also occurs
as a physiological process in pregnancy. Reduction of
haematocrit lowers blood viscosity and increases blood
Drainage Dialysate
flow, although O2 content falls. Optimal haematocrit fol-
(d) lowing acute blood loss is thought to be about 0.3; in
addition to improved tissue blood flow, hazards of blood
Vein Vein transfusion and risk of DVT are reduced. Animal studies
of cerebral ischaemia have suggested reduced infarct
size if early haemodilution is achieved, although human
+ heparin + replacement fluid evidence is lacking.

Pump Haemofiltration. Common form of renal replacement

Filter therapy used in the ICU. First described in 1977; its main
benefit over haemodialysis is cardiovascular stability.
Initially described as continuous arteriovenous haemo-
Drainage Dialysate filtration (CAVH; Fig. 79a) using an extracorporeal
circuit via a surgically performed arteriovenous shunt
Fig. 79 Circuits used for (a) continuous arteriovenous haemofiltration (see Shunt procedures) or using large-bore arterial and
(CAVH); (b) continuous venovenous haemofiltration (CVVH); venous cannulae. Blood flow through the circuit relies
(c) continuous arteriovenous haemodiafiltration (CAVHD); upon the arterialvenous pressure difference.
(d) continuous venovenous haemodiafiltration (CVVHD). Now more frequently employs a continuous veno-
Replacement fluid is often given pre-filter (termed pre-dilution) in venous circuit (CVVH; Fig. 79b) using a large-bore
order to prolong life of the filter double-lumen venous cannula and a peristaltic roller
pump that incorporates monitors to detect air embolism
and extremes of circuit pressure. Blood is pumped at
thereby removing water (ultrafiltration); solutes 100200ml/min. Anticoagulation of the extracorporeal
that can pass through the membrane pores are circuit, but not the patient, is achieved using heparin
swept along with the water (solvent drag). (2001000U/h) or prostacyclin (210ng/kg/min). Anti-
- water: removed by ultrafiltration. The amount of coagulation is not usually necessary if the patient has a
water extracted depends on the magnitude of the coagulopathy.
pressure gradient; positive pressure may be Both CAVH and CVVH rely on the passage of blood
applied to the blood side of the membrane, or through a filter containing a highly permeable mem-
negative pressure to the dialysate side. brane (polysulphone, polyamide or polyacrylonitrile;
 Haemolysis 261

surface area 0.61.0m2) that acts as an artificial glom- -globin chains and produces a more relaxed
erulus. Ultrafiltration occurs by virtue of the hydrostatic configuration. This results in increased affinity
pressure gradient between the blood and ultrafiltrate for further binding (cooperativity), resulting in
sides of filter; solute removal occurs because of convec- the sigmoid-shaped oxyhaemoglobin dissociation
tion. Water and solutes lost from the plasma are replaced curve. Affinity is reduced by increasing PCO2 (Bohr
by haemofiltration fluid containing water and electro- effect), acidity, temperature and amount of 2,3-
lytes. Ultrafiltration can be slow and titrated to the DPG present. Fetal Hb has greater affinity for O2
patient response. Replacement fluid is infused into the than has adult Hb.
arterial limb of the circuit (pre-dilution) or, more CO2 may bind reversibly to amino groups of the
usually, into the venous limb after the filter (post- polypeptide chains, forming carbamino compounds
dilution). Pre-dilution may be useful when there is a high (RNH2 + CO2 RNHCO2H). Deoxygenated Hb
filtrate removal rate (> 10l/day) or a high haematocrit has a greater affinity for CO2 than oxygenated
(> 35%) as it decreases viscosity and subsequent clotting (Haldane effect).
in the circuit. However, pre-dilution decreases the effi- imidazole groups of histidine residues act as buffers
ciency of the system as the blood being filtered contains in the blood and provide a large buffering capacity
a lower concentration of waste products. owing to their abundance. Deoxygenated Hb is a
Both CAVH and CVVH require an exchange of 12 weaker acid and better buffer than oxygenated.
20l/day to achieve adequate solute clearance. Filtration others:
can be increased by applying a negative pressure to the - with carbon monoxide, forming carboxyhaemo-
filtrate side of the filter or by increasing the distance globin.
between the filter and filtrate collecting chamber. In - formation of methaemoglobin.
haemodiafiltration, dialysate fluid is passed through - causing sulphaemoglobinaemia.
the filter to improve efficiency and solute clearance rate - prolonged exposure to raised glucose levels in
(Fig. 79c and 79d). diabetes mellitus, forming glycosylated Hb.
Complications are related to the extracorporeal Normal blood Hb concentration is 1317g/dl (men),
circuit and vascular access (air embolism, clotting, haem- 1216g/dl (women).
orrhage, complement activation, infection), ultrafiltra- Hb is split into globin and haem portions when eryth-
tion (hypovolaemia), electrolyte loss (hyponatraemia, rocytes are destroyed. The iron is extracted and reused,
hypocalcaemia), hypothermia, metabolic alkalosis (use the porphyrin ring opened to form biliverdin. The latter
of large volumes of lactate-rich replacement fluid) and is converted to bilirubin and excreted via bile.
removal of therapeutic drugs, including parenteral Hsia CCW (1998). N Engl J Med; 338: 23947 old but
nutrition. still the best
It has been suggested that CAVH and CVVH have a See also, Anaemia; Carbon dioxide transport; Carbon
beneficial effect in sepsis by removing pro-inflammatory monoxide poisoning; Methaemoglobinaemia; Myoglo-
cytokines, although this is controversial. bin; Oxygen transport; Polycythaemia
See also, Haemodialysis; Renal failure
Haemoglobinopathies. Diseases of abnormal haemo-
Haemoglobin (Hb). Red-coloured pigment in erythro-
globin production (cf. thalassaemias: impaired produc-
cytes, composed of:
tion of normal haemoglobin). Over 300 variants have
globin: four polypeptide subunits, in two pairs. Dif-
been described, mostly due to single amino acid substitu-
ferent types of haemoglobin contain different types
tions. Originally named after letters of the alphabet, then
of polypeptide:
after the place of origin of the first patient described.
- Hb A (adult): two chains, two chains.
Most are clinically insignificant, but some may lead to
- Hb A2 (usually 23%): two chains, two chains.
acute or chronic haemolysis, and some are associated
- Hb F (fetal): two chains, two chains.
with impaired O2 binding and secondary polycythaemia.
There are 141 amino acid residues in chains; 146
Sickle cell anaemia is the most important; it may be
in , and chains.
combined with other abnormalities, e.g. haemoglobin C.
Fetal Hb is normally replaced by Hb A within 6
The latter on its own may cause mild haemolytic anaemia
months of birth, unless polypeptide chain produc-
and splenomegaly.
tion is abnormal, e.g.:
- thalassaemia: reduced synthesis of normal chains.
- haemoglobinopathies, e.g. sickle cell anaemia: Haemolysis. Abnormal destruction of erythrocytes.
abnormal chains are synthesised. Normal red cell survival is about 120 days; bone marrow
haem: porphyrin derivative containing iron in the compensation may restore red cell volume if the lifespan
ferrous (Fe2+) state. One haem moiety, containing is shortened. Anaemia may result if haemolysis is exces-
one iron atom, is conjugated to each polypeptide. sive, bone marrow abnormal, or haematinics (e.g. iron)
Oxidation of the iron to the ferric (Fe3+) state forms are deficient. Haemolysis may result in jaundice,
methaemoglobin (high levels of which cause decreased haptoglobin concentration (see below) and
methaemoglobinaemia). reticulocytosis.
Reactions of Hb: Caused by:
the iron atom in each haem moiety, remaining in the genetic red cell abnormalities:
ferrous state but sharing one of its electrons, can - membrane abnormalities, e.g. hereditary sphero-
reversibly bind one O2 molecule, forming oxyhae- cytosis, elliptocytosis.
moglobin. Thus each Hb molecule can bind four O2 - haemoglobinopathies, thalassaemia.
molecules. In its deoxygenated form, the Hb mole- - enzyme deficiencies, e.g. glucose 6-phosphate
cule exists in a taut configuration. Binding of one dehydrogenase deficiency, pyruvate kinase
O2 molecule breaks salt linkages between - and deficiency.
262 Haemolyticuraemic syndrome

acquired disorders: resin, activated charcoal granules coated in acrylic gel or

- immune: cellulose. Performed in poisoning and overdoses, and
- autoimmune: hepatic failure. Modern devices are extremely efficient;
- primary. complete removal of toxin from the body is limited by
- secondary to: tissue binding. Thus haemoperfusion is most effective for
- connective tissue diseases. poisons with small volumes of distribution, e.g. barbitu-
- malignancy. rates, disopyramide, theophylline, meprobamate and
- infection, e.g. viral, mycoplasma. methaqualone; these are rarely taken in overdose. Tricy-
- drugs, e.g. penicillins, methyldopa, rifampi- clic antidepressants are not removed. Requires vascular
cin, sulphonamides. cannulation (e.g. femoral vein), extracorporeal circuit
- incompatible blood transfusion (including and heparinisation. Blood flow of 100200ml/min is
rhesus blood group incompatibility). employed, continued for several hours according to the
Antibodies bound to red blood cells may be clinical condition or plasma toxin levels.
detected by the direct Coombs test; those circu- Complications: as for dialysis. Thrombocytopenia was
lating in the blood may be detected by the indirect common with earlier adsorption columns.
Coombs test.
- non-immune: Haemophilia. X-linked recessive coagulation disorder
- infection, e.g. malaria, generalised sepsis. with an incidence (type A) of 1:500010000. One-third
- drugs, e.g. sulphonamides, phenacetin. of cases are new mutations. Predominantly affects males,
- lead poisoning. although female carriers may exhibit mild disease.
- renal and hepatic failure. Female homozygotes almost always die in utero. Results
- hypersplenism. in deficiency of factor VIII (haemophilia A) or IX (hae-
- trauma, e.g. prosthetic heart valves, extracor- mophilia B; Christmas disease; one-tenth as common),
poreal circuits. Also associated with red cell leading to increased bleeding into muscles, joints and
damage following contact with vasculitic endo- internal organs. The intrinsic coagulation pathway is
thelium (e.g. haemolyticuraemic syndrome). slowed, with activated partial thromboplastin time pro-
- burns. longed; prothrombin and bleeding times are normal.
- paroxysmal nocturnal haemoglobinuria. Specific factor VIII/IX assay reveals reduced activity,
Haemolysis may be: and von Willebrand factor assay is normal.
extravascular: most common type; involves seques- Intensive care/anaesthetic considerations:
tration of red cells from the circulation. risk of haemorrhage:
intravascular, e.g. haemolyticuraemic syndromes, - spontaneous bleeding may occur at factor VIII
paroxysmal nocturnal haemoglobinuria, incompat- levels below 5%; prolonged bleeding may follow
ible blood transfusion. In the last example, renal surgery or trauma at 515%. At 1535%, bleeding
damage results from immune complex and red cell is likely only if surgery or trauma is major; it is
stroma deposition. Haemoglobin is released into unlikely if levels exceed 35%, but over 50% is
the plasma and binds to haptoglobulin; the resultant suggested for surgery where possible.
complex is rapidly removed by the liver. Thus the - factor VIII is given as a concentrate (preferred),
amount of plasma haptoglobulin is inversely related as cryoprecipitate, or as fresh frozen plasma, with
to the degree of haemolysis. If haemolysis is severe, haematological advice and monitoring of blood
free haemoglobin may appear in glomerular filtrate; levels. Half-life is 812h; adequate levels are
if proximal tubular reabsorption is exceeded, hae- required for at least a week postoperatively.
moglobinuria and haemosiderinuria may result. About 15% of patients have circulating antibod-
[Robin RA Coombs (19212006), Cambridge ies to factor VIII or IX, making control more dif-
immunologist] ficult; eptacog alfa may be useful in such cases.
Desmopressin 0.4g/kg iv may transiently
Haemolyticuraemic syndrome. Acquired condition increase levels of factor VIII by 36 times in mild
involving thrombocytopenia, a microangiopathic hae- cases, and tranexamic acid 1g orally may also
molytic anaemia and endothelial injury to the renal vas- be given.
culature, leading to acute kidney injury. Usually occurs - im injections are avoided.
in children, especially following diarrhoea (usually due - care should be taken with any invasive procedure,
to Shiga toxin-producing Escherichia coli) or upper including venesection or arterial blood sampling.
respiratory infection, but may occur in adults. May occur - NSAIDs and antiplatelet drugs should be avoided.
in cancer, infections and during chemotherapy adminis- high risk of HIV infection in haemophiliacs given
tration. Closely related to thrombotic thrombocytopenic pooled factor VIII before the availability of recom-
purpura, but neurological features such as CVA that binant factor VIII in the mid/late 1980s and of
characterise the latter are uncommon. A similar condi- recombinant factor IX in 1997.
tion may occur postpartum or in women taking the con- [Stephen Christmas (19471993); name of British patient
traceptive pill. in whom the disease was first described]
Treatment is mainly supportive. Although heparin Finjvandraat K, Cnossen MH, Leebeek FWG, Peters M
and prostacyclin have been used, their benefit is (2012). Br Med J; 344: 3640
unproven. Plasmapheresis and immunosuppressive See also, Coagulation studies; von Willebrands disease
drugs have also been used.
See also, Haemolysis Haemorrhage. Physiological effects of acute
haemorrhage:
Haemoperfusion. Removal of toxic substances from blood volume is reduced, leading to reduced venous
plasma by adsorption on to special filters, e.g. amberlite return and cardiac output.
 Haloperidol 263

arterial BP falls, with activation of the barorecep- Originally derived by observing flow of liquid through
tor reflex, reduced parasympathetic activity and rigid cylinders of different dimensions, with different
increased sympathetic activity. Tachycardia, periph- driving pressures. Applied to blood flow through blood
eral arterial vasoconstriction (to skin, viscera and vessels, and gas flow through breathing systems and
kidneys) and venous constriction restore BP, ini- airways, although these tubes are neither rigid nor
tially. Classified in ATLS guidelines as follows: perfect cylinders.
- I: up to 15% of blood volume lost (usually little [Jean Poiseuille (17971869), French physiologist;
physiological change). Gotthilf HL Hagen (17971884), German engineer]
- II: 1530% lost (tachycardia, peripheral vasocon-
striction, postural hypotension). Haldane apparatus. Burette for measuring gas volumes
- III: 3040% lost (hypotension, mental confusion, before and after removal of CO2 by reaction with potas-
maximum tachycardia). sium hydroxide. The volume percentage of CO2 in the
- IV: > 40% lost (cardiovascular collapse and original gas mixture may thus be determined. Similar
shock). Bradycardia and hypotension may occur determination of O2 concentration may be performed,
with over 2030% of loss; thought to be vagally using pyrogallol as the absorbant.
mediated, due to cardiac afferent C-fibre dis- [John Haldane (18601936), Scottish-born English
charge caused by ventricular distortion and physiologist]
underfilling. See also, Carbon dioxide measurement; Gas analysis
increased vasopressin secretion and renin/
angiotensin system activity causes vasoconstriction,
sodium and water retention and thirst. Haldane effect. Increased capacity of deoxygenated
catecholamine and corticosteroid secretion increase blood for CO2 transport compared with oxygenated
as part of the stress response. blood.
Results from:
increased movement of interstitial fluid to the intra-
vascular compartment and third space. increased binding of reduced haemoglobin to CO2,
Long-term effects: forming carbamino groups (accounts for 70% of the
increased 2,3-DPG production, increasing tissue O2 effect).
delivery. increased buffering ability of reduced haemo

increased plasma protein synthesis. globin, allowing more CO2 to be transported as

increased erythropoietin secretion and bicarbonate.
erythropoiesis. See also, Haldane apparatus
Volume restoration takes 13 days after moderate
haemorrhage, with reduction of haematocrit and Half-life (t1/2). The time taken for a substance undergo-
plasma protein concentration. ing decay to decrease by half. Commonly used to describe
Features: as for hypovolaemia. an exponential process (in which the half-life is con-
Management: stant), but may also refer to a non-exponential process
local pressure over bleeding points/pressure points, (in which the half-life varies).
supine position, raising the feet, O2 therapy, military Examples:
antishock trousers, specific haemostatic measures. radioactive half-life (time taken for half the number
large-bore intravenous cannulae and iv fluid of atoms to disintegrate).
administration: drug half-life (time taken for drug concentration to
- cross-matched blood is best (but some benefit in fall by half, whether resulting from redistribution or
cardiac output and tissue flow is derived from clearance).
haemodilution). In pharmacokinetics, context-sensitive half-life refers to
- O Rhesus-negative blood is used in life- the time for plasma concentration of a drug to decrease
threatening haemorrhage, but ABO-compatible by 50% after terminating an iv infusion that has main-
blood should be used if available. tained steady-state plasma concentration. For example,
- colloid maintains intravascular expansion for for propofol it is approximately 20min after 2h infu-
longer than crystalloid. sion, 30min after 6h infusion and 50min after 9h infu-
- crystalloid: saline is more effective than sion. Corresponding figures for midazolam and alfentanil
dextrose. are in the order of 40min, 70min and 80min; for fen-
- CVP and urine output measurement are useful tanyl: 40min, 4h and 5h. Ultra-short-acting drugs are
for monitoring volume replacement. less affected by context (i.e. duration of infusion); for
See also, Blood loss, perioperative; Blood transfusion; example, for remifentanil it is approximately 3min, irre-
Colloid/crystalloid controversy; Damage control spective of the duration of the infusion.
resuscitation See also, Time constant
Haemostasis, see Coagulation
Hall, Richard see Halsted, William Stewart
HAFOE, High air-flow oxygen enrichment, see Oxygen
therapy Haloperidol. Butyrophenone used as a sedative and
HagenPoiseuille equation. For laminar flow of a fluid antipsychotic drug. Acts by blocking central dopamine
of viscosity through a tube of length L and radius r, receptors. Also acts on cholinergic, serotonergic, hista-
with pressure gradient P across the length of the tube: minergic and -adrenergic receptors. Has tranquillis-
ing effects without impairing consciousness; used to
Pr 4 sedate psychotic patients in ICU. Half-life is approxi-
Flow =
8 L mately 20h.
264 Halothane

- sensitises the myocardium to catecholamines, e.g.

F Br
endogenous or injected adrenaline.
other:
F C C H
- dose-dependent uterine relaxation.
F CI - nausea/vomiting is uncommon.
- may precipitate MH.
Fig. 80 Structure of halothane Up to 20% is metabolised in the liver. Metabolites
include bromine, chlorine and trifluoroacetic acid; negli-
gible amounts of fluoride ions are produced. Repeat
Dosage: administration after recent use may result in hepatitis.
1.55.0mg orally bd/tds; up to 100mg may be 0.52.0% is usually adequate for maintenance of
needed in severe schizophrenia. anaesthesia, with higher concentrations for induction.
210mg im/iv 48-hourly, depending on the Tracheal intubation may be performed easily with spon-
response, up to 18mg. A depot preparation, halo- taneous respiration, under halothane anaesthesia.
peridol decanoate, is given by deep im injection for See also, Vaporisers
long-term therapy (50300mg 4-weekly).
Side effects include prolonged QT syndromes, extra- Halothane shakes, see Shivering, postoperative
pyramidal symptoms (parkinsonism, dystonia, rest-
lessness and tardive dyskinesia); can trigger the Halsted, William Stewart (18521922). US surgeon,
neuroleptic malignant syndrome. Other side effects pioneer of local anaesthetic nerve blocks with Hall and
are similar to those of chlorpromazine, but with less others. He and Hall described blocks of most of the
sedation and fewer antimuscarinic effects. nerves of the face, head and limbs, experimenting on
each other and becoming cocaine addicts in the process.
Halothane. 2-Bromo-2-chloro-1,1,1-trifluoroethane (Fig. Chief of surgery and professor at Johns Hopkins Uni-
80). Inhalational anaesthetic agent, introduced in 1956. versity, where he started the first formal surgical training
Its use rapidly spread because of its greater potency, programme in the USA. Pioneer of aseptic technique,
ease of use, non-irritability and non-inflammability com- introducing use of rubber gloves during surgery.
pared with diethyl ether and cyclopropane. Risks of [Richard J Hall (18561897), Irish-born US surgeon]
arrhythmias and liver damage on repeated administra- Osborne MP (2007). Lancet Oncol; 8: 25665
tion (halothane hepatitis) and introduction of newer
agents (e.g. sevoflurane, which has replaced halothane as
Hamburger shift, see Chloride shift
the agent of choice for inhalational induction) have led
to a decline in its use. Discontinued for human use in the
UK in 2007. Hanging drop technique. Method of identifying the
Properties: epidural space, e.g. during epidural or spinal anaesthesia.
colourless liquid; vapour has characteristic pleasant
A drop of saline is placed at the hub of a needle that is
smell and is 6.8 times denser than air. advanced towards the epidural space; when the space
mw 197.
has been entered the drop is drawn into the needle by
boiling point 50C.
the negative pressure within the space. Not always reli-
SVP at 20C 32kPa (243mmHg).
able, since negative pressure is not always present.
partition coefficients:
- blood/gas 2.5. Haptoglobin. Alpha-globulin synthesised by the liver,
- oil/gas 225. that binds free haemoglobin in the blood. Normal serum
MAC 0.76%. level is 30190mg/dl; this usually binds 100140mg
non-flammable. free haemoglobin per 100ml plasma. Haptoglobin
supplied in liquid form with thymol 0.01%; decom- haemoglobin complex is rapidly removed from the cir-
poses slightly in light. culation by the reticuloendothelial system; if the liver is
Effects: unable to produce new haptoglobin quickly enough, the
CNS: plasma haptoglobin level falls. Although the reduction
- smooth rapid induction, with rapid recovery. in haptoglobin is used mainly as a sensitive indicator of
- anticonvulsant action. intravascular haemolysis, it may also occur if haemolysis
- increases cerebral blood flow but reduces intra- is extravascular.
ocular pressure. Haptoglobin is an acute-phase protein, but may also
RS: be raised in carcinoma and inflammatory disease and
- non-irritant. Pharyngeal, laryngeal and cough after trauma or surgery.
reflexes are abolished early, hence its value in dif- See also, Acute-phase response
ficult airways.
- respiratory depressant, with increased respiratory Harmonics. Related sine waveforms; the frequency of
rate and reduced tidal volume. each is a multiple of the fundamental frequency of the
- bronchodilatation and inhibition of secretions. first harmonic, the slowest component of the series.
CVS: Complex waveforms may be produced by adding
- myocardial depression and bradycardia. Has gan- higher harmonics to the first (fundamental) harmonic
glion blocking and central vasomotor depressant (Fourier analysis). Monitoring equipment must be able
actions. Hypotension is common. to reproduce harmonics of high enough frequency for
- myocardial O2 demand decreases. the signal recorded; e.g. up to the 10th harmonic for
- arrhythmias are common, e.g. bradycardia, nodal many recorders. More harmonics are required for more
rhythm, ventricular ectopics/bigemini. complex waveforms with higher frequencies, increasing
 Head injury 265

the required frequency response of the monitor con- chest and neck. Divided into closed or penetrating (the
cerned, e.g. ECG 0.580Hz, EEG 160Hz, EMG latter having worse outcomes), whilst brain injury can be
21200Hz. divided into:
that occurring at time of injury (primary) and
Harnesses. Used to secure breathing attachments or cannot be influenced by treatment. Injury results
facemasks to the patient. May damage soft tissues from deceleration of the brain inside the bony skull,
around the face, and airway obstruction may still occur. lacerations from bony prominences on the base of
Examples: the skull, shearing effects, rotational forces and the
Clausen harness: triangular back placed behind the cheese-cutter effect of blood vessels. Effects range
head, with straps at each corner for attachment to from macroscopic contusions to diffuse axonal
hooks around the facemask. injury. Injury may be on the side of the injury (coup)
Connell harness: square back placed behind the or opposite (contrecoup).
head, with attachments at each end for the sides of that occurring after the initial injury (secondary)
the facemask. resulting from potentially preventable or treatable
Hudson harness (for dental surgery): long strap for causes (e.g. hypoxaemia, hypotension, hypercapnia).
fixation of the catheter mount from the nasotra- Compression due to cerebral oedema or intra
cheal tube; binds around the patients forehead. cerebral, intraventricular, epidural or subdural
Formerly widely used during mask anaesthesia, their haemorrhage can be included here, although the
use has declined with increasing use of the LMA, though first two are usually associated with direct brain
many modern facemasks are still supplied with plastic injury.
hooks for attachment. Their disposable silicone/rubber Features:
equivalents are used for non-invasive positive pressure external signs of head injury, e.g. bruising, lacera-
ventilation or CPAP. tions. Cervical spine fractures or serious ligamen-
[RJ Clausen (18901966), English anaesthetist; Karl tous injuries should be assumed until proven
Connell (18731941), US surgeon; Maurice WP Hudson otherwise. Chest trauma and other injuries may be
(19011992), London anaesthetist] present.
impaired consciousness and amnesia. Often associ-
Hartmanns solution (Ringers lactate; Compound ated with alcohol or other cause of coma. Brainstem
sodium lactate). IV fluid containing sodium 131mmol/l, death may occur.
potassium 5mmol/l, calcium 2mmol/l, chloride pupils: the third cranial nerve on the side of an
111mmol/l and sodium lactate 29mmol/l. pH is 57. expanding cerebral lesion is stretched over the edge
Originally formulated from Ringers solution for fluid of the tentorium cerebelli, causing ipsilateral dilata-
replacement and treatment of metabolic acidosis in chil- tion and absence of the direct light reflex with the
dren, using an isotonic solution containing more sodium consensual light reflex preserved. Eventually, the
than chloride. Lactate is metabolised to glucose and contralateral pupil is also affected.
bicarbonate within a few hours, and the hazards of bicar- bradycardia and hypertension may occur (Cush-
bonate administration avoided. Now widely used as ings reflex), and irregular respiration as compres-
the crystalloid of choice for ECF replacement, since it sion continues.
is more physiological in make-up; however, its advan- hemiparesis/hemiplegia, upward plantar reflexes.
tage over saline solutions for routine use has been Cranial nerve involvement may reflect the site of
questioned. injury; e.g. 16 in anterior fossa, 78 in middle fossa
Often avoided in patients with renal failure because and 910 in posterior fossa injuries. Other CNS
of the risk of hyperkalaemia, in sick patients or those signs are often variable.
with hepatic failure because of the risk of hyperlactatae- other:
mia (although the clinical relevance of this is unclear), - infection.
and in diabetics because of the risk of hyperglycaemia - Cushings ulcers.
(although the actual increase in blood glucose concen- - convulsions.
tration is likely to be small). Due to its calcium content, - disturbance of CSF dynamics, causing CSF leak
may cause clotting of stored blood when transfused (rhinorrhoea or otorrhoea) or hydrocephalus.
through a line that has not first been flushed with saline. - respiratory, e.g. aspiration pneumonitis, infection,
[Alexis Hartmann (18981964), US paediatrician] PE, pulmonary oedema, ARDS.
Lee JA (1981). Anaesthesia; 36: 111521 - diabetes insipidus or syndrome of inappropriate
antidiuretic hormone secretion, cerebral salt-
Hayek oscillator, see Intermittent negative pressure wasting syndrome.
ventilation - DIC.
Management:
Hb, see Haemoglobin as for coma and trauma, i.e. CPR: O2 administration,
maintenance of airway, breathing, circulation. The
HBE, see His bundle electrography Glasgow coma scale and the simpler AVPU scale
are widely used for assessment. Frequent reassess-
Hct, see Haematocrit ment is important.
opioid analgesic drugs should be used with caution
HDU, see High dependency unit in spontaneously breathing patients, because of the
risk of central and respiratory depression and their
Head injury. Common cause of morbidity and mortality effects on the pupils.
in trauma, especially in young males; it should be sus- cervical spine and skull X-rays to identify fractures,
pected in all trauma cases, especially those involving the and CT scanning to identify haemorrhage, oedema
266 Heads paradoxical reflex

and evidence of raised intracranial pressure. Ultra- - whole body cooling may lower ICP but does not
sound has been used to identify midline shift, before improve outcome; however, hyperthermia does
subsequent CT scanning. worsen brain injury and should be treated
criteria for skull X-ray: aggressively.
- unconsciousness or amnesia at any time. in some ICUs, ICP monitoring is undertaken and
- neurological signs. cerebral perfusion pressure calculated. EEG and
- CSF/blood from nose or ear. related monitoring, evoked potentials, transcranial
- serious scalp injury. Doppler ultrasound and jugular bulb catheterisa-
- difficulty in assessment, e.g. confusion, alcohol. tion have been used to follow progress.
criteria for CT scan: other drug therapy includes antibiotic cover for
- deterioration in conscious level, pupillary signs or CSF leaks and prophylaxis for stress ulcers (e.g.
other observations. pantoprazole sodium).
- focal neurological signs. Surgery may be required for associated injuries, eleva-
- fractured skull and confusion. tion of depressed fractures or evacuation of intracranial
- continuing unconsciousness. haemorrhage; the latter may require burr holes or
criteria for consulting a neurosurgeon: craniotomy.
- fractured skull with confusion or worse impair- Anaesthesia for patients with head injuries: as for
ment of conscious level, focal neurology or neurosurgery and emergency surgery. In particular:
convulsions. other injuries may be present.
- coma persisting after resuscitation (i.e. Glasgow regional techniques are often difficult, especially if
coma score [GCS] < 8). the patient is confused. Burr holes may be drilled
- deterioration in conscious level or the develop- under local anaesthesia.
ment of other neurological signs. spontaneous ventilation must be avoided, even for
- persistent confusion, even without a skull minor procedures, since a small increase in cerebral
fracture. blood flow and intracranial volume due to hyper-
- compound depressed skull fracture. capnia may cause a catastrophic rise in ICP. All
- suspected base of skull fracture. patients should be managed as if ICP is raised.
Transfer for CT scan requires tracheal intubation if Moppett IK (2007). Br J Anaesth; 99: 1831
conscious level is depressed, i.e. GCS 8. Helmy A, Vizcaychipi M, Gupta AK (2007). Br J Anaesth;
if injury is severe, tracheal intubation and IPPV are 99: 3242
performed, traditionally maintaining arterial PCO2 See also, Cerebral metabolic rate for oxygen; Coning;
at about 44.5kPa to reduce ICP and cerebral Maxillofacial surgery
oedema. During intubation, steps should be taken
to prevent aspiration of gastric contents or worsen- Heads paradoxical reflex. Sustained diaphragmatic
ing of any associated cervical spine injury. Contin- contraction, followed by shallow respiration, after a
ued hyperventilation is less often employed now small passive lung inflation. A rare example of a positive
as it is recognised that in head injury cerebral feedback loop in the human nervous system; thought to
blood flow may already be reduced and aggressive be important in the first breaths of the neonate. May also
hyperventilation may result in excessive cerebral be elicited in apnoeic anaesthetised patients.
vasoconstriction and cerebral ischaemia; PCO2 is Widdicombe J (2004). J Physiol; 559: 12.
therefore acutely lowered by hyperventilation only [Sir Henry Head (18611940), English neurologist]
to offset any acute increases in ICP. Other indica- See also, Gasp reflex
tions for IPPV include:
- hypoxaemia. Health and safety issues, see COSHH regulations;
- respiratory irregularity, hypo- or hyperventila- Environmental safety of anaesthetists; Scavenging
tion.
- uncontrolled convulsions, raised ICP or Healthcare Commission. Non-governmental organisa-
hyperthermia. tion, formed in 20034 from the Commission for Health
- extensor or flexor posturing. Improvement (CHI), the Audit Commission (audits
Other measures to prevent a high ICP and reduce NHS organisations and evaluates their cost-effectiveness)
cerebral O2 requirements include: and the National Care Standards Commission (regulates
- heavy sedation + neuromuscular blockade (the independent hospitals and care homes). Its remit was the
latter has been implicated in increased mortality improvement of patient care by assessing NHS organisa-
but the evidence is weak). Thiopental coma or tions, investigating serious failures, ensuring compliance
other forms of cerebral protection/resuscitation with national guidelines and advising on best practice in
are sometimes employed, although controversial. clinical governance.
- head-up tilt of about 15. Abolished in 2009, with its responsibilities assumed
- use of diuretics to reduce cerebral oedema (e.g. by the Care Quality Commission.
mannitol). Recent evidence (CRASH trial: corti-
costeroid randomisation after significant head Healthcare Quality Improvement Partnership
injury) suggests that corticosteroids may increase (HQIP). Body established in 2008 and contracted by the
mortality. UK Department of Health to oversee national audits,
- hyperglycaemia may worsen outcome and glycae- registers and confidential enquiries. Led by a consortium
mic control should be instituted. including the Academy of Medical Royal Colleges, the
- prophylactic use of anticonvulsant drugs is con- Royal College of Nursing and patient representatives.
troversial but is common if craniotomy is required Programmes of relevance to anaesthesia include audits/
or if the cerebral perfusion pressure falls. registers of various cancers, paediatric intensive care,
 Heart block 267

cardiac surgery/cardiology, pain, carotid endartectomy, interaction between multiple moving parts (includ-
hip fracture, and the Confidential Enquiries into Mater- ing valves) and thus had a high failure rate. Newer,
nal Deaths. non-pulsatile flow devices do not require valves and
are more reliable; they utilise a spinning impeller
within a conduit, drawing blood in a continuous
Heart. Develops from a single tube that doubles up
stream from the left ventricular apex and delivering
forming primitive atrium and ventricle; divided by septa
it to the descending aorta. Significant reduction in
into left and right sides (see Atrial septal defect; Ventricu-
mortality and morbidity (compared with medical
lar septal defect). The primitive arterial outlet (truncus
therapy alone) is achievable, but requires adequate
arteriosus) splits to form the aorta and pulmonary trunk;
right ventricular function. Stable patients may be
the venous inlet (truncus venosus) absorbs into the
discharged home.
smooth-walled part of the right atrium.
total artificial heart: indicated in patients with
Surface anatomy:
biventricular failure awaiting heart transplant (i.e.
right border: from third to sixth right costal carti-
not currently licensed as a definitive therapy).
lages, 11.5cm from the left sternal edge.
Consist of two pneumatically driven pumps with
left border: from second left costal cartilage,
tilting disc valves. Patients must remain in
11.5cm from the left sternal edge, to the apex beat
hospital.
(usually at the fifth left intercostal space in the mid-
Main problems are related to infection, thromboembo-
clavicular line).
lism, and reliability and flexibility of the devices.
upper limit: level with the angle of Louis (T45).
Shah KB, Tang DG, Cooke RH, etal. (2011). Clin
base: level with the xiphisternum (T89).
Cardiol; 34: 14752
The left border is composed mainly of left ventricle, the
right border mainly of right atrium, and the base mainly
Heart block. Usually refers to atrioventricular (AV)
of right ventricle, as on the CXR. Weighs about 300g.
block, i.e. interruption of impulse propagation between
Enclosed within pericardium.
Chambers:
atria and ventricles. Bundle branch block refers to inter-
ruption distal to the atrioventricular node.
right atrium:
Classification:
- bears the right auricular appendage (remnant of
first-degree (Fig. 81a): delay at the AV node:
the original atrium).
- PR interval > 0.2s at normal heart rate.
- receives superior and inferior venae cavae, and
- usually clinically insignificant.
coronary sinus.
- caused by:
right ventricle:
- ageing.
- crescent-shaped in cross-section, due to bulging of
- ischaemic heart disease.
the left ventricle.
- increased vagal tone.
- tendinous cords from the interventricular
- drugs, e.g. halothane, digoxin.
septum and papillary muscles attach to the tricus-
- cardiomyopathy, myocarditis.
pid valve.
- pulmonary valve: composed of three cusps.
left atrium: receives four valveless pulmonary
veins.
left ventricle: (a)
- thick-walled.
- the bicuspid mitral valve is anchored by tendinous
cords as for the tricuspid valve. The anterior cusp
is larger.
- aortic valve: composed of three semilunar cusps,
one anterior and two posterior. (b)
Blood supply: see Coronary circulation
Nerve supply: from vagus and sympathetic nervous
system from upper thoracic and cervical ganglia; P P P P P
mainly T14. The cardiac plexus receives branches
from both components of the autonomic nervous
system.
[Antoine Louis (17231792), French surgeon] (c)
See also, Action potential; Atrial . . .; Cardiac . . .;
Coronary . . .; Heart . . .; Left ventricular . . .; Myocardial P P P P
. . .; Ventricular . . .

Heart, artificial. Device used to replace or assist the (d)

heart in end-stage heart failure when heart transplanta- P P P P P
tion is unavailable, or following cardiac surgery.
Main types:
left ventricular assist devices (LVAD): previously
used solely as a bridging therapy pending heart
QRS QRS QRS QRS
transplant, now increasingly used as a definitive
(or destination) therapy. First-generation pneu- Fig. 81 Heart block: (a) first-degree; (b) second-degree, Mobitz I;
matic pumps provided pulsatile flow but involved (c) second-degree, Mobitz II; (d) third degree
268 Heart, conducting system

second-degree: occasional complete block. May be: - the left bundle branch divides into anterior and
- Mobitz type I (Wenckebach phenomenon) posterior fascicles.
(Fig. 81b): - Purkinje fibres spread from the ends of bundle
- AV delay; PR interval lengthens with succes- branches/fascicles to the rest of the ventricles.
sive P waves until complete AV block occurs, i.e. Impulses pass from node to node through normal atrial
no QRS complex follows the P wave. The cycle muscle, then via specialised cardiac muscle cells, insu-
then repeats. lated from the rest of the myocardium by connective
- usually due to AV conduction delay. tissue sheaths. Conduction through each of the following
- rarely proceeds to complete heart block. takes about 0.1s:
- Mobitz type II (Fig. 81c): atria.
- sudden block below the AV node; i.e. PR inter- AV node.
val may be normal. May occur regularly, e.g. bundle of His/Purkinje system.
every second or third complex (termed 2:1 or Vagal and sympathetic innervation is directed to both
3:2 block, respectively). nodes; conduction through the AV node is slowed by the
- at risk of developing complete heart block, par- former and speeded by the latter.
ticularly if it occurs regularly. Ventricular depolarisation begins at the hearts apex
third-degree (Fig. 81d): complete heart block, at the and spreads outwards and upwards, encouraging upward
AV node or below: expulsion of blood from the ventricles.
- ECG demonstrates independent atrial and ven- Interruption of impulse conduction may result in
tricular activity, the latter arising from an ectopic bundle branch block and heart block.
site. The ventricular rate is usually slow, especially [Wilhelm His (18631934), German anatomist; Albert
if the ectopic site is far from the AV node (wide Kent (18631958), English physiologist and radio
QRS complexes; rate < 45/min). logist; Johannes von Purkinje (17871869), Czech
- clinical findings: physiologist]
- hypotension is common.
- wide pulse pressure (large stroke volume). Heart failure, see Cardiac failure
- cannon waves in the JVP.
- escape ventricular arrhythmias may occur. Heartlung transplantation. First performed in 1968
- caused by: but with poor results; outcomes have steadily improved
- old age. since the 1980s. In the UK ~50 are performed each year,
- ischaemic heart disease. with 1-year survival ~85%. Isolated lung transplantation
- myocarditis/cardiomyopathy. initially produced poor results but interest has increased
- cardiac surgery. more recently.
- increased vagal tone. Indications include: pulmonary hypertension, Eisen-
- -adrenergic antagonists, digoxin. mengers syndrome, pulmonary fibrosis, cystic fibro-
- hyperkalaemia. sis and emphysema.
- congenital abnormality. Donor:
For patients undergoing surgery who have pre-existing as for heart transplantation, with normal CXR,
complete heart block or predisposing conditions, a minimal sputum and no history of aspiration or pul-
pacing wire should be inserted preoperatively. Drugs monary oedema. Arterial PO2 should exceed
decreasing AV conduction (e.g. -receptor antagonists 13.3kPa (100mmHg) with FIO2 0.4.
and halothane) should be avoided. Isoprenaline 0.02 the heart and lungs are placed into a bag and
0.2g/kg/min may be used to increase ventricular rate immersed in cold electrolyte solution, with IPPV at
in complete heart block, and should be available, as low rates and perfusion of the coronary arteries
should a back-up pacing box. Cardiac output should be with donor blood. Whole body transfer using car-
maintained where possible. Antiarrhythmic drugs sup- diopulmonary bypass has also been used.
pressing ventricular activity should be avoided. Recipient:
[Karl Wenckebach (18481904), Dutch physician; immunosuppression and general management as
Woldemar Mobitz (18891951), German cardiologist] for heart transplantation.
See also, Pacemakers the trachea is divided above the carina. Damage to
vagi, phrenic and recurrent laryngeal nerves is
Heart, conducting system. Composed of: possible.
sinoatrial node: at the junction of the superior vena PEEP and inotropes are usually required; isoprena-
cava and right atrium. Normally discharges more line is particularly useful because of its ability to
rapidly than the rest of the heart, thus setting the reduce pulmonary vascular resistance. Pulmonary
rate of contraction, although all cardiac muscle is oedema and sputum retention are common. The
capable of depolarising spontaneously. cough reflex is destroyed and ciliary activity
atrioventricular node (AV node): lies in the atrial impaired.
septum, above the coronary sinus opening. Nor- weaning from IPPV is as for cardiac surgery.
mally the only means of conduction between atria lung rejection may occur without heart rejection,
and ventricles; the bundle of Kent is an abnormal and may be difficult to detect. Graft-versus-host
accessory conduction pathway that bypasses the AV disease may also occur.
node, and is present in WolffParkinsonWhite
syndrome. Heart murmurs. General principles:
bundle of His: divides into left and right bundle caused by turbulent flow of blood, including abnor-
branches above the interventricular septum, passing mal flow through a normal valve or normal flow
down on either side subendocardially: though an abnormal valve or orifice.
 Heart transplantation 269

systolic murmurs may be physiological; diastolic Heart sounds. The first sound is due to closure of the
murmurs are always pathological. tricuspid and mitral valves; it lasts 0.15s with frequency
low murmurs are heard best with the stethoscope 2545Hz. The second is due to closure of the aortic and
bell, high-pitched ones with the diaphragm. pulmonary valves; it lasts 0.12s with frequency 50Hz.
left-sided murmurs are heard best at end-expiration; Valve opening is normally silent.
right-sided ones best at end-inspiration. Intensity:
murmurs radiate usually in the direction of turbu- quiet in obese or well-built subjects. Also in
lent flow. pericarditis.
when auscultating the heart, murmurs are best second sound is quiet in aortic stenosis, since valve
described by: mobility is reduced.
- time of occurrence. first sound is quiet in mitral regurgitation, since
- site and radiation. valve closure is incomplete.
- character including relation to respiration. first sound is increased in mitral stenosis, since the
Loudness is usually expressed as a score of 15, valve is kept open right up to systole by increased
where 1 = only just audible; 5 = audible without a left atrial pressure, instead of gradual closure at end
stethoscope. of diastole.
- associated heart sounds. Splitting of the second sound:
Classification: heard at the left sternal edge.
systolic: the aortic component normally precedes the pulmo-
- pansystolic: nary component, since left ventricular contraction
- VSD. is faster than that of the right.
- mitral regurgitation. increased in inspiration, when right ventricular con-
- tricuspid regurgitation. traction is delayed by increased preload. Fixed in
- ejection: ASD; reversed in left bundle branch block and
- aortic stenosis or sclerosis (although severe severe aortic stenosis, when left ventricular contrac-
disease can produce a pansystolic murmur). tion is markedly delayed.
- pulmonary stenosis. Extra sounds:
- ASD. third heart sound (thought to be due to ventricular
diastolic: filling). Occurs shortly after the second sound. May
- mitral stenosis. occur in normal subjects, also in reduced ventricular
- aortic regurgitation. compliance/increased volume, e.g. in cardiac failure,
continuous: mitral regurgitation, VSD.
- patent ductus arteriosus. fourth heart sound (thought to be due to atrial con-
(N.B. Venous hum: due to kinking of major neck veins, traction under pressure with forceful ventricular
especially in children. Abolished by pressure on the distension). Occurs shortly before the first sound.
neck.) Always pathological, reflecting poor ventricular
See also, Cardiac cycle; Preoperative assessment; Pulmo- compliance; may occur in aortic stenosis, pulmonary
nary valve lesions; Tricuspid valve lesions stenosis, hypertension.
gallop rhythm: all four sounds, e.g. cardiac failure.
Heart rate. Normal range in adults is usually defined as others, e.g. the late ejection click of aortic stenosis,
60100 beats/min, but it may be less than 50 beats/min the late systolic click of mitral valve prolapse,
in fit young subjects, and increase up to 200 beats/min and the early diastolic opening snap of mitral
on exercise. Rate is about 100 beats/min in the dener- stenosis.
vated heart. In children, heart rate decreases with age heart murmurs.
from 110160 beats/min during infancy, reaching adult See also, Cardiac cycle; Preoperative assessment
values at about 12 years.
Rate is increased by: Heart transplantation. First performed in humans in
sympathetic activity, e.g. secondary to hypotension, 1967 by Barnard. Initial problems were infection and
hypoxaemia, hypercapnia, pain, fear, anger, rejection. Interest resurged in the late 1970s with the
exercise. introduction of ciclosporin, leading to establishment of
hormones, e.g. catecholamines, thyroxine. centres worldwide.
infection and fever. Indications: mostly end-stage ischaemic heart disease
Bainbridge reflex and inspiration. and cardiomyopathy; also congenital heart disease,
drugs, e.g. salbutamol. valvular disease and others.
Rate is decreased by: Contraindications include age over 50 years, insulin-
parasympathetic activity via the vagus nerve, e.g. dependent diabetes mellitus, active infection, and
secondary to the baroreceptor reflex, fear, pain, recent PE/MI; these contraindications have been
raised ICP, expiration. relaxed as expertise increases and chances of survival
hypoxaemia. improve.
drugs, e.g. neostigmine, -adrenergic receptor Donor:
antagonists. normal past medical history/examination and ECG.
Critically ill children often respond to handling, tracheo- A short period of cardiac arrest, and minimal
bronchial suction, hypoxaemia and acidosis with a requirements for inotropic support are acceptable.
profound bradycardia. Age should be < 40 years. ABO compatibility with
See also, Arrhythmias; Pacemaker cells; Sinus the recipient is required.
arrhythmia; Sinus bradycardia; Sinus rhythm; Sinus initial management including heparin and cardio-
tachycardia plegia is as for cardiac surgery. The heart is placed
270 Heat

in cold crystalloid solution and both the atria All these routes may be important in heat loss during
opened; it is transported in ice. anaesthesia.
Recipient: See also, Temperature regulation
most patients are prepared for the possibility of
emergency transplantation. By definition, they are Heat capacity. Quantity of heat required to raise the
in poor general health, i.e. high-risk patients. temperature of a mass by 1K (J/K). Specific heat capac-
immunosuppressive drugs include ciclosporin, ity (C) is the quantity of heat required to raise the tem-
corticosteroids, azathioprine and antithymocyte perature of unit mass of substance by 1K (J/kg/K). The
immunoglobulin. total heat capacity of an object may be calculated from
all iv lines, tracheal tube, laryngoscope, tubing, knowledge of the mass and values for C of its constituent
etc., are sterile to reduce infection, with gown and parts.
gloves worn. Examples of C:
general management is as for cardiac surgery. After human tissues, including blood: 3.5kJ/kg/K.
cardiopulmonary bypass and aortic cross-clamping, water: 4.18kJ/kg/K (1Cal/kg/C).
the ventricles are removed, leaving most of the For a gas, Cp is specific heat capacity at constant pressure,
atria. The atria and aortas are anastomosed. The and Cv is specific heat capacity at constant volume. CpCv
donor heart may also be piggy-backed next to equals the work done in expansion of the gas. For an
the original heart, anastomosing left atria, aortas, ideal gas, CpCv = R (universal gas constant).
pulmonary arteries and venae cavae. Since gases are much less dense than liquids, the
inotropes are usually required for over 24h. The energy required to heat unit volume is much less. Thus
denervated heart rate is usually faster than that little energy is expended in heating inspired air (although
of the innervated heart, with no response to indi- significant energy is expended humidifying it).
rectly acting drugs, e.g. atropine. Drugs acting See also, Latent heat
directly on the myocardium (e.g. isoprenaline) are
used. The rate responds slowly to circulating Heat loss, during anaesthesia. Prevention is important
catecholamines. because of the adverse effects of hypothermia and the
Postoperative care is as routine, but barrier nursing increased postoperative O2 consumption (up to 10 times)
is required. caused by shivering. In addition, the duration of action
regular endocardial biopsy via the right internal of neuromuscular blocking drugs is prolonged and drug
jugular vein is performed to detect rejection, clearance delayed. Particularly important in neonates
e.g. weekly, then monthly for 3 months, then and children, and in the elderly, because of reduced
6-monthly. reserves.
late complications include cardiac allograft vascu- Temperature may fall by several C during prolonged
lopathy (obliterative vasculopathy that leads to late surgery, via:
allograft failure). increased loss of heat:
For anaesthesia in a heart recipient, aseptic techniques - radiation (accounts for 4050% of loss): increased
are used, and directly acting cardiovascular drugs as if the patient is uncovered and surrounded by cold
above. Otherwise, management is as for any high-risk objects. Also increased by vasodilatation.
cardiac case. - convection (15%): increased if the patient is
90% of recipients return to full activity and 40% to uncovered.
work 1 year after transplantation. However, current - evaporation (3035%): increased if a body cavity
demand for hearts for transplantation exceeds supply. is opened, especially if ambient humidity is low.
Cardiac denervation during transplantation means that Heat loss via evaporation in the trachea and
many patients (about 90%) do not suffer angina. Xeno- airways may be considerable if inspired gases are
transplantation is an exciting potential development, but not humidified.
at present, concerns have been raised about its safety. - conduction (3%): usually a less important route;
Ramakrishna H, Jaroszewski DE, Arabia FA (2009). increased by use of cold irrigating solutions.
Ann Card Anaesth; 12: 718 reduced heat production and impaired temperature
[Christian N Barnard (19222001), South African regulation. The latter may be peripheral (e.g. vaso-
surgeon] dilatation, shivering and impaired piloerection) or
See also, Heartlung transplantation central (central effects of drugs).
Prevention:
Heat. Form of energy associated with movement of par- identification of high-risk patients:
ticles (e.g. molecules, atoms) within a substance or - extremes of age.
system; temperature describes the propensity for trans- - ill, malnourished patients.
fer of heat energy between systems. - prolonged surgery/open body cavity.
Heat is transferred by: - major blood loss.
radiation: especially from bright shiny bodies to - sickle cell anaemia.
dark matt bodies. temperature measurement during anaesthesia.
convection: as air next to a warm body is warmed, covering during transfer to the operating suite.
it expands and becomes less dense, rising and being maintenance of ambient temperature at 2224C
replaced by colder air. and humidity about 50% (compromise between
evaporation: heat is transferred to liquid molecules, patient temperature and staff comfort).
providing the energy required to break the bonds covering with drapes, reflective garments and head
between them in forming a vapour. coverings (especially children).
conduction: especially via good conductors of heat, warming of all skin cleansing solutions and iv fluids.
e.g. metals. humidification of inspired gases.
 HendersonHasselbalch equation 271

warming blankets, e.g. using heated water or air. thoracostomy tube, it allows the venting of air from
warming of the bed/blankets postoperatively. within the chest and prevents the ingress of air. May
Sessler DI (2008). Anesthesiology; 109: 31838 block/malfunction if blood passes through valve. Useful
during the prehospital phase of resuscitation or during
Heat of vaporisation, see Latent heat interhospital transfer. Now infrequently used since the
introduction of plastic underwater seal bottles and por-
Heatmoisture exchanger (HME; Swedish nose; table, disposable bag/valve assemblies.
hygroscopic condenser). Passive humidifier device. Posi- See also, Chest drainage
tioned between the breathing tubing and the facemask,
tracheal/tracheostomy tube or other airway device. Con- Helium. Inert gas, present in natural gas and to a lesser
tains material (e.g. sponges, paper or metal gauze) that extent in air. Less dense than nitrogen. Thus, if flow is
acts as a screen that can absorb large amounts of water. turbulent, greater flow of a helium/O2 mixture will occur
As expired gas passes through, water vapour condenses than of a nitrogen/O2 mixture, as turbulent flow depends
on the filter screen that also gains heat. The water and on fluid density (and density of 21% O2 in helium is 34%
heat are given up when dry, cool inspired gas passes of that of 21% O2 in nitrogen). Used therefore to increase
through in the next phase of breathing. May be dispos- alveolar O2 supply in upper airway obstruction. Of less
able or refillable. use in lower airway obstruction (e.g. asthma) because
Light and cheap; with up to 90% efficiency for modern most peripheral flow is laminar and therefore depends
devices. Minimum recommended moisture output is on viscosity, which is greater for helium/O2 mixtures than
20g/m3 for anaesthesia and 30g/m3 for intensive care. for nitrogen/O2. However, some benefit may occur where
Newer hydrophobic filters are efficient humidifiers as flow is turbulent.
well as being protective against bacterial and viral trans- Supplied in cylinders with brown shoulders and body,
mission. Efficiency is reduced in the presence of large at 137 bar. Also available with 21% O2, in brown-bodied
tidal volumes, drug nebulisers and copious secretions. cylinders with brown and white quartered shoulders, at
All devices increase dead space and resistance to spon- the same pressure.
taneous ventilation. Has also been used to investigate small airway resis-
Wilkes AR (2011). Anaesthesia; 66: 3139, 4051 tance to flow, by comparing flowvolume loops breath-
See also, Filters, breathing system; Humidification ing air and helium/O2. The two curves are more similar
in small airway obstruction than in normal lungs.
Heatstroke, see Hyperthermia Because of its very low solubility, helium is also used
in measurement of lung volumes.
Heavy metal poisoning. Poisoning by exposure to Harris PD, Barnes R (2008). Anaesthesia; 63: 28493
any toxic metal (regardless of its molecular weight),
including lead, mercury, arsenic, cadmium, bismuth, HELLP syndrome (Syndrome of haemolysis elevated
aluminium, antimony, chromium, cobalt, copper, gold, liver enzymes and low platelets). Condition first recog-
manganese, nickel, thallium, vanadium and zinc. Renal, nised in 1982; thought to represent part of the spectrum
hepatic, neurological and gastrointestinal damage are of pre-eclampsia characterised primarily by abnormal
common following ingestion; acute lung injury often blood tests rather than hypertension, proteinuria and
follows inhalation of fumes. Antidotes (chelating agents) oedema (although they may occur). HELLP syndrome
include dimercaprol (for antimony, arsenic, bismuth, is associated with significant maternal morbidity, includ-
gold, mercury, thallium and lead), penicillamine (copper ing DIC, placental abruption, acute kidney injury, pul-
and lead), ascorbic acid (chromium), succimer (arsenic, monary oedema and hepatic rupture. General principles
mercury), unithiol (arsenic, mercury, nickel) and sodium of management are as for pre-eclampsia; in addition
calcium edetate (lead, manganese, zinc). plasma exchange, administration of fresh frozen plasma
and prostacyclin have been used.
Hedonal. Obsolete anaesthetic agent, used iv (1905), Sibai BM (2004). Obstet Gynecol; 103: 98191
rectally and orally. Very slow in onset and offset.
Hemo. . ., see Haemo . . .
Heidbrink valve see Adjustable pressure-limiting valve
HendersonHasselbalch equation. Equation describ-
Heimlich manoeuvre. Method of relieving choking ing the relationship between the concentrations of dis-
caused by a foreign body using forceful compression of sociated and undissociated acid or base, acid or base
the upper abdomen. The resultant rise in intrathoracic dissociation constants (Ka and Kb respectively) and pH.
pressure expels the object from the upper airway. The In its generic form for weak acids (e.g. carbonic acid,
operator stands behind the subject with hands clenched thiopental sodium):
over the subjects epigastrium, the operators arms
passing under the subjects. A sharp thrust is delivered pH = pKa + log
[A ]
inwards and upwards. A similar manoeuvre may be per- [AH ]
formed with the subject lying. Compression of the lower and for weak bases (e.g. local anaesthetic agents):
chest has been found to be as effective. Clearance of [ B]
ones own airway by falling forwards on to the back of pH = pK b + log
a chair has been reported. [BH + ]
[Henry J Heimlich, US surgeon] Applicable to any buffer system; commonly illustrated
using the bicarbonate buffer system. For the reaction of
Heimlich valve. Disposable device used in the treat- CO2 with water to form carbonic acid, which dissociates
ment of pneumothorax. Consists of a flattened rubber to form bicarbonate and hydrogen ions:
tube within a clear plastic tube; attached to a CO2 + H 2O H 2CO3 H + + HCO3
272 Henrys law

The acid dissociation constant Ka for the dissociation of (APTT), although thrombin and clotting times are also
H2CO3 then equals prolonged. In low dosage, acts by preventing spontane-
[H + ][HCO3 ] ous activation of factor X in hypercoagulable states (e.g.
postoperatively), without affecting the ability to form
[H 2CO3 ] clots when required. Thus given sc to prevent DVT,
Taking logarithms of both sides: although there may be individual variation in effect.
[HCO3 ] Low-mw heparins inhibit factor X preferentially and
log Ka = log[H + ] + log thus cause fewer systemic anticoagulation effects, with
[H 2CO3 ] less effect on platelet function. Also have longer half-
[HCO3 ] lives. They do not require regular monitoring, may be
therefore log[ H + ] = log Ka + log given once daily and cause fewer haemorrhagic effects
[H 2CO3 ]
than unfractionated heparin when given for DVT pro-
[HCO3 ] phylaxis. Several low-mw heparins exist, with varying
or, pH = pKa + log
[H 2CO3 ] properties according to the particular preparation (e.g.
Since [H2CO3] is related to [CO2] by the original reac- ratio of anti-X to anti-II activity).
Dosage:
tion, and [CO2] is related to PCO2 and a solubility factor
unfractionated heparin:
(0.03mmol/l/mmHg, or 0.23mmol/l/kPa),
- prophylaxis of DVT: 5000 units sc 2h preopera-
[HCO3 ] tively, then bd/tds until the patient is walking.
pH = pKa + log
PCO2 0.03 - treatment of thrombosis: 5000 units iv, then 1000
with PCO2 measured in mmHg 2000 units/h (1428 units/kg/h) by infusion, or
500010000 units iv 4-hourly by bolus. APPT is
[HCO3 ] kept at 1.52.5 times normal. Oral anticoagulation
or pKa + log
PCO2 0.23 is usually commenced at the same time as heparin.
with PCO2 measured in kPa. - during arterial surgery, 100 units/kg iv; for cardiac
surgery, 300 units/kg. Also used to anticoagulate
Thus used to explain changes in pH, PCO2 and [HCO3] extracorporeal circuits, e.g. cardiopulmonary
in disturbances of acidbase balance. bypass, haemofiltration.
Maximal efficiency of a buffering system occurs at pH low-mw heparin:
values close to its pKa. pKa for carbonic acid/bicarbonate - prophylaxis of DVT:
is 6.1 at body temperature; its importance arises from the - dalteparin sodium: 2500 units sc 12h preop-
ability to excrete CO2 via the lungs. eratively (repeated after 12h in high-risk
When applied to pharmacokinetics, the equation can patients), followed by 2500 units od (5000 units
be used to predict the effect of plasma/tissue pH on the if high risk) for 5 days.
fraction of unionised drug; e.g. acidosis reduces the - enoxaparin: 2000 units (20mg) sc 12h preop-
unionised fraction of lidocaine hydrochloride, rendering eratively (4000 units [40mg] 12h preopera-
it less effective in infected tissues. tively in high risk patients), followed by 2000
[Lawrence Henderson (18781942), US biochemist; Karl units od (4000 units if high risk) for 710 days.
Hasselbalch (18741962), Danish physiologist] - tinzaparin: 3500 units sc 2h preoperatively
See also, Acidbase balance (4500 units 12h preoperatively in high-risk
patients), followed by 3500 units od (4500 units
Henrys law. Amount of gas dissolved in a solvent is if high risk) for 710 days.
proportional to the partial pressure of the gas when in - bemiparin sodium: 2500 units sc 2h pre
equilibrium with the solvent, at constant temperature. operatively or 6h postoperatively, followed
[William Henry (17441836), English chemist] by 2500 units od (3500 units if high risk) for 710
days.
Heparin sodium/calcium. Anticoagulant drug, used for - treatment of venous thrombosis: may be more
secondary prevention in acute coronary syndromes and effective than unfractionated heparin and does
for the prophylaxis and treatment of thromboembolism. not require dose adjustment according to labora-
Has also been used in DIC. Discovered in 1916. A muco- tory tests. Treatment should be continued for at
polysaccharide, derived from animal lung and intestine. least 56 days, during which time oral anticoagu-
Strongly acidic and electronegative, binding strongly to lants should also be given:
proteins and amines. - dalteparin: 200 units/kg od (100 units/kg bd in
Actions: patients at risk of haemorrhage) (maximal daily
potentiates the action of antithrombin III, a natu- dose 18000 units).
rally occurring inhibitor of activated coagulation - enoxaparin 150 units/kg (1.5mg/kg) od.
factors XII, XI, IX, X and thrombin. - tinzaparin 175 units/kg od.
inhibits platelet aggregation by fibrin. - bemiparin: 115 units/kg od for 59 days.
activates lipoprotein lipase, involved in fat - treatment of acute coronary syndromes:
transport. - dalteparin: 120 units/kg bd (maximum 18000
thought to be involved in immunological/ units bd).
inflammatory reactions, possibly via binding to his- - enoxaparin 100 units/kg (1mg/kg) bd.
tamine and 5-HT. Contained within mast cells. Higher doses are required in pregnancy.
Fast onset but short-acting, with half-life of about 90min; Side effects:
therefore most effectively given by iv infusion (heparin increased bleeding: cessation of infusion is usually
sodium). Effects persist for 46h and are monitored by adequate; protamine may be given but only par-
measuring the activated partial thromboplastin time tially reverses low-mw heparin.
 Hepatic failure 273

heparin-induced thrombocytopenia (HIT): reflexes, with plantar response up or down.

antibody-mediated condition occurring in up to 3% EEG is abnormal.
of cases, typically 510 days after starting therapy. - stage 3: marked somnolence and confusion, with
May be associated with increased tendency to inability to perform fine movements. Responds
thrombosis. Heparinoids and hirudins are alterna- to painful stimuli.
tives if this occurs. - stage 4: unresponsive; comatose with depressed
hypersensitivity. reflexes.
osteoporosis following prolonged use. Treatment includes reduction of nitrogen intake,
inhibition of aldosterone secretion has been and oral administration of lactulose (2050ml/
described and regular monitoring of plasma potas- day) and/or neomycin (1g 46-hourly) to reduce
sium concentration is recommended if the duration ammonia-producing GIT bacteria and encourage
of therapy exceeds 7 days. nitrogen-utilising bacteria.
Side effects are less frequent with low-mw heparins than - portal hypertension is caused by vascular
with unfractionated heparin. occlusion, possibly due to fibrotic changes in cir-
See also, Coagulation studies rhosis. It may cause splenomegaly and enlarge-
ment of portalsystemic vascular anastomoses,
e.g. oesophagogastric junction, retroperitoneal
Heparinoids. Heteropolysaccharide derivatives of
and umbilical vessels. Oesophageal varices may
heparin; used for the prevention and treatment of throm-
cause severe haemorrhage; treatment may include:
boembolism in patients with a history of heparin-induced
- medical treatment: iv vasopressin analogues
thrombocytopenia. Danaparoid is the only preparation
(e.g. terlipressin), somatostatin, proton pump
licensed for use in the UK.
inhibitors (e.g. pantoprazole sodium).
- band ligation or injection of varices with
Hepatic failure. May follow: sclerosant/tissue adhesive.
chronic disease and cirrhosis: - use of a SengstakenBlakemore tube.
- chronic autoimmune hepatitis. - transjugular intrahepatic portosystemic shunt-
- chronic viral hepatitis. ing (TIPS); 95% success rate for controlling
- drugs, e.g. methyldopa, alcohols. variceal bleeding, but can precipitate encepha-
- non-alcoholic fatty liver disease. lopathy or heart failure due to shunting of
- metabolic disease, e.g. haemochromatosis, portal blood into the systemic circulation.
Wilsons disease, 1-antitrypsin deficiency, other - rarely, surgery.
inborn errors of metabolism. - cirrhotic cardiomyopathy may be present, with
- biliary disease, e.g. primary biliary cirrhosis. features of heart failure, arrhythmias and reduced
- vascular lesions, e.g. venous occlusion, chronic response to inotropic drugs.
cardiac failure. - GIT haemorrhage: apart from oesophageal
acute disease (fulminant hepatic failure): varices, may also be caused by gastric erosions or
- acute viral hepatitis. peptic ulcer disease. Coagulation factors and
- drugs, e.g. paracetamol, halothane, chloroform, platelets may be reduced. Anaemia is common.
chlorpromazine, monoamine oxidase inhibitors, - hypoproteinaemia, with reduced plasma oncotic
phenytoin, isoniazid. pressure, drug binding, immunoglobulins, cholin-
- others: less common, including: esterase and coagulation factors.
- poisons, e.g. carbon tetrachloride. - fluid retention: may cause ascites, pleural effusion,
- portal vein thrombosis. peripheral oedema and hyperdynamic circulation.
- acute fatty liver of pregnancy. Treatment includes spironolactone, sodium restric-
- shock. tion and drainage of ascites/pleural effusion.
- Reyes syndrome. - hypoxaemia is common, caused by V/Q mismatch,
Features: atelectasis, diaphragmatic splinting or pleural
chronic liver disease: effusion. Portopulmonary hypertension may be
- malaise, GIT symptoms. present in end-stage disease due to accumulation
- jaundice. of vasoactive substances normally cleared by
- skin: spider naevi, palmar erythema, leukonychia, the liver.
finger clubbing, Dupuytrens contracture, bruis- - infection is common, especially bacterial.
ing, pigmentation, caput medusae (engorged - renal impairment may occur.
paraumbilical veins). - metabolic and respiratory alkalosis may occur.
- hepatic fetor. Acute decompensation of stable chronic liver
- gynaecomastia and testicular atrophy, caused by disease may be provoked by any acute illness,
decreased metabolism of circulating oestrogens. trauma or surgery.
- encephalopathy: thought to be caused by reduced acute fulminant hepatic failure: defined as hepatic
clearance of toxic waste products, e.g. ammonia, failure occurring within 8 weeks of illness, in a
methionine and fatty acids. May be provoked by previously normal liver. It presents with rapidly
stress, including surgery, trauma and infection. progressing encephalopathy, coma and cerebral
Classified thus: oedema, hypoglycaemia, hyponatraemia, hypoka-
- stage 1: altered personality or cognition. EEG laemia, alkalosis, hypothermia, acute lung injury,
is usually normal. haemorrhage, coagulopathy and renal failure. Renal
- stage 2: confusion, abnormal sleep and drowsi- failure may be due to hepatorenal syndrome or
ness. Asterixis (flapping tremor especially acute tubular necrosis. Jaundice is uncommon
affecting the hands/wrists) and increased initially. DIC and infection may occur.
274 Hepatitis

Treatment is supportive and includes O2 therapy, IPPV, - causes fever, headache, GIT symptoms,
vitamin K, blood products, neomycin/lactulose, H2 recep- impaired liver function tests, jaundice and
tor antagonists/omeprazole, prophylactic antibiotics and hepatomegaly.
nutritional support with dextrose. ICP monitoring may - recovery is usually within 6 weeks, although
be useful and measures (e.g. head-up tilt, mannitol) malaise may persist longer.
employed to reduce ICP if raised. Liver dialysis tech- - passive immunisation with immunoglobulin is
niques have been used and liver transplantation may be available.
required. Experimental therapies include auxiliary liver - hepatitis B:
transplantation, temporising hepatectomy, artificial liver - DNA virus, spread mainly via blood/blood
systems (live liver cells within an extracorporeal circuit), products and body secretions, including sexual
intraperitoneal hepatocyte transplantation, use of liver contact, tattooing, iv drug abuse and childbirth.
growth factors and xenotransplantation. Incubation period is 26 months.
Anaesthetic management of patients with hepatic - features are as for hepatitis A but more severe.
failure or chronic liver disease: May lead to recovery, acute fulminant hepatic
directed towards the above complications, particu- failure (rarely) or a chronic infective state. The
larly preoperative assessment for, and improve- last includes asymptomatic carriage or chronic
ment of: hepatitis that may lead to hepatocellular carci-
- encephalopathy, and haematological and coagula- noma or hepatic failure.
tion abnormalities. - serological markers include surface (Australia)
- pulmonary and renal function. antigen (HBsAg), e antigen (HBeAg), corre-
- fluid, acidbase and electrolyte disturbance. sponding antibodies (anti-HBs, anti-HBe) and
Vitamin K may be given if coagulation is abnormal, antibody to core antigen (anti-HBc). Pattern:
fresh frozen plasma if surgery is urgent. - HBsAg: increases 1 month after exposure,
anaesthetic technique: increased doses of iv agents peaks at 23 months, and falls at 45 months.
and neuromuscular blocking drugs may be required - HBeAg: increases at 1 month, peaks at 2
in cirrhosis, due to increased volume of distribution, months and falls at 3 months.
but elimination may be prolonged; all sedative - anti-HBc: increases at 2 months, peaks at 4
drugs require careful titration if encephalopathy is months and falls slowly thereafter.
present. Opioids should be used cautiously. Drug - anti-HBe: increases at 23 months, remaining
metabolism is reduced; isoflurane/desflurane and elevated.
atracurium are often preferred as reliance on - anti-HBs: increases at 12 months, remaining
metabolism is less than with other agents. Hypocap- elevated.
nia exacerbates the reduction in hepatic blood flow Asymptomatic carrier state is associated with
during general anaesthesia. HBsAg, HBeAg and anti-HBc expression. Its
screening for infectious hepatitis should be incidence is under 0.1% in the West, and up to
performed. 20% in South-East Asia. Serum viral DNA levels
maintenance of good peri- and postoperative renal may also be measured; they may distinguish
function is important (see Jaundice). between chronic hepatitis B (> 105 copies/ml) and
A scoring system has been devised for assessment of the inactive state (< 105 copies/ml). Patients with
risk, depending on preoperative blood tests and clinical chronic infection may receive interferon- or
assessment (Table 23). Good operative risk is suggested lamivudine.
by < 6 points, moderate by 79 points, and poor risk by - prevention:
> 10 points. - active immunisation (against HBsAg) of
[Baron Guillaume Dupuytren (17771835), French medical workers and high-risk groups, e.g.
surgeon; Samuel AK Wilson (18781937), US-born homosexuals, drug abusers, multiple blood
English neurologist] transfusion recipients, renal dialysis patients
Al-Khafaji A, Huang DT (2011). Crit Care Med; 39: and babies of infected mothers.
115766 - passive immunisation using immunoglobulin;
preferably performed within 24h of exposure
Hepatitis. Acute hepatitis may be: and certainly within 7 days.
viral: - screening of blood for transfusion, use of dis-
- hepatitis A: posable needles, etc.; operating theatre pre-
- RNA enterovirus, spread via the orofaecal cautions as for HIV infection. Pregnant
route. Incubation period is 35 weeks. women should be screened for HbsAg to
reduce fetal transmission.
- hepatitis C (causes most cases of what was previ-
Table 23 Scoring system for anaesthesia in hepatic failure
ously called non-A non-B hepatitis):
- RNA virus, identified with a serological
Points scored marker.
- thought to be responsible for over 90% of post-
1 2 3 tranfusion hepatitis in the Western world before
screening. Also common in patients receiving
Bilirubin (mol/l) <25 2540 >40 renal dialysis.
Albumin (g/l) >35 2835 <28 - acute infection is usually asymptomatic;
Prothrombin time prolongation (s) <4 46 >6 however, about 85% become carriers, with 20
Encephalopathy stage 0 12 34 40% developing chronic liver disease and
cirrhosis. About 5% develop hepatocellular
 Hereditary angio-oedema 275

carcinoma. Patients with chronic infection may renal hypoperfusion due to hypotension and intrarenal
receive interferon- and ribavirin. vasocontriction; a functional aetiology is suggested by
- screening of blood products began in the UK in normal renal histology in HRS and the observation that
1991. kidneys donated by HRS patients function normally in
- Since 2002, infected staff have been restricted their recipients.
from performing invasive procedures, as for Classified according to speed of onset and progres-
HIV infection. Individuals about to start careers sion; type 1 is rapidly progressive (often due to a pre-
or training that would rely on the performance cipitating cause, such as infection) and associated with
of exposure prone procedures are also tested. MODS, while type 2 is associated with slowly worsening
- hepatitis D (delta): RNA virus, dependent on ascites and haemodynamic function. Median survival is
coexistent hepatitis B infection. 13 weeks and 6 months respectively.
- hepatitis E (enteral non-A non-B infection): Prognosis is poor, even with renal replacement
RNA virus, spread by orofaecal route and usually therapy, unless hepatic function improves or transplant
causing mild illness. is performed. Administration of albumin and inotropic
- other viral infections include cytomegalovirus, drugs (e.g. terlipressin, noradrenaline) improves renal
herpes simplex, varicella zoster and glandular function in up to 50% of patients; early improvement in
fever. MAP predicts response to treatment.
due to other infections, e.g. toxoplasmosis, Arroyo V, Fernandes J (2011). Nat Rev Nephrol; 7:
leptospirosis. 51726
chemical:
- idiosyncratic, e.g. phenothiazines, monoamine Herbal medicines. Taken by up to 2030% of patients
oxidase inhibitors, tricyclic antidepressants, chlo- presenting for surgery and often overlooked by medical
roform, methyldopa, indometacin, erythromycin, staff. May have unpredictable physiological and pharma-
rifampicin, chlorpropamide. Halothane hepati- cological effects relevant to the perioperative period.
tis was first described in 1958, with an estimated Common examples include:
incidence of 1:6000 to 1:30000, typically follow- Echinacea: activates the immune system with
ing repeated exposure within a short period. The reports of allergy (including anaphylaxis), decreased
cause is uncertain but a direct toxic effect, an effectiveness of immunosuppressive drugs with
immune reaction to halothane or hepatocytes short-term use and immunosuppression with long-
altered by halothane, or halothane-induced term use.
hepatic hypoxia have all been implicated. Hepa- Ephedra (ma huang): contains ephedrine and other
titis has also followed exposure to more modern sympathomimetic alkaloids. Causes dose-dependent
volatile anaesthetic agents, but a causative role is tachycardia and hypertension with subsequent risk
unclear, the incidence is thought to be extremely of myocardial ischaemia and CVA. Increases risk of
low, and repeated exposure is generally consid- arrhythmias when inhalational anaesthetic agents
ered safe. such as halothane are used. Haemodynamic insta-
- dose-related, e.g. paracetamol, carbon tetrachlo- bility may occur with concomitant use of mono-
ride, alcohol. amine oxidase inhibitors. Should be discontinued
metabolic, e.g. Wilsons disease, or associated with 24h preoperatively.
pregnancy. garlic (ajo): inhibits platelet aggregation (some-
associated with circulatory abnormalities, e.g. right times irreversibly), increasing the risk of peri
ventricular failure, severe hypotension. operative bleeding. Should be discontinued 7 days
The cause of postoperative hepatitis is difficult to deter- preoperatively.
mine as many factors may be involved. 1 in 700 healthy ginkgo: inhibits platelet-activating factor with
patients have incidental impaired liver function tests potential for increased bleeding. Should be discon-
preoperatively. tinued 36h preoperatively.
[Samuel AK Wilson (18781937), US-born English ginseng: may cause hypoglycaemia and inhibition of
neurologist] platelet aggregation. Should be discontinued 7 days
See also, Environmental safety of anaesthetists preoperatively.
kava and valerian: cause sedation and may potenti-
Hepatorenal syndrome (HRS). Renal impairment sec- ate the effects of anaesthetic agents. Should be dis-
ondary to severe hepatic dysfunction, usually cirrhosis. continued 24h preoperatively.
May coexist with or mimic other causes of renal failure St Johns wort (Hypericum): causes enzyme induc-
(e.g. hypovolaemia, glomerulonephritis, urinary tract tion of the cytochrome oxidase system (especially
obstruction); therefore considered a diagnosis of the cytochrome P450 family). Should be discontinued
exclusion. at least 5 days preoperatively.
Diagnostic criteria: Hodges PJ, Kam PCA (2002). Anaesthesia; 57: 889900
cirrhosis with ascites.
serum creatinine > 130mol/l and no improvement Hereditary angio-oedema. Congenital deficiency of C1
after 2 days of volume expansion with albumin and esterase inhibitor, leading to complement activation
withdrawal of diuretics. with swelling of the face, mouth, skin and intestine. Of
absence of shock. autosomal dominant inheritance, but new mutations
no recent/current treatment with nephrotoxic drugs. account for 25% of cases; prevalence is 1 in 50000. May
normal renal ultrasound and no evidence of renal occur spontaneously or after a trigger (e.g. trauma, infec-
parenchymal disease. tion, surgery, stress), possibly via activation of kinins,
Patients with cirrhosis and ascites have a 20% 1-year plasmins or other proteases. An acquired form may
probability of developing HRS. Mechanism involves occur in lymphomas.
276 Hereditary angioneurotic oedema

Attacks may mimic an acute surgical abdomen, with Hexobarbital. Obsolete iv anaesthetic agent, introduced
pain, diarrhoea and vomiting. May also cause upper in 1932. Replaced by the safer and more predictable
airway obstruction, carrying a mortality of 2540%. thiopental.
Management of an acute episode is as for airway obstruc-
tion; iv adrenaline, corticosteroids, antihistamine drugs, HFJV, HFPPV, HFO, HFV, see High-frequency
aprotinin, antifibrinolytic drugs and danazol have been ventilation
tried, with varying results. Synthetic, partially purified C1
esterase inhibitor is the treatment of choice for the ter- Hiatus hernia. Protrusion of stomach through the
mination of acute attacks, and is effective in 3045min. diaphragmatic crura into the thorax. May be sliding
23 units of fresh frozen plasma (which contains C1 (type I), when the oesophagocardiac junction and upper
esterase inhibitor) may also be given. stomach move into the thorax, or rolling (type II), when
Perioperative prophylaxis consists of 7 days preop- this junction remains intra-abdominal but part of the
erative treatment with danazol or administration of C1 fundus herniates. The former is more common and more
esterase inhibitor 24h in advance. Additional inhibitor likely to cause gastro-oesophageal valve incompetence;
or fresh frozen plasma should be immediately available. the latter is more likely to strangulate.
Upper airway instrumentation should be minimised and More common in the elderly and in obesity.
patients should be monitored in a critical care environ- Symptoms:
ment postoperatively. epigastric pain, belching, indigestion.
Levy JH, Freiberger DJ, Roback J (2010). Anesth Analg; regurgitation; may lead to stricture formation.
110: 127180 GIT bleeding may occur.
Anaesthetic problems:

Hereditary angioneurotic oedema, see Hereditary aspiration of gastric contents:

angio-oedema - chronic pulmonary damage due to repeated

aspiration.
- risk of acute aspiration perioperatively.
HeringBreuer reflex (Inflation reflex). Inhibition of chronic anaemia.
respiratory muscles following lung inflation, leading to Management:
termination of inspiration. Afferent pathway is thought medical: weight loss, antacids, H2 receptor
to be from pulmonary stretch receptors via the vagus. Of antagonists.
minor importance in humans, but active in many other surgical: repair of the diaphragmatic defect and fun-
mammals; bilateral vagotomy produces slow deep doplasty: the oesophagogastric junction is invagi-
breathing in the latter but not the former. nated into a sleeve of fundus (Nissens plication).
[Karl Hering (18341918), German physiologist; Josef Requires laparotomy and possibly thoracotomy,
Breuer (18521925), Austrian psychiatrist] and may be lengthy.
[Rudolph Nissen (18961981), Swiss surgeon]
Heroin, see Diamorphine See also, Diaphragmatic herniae; Gastro-oesophageal
reflux; Lower oesphageal sphincter
Hertz. SI unit of frequency. 1Hz = 1 cycle per second.
[Heinrich Hertz (18571894), German physicist] Hiccups. Intense synchronous contraction of the dia-
phragm and inspiratory intercostal muscles lasting about
500ms, followed approximately 30ms after its onset by
Hetastarch, see Hydroxyethyl starch
glottic closure. May involve phrenic or vagal efferents.
Results in a characteristic inspiratory sound associated
Hewer, Christopher Langton (18961986). English with discomfort. On average, occur at a rate of less than
anaesthetist, of major importance in the establishment 30/min. Frequent in the newborn. Frequency is decreased
and evolution of anaesthesia in the UK. Popularised the by breath-holding or a raised arterial PCO2 and increased
use of trichloroethylene in 1941. Edited Anaesthesia for by a lowered arterial PCO2. Episodes may be terminated
its first 20 years, also Recent Advances in Anaesthesia and by a sudden shock. May occur recurrently with neuro-
Analgesia for 50 years. Received many honours and logical disease (e.g. brainstem tumours, encephalitis,
medals. meningitis), metabolic disease (e.g. uraemia) and many
thoracic, abdominal or cardiac conditions. During anaes-
Hewitt, Frederick (18571916). English anaesthetist, thesia, hiccups may be provoked by surgical stimulation,
practised at St Georges Hospital. Renowned for many especially around the diaphragm, and particularly in the
contributions to anaesthesia, including the first fixed presence of inadequate paralysis or anaesthesia.
proportion N2O/O2 machine, inhalers, airways and other Rarely troublesome, but the following have been sug-
equipment. A strong advocate of teaching and high stan- gested as treatment:
dards in anaesthesia. Knighted in 1911. hyperventilation.
metoclopramide, chlorpromazine, haloperidol,
Hexafluorenium. Obsolete drug used to prolong the baclofen, anticonvulsant drugs.
nasopharyngeal stimulation.
action of suxamethonium by inhibiting plasma cholines-
during anaesthesia, all the above have been used, as
terase. May cause arrhythmias and bronchospasm.
has deepening anaesthesia increasing analgesia
and muscle relaxation.
Hexamethonium. Obsolete ganglion blocking drug
used in hypotensive anaesthesia. Hickman, Henry Hill (18001830). English surgeon,
practising in Ludlow and Shifnall, Shropshire. First
Hexastarch, see Hydroxyethyl starch described the production of insensibility in animals by
 Histamine and histamine receptors 277

exposure to a gas (CO2) and suggested its use for pain- in the coagulation pathway; unlike heparin, it does not
less surgery, in 1824. His efforts to publicise his experi- require antithrombin III as a cofactor and is not inhib-
ments were unsuccessful, both in the UK and abroad. ited by anti-heparin proteins. It also does not affect
platelets directly and may also inhibit thrombin bound
Hickman line, see Central venous cannulation, to a fibrin clot. Has been studied as a means of prevent-
long-term ing primary and recurrent MI and DVT; initial studies
have been encouraging, although bleeding may be a
High dependency unit (HDU). Area providing a level problem, as with heparin. Lepirudin and bivalirudin are
of care between that of a general ward and an ICU (i.e. recombinant forms available in the UK.
level 1 and 2 care). Provides care for patients with a
single failing organ system, those stepping down from His bundle electrography. Technique for investigating
ICU and high-risk patients requiring postoperative care. cardiac conduction defects and tachycardias, using trans-
Costs and nursing requirements are less than for an ICU; venous intracardiac bipolar electrodes at various sites.
they usually have a nurse:patient ratio of 1:2. Concurrent recording of a formal ECG is usually under-
See also, Care of the critically ill surgical patient; Medical taken. Assesses conduction through different parts of
emergency team; Postoperative care team; Safe transport the heart conducting system, identifying conduction
and retrieval team; Transportation of critically ill patients defects and accessory pathways. May also be used to
distinguish supraventricular from ventricular arrhyth-
High-frequency ventilation (HFV). Mechanism mias; ventricular complexes in the former are preceded
of respiratory support developed in the 1970s. Small by His bundle activity. The effects of pacing stimuli at
breaths are delivered at high frequencies, maintaining different sites may also be observed, e.g. in assessment
gas exchange without barotrauma or other deleterious of refractory tachycardias.
effects of IPPV. May be superimposed on spontaneous [Wilhelm His (18631934), German anatomist]
ventilation.
Three modes are used: Histamine and histamine receptors. Histamine, an
high-frequency positive pressure ventilation amine, is present in mast cells, basophils, gastric mucosa
(HFPPV): 60150 cycles/min, delivered via an intra- and the CNS. It is involved in the inflammatory response
tracheal insufflation catheter, bronchoscope or tra- and gastric acid secretion, and is thought to be a neu-
cheal tube. Tidal volumes of 100400ml are used. rotransmitter, although its role as the latter is unclear.
Fluidic valves are often used, without moving parts. Involved in many other inflammatory mediator path-
Possible using some conventional ventilators, espe- ways (e.g. cytokines, complement, leukotrienes) and
cially paediatric ones. with coagulation and other processes. Synthesised by
high-frequency jet ventilation (HFJV): 60600 decarboxylation of L-histidine, and broken down by
cycles/min, delivered via a cannula inserted through deamination and/or methylation with renal excretion.
the cricothyroid membrane, placed within a bron- Histamine receptor subtypes have been identified:
choscope, or incorporated near the tip of a tracheal H1:
tube. Expiration is continuous through the open - cause smooth muscle contraction in the GIT and
system. Principles of gas entrainment are as for uterus, and bronchoconstriction via cholinergic
injector techniques. Tidal volume is up to 150ml. pathways following stimulation of irritant pulmo-
Produces positive airway pressure of about 5 nary receptors.
cmH2O. Most ventilators employ electrical solenoid - cause vascular smooth muscle relaxation and dila-
valves. tation, with increased vascular permeability.
high-frequency oscillation (HFO): 5003000 cycles/ - cause stimulation and irritation of cutaneous
min; the gas column is oscillated with an O2 input nerve endings.
via a side arm, or more recently using a vibrating H2:
membrane (similar to a loudspeaker) applied - cause some vasodilatation (but less than H1
directly to the gas column (thus providing active receptors).
exhalation unlike the other systems in which exha- - have direct inotropic and chronotropic effects on
lation is passive). Mean airway pressure determines isolated hearts, but hypotension usually results
oxygenation, whilst oscillatory amplitude deter- from vasodilatation.
mines CO2 removal. - increase acid, pepsin and intrinsic factor secretion
The mechanism of gas exchange is unclear but is thought from gastric mucosa.
to involve continuous mixing of gases. HFJV is most H3: present in the CNS and of uncertain clinical
commonly used, particularly for ENT and thoracic pro- significance. Thought to inhibit histamine and ace-
cedures such as sleeve resection of the trachea/bronchi tylcholine release.
and tracheobronchial fistula, in which increased airway H4: present in GIT and basophils and involved in
pressures and excessive movement may be especially chemotaxis.
detrimental. HFO has been used in acute lung injury in The histamine receptors are all G protein-coupled
all ages. It reduces airway pressures and splints the lungs receptors; H2 actions are thought to be mediated via
above closing capacity, unlike conventional IPPV, in cAMP, and H1 via cyclic guanosine monophosphate.
which pressure and volume changes exhibit large swings. Specific receptor antagonists have been developed;
HFJV via cricothyrotomy is an alternative to tracheal they are called antihistamine drugs (H1) and H2 receptor
intubation and IPPV in respiratory failure. antagonists largely for historical reasons (the latter were
designed many years after the former).
Hirudin. Peptide (65 amino acid) originally derived Histamine is released from mast cells following iv
from leech saliva, now manufactured using recombinant injection of certain drugs, e.g. tubocurarine and mor-
techniques. Specifically inhibits the actions of thrombin phine. The amount released depends partly on the rate
278 Histamine receptor antagonists

of injection. Skin wheals, hypotension and broncho- 5-HT, see 5-Hydroxytryptamine

spasm may occur.
See also, Anaphylactoid reactions; Carcinoid syndrome 5-HT3 receptor antagonists. Group of drugs including
ondansetron, granisetron, tropisetron, dolasetron and
Histamine receptor antagonists, see Antihistamine palonosetron, used in the prevention and treatment
drugs; H2 receptor antagonists of PONV and cytotoxic-induced nausea and vomiting.
5-HT is released by the action of anticancer drugs on
HIV, see Human immunodeficiency viral infection enterochromaffin cells in the gut mucosa, stimulating gut
5-HT3 receptors and activating vagal afferents, resulting
HME, see Heatmoisture exchanger in vomiting. 5-HT3 receptors are also thought to be
involved centrally in the vagal reflex pathways; 5-HT3
Hofmann degradation. Spontaneous degradation of receptor antagonists therefore have both a central and
amides (RCONH2) to amines (RNH2), and quaternary a peripheral action. May also be useful in the treatment
ammonium salts to tertiary ones, under certain physical of opioid-induced pruritus (unlicensed use).
conditions. Atracurium (a quaternary ammonium com-
pound) spontaneously degrades to laudanosine at body Hfner constant. The volume of O2 carried by 1g hae-
temperature and plasma pH. moglobin; e.g. used in the calculation of O2 delivery and
[August von Hofmann (18181892), German chemist] O2 flux. Figures vary, according to whether it is measured
Alston TA (2003). Anesth Analg; 96: 6225 in vitro or in vivo; 1.39 and 1.34ml are most commonly
quoted respectively. The latter value is the more relevant
Holmes, Oliver Wendell (18091894). US physician, clinically.
poet and author; Professor of Anatomy at Harvard, [Carl von Hfner (18401908), German physician]
Boston. Famous for his treatise on puerperal fever and
its prevention, and for his non-medical writing. Sug- Human immunodeficiency viral infection (HIV
gested anaesthesia as a suitable term for ether narcosis infection). First recognised in 1981 in the USA as
in a letter written to Morton in 1846. the acquired immunodeficiency syndrome (AIDS) in
otherwise healthy homosexual males. The retrovirus,
Homeostasis. Concept first proposed by Bernard, relat- human immunodeficiency virus type 1 (HIV-1) was first
ing to maintenance of physiological variables within isolated in 1983. HIV-2 was identified in 1986, limited
normal limits, allowing optimal functioning of tissues mainly to West Africa, where the disease is thought to
and cells. Includes maintenance of acidbase balance, have originated; most HIV disease worldwide is caused
fluid balance, temperature regulation, arterial BP and by HIV-1. The virus binds to CD4 receptors on T-helper
hormone secretion. Most mechanisms involve negative lymphocytes and introduces its RNA genome into the
feedback; i.e. an increase of a substance or parameter cells, where the viral enzyme reverse transcriptase gen-
causes direct inhibition of mechanisms that increase it, erates a DNA copy that is then incorporated into the
bringing about its restoration to normal; deficiency human DNA. It may then remain latent or produce viral
results in stimulation of these mechanisms. copies; viral protease cleaves viral precursor proteins
into their active forms, which are released from infected
Hormone replacement therapy (HRT). Use of oes- cells. Tcells are eventually destroyed in the process,
trogen or oestrogen/progestogens to prevent unpleas- leading to increased susceptibility to infection and
ant symptoms associated with the menopause (e.g. hot malignancy.
flushes, night sweats and vaginal dryness). Also protects The history and epidemiology of HIV are complex;
against cardiovascular disease and osteoporosis but however, a fall in new infections in the last decade has
may increase the risk of CVA, MI and certain cancers been offset by a reduction in AIDS-related deaths,
(e.g. breast) and DVT, e.g. perioperatively. Periopera- causing global prevalence to stabilise at 0.8%. An esti-
tive precautions similar to those used for oral contra- mated 1.2 million people are infected in the USA and
ceptives have been suggested for women on HRT, 750000 in western Europe, with over 40 million people
although this is controversial since the risk is thought to infected worldwide (65% of them in sub-Saharan
be less. Africa); over 25 million deaths have occurred since the
Brighouse D (2001). Br J Anaesth; 86: 70916 disease was first recognised.
Transmitted mainly via semen and blood, i.e. via:
Horners syndrome. Clinical picture results from inter- sexual contact (especially malemale).
ruption of sympathetic innervation to the head. Origi- transfusion of blood products.
nally described with cervical lesions, it may be due to infected needles, e.g. used by drug addicts.
lesions anywhere along the sympathetic pathway, includ- transplacentally, at delivery or via breast milk.
ing epidural anaesthesia. Consists of partial ptosis, spillage of infected blood on to broken skin, or into
meiosis, apparent enophthalmos, lack of sweating and the eye.
nasal stuffiness on the affected side. The virus may be isolated from other body fluids, e.g.
[Johann Horner (18311886), Swiss ophthalmologist] vaginal secretions, saliva, tears. Transmission by mouth-
to-mouth contact (e.g. during CPR) is not thought to
Hospital-acquired infections, see Nosocomial occur.
infection High-risk groups include the sexually promiscuous, iv
drug abusers, haemophiliacs, Haitians and Central/West
HQIP, see Healthcare Quality Improvement Africans.
Partnership Features:
most infected people are thought to be
HRT, see Hormone replacement therapy asymptomatic.
 Human immunodeficiency viral infection 279

an acute, flu-like seroconversion illness may occur nucleoside reverse transcriptase inhibitors (NRTIs),
13 weeks after infection. The incubation period e.g. zidovudine, didanosine, abacavir, zalcitabine,
may be as long as several years. stavudine, lamivudine.
weight loss, diarrhoea, fever and thrush (AIDS- protease inhibitors, e.g. indinavir, ritonavir, lopina-
related complex) commonly progress to AIDS vir, nelfinavir, amprenavir, saquinavir. Inhibition of
itself. Thrombocytopenic purpura and anaemia, hepatic cytochrome P450 may give rise to interac-
dementia, encephalitis and psychosis may occur, tions with other drugs.
related to HIV infection itself or secondary infec- non-nucleoside reverse transcriptase inhibitors
tion by other organisms. (NNRTIs), e.g. efavirenz, nevirapine: used in com-
AIDS: presence of indicator diseases, e.g. opportu- bination therapy.
nistic infection (e.g. Pneumocystis jiroveci [formerly Side effects and syndromes associated with HAART
P. carinii] chest infection, pneumonia, candidiasis, include:
cytomegalovirus), Kaposis sarcoma, lymphoma, lactic acidosis, particularly with NRTIs: due to mito-
encephalopathy. chondrial toxicity. May be asymptomatic or prog-
Classified using the CD4 count ( 500/l; 200499/l; ress to MODS and death. Treatment involves
200/l), viral load and the World Health Organiza- cessation of the triggering agent, bicarbonate and
tion Staging System for HIV infection: haemofiltration in severe cases.
stage 1: asymptomatic or lymphadenopathy hypersensitivity syndromes, including: anaphylaxis;
only. interstitial pneumonitis; hepatitis and toxic epider-
stage 2: minor mucocutaneous manifestations (e.g. mal necrolysis.
oral ulceration, seborrhoeic dermatitis) and upper immune reconstitution inflammatory syndrome:
respiratory tract infections. paradoxical worsening of inflammatory processes
stage 3: chronic diarrhoea, weight loss, severe after initiation of HAART, due to improved
bacterial infections, hairy leucoplakia, pulmonary immune response to infectious agents (especially
tuberculosis. tuberculosis). May result in pericarditis, meningitis
stage 4: presence of AIDS-defining illness as and lymphadenitis; difficult to distinguish from
above. infection.
Diagnosis, monitoring and progression: lipodystrophy syndrome: redistribution of fat,
testing for HIV is a two-step process consisting of insulin resistance and dyslipidaemia may occur
initial screening for serum antibodies followed by after long-term HAART.
confirmation of positive results with a more specific non-specific side effects include GIT upset,
test, e.g. immunofluorescence assay. neuropathies, psychological disturbances,
seroconversion occurs on average 1 month after hepatotoxicity.
infection. Before HAART (see below) two-thirds Anaesthetic/ICU considerations:
progressed to AIDS within 10 years, with a 5-year features of illness and complications of drug therapy
survival about 20% once AIDS was diagnosed. With as above.
current therapy, meticulous adherence to drug regi- patients are at risk from infection as for
mens and follow-up, many patients may live for immunodeficiency.
several decades. measures to protect staff and other patients from
in Africa, due to poorer access to treatment, sur- HIV infection:
vival is shorter, with about 30% HIV-positive - avoidance of use of needles/parenteral
cases progressing to death without passing through medication.
AIDS itself. - wearing of gowns, goggles, gloves and overshoes.
the CD4 count may fall gradually or suddenly; - careful disposal of sharps; needles should not
a count below 200/l (normal 6001500/l) indi- be resheathed after use. Hospitals should have
cates increased risk of opportunistic infection. policies for management of accidental needlestick
Plasma viral load refers to the amount of viral RNA injuries, from which the risk of transmission
measurable in the plasma and correlates is about 0.3% (see Environmental safety of
with speed of disease progression; current practice anaesthetists).
uses viral load with CD4 count to guide - use of disposable equipment where possible.
management. - filters on breathing tubing if not disposable.
Treatment: previously reserved for AIDS, drug - all non-disposable equipment is soaked in hypo-
therapy is now commonly used before immunosup- chlorite or glutaraldehyde solution after use;
pression occurs. Typically consists of triple therapy theatre equipment, walls, floors, etc., are washed
(e.g. two nucleoside reverse transcriptase inhibitors down.
and a protease inhibitor), termed highly active - general considerations:
antiretroviral therapy (HAART). Indications for - blood and its products are used increasingly
HAART in confirmed HIV infection: sparingly; although donor blood is screened for
stage 1 or 2 disease with CD4 count < 200/l. anti-HIV antibodies, virus infection without
stage 3 disease with CD4 < 350/l. seroconversion cannot be excluded.
stage 4 disease regardless of CD4 count. - iv equipment should not be used for more than
Treatment consists of: one patient.
supportive measures, e.g. nutrition, treatment of staff with HIV infection should not perform inva-
infection. Co-trimoxazole and pentamidine are sive procedures, although they may provide other
usually used for pneumocystis pneumonia; the latter aspects of care under the guidance of their occupa-
drug may be given iv, im or by nebuliser to reduce tional health department. If such procedures have
side effects (and as prophylaxis). been performed, all exposed patients should be
280 Human Rights Act

offered counselling and testing. Routine testing coated (calcium or lithium chloride) paper mem-
of healthcare workers is not current practice in brane. Many HMEs are also filters. Efficiency is
the UK. up to 90%. Useful for short-term IPPV provided
[Moricz K Kaposi (18371902), Austrian dermatologist] secretions are not tenacious. Should be changed
Morris A, Masur H, Huang L (2006). Crit Care Med; 34: every 2448 hours.
429 active, i.e. energy source required; commonly used
in ICU because efficiency is high:
Human Rights Act. Introduced in the UK in 1998 - hot water bath: up to 60C is employed in some,
(coming into force in 2000), the Act incorporates the to reduce bacterial contamination. Inspired gas is
European Convention on Human Rights, ratified by the passed over or through the water. Efficiency is
UK in 1951. Has 18 Articles, many of which have particu- increased by passing gas through a perforated
lar relevance to clinical anaesthesia/critical care: screen to form tiny bubbles (cascade humidifier),
2: right to life. Withdrawal/withholding of treatment or using absorbent wicks to increase surface area.
is still permissible if it is in the patients best Humidified gas is unsaturated at the working tem-
interests. perature, but becomes near-saturated as the tem-
3: prohibition of torture and inhuman or degrading perature falls along the tubing to the patient.
treatment. This Article is absolute; i.e. there are no Condensation of water within the tubing may be
exceptions. reduced by heating wires within the tubing, giving
5: right to liberty and security. Relevant to treat- closer control of the temperature drop between
ment or restraint of patients against their will. machine and patient. Risk of delivering exces-
8: right to respect for private and family life. Rele- sively hot gases is reduced by monitoring the tem-
vant to disclosure of information. Requires qualifi- perature within the humidifier and at the patient
cation by balancing individuals and societys end of the tubing (usually kept at about 35C),
interests. using thermostat controls and alarms.
9: freedom of thought, conscience and religion. - other heated humidifiers, e.g. dropping water on
Relevant to refusal of treatments for religious to a heated element.
reasons. - nebulisers.
14: prohibition of discrimination. Relevant to Infection risks (typically with pseudomonas) are reduced
rationing of scarce resources on the grounds of age by addition of antiseptic to the water, maintenance at
or race. high temperature where appropriate, and changing
Other Articles may be relevant to doctors rights as tubing and water daily. Condensation within tubing may
employees. All public authorities (including the NHS provide foci for infection, obstruct ventilation or drain
and its employees) must comply with the Convention. water into the patients airways. The level of the water
White SM, Baldwin TJ (2002). Anaesthesia; 57: 8828 source should be kept below that of the patient. Over-
heating and electrocution may also occur.
Humidification. Inspired air is normally maximally Ward B, Park GR (2000). Clin Intensive Care; 11:
humidified in the naso/oropharynx, becoming saturated 16976
by the time it reaches the trachea. Absolute humidity in See also, Filters, breathing system
the upper trachea is 34g/m3 (i.e. fully saturated at 34C);
in alveoli it is 43g/m3 (i.e. fully saturated at 37C). Deliv- Humidity. Absolute humidity is the mass of water
ery of dry gases to the trachea (e.g. via a tracheal tube vapour per unit volume of gas at given temperature and
or tracheostomy) may cause drying of the respiratory pressure, in g/m3 or mg/l.
mucosa with reduced ciliary activity, keratinisation and Relative humidity (%) is the absolute humidity
ulceration, increased tenacity of mucus with plugging of divided by the amount present when the gas is fully satu-
airways, atelectasis and reduced gas exchange. Humidi- rated at the same temperature and pressure.
fication of inspired gases prevents this and reduces heat Maximal possible water content varies with tempera-
loss, partly by warming the gases (under 2% of total ture (Fig. 82). Thus heating a gas does not affect its
basal heat loss) but more importantly by avoiding the absolute humidity, since the amount of water contained
requirement for latent heat of vaporisation (1015% of
total basal heat loss) within the trachea.
Humidification is thus mandatory during ventilation
on ICUs and during prolonged general anaesthesia. 50
Humidification of the patients environment may be
Water content (g/m3)

achieved (e.g. with an O2 tent) but it is usually 40

restricted to inspired gases only. Methods:
passive: 30
- tracheal water/saline instillation; inefficient and
potentially dangerous if large volumes are used.
20
- bubbling inspired gas through cold water; simple
but relatively inefficient (up to 10g/m3 produced).
Vaporisation cools the water, decreasing effi- 10
ciency further.
- heatmoisture exchanger (HME): light, simple 0
and highly efficient with a small dead space. Heat 0 10 20 30 40
is conserved during expiration, allowing inspired Temperature (C)
gas to be heated and humidified. Most HMEs are
hygroscopic, consisting of a foam or chemically Fig. 82Water content of saturated air at different temperatures
 Hydrostatic pressure 281

remains constant, but relative humidity is reduced, communicating: blockage distal to the fourth ven-
because warmer gas can contain more water vapour. tricular outlets, e.g. at the basal cisterns.
Normal values of absolute humidity in: Causes:
3
upper trachea: 34g/m (fully saturated at 34C). congenital, e.g. narrowed aqueduct, obstruction of
3
alveoli: 43g/m (fully saturated at 37C). fourth ventricle outlet by a membrane (Dandy
Usual value of relative humidity in operating theatres: Walker syndrome), herniation of the cerebellar
5060%. Higher values are too uncomfortable; lower tonsils through the foramen magnum (Arnold
values increase risk of sparks. Measured using a Chiari syndrome).
hygrometer. acquired: meningitis with adhesions, surgery, head
See also, Humidification injury, subarachnoid haemorrhage, tumour, etc.
Usually accompanied by increased ICP; it may be acute,
Hunters syndrome, see Inborn errors of metabolism requiring urgent drainage. Pressure may be normal in
some chronic forms, with slow ventricular enlargement.
Huntingtons disease. Rare autosomal dominant inher- Head size is increased in children, with bulging of fon-
ited disorder, resulting in neurological degeneration in tanelles. Cerebral or cerebellar atrophy may be present.
Treatment:
middle life. Ataxia, dementia and choreiform move-
ments occur, with emaciation and death usually within surgery to the obstructive lesion.

15 years. Anaesthetic considerations include the man- shunt insertion: e.g. from the lateral ventricle to the

agement of the uncooperative patient and interactions peritoneum or right atrium

Anaesthetic considerations:
between anaesthetic and psychiatric medication.
[George Huntington (18501916), US physician] as for neonates/paediatric anaesthesia.

Kwella JE, Sprung J, Southorn PA, Watson JC, as for neurosurgery.

Weingarten TN (2010). Anesth Analg; 110: 51523 head enlargement may hinder tracheal intubation.
[Walter E Dandy (18861946) and Arthur E Walker
Hurlers syndrome, see Inborn errors of metabolism (19071995), US neurosurgeons; Julius Arnold (1835
1915), German pathologist; Hans von Chiari (1851
1916), Austrian pathologist]
Hyaline membrane disease, see Respiratory distress
syndrome
Hydrocodone bitartrate. Opioid analgesic drug, avail-
Hyaluronidase. Enzyme that reversibly depolymerises able in the USA together with other ingredients in oral
hyaluronic acid, a polysaccharide present in connective preparations for cough and pain.
tissue. Aids dispersal and absorption of drugs and fluids,
given sc or im, by intention or accident. Has also been Hydrocortisone. Natural corticosteroid, with consider-
mixed with local anaesthetic agents to aid spread. able glucocorticoid activity but little mineralocorticoid
Administration: 1500IU in 12ml water is injected into activity. Used therapeutically in adrenocortical insuffi-
the absorption site, before, after or together with the ciency, hypopituitarism, acute immunological reactions
drug. May be injected through a sc cannula before (e.g. anaphylaxis) and various inflammatory/autoimmune
administration of fluid (hypodermoclysis), allowing up conditions.
to 1000ml to be given into the thigh, calf, chest, abdomen Dosage:
or back regions. acutely iv/im as the sodium succinate or sodium
phosphate (iv injection of the latter may cause peri-
Hydatid disease, see Tropical diseases neal irritation): 100500mg tds/qds.
orally in replacement therapy: 2030mg/day in two
Hydralazine hydrochloride. Vasodilator drug, acting doses.
mainly on arterioles. Used to lower BP, e.g. in hyperten- other routes: rectally, intra-articularly or topically as
sion, hypotensive anaesthesia and pre-eclampsia. Half- the acetate.
life is 23h; up to 16h in renal failure. Certain patients
acetylate the drug quickly, reducing half-life to under Hydrogen ions (H+). About 1250013000mmol are
1h. Its onset of action may be up to 15min after iv bolus, produced in the body per day, mainly from the reaction
with effects lasting up to 90min. of CO2 (produced during respiration) with water. Also
Dosage:
produced during metabolism of foodstuffs, etc. Acid
2550mg orally bd.
base balance requires buffering and excretion to main-
510mg increments iv.
tain extracellular hydrogen ion concentration at
200300g/min by infusion initially, then 50150g/
3446nmol/l, equivalent to pH of 7.347.46. Hydrogen
min. ion homeostasis is required to maintain proper function-
Side effects:
ing of proteins (especially enzymes).
hypotension, tachycardia, fluid retention, nausea.
See also, Acidosis; Alkalosis; Buffers
systemic lupus erythematosus syndrome, especially
in slow acetylators and following prolonged oral
therapy at doses greater than 100mg/day. Hydromorphone hydrochloride. Opioid analgesic
drug, widely used in the USA but less so in the UK.
Hydrocephalus. Increased CSF volume. May be caused 1.5mg is equivalent to 10mg morphine, from which it is
by increased production or decreased drainage, usually derived. Action lasts 35h. Available for rectal, oral and
the latter: parenteral administration.
non-communicating: blockage between the lateral
ventricles and fourth ventricular outlets. Hydrostatic pressure, see Starling forces
282 -Hydroxybutyric acid

-Hydroxybutyric acid (GHBA). Drug related to lower mean mw (200250kDa) and lower MS; half-
GABA and used as an iv anaesthetic agent in the 1960s life and accumulation are reduced as a result.
and 1970s. Present as a neurotransmitter, especially in tetrastarch (0.4 MS ratio): mean mw is 130kDa.
the hypothalamus and basal ganglia. Causes slow onset Latest generation of HES solution, with minimal or
of anaesthesia, lasting up to 90min. Has been used for no effect on coagulation and renal function.
paediatric anaesthesia (especially cardiac catheterisa- Degraded to smaller molecules (~70kDa) at a con-
tion) because of its relative lack of cardiorespiratory stant rate, providing a more consistent concentra-
depression, although bradycardia may occur. No longer tion in the plasma that lasts ~ 4h, with almost
available medicinally in the UK, although still used else- complete renal clearance and low risk of accumula-
where in the world, e.g. certain other parts of Europe tion. May also have an anti-inflammatory effect in
and Russia. sepsis and after surgery. Available as 6% and 10%
Has become a drug of abuse for body builders (in an solutions in 0.9% saline or in a balanced electrolyte
attempt to increase growth hormone production) and as solution.
a recreational drug (liquid ecstasy). Has also been used Westphal M, James M, Kozek-Langenecker S (2009).
by criminals to induce unconsciousness in victims since Anesthesiology; 111: 187202
the drug is difficult to detect when added to drinks. See also, Intravenous fluids
Overdose results in confusion, ataxia, visual distur-
bances, hallucinations, coma and convulsions; effects are
5-Hydroxytryptamine (5-HT, Serotonin). Monoamine
increased when combined with alcohol. Treatment is
neurotransmitter, abundant in GIT enterochromaffin
largely supportive; gastric lavage and activated charcoal
cells (90%), smooth muscle, platelets, mast cells and
are of little value because absorption from the GIT is
peripheral and central nervous systems. Acts on at least
rapid. Classified in the UK as a class C controlled drug
seven receptor subtypes; all are G protein-coupled
from 2003.
receptors except the 5-HT3 receptor, which is a ligand-
Snead OC 3rd, Gibson KM (2005). N Engl J Med; 352:
gated ion channel permeable to Na+ and K+.
272132 Involved in:
Hydroxydione. Obsolete corticosteroid iv anaesthetic inflammatory mechanisms: increases vascular per-
agent, introduced in 1955. Produced slow induction of meability and platelet aggregation, causes broncho-
anaesthesia and delayed recovery, with a high incidence constriction and modulates local vascular tone.
of thrombophlebitis. GIT function: increases motility, water and electro-
lyte secretion.
Hydroxyethyl starch (HES). Synthetic colloid compo-
neurotransmission affecting arousal, muscle tone,
nent. Of similar structure to glycogen, consisting of
hypothalamic/parasympathetic regulatory mecha-
chains of glucose molecules (> 90% amylopectin), ether-
nisms, mood, memory and spinal modulation
ified with hydroxyethyl groups. Properties of each HES
of pain.
solution depend on:
Formed by hydroxylation and decarboxylation of
concentration: determines the initial volume expan-
tryptophan and stored in cytoplasmic vesicles. Taken up
sion effect, e.g. 6% HES is isotonic with a given
from synaptic clefts via the presynaptic membrane and
volume replacing the same volume of blood; 10%
metabolised mainly by monoamine oxidase to form
HES is hypertonic, drawing water from the intersti-
5-hydroxyindoleacetic acid (5-HIAA); urinary levels of
tium into the vasculature, thus expanding the circu-
the latter reflect the rate of metabolism.
lating volume by 145% of the infused volume. Drugs acting on 5-HT receptors:
molar substitution (MS) ratio (degree of hydroxy-
the serotonin reuptake inhibitors (e.g. fluoxetine
ethyl substitution): determines the half-life of the
and related antidepressant drugs).
starch in plasma; the first HES solution had a high
5-HT1D receptor agonists (e.g. sumatriptan) used in
substitution ratio of 0.7 (i.e. 7 hydroxyethyl residues
migraine.
for every 10 glucose molecules termed a heta
5-HT2 receptor antagonists (e.g. ketanserin) used in
starch), resulting in extensive accumulation in
various vascular disorders, including carcinoid
tissues and persistence in plasma for > 24h.
syndrome.
mean molecular weight (mw): may contribute to
pizotifen and methysergide (also 5-HT2 receptor
plasma half-life, although MS ratio is thought to be
antagonists) used in migraine prophylaxis.
more important in vivo.
5-HT3 receptor antagonists used as antiemetic
carrier solution: either 0.9% saline or a balanced
drugs.
electrolyte solution; the latter reduces the risk of
Others are in development for use in hypertension and
hyperchloraemic metabolic acidosis, although the
psychiatric or GIT disorders. Many other drugs also
clinical relevance of this is unclear.
affect 5-HT as part of a wider spectrum of activity, e.g.
Thus, HES preparations are identified by three
octreotide, reserpine, MAO inhibitors, tricyclic antide-
numbers, e.g. HES 6% 670/0.7 refers to 6% starch
pressant drugs.
solution with a mean mw of 670kDa and MS ratio
of 0.7.
Specific solutions: Hygrometer. Device for measuring atmospheric
hetastarch (0.70.75 MS): first HES product, intro- humidity.
duced in the 1970s. Mean mw is 450670kDa. Elim- Examples:
ination half-life of 17 days; moderate doses are hair hygrometer: pointer attached to a hair whose
associated with significant accumulation in tissues, length increases with increasing humidity. Human
coagulopathy and renal impairment, limiting its use. hair, animal tissue and paper have been used. Inac-
hexastarch and pentastarch (0.6 and 0.5 MS ratios curate but simple. The first hair hygrometer was
respectively): development of hetastarch with a built by da Vinci.
 Hypercalcaemia 283

Regnaults hygrometer: silver tube containing - causes hypertension, hypervolaemia, hypokalae-

ether; cooled by blowing air through it with a rubber mia and metabolic alkalosis. Plasma sodium level
bulb. When condensation appears on the outside, is usually at the upper end of the normal range.
the air is saturated with water at that temperature - spironolactone (aldosterone receptor antagonist)
(dew point). From a graph of water content of is used to treat hyperplasia. Some forms are cor-
saturated air against temperature, water content at rected by dexamethasone. Adenomas are treated
dew point and that at room temperature may be by surgery.
found. Relative humidity is the latter divided by the - anaesthetic considerations are related to appro-
former. priate preoperative correction of electrolyte, fluid
wet and dry bulb hygrometer: consists of two ther- and acidbase imbalances. Spironolactone is
mometer bulbs: one dry, the other wrapped in a wet useful preoperatively. Cardiovascular instability
wick. The wet thermometer bulb loses heat due to may occur peri- and postoperatively. Postopera-
water evaporation, which varies with atmospheric tive mineralocorticoid deficiency may be treated
humidity. Humidity is read from tables, according with fludrocortisone 50300g/day orally.
to the temperatures measured by the two ther- secondary: may occur in cardiac and hepatic failure,
mometers. Accuracy depends on adequate air malignant hypertension and renal artery stenosis.
movement. Measurement of plasma renin activity may aid diagnosis
humidity transducers: electrical properties of certain (low in primary disease, increased in secondary forms).
compounds (e.g. lithium chloride) alter as they [Jerome Conn (19071981), US physician]
absorb water. Electrical resistance or capacitance is Foo R, OShaughnessy KM, Brown MJ (2001). Postgrad
usually measured. Med J; 77: 63944
mass spectrometer.
ultraviolet light absorption: depends on water Hyperalgesia. Increased pain from a normally painful
content of air. stimulus. The term usually refers to a feature of chronic
[Leonardo da Vinci (14521519), Italian polymath; Henri pain, but is similar to the antanalgesia seen with certain
Regnault (18101878), French physicist] centrally depressant drugs.

Hygroscopic condensers, see Heatmoisture exchanger Hyperalimentation, see Nutrition, total parenteral

Hypercalcaemia. Effects are due to raised ionised

Hyoscine hydrobromide. Anticholinergic drug, used
calcium levels; symptoms are usually present when total
mainly for premedication and in palliative care. Tertiary
calcium exceeds 3.5mmol/l.
ammonium compound, an ester of tropic acid and Caused by:
scopine; found naturally in the henbane plant. Has
primary or secondary hyperparathyroidism
greater sedative, antiemetic and antisialagogue action
(e.g. parathyroid adenoma or renal failure,
than atropine, but with less action on the heart and
respectively).
bronchial muscle. Also used to prevent travel sickness,
malignancy, both primary and bony metastases.
and (as the quaternary ammonium compound, hyoscine
less commonly:
butylbromide) to prevent or reduce gut spasm.
Effects:
- increased intake, e.g. milk-alkali syndrome.
- others: hyperthyroidism, sarcoidosis, adreno
sedation, amnesia, mydriasis, antiemetic action via
cortical insufficiency, immobilisation, thiazide
the vomiting centre; may cause the central anticho-
diuretics.
linergic syndrome. Features:
reduced bronchial and GIT secretions; reduced gut
psychiatric disturbances.
motility.
dehydration, polyuria/polydipsia.
tachycardia (bradycardia is possible following a
nausea/vomiting, constipation.
small dose).
muscle weakness.
Dosage:
drowsiness, coma.
200600g sc/im for premedication (15g/kg in
shortened QT interval; prolonged PR interval
children). Confusion is more likely in the elderly.
on the ECG.
300g, repeated 6-hourly for travel sickness
may lead to renal calculi/nephrocalcinosis and renal
(maximum 900g/day). Slow-release cutaneous
failure.
patches are available, and have been used to reduce Urgent treatment (before investigation) is required
PONV.
in severe hypercalcaemia:
60300mg butylbromide sc daily for GIT spasm;
of underlying cause (if known).
20120mg for excessive respiratory secretions.
rehydration followed by induced diuresis to increase
renal calcium loss, e.g. with furosemide and saline
Hyperaesthesia. Increased sensitivity to a sensory stim- administration (caution with furosemide in renal
ulus, excluding the special senses. Includes allodynia and impairment). Careful fluid balance and CVP moni-
hyperalgesia. toring are required.
if severe hypercalcaemia persists, the following may
Hyperaldosteronism. Excessive aldosterone secretion. be used:
May be: - bisphosphonates, e.g.:
primary (Conns syndrome): - disodium pamidronate: 1560mg, given once or
- causes include adrenal adenoma (most common), divided over 24 days, up to a maximum of
hyperplasia and carcinoma. Twice as common in 90mg in total.
women. - ibandronic acid: 24mg by a single infusion.
284 Hypercapnia

- sodium clodronate: 300mg/day for 710 days or dioxide may be potentially protective in acute organ
1.5g by a single infusion. injury.
- zoledronic acid: 4mg over 15min by a single See also, Breathing, control of
infusion.
corticosteroids (e.g. prednisolone up to 120mg/ Hyperglycaemia. Plasma glucose over 6.0mmol/l
day), act by inhibiting vitamin D. (108mg/dl).
calcitonin from 510 units/kg/day im/sc in 12 Caused by:
divided doses up to 400 units tds/qds. Reduces bone pancreatic failure, e.g. diabetes mellitus, pancreati-
resorption. tis, sepsis, pancreatectomy.
trisodium edetate up to 70mg/kg/day iv over 3h; stress response, due to actions of catecholamines,
rapidly acting but may cause renal failure. Chelates growth hormone, glucocorticoids, glucagon. May
circulating calcium. occur following trauma, surgery, burns, etc. (see
others include enteral or parenteral phosphate Stress response to surgery).
(precipitates calcium phosphate into the tissues, administration of glucose, e.g. TPN.
including kidneys, thus no longer recommended); drugs, e.g. diethyl ether, thiazide diuretics.
and plicamycin (mithramycin; a cytotoxic agent, Effects:
no longer available in the UK). Dialysis has osmotic diuresis, causing dehydration, sodium and
been used. potassium loss.
Ariyan CE, Sosa JA (2004). Crit Care Med; 32(Suppl): diabetic coma, e.g. ketoacidosis.
S14656 increased blood osmolality and viscosity.
may impair platelet function, increase susceptibility
Hypercapnia. Arterial PCO2 over 6kPa (45mmHg). to infection and exacerbate effects of cerebral
Caused by: ischaemia.
increased production, e.g. MH, TPN using high car- chronic effects of diabetes.
bohydrate content. Average normal production is Treatment:
approximately 200ml/min. of primary cause.
reduced alveolar ventilation. hypoglycaemic drugs.
V/Q mismatch, e.g. severe COPD.
increased inspired CO2. Hyperkalaemia. Plasma potassium > 5.5mmol/l.
Effects: Caused by:
respiratory: increased intake, e.g. iv administration, rapid blood
- arterial O2 saturation falls below about 90% at an transfusion.
alveolar PCO2 over about 8kPa (60mmHg), decreased renal excretion:
breathing air. - renal failure (accounts for 75% of severe cases of
- increased respiratory drive via central/peripheral hyperkalaemia).
chemoreceptors. Tidal volume and respiratory - adrenocortical insufficiency.
rate increase; the extent varies with other factors - drugs: ciclosporin, angiotensin converting enzyme
(see Carbon dioxide response curve). Respiration inhibitors, NSAIDs, potassium-sparing diuretics,
is depressed at very high levels. e.g. amiloride, spironolactone.
- response to hypoxaemia is increased. movement of potassium out of cells:
- oxyhaemoglobin dissociation curve shifts to the - trauma, crush syndrome, rhabdomyolysis, MH,
right. severe exercise.
cardiovascular: - action of suxamethonium; exaggerated in burns,
- increased sympathetic activity (causing increases nerve injury, etc.
in circulating catecholamine levels, heart rate and - acidosis.
arterial BP), overriding CO2s direct myocardial - familial periodic paralysis.
depressant effect. Arrhythmias may occur. artefactual, e.g. haemolysed blood sample, very high
- increased cerebral blood flow, ICP and intraocu- white cell counts.
lar pressure. Effects:
other: nausea, vomiting, diarrhoea, muscle weakness,
- dilated pupils, with sluggish response. paraesthesiae.
- respiratory acidosis and hyperkalaemia. Initial myocardial depression, ECG changes (peaked T
bicarbonate increase is about 0.76mmol/l per kPa waves, absent P waves, widened QRS complexes,
rise above 5.3 if hypercapnia is acute (1mmol/l and slurring of ST segments into T waves). Ven-
per 10mmHg above 40). Renal compensation tricular arrhythmias including VF are common at
includes bicarbonate retention and excretion of above 7mmol/l. Cardiac arrest may occur.
hydrogen ions; bicarbonate increase in chronic Treatment:
hypercapnia is about 3mmol/l per kPa (4mmol/l calcium 510mmol iv repeated after 10min if
per 10mmHg). no effect (acts as a physiological antagonist of
- confusion, headache and coma may result (CO2 potassium). ECG changes are reversed within
narcosis). 13min.
The CNS may adjust to higher CO2 levels in chronic insulin 10 units in 50ml of 50% dextrose iv over
hypercapnia. 515min, repeated as necessary (drives potassium
Treated according to cause. If PCO2 is reduced into cells).
too rapidly, alkalosis and potassium shift may occur, nebulised (5mg) or iv (50g bolus/510g/min
causing convulsions, hypotension and arrhythmias. infusion) salbutamol (increases cellular uptake of
Recent animal data suggest that raised levels of carbon potassium).
 Hyperphosphataemia 285

bicarbonate 50mmol iv if acidosis is present

controversial but full correction should take at
(exchanges potassium ions for hydrogen ions across least 48h.
cell membranes). Decreasing the PaCO2 by increas- correction of any accompanying hypovolaemia.
ing minute ventilation (if artificially ventilated) has Reynolds RM, Padfield PL, Seckl JR (2006). Br Med J;
the same effect by reducing H+ concentration. 332: 7025
furosemide if renal function is adequate.
polystyrene sulphonate resins: 15g tds/qds orally; Hyperosmolality. Plasma osmolality over 305mosmol/
30g rectally. May take 6h to achieve full effect. kg. Features are as for hypernatraemia, which usually
dialysis. accompanies it. May also occur in hyperglycaemia, e.g.
Urgent iv treatment is required for potassium > due to diabetic coma, TPN, and ingestion/administration
6.5mmol/l or if ECG changes are present. Hyper of osmotically active substances, e.g. hypertonic manni-
kalaemia should be corrected before anaesthesia tol solutions, alcohol poisoning. Detected by hypotha-
and surgery, although the ratio of intracellular:extracel- lamic osmoreceptors, causing compensatory changes in
lular potassium is more important than isolated plasma water ingestion/excretion.
levels.
Nyirenda MJ, Tang JI, Padfield PL, Seckl JR (2009). Br Hyperparathyroidism. Increased parathyroid hormone
Med J; 339: 101924 production:
primary: usually from a single adenoma; multiple
Hypermagnesaemia. Plasma magnesium over adenomata and carcinoma may be responsible.
1.05mmol/l. May be associated with multiple endocrine
Caused by: adenomatosis.
renal failure. secondary: hyperplasia arising from prolonged
magnesium administration. hypocalcaemia, e.g. in renal failure.
laxative/antacid abuse. tertiary: secondary hyperparathyroidism where
adrenocortical insufficiency, hypothyroidism. autonomous secretion develops, e.g. after renal
Effects: transplantation. Hormone secretion may occur in
vasodilatation, hypotension, cardiac conduction certain tumours, e.g. bronchial carcinoma (pseudo-
defects. hyperparathyroidism). May be asymptomatic.
sedation, coma, weakness, areflexia, respiratory Features:
depression. Potentiation of non-depolarising neuro- those of hypercalcaemia; renal stones are common.
muscular blockade. bony erosion and cystic changes may occur.
Treatment: Treatment:
iv calcium (physiological antagonist). as for hypercalcaemia.
diuretics and haemodialysis. surgery; primary adenomata may be difficult to find.
Anaesthetic considerations:
Hypernatraemia. Plasma sodium over 145mmol/l. preoperative hypercalcaemia, dehydration and
Caused by: renal impairment should be corrected before
sodium excess (urine sodium > 20mmol/l): surgery.
- hyperaldosteronism (although it is rare for the decalcified bone is easily fractured, e.g. during
sodium concentration to rise above the normal positioning.
range). practical management of anaesthesia is as for
- Cushings syndrome. hyperthyroidism.
- iatrogenic, e.g. sodium bicarbonate, hypertonic Marx SJ (2000). N Engl J Med; 343: 186375
saline administration.
water depletion (urine sodium variable): Hyperpathia. Increased sensation from a sensory stimu-
- renal loss, e.g. diabetes insipidus. lus, but with raised threshold of sensation. Pain may
- insensible water loss. increase during stimulation, and linger afterwards.
- insufficient water intake.
sodium deficiency, with greater water deficiency: Hyperphosphataemia. Plasma phosphate above
- renal loss (urine sodium > 20mmol/l), e.g. osmotic 1.4mmol/l.
diuresis caused by mannitol, glucose, urea, etc. Caused by:
- other loss (urine sodium < 10mmol/l): factitious: haemolysis, prolonged contact of plasma
- vomiting, diarrhoea. with red blood cells.
- sweating, weeping wounds. increased intake: diet, iv administration, excess
- adrenocortical insufficiency. vitamin D.
Effects: increased release from cells/bone: diabetes mellitus,
features of dehydration if present. starvation, rhabdomyolysis, acidaemia, malignancy,
thirst, drowsiness, confusion, coma. Cerebral dehy- renal failure.
dration, with ruptured vessels and intracranial decreased excretion: renal failure, hypopara
haemorrhage, may occur. thyroidism, excess growth hormone secretion.
Treatment: Effects are difficult to distinguish from those of
of underlying cause. the almost inevitable accompanying calcium abnor-
oral water is given when possible, and/or diuretics mality but skin lesions and renal stones have been
in sodium excess. Normal saline may be given iv, reported.
hypotonic saline in severe water and sodium defi- Treatment: reduced protein intake; aluminium
ciency. Rapid infusion may lead to cerebral oedema hydroxide or calcium carbonate orally (the latter con-
and convulsions. Optimal rate of correction is traindicated in hypercalcaemia); hypertonic dextrose
286 Hyperpyrexia, malignant

solutions have been used to shift phosphate from the - Step 1: A (for patients < 55 years) or C (for
ECF into the cells; haemodialysis. patients > 55 years and all of African or Carib-
bean descent).
Hyperpyrexia, malignant, see Malignant hyperthermia - Step 2: A + C.
- Step 3: A + C + D.
Hypersensitivity, see Adverse drug reactions; Atopy - Step 4 (resistant hypertension): A + C + D +
further diuretic or - or -adrenergic receptor
Hypertension. Raised arterial BP; defined and graded antagonists.
by the British Hypertension Society, European Society benefits of treating severe hypertension are
of Hypertension and World Health Organization as undoubted; those of treating milder forms are con-
follows, according to BP measured in the clinic (as troversial. Recent guidance recommends maintain-
opposed to ambulatory): ing BP < 130/80mmHg in patients at increased
grade 1 (mild): systolic 140159mmHg; diastolic risk of ischaemic heart disease. The incidence of
9099mmHg. CVA is thought to be reduced if diastolic pressures
grade 2 (moderate): systolic 160179mmHg; dia- > 90mmHg are treated. Screening is widely
stolic 100109mmHg. practised.
grade 3 (severe): systolic 180mmHg; diastolic Anaesthesia for patients with hypertension:
110mmHg. preoperatively:
isolated systolic hypertension: > 140mmHg with - assessment for ischaemic heart disease, car-
diastolic < 90mmHg. BP increases with age in diac failure, cerebrovascular disease and renal
normal subjects. impairment.
In 5% of cases, hypertension is secondary to: - if not on treatment, surgery should be postponed
adrenal disorders, e.g. hyperaldosteronism, Cush- unless it is an emergency. Patients with diastolic
ings syndrome, phaeochromocytoma. pressure above 110mmHg should be investigated
unilateral or bilateral renal disease, e.g. renal artery and hypertension treated before anaesthesia and
stenosis, infection, reflux, glomerulonephritis, con- surgery, since morbidity and mortality are greater
genital abnormalities, diabetes mellitus, connective if untreated. Antihypertensive drugs are contin-
tissue diseases, obstruction, tumour. ued up to the morning of surgery.
others: coarctation of the aorta, pre-eclampsia, - sedative premedication is often advocated to
drugs, e.g. corticosteroids, oral contraceptives. reduce endogenous catecholamine levels.
In the remaining 95% of cases, hypertension is termed perioperatively:
primary or essential, i.e. has no apparent cause. - induction and maintenance as for ischaemic heart
Associated with family history and obesity, possibly disease. Swings in BP are more likely because
alcohol and salt intake, diet and stress. Caffeine and of arteriolar hypertrophy; e.g. hypotension on
smoking increase BP. induction and hypertension on intubation (see
Pathophysiological effects: Intubation, complications of).
arteriolar wall thickening, with greater reduction in - marked cardiovascular instability may accom-
vessel radius for a given vasoconstrictive stimulus. pany spinal/epidural anaesthesia if hypertension
degenerative changes (e.g. fibrinoid necrosis and is uncontrolled.
atheroma formation) lead to reduced blood flow postoperatively:
and propensity to aneurysm formation and rupture. - adequate analgesia is particularly important.
baroreceptor sensitivity is reduced. - treatment of persistent hypertension may be
increased myocardial workload, with left ventricu- required.
lar hypertrophy. Increased end-diastolic pressure Hypertension during anaesthesia may be due to:
and coronary atheromatous plaques reduce coro- inadequate anaesthesia/analgesia.
nary blood flow despite increased O2 demand. tracheal intubation/extubation.
Angina and/or cardiac failure may result. inadequate paralysis.
Features: underlying hypertensive disease.
of ischaemic heart disease. aortic clamping.
of cardiac failure. hypercapnia, hypoxaemia.
CVA, encephalopathy. cerebral ischaemia, CVA, raised ICP.
due to renal impairment. drugs, e.g. ketamine, adrenaline, cocaine.
hypertensive crisis may occur. rarely, MH, phaeochromocytoma, thyroid crisis,
hypertensive retinopathy: arteriovenous nipping, carcinoid syndrome.
increased light reflex, increased tortuosity, cotton- Postoperatively, urinary retention, residual neuromuscu-
wool exudates, haemorrhages and papilloedema. lar blockade, pain and anxiety may cause hypertension,
ECG features include those of ischaemia and left in addition to the above factors. In the ICU, hyperten-
ventricular hypertrophy. CXR features may include sion is often due to inadequate sedation, but many of the
left ventricular dilatation and those of left ventricu- factors above should also be considered.
lar failure. Management is directed towards the underlying
Treatment: cause. Labetalol, hydralazine, nifedipine, sodium nitro-
weight loss, cessation of smoking, exercise. prusside and GTN are commonly used to control BP;
NICE guidelines (2011) suggest four sequential the first three drugs are usually most convenient. Vaso-
steps in the antihypertensive drug treatment of dilator therapy is less likely to be successful in athero-
hypertension until BP is controlled. Drugs used sclerosis, since the arterial tree is relatively rigid;
include ACE inhibitors, Calcium channel blocking labetalol or other -adrenergic antagonists may be
drugs and thiazide Diuretics: more effective.
 Hyperthyroidism 287

Hypertensive crisis. Severe hypertension (> Treatment:

180/120mmHg) with or without acute end-organ specific, e.g. MH.
damage. May occur as a feature of chronic hypertensive cooling with tepid water; cold water may induce
disease, postoperatively after cardiac/vascular surgery, peripheral vasoconstriction with impairment of
or other conditions including pre-eclampsia and further heat exchange. Cold iv fluids and irrigation
phaeochromocytoma. Features represent end-organ of body cavities may be used.
impairment: drugs, e.g. aspirin, paracetamol.
acute coronary syndromes, cardiac failure and Bouchama A, Knochel JP (2002). N Engl J Med; 346:
CVA. 197888
renal failure.
encephalopathy: confusion, headache, visual distur- Hyperthermia, malignant, see Malignant
bances, convulsions, coma. hyperthermia
retinal haemorrhage, papilloedema and
epistaxis. Hyperthyroidism (Thyrotoxicosis). In 99% of cases,
Treatment: hyperthyroidism is caused by primary thyroid overactiv-
if not associated with end-organ damage, oral ity produced by thyroid stimulating autoantibodies
therapy is used (e.g. atenolol, labetalol or nife (Graves disease) or hyperactive nodules. It is rarely due
dipine), aiming to reduce BP cautiously to to carcinoma, thyroid stimulating hormone secretion, or
< 160/100mmHg over hours to days. Large loading administration of thyroid hormones. 710 times more
doses or iv drugs may cause precipitous falls in BP, common in women.
resulting in CVA/blindness, renal impairment or Features:
myocardial ischaemia. malaise, anxiety, sweating, heat intolerance,
extreme hypertension (e.g. > 220/130mmHg) is tremor, psychological changes, myopathy (usually
usually associated with life-threatening end-organ proximal).
damage, and requires admission to a critical care weight loss, increased appetite, diarrhoea.
unit for invasive BP monitoring and prompt, titrat- palpitations, tachycardia, AF, cardiac failure.
able BP control (e.g. 1520% reduction in BP over goitre, oligomenorrhoea, gynaecomastia.
the first hour then reduction to 160/110mmHg over eye features: usually lid retraction and mild propto-
the next 26h). Suitable agents include sodium sis; occasionally severe with visual disturbances.
nitroprusside, esmolol and labetalol. Some patients May be associated with pretibial myxoedema (pink/
may also be intravascularly deplete and require brown subcutaneous infiltration on the lower leg)
cautious iv fluid loading. and pseudoclubbing.
Rodriguez MA, Kumar SK, De Caro M (2010). Cardiol thyroid crisis may occur, triggered by surgery, infec-
Rev; 18: 1027 tion, etc.
Investigation: measurement of plasma thyroxine and
triiodothyronine (either or both of which may be
Hyperthermia. Raised body temperature, sometimes raised), thyroid stimulating hormone, and, rarely, thy-
defined as greater than 41.6C (107F). Implies thermo- rotrophin releasing hormone. Radioisotope and ultra-
regulatory failure, whereas pyrexia or fever (often sound scanning may be performed.
defined as body temperature above 38C [100.4F], Treatment:
although the threshold varies between sources) implies antithyroid drugs:
intact homeostatic mechanisms. Heatstroke is the clini- - carbimazole (UK) or methimazole (USA); pro-
cal syndrome caused by exposure to excessively high pyluracil: prevent formation of thyroid hormones.
environmental temperature, especially if unaccustomed, Pruritus and rash are common; agranulocytosis
and if temperature regulation is impaired. may occur. Increase vascularity of the gland,
Caused by: therefore sometimes stopped 2 weeks preopera-
hypothalamic lesions, e.g. tumour, surgery, CVA, tively. Usually given for a course of 11.5 years.
infection. Act within at least 12 weeks.
increased heat production: - iodine: temporarily inhibits hormone release;
- exercise. sometimes given for 2 weeks preoperatively to
- drug-induced, e.g. MH, neuroleptic malignant syn- reduce glandular vascularity.
drome, salicylate poisoning, cocaine poisoning, - radioactive iodine: increasingly used as fears of
methylenedioxymethylamphetamine ingestion. subsequent sterility and tumours diminish.
- hyperthyroidism. -adrenergic receptor antagonists: act by reducing
- phaeochromocytoma. conversion of thyroxine to triiodothyronine and
- status epilepticus. direct antagonism of the peripheral effects of hyper-
- tetanus. thyroidism. Act within 1224h.
impaired heat loss: surgery: requires adequate medical control preop-
- autonomic neuropathy. eratively, in order to prevent thyroid crisis.
- drug-induced, e.g. anticholinergic drugs, pheno- Anaesthetic management:
thiazines, neuroleptic malignant syndrome. preoperatively:
- dehydration. - assessment of thyroid state, especially cardiovas-
- excessive warming during anaesthesia. cular and neurological aspects. Emergency treat-
Features of heatstroke include dry hot skin, confusion, ment is as for thyroid crisis. Other autoimmune
headache, coma and raised temperature. Hyperventila- disease may be present, e.g. myasthenia gravis.
tion may be followed by metabolic acidosis, convulsions, - assessment for possible upper airway obstruction.
and cardiovascular and multisystem failure. CXR including thoracic inlet views is useful.
288 Hypertonic intravenous solutions

Elective tracheostomy is sometimes performed if improving BP and reducing ICP in these contexts;
the goitre is very large. Indirect laryngoscopy is however, morbidity and mortality outcomes are similar
performed to assess vocal cord function in case of when compared with conventional resuscitation fluids.
pre-existing damage to the laryngeal nerves. Various solutions have been used. Combinations of
perioperatively: hypertonic 7.5% saline with colloid (usually 6% dextran
- tracheal intubation may be difficult. IPPV is 70) are thought to maximise the benefits of rapid and
usually used; spontaneous ventilation is preferred sustained plasma expansion by virtue of the saline and
by some. Reinforced tracheal tubes are some- colloid components respectively.
times preferred. Strandvik GF (2009). Anaesthesia; 64: 9901003
- because of the risk of damage to the laryngeal
nerves, special tracheal tubes have been described Hyperventilation. Abnormally increased pulmonary
through which the vocal cord muscles electrical ventilation, resulting in increased excretion of CO2. It
potentials may be monitored during surgery. The may occur in both awake and anaesthetised spontane-
surgeon stimulates tissues electrically, allowing ously breathing patients, e.g. due to pain, hypoxaemia,
the nerves to be identified and thus avoided. Neu- hypercapnia, acidosis and pregnancy. Sometimes occurs
romuscular blocking drugs must be avoided if this in midbrain/pontine lesions. Commonly performed
technique is used. during IPPV, intentionally or unintentionally.
- the eyes should be protected from pressure. Its main effects are related to resultant hypocapnia
- operative bleeding may be reduced by infiltration (e.g. tetany), or the adverse cardiovascular effects of
with adrenaline solutions, head-up position and IPPV. Increases the work of breathing.
hypotensive anaesthesia.
- arrhythmias may result from poor thyroid control Hypnosis. Sleep-like state, with persistence of certain
or manipulation of the carotid sinus. Risk of air behavioural responses. The subject is susceptible to, and
embolism exists in the steep head-up position. may respond to, the hypnotists suggestions concerning
- pneumothorax and tracheal trauma may occur. behaviour, environment and memory, despite possible
- regional anaesthesia may also be used in high-risk contradiction by actual stimuli and character. The effects
patients, using 0.5% prilocaine or lidocaine with may persist after return to normal consciousness, but
adrenaline: possibly without recall of the hypnotic state.
- from the midpoint of the sternomastoid muscle Has been used:
on both sides, 10ml is injected into the muscle to help smoking cessation.
body, 10ml anteriorly and 10ml infiltrated cau- to aid recall of subconscious thoughts, e.g.
dally and cranially. psychiatric/psychological research and therapy,
- 20ml is injected sc to each side from the midline, investigation of awareness under anaesthesia.
below the thyroid gland. to modify pain perception, e.g. in obstetrics, periop-
postoperatively: eratively, and in chronic pain.
- assessment of the vocal cords activity is often for entertainment.
requested by the surgeon after extubation, Originally expounded as mesmerism in the mid/late
although direct laryngoscopy may be difficult at 1700s, although evidence of similar techniques dates
this stage. Fibreoptic inspection, e.g. through an back thousands of years. The term was coined in the
LMA, has been described. 1840s.
- airway obstruction may be caused by: Whether hypnosis represents a separate physiological
- haemorrhage into the tissues of the neck. Skin state, or an interpersonal social interaction (i.e. obeyer/
sutures or clips must be easily removable. commander) is controversial. Certainly suggestion is
- tracheomalacia (floppy, collapsible trachea) if widely used, e.g. by doctors and dentists, to reduce fear,
the goitre is large. Reintubation or tracheos- anxiety and use of drugs.
tomy may be required. [Hypnos, Greek god of sleep]
- laryngeal nerve damage. Wobst AHK (2007). Anesth Analg; 104: 1199208
- hypoparathyroidism causing hypocalcaemia
and tetany may occur from several hours to Hypoadrenalism, see Adrenocortical insufficiency
several days later.
thyroid crisis or subsequent hypothyroidism may Hypoaesthesia. Reduced sensitivity to a sensory stimu-
also occur. lus, excluding special senses.
[Robert Graves (17961853), Irish physician]
Farling PA (2000). Br J Anaesth; 85: 1528 Hypoalgesia. Reduced pain from a normally painful
See also, Neck, cross-sectional anatomy; Thyroid gland stimulus.

Hypocalcaemia. Effects are usually present when total

Hypertonic intravenous solutions. Intravenous solu- plasma calcium is under 2.0mmol/l, and are due to
tions (typically saline) of high osmolality; have been decreased plasma ionised calcium. Although total
used in small volumes (e.g. 250ml boluses) for initial calcium is reduced in hypoproteinaemia, the ionised
resuscitation in shock (e.g. due to haemorrhage). Have portion is normal and clinical features are absent.
also been used as an alternative to mannitol to reduce Caused by:
ICP after head injury. Effects include: expansion of the decreased parathyroid hormone activity, e.g. hypo-
intravascular volume by drawing in fluid from the intra- parathyroidism, hypomagnesaemia.
cellular and interstitial spaces; reduced SVR and after- decreased vitamin D activity, e.g. the above, chronic
load; direct inotropy; and anti-inflammatory effects. renal failure, intestinal malabsorption, inadequate
Current evidence suggests that they are effective in diet, liver disease.
 Hypoglycaemic drugs 289

increased calcium loss, e.g. chelating agents, calcifi- - sarcoma, hepatoma, adrenocortical and other
cation of soft tissues (e.g. rhabdomyolysis, pancrea tumours. Thought to be caused by secretion of
titis, hyperphosphataemia). an insulin-like factor.
decreased ionised calcium, e.g. alkalosis. - sepsis, malaria.
Features (exacerbated by hypomagnesaemia): reactive, i.e. 25h postprandially:
paraesthesiae. - idiopathic.
muscle cramps/spasm/tetany. Stridor may occur. - gastric surgery; causes rapid glucose absorption
Chvosteks sign is facial spasm following tapping and excessive insulin release (cf. dumping syn-
over the facial nerve. Trousseaus sign is carpopedal drome, due to sudden osmotic load and/or other
spasm following inflation of a tourniquet around gut hormone release).
the arm. - may occur in diabetes mellitus.
mental excitability, convulsions. - inborn errors of metabolism, e.g. glycogen storage
prolonged QT interval on the ECG; decreased diseases.
cardiac output. rebound hypoglycaemia may follow sudden cessa-
Treatment: tion of TPN, due to high levels of circulating insulin.
of predisposing cause. Features:
supportive (airway, etc.). secretion of hyperglycaemic hormones, e.g. adrena-
iv calcium if severe, e.g. chloride 10% 510ml or line, glucagon, growth hormone and cortisol; the
gluconate 10% 1020ml slow bolus, followed by former causes tachycardia, sweating and pallor.
infusion if required. confusion, restlessness, dysarthria, diplopia, convul-
magnesium if deficient. sions, coma. Permanent brain damage may occur
[Frantisek Chvostek (18351884), Austrian physician; with coma of increasing duration, but is rare if < 4h.
Armand Trousseau (18011867), French physician] May be exacerbated by hypoxaemia and hypoten-
Aguilera IM, Vaughan RS (2000). Anaesthesia; 55: sion. Cerebral oedema may contribute.
77990 may be masked by anaesthesia, presenting only
during recovery.
Treatment:
Hypocapnia. Arterial PCO2 < 4.7kPa (35mmHg).
2550ml 50% glucose iv if unconscious, repeated as
Caused by:
necessary. Risk of venous thrombosis is reduced by
hyperventilation. May be iatrogenic (in ventilated
flushing the cannula with saline after injection. Oral
patients), self-induced or a compensatory response
glucose is given if able to drink.
to metabolic acidosis.
glucagon 1mg has been used im, but is ineffective in
reduced CO2 production, e.g. in brainstem death.
Effects:
hepatic dysfunction and alcohol ingestion, and may
exacerbate insulinoma-induced hypoglycaemia.
vasoconstriction; reduced cerebral blood flow may
mannitol and dexamethasone have been used if
cause dizziness, light-headedness and confusion.
cerebral oedema is suspected and coma persists.
Risk of convulsions if predisposed, e.g. if enflurane
is used. Placental blood flow is reduced. If IPPV is
Hypoglycaemic drugs. Strictly, refers to all drugs used
employed, cardiovascular effects are increased.
to lower plasma glucose concentration, although the
alkalosis, hypokalaemia and hypocalcaemia may
term is often used to refer to oral drugs only. Used pri-
occur.
marily in the treatment of diabetes mellitus, although
reduced respiratory drive; apnoea may occur
insulin is also used in the treatment of hyperkalaemia.
postoperatively.
Divided into:
reduced requirement for anaesthetic agents has
oral:
been inconsistently demonstrated.
- biguanides (e.g. metformin): decrease gluconeo-
If iatrogenic, corrected by reducing alveolar ventilation,
genesis and increase peripheral glucose uptake.
e.g. by increasing dead space and rebreathing, or reduc-
- sulphonylureas (e.g. glibenclamide): increase pan-
ing minute volume. If compensatory, best not corrected
creatic secretion of insulin, and possibly increase
until the underlying cause of acidosis is treated.
peripheral glucose uptake.
Cooper MS, Gittoes NJL (2008). Br Med J; 1298302
- thiazolidinediones (e.g. pioglitazone): increase
peripheral sensitivity to insulin. Rosiglitazone has
Hypoglycaemia. Low plasma glucose level; symptoms been withdrawn due to increased risk of cardiac
are uncommon until level falls to 23mmol/l (4050mg/ events.
dl); the threshold is lower in chronic hypoglycaemia and - meglitinides (e.g. nateglinide): stimulate release
higher in chronic hyperglycaemia. of insulin from the pancreas.
Types: - -glucosidase inhibitors (e.g. acarbose): inhibit
fasting, i.e. only after several hours without food: absorption of carbohydrate from the GIT.
- reduced glucose output from liver: parenteral, i.e. insulin and insulin analogues (e.g.
- starvation (especially children). glargine).
- alcohol ingestion. Novel agents undergoing evaluation:
- hepatic failure. glucagon-like peptide-1 (GLP-1) receptor agonists
- adrenocortical insufficiency. (e.g. exenatide): stimulate insulin secretion, inhibit
- renal failure, growth hormone deficiency, glucagon secretion, slow gastric emptying and sup-
pregnancy. press appetite.
- increased insulin activity: dipeptidyl peptidase-IV (DPP-4) inhibitors (e.g.
- insulin/sulphonylurea administration. sitagliptin): inhibit breakdown of GLP-1.
- insulinoma. Over 90% are benign. Nicholson G, Hall GM (2011). Br J Anaesth; 107: 6573
290 Hypokalaemia

Hypokalaemia. Plasma potassium under 3.5mmol/l. Hyponatraemia. Plasma sodium under 135mmol/l.
Symptoms usually occur below 2.5mmol/l, although Usually results in hypo-osmolar plasma (not always, e.g.
complications may occur at higher levels in predisposed hyperglycaemia or hypertonic mannitol infusion causing
patients (e.g. acute MI). Total deficit may be up to hyperosmolar plasma).
500mmol. Caused by:
Caused by: water excess; relative euvolaemia:
reduced intake, e.g. iv fluid therapy without potas- - excessive intake (urine sodium < 10mmol/l):
sium supplementation. - iv administration of sodium-deficient fluids.
excessive losses: - TURP syndrome.
- renal: - excessive drinking.
- solute diuresis, e.g. saline, glucose, mannitol, - reduced excretion (urine sodium > 20mmol/l):
urea. - syndrome of inappropriate antidiuretic
- diuretic therapy. hormone secretion (SIADH).
- hyperaldosteronism and disorders of the renin/ - drugs, e.g. chlorpropamide, oxytocin (have
angiotensin system. antidiuretic effect).
- Cushings syndrome. water excess with (smaller) sodium excess (urine
- diuretic phase of acute kidney injury. sodium < 10mmol/l); hypervolaemia:
- GIT, e.g. diarrhoea, vomiting, fistulae. - cardiac and hepatic failure.
movement of potassium into cells: - nephrotic syndrome.
- alkalosis. water deficiency with greater sodium deficiency;
- drugs, e.g. insulin, catecholamines. hypovolaemia:
Effects: - renal loss (urine sodium > 20mmol/l):
muscle weakness, ileus. - diuretic therapy.
arrhythmias, ECG changes (ST segment depres- - hypoadrenalism.
sion, QT and PR interval prolongation, T wave - cerebral salt-wasting syndrome.
inversion, U wave). Cardiac arrest may occur. - salt-losing nephritis.
impaired renal concentrating ability. - renal tubular acidosis.
increased sensitivity to non-depolarising neuromus- - post-relief of urinary obstruction.
cular blocking drugs. - other loss (urine sodium < 10mmol/l):
increased adverse effects of digoxin. - diarrhoea and vomiting.
may cause metabolic alkalosis. - pancreatitis.
Treatment: redistribution of sodium/water:
oral supplementation: up to 200mmol (15g)/day. - sick cell syndrome in terminally ill patients:
iv potassium chloride: up to 40mmol (3g)/l fluid thought to be caused by impaired cell membrane
peripherally, infused at up to 40mmol/h. Exces- sodium/potassium transport, resulting in sodium
sively concentrated solutions may cause vascular redistribution to the intracellular compartment.
necrosis, and too rapid administration may cause - water shift from intracellular to extracellular
VF; in severe cases, the above limits may be compartments, e.g. due to hyperglycaemia. Cor-
exceeded with ECG monitoring. rected plasma sodium concentration in hypergly-
Hypokalaemia should be corrected before anaesthesia caemia: [Na+] + ([glucose] 4).
and surgery, although the ratio of intracellular: extracel- pseudohyponatraemia, e.g. in hyperlipidaemia: the
lular potassium is more important than isolated plasma sodium-poor lipid portion is analysed together with
levels. the aqueous portion. Modern equipment analyses
Unwin RJ, Luft FC, Shirley DG (2011). Nat Rev Nephrol; only the aqueous portion.
7: 7584 Features:
of dehydration and hypovolaemia in sodium
deficiency.
Hypomagnesaemia. Plasma magnesium under symptoms attributed to water entering cells by
0.75mmol/l. Because only 1% of magnesium is present osmosis include headache, nausea, confusion, coma
in ECF, plasma levels may not correlate with clinical and convulsions with possibly permanent neuro-
features. logical defects. Premenopausal women are espe-
Caused by: cially at risk; the threshold for convulsions and/or
reduced magnesium intake, e.g. TPN, respiratory arrest in this group may be as high as
alcoholism. 130mmol/l, compared with 115120mmol/l in men
malabsorption. and postmenopausal women.
increased loss, e.g. GIT (prolonged diarrhoea/ Treatment:
vomiting), renal (diuretics, diabetes). of underlying cause.
Features: as for SIADH: water restriction, demeclocycline.
arrhythmias. iv hypertonic saline (1.8%, 4.5% or 5%) has been
neurological: confusion, irritability, tremor, used in severe cases of sodium and water deficiency
convulsions. (sodium under 115mmol/l). The optimal rate of
exacerbation of the effects of hypocalcaemia. plasma sodium increase is controversial, but correc-
Treatment: tion should be slow, since subdural haemorrhage,
of primary cause. central pontine myelinosis and cardiac failure may
acutely: 1020mmol MgSO4 iv over 12h, occur if too rapid. 510mmol/l/day has been sug-
repeated as required with plasma monitoring, up to gested as the maximal safe rate; up to 2mmol/l/h
50mmol/day. until a plasma sodium of 120mmol/l is reached.
 Hypotensive anaesthesia 291

Total sodium deficit (mmol) assuming distribution Treatment:

throughout total body water = (125 measured of underlying cause.
sodium) 60% of body weight (kg). Normal hormone replacement, e.g. hydrocortisone, thyrox-
saline with furosemide has been used in less severe ine and testosterone or oestradiol.
cases. [Harold Sheehan (19001988), English pathologist]
V2 vasopressin receptor antagonists (e.g. tolvaptan):
increase free water excretion; used in euvolaemic or Hypoproteinaemia. Plasma proteins under 60g/l. Most
hypervolaemic patients with SIADH. commonly due to low albumin levels (under 35g/l). May
Elhassan EA, Schrier RW (2011). Curr Opin Nephrol occur in hepatic/renal failure, protein-losing nephropa-
Hypertens; 20: 1618 thy or enteropathy, and in severely ill catabolic patients,
e.g. on ICU.
Anaesthetic significance:
Hypo-osmolality. Plasma osmolality < 280mosmol/kg.
Features are as for hyponatraemia. Detected by hypo- for drugs that are largely protein-bound, reduced

thalamic osmoreceptors, causing compensatory changes available binding sites increase the proportion of
in water ingestion and excretion. unbound drug, increasing the clinical effect; e.g.
opioid analgesic drugs, thiopental, antibiotics.
Effects are increased further if available binding
Hypoparathyroidism. Most commonly occurs postop-
sites are already occupied by other protein-bound
eratively, e.g. following parathyroid/thyroid/laryngeal
drugs. Albumin is usually involved in protein-
surgery; may be acute or occur several years later. May
binding, but others are also involved, e.g. gamma-
also be idiopathic, sometimes familial.
globulin and acid 1-glycoprotein.
Pseudohypoparathyroidism: same features, due to
decreased plasma oncotic pressure may lead to
lack of peripheral response to parathyroid hormone;
tissue oedema.
may be associated with hypothyroidism.
specific protein deficiencies, e.g. coagulation disor-
Pseudopseudohypoparathyroidism: features of pseu-
ders, plasma cholinesterase deficiency.
dohypoparathyroidism but with normal calcium and
phosphate levels.
Features:
Hypotension. Since MAP = cardiac output (CO) SVR,
hypotension may result from reduction of:
hypocalcaemia.
CO:
hyperphosphataemia.
Treatment: calcium and vitamin D supplements.
- reduced heart rate:
- vagal reflexes.
Anaesthetic considerations are related to
- drugs, e.g. halothane, -adrenergic receptor
hypocalcaemia.
antagonists, neostigmine.
Shoback D (2008). N Engl J Med; 359: 391403
- arrhythmias.
See also, Thyroid gland
- reduced stroke volume:
- reduced venous return, e.g. hypovolaemia,
Hypophosphataemia. Plasma phosphate < 0.8mmol/l. spinal/epidural/caudal anaesthesia, head-up
Caused by: posture, aortocaval compression, IPPV, tension
mild: hyperparathyroidism, osteomalacia, increased pneumothorax, cardiac tamponade.
carbohydrate metabolism, hypomagnesaemia, hae- - arrhythmias.
modialysis, acute alkalosis. - increased afterload, e.g. aortic stenosis, PE
severe: ketoacidosis, TPN and refeeding syndrome, (including air and amniotic fluid embolism),
chronic alcoholism/withdrawal. pneumothorax, tamponade.
Effects:
- reduced myocardial contractility, e.g. drugs,
muscle weakness, myocardial depression. hypoxia, hypercapnia, ischaemic heart disease,
irritability, dysarthria, encephalopathy, peripheral MI, cardiomyopathy, myocarditis, cardiac
neuropathy, convulsions, coma. failure, acidosis, hypothermia.
rhabdomyolysis, haemolysis, platelet and leucocyte SVR:
dysfunction. - drugs, e.g. vasodilator drugs, volatile and iv anaes-
Treatment: sodium or potassium phosphate: 10
thetic agents.
20mmol orally or 520mmol/h iv. Overtreatment - adverse drug reactions.
and resultant hyperphosphataemia may cause hypo- - spinal/epidural/caudal anaesthesia.
calcaemia and hypomagnesaemia. - sepsis.
Reduction in blood flow to vital organs may result, with
Hypopituitarism. Reduced secretion of anterior pitu- risk of permanent ischaemic damage, e.g. CVA, MI, renal
itary gland hormones (hyposecretion of posterior failure. Autoregulation maintains cerebral, coronary and
portion causes diabetes insipidus). Most commonly renal blood flows at systolic BP of approximately
caused by pituitary tumour; may also follow surgery/ 7080mmHg.
radiotherapy, granulomatous disease, cysts or ischaemic Treatment consists of O2 administration, raising the
necrosis of the pituitary during pregnancy (Sheehans feet and specific treatment directed towards the cause.
syndrome).
Features: Hypotensive anaesthesia. Usually defined as deliberate
absent axillary/pubic hair, breast and genital lowering of BP during anaesthesia by more than 30% of
atrophy, pale skin, muscle wasting. resting value. Techniques usually involve reduction of
of hypothyroidism and adrenocortical insufficiency. systolic BP to about 80mmHg (MAP 5060mmHg),
Main anaesthetic considerations are related to the although levels of 6070mmHg (MAP 40mmHg) have
latter two features. been employed. Performed in circumstances where
292 Hypothalamus

surgery may be hindered by bleeding and to reduce derivatives have been used to monitor cerebral
blood loss (e.g. middle ear surgery, neurosurgery, plastic activity.
surgery) and extensive major surgery, e.g. cystectomy, careful positioning of patient, with the site of
pelvic clearance. Its use is controversial, since hypoten- surgery raised above the heart, and avoidance of
sion may cause organ ischaemia, dysfunction and infarc- venous kinking and obstruction. Head-up tilt is
tion, particularly of heart, liver, kidneys, brain and spinal introduced gradually to avoid sudden severe hypo-
cord. Considered by some to be too dangerous for non- tension. 2030 tilt is usually sufficient; BP at
life-saving surgery, but by others to be routinely accept- the head is about 1520mmHg less than that at
able. Risks are lowest in fit young patients, but the heart.
consequences of major infarction are more dramatic in a typical anaesthetic sequence consists of thiopental
this group. or propofol, IPPV, maintenance with volatile agent
Contraindications are also controversial, but (e.g. isoflurane), with increments of labetalol or
include: hydralazine. Infusions of nitroprusside, GTN and
impaired organ blood flow or function, e.g. isch- remifentanil may be used. Relative importance of
aemic heart disease, renal disease, cerebrovascular BP over blood flow is controversial, e.g. whether use
disease, age (implies the foregoing). of vasodilators is better than reduction of cardiac
hypertension. output.
diabetes mellitus: there may be increased sensitivity careful postoperative observation is important,
to hypotensive agents as autonomic function may since cardiovascular instability may persist.
be impaired already. Increased sensitivity to insulin
has followed ganglion blockade. Hypothalamus. Ventral part of the diencephalon, situ-
severe respiratory disease. Bronchospasm may ated inferior to the thalamus and forming the floor of
follow use of ganglion-blocking drugs or -adrenergic the third ventricle. Lies posterior to the optic chiasma
receptor antagonists in asthmatics. and infundibular stalk attached to the posterior lobe of
pregnancy, anaemia, hypovolaemia. the pituitary gland. Important controlling area for auto-
anaesthetist and surgeon unfamiliar with the nomic nervous system activity; sympathetic mainly
technique. restricted to the posteromedial part, parasympathetic to
Originally achieved in the 1940s by deliberate hypovo- the anterolateral part. Also involved in regulation of
laemia and/or high spinal anaesthesia. Now achieved by pituitary hormone secretion, temperature regulation,
using: thirst, hunger, memory formation and sexual activity.
anaesthetic drugs/techniques that lower BP: See also, Brain
- reduced cardiac output, e.g. IPPV, head-up posi-
tioning of the patient, halothane. Hypothermia. Core temperature below 36C. May
- reduced SVR, e.g. tubocurarine, isoflurane, result from exposure or near-drowning (e.g. complicat-
spinal/epidural anaesthesia. ing trauma and coma from any cause), especially involv-
specific hypotensive drugs, e.g.: ing depressant drug overdose, hypothyroidism and
- -receptor antagonists, including labetalol. phenothiazine therapy. May also result from excessive
- vasodilator drugs, e.g. sodium nitroprusside, heat loss during anaesthesia.
GTN, hydralazine. Induced for surgery, e.g. cardiac surgery; techniques
- ganglion-blocking drugs, e.g. trimetaphan. include surface cooling by sponging or immersion,
Management: central cooling with heat exchangers and irrigation of
preoperative assessment with regard to body cavities with cold solutions.
contraindications. Induced hypothermia to 3234oC for 24h improves
premedication may be given to improve smooth- neurological outcomes in patients who have suffered
ness of induction. Atropine is avoided. out-of-hospital cardiac arrest due to VF. Has been inves-
smooth induction of anaesthesia, with minimal tigated in the treatment of head injury, but with con
coughing, straining, etc. Attempts may be made to flicting results. Permissive hypothermia refers to the
reduce the hypertensive response to intubation (see technique of allowing body temperature to decrease pas-
Intubation, complications of). Drugs increasing sively (e.g. during neurosurgery) to afford a degree of
heart rate or BP are avoided, e.g. atropine, keta cerebral protection.
mine, pancuronium. Effects:
tracheal intubation is usually performed. Spontane- cardiovascular:
ous ventilation is preferred by some, since it may - reduced cardiac output (a 30% reduction at
indicate adequacy of brainstem blood flow. IPPV is 30C).
often employed to avoid hypercapnia and vasodila- - J waves (positive deflections at the end of
tation associated with spontaneous respiration; it QRS complexes) may appear on the ECG at 30C
also reduces venous return. PEEP has been used to (Fig. 83). They are clinically insignificant.
augment the latter but may increase venous bleed-
ing. Dead space and V/Q mismatch are increased
at low blood pressures, therefore FIO2 is usually
increased to 0.5.
intra-arterial BP measurement is usually employed
if profound hypotension or infusions of potent J wave
hypotensive agents are used; otherwise indirect
methods of measurement are usually adequate.
CVP measurement is useful in major surgery. A
large-bore iv cannula is required. EEG and its Fig. 83 ECG showing J waves
 Hypoventilation 293

- ventricular arrhythmias at 30C, VF at 28C. Hypothyroidism. Usually follows thyroid disease (e.g.
- vasoconstriction. Vasodilatation occurs below autoimmune) or treatment for hyperthyroidism (includ-
20C. ing surgery and radiotherapy). May also follow treat-
- increased blood viscosity. ment with other drugs, e.g. amiodarone and lithium.
- increased haematocrit below 30C. Thrombocyto- Also rarely occurs in hypopituitarism. Approximately 10
penia may be caused by sequestration, mainly times more common in women; the incidence increases
hepatic. Fibrinolytic activity and prothrombin with age.
time increase. DIC may occur. Features:
respiratory: severely impaired physical and mental development
- apnoea at 24C. in children.
- reduced tissue O2 delivery because of reduced lethargy, slowed reactions, delayed relaxation of
cardiac output, vasoconstriction, increased viscos- tendon reflexes (classically plantar reflex).
ity and shift of the oxyhaemoglobin dissociation coarse skin and hair. Loss of the outer part of the
curve to the left, despite increased dissolved eyebrows is classically described but is uncommon.
volume of O2 in blood. weight gain, reduced appetite, constipation.
- reduced O2 demand and CO2 production. hoarse voice, hypothermia.
- arterial blood gas tensions are measured at anaemia: from menorrhagia or associated perni-
37C; values are traditionally corrected to body cious anaemia.
temperature but correction is now considered bradycardia, cardiomegaly and pericardial effusion
unnecessary. may occur. Typical ECG findings include low-
neurological: voltage complexes, bradycardia and T wave
- confusion below 35C. flattening/inversion. Hyperlipidaemia and isch-
- unconsciousness at 30C. aemic heart disease are common.
- reduced requirement for volatile agents. nerve entrapment, myopathy, confusion. Coma may
- cessation of all cerebral electrical activity below occur (see below).
18C. Investigations: thyroxine (T4) and triiodothyronine
other: (T3) are low. Thyroid stimulating hormone is high in
- diuresis due to inability to reabsorb sodium and primary thyroid failure, and low in pituitary failure.
water. GFR is reduced by 50% at 30C. Treatment: thyroxine replacement (50200g/day).
- respiratory and metabolic acidosis. Increased Initial dosage is reduced in the elderly and those with
blood glucose and potassium. heart disease, to reduce the risk of myocardial
- metabolic rate increases initially, then decreases. ischaemia.
Hyperglycaemia and increased fat mobilisation Hypothyroid coma (myxoedema coma):
may occur. particularly common during winter when hypother-
Management: mia is common, especially in the elderly. May be
investigation: both routine and as for coma, in par- precipitated by infection, CVA or anaesthesia.
ticular those causes mentioned above. mortality may exceed 50%.
routine ICU monitoring. treatment:
treatment of hypoxia/hypoventilation/acidosis as - T3 (liothyronine) 520g slowly iv, repeated
required. Antiarrhythmic treatment may be ineffec- 412-hourly depending on severity and response.
tive at low temperatures. Alternatively, 50g iv may be followed by 25g
rewarming methods include: tds, reducing to 25g bd. ECG monitoring is
- heating blankets and baths. required.
- radiant heaters. - hydrocortisone is often given but its place is uncer-
- warmed iv fluids. tain if adrenocortical insufficiency is not present.
- irrigation of body cavities (e.g. bladder via cath- - treatment of hypoventilation, hypothermia, hypo-
eter, peritoneal cavity via dialysis catheter, tension, bradycardia, acidosis, hyponatraemia,
stomach via nasogastric tube) with warm hypoglycaemia and convulsions as required. Fluid
solution. restriction is usually advocated for treatment of
- humidification and warming of inspired gases. hyponatraemia and prevention of cardiac failure.
- extracorporeal circulation using heat exchangers. Anaesthetic considerations in hypothyroidism:
External warming may cause peripheral vaso- other autoimmune diseases may be present, e.g.
dilatation and hypotension, or subsequent rebound myasthenia gravis.
hypothermia if the core is relatively unwarmed. patients show increased sensitivity to depressant
Rapid rewarming is thought to be best in hypother- drugs, especially opioids.
mia of rapid onset; gradual rewarming if of gradual CO2 and heat production, and drug metabolism/
onset (i.e. up to 1C/h). excretion are reduced.
treatment of the underlying cause. hypoventilation and coma may occur.
Complications include chest infection, frostbite and pan- Farling PA (2000). Br J Anaesth; 85: 1528
creatitis. Residual hypothalamic damage may remain,
especially in the elderly, with susceptibility for future Hypoventilation. Reduced alveolar ventilation; it may
episodes of hypothermia. result from reduction of respiratory rate and/or tidal
Epstein E, Anna K (2006). Br Med J; 332: 7069 volume.
See also, Temperature regulation Caused by:
reduced central respiratory drive:
- drugs, e.g. opioid analgesic drugs, barbiturates,
Hypothesis testing, see Null hypothesis inhalational anaesthetic agents.
294 Hypovolaemia

- hypocapnia, e.g. following IPPV. Also may occur (e.g. sedatives, anaesthetic agents) that cause vaso-
in extreme hypercapnia. dilatation or reduce cardiac output may thus
- metabolic disturbances, e.g. primary metabolic cause severe hypotension, as may spinal/epidural
alkalosis, hyperglycaemia. anaesthesia.
- administration of high FIO2 to patients with vital organs receive a greater proportion of cardiac
COPD who rely on hypoxic respiratory drive. output than normal, at the expense of other tissues,
- intracranial pathology, e.g. CVA, tumour, infec- e.g. skin and GIT. Smaller doses of anaesthetic
tion, head injury, raised ICP. agents are therefore required to produce clinical
- hypothermia. effects, including side effects (e.g. myocardial
- alveolar hypoventilation and sleep apnoea depression).
syndromes. renal failure may occur.
impaired peripheral mechanism of breathing: Hypovolaemia should therefore be detected and cor-
- airway obstruction. rected whenever possible before induction of anaesthe-
- restriction, e.g. due to pain, obesity, severe ascites, sia, and treated promptly when it occurs intra- and
tight bandages, circumferential chest burns. postoperatively.
- chest disease, e.g. COPD, pneumothorax, asthma, Features:
flail chest. pallor (peripheral vasoconstriction).
- muscular weakness, e.g. electrolyte disturbances, tachycardia.
muscular dystrophy, dystrophia myotonica, myo hypotension with low CVP and pulmonary capillary
pathy associated with critical illness. wedge pressure.
- neuromuscular junction impairment, e.g. non- oliguria, thirst.
depolarising and depolarising neuromuscular reduced O2 delivery, e.g.:
blockade, myasthenia gravis. - to tissues: lactic acidosis.
- nerve lesions, e.g. spinal cord injury, phrenic nerve - to brain: confusion, restlessness.
injury, motor neurone disease, poliomyelitis, - to carotid/aortic bodies: breathlessness.
GuillainBarr syndrome, critical illness - to heart: angina if susceptible.
polyneuropathy. haematocrit and urea and electrolyte abnormalities
increased dead space, e.g. embolism, anaesthetic depending on aetiology.
apparatus. Treatment:
Effects are those of hypercapnia, respiratory acidosis O2 administration, supine position and raising the
and hypoxaemia. During anaesthesia, uptake and excre- feet.
tion of inhalational anaesthetic agents are slowed. fluid replacement.
Treatment: of the cause.
O2 therapy. Restores alveolar PO2 as indicated by
the alveolar air equation. Assisted or controlled
ventilation may be required if arterial PCO2 is high Hypoxaemia. Arterial PO2 < 12kPa (90mmHg).
or rising. Caused by:
directed at the cause. Neuromuscular blockade hypoventilation (see Alveolar air equation).
monitoring helps distinguish central from periph- diffusion impairment, e.g. due to pulmonary fibro-
eral causes. sis, connective tissue diseases; V/Q mismatch is
doxapram may be used to treat perioperative thought to be more significant.
hypoventilation and acute exacerbations of COPD. shunt.
Naloxone is used in opioid overdose. V /Q mismatch.
See also, Carbon dioxide response curve reduced FIO2, e.g. due to high altitude or accidental
hypoxic gas delivery during IPPV, resuscitation or
Hypovolaemia. Reduced circulating blood volume. May anaesthesia.
be caused by deficiency of: In acute illness or during anaesthesia, hypoxaemia may
blood; i.e. haemorrhage. occur because of respiratory depression, airway obstruc-
plasma; e.g. burns. tion, atelectasis and V /Q  mismatch, including reduced
extracellular and/or intracellular fluid; e.g. dehydra- FRC. It is especially common after upper abdominal
tion, diuretic therapy, haemodialysis/haemo- surgery, due to the same factors plus hypoventilation
filtration, third-space losses (e.g. surgery, sepsis) and caused by pain, depressant drugs and inability to cough.
evaporative losses (e.g. pyrexia, during surgery). Impaired ciliary activity may also contribute. Hypoxae-
Relative hypovolaemia refers to pooling of blood, e.g. mia may persist for 23 days after upper abdominal
during sepsis, as a result of drugs or following spinal/ surgery. All of these factors may be exacerbated by pre-
epidural anaesthesia. Less blood is available for circula- existing obstructive sleep apnoea.
tion despite an unchanged blood volume. Effects:
Results in increased sympathetic activity, reduced direct effects:
parasympathetic activity and other compensatory - cyanosis.
mechanisms, as in acute haemorrhage. Important - confusion, drowsiness, agitation, headache, nausea.
clinically because: Unconsciousness, convulsions and death follow
many patients presenting with acute illness or unless corrected.
for emergency surgery have a degree of - myocardial depression, arrhythmias, bradycardia,
hypovolaemia. coronary and cerebral vasodilatation.
BP and perfusion of vital organs (e.g. heart, - hypoxic pulmonary vasoconstriction and pulmo-
brain) are maintained largely by sympathetically nary hypertension.
mediated vasoconstriction and tachycardia. Drugs - renal impairment.
 Hysteresis 295

effects of carotid and aortic body stimulation:

Stimulation of the carotid and aortic bodies occurs when
- tachycardia, hypertension. arterial PO2 falls; i.e. it may not occur in anaemic and
- hyperventilation. histotoxic hypoxia.
Acute hypoxaemia with 85% haemoglobin saturation See also, Oxygen cascade; Regional tissue oxygenation
may cause mental impairment, becoming severe at 75%
saturation. Unconsciousness usually occurs at 65% satu- Hypoxic pulmonary vasoconstriction. Reflex vaso-
ration. Chronic hypoxaemia, e.g. at altitude, leads to constriction of pulmonary arterioles in response to low
adaptation. PO2 (under 1113kPa; 80100mmHg) in nearby alveoli.
Treatment: Does not rely on innervation of vessel walls, and is less
directed at the cause. dependent on PO2 in blood; thus it occurs in isolated lung
O2 therapy: increases alveolar PO2, resulting in perfused with blood of high O2 content and ventilated
increased arterial PO2. The increase will be minimal with gas of low O2 content. Results in flow of blood away
if hypoxaemia is due to shunt. from poorly ventilated areas of lung, helping to reduce
See also, Breathing, control of; Hypoxia; Respiratory V/Q mismatch.
failure Before birth, decreased pulmonary blood flow is
caused by pulmonary vasoconstriction, relieved at birth
Hypoxia. Reduced O2 for tissue respiration. when O2 enters the lungs at the first breath.
Classically divided into: Important in cardiac defects; hypoxaemia may cause
hypoxic hypoxia (hypoxaemia). a generalised increase in pulmonary vascular resistance,
anaemic hypoxia: normal arterial PO2 but reduced with increased right ventricular work and increased
available haemoglobin, e.g. due to anaemia, carbon right-to-left shunting, particularly if SVR is lowered. Of
monoxide poisoning. major importance in the development of pulmonary
stagnant (ischaemic) hypoxia: normal arterial PO2 hypertension and right heart failure (cor pulmonale) in
and haemoglobin availability, but reduced tissue patients with chronic lung disease.
blood flow; may be due to reduced cardiac output Reduced by:
or local interruption of blood flow. hypocapnia.
histotoxic (cytotoxic) hypoxia: normal arterial PO2, increased distension of arterioles.
haemoglobin availability and blood flow, but inabil- vasodilator drugs.
ity of tissues to utilise O2, e.g. due to cyanide poison- volatile anaesthetic agents in animal and laboratory
ing, carbon monoxide poisoning. experiments; the clinical relevance of this is
Effects: controversial.
aerobic metabolism at the cytochrome oxidase
system is replaced by anaerobic metabolism, with Hysteresis. A property of certain systems whose output
increasing lactate production. Membrane pumps variable depends on both the input variable and the
cease functioning, with impairment of normal intra/ internal state of the system, i.e. the output cannot be
extracellular ion balance; irreversible cell damage readily predicted simply by observing the recent history
may follow. Brain and heart are most susceptible. of the system. Commonly cited examples include elastic
Other tissues may continue for long periods under hysteresis and changes in lung compliance throughout
hypoxic conditions. The critical value for intracel- the respiratory cycle and hysteresis as a source of error
lular O2 tension is not known, but is thought to be within measuring systems (e.g. direct arterial blood pres-
about 0.3kPa (2.3mmHg) at the mitochondrial sure measurement).
level (Pasteur point). See also, Breathing, Work of
local stagnant hypoxia effects depending on the
tissue involved.
general effects of hypoxia are as for hypoxaemia.
 I
Ibandronic acid, see Bisphosphonates (e.g. alcohol, nicotine), metabolic disturbance,
immobilisation.
Ibsen, Bjrn (19152007). Danish anaesthetist, consid- The incidence is thus reduced by consistent and sympa-
ered by many to be the founding father of intensive care. thetic staffing, provision of clear explanations to the
Created a dedicated respiratory care unit for patients patient and family, relatively unrestricted visiting hours,
with poliomyelitis during the Copenhagen outbreak in providing the patient with familiar objects (e.g. family
1952. Drastically cut mortality by employing positive photographs), availability of calendars and clocks and
pressure ventilation, mainly via tracheostomy. Opened promotion of a normal day/night routine. Specific treat-
the first general intensive care unit in 1953, a concept ment is directed at any underlying organic cause. Seda-
that was rapidly adopted worldwide. tive drugs (e.g. benzodiazepines, haloperidol) may be
Richmond C (2007). Br Med J; 335: 674 required to control agitation and establish a normal
See also, Intensive care, history of sleep pattern, but may also induce or exacerbate delir-
ium. Recent evidence suggests that the -adrenergic
Ibuprofen. NSAID used to treat musculoskeletal receptor agonists (e.g. dexmedetomidine) cause less
pain and headache. Also used for postoperative analge- delirium than benzodiazepines when used for routine
sia. Has weaker anti-inflammatory and analgesic proper- sedation.
ties than other NSAIDs, although has fewer GIT side Frontera JA (2011). Neurocrit Care; 14: 46374
effects. See also, Confusion in the intensive care unit; Confusion,
Dosage: 400600mg orally, tds/qds (max 2.4g daily). postoperative
A modified release preparation (1600mg od or 300
900mg bd), a topical gel and a combination prepara- ID interval. Time between induction of anaesthesia
tion with codeine are also available. and delivery of the infant in caesarean section. Infant
thiopental levels may be high if the interval is very short.
ICAM, intracellular adhesion molecules, see Adhesion If very long, inhalational anaesthetic agents may accu-
molecules mulate in the infant. An ID interval of less than 30min
is not thought to influence fetal acidosis if aortocaval
Iceberg theory, see Clathrates compression and hypoxaemia are avoided.

ICISS, see International classification injury severity Ideal gas law. For a perfect gas:
score pressure, P volume, V
= constant
ICNARC, see Intensive Care National Audit and temperature, T
Research Centre rearranged as PV = nRT,
where n = number of moles of gas
ICP, see Intracranial pressure R = universal gas constant
ICU, see Intensive care unit; Critical care Thus a combination of Boyles law, Charles law and
Avogadros hypothesis.
ICU delirium. Broad term denoting acutely abnormal
behaviour exhibited by patients in the ICU. Consists IDICM, see Intercollegiate Diploma in Intensive Care
of agitation, confusion, hallucinations and fluctuating Medicine
levels of attentiveness. Usually occurs 35 days after
admission, reportedly occurring in up to 70% of patients. Idioventricular rhythm, see Atrioventricular dissocia-
Associated with long-term cognitive impairment in ICU tion
survivors.
Aetiology is multifactorial: I:E ratio, see Inspiratory:expiratory ratio
patient factors: premorbid psychological state,
advanced age, communication difficulties. Ignition temperature. Lowest temperature at which
environmental factors: unfamiliar surroundings, combustible mixtures ignite (energy required = activa-
isolation from friends/family, lack of privacy, dis- tion energy). Lowest for stoichiometric mixtures.
rupted day/night cycle, sleep disruption, noise level, See also, Explosions and fires
monotony.
staff factors: insensitivity of staff, inappropriate con- IHD, see Ischaemic heart disease
versations by the bedside, inadequate explanation.
physiological factors: pain, fever, hypoxaemia, drug ILCOR, see International Liaison Committee on
treatment (e.g. sedatives), substance withdrawal Resuscitation

297
298 Ileus

Ileus. Small bowel atony (although the term is often Techniques include:
used to describe gastric and colonic stasis). conventional radiography:
Causes include: - CXR: demonstrates anatomical (as opposed to
GIT pathology, e.g. surgery, haemorrhage, functional) abnormalities of the lungs, tracheo-
peritonitis. bronchial tree, pleura, diaphragm, heart and
drugs, e.g. anticholinergic drugs, opioid analgesic great vessels, chest wall, thoracic spine and soft
drugs. tissues. May also detect foreign bodies, including
severe sepsis. invasive lines and tubes. Commonly performed
autonomic failure (e.g. in GuillainBarr syndrome, every 13 days in the ICU (depending on the
spinal cord injury) severity of illness; may require repeating several
others: acute kidney injury, diabetic coma, electro- times per day) to check tubes, monitor progress
lyte imbalance, especially hyperkalaemia. and check for complications (e.g. pneumothorax)
Clinical features include a distended and silent abdomen, after invasive procedures.
with constant (usually mild) abdominal discomfort. - abdominal X-ray: useful for demonstrating dilated
Upright abdominal X-ray may reveal gas-filled loops of loops of bowel and fluid levels in intestinal
small intestine. If prolonged, fluid and electrolyte loss obstruction, free abdominal gas, kidney and
may occur. Distension may impair ventilation if severe. gallstones.
The presence of colicky pain and increased bowel sounds others: include cervical spine and other bony
suggests intestinal obstruction, which may follow para- structures, soft tissues for presence of gas in gas
lytic ileus. Pseudo-obstruction of the colon occurs in gangrene.
bedridden patients with severe systemic illness and may ultrasound:
present in a similar way. Abdominal X-ray however - abdomen:
shows greatly dilated colonic loops; urgent decompres- - general, e.g. in trauma, intra-abdominal sepsis.
sion (e.g. via a colonoscope) may be required to prevent - renal tract in acute kidney injury; demonstrates
caecal rupture. renal size, obstructive nephropathy, vascular
Management: occlusion.
supportive: restriction of oral intake with free - biliary tract (e.g. in cholecystitis, ascending
nasogastric drainage. Early oral administration of cholangitis) and pancreas (pancreatitis).
small amounts of clear fluids is becoming more - chest:
common in uncomplicated cases. Fluid and electro- - echocardiography (and transoesophageal
lyte imbalance should be corrected. echocardiography).
metoclopramide and erythromycin are used to stim- - both echocardiography and abdominal ultra-
ulate intestinal activity. sound may provide information about the lungs,
methylnaltrexone, a peripherally acting mu opioid diaphragm and pleura.
receptor antagonist, is currently under investigation - central venous cannulation using ultrasound
as a treatment for postoperative ileus, which devices.
is thought to arise from a combination of endoge- CT scanning: remains the most sensitive and appro-
nous endorphins and exogenous opioids given for priate modality for critically ill patients with head
pain relief. injury, cerebral oedema, subdural, subarachnoid
and extradural haemorrhage and hydrocephalus.
Iliac crest block. Blocks the ilioinguinal, iliohypogastric Thoracic CT scanning gives detailed information of
and lower 23 intercostal nerves, providing anaesthesia all structures, including lung pathology in ARDS.
of the lower ipsilateral abdomen. An 8cm needle is Abdominal scanning is especially useful for imaging
introduced 23cm inferior and medial to the superior biliary tract, liver, pancreas and retroperitoneal
anterior iliac spine, and directed cranially and laterally structures. Portable bedside CT scanners are becom-
to reach the inner ilium. 10ml local anaesthetic agent is ing available.
MRI: although more sensitive than CT scanning for
injected whilst the needle is withdrawn. Injection is
repeated, directed more deeply. imaging cerebral and spinal structures, practical dif-
See also, Inguinal hernia field block ficulties (including long scan times and problems
with monitoring) preclude it from routine use.
positron emission tomography: remains primarily a
Iliacus compartment block, see Fascia iliaca compart- research tool in critically ill patients, although it has
ment block provided useful information about cerebral blood
flow and metabolism in head injury.
Iliohypogastric nerve block/Ilioinguinal nerve block, radioisotope scanning: used to assess organ blood

see Iliac crest block; Inguinal hernia field block flow and perfusion, presence of infection and
cardiac function.
Image guidance techniques may allow percutaneous
ILS, see Immediate Life Support drainage (e.g. of obstructed ureters, intra-abdominal
abscesses, empyema) to be performed by radiologists,
Imaging in intensive care. Many modalities are thereby avoiding the risks of surgery in critically ill
available; usage depends on the body area involved patients.
and whether the patient is stable enough to be trans- See also, Functional imaging; Radiography in intensive
ferred to the radiology suite. In general, portable imaging care
equipment produces less clear images. Discussion with
radiology staff is useful for making the correct choice Imipenem. Extremely broad-spectrum carbapenem and
of imaging. antibacterial drug, active against most pathogenic
 Immunoglobulins 299

aerobic and anaerobic Gram-negative and -positive anaesthesia may be protective against recurrence
organisms. Broken down in the kidney by dehydropep- of cancer.
tidase, thus combined with cilastatin (1:1 ratio by weight)
which inhibits the enzyme. Usually reserved for severe Immunodeficiency. Results in increased susceptibility
or mixed infections (excluding CNS infection). to infection and malignancy, the former a more common
Dosage: 0.51.0g iv qds. problem acutely. May result from deficient cell-mediated
Side effects: GIT upset, blood dyscrasias, allergic (T-cell lymphocyte) or antibody-mediated (B-cell lym-
reactions, convulsions, confusion, hepatic/renal phocyte) function, phagocytic activity or complement
impairment, red urine. activity. Results in repeated and persistent infection,
often with atypical organisms.
Imipramine hydrochloride. Tricyclic antidepressant May be:
drug, similar to amitriptyline but less sedating. Used in primary, often inherited, e.g. B- or T-cell deficiency.
endogenous depression and panic disorders. Also used Specific immunoglobulin types may be deficient.
in nocturnal enuresis. Neutrophil and complement disorders may also be
Dosage: 75mg/day orally, increased up to 300mg/day inherited.
(usually 50100mg/day). 2550mg is used in pain secondary to:
management. - infection, e.g. HIV infection, sepsis.
Side effects: as for amitriptyline. - drugs, e.g. immunosuppressive drugs, gold, peni-
cillamine, cancer chemotherapy.
Immediate Life Support (ILS). One-day course devel- - connective tissue diseases.
oped in 2002 by the Resuscitation Council (UK) in order - severe illness, trauma, burns, i.e. it may occur in
to standardise much of the in-hospital training under- any critically ill patient.
taken already by resuscitation officers. Trains healthcare - malignancy.
personnel in recognition of sick patients, prevention of - splenectomy.
cardiac arrest, cardiac arrest rhythms, basic life support Management:
(BLS), simple airway management and safe defibrilla- prevention of infection, e.g. meticulous aseptic
tion (manual and/or automatic). Aims to enable staff to technique, barrier nursing, prophylactic antibacte-
manage patients in cardiac arrest until the arrival of a rial therapy.
cardiac arrest team. prompt diagnosis and treatment of infection.
Soar J, Perkins GD, Harris S, Nolan JP (2003). Resuscita- treatment of the underlying cause.
tion; 57: 216. immunoglobulin administration (see Immunoglob-
ulins, intravenous).
Immune system, anaesthesia and. Normal immune immune-stimulant therapy may be indicated in
defences are: certain contexts (e.g. granulocyte colony-stimulating
innate (non-specific), e.g. epithelial surface barriers, factor in chemotherapy-induced neutropenic
secreted immunoglobulins, local inflammatory sepsis).
responses, including phagocytes and macrophages,
complement system, pH of gastric juice, ciliary Immunoglobulins (Antibodies). Proteins secreted by
action. plasma cells, involved in immunological defence systems.
adaptive (specific): Each molecule consists of two heavy chains (that deter-
- humoral: B lymphocytes; under the influence of mine the class of immunoglobulin) and two light chains.
T-cell cytokines, form plasma cells that secrete The Y-shaped molecule presents two highly specific
specific immunoglobulins. antigen-binding sites, each made up of portions of heavy
- cellular: T lymphocytes conditioned in the thymus and light chains, at one end (the Fab portion). The other
have killer activity and regulatory effects via end (the Fc portion) is made up of heavy chain only, and
helper/suppressor subsets. may bind to complement, or to the surface of mediator
- natural killer cells. cells, e.g. mast cells, macrophages.
Main areas of anaesthetic importance: Types of immunoglobulins:
patients with immunodeficiency. IgG: the most abundant in plasma. Involved in
adverse drug reactions, blood compatibility complement fixation. The only one that crosses the
testing. placental barrier.
effects of anaesthesia on immunocompetence, espe- IgA: secreted from epithelial barriers, e.g. GIT.
cially against infection and malignancy. Difficult IgM: comprises five joined molecules; involved in
to study clinically, because of other factors (e.g. complement fixation.
surgery, drugs, pre-existing disease, stress response IgD: involved in antigen recognition by
to surgery), although phagocyte, monocyte and lymphocytes.
B-lymphocyte activity is reduced in vitro. Ciliary IgE: on the surface of mast cells; involved in hista-
activity may be affected. Natural killer cell activity, mine release and anaphylaxis.
lymphocyte proliferation and plasma cell formation Most adverse drug reactions to anaesthetic drugs via
are also reduced following anaesthesia with most immunoglobulins involve IgG and IgM (complement
inhalational agents. Lysosomal free radical forma- activation) or IgE (anaphylaxis).
tion may also be suppressed. Effects on spread and Immunoglobulins may be administered therapeuti-
metastasis of malignancy are controversial, although cally, and are obtained from:
spread in animals may be increased by anaesthesia pooled human plasma:
and blood transfusion may be detrimental in colonic - from blood donated for transfusion (normal
and ovarian cancer surgery and renal transplanta- immunoglobulin): given im for prophylaxis of
tion. A number of studies suggest that regional certain infections, e.g. measles, hepatitis, rubella in
300 Immunoglobulins, intravenous

pregnant women. Certain forms may be given iv the latter makes little difference to the overall input
as replacement therapy in immunodeficiency, and impedance.
in various other immune-related disorders (see See also, Impedance plethysmography
Immunoglobulins, intravenous).
- from donors who are convalescing, or whose anti- Impedance plethysmography. Method of determining
body production has been boosted (specific changes in intrathoracic gas and fluid volumes by mea-
immunoglobulins): given im and available against suring transthoracic impedance, which varies according
hepatitis B, tetanus, rabies, Rhesus D antigen and to the composition of thoracic contents.
herpes viruses. Used for:
- They are screened for hepatitis and HIV monitoring respiration, e.g. on ICU: a small high-
infection. frequency current is passed between ECG elec-
monoclonal cell biology and recombinant genetic
trodes; the changes in impedance between them
engineering: not yet widespread. Infliximab is a represent ventilatory movements. Has been used to
monoclonal antibody against tumour necrosis detect oesophageal intubation (produces a different
factor, used in rheumatoid arthritis. impedance pattern to tracheal intubation).
Hypersensitivity reactions are more likely with immuno- cardiac output measurement: two sets of circular
globulins from pooled plasma. Digoxin specific antibody wire electrodes are placed around the chest and
fragments (Fab) derived from sheep immunoglobulins neck. Current is passed between the outer two, with
are used in digoxin toxicity. measurement of potential difference between the
inner two. Maximal rate of change of impedance
Immunoglobulins, intravenous (IVIG). Obtained from occurs with peak aortic flow, although absolute
a plasma pool of 100010000 donors and provide poly- values do not correlate well.
clonal immunoglobulins to a wide variety of pathogens. others, e.g. lung water measurement.
Originally used to treat idiopathic thrombocytopenia May also be applied to other parts of the body, e.g. leg
and congenital agammaglobulinaemia, also effective in veins to diagnose DVT.
GuillainBarr syndrome and other peripheral neuro See also, Inductance cardiography
pathies, myasthenia gravis and the myasthenic syn-
drome. Proposed mechanisms of action include an IMV, see Intermittent mandatory ventilation
anti-inflammatory and complement effect, reduction in
cytokine synthesis and blocking of IgG-binding Fc
receptors on macrophages. Inborn errors of metabolism. Group of disorders
Despite pre-donation testing, transmission of hepati- caused by inherited single enzyme defects. Over 200 are
tis C has been reported. known; some are clinically insignificant and others fatal.
Dosage varies widely according to indication: e.g. Most are rare (1:20000500000), caused by autosomal
0.4g/kg iv daily for 5 days for GuillainBarr syn- recessive genes, and present in infancy/early childhood.
Include disorders of:
drome; 1g/kg iv weekly during pregnancy for gesta-
porphyrin metabolism (see Porphyrias).
tional immune thrombocytopenia.
Side effects: malaise, fever, acute meningism, acute carbohydrate metabolism, e.g. glycogen storage

kidney injury, anaphylaxis. Contraindicated in disorders, galactosaemia and fructose metabolic

patients with class-specific anti-IgA antibodies. disorders. Liver, brain, skeletal and cardiac muscle
may be affected. Hypoglycaemia is common, also
metabolic acidosis and electrolyte imbalance.
Immunosuppressive drugs. Used to treat inflammatory/ amino acid metabolism, e.g. phenylketonuria,
autoimmune diseases and connective tissue diseases, homocystinuria, alcaptonuria. Mental handicap,
and to prevent rejection following transplantation. neurological abnormalities and metabolic distur-
Types of drug used:
bances are common. Skeletal abnormalities may
cytotoxic drugs, e.g. cyclophosphamide, azathio-
present difficulty with tracheal intubation in the
prine, chlorambucil, mycophenolate. All depress latter two disorders. Hypoglycaemia may occur.
bone marrow haemopoiesis and increase suscepti- lysosomal storage; results in accumulation of mac-
bility to infection. romolecules within lysosomes. Most conditions
corticosteroids.
cause severe mental retardation and neurological
anti-lymphocyte agents, e.g. ciclosporin, tacrolimus.
abnormalities, with death in childhood. Include:
immunoglobulins or immuno-active receptor - sphingolipidoses, e.g. Gauchers disease; coagula-
agonists/antagonists, e.g. tumour necrosis factor tion abnormalities and hepatosplenomegaly are
(TNF) receptorantibody complexes, anti-TNF common.
antibodies or interleukin-1 receptor antagonist, - mucopolysaccharidoses, e.g. Hurlers and
used to treat rheumatoid arthritis. Hunters syndromes (the latter is sex-linked
recessive). CNS, skeleton and viscera are affected.
Impedance, electrical. Resistance to flow of an alter- Characteristic gargoyle facies occur, with possi-
nating current in an electrical circuit, dependent on the ble upper respiratory obstruction, and thoracic
currents frequency. Represented by the letter Z, spinal deformities. Hurlers syndrome is more
although measured in ohms. Different components severe than Hunters, with corneal clouding,
within circuits (e.g. loudspeakers, monitor screens) valvular and ischaemic heart disease.
should be matched for impedance to maximise efficiency. purine metabolism: may lead to gout, with tissue
Amplifiers in monitoring equipment generally have high deposition of urate crystals, especially in the joints.
input impedance to minimise the effect of poor contact This group includes LeschNyhan syndrome, with
with the patient; any increased impedance because of mental and neurological abnormalities.
 Inductance 301

red blood cell metabolism, e.g. glucose 6-phosphate and/or the volume of calls from the press, public and
dehydrogenase deficiency. Haemolysis may also staff may be overwhelming.
feature in other defects. sudden need for specific equipment (e.g. breathing
copper metabolism (Wilsons disease): impaired apparatus, protective suits), drugs, blood products
hepatic and central nervous motor function. and other support services, e.g. X-ray.
iron metabolism (haemochromatosis): hepatic and dispersal of patients once initially treated; identifi-
myocardial impairment are common; diabetes mel- cation and holding of corpses.
litus may occur. Major incident plans of most hospitals are similar:
[Philippe Gaucher (18541918), French physician; affected hospitals are informed, and main receiving
Gertrud Hurler (18891965), German paediatrician; hospitals designated. Use is made of nearby special-
Charles Hunter (18721955), US physician; Michael ist centres, e.g. thoracic, neurosurgical.
Lesch (19392008), US cardiologist; William Nyhan, US specific duties are assigned to each member of
paediatrician; Samuel Wilson (18781937), US-born staff on duty, including formation of a mobile team.
English neurologist] Assignment of a team leader and establishment of
routes of communication in each area are vital.
Incentive spirometry. Lung expansion technique duties of anaesthetists include triage and treatment
designed to encourage deep breathing to reduce atelec- at the scene of the incident, resuscitation in the
tasis and improve respiratory muscle function, e.g. receiving area, and anaesthesia for surgery.
postoperatively. duties of ICU staff include resuscitation and man-
Apart from verbal encouragement and teaching of aging admissions to ICU.
breathing exercises, the following techniques have pre-prepared emergency drug and resuscitation
been used: equipment boxes. Triservice apparatus has been
inspiration from bellows; when the preset tidal suggested as suitable for field anaesthesia, but most
volume has been reached, a light illuminates. anaesthetists experience of this is limited, and
inspiration or expiration through flowmeters, e.g. anaesthesia is rarely required before transfer to
glass cylinders containing coloured balls; the patient hospital.
attempts to reach preset targets. Aylwin CJ, Knig TC, Brennan NW (2006). Lancet; 368:
inflation of a balloon on expiration. 221925
expiration through a blow-bottle: the patient See also, Biological weapons; Chemical weapons; Trans-
breathes out through a tube passing into a sealed portation of critically ill patients; Trauma
jar containing water, which is displaced through a
second tube into a second jar.
Independent lung ventilation, see Differential lung
Evidence suggests that the technique is useful in reduc-
ventilation
ing breathlessness in COPD but evidence for its efficacy
in preventing postoperative pulmonary complications is
lacking. Indocyanine green. Strongly infrared absorbing and
Overend TJ, Anderson CM, Lucy SD, etal (2001). Chest; fluorescent agent, given iv as a marker substance to
120: 9718 permit organ blood flow, liver function or cardiac output
See also, Physiotherapy measurement. Has also been used to study cerebral per-
fusion using near infrared spectroscopy. Transported on
proteins, it is exclusively eliminated by the liver but does
Incident, major. Practical hospital definition: any event not undergo enterohepatic circulation. Elimination is
involving casualties causing significant disruption of dependent on both liver blood flow and parenchymal
normal running of the hospital. Has also been defined cellular function.
according to the number of casualties. May refer to
transport accidents, riots, terrorist activities or natural
Indometacin (Indomethacin). Analgesic NSAID, avail-
disasters.
Main problems:
able for oral and rectal use. Also used to promote closure
of a patent ductus arteriosus (PDA).
large number of patients to be sorted (triage) for
Dosage:
treatment and transfer, with their sudden arrival
100mg rectally od/bd.
at hospital. Although there have been arguments
2550mg orally tds/qds.
over whether pre-hospital treatment is better than
for PDA closure: 200g/kg iv initially.
a scoop and run policy, it is now generally accepted Side effects: as for NSAIDs; in addition, dizziness and
that certain interventions (e.g. airway management)
headache may occur.
should ideally be carried out before transfer to
hospital if competent staff are available on
site. Adequate record-keeping is difficult, e.g. Inductance. Capacity for an inductor to generate an
patient identification, assessment, treatment given, electromotive force in opposition to a changing current
location. flowing in that circuit, or in a neighbouring one. Flow of
coordination of emergency services, with organisa- current induces a magnetic field, that in turn induces an
tion of staff and resources at the scene of the inci- electromotive force proportional to the rate of change
dent and receiving (designated) hospitals. of current. In effect, this acts as a store of energy within
clearing of non-urgent cases from wards and oper- the circuit. May give rise to interference in electrical
ating theatres. equipment, or occur intentionally in transformers. Has
communication between medical teams, hospitals, been used as a basis for measuring cardiac output and
police, fire brigade and public. Telephone and com- monitoring respiration, by using two coils placed on the
puter networks may be non-functioning or disabled, chest, e.g. one anteriorly, one posteriorly.
302 Inductance cardiography

Inductance cardiography (Thoracocardiography). Respiratory and cardiac depression may follow both
Method for measuring changes in intrathoracic volume, methods of induction, but are more sudden after iv
and thus estimating cardiac output. An insulated electri- induction. Use of other depressant drugs (e.g. for pre-
cal conductor placed around the chest, level with the medication) may reduce the amount of iv agent required
heart, is connected to an alternating current, and changes and allow smoother induction. Respiratory depressants
in cross-sectional area detected via changes in its self- (e.g. opioids) may slow inhalational induction. Other
inductance (via changes in the oscillatory frequency of routes of induction, e.g. rectal and im, are rarely
the induced current). Accuracy is generally not as good used now.
as other methods of measuring cardiac output; thus Emergency drugs and equipment, a tipping trolley
absolute values are less useful than trends. and skilled assistance should always be present before
inducing anaesthesia. Equipment should always be
Induction agents, see Intravenous anaesthetic agents checked before use.
See also, Anaesthesia, stages of; Checking of anaesthetic
Induction of anaesthesia. Transition from the awake to equipment; Induction, rapid sequence
the anaesthetised state, although the end-point is diffi-
cult to define. Induction, rapid sequence (Crash induction). Induc-
Represents a period of great physiological change tion of anaesthesia in which risks of regurgitation and
during which the following may occur: aspiration of gastric contents are minimised by:
cardiovascular changes, e.g. hypotension, presence of emergency drugs and equipment, a
arrhythmias. tipping trolley and skilled assistance (should be
hypoventilation/apnoea. Particularly dangerous in present before inducing anaesthesia in any patient,
patients with airway problems. but especially important in rapid sequence induc-
aspiration of gastric contents. tion, as is checking of anaesthetic equipment).
laryngospasm, hiccups and vomiting during the suction equipment should be turned on before
stage of excitement, particularly if disturbed, e.g. by induction and within easy reach of the
movement, noise or pain. anaesthetist.
adverse drug reactions, especially following iv aspiration of gastric tube if in place, before induc-
injections. tion. Pre-induction passage of a stomach tube is
others, e.g. involuntary movement/convulsions, rarely done routinely. A nasogastric tube is usually
MH/masseter spasm. left in situ during induction.
Inhalational induction: use of a rapidly acting iv induction agent and suxa-
usually reserved for children, patients with airway methonium to achieve rapid muscle relaxation.
obstruction and in difficult intubation. By allowing Rocuronium has been suggested as an alternative
continuous spontaneous ventilation, the anaesthe- when suxamethonium is contraindicated, but takes
tist avoids being unable to ventilate an apnoeic longer for recovery; thus spontaneous ventilation
patient. May also be used in patients with poor veins takes at least 30min to return should intubation
or needle phobia. fail. Regurgitation and aspiration have been
the anaesthetic agent is gradually introduced to the reported during use of the priming principle. Other
patient in increasing concentrations. The character- analgesic or sedative drugs should not precede the
istics of induction depend on the inhalational anaes- iv agent.
thetic agent used. More rapid induction has been application of cricoid pressure.
achieved using maximal breaths of high percentage avoidance of manual inflation of the lungs by face-
of volatile agent, e.g. 45% halothane or 48% sevo- mask to prevent inflation of the stomach and thus
flurane (single breath induction). increase risk of regurgitation. Preoxygenation is
the progressive stages of anaesthesia may be seen, therefore required to prevent hypoxaemia during
especially in unpremedicated patients. apnoea until tracheal intubation is achieved.
induction is slower than with iv agents. The stage of tracheal intubation and inflation of the cuff before
excitement may be prolonged. cricoid pressure is released.
IV induction: Spare laryngoscopes and tubes must be prepared in
much faster, allowing rapid passage through the advance, as must a plan in case of difficult or impossible
stage of excitement. Usually more pleasant for intubation.
adults than an inhalational technique. Rapid sequence induction should be performed in all
an estimated appropriate dose should be given cases known to be at risk of regurgitation or aspiration,
slowly, and the patient observed for its effect before including all emergency abdominal operations, except in
injecting more. Considerable time may be required cases where intubation is expected to be particularly
if the armbrain circulation time is prolonged, difficult.
e.g. in the elderly and those with cardiovascular See also, Intubation, difficult; Intubation, failed; Nasogas-
disease. tric intubation
the characteristics of induction depend on the iv
anaesthetic agent used. Inductor. Electrical component usually consisting of a
carries risk of extravasation, intra-arterial or painful conducting coil within a magnetic field. Applications
injection, thrombosis, chemical reaction with other include: signal filtering, transformers, current dampening
drugs in the cannula, and adverse drug reactions. (e.g. in defibrillation equipment).
movement and hiccuping may occur. See also, Inductance
overdosage is more likely because induction is
faster, especially if injection is rapid without pausing Inert gas narcosis. Loss of consciousness caused by
to observe the effect. inhalation of high partial pressures of inert gases, e.g.
 Influenza 303

xenon, neon, argon and nitrogen (nitrogen narcosis). joint daily ward rounds between microbiologists
Nitrogen has no anaesthetic properties at sea level pres- and the ICU team. Antimicrobial therapy should
sures, but impairs cognitive and motor function at partial only be used when clinically necessary and the
pressures above 45 atmospheres, e.g. diving to depths choice of agent informed by bacterial sensitivity.
greater than 3040 metres whilst breathing air. Use of regular cleaning/decontamination of the ICU.
helium in breathing apparatus allows deeper dives. better ward design to minimise environmental
contamination, including air filtration and
Infection. Most common cause of disease worldwide. conditioning.
Anaesthetic and ICU implications may be related to: The routine use of selective decontamination of the
primary cause of illness, e.g. meningitis, chest infec- digestive tract is controversial.
tion, hepatitis. See also, Bacterial resistance; Staphylococcal infections
complication of surgery, anaesthesia, intensive care,
trauma, e.g. nosocomial infection. Infection, hospital-acquired, see Nosocomial infection
treatment, e.g. side effects of antibacterial or antivi-
ral drugs. Infiltration anaesthesia. Commonly performed for
risk of transmission to susceptible patients or from minor surgery and suturing. Subcutaneous and intrader-
infected patients to staff. mal infiltration is performed around the lesion, with
Whatever its cause and site, infection may result in SIRS further injection as required. May also be used for
and/or septic shock. manipulations and more extensive surgery (e.g. caesar-
See also, Infection control; individual infections and ean section) in which the deeper tissues are also infil-
organisms trated. The maximal safe dose of local anaesthetic agent
should not be exceeded. Dilute solutions are usually
Infection control. Important in anaesthetic and ICU adequate. Excessive volumes of injectate containing
practice for prevention of nosocomial infection. Many adrenaline may cause skin necrosis. Adequate time must
hospitals have an infection control team (microbiologist, be allowed before starting surgery.
nurse and laboratory staff) with major responsibility
for surveillance/investigation of infection, review of anti- Inflammatory bowel disease. Chronic inflammatory
biotic therapy/resistance and education of staff. GIT disease of uncertain aetiology. Comprises:
Measures include: Crohns disease: transmural granulomatous disease;
provision of isolation rooms for patients susceptible commonly affects the terminal ileum and ascending
to infection or those who pose a cross-infection colon, although it may affect the GIT from mouth
hazard to other patients. Barrier nursing is often to anus.
necessary. Patients returning from ICUs to general ulcerative colitis (UC): characterised by inflamma-
wards should also be isolated until they are clear of tion of the colonic and rectal mucosa.
infections with organisms such as meticillin-resistant Features include fever, malaise, weight loss, anaemia,
Staphylococcus aureus (MRSA) and vancomycin- vitamin deficiencies, dehydration, abdominal pain and
resistant enterococcus. tenderness and diarrhoea (often bloody). Chronic
maintaining sufficient nurse:patient ratios to inflammation may lead to intestinal obstruction; Crohns
manage fluctuating workload. disease typically is associated with fistula formation.
staff hygiene: often poor, it is the major controllable Non-intestinal manifestations include arthritis, sacroili-
factor in cross-infection. Hands should be decon- itis, ankylosing spondylitis, uveitis, skin involvement
taminated before and after each patient contact, and liver/gallbladder disease. Diagnosis is confirmed by
watches/jewellery not worn, and meticulous aseptic intestinal biopsy.
technique used during medical and nursing proce- Management:
dures. Gloves (and, in ICU, aprons) should be worn medical: correction of nutritional deficiencies
during all procedures. and anaemia; sulfasalazine, 5-aminosalicylic acid
early identification and treatment of infection. enemas; corticosteroids.
Immediate screening (e.g. for MRSA) with decolo- surgical: may be required for Crohns disease (e.g.
nisation of high-risk patients is essential when for obstruction, fistulae) or UC (e.g. in toxic mega-
patients are admitted from other ICUs or hospitals. colon when extensive disease is unresponsive to
Regular culture of sputum and urine should medical therapy, or in total colitis lasting more than
continue for all patients on ICU. 10 years when malignant change becomes more
identification and avoidance of catheter-related common).
sepsis, and use of care bundles Anaesthetic considerations encompass the above com-
use of bacterial filters on breathing systems and plications and the need for emergency surgery. Severe
regular changing of disposable ventilator tubing toxic megacolon may require admission to ICU for
(e.g. every 48h). resuscitation.
use of disposable syringes and pressure transducers, [Burrill B Crohn (18841983), US physician]
which should not be reused.
safe use and disposal of sharps. Inflation pressure, see Airway pressure
restricting drug ampoules to single patients only
and preparing syringes immediately before use. Inflation reflex, see HeringBreuer reflex
avoiding contamination of anaesthetic equipment
by appropriate cleaning/disposal of equipment after Influenza. Acute illness caused by influenza virus infec-
each patient. tion. Epidemiologically characterised by regular sea-
appropriate management of patients with proven or sonal epidemics with a larger pandemic occurring every
possible CreutzfeldtJakob disease. few decades; the latter arises when there is a major shift
304 Informed consent

in viral antigenic type (against which the population has component (usually the amount of drug) according to
little immunity). the patients weight to produce a concentration expressed
All strains are single-stranded RNA viruses classified in terms of amount of drug per kilogram. Other consid-
according to their haemagglutinin and neuraminidase erations relate to the kind of infusion device used and
surface proteins (e.g. H1N1, H2N2). H1N1 influenza whether the dose is commonly expressed as drug per
(swine flu) is responsible for the recent pandemic of unit time (e.g. g/h), volume per unit time (e.g. ml/h)
2009, causing > 375000 infections worldwide with > 4500 or drug per kilogram per unit time (e.g. g/kg/h). A
deaths (137 in the UK). While the majority of infections common and useful method of preparing drugs (e.g. ino-
were self-limiting, a small proportion of patients (includ- tropic drugs) is to add (body weight 3) mg of drug to
ing previously well, young adults) developed severe/fatal diluent to make 50ml solution; 1ml/h is then equivalent
complications. Pregnant women, the immunosuppressed, to 1g/kg/h.
and those with respiratory co-morbidities were over-
represented in those requiring ICU admission. Inguinal hernia field block. May be used as the sole
Vaccines are available against influenza (including technique for surgery in high-risk patients, or as an
pandemic H1N1) and may prevent 5080% of cases in adjunct to general anaesthesia to reduce the anaesthetic
healthy adults; their use is recommended in all at-risk requirement and to provide postoperative analgesia.
groups (e.g. healthcare workers, pregnant women). Anatomy (see Fig. 67; Femoral triangle):
Features: the inguinal canal represents the path taken by the
common symptoms: fatigue, fever, cough, sore descending testicle, and contains the spermatic cord
throat, rhinitis, dyspnoea, headache, myalgia, diar- in the male (round ligament in the female). It runs
rhoea and vomiting. downwards and medially, above and parallel to the
complications requiring ICU admission: respiratory inguinal ligament, which passes from the superior
failure, acute lung injury, secondary bacterial infec- anterior iliac spine to the pubic tubercle.
tion, septic shock and MODS. anterior abdominal wall muscle layers, from within
Investigations: outwards: transversus abdominis, internal oblique,
general: CXR, arterial blood gases, routine blood external oblique.
tests. the canal emerges through the deep ring of the
diagnostic tests: antigen detection tests (e.g. rapid transversalis fascia and transversus abdominis
influenza detection test); immunofluorescence above the midpoint of the inguinal ligament. The
assay; viral culture; RT-PCR (reverse transcription internal oblique lies in front laterally, but its con-
polymerase chain reaction). The latter two have the joint tendon (formed with transversus abdominis)
greatest sensitivity and specificity, and are able to arches over the canal superiorly to lie behind it
distinguish H1N1 pandemic influenza from other medially. The external oblique lies anteriorly along
types. its length. The superficial ring is the defect in the
Treatment: external oblique aponeurosis just lateral and above
general measures: O2, iv fluids, analgesia, isolation/ the pubic tubercle.
infection control measures. nerve supply (branches from the lumbar plexus):
antiviral therapy for pandemic H1N1: - iliohypogastric (L1): anterior cutaneous branch is
- oseltamivir: 75mg orally bd in adults; weight- given off at the iliac crest; it passes between trans-
adjusted dosage scale for children. versus abdominis and the internal oblique, pierc-
- zanamivir: 10mg bd via metered dose inhaler; ing the latter 2cm medial to the anterior superior
first-line in pregnant patients as inhalational iliac spine. It then runs deep to the aponeurosis of
administration reduces fetal exposure. the external oblique, piercing it above the super-
ICU management includes: early intubation and ficial ring to supply the skin above the pubis.
IPPV (interim non-invasive ventilation may worsen - ilioinguinal (L1): passes just caudal to the iliohy-
outcome); high-frequency ventilation; extracorporeal pogastric nerve, passing through the superficial
membrane oxygenation where available; fluid resus- ring to supply the skin of the groin and scrotum/
citation and cardiovascular support with avoidance of labia majora.
overhydration. - genitofemoral (L1, 2): genital branch passes
The potential for pandemic influenza to place extreme with the spermatic cord (in the male) through the
demands on healthcare resources (particularly ICU pro- deep ring, supplying the skin of the scrotum/labia
vision) has led to the development of detailed triage, majora.
admission and treatment guidelines by the Department Technique of block:
of Health. iliohypogastric and ilioinguinal nerves: with the
Patel M, Dennis A, Flutter C, Khan Z (2010). Br J patient supine, a short bevelled needle is introduced
Anaesth; 104: 12842 vertically downwards, 2cm medial and caudal to
the anterior superior iliac spine. A click is felt as
Informed consent, see Consent the external oblique aponeurosis is penetrated.
1020ml local anaesthetic agent is injected,
Infraorbital nerve block, see Maxillary nerve blocks
repeated with the needle directed medially and lat-
Infratrochlear nerve block, see Ophthalmic nerve erally. Subcutaneous infiltration from the pubis,
blocks 10cm cranially, blocks fibres from the other side.
subcutaneous infiltration along the incision site.
Infusion regimens. Used to facilitate administration of genitofemoral nerve: injection of 20ml solution at
potent iv drugs whilst minimising errors. Generally rely the deep ring, 12cm above the midpoint of the
on adding a fixed amount of drug to a fixed volume of inguinal ligament, deep to the external oblique
diluent to produce a set concentration, or varying one aponeurosis as before. This may be left to the
 Inhalational anaesthetic agents 305

surgeon to reduce risk of vascular or peritoneal - non-irritant, with pleasant smell.

puncture. - no corrosion of metal or adsorption on to rubber.
the neck of the hernia sac may also be infiltrated by - SVP should be high enough to enable production
the surgeon. of clinically useful concentrations (depends on
Prilocaine 0.5% with adrenaline is suitable, and allows potency; MAC).
use of a large volume of solution. The maximal safe dose - low blood/gas partition coefficient.
allowable is calculated and divided between the above - cheap.
injections. For an adjunct to general anaesthesia and pharmacology:
postoperative analgesia, smaller volumes of bupivacaine - smooth rapid induction with no breath holding,
with adrenaline may provide several hours analgesia. laryngospasm, coughing or increased secretions.
Leg weakness has been reported due to unintentional - sufficiently potent to allow concurrent high FIO2.
femoral nerve block. - analgesic, antiemetic and anticonvulsant proper-
ties, with skeletal muscle relaxation. No increase
Inhalational anaesthetic agents. Since the discovery of in cerebral blood flow or ICP.
anaesthesia, a variety of gases and volatile agents have - no respiratory depression. Bronchodilatory
been tried and discarded, including: diethyl ether (first action.
used in 1842), N2O (1844), chloroform (1847), ethyl chlo- - no cardiovascular depression or sensitisation of
ride (1848), ethylene (1923), cyclopropane (1930), divinyl myocardium to catecholamines. No decrease in
ether (1933), trichloroethylene (1935), xenon (1946), coronary, renal or hepatic perfusion.
halothane and fluroxene (1956), methoxyflurane (1960), - minimal metabolism, with excretion via the lungs.
enflurane (1966), isoflurane (1971), desflurane (1994) No fluoride ion production.
and sevoflurane (1996). Some properties of inhalational - no adverse renal, hepatic or haematological
agents are shown in Table 24. effects.
Inhalational agents are popular because alveolar - non-trigger for MH.
levels (and thus blood levels) are easily controllable by - no effects on the uterus.
adjusting inspired concentration. However, side effects - non-teratogenic/carcinogenic.
and pollution concerns have led to increased use of iv No currently available agent fulfils all the above. All of
anaesthetic agents, i.e. TIVA. the volatile agents currently used have undesirable
Volatile anaesthetic agents are convenient to supply effects; in addition to those listed in Table 25, they all
and store, but require special vaporisers. Many are depress respiration, reduce uterine tone, and may trigger
ethers; flammability and risk of explosion and fires are MH. All increase cerebral blood flow, although isoflu-
reduced by addition of halogen atoms to the basic rane and sevoflurane less so. N2O is not potent enough
molecule. for use as a sole agent and is losing popularity because
Gases are supplied in cylinders or via pipelines. Cyl- of its emetic action, effects on methionine metabolism,
inders are bulky to store. Administration of gases is con- cardiovascular and cerebral function, expansion of
trolled using flowmeters alongside the O2 flowmeter of gas-containing cavities (e.g. pneumothorax) and its envi-
an anaesthetic machine. ronmental effects. Trichloroethylene is analgesic and
Features of the ideal inhalational anaesthetic agent: extremely cheap but is no longer produced due to costs
physical/chemical properties: associated with renewal of its product licence. Diethyl
- chemically stable, e.g. in the presence of heat, ether has been available on a named-patient basis.
light, soda lime; long shelf-life. No additives (e.g. Cyclopropane, previously used mainly in paediatric
thymol) required and non-flammable. anaesthesia, is now no longer available. Sevoflurane and

Table 24 Properties of inhalational anaesthetic agents

Partition coefficients at 37C

Molecular Boiling SVP at 20C MAC (% vol.)

Agent Structure weight point (C) (kPa [mmHg]) (young adults) Blood/gas Oil/gas

Chloroform CHCl3 119 61 21 (160) 0.5 110 260

Cyclopropane (CH2)3 42 33 9.2 0.45 11.5
Desflurane CF3CHFOCF2H 168 23 88 (673) 510 0.42 19
Diethyl ether CH3CH2OCH2CH3 74 35 59 (425) 1.9 12 65
Divinyl ether CH2=CHOCH=CH2 70 28 74 (553) 3 2.8 60
Enflurane CHFClCF2OCF2H 184.5 56 24 (175) 1.68 1.9 98
Ethyl chloride CH3CH2Cl 64.5 13 131 (988) 2 3
Ethylene CH2=CH2 28 104 65 0.4 1.3
Fluroxene CF3CH2OCH=CH2 126 43 38 (286) 3.4 1.4 48
Halothane CF3CHClBr 197.4 50 32 (243) 0.76 2.4 225
Isoflurane CF3CHClOCF2H 184.5 49 33 (250) 1.28 1.4 97
Methoxyflurane CFCHClOCH3 165 105 3 (23) 0.2 13 14
Nitrous oxide N2O 44 88 105 0.47 1.4
Sevoflurane (CF3)2CHOCH2F 200 58 21 (160) 2.5 0.69 53
Trichloroethylene CCl2=CHCl 131 87 8 (60) 0.17 9 960
Xenon Xe 131 108 71 0.14 1.9
306 Inhalational anaesthetic agents

Table 25 Undesirable features of the more modern volatile anaesthetic agents

Feature Halothane Isoflurane Enflurane Desflurane Sevoflurane

Thymol required +
Decomposed by light +
Approximate cost/100ml () 45 1520 1013 1520 4550
Irritant to breathe + +/ ++
Cardiac output
SVR ()
Heart rate
Sensitivity to catecholamines +++ + ++
Metabolised (%) 20 0.2 2 0.02 35
Others Halothane hepatitis Coronary steal Epileptiform EEG Direct metering vaporiser Decomposed by soda
required lime/baralyme

desflurane are increasingly being used for day-case

Fractional alveolar concentration/

surgery since their low blood-gas solubility promotes

fractional inspired concentration

rapid recovery. 1.0 Nitrous oxide
Desflurane
The potency of anaesthetic agents depends on their Sevoflurane
0.8 Isoflurane
solubility in the CNS, estimated by the oil/gas parti- Enflurane
tion coefficient. Clinical effect depends on the partial 0.6 Halothane

(FA/FI)
pressure (rather than the total amount present) of the
agent in the brain, which is related to arterial partial 0.4
pressure, which is related to alveolar partial pressure. 0.2
Thus steady-state brain concentration requires
steady-state alveolar concentration. Drug is distrib- 0
uted from alveoli via bloodstream to: 0 20 40 60
vessel-rich tissues (e.g. brain, heart, kidney, liver;
Time (min)
receive 7080% of cardiac output) until equilibrium
Fig. 84 Wash-in curves for some inhalational anaesthetic agents:
is reached, then:
equilibration between inspired and alveolar concentrations is faster for
vessel-intermediate tissues (muscle, skin; 18% of
agents with lower solubility in blood
cardiac output).
fat (6% of cardiac output) and other vessel-poor
tissues, e.g. bone, ligaments. concentrations with insoluble agents than with
In prolonged anaesthesia, the agent dissolves in fat, soluble ones.
especially if it is very fat-soluble (i.e. potent). Thus it - cardiac output and pulmonary blood flow: uptake
takes 80min for the partial pressure of N2O in fat to is more rapid if cardiac output is high, leading to
equal half that in arterial blood; halothane requires 32h. slow build-up of alveolar concentration. If cardiac
Factors affecting uptake: output is low, alveolar partial pressure builds up
delivery to alveoli: more quickly; in addition, a greater proportion of
- vaporisation: SVP, gas flow, temperature, vapo- cardiac output goes to vital organs, e.g. brain and
riser design, pumping effect. heart, increasing clinical effects. Thus overdose is
- anaesthetic breathing system: gas flow, volume of more likely if cardiac output is low. The effect is
system and dilution of agent, adsorption on to more marked with soluble agents.
rubber. - concentration of agent in the pulmonary artery
- alveolar ventilation: increased alveolar ventila- (i.e. mixed venous). As it approaches pulmonary
tion shortens the time required for equilibration venous concentration, alveolar and arterial levels
between inspired agent partial pressure and alve- approach equilibrium. Occurs as body tissues
olar agent partial pressure. Hyperventilation thus become saturated, or in severe low output states
hastens onset of anaesthesia. when tissue perfusion is reduced.
- concentration effect and second gas effect. - V/Q mismatch: rarely significant unless large, e.g.
uptake from alveoli: accidental endobronchial intubation. Effects are
- blood/gas partition coefficient (solubility in greater for insoluble agents.
blood): if high, uptake and dissolution into blood - impaired diffusion across alveolar wall is rarely
are rapid, thus alveolar concentration falls rapidly significant.
until the next breath. Build-up of stable alveolar Factors affecting recovery are similar to those above. If
partial pressure and thus arterial partial pressure body tissues are unsaturated, recovery is more rapid
is therefore slow. If solubility is low, only a small because the agent moves from arterial blood to both
proportion of agent dissolves in the blood, leaving tissues and alveoli. If tissues are saturated after pro-
a large reserve in the lungs. Thus alveolar and longed anaesthesia, recovery is slower, but is hastened
arterial partial pressures build up rapidly, with by hyperventilation. However, drug movement from
rapid clinical effects (Fig. 84). Changes in vapo- tissues into blood may cause reaccumulation of anaes-
riser settings are more rapidly reflected in arterial thetic alveolar concentrations after initial wakening.
 Inotropic drugs 307

See also, Anaesthesia, mechanisms of; Coronary steal; Inotropic drugs. Drugs that increase myocardial con-
MeyerOverton rule tractility, increasing cardiac output.
Drugs available include:
catecholamines: act via G protein-coupled receptors
Injector techniques. Use of intermittent jets of driving
gas, usually O2, for IPPV by entraining room air. The jet to increase intracellular cAMP levels via adenylate
is delivered to the proximal end of a bronchoscope by a cyclase stimulation; cAMP increases intracellular
metal cannula (Sanders injector), and entrains stationary calcium ion mobilisation and force of contraction.
gas within the scope by jet mixing. Room air is drawn - adrenaline: -adrenergic receptor agonist mainly
in from the open end to replace the air delivered to the at low doses, -adrenergic receptor agonist mainly
lungs. Expiration occurs by passive recoil of the lungs. A at higher doses. Causes peripheral and renal
1416G cannula is suitable for adults (delivers up to vasoconstriction, especially at higher doses.
3050 cmH2O pressure); 1718G for adolescents and Tachycardia and arrhythmias may occur, increas-
small adults (up to 25 cmH2O); 19G for children (up ing myocardial O2 demand.
to 15 cmH2O). The Carden jetting device was described - noradrenaline: -receptor agonist mainly,
for attachment to a bronchoscope side-arm; higher infla- with some -receptor agonist properties. Causes
tion pressures and FIO2 are achieved with lower driving peripheral and renal vasoconstriction, with raised
pressures. BP and compensatory bradycardia. Depending
The system usually consists of tubing and a connector on the SVR, myocardial O2 demand may be
for wall socket or gas cylinder, a pressure-reducing valve markedly increased.
and gauge, a hand-operated trigger and attachment for - isoprenaline: -receptor agonist only. Increases
the cannula. It may also be attached to commercially cardiac output and rate, with peripheral and pul-
available cricothyrotomy devices, or to iv cannulae used monary vasodilatation. Arrhythmias are common,
for emergency cricothyrotomy. Similar principles are and myocardial O2 demand is increased; isch-
also used in high-frequency jet ventilation. aemia may occur due to lowered BP.
Commonly used for bronchoscopy and laryngoscopy - dopamine: 1-receptor agonist at lower doses,
because of its convenience. with increased cardiac output and BP. -Receptor-
Disadvantages: mediated vasoconstriction occurs at higher doses.
tidal volume and minute ventilation are difficult to
Myocardial O2 demand is increased, but isch-
assess. aemia is less likely as BP also increases. Tachycar-
trachea is unprotected during airway surgery.
dia is less common. Dopamine receptor-mediated
possible interference with surgery from movement
renal and mesenteric vasodilatation may occur
of vocal cords during ventilation. at low doses (so-called renal dose), although
barotrauma is possible if expiration is obstructed.
accompanying diuresis may be simply due to
volatile anaesthetic agents cannot be delivered.
improved cardiac output.
[Richard D Sanders (19061977) and Edward Carden, - dobutamine: mainly a 1-receptor agonist, with
US anaesthetists] weak 2- and weaker -receptor agonist proper-
See also, High-frequency ventilation ties. Causes less tachycardia than other catechol-
amines for a given inotropic effect, possibly due
to a smaller effect on the sinoatrial node, and
Injury severity score (ISS). Trauma scale used to grade activation of the baroreceptor reflex by increased
severity of multiple injuries and based on the abbrevi- BP. Coronary perfusion may increase as left ven-
ated injury scale (AIS). Mostly used for audit purposes, tricular end-diastolic pressure falls.
it takes the square of the AIS scores for the three worst - dopexamine: derived from dopamine; more active
affected anatomical regions, with scores ranging from 0 at 2-receptors and less active at dopaminergic
to 75 (any AIS score of 6 automatically converts the total receptors. Causes peripheral and renal vasodilata-
to 75). A score under 24 indicates probable survival, tion, with little tachycardia.
2550 reflects progressive increase in mortality and > 50 - pirbuterol: mainly a 1-receptor agonist. Causes
suggests very high mortality rates. Accounts only for some vasodilatation.
anatomical injury, not other factors, and concentrates on - salbutamol: not a direct inotrope but sometimes
only one injury per anatomical site. used in circulatory failure. A 2-receptor agonist,
The new injury severity score (NISS) differs by reducing SVR. Tachycardia is common.
including all the most severe injuries rather than the phosphodiesterase inhibitors:
most severe injury per body area. NISS performs better - specific for cardiac phosphodiesterase: e.g. amri-
than ISS and is more accurate in distinguishing between none, milrinone, enoximone. Cause vasodilatation
survivors and non-survivors. and increased cardiac output.
Baker SP, ONeill B (1976). J Trauma; 16: 8825 - non-specific: e.g. aminophylline.
calcium sensitisers: e.g. levosimendan. Increase
Inosine. Metabolite of adenosine, with some similar myocardial contractility without increasing myocar-
actions. Causes vasodilatation via a direct action on vas- dial energy/O2 requirements. Also cause vasodilata-
cular smooth muscle. Also has a positive inotropic effect, tion (by opening K+ channels in vascular smooth
but not via -adrenergic receptors. Thought to improve muscle), thus reducing afterload and preload.
cell survival following ischaemia and reperfusion (e.g. in others:
cardiac and renal surgery), possibly by increasing intra- - calcium: effect lasts for about 5min. Used as a
cellular levels of energy-rich phosphates and reducing temporary measure. Ventricular arrhythmias may
ATP depletion. Has been used in proximal aortic and occur.
renal surgery; e.g. 30mg/kg iv before clamping. Hypo- - cardiac glycosides: e.g. digoxin. Increase cardiac
tension may occur. output and reduce heart rate; possibly also cause
308 INPB

vasoconstriction. Thought to increase intracellu- rate during weaning from ventilators. However, negative
lar calcium ion activity via other ionic effects. pressure must be generated by the patient to trigger
Their use in circulatory failure is controversial. augmentation. Tidal volume may vary according to the
- glucagon: mechanism is unclear; adrenergic recep- patients inspiratory flow pattern. During weaning, the
tors are not thought to be involved. May increase amount of support supplied may be reduced either by
calcium flux into myocardial muscle by stimulat- lowering the preset airway pressure, or by increasing
ing adenylate cyclase. the negative pressure required to trigger the support.
Choice of drug depends on clinical context. Dopamine A combination of pressure support and a decelerat-
is sometimes used in low dosage for its purported renal ing inspiratory flow pattern and a guaranteed tidal
effect; dobutamine is commonly used for cardiac support. volume, inspiratory volume support, has recently been
Adrenaline and noradrenaline are also used, the latter, developed, in which changes in lung properties during
for example, when vasodilatation is a particular problem, inspiration are continuously monitored.
e.g. septic shock. Enoximone is often used where tachy-
cardia is particularly undesirable, e.g. after cardiac Inspiratory reserve volume. Inspiratory capacity
surgery. Isoprenaline is indicated in bradycardia, and minus tidal volume. Normally 3.54.0 litres.
raised pulmonary vascular resistance. See also, Lung volumes
Often used in combination with vasodilator drugs, to
reduce filling pressures whilst providing inotropic Inspiratory volume support. Spontaneous ventilator
support. Enoximone and dopexamine especially fulfil breathing mode combining the benefits of inspiratory
both functions. pressure support with a decelerating inspiratory flow
pattern and a guaranteed tidal volume. The ventilator
INPB, Intermittent negative pressure breathing, see automatically monitors the lung properties and modifies
Intermittent negative pressure ventilation the inspiratory pressure support to deliver a predeter-
mined volume. Maximum inspiratory pressure support
permitted is just below the preset upper pressure limit
INPV, see Intermittent negative pressure ventilation and, if the tidal volume cannot be delivered with this
degree of pressure support, the ventilator alarms, indi-
INR, International normalised ratio, see Coagulation cating that the breath has been pressure-limited. Useful
studies mode when there is a large variation in lung/chest com-
pliance during inspiration, e.g. atelectasis, bronchospasm.
Insensible water loss. Volume of pure water (i.e. solute- As the patient increases spontaneous ventilation, the
free) lost per day through evaporation from the respira- inspiratory support from the ventilator decreases. If
tory tract or diffusion through the skin (with subsequent apnoea occurs, volume support also ensures a back-up
evaporation). Normally up to 1200ml at rest, increasing of pressure-regulated volume control ventilation. The
with body temperature (by up to 20% per C above maximum pressure change between two breaths is preset
normal) and metabolic rate, and also in tachypnoea. by the ventilator (approximately 3 cmH2O).
Reduced as ambient humidity increases. During IPPV,
exhaled losses may be reduced by humidification of Insufflation techniques. Passage of 46 l/min fresh gas
inspired gases. through a fine-bore catheter, passed through the larynx
See also, Fluid balance into the trachea; the tip usually lies near the carina (tra-
cheal insufflation). With spontaneous ventilation, fresh
Inspiratory capacity. Maximal possible volume of air gas and room air are inhaled into the lungs, with exhaled
inspired from FRC. Composed of tidal volume and inspi- gas passing out around the catheter. May also be used
ratory reserve volume. Normally 4.05.0 litres. to maintain oxygenation in apnoeic patients, although
See also, Lung volumes with build-up of CO2 (apnoeic oxygenation). Used to
maintain oxygenation during brainstem death testing.
First used in the early 1900s. Magill and Rowbotham
Inspiratory:expiratory ratio (I:E ratio). Ratio of inspi- later provided a separate tube for expired gases, both
ratory time to expiratory time. Usually 1:2, allowing tubes subsequently replaced by a single wide-bore tra-
recovery from the cardiovascular effects of IPPV during cheal tube. Still used by some anaesthetists for bronchos-
expiration. Adjustable on most ventilators between 1:1 copy and laryngoscopy, especially in children. Fresh gas
and 1:4. If expiration is too short, air trapping may occur, may also be delivered via the rigid endoscope.
with increasing intrathoracic volume and pressure, Pharyngeal insufflation is also possible, using a pha-
increasing adverse effects of IPPV. However, a reversed ryngeal catheter, or by attaching the fresh gas source to
I:E ratio of up to 4:1 (inverse ratio ventilation) has been a gag or airway.
used to improve oxygenation in respiratory failure, espe- Barotrauma may occur if escape of gas is obstructed.
cially combined with PEEP.
If expiration is too long, dead space is thought to Insulin. Hormone secreted by B () cells of the pancre-
increase. atic islets of Langerhans (A [] cells secrete glucagon,
and D [] cells somatostatin). Composed of two polypep-
Inspiratory pressure support. Augmentation of spon- tide chains specific to species, linked by disulphide
taneous inspiration with supplementary gas flow. A more bridges. Synthesised as a precursor molecule, subse-
refined form of assisted ventilation, provided by modern quently split before secretion.
ICU ventilators. Inspiratory flow rate is adjusted to Secretion is increased by:
produce a preset inspiratory airway pressure; when flow glucose, mannose, fructose.
rate falls to a certain value, inspiration ends. Increases amino acids.
tidal volume, reducing work of breathing and respiratory glucagon and other gut hormones.
 Intensive care, history of 309

-adrenergic receptor stimulation. intermediate and long-acting:

vagal stimulation. - isophane insulin (suspension with protamine) and
phosphodiesterase inhibition, e.g. due to drugs. amorphous insulin zinc suspension. Acts within
sulphonylureas. 12h, lasting up to 20h.
Secretion is decreased by: - insulin detemir and insulin glargine: recombinant
hypoglycaemia. human insulin analogues: exhibit slower absorp-
somatostatin. tion from injection sites via protein-binding and
-receptor stimulation. precipitation respectively. Act within 12h with
insulin. duration of action up to 24h.
drugs: - crystalline insulin zinc suspension. Acts within
- diazoxide. 12h, lasting up to 36h.
- thiazide diuretics. The last group is mainly used for maintenance sc admin-
- -adrenergic receptor antagonists. istration. Several insulin mixtures (biphasic) are also
Actions: available. Available as 100 units/ml in the UK; dosage is
increases: adjusted for each patient.
- glucose uptake by muscle and fat. [Paul Langerhans (18471888), German pathologist]
- glycogen and protein synthesis. See also, Glycolysis
- fat synthesis and deposition.
- potassium uptake by cells. Intensive care, costs of, see Costs of intensive care
decreases:
- glycogen breakdown and gluconeogenesis. Intensive care follow-up. Programme of ward visits,
- fat and protein breakdown. outpatient clinics and support groups for patients dis-
- hepatic ketone body synthesis. charged from ICUs. Results in improved communication
Thus lowers blood glucose levels and increases between ICU and ward staff, and may prevent readmis-
glucose utilisation. Binds to the extracellular portion sion of patients to ICU through early detection of com-
of the transmembrane insulin receptors (tyrosine plications. Clinic appointments allow better assessment
kinase family), causing autophosphorylation of intra- of the patients post-ICU quality of life and the identifi-
cellular enzymes. cation of late psychological (e.g. anxiety, depression,
Insulins for therapeutic administration (e.g. in diabetes memory loss) and physical complications (e.g. critical
mellitus) are now most commonly produced by recom- illness polyneuropathy, impotence, poor balance, voice
binant genetic engineering; older preparations were changes and skin, hair and nail disorders) of intensive
derived from bovine or porcine pancreatic extract. care treatment not usually detected during the ICU stay.
Substitution/deletion of amino acids at specific sites of Specific problems include the undesirable effects of
the insulin molecule confers different properties with sedation withdrawal (e.g. exaggerated sympathomimetic
regard to onset and duration of action, mostly via altered effects, phobias, perceptual disorders) and post-traumatic
absorption from the injection site. Changing from one stress disorder. Physical status can be measured using
type to another, especially from bovine to human, may pulmonary function testing. Physical and psychological
result in hypoglycaemia. progress can be monitored over serial appointments.
Usually administered sc; may also be injected iv, im Dowdy DW, Eid MP, Sedrakyan A, etal (2005). Inten-
and intraperitoneally. Recently an inhaled form has been sive Care Med; 31: 61120
developed. Insulin pumps that deliver a continuous infu-
sion sc with additional calculated boluses depending on Intensive care, history of. Closely linked to the history
blood glucose levels are increasingly used. of anaesthesia, CPR, pain relief and monitoring. Modern
Generally classified according to their onset and techniques originate from respiratory care units in 1940
duration of action: 1950 along with developments in IPPV and CPR. Coro-
short-acting: nary care units were the first specialised units, set up in
- insulin lispro: recombinant human insulin ana- the 1960s.
logue with a lesser tendency to form hexamers in Major developments relating to ICUs include:
solution (responsible for slowing uptake). Acts various tank ventilators described and used: 1800s.
within 1530min of sc injection with duration of iv salt solutions first used to treat cholera: 1830s.
action 13h. concept of keeping all patients requiring special
- insulin aspart: recombinant human insulin ana- attention and nursing in one place pioneered by
logue; rapidly dissociates into monomers and Florence Nightingale: 1852.
dimers after injection, resulting in rapid absorp- curare used in the treatment of tetanus: 1872.
tion. Acts within 1020min of sc injection with blood gas interpretation performed: 1872.
duration of action 35h. venous pressures measured in humans: 1902.
- insulin glulisine: similar properties to insulin pulse oximetry described: 1913.
aspart. modern oxygen therapy introduced by Haldane:
- soluble insulin. Acts within 3060min of sc injec- 1917.
tion, with effects lasting up to 8h (half-life is haemodialysis described: 1940s.
5min after iv injection, with effects lasting worldwide poliomyelitis epidemic in the 1950s.
30min). Used for emergency treatment of hyper- Early tracheostomy, chest physiotherapy and
glycaemia and perioperatively; also to lower manual IPPV by medical students used in Copen-
plasma potassium in hyperkalaemia. When added hagen in 1952 resulted in the establishment of the
to iv infusions, adequate mixing is essential to first ICU by Ibsen: 1953.
prevent uneven administration. May be adsorbed first clinical description of brainstem death: 1959.
on to the infusion set plastic. modern CPR developed: 1960s.
310 Intensive Care Medicine

ARDS described: 1967. High-frequency ventilation Intensive care, outcome of. Survival from ICU admis-
described and developed in the 1970s. sion is influenced by:
Intensive Care Society formed in the UK; Society patient factors: age, pre-existing morbidity, physio-
of Critical Care Medicine formed in the USA: 1970. logical reserve, genetic makeup.
critical care training programmes commenced in disease factors: type, site, severity.
Canada and the USA: 1970s. treatment factors: available therapies, appropriate
intermittent mandatory ventilation introduced: usage, response to therapy.
1971. organisational factors: early referral/admission,
bedside pulmonary artery catheterisation described; resources, quality of ICU care.
journal Critical Care Medicine first published: 1972. Scoring systems (e.g. APACHE) are used to estimate
Intensive Care Medicine first published: 1975. the risk of hospital mortality for a group of patients.
first conference of UK Royal Colleges on diagnosis Mortality in ICU varies between ICUs and is dependent
of brainstem death: 1976. upon patient population and case mix factors. In the UK,
haemofiltration introduced: 1977. unadjusted ICU mortality varies between about 11%
APACHE, SAPS and MPM severity of illness and 30%; post-ICU in-hospital mortality varies between
scoring systems described: 1980s. about 20% and 45%.
European Society of Intensive Care Medicine There is an increasing awareness that other outcome
formed: 1982. measures, such as post-ICU morbidity and quality of life,
Resuscitation Council (UK) formed: 1982. are also important.
etomidate found to cause adrenal suppression in See also, Intensive care follow-up; Mortality/survival pre-
intensive care patients if used as an infusion: 1983. diction on intensive care unit
British Association of Critical Care Nurses formed:
1984. Intensive Care Society. British society founded in 1970,
first CEPOD report: 1987 (see National Confiden- for the furtherance of intensive care medicine. Aims
tial Enquiry into Patient Outcome and Death). include the promotion of education and research, defin-
European Resuscitation Council formed; European ing standards of intensive care and providing informa-
Diploma in Intensive Care Medicine held: 1989. tion on the availability, coding and costing of care to its
International Liaison Committee on Resuscitation members, the Department of Health and NHS Execu-
formed: 1992. tive. Currently has over 2400 members, the majority of
Intensive Care National Audit and Research Centre whom are anaesthetists.
established: 1994.
Intercollegiate Board for Training in Intensive Care Intensive care, training in. Previously obtained in the
Medicine formed; first running of UK Intensive UK during anaesthetic posts or by ad hoc arrangements
Care Diploma examination: 1998. by individual medical/surgical trainees; now coordinated
intensive care medicine granted specialty status by by the Faculty of Intensive Care Medicine (formerly the
Specialist Training Authority: 1999. Intercollegiate Board for Training in Intensive Care
creation of care bundles summarising best practice: Medicine), comprising representatives of seven Royal
early 2000s. Colleges and the Intensive Care Society. Recommenda-
first programmes towards Certificate of Completion tions include:
of Specialist Training in Intensive Care Medicine training undertaken only in ICUs accredited by the
commenced: 2002. Faculty.
Faculty of Intensive Care Medicine established at educational adviser for Intensive Care Medicine
the Royal College of Anaesthetists: 2010. (ICM) in each area of the UK.
[Florence Nightingale (18201910), English nurse] local educational supervisor in each ICU.
See also, Anaesthesia, history of; individual topics structured training in ICM during undergraduate
medical training.
Intensive Care Medicine. Official journal of the Euro- set periods of training for doctors:
pean Society of Intensive Care Medicine and European - junior doctors intending careers in acute hospital
Society of Paediatric Intensive Care, originally pub- specialties: 3 months training.
lished in 1975 as the European Journal of Intensive Care. - doctors intending careers in intensive care:
minimum of 6-month modules in each of medi-
Intensive Care National Audit and Research Centre cine, anaesthesia and intensive care (Step I
(ICNARC). Charitable company established in the UK training).
in 1994 with funding from the Department of Health to - prospective ICU directors: 2-year Step II
develop and undertake comparative audit and evalua- programme.
tive research in intensive care. Its development results The Faculty oversees dual accreditation on completion
directly from the Intensive Care Societys study of the of training programmes (i.e. Certificate of Completion
APACHE II severity of illness system. Now a non-profit- of Specialist Training [CCST] in Medicine/ICM,
making organisation, funded primarily by research Anaesthesia/ICM or Surgery/ICM) and the Diploma in
grants and subscription of ICUs to ICNARCs Case Mix Intensive Care Medicine.
Programme. Has developed an ICU coding method gen-
erated from data from over 10000 patients admitted to Intensive care unit (ICU). Modern techniques origi-
26 UK ICUs; the system describes over 700 conditions nate from postoperative recovery units and respiratory
categorised by body system, anatomical site, physiological/ care units in 1940s50s along with developments in
pathological process and condition. IPPV and CPR. Coronary care units were the first spe-
Harrison DA, Rowan KM (2008). Curr Opin Crit Care; cialised units, set up in the 1960s. An ICU usually pro-
14: 50612 vides 12% of total hospital beds, although factors
 Intercostal nerve block 311

affecting this proportion include the number of operat- Problems may be related to:
ing theatres, the type of surgery (e.g. surgery such as original condition.
cardiac surgery and neurosurgery has greater require- multiple organ failure; may follow many disease
ments), location of the hospital (e.g. near major motor- processes (e.g. renal failure and ARDS are common
ways), the overall provision of ICUs within the region in critical illness of any cause). Prognosis worsens
and the presence of an accident and emergency depart- as more organ systems are involved.
ment. In general, the unit should have the capacity to infection and sepsis.
accept around 95% of all appropriately referred cases adequate nutrition, and fluid and electrolyte balance.
and bed occupancy should be 6070%. Units larger than gastric ulceration (stress ulcers). Prophylaxis is as
10 beds should be subdivided into specialised units; for peptic ulcer disease; proton pump inhibitors and
those smaller than four beds are felt to be uneconomic. H2 receptor antagonists are most commonly used.
Distinction is no longer made between ICU and HDU immobility: DVT and decubitus ulcers may occur.
beds (most units now have a mix of beds), with defined Prophylactic sc heparin is usually administered, and
levels of critical care provided according to the type of pressure area care and physiotherapy instituted.
support required. sedation.
Design considerations: Other considerations relate to the cost of intensive care,
2
size of unit/bed space (approximately 20m sug- consent, and the ethics and audit of ICU practice.
gested per patient). Adequate bed separation See also, Care of the critically ill surgical patient; Intensive
is important for infection control. Provision of care follow-up; Intensive care, history of; Medical emer-
cubicles (e.g. one per six open beds) is necessary gency team; Postoperative care team; Safe transport and
for isolation of infectious/immunocompromised retrieval team; Selective decontamination of the digestive
patients. tract; Transportation of critically ill patients
proximity to theatres, accident and emergency
department, X-ray and laboratory facilities. Intensive care unit, transport to, see Transportation of
equipment: ventilators, monitoring, infusion pumps,
critically ill patients
cardiac arrest trolley. Adequate electrical points, gas
pipelines and suction.
lighting and basins.
Intercollegiate Diploma in Intensive Care Medicine
staff facilities, e.g. on-call room, kitchen.
(IDICM), see Diploma in Intensive Care Medicine
security measures, e.g. single entrance, closed circuit
television surveillance. Intercostal nerve block. Used for peri- and postopera-
Staffing requirements: tive analgesia, and for analgesia in patients with frac-
designated consultant with administrative responsi- tured ribs.
bility for the unit. 85% of ICUs are run by anaes- Technique:
thetists in the UK, although intensive care medicine may be performed with the patient sitting, with
is rapidly becoming an independent specialty (see shoulders flexed to pull the scapulae forwards
Intensive care, training in). (e.g. with the forearms resting on pillows), or in
adequate consultant sessions (15 per week for a unit the lateral position, with the side to be blocked
larger than four beds has been suggested, with more uppermost.
for larger units). identification of selected ribs: by counting down
resident trainee medical staff with responsibility from the spinous process of T1 (the most prominent
solely to the unit. palpable at the base of the neck) or up from L45
nursing staff (one nurse per patient required for (level with the iliac crests). The rib is palpated later-
24h/day). ally to the angle, about 610cm from the midline.
Patient selection criteria: Injection at the angle blocks the lateral cutaneous
according to the requirements in the defined levels branch of the intercostal nerve, that may be missed
of critical care. if injection is performed in the mid- or posterior
reasons for admission: the disease state should be axillary line.
potentially reversible. a needle (attached to a syringe of local anaesthetic
premorbid general health, age and mortality/ agent) is introduced at the lower edge of the rib,
survival prediction scores (although severity of directed cranially. It contacts bone, and is walked
illness scoring systems cannot be used to predict inferiorly until it slips off the ribs inferior surface.
outcome of intensive care in individual patients). It is then advanced 23mm. The patient is asked to
response to treatment so far. breath-hold to reduce lung movement and risk of
anticipated quality of life and the wishes of the pneumothorax.
patient and relatives. stretching of the overlying skin cranially before
availability of beds. needle insertion has been suggested: release of
Admission to ICU should be: stretch following insertion aids angling of the needle
before the patients condition reaches a point from tip into the subcostal groove.
which recovery is impossible. following aspiration to exclude intravascular place-
according to clear criteria to identify at-risk ment, 35ml of local anaesthetic agent is injected
patients. whilst moving the needle inwards and outwards
undertaken at senior level using appropriate trans- 12mm. Bupivacaine 0.250.5% with adrenaline
fer equipment. Unless the referral area is close to may provide analgesia lasting up to 12h; lidocaine
the ICU, full stabilisation (e.g. intubation, IPPV and 1% with adrenaline up to 24h. A catheter may be
inotropic therapy) should be undertaken before inserted for continuous infusion or intermittent
transfer. boluses.
312 Intercostal spaces

studies with dyes have shown extensive overlap of innermost intercostal muscle, attached to the ribs
injected solution to adjacent spaces (and even to inner surfaces.
the other side). Systemic absorption of solution is Intercostal nerves:
significant; maximal safe doses should not be ventral rami of spinal nerves T111. Each spinal
exceeded. nerve has dorsal and ventral roots, that join and
pneumothorax and puncture of intercostal blood then divide into dorsal and ventral rami. The dorsal
vessels may occur. Intra- or epidural spread via a rami supply the extensor muscles and skin of
dural cuff surrounding the proximal nerve is also the back.
possible. lie below the blood vessels in the intercostal space,
See also, Intercostal spaces; Interpleural analgesia running between the internal and innermost inter-
costal muscle layers.
Intercostal spaces. Contain the intercostal nerves and each (except the first) gives off a lateral cutaneous
blood vessels as they run around the width of the body branch anterior to the rib angles, and ends as the
(Fig. 85). anterior cutaneous branch.
Muscle layers between ribs: collateral branch arises at the angle, passing forward
external intercostal muscle, passing down and with main nerve.
forwards. Intercostal arteries:
internal intercostal muscle, passing down and back- two anterior and one posterior supply each space
wards. Becomes the internal intercostal membrane except the lower two (posterior only).
posterior to the rib angles. anterior arteries arise from the internal thoracic
artery or its terminal branch. They anastomose with
the posterior artery and its collateral.
posterior arteries arise from the superior intercostal
artery (first and second) or descending aorta. They
each give off a collateral branch.
Venous drainage is via two anterior and one posterior
intercostal veins, to internal thoracic and azygos veins.

Intercostal vein Interferometer, see Gas analysis

External intercostal Intercostal artery
muscle Intercostal nerve Interferons, see Cytokines
Internal intercostal
muscle
Interleukins, see Cytokines
Innermost intercostal
muscle Intermittent-flow anaesthetic machines. To be distin-
guished from apparatus used for draw-over techniques,
in which the patients own inspiratory effort causes gas
flow. Intermittent-flow machines provide gas flow usually
on demand, i.e. when triggered by the patients inspira-
tion, but are more sophisticated than simple demand
valves. Allow mixing of gases, usually O2 and N2O, and
Nerves Arteries addition of volatile agents using conventional vaporisers.
External intercostal muscle Dorsal branch of posterior
Minnitts machine (described in 1933) using an N2O cyl-
intercostal artery inder with indrawn air was used for analgesia in labour.
Inspiration reduces pressure within the apparatus,
Dorsal ramus Posterior moving a valve and allowing gas flow. In the McKesson
intercostal artery machine, the force opposing fresh gas flow may be
adjusted, so that continuous low flow may be provided
if required, between breaths. Further adjustment pro-
vides continuous high flow, as with conventional anaes-
thetic machines.
Ventral Some machines feature O2 warning devices, O2 flushes
ramus and valves to cut off N2O in case of potentially hypoxic
gas mixtures.
Traditionally used for dental surgery, but less com-
Lateral cutaneous branch
monly used now because of unfamiliarity, inaccuracy of
flow rates and gas composition, and relative lack of
Internal intercostal muscle
safety features.
[Robert J Minnitt (18891974), Liverpool anaesthetist]

Intermittent mandatory ventilation (IMV). Ventila-

tory mode used to assist weaning from ventilators. A
Anterior cutaneous Internal thoracic artery mandatory minute volume is preset and delivered by the
branch ventilator, but the patient is allowed to breathe sponta-
neously between ventilator breaths. As the patient
Fig. 85 Anatomy of intercostal spaces weans, the proportion of minute volume delivered by the
 Intermittent positive pressure ventilation 313

ventilator may be reduced, usually by reducing the ven- anaesthesia:

tilator rate. - when neuromuscular blockade is required;
IMV reduces average intrathoracic pressures and risk often performed when tracheal intubation is
of barotrauma. The patients progress may be monitored indicated.
by counting the spontaneous respiratory rate. - thoracic surgery.
Some ventilators will not deliver positive pressure - when ventilation is inadequate.
breaths within a certain period of spontaneous breaths, - to control arterial PCO2.
to prevent over-distension of the patients lungs and - to reduce requirement for inhalational agents, e.g.
barotrauma (synchronised intermittent mandatory in cardiovascular disease.
ventilation). Others simply incorporate a pressure- - to ensure adequate air entry, e.g. in respiratory
relief valve. disease.
Although the weaning process is not shortened, Technique:
IMV allows it to start earlier and be monitored more usually via tracheal intubation, tracheostomy or
easily whilst requiring less sedation, and reducing risks LMA, but it may be performed via facemask.
of IPPV. manual ventilation was formerly used extensively;
ventilators are now widespread. Injector techniques
Intermittent negative pressure ventilation (INPV). may also be used.
Advocated in the 1800s as a means of controlled ventila- a tidal volume of 1015ml/kg, at a rate of 1012
tion without the adverse effects of IPPV, although the breaths/min, is commonly used, ideally adjusted
latter were then overestimated. Tank ventilators (iron to arterial (or end-tidal) PCO2. PEEP is often
lungs) were described first, then cuirass types; motor- applied to reduce alveolar collapse and atelectasis.
driven devices were used in the 1930s. Negative end-expiratory pressure is no longer
Avoids the risk of barotrauma and other dangers of recommended.
IPPV, whilst allowing the respiratory muscles to rest. Mean intrathoracic pressure is lowest with accel-
Does not require tracheal intubation, although the risks erating gas flow, but ventilation is uneven. Ventila-
of regurgitation and aspiration are still present. Indraw- tion is more uniform with decelerating flow, but
ing of the soft tissues of the neck may result in upper mean pressure is highest. Inspiratory:expiratory
airway obstruction. Sedation is not required. Continuous ratio of 1:2 is usually employed but may be varied
end-expiratory negative extrathoracic pressure has according to clinical requirements.
similar beneficial effects to PEEP, but without its neuromuscular blockade is usually employed;
adverse effects. deep anaesthesia using volatile agents may also be
Largely superseded by IPPV, but still used for chronic used, combined with opioid analgesic drugs and
ventilation, e.g. domiciliary night-time ventilation for hypocapnia to suppress respiratory drive. Sedative/
neuromuscular disease; it has been used to aid weaning opioid infusions are commonly used in ICU (see
from prolonged IPPV. Sedation).
The Hayek oscillator, first described in the late 1980s, monitoring is important to ensure adequate ven
consists of a clear plastic cuirass that fits over the chest tilation and gas exchange, and to detect
and abdomen, connected to a power unit with wide-bore disconnection.
tubing. A wide range of frequencies (usually 30300Hz) Physiological effects/hazards:
and negative pressures may be generated. It has been cardiovascular effects, due to increased intratho-
used in respiratory failure, weaning, laryngeal surgery, racic pressure:
and perioperatively in cases of failed intubation. - reduced venous return and cardiac output; may
[Zamir Hayek, Israeli-born English neonatologist] reduce BP, especially in autonomic neuropathy or
hypovolaemia.
Intermittent positive pressure ventilation (IPPV). - increased pulmonary vascular resistance, reduc-
Form of controlled ventilation. Performed by Vesalius in ing right ventricular output.
1543 (via a tracheotomy in a pig) and Hooke in 1667 - reduced left ventricular compliance and filling,
(used bellows via a tracheotomy in a dog). Used initially especially with PEEP. Bulging of the right ven-
for CPR; later employed in animal experiments with tricle and direct effects of lung expansion are
curare by Waterton in the 1820s. Used in the late 1800s/ thought to be responsible.
early 1900s during anaesthesia, but wider acceptance - measured CVP is raised, and venous drainage
accompanied the introduction of neuromuscular block- from head and neck is reduced. ICP may increase.
ing drugs in the 1940s. Use in respiratory failure devel- respiratory effects:
oped largely following the 1952 Danish poliomyelitis - intrapleural pressure is about 5 cmH2O during
epidemic. expiration and up to + 5 cmH2O during inspira-
Modified forms (e.g. IMV, pressure control ventila- tion, in contrast to spontaneous ventilation.
tion, pressure-regulated volume control ventilation) are - lung compliance and FRC fall. Atelectasis occurs
mainly used in ICU during weaning from ventilators. in dependent lung tissue, increasing alveolar
High-frequency ventilation was developed from the arterial O2 difference and dead space. Adding
early 1970s. Non-invasive positive pressure ventilation PEEP and increasing tidal volume may reduce
has recently been introduced for patients with neuro- these effects.
muscular respiratory failure and COPD. others:
Indications: - renal: reduced arterial BP and increased venous
ICU: pressure lower renal perfusion. Glomerular filtra-
- respiratory failure. tion is reduced, and the renin/angiotensin system
- head injury. stimulated. Atrial natriuretic peptide secretion
- others, e.g. coma, post-CPR. is lowered and vasopressin secretion may be
314 Internal jugular venous cannulation

increased. The overall effect is reduced urine towards the ipsilateral nipple. When blood is
output (by up to 40%) and sodium retention. aspirated, the needle is lowered to align it more
- ileus is common with prolonged IPPV; the cause with the vein, and the cannula advanced or wire
is unclear but may involve changes in GIT neural inserted (Seldinger technique). If no blood is aspi-
activity and pressures. It may also be related to rated, the needle may be redirected slightly medi-
concurrent illness or drug therapy. ally. Some prefer to locate the vein with a small
- risks of tracheal intubation. needle first before using the larger introducer
- barotrauma, undetected disconnection. needle.
[Andreas Vesalius (15141564), German anatomist; - alternatively, a slightly lower approach involves
Robert Hooke (16351703), Curator of the Royal needle insertion at the apex of the triangle formed
Society, England] by the two heads of sternomastoid, a more reli-
See also, Intermittent negative pressure ventilation; Intu- able landmark when the carotid pulsation is weak
bation, tracheal; Ventilator-associated lung injury or absent (e.g. cardiac arrest).
low approach: the needle is introduced just above
Internal jugular venous cannulation. The internal the sternoclavicular joint and directed caudally. A
jugular vein lies deep to the sternomastoid muscle, and higher incidence of pneumothorax may result from
follows a course from just anterior to the mastoid process this approach.
to behind the sternoclavicular joint (Fig. 86). Cannula- The routine use of ultrasound probes for location of the
tion may be performed at a number of sites; the most vein is now recommended by NICE.
common are outlined below. See also, Central venous cannulation, for complications
Technique: and comparisons with other techniques
head-down position distends the vein and reduces
the risk of air embolism. The head is turned to the International classification injury severity score
contralateral side. Aseptic techniques are used. (ICISS). Trauma scale based on the International Clas-
the distended vein may be palpable (or even visible) sification of Diseases, 9th edition (ICD-9). Has the
in thin subjects, lateral to the carotid pulsation. advantage that most hospitals use the ICD for routine
a right-side approach is usually employed, since admission and discharge coding. Has been used for
the right internal jugular vein, superior vena cava predicting survival, costing treatment and assessing
and right atrium are more directly aligned than on outcome. Initial trials suggest it is superior in this respect
the left. to the injury severity score and trauma revised injury
local anaesthetic is used if the patient is awake. severity score.
high approach: Rutledge R, Osler T, Emery S, Kromhout-Schiro S
- the carotid pulsation is located level with the (1998). J Trauma; 44: 419
cricoid cartilage (C6). With the fingers of one
hand guarding the artery, the needle is introduced International Liaison Committee on Resuscitation
just laterally, angled at 30 to the skin and directed (ILCOR). Formed in 1992 to provide a forum for
liaison between principal resuscitation organisations
worldwide, producing its first advisory statements in
1997. Currently comprises the American Heart Associa-
tion, the European Resuscitation Council, the Heart
and Stroke Foundation of Canada, the Australian and
New Zealand Resuscitation Council, the Resuscitation
Councils of Southern Africa, the Inter American Heart
Foundation and the Resuscitation Council of Asia. It
aims to provide consensus opinions on all aspects of
resuscitation, thereby producing consistent international
guidelines.

Sternomastoid International normalised ratio, see Coagulation

muscle studies
Carotid artery
Interonium distance. Distance between quaternary
Phrenic nerve
ammonium groups in molecules of non-depolarising
External jugular vein neuromuscular blocking drugs. Thought to relate to drug
Internal jugular vein activity in blocking acetylcholine receptor sites at differ-
Brachial plexus ent locations; drugs with short interonium distances
show a tendency for ganglion blockade, while those
with longer distances favour neuromuscular junction
blockade.
Lee C (2001). Br J Anaesth; 87: 75569
Clavicle
Interpleural analgesia. Injection of local anaesthetic
Subclavian artery Pleura 1st rib agent into the pleural cavity, performed for analgesia
Subclavian vein after thoracic and upper abdominal surgery and in rib
fractures. Unilateral pain is the most suitable indication.
Fig. 86 Anatomy of right internal jugular vein An epidural catheter may be placed either under direct
 Intra-aortic counter-pulsation balloon pump 315

vision during thoracotomy, or via an epidural needle as Intra-abdominal pressure (IAP). Usually measured
follows: using a closed urinary drainage system, with the bladder
the midaxillary line or ~10cm from the dorsal acting as a transducer. Has also been measured using
midline, in the 4th8th interspace is usually nasogastric or gastrostomy tubes. IAP is normally sub-
employed. atmospheric to zero relative to the symphysis pubis. In
the pleural space is identified using a loss of resis- animals, IAP > 10mmHg has potentially deleterious
tance syringe, allowing the syringe plunger to be effects on hepatic arterial flow, and > 20mmHg on mes-
drawn in by the negative interpleural pressure, or a enteric and bowel mucosal blood flow, portal venous
catheter is pushed through the needle as the latter flow and intestinal barrier function. In humans, there
is advanced; unobstructed passage of the catheter seems to be a strong relationship between IAP >
occurs when the parietal pleura is punctured. Alter- 20mmHg and subsequent development of renal failure.
natively, to avoid entrainment of air when the There is consensus that abdominal decompression
syringe is removed from the needle, a continuous should occur at levels of IAP > 2025mmHg.
infusion of saline attached via a three-way tap to Malbrain ML, Cheatham ML, Kirkpatrick A, etal
the epidural needle allows demonstration of the (2006). Intensive Care Med; 32: 172232
negative pressure by free flow of saline; the catheter Cheatham ML, Malbrain ML, Kirkpatrick A (2007).
may be threaded though the needle without detach- Intensive Care Med; 33: 95162
ing the saline infusion. See also, Abdominal compartment syndrome
advancement of the needle is during the expiratory
phase. Intra-abdominal sepsis. The leading cause of death in
830ml of 0.250.5% bupivacaine with adrenaline general surgical practice. May involve a wide variety of
produces up to 24 h analgesia. 0.10.5ml/kg/h infu- anaerobic and aerobic organisms; bacterial translocation
sion may also be used. Gravity and positioning may has been implicated in many cases.
be used to extend the block if inadequate. Solution Caused by:
may also be instilled through a pleural drain. Mech- spontaneous intra-abdominal disease (60%), e.g.
anism of analgesia is unclear, but is thought to perforated appendix, diverticulitis, primary liver
involve blockade of intercostal nerves. abscess, perforated colonic cancer, pancreatitis.
Complications are uncommon, and include pneumotho- trauma (10%).
rax, haemorrhage, local anaesthetic toxicity (maximal complications of abdominal surgery (30%), espe-
levels occur within 20min of bolus injection), phrenic, cially colonic and biliary.
recurrent laryngeal or sympathetic nerve blockade. Diagnosis:
Dravid RM, Paul RE (2007). Anaesthesia; 62: 103949; clinical: fever, leucocytosis, localised tenderness.
114353 ultrasound: fluid collection may be demonstrated.
radiological:
Interstitial fibrosis, see Pulmonary fibrosis - plain abdominal X-ray may reveal abnormal fluid
and/or gas collections.
Interstitial fluid. Fluid compartment comprising most - contrast studies may reveal filling defects, suggest-
of the ECF. Volume is approximately 9.5 litres, about ing abscess.
14% of body weight of an average man; it is determined - radiolabelled leucocyte scan or gallium-67
by subtracting plasma volume from ECF volume. imaging: may reveal collections.
See also, Fluids, body, for composition. - abdominal/pelvic CT scan: in general, more sensi-
tive than the above.
Intestinal obstruction. Mechanical obstruction of If sepsis is strongly suspected, exploratory laparotomy/
transit of GIT contents, to be distinguished from ileus. laparoscopy should be performed, even in the absence
May be caused by impaction within the lumen (e.g. of positive imaging tests.
faeces, foreign object), narrowing arising within the GIT Management:
wall (e.g. tumours, strictures) or compression from prevention: maintenance of careful asepsis during
outside the GIT wall (e.g. strangulation, adhesions). In surgery; preoperative bowel preparation; prophy-
acute obstruction, gas and intestinal secretions accumu- lactic antibiotics.
late, causing distension of the GIT proximal to the treatment: general resuscitation; antibiotic therapy;
obstruction, resulting in pain, increased bowel activity drainage by open surgical procedure or percutane-
and vomiting (especially in high obstruction). Dehydra- ously using CT/ultrasound guidance.
tion and electrolyte disturbances may rapidly develop. If See also, Peritonitis
severe and unrelieved, obstruction may lead to bowel
ischaemia, necrosis and perforation. Abdominal X-rays Intra-aortic counter-pulsation balloon pump. Device
may reveal dilated loops of bowel with fluid levels. used to support cardiac output by inflating a balloon
Treatment includes nasogastric intubation and iv within the descending aorta at the beginning of diastole,
fluid replacement; surgery is often required. Anaesthetic with deflation immediately before systole. Introduced
and ICU considerations are those of emergency surgery percutaneously (e.g. via the femoral artery) and inflated
in general, especially relating to dehydration, the risk with helium or CO2. Triggered and timed according to
of aspiration of gastric contents and sepsis if perforation the ECG and arterial waveform. Increases coronary and
occurs. tissue blood flow, with reduced afterload and left ven-
Chronic obstruction presents with distension and tricular work; i.e. increases myocardial O2 supply whilst
constipation; emergency surgery is less often indicated, decreasing demand.
although acute-on-chronic obstruction may occur. Mal- Used as a temporary measure, e.g. in left ventricular
nutrition is more likely to be present than in acute failure and cardiogenic shock pre/post cardiac surgery
obstruction. or after MI. Complications include: trauma and
316 Intra-arterial regional anaesthesia

haemorrhage during insertion; aortic dissection and - papilloedema (may take 24h of raised ICP for it
rupture; distal thrombus; embolism and ischaemia; and to occur), impaired consciousness, hypertension
damage to platelets and red cells. and bradycardia (Cushings reflex) as ICP contin-
ues to rise.
Intra-arterial regional anaesthesia. Obsolete method - hypotension, coma, irregular respiration or
of producing anaesthesia of the arm, described in 1908 apnoea, fixed and dilated pupils.
by Goyanes, by injecting local anaesthetic agent into the Raised ICP is caused by increased volume of the fol-
brachial artery, a tourniquet having been inflated proxi- lowing compartments:
mally to above systolic BP. blood:
[J Goyanes (18761964), Spanish surgeon] - increased cerebral blood flow due to cerebral
vasodilatation, e.g. with use of volatile anaesthetic
Intracellular fluid. Similar in composition between dif- agents.
ferent cells; thus considered a single fluid compartment - impaired venous drainage, e.g. coughing,
comprising about 28 litres (40% of body weight) in an straining, obstructed jugular veins, head-down
average man. Determined by subtracting ECF from total position.
body water (measured using a dilution technique with brain:
deuterium oxide). - tumour, abscess, haematoma.
See also, Fluids, body, for composition, etc. - cerebral oedema.
CSF: as for hydrocephalus.
Intracranial haemorrhage, see Cerebrovascular acci- Rarely, benign (idiopathic) intracranial hypertension is
dent; Extradural haemorrhage; Head injury; Subarach- associated with none of the above, especially in young
noid haemorrhage; Subdural haemorrhage women. It may cause permanent visual impairment due
to optic nerve damage. Its management includes thera-
Intracranial pressure (ICP). Pressure exerted by the peutic lumbar puncture and CSF drainage, corticoste-
CSF in the frontal horns of the lateral ventricles of the roids, acetazolamide and shunt insertion.
brain. Normally 715mmHg (12 kPa) supine; fluctua- Treatment of raised ICP involves reduction in
tions may be revealed by ICP monitoring. Because the volume of:
skull is rigid, and its contents incompressible, ICP blood:
depends on the volume of intracranial contents: nor- - facilitation of venous drainage: head-up posture,
mally 5070ml blood (57%), 50120ml CSF (512%), adequate sedation/relaxation, avoiding jugular
and 1.4kg brain tissue (8085%) (see MonroKellie compression/kinking.
doctrine). - hyperventilation to arterial PCO2 3.54 kPa
Effects of increased intracranial volume: to produce cerebral vasoconstriction may be
movement of CSF into the spinal canal, increased employed as a temporary measure in life-
absorption of CSF into the venous circulation, and threatening raised ICP. However, effectiveness is
venous sinus compression. Thus ICP is maintained short-lived and it may cause cerebral ischaemia
at near-normal levels initially. by impairing cerebral oxygen delivery; mainte-
eventually, compensatory mechanisms are over- nance of low normocapnia (PCO2 44.5 kPa) is
whelmed; small changes in volume are then accom- preferred.
panied by large increases in ICP (Fig. 87). brain:
as ICP rises, cerebral perfusion pressure and cere- - surgical decompression.
bral blood flow are decreased. When venous blood - diuretics and corticosteroids in certain circum-
vessels are obstructed, brain parenchymal swelling stances (see Cerebral oedema).
occurs. Regional ischaemia, structural distortion - fluid restriction to 1.52 l/day is often instituted.
and coning may follow. During surgery, raised ICP CSF: drainage, e.g. via the lateral ventricle. Long-
is prevented by the open skull, but the brain may term shunts as for hydrocephalus.
bulge and hinder surgery or closure. Effects of anaesthetic agents on ICP:
clinical features: iv agents: barbiturates, etomidate, propofol, benzo-
- headache, nausea/vomiting, confusion. Headache diazepines: reduce ICP. Opioids: no change or
is classically worse in the early morning and exac- reduction, if normocapnia is maintained. Ketamine
erbated by stooping or straining. increases ICP.
inhalational agents: halothane, enflurane, isoflu-
rane, sevoflurane and desflurane: cause a dose-
dependent increase in ICP via increased cerebral
blood flow and volume. At high concentrations
cerebral vessel reactivity to CO2 is lost and hyper-
Intracranial pressure

ventilation will not counteract the effect. N2O also

increases ICP via increased blood flow, or if air is
contained in cavities within the skull, e.g. following
surgery, head injury.
others: non-depolarising neuromuscular blocking
drugs cause no change in ICP since they do not
cross the bloodbrain barrier. Suxamethonium may
cause a transient increase (57mmHg) during fas-
Intracranial volume
ciculation, due to an increase in intrathoracic pres-
Fig. 87 Effects of increasing intracranial volume on intracranial sure. ICP is increased by laryngoscopy and tracheal
pressure intubation.
 Intraocular pressure 317

hypotensive drugs: ICP may increase following underlying condition, speed of deterioration and clinical
sodium nitroprusside and nitrates, due to vasodila- situation.
tation and increased intracranial blood volume. No [Nils Lundberg (19082002), Swedish neurosurgeon]
rise is associated with trimetaphan. Lavinio A, Menon DK (2011). Curr Opin Anesthesiol;
Anaesthesia for patients with raised ICP: as for 24: 11723
neurosurgery.
Lescot T, Abdennour L, Boch AL, Puybasset L (2008). Intractable pain, see Pain; Pain management
Curr Opin Crit Care; 14: 12934
See also, Cerebral protection/resuscitation Intradural . . ., see Spinal . . .

Intracranial pressure monitoring. Indications vary Intramucosal pH, see Gastric tonometry
between units but include any cause of coma and raised
ICP, most commonly head injury, intracranial haemor- Intraocular pressure (IOP). Normally 1.32 kPa (10
rhage, postoperatively and encephalopathies. Associated 15mmHg), increased in glaucoma. Important during
with significant risk of infection, especially with > 3 open ophthalmic surgery because of the risk of expul-
days use. sion of intraocular contents and haemorrhage, with sub-
Types of monitoring: sequent distortion of anatomy, scarring and loss of vision.
extradural fibreoptic probe, laid between the dura Related to:
and skull via a burr hole. Easy to position, with low external pressure on the eye:
infection rates. CSF drainage is impossible, and - from facemask or leaning on the eye.
accuracy is less reliable. Fully implantable devices - retrobulbar haematoma.
have been described. - extrinsic muscles.
subarachnoid screw, applied via a burr hole. Easy to - venous congestion of orbit.
position, but infection rate is higher. More accurate scleral rigidity: increased in severe myopia and in
unless oedema is present. CSF drainage is some- the elderly.
times possible. Subdural catheters have also been intraocular contents:
described. - choroidal blood volume:
ventricular drain, placed during craniotomy, - increases with arterial PCO2 and hypoxaemia,
although the ventricle may be difficult to cannulate and vasodilatation.
in the presence of brain swelling. Also allows thera- - increases transiently with acute rises in
peutic drainage of CSF. Infection risk is the highest systolic BP; falls at systolic pressure of under
(35%), especially if in situ for over 3 days. Fibre- 8090mmHg.
optic devices may also be used, or a catheter - increases with CVP, e.g. due to straining, cough-
attached to a subcutaneous device for percutaneous ing, vomiting, head-down or prone position.
puncture, for chronic use. - aqueous humour:
intracerebral transducer, placed within brain - formed by the choroidal plexus of the posterior
tissue itself. chamber, at about 0.08ml/h. A small amount is
Devices are flushed infrequently using small volumes formed in the anterior chamber.
(under 0.2ml). Output is best displayed as a continuous - passes through the pupil to the anterior
recording, ideally with simultaneous calculation of cere- chamber; drains from the angle between the iris
bral perfusion pressure. Injecting small volumes into and cornea via the canal of Schlemm into the
the ventricular system may be used to calculate ven- venous circulation.
tricular compliance or pressure/volume index (volume - reduced by acetazolamide, although it also
required to raise CSF pressure by a factor of 10); increases choroidal blood volume. Also reduced
however, this is not routinely performed. The waveform by oral glycerol and meiosis. Control is impor-
obtained resembles the arterial waveform, correspond- tant in glaucoma, but less so during surgery.
ing to the pulsation of large vessels within the brain. - vitreous humour: may be reduced by administra-
The waveform also varies with respiration, reflecting tion of mannitol 0.51.5g/kg iv, 45min preopera-
changes in CVP. Mean ICP is calculated in a similar tively. Urinary catheterisation is usually required.
way to MAP and is normally 715mmHg (12 kPa) in Sucrose 50% 1g/kg is shorter acting.
the supine position. - other structures, e.g. lens.
Three variations in ICP waveform (Lundberg waves) - sulphur hexafluoride (SF6) is sometimes injected
have been described: into the vitreous in retinal surgery to splint the
A (plateau) waves: amplitude 50100mmHg, they retina; N2O markedly expands the SF6 volume
last 520min. Associated with cerebral vasodilata- and increases IOP by diffusing into the bubble
tion. Most common in patients with intracranial faster than SF6 diffuses out (blood/gas solubility
tumours and often represent severely reduced of N2O is over 100 times that of SF6). When N2O
intracranial compliance. is stopped at the end of surgery, IOP may decrease
B waves: amplitude < 50mmHg; occur at about 1/ markedly. N2O is therefore usually avoided.
min. Associated with changes in respiratory pattern. Atmospheric nitrogen diffuses into the bubble
Less useful clinically. Variations of B waves (ramp postoperatively, but its effect is smaller and slower
waves) are seen in hydrocephalus. because its blood/gas solubility is only 23 times
C waves: amplitude < 20mmHg; occur at 48/min. that of SF6.
Related to systemic vasomotor tone and BP. Not Effects of anaesthetic agents on IOP:
useful clinically. little effect, if any, of premedicant drugs.
Active management is usually advocated at pressures no effect of atropine, unless administered topically
exceeding 1530mmHg (23 kPa), depending on the to glaucomatous eyes (IOP may rise).
318 Intraosseous fluid administration

reduced by all iv induction agents except ketamine; returns to its original value unless expiration is forced or
propofol and etomidate cause a greater reduction resistance increased; it may then exceed zero.
than thiopental. During IPPV, pressure increases from the resting
reduced slightly by benzodiazepines and value, depending on the inflating pressure (usually by
neuroleptanaesthesia. 1020cm H2O). Thus it usually exceeds zero during
reduced by all volatile agents; the mechanism is inspiration. Increased by CPAP and PEEP (i.e. towards
unclear. Unaffected by N2O. or beyond zero).
increased by suxamethonium, possibly via choroidal
vasodilatation and extrinsic eye muscle contraction, Intrathecal. . ., see Spinal . . .
although the increase in IOP still occurs when
the muscles are cut. The increase lasts only a few Intravenous anaesthetic agents. Development of
minutes. The use of suxamethonium in the presence drugs and iv techniques occurred later than for inhala-
of penetrating eye injury is controversial (see Eye, tional anaesthetic agents, but iv induction of anaesthesia
penetrating injury). is usually preferred now because it is faster with less risk
non-depolarising neuromuscular blocking drugs of excitement or laryngospasm. Popularised in the 1930s
may lower IOP slightly. by Weese, Lundy and Waters, although Ore had used
Anaesthesia for open eye operations thus involves iv chloral hydrate in 1872. Subsequent agents include
avoidance of factors that increase IOP and use of tech- hedonal (1905), phenobarbital (1912), paraldehyde
niques and drugs that lower IOP, e.g. head-up tilt, hypo- (1913), bromethol (1927), hexobarbital (1932; the first
capnia, smooth anaesthesia. widely used iv barbiturate), thiopental (1932), hydroxy
IOP is estimated by measuring corneal indentation dione (1955), methohexital (1957), propanidid (1956),
by a weighted plunger, or by measuring the force -hydroxybutyric acid (1962), ketamine (1965), Althesin
required to flatten an area of cornea. (1971), etomidate (1973) and propofol (1986). Diethyl
[Friedrich Schlemm (17951858), German anatomist] ether has been injected iv.
Used for induction and maintenance of anaesthesia,
including TIVA, and for sedation. Many iv agents have
Intraosseous fluid administration. Infusion of fluids
also been given im or rectally. Benzodiazepines (e.g.
though a metal cannula into the bone marrow and
midazolam) are also used for induction, as are high doses
thence, via a system of non-collapsible veins, into the
of opioid analgesic drugs.
general circulation. Used in emergencies when intrave- May be classified thus:
nous access is not readily available. Previously reserved
rapid onset:
for the resuscitation of infants and children; adult
- barbiturates: thiopental, methohexital.
needles and insertion devices are now also routinely
- imidazole compounds: etomidate.
available. The upper tibia (anteromedial surface 13cm
- alkyl phenol: propofol.
below the tibial tuberosity) and proximal humerus are
- corticosteroids: Althesin, minaxolone, hydroxy
the most common sites chosen. A manual needle and
dione.
trocar kit may be used to pierce the thin bony cortex,
- eugenols: propanidid.
advancement continuing until a loss of resistance is felt.
slow onset:
Alternatively, a battery-powered drill may be used.
- ketamine.
Easy injection of saline without obvious subcutaneous
- benzodiazepines.
infiltration suggests correct placement. Aspiration of
- opioids.
marrow is not always possible, but if successful, samples Features of the ideal iv anaesthetic agent:
can be used for cross-matching. All standard drugs may
physical/chemical properties:
be given by this route; they should be flushed through
- chemically stable at room temperature and on
with 510ml saline to ensure they reach the circulation.
exposure to light; long shelf-life.
Fluids should be given under pressure to overcome
- water-soluble, not requiring reconstitution before
venous resistance. Osteomyelitis is the major complica-
use, nor any additives.
tion and can be minimised by sterile technique and
- compatible with iv fluids and other drugs.
by reverting to conventional venous cannulation follow-
pharmacology:
ing resuscitation. Compartment syndrome has been
- painless on injection, without causing thrombo-
reported.
phlebitis. Harmless if extravasated or injected
intra-arterially.
Intrapleural pressure. Pressure within the pleural - low incidence of adverse drug reactions.
cavity, perhaps better termed interpleural pressure. Mea- - smooth onset of anaesthesia within one arm
sured indirectly using a balloon catheter placed within brain circulation time, without unwanted move-
the lower third of the oesophagus (i.e. within the thorax ment, coughing or hiccups.
but outside the lungs). Normally negative, due to the - anticonvulsant, antiemetic and analgesic proper-
thoracic cages tendency to spring outwards, and the ties. No increase in cerebral blood flow, ICP or
lungs tendency to collapse inwards. In the erect posture intraocular pressure. Reduces CMRO2.
at normal resting lung volume, intrapleural pressure - no respiratory depression. Bronchodilator.
equals approximately 10cm H2O at the lung apex, - no cardiovascular depression or stimulation, or
2.5cm H2O at the base. arrhythmias.
Increases in magnitude as lung volume (and thus - predictable recovery, related to the dose injected.
elastic recoil) increases. During spontaneous ventilation, - rapid metabolism to non-active metabolites; i.e.
it thus becomes more negative during inspiration. Nor- non-cumulative.
mally changes by 34cm H2O, more if airway resistance - no impairment of renal or hepatic function or
is increased or breathing forceful. During expiration, it corticosteroid synthesis.
 Intravenous fluid administration 319

Table 26 Properties of iv anaesthetic agents

Agent Thiopental Methohexital Ketamine Etomidote Propofol Midazolam

Additives Sodium Sodium Benzethonium Propylene glycol Soya-bean oil

carbonate carbonate chloride emulsion
Aqueous solution + + + +
Approximate cost/induction dose in UK () 3 unavailable 24 12 24 24
Painful injection + + +
Rapid onset + + + +
Unwanted movement + +
Respiratory/cardiovascular depression + + +
Analgesic +
Vomiting + +
Steroid inhibition +
Rapid recovery + + + +
Emergence phenomena +
pKa 7.6 7.9 4.2 11 6.2
Protein-binding (%) 85 85 12 75 98 98
Volume of distribution (l/kg) 1.52.5 12 23 25 35 12
Distribution half-life (min) 26 56 1015 14 12 715
Elimination half-life (h) 510 24 23 15 15 25
Clearance (ml/kg/min) 24 1012 1820 1825 2530 611

- no emergence phenomena.
- no teratogenicity. 60
No currently available agent fulfils all of the above 50
% injected dose

(Table 26).
Agents should be injected slowly, titrated to effect 40
(except during rapid sequence induction), especially if 30
the patient has reduced cardiac output. Overdose is 20
easily produced by rapid injection of a large dose.
Following iv injection, brain levels depend on the 10
amount of drug crossing the bloodbrain barrier,
related to: 1 10 100
protein-binding.
Time (min)
ionisation; e.g. at pH of 7.4, 61% of thiopental and
over 90% of propofol is unionised. Vessel-rich tissue
cerebral blood flow: increased as a proportion of Vessel-intermediate tissue
cardiac output in hypovolaemia. Vessel-poor tissue
fat solubility: high for most anaesthetic agents; pro-
Blood
pofol and ketamine are particularly fat-soluble.
distribution, metabolism and excretion. Fig. 88 Fate of thiopental after iv injection
Recovery from, for example, thiopental occurs by redis-
tribution from vessel-rich tissues (brain, heart, liver, Practical considerations:
kidney; 7080% of cardiac output) to vessel-intermediate site of administration: usually forearm, since it is the
tissues (muscle, skin; 18% of cardiac output), thence least awkward for the patient. The arm or hand is
to fat (6%) and vessel-poor tissues such as ligaments preferred to the legs, since venous stasis is com-
(Fig. 88). Thus significant amounts of thiopental remain moner in the latter. Placement near joints or known
in the body after recovery, compared with more rapidly arteries is avoided when possible. Central venous
metabolised agents, e.g. propofol. cannulation is used for irritant or vasoactive
See also, Pharmacokinetics drugs, if peripheral cannulation is unsuccessful or if
long-term administration or CVP measurement is
Intravenous fluid administration. Described in the required.
1600s. Saline solutions were used sporadically in dehy- cannulation: venous filling is increased by gentle
dration due to cholera, diabetes mellitus and diarrhoea slapping, squeezing of the hand or immersion of the
in the 1800s. Infusions were widely used in World War I, limb in warm water. Intradermal injection of local
including acacia solution as a colloid. Bacterial and anaesthetic or use of EMLA reduces the pain of
chemical contamination and allergic reactions were insertion of large cannulae. Attempts are made to
common. Sterile fluids and administration sets became cannulate distal veins first, moving proximally if
available in World War II; investigation into fluid balance unsuccessful. Rarely, cut-down may be required:
since then has been prompted by subsequent wars, e.g. - an anatomically constant venous site is chosen,
Korea, Vietnam. Balanced fluid therapy was developed e.g. long saphenous vein (above and anterior to
in the 1950s1960s. the medial malleolus).
320 Intravenous fluids

- the vein is exposed and two ties placed around it; with a GTN patch applied topically. Addition of
only the distal one is tightened. heparin or hydrocortisone to the fluid bag has also
- the cannula is introduced and secured with the been used. Heparinoid cream may be applied to
proximal tie. existing phlebitis.
cannulae: plastic cannulae were developed in the interactions between infused drugs or fluids, espe-
1970s. Their general design is similar but flow char- cially if multiple infusions are used through a single
acteristics differ widely between different makes. cannula.
More recent designs incorporate protective mecha- air embolism.
nisms to prevent needlestick injury, e.g. a metal related to the iv fluid infused, e.g. hyponatraemia,
clip or plastic cover that automatically shields the pulmonary oedema.
sharp point when the needle is withdrawn from the when one cannula is used for more than one infu-
cannula. British Standard for determining flow rate: sion, temporary blockage of the cannula may lead
a constant pressure of 10 kPa is maintained using to one infusion (e.g. of a drug) retrogradely filling
a constant-level tank of distilled water at 22C. It the tubing of the second infusion (e.g. a saline infu-
is connected via 110cm tubing (inside diameter sion), especially if the former is driven by a pump.
4mm) to the cannula, with the distal 4cm and the When the obstruction is relieved, a bolus of drug
cannula horizontal. The volume of water is collected may be delivered instead of a saline flush; therefore
over at least 30s; an average of three readings is a non-return valve/connector should be used.
taken. Thus the flows are different from those Fluids may also be delivered into the circulation by
achieved clinically, but the values are useful for intraosseous fluid administration; other routes, e.g. rectal,
comparison between differently sized cannulae: im or sc administration (the latter two aided by hyal-
- 10G: 550600ml/min. uronidase), are rarely used now.
- 12G: 400500ml/min. See also, Venous drainage of arm
- 14G: 250360ml/min.
- 16G: 130220ml/min. Intravenous fluids. May be divided into colloids and
- 18G: 75120ml/min. crystalloids (Table 27).
- 20G: 4080ml/min. Simplistic effects of infused fluid on body fluid
Gauge (G) numbers are equivalent to those used for compartments:
needles. Colour-coding standard for iv cannulae: initial expansion of the vascular compartment.
- 14G: orange Extent and duration depend on whether it can
- 16G: grey freely cross the vascular endothelium; i.e. crystal-
- 18G: green loids do, colloids do so only slowly, e.g. gelatin solu-
- 20G: pink tions after a few hours. Colloids may draw water
- 22G: blue into the vascular space by osmosis in addition to the
- 24G: yellow volume infused (hence plasma expanders).
- 26G: black expansion of the interstitial fluid compartment as
giving sets: internal diameter is 4m, but increased fluids pass into it from the vascular compartment.
turbulence and resistance arise from extra length, Fluids distribute within the ECF thus: three-quarters
drip chambers and filter (170 m pore size). Non- in interstitial fluid, one-quarter in plasma.
blood giving sets have no filter or float, and are expansion of the intracellular space. Water moves
narrower and cheaper. across cell membranes by osmosis only if osmolality
syringe pumps, volumetric pumps, drip counters; on one side of the membrane changes. Thus, if saline
high pressures may occur with the former two if 0.9% is added to ECF, osmolality is unchanged, and
obstruction to flow occurs. Some syringe pumps thus no movement of water occurs; i.e. saline is con-
may empty rapidly if placed above the patient. fined to ECF. The dextrose in dextrose solutions is
microfiltration: not routinely used, but 0.2m filters rapidly metabolised after administration; the resul-
are claimed to reduce phlebitis, especially when tant free water then redistributes to both intracel-
repeated drug injections are given. They may also lular and extracellular compartments.
retain endotoxin and prevent air embolism. The Summary:
routine use of blood filters is controversial. colloids cause greater expansion of the vascular
Hazards: compartment for the volume infused, and are
during cannulation: haemorrhage, haematoma, ideally suited to replace plasma/blood losses.
trauma. saline 0.9% and Hartmanns solution expand ECF
extravasation: especially harmful if the fluid is irri- (three-quarters interstitial, one-quarter plasma)
tant, e.g. potassium or bicarbonate solutions, thio- and are ideally suited to replace ECF losses.
pental, antimitotic drugs. Flushing with saline, dextrose 5% expands total body water (one-third
hyaluronidase or corticosteroids has been suggested ECF, two-thirds interstitial). Thus only 1/12 infused
as treatment. volume of dextrose 5% remains in the vascular
thrombophlebitis: venous thrombosis accompanied compartment. The main use of dextrose is to replen-
by venous wall inflammation. Superficial thrombo- ish a water deficit; infusing pure water would cause
phlebitis does not lead to DVT. More common with haemolysis.
small veins and concentrated or irritant infusates. See also, Bicarbonate; Colloid/crystalloid controversy;
Reduced if infusion sites are changed regularly, e.g. Dextrans; Haemorrhage; Hypertonic intravenous solu-
2448-hourly. Features include pain, redness of the tions; Intravenous fluid administration
overlying skin and hardening of the vein; there may
be swelling and systemic features (e.g. pyrexia) if Intravenous oxygenator (IVOX). Intravascular gas
infection is involved. Infusion life may be prolonged exchange device, consisting of a 3040cm long bundle
 Intravenous regional anaesthesia 321

Table 27 Compositions of commonly used iv fluids (in mmol/l unless otherwise stated)

Fluid Na+ K+ Ca2+ Cl Other pH

Crystalloids*
Saline 0.9% (normal) 154 154 5.0
Dextrose 4%saline 0.18% 30 30 Dextrose 40g 45
Dextrose 5% Dextrose 50g 4.0
Hartmanns solution 131 5 2 111 Lactate 29 6.5
Bicarbonate
8.4% 1000 HCO31000 8.0
1.26% 150 HCO3 150 7.0

Colloids
Haemaccel 145 5.1 6.25 145 Gelatin 35g 7.4
Gelofusine 154 <0.4 <0.4 125 Gelatin 40g 7.4
Mg2+ <0.4
Hetastarch/pentastarch/tetrastarch 6% /10%
In 0.9% saline 154 154 Starch 60g/100g 5.05.5
In balanced solution 137140 4 02.5 110118 Mg2+ 11.5; acetate 034; malate 05
Albumin 4.5% < 160 <2 136 Albumin 4050g 7.4
Citrate < 15
Dextran
In saline 0.9% (as above) 60g dextran 70 or 100g 4.55
In dextrose 5% (as above) dextran 40 56

*All have an osmolality of 280300 mosmol/kg, except for bicarbonate 8.4% (200 mosmol/kg)

Osmolality ranges between approximately 280 and 320 mosmol/kg

of hollow gas-permeable polypropylene fibres (internal bupivacaine is contraindicated because of its

diameter 200 m), introduced into the superior and cardiotoxicity.
inferior venae cavae via the right internal jugular or Mechanism of action is unclear, but may include:
femoral veins. Was used in the 1990s for acute respira- compression by the tourniquet.
tory failure but its use was hampered by technical prob- ischaemia.
lems, e.g. obstruction of venous return, bleeding. No drug action on nerve trunks.
longer available. drug action on nerve endings.
IVRA is a potentially dangerous technique, involving
direct iv injection of local anaesthetic; therefore the
Intravenous regional anaesthesia (IVRA; Bier block). following must apply:
First described in 1908 by Bier, who injected procaine iv all equipment is checked for leaks and other defects.
into an exsanguinated portion of the arm between two the patient is prepared and starved as for any anaes-
inflated tourniquets, to provide distal analgesia. thetic procedure, with resuscitative drugs and
Modern technique (described in the 1960s): equipment available.
an iv cannula is placed in each hand. full monitoring is applied throughout.
the limb is exsanguinated by raising it with the rapid injection is avoided (may force solution past
brachial artery compressed, or by using a rubber the tourniquet).
bandage. injection near the antecubital fossa is avoided (solu-
a tourniquet is inflated around the upper arm to a tion may be forced into the systemic circulation).
value higher than systolic BP (twice systolic BP is the technique is used with caution in patients
usually quoted). with severe arteriosclerosis and hypertension,
local anaesthetic agent is injected slowly. since the tourniquet may not completely compress
a more distal tourniquet may be inflated after their arteries. Similar caution has been suggested in
510min and the original deflated, to reduce obesity.
discomfort. contraindication has been suggested in prepubertal
motor and sensory block occurs within 510min. children, since intraosseous vessels may allow local
for prolonged surgery, the cannula is left in situ. The anaesthetic to bypass the tourniquet.
cuff may be deflated after 6090min for 5min, the the tourniquet is not deflated for at least 20min.
arm re-emptied of blood and the tourniquet Intermittent deflation/reinflation has been sug-
re-inflated. Half the initial dose is then injected. gested to reduce blood drug levels, e.g. deflation for
Thus safe tourniquet time is not exceeded. 510s, inflation for 1s.
Solutions: not to be used in patients with sickle cell anaemia
prilocaine is safest but lidocaine may also be used; or trait.
3mg/kg (0.6ml/kg) 0.5% solution is suitable, May be used for the leg, although larger volumes are
without adrenaline. Preservative-free prilocaine is required, e.g. 1.0ml/kg. The block may be less effective
no longer available for IVRA, but solution contain- than in the arm.
ing preservative has been safely used for many Has also been used for sympathetic nerve block, e.g.
years. using guanethidine 1025mg in 20ml saline for the arm
322 Intrinsic activity

(3040mg in 40ml for the leg); lidocaine or prilocaine - laryngoscope blades have been described that
is often added. The tourniquet is deflated after 10 incorporate forceps, allowing manipulation of the
20min. Hypotension may occur up to several hours tracheal tube.
later. It may be repeated for several weeks, e.g. on alter- - hooks introduced orally for pulling the tube
nate days. anteriorly.
allowing intubation without laryngoscopy:
Intrinsic activity. Ability of a substance (e.g. drug) to - malleable stylet with a bulb at its distal end (light-
produce a response by interacting with a surface recep- wand): passed through the tube and introduced
tor. Refers to the amount of response produced, i.e. through the mouth, with observation of the ante-
efficacy. rior neck. The light may be followed down the
See also, Affinity anterior larynx into the trachea; it disappears if
intra-oesophageal.
Intrinsic sympathomimetic activity (ISA). Ability - intubating LMA: either blind technique or using
of -adrenergic receptor antagonists to stimulate a fibreoptic scope (the latter may also be passed
-adrenergic receptors as well as block them. Oxpreno- through a standard LMA or other airway support
lol, labetalol, pindolol, celiprolol and acebutolol have device).
ISA and are therefore partial agonists; they may cause - retrograde epidural catheter technique: the cath-
less bradycardia than other -receptor antagonists, eter is introduced through the cricothyroid mem-
although the importance of this is unclear. brane via an epidural needle and passed upwards
through the larynx and out of the mouth. The
Intubation aids. Used in difficult tracheal intubation. tracheal tube is advanced over it from the mouth
Designed for: into the trachea as the catheter is held from above.
avoiding obstruction of the laryngoscope handle on For nasal intubation, the catheter is tied with
the chest during insertion of the blade into the thread to a suction catheter passed through the
mouth: nose and out through the mouth, then both are
- laryngoscopes with adjustable handles or an pulled out of the nose. Central venous cannulae
increased angle between the blade and handle and threads have also been used.
(e.g. polio laryngoscope blade). detecting oesophageal intubation.
- adaptor to swing the handle to one side during [John P Huffman, US nurse-anaesthetist; Eamon P
insertion (Yentis adaptor). McCoy, Belfast anaesthetist; SM Yentis, London
- short-handled laryngoscope. anaesthetist]
improving the view of the glottis: See also, Intubation, difficult; Intubation, fibreoptic; Intu-
- specialised laryngoscope blades (e.g. McCoy). bation, oesophageal; Intubation, tracheal
- fibreoptic instruments: may be flexible, rigid or
malleable; extendable forceps and stylets may be Intubation, awake.
attached. Indications:
- optical devices and mirrors attached to or incor- known or suspected difficult airway or intubation,
porated in the laryngoscope. The Huffman prism including an unstable cervical spine.
clips to a standard laryngoscope blade, allowing a to isolate a leak and/or protect lung segments
view of the larynx by refracting light 30 from its before applying IPPV, e.g. bronchopleural fistula,
original path. It must be warmed before use to tracheo-oesophageal fistula.
prevent misting. in neonates: controversial, it is felt to be safer by
enabling intubation despite poor view: many but with the possibility of causing undue
- long flexible introducer (often called a bougie, stress and raised ICP.
although this term refers to devices used for serial Requires anaesthesia of the pharynx, larynx and
dilatation of strictures. Traditionally these were trachea, and tongue or nasal passages:
made of gum elastic). Usually bears an angled nose: cocaine spray 410% to provide anaesthesia
tip that assists placement through the larynx; and vasoconstriction (3mg/kg maximum). Alterna-
may be inserted through the tracheal tube before tively, xylometazoline 0.1% and lidocaine 14%
intubation or placed first and the tracheal tube may be used.
passed over it, with gentle rotation if required. It tongue and oropharynx: benzocaine lozenge 100mg,
may be placed blindly; correct placement is sug- sucked 30min beforehand.
gested by feeling the tracheal rings during inser- pharynx and larynx above the vocal cords: lido-
tion, and feeling the distal end reach the carina. caine or prilocaine 14% via metered spray
Directional bougies, controllable from their prox- or swabs at increasing depths into the mouth.
imal end, are also available. Airway exchange Maximum safe doses should be observed. Glos-
catheters allow insufflation of O2 during attempted sopharyngeal nerve block has been used, but
intubation. topical anaesthesia is easier to perform. Superior
- malleable stylet, inserted through the tube before laryngeal nerve block provides anaesthesia of the
intubation. Plastic-coated ones are less traumatic epiglottis, base of tongue and mucosa down to the
than those of bare metal; trauma is reduced by cords, and is performed either by holding a
avoiding protrusion of the stylet from the distal lidocaine-soaked pledget for 23min in the piri-
end of the tube. form fossa on each side (e.g. using Krauses
- forceps to guide the tube. forceps) or by injecting 23ml 1% lidocaine from
- some tracheal tubes are able to be flexed by the front of the neck just below the greater cornu
pulling a cord within their walls, aiding direction of the hyoid bone on each side, with the bone dis-
during placement. placed towards the side to be blocked with the
 Intubation, complications of 323

operators other hand. A click may be felt as the further. Posterior external pressure on the larynx
thyrohyoid membrane is pierced. may help.
trachea and larynx below the cords: rapid transtra- - meet obstruction level with the larynx; the tubes
cheal injection of 35ml 1% lidocaine through the tip may be:
cricothyroid membrane, following aspiration of air - lateral to the glottis, e.g. in a piriform fossa, or
to confirm correct placement. The patient is asked against a false cord or arytenoid cartilage.
to breathe out fully before injection; the resultant A bulge may be visible at one side of the larynx
inspiration and coughing aid spread of solution at the front of the neck. The tube is partially
within the upper tracheobronchial tree. To reduce withdrawn, rotated and reinserted. Head rota-
the risk of breakage and trauma during coughing, tion or lateral external pressure on the larynx
the needle is withdrawn immediately following may help.
injection, or an iv cannula used instead. - against the anterior part of the cricoid or in
nebulised 4% lidocaine may be used as the sole the vallecula; tube rotation or head flexion
local anaesthetic. may help.
Alternatively, awake intubation can be performed solely Practice is required to achieve proficiency. Differently
using a remifentanil infusion at low dose. curved tubes may be required. Partial inflation of the
Tracheal intubation then proceeds as usual, using tracheal tube cuff when the tubes tip is in the orophar-
laryngoscopy or a blind nasal technique. ynx may help to centre it and aid insertion into the
The upper airways are rendered insensitive to aspi- larynx.
rated material, and the patient should be kept nil by See also, Intubation, awake; Intubation, difficult; Intuba-
mouth for 4h. Patients already at risk of regurgitation tion, oesophageal; Intubation, tracheal
and aspiration are placed at further risk.
A similar technique may be used for awake fibreoptic
bronchoscopy. Fibreoptic instruments for bronchoscopy/ Intubation, complications of. Complications may occur
intubation have injection ports through which local at the time of tracheal intubation or afterwards.
anaesthetic may be sprayed as the scope is advanced. During intubation:
See also, Intubation, blind nasal; Intubation, fibreoptic; trauma:
Intubation, tracheal - caused by leaning on the eyes.
- to the neck or jaw.
Intubation, blind nasal. Technique of tracheal intuba- - to the teeth, lips, nasal mucosa, mouth, tongue,
tion without using laryngoscopes or other instruments; pharynx, larynx, laryngeal nerves and trachea.
developed by Magill and Rowbotham as their first Infection, surgical emphysema and bleeding may
method of tracheal intubation (without use of neuro- result. Rigid introducers and bougies are particu-
muscular blocking drugs). Of particular use in difficult larly traumatic. Nasal polyps may be carried into
intubation, since visualisation of the larynx is not the trachea during nasal intubation.
required. Also used in awake intubation. hypertensive response:
Originally described in spontaneously breathing - associated with sympathetic activity and
patients, with use of 510% inspired CO2 to increase tachycardia.
ventilation. May also be performed in paralysed patients, - may increase ICP and intraocular pressure.
although induction of muscle paralysis may be hazard- - particularly undesirable in patients with hyper-
ous in difficult intubation. Use of CO2 is now generally tension and ischaemic heart disease.
considered dangerous. - caused by laryngoscopy alone; thus not obtunded
Technique: by lidocaine spray.
the patients head is positioned in the sniffing - methods to reduce the response:
position. - antihypertensive drugs, e.g. -adrenergic
a lubricated tracheal tube is inserted into a nostril receptor antagonists, hydralazine, nitrogly
(usually the right, since most bevels face left). cerine, sodium nitroprusside. Some may be
Uncuffed rubber tubes were originally used; cuffed effective given orally, preoperatively, e.g.
tubes are also suitable. Epistaxis may occur; it is -receptor antagonists, but bradycardia may
reduced if a soft tube, little force and cocaine paste occur.
or spray are used. Trauma to the nasopharynx may - benzodiazepines.
also occur, and the incidence of bacteraemia is - deep inhalational anaesthesia.
higher than with oral intubation. - iv lidocaine 12mg/kg.
the tube is passed into the pharynx, keeping - fentanyl 68g/kg, alfentanil 3050g/kg or
the head extended and mandible elevated. The sufentanil 0.51.0g/kg obtund the response if
head is rotated slightly towards the side of the given 12min before intubation.
nostril used. arrhythmias, particularly if hypoxaemia and hyper-
in spontaneous ventilation, the opposite nostril is capnia are present.
occluded. Audible breath sounds from the tube are laryngospasm, bronchospasm, breath-holding, if
used as a guide to the position of the tubes tip; i.e. intubation is attempted too early.
if they disappear, the tube is withdrawn slightly and aspiration of gastric contents.
redirected. misplaced tube, e.g. oesophageal or endobronchial.
the tube is gently inserted further; it may: Auscultation over both lungs and axillae and the
- enter the trachea in approximately a third of stomach should be performed following intubation
cases. and positioning.
- enter the oesophagus; the tube is partially with- difficult/failed intubation: risk of misplacement
drawn and reinserted with the head extended of the tube. Hypoxaemia, hypercapnia, awareness,
324 Intubation, difficult

trauma and aspiration may occur during repeated

(a)
attempts at intubation.
bacteraemia has been reported but the clinical Grade 1 Grade 2 Grade 3 Grade 4
significance is unclear. More likely with nasal
intubation.
Once the trachea is intubated:
displacement of the tube:
- extubation. (b)
- endobronchial intubation. Suggested by: Class 1 Class 2 Class 3 Class 4
- lightening anaesthesia.
- increased airway pressures.
- hypoxaemia.
- unequal lung expansion.
Usually occurs on the right side. It may cause
collapse of the unventilated lung ( right upper
lobe) and postoperative infection. On the CXR,
the tubes tip should be at T13 (carina lies at
T45). The tube may move up to 2cm with neck
Fig. 89 (a) Cormack and Lehane classification of laryngoscopic views.
movement (caudad with flexion, cephalad with (b) Modified Mallampati classification of pharyngeal appearance
extension).
- disconnection from the fresh gas supply.
- airway obstruction:
- blockage by sputum, blood or foreign object. reduced neck mobility, e.g. caused by osteoarthrosis,
- compression by mouth gag, surgeon or rheumatoid arthritis, ankylosing spondylitis, surgi-
kinking. cal fixation/traction.
- related to the cuff. reduced mouth opening, e.g. reduced temporoman-
- tube ignition by laser. dibular joint (TMJ) mobility, trismus, scarring,
- complications of extubation. fibrosis, local lesions/swelling.
Late complications: lesions/swelling/fibrosis of larynx, pharynx, tongue.
cord ulceration and granuloma: uncommon; typi- congenital conditions, often associated with the
cally occur at the junction of the posterior and above, e.g. facial deformities, achondroplasia,
middle thirds of the cord. Marfans syndrome, cystic hygroma.
damage to the recurrent/superior laryngeal nerves. anatomical variants of normal; they may be associ-
Stretching and compression are thought to be the ated with the above but difficult intubation may
most likely causes. Slow recovery usually occurs. occur in otherwise unremarkable patients.
tracheal stenosis following prolonged intubation. Studies investigating difficult intubation have described
nasal/oral ulceration. many associated features; the large number of contribut-
sinusitis may occur in prolonged nasotracheal ing factors may hinder reliable prediction of difficulty.
intubation. Also, although many difficult cases share common fea-
Tracheostomy is performed to avoid late complications. tures, many patients with these features present no dif-
See also, Anaesthetic morbidity and mortality; Intubation, ficulty; i.e. the specificity of most tests is poor.
difficult; Intubation, failed; Intubation, oesophageal; Intu- Difficulty may be suggested by:
bation, tracheal previous difficulty recorded in the medical notes.
obesity, with short neck and reduced movement at
Intubation, difficult. Incidence is thought to be about the cervical spine, especially the atlanto-occipito-
1% in the general population, although definitions vary. axial complex. The latter is tested by asking for full
Widely accepted classification (of Cormack and neck flexion, then asking the patient to look up with
Lehane) according to the best view possible at direct the examiners hand at the back of the neck, holding
laryngoscopy (Fig. 89a): it flexed. Normal movement exceeds 15.
grade 1: complete glottis visible. reduced TMJ movement: anterior/posterior sliding
grade 2: anterior glottis not seen. of lower jaw (inability to protrude the lower teeth
grade 3: epiglottis seen but not glottis. beyond the upper) or mouth opening (< 3cm).
grade 4: epiglottis not seen. protruding teeth, small mouth, high, narrow arched
Grades 3 and 4 together are often termed difficult. palate, receding mandible.
The grading system has been criticised for being too poor view of the pharyngeal structures with open
insensitive, especially for laryngoscopies between grades mouth and tongue protruded maximally, with the
2 and 3 (grades 2a [cords visible] and 2b [only corniculate/ observer level with the seated patient. The modified
cuneiform cartilages or posterior glottis visible] have Mallampati classification is commonly used (Fig.
been suggested). 89b): soft palate, uvula, fauces and pillars visible
Caused by: (class 1); soft palate, fauces and uvula visible (class
inexperienced practitioner. 2); only soft palate visible (class 3); and soft palate
difficulty inserting the laryngoscope into the mouth, not visible (class 4). A class 0 has been suggested
e.g. because its handle is obstructed by the patients in which the tip of the epiglottis itself is visible.
chest or by the hand applying cricoid pressure (e.g. The test is also valid if performed with the patient
obesity, caesarean section, barrel chest). This may supine but there may be significant interobserver
also occur with reduced mouth opening and neck differences in any position. Phonation during testing
mobility. misleadingly improves the rating.
 Intubation, failed 325

thyromental distance, with neck extended, of < - persisting in intubation attempts as above.
6.5cm. Increases the risk of trauma, awareness and
X-ray assessment: formal measurement of jaw oesophageal intubation.
dimensions is rarely done. Movement of the neck in - a failed intubation drill should be instituted
extension/flexion, especially middle/upper verte- early, especially if at risk of regurgitation.
brae, may be useful. There should be a gap between airway obstruction may follow tracheal extubation
the occiput and posterior arch of the atlas. The gap unless measures are taken to protect the airway;
should increase on neck flexion. An absent gap or options include tracheostomy/cricothyrotomy, use
little change on flexion suggests limited movement of an airway exchange catheter or delaying extuba-
at the top of the spine. Not performed routinely, tion until further equipment and/or personnel are
unless neck disease is suspected. available or until airway oedema has subsided.
Grouping of several tests in various combinations has anaesthetic records and notes should be clearly
been proposed to improve the predictive power, although marked to warn other anaesthetists. The patient
since the incidence of difficulty (and especially failure) should be visited postoperatively, to discuss the
is low, even the best tests have poor positive predictive events and implications.
value. The routine availability of a difficult airway trolley,
Management: containing all the equipment required, is considered
known or anticipated difficulty: essential.
- consideration of alternatives to intubation: [Ronald S Cormack, London anaesthetist; John R
- regional anaesthesia. Lehane, Oxford anaesthetist; S Rao Mallampati, Indian-
- facemask airway. born Boston anaesthetist]
- LMA. See also, Intubation, awake; Intubation, blind nasal; Intu-
- tracheostomy/cricothyrotomy. bation, complications of; Intubation, failed; Intubation,
- if oro/nasal intubation is deemed necessary, it may fibreoptic; Intubation, oesophageal; Intubation, tracheal
be performed with the patient awake or anaesthe-
tised. In the latter, inhalational induction (e.g. Intubation, endobronchial, see Differential lung ventila-
with sevoflurane) with maintenance of spontane- tion; Endobronchial tubes and blockers; Intubation, com-
ous ventilation during intubation is classically plications of
advocated.
- IV induction may be performed if ventilation by Intubation, failed. Incidence is approximately 1:2500
facemask or LMA is unlikely to be difficult, 3000 in general patients, and 1:300500 in obstetrics.
although this approach should be undertaken If it occurs, management is directed towards maintain-
with extreme caution as it may precipitate a ing oxygenation and preventing aspiration of gastric
cannot intubate, cannot ventilate scenario. contents.
- techniques of intubation: A failed intubation drill is widely practised for cae-
- the position of the head should be optimised. sarean section, but is applicable to all patients:
Cricoid pressure (especially backward, upward early recognition of failure is important; i.e. not per-
and to the patients right [BURP]) may help if sisting with attempts at intubation if the patient is
the larynx is anteriorly placed. becoming hypoxaemic.
- blind nasal intubation. help should be summoned.
- use of intubation aids, e.g. bougies, forceps, cricoid pressure should be maintained, although it
fibreoptic instruments, specialised laryngo- may be worth releasing it gradually and momen-
scopes and tracheal tubes, retrograde catheter tarily during attempted laryngoscopy to see if the
technique. view improves.
Preoxygenation must precede all attempts at intu- traditional advice to place the patient in the left
bation. Neuromuscular blocking drugs are avoided lateral head-down position has been criticised as
by some until the airway is secure; others advocate this is an unfamiliar position in which to continue
their use in order to provide optimum intubating attempts to improve the airway. However, it should
conditions. Experienced help and facilities for tra- be considered if the patient is breathing spontane-
cheostomy or cricothyrotomy should be available. ously as the airway may improve in the lateral
Special considerations apply if airway obstruction is position.
present. oxygenation should proceed via a facemask, using
In patients at risk of regurgitation, risk of 100% O2. Difficult ventilation may be associated
aspiration is increased if laryngeal protective with obesity, copious facial hair and poor neck
reflexes are obtunded by local anaesthetic during movement. Oxygenation may be aided by:
awake intubation. If inhalational induction is - an assistant squeezing the reservoir bag if both
chosen, the left lateral head-down position is hands are needed to support the airway.
traditionally advocated, but reduced familiarity - LMA: although it does not protect the airway
with the position may exacerbate difficulty in from aspiration of gastric contents, the LMA has
intubation. proved life-saving in many different situations.
unanticipated difficulty: Insertion during application of cricoid pressure
- maintenance of oxygenation. may be unsuccessful; use of bimanual cricoid
- consideration of alternative strategies: pressure or temporary release may facilitate
- allowing the patient to wake, with subsequent insertion.
management as above. - an oesphageal obturator/airway if available.
- continuing inhalational anaesthesia without Deliberate oesophageal intubation using an ordi-
intubation. nary tracheal tube may improve the airway.
326 Intubation, fibreoptic

Oesophageal obturation has been suggested early passage of an illuminated stylet down the tube; tra-
if the patient cannot be turned into the lateral cheal placement is suggested by visible light at the
position. front of the neck.
if surgery is not required as an emergency (e.g. elec- use of sound: a simple stethoscope attachment at
tive caesarean section) the patient should be kept the proximal end of the tracheal tube has been used
oxygenated and allowed to wake up. Alternative to distinguish tracheal and oesophageal tube place-
techniques (e.g. regional techniques, awake intuba- ment. A hand-held device (SCOTI: Sonomatic Con-
tion) should be considered. firmation of Tracheal Intubation) that emits sound
in life- or limb-saving emergency surgery, proceed- waves along the tracheal tube and analyses the
ing with inhalational anaesthesia may be consid- reflected waves has also been used but is no longer
ered, but only if the airway is clear. Cricoid pressure manufactured because of poor performance.
should remain applied if the airway is unprotected. capnography; although CO2 may be present in the
The stomach should be emptied only in the head- stomach, sustained levels in repeated expirations
down, left lateral position, using a wide-bore tube. indicate tracheal intubation. Disposable detectors
Local anaesthetic infiltration of the surgical field may be attached to the tube, giving breath-by-
may reduce requirements for volatile agents. breath colour changes in response to exhaled CO2.
if oxygenation is impossible by facemask, LMA fibreoptic endoscopy through the tube.
or other device, cricothyrotomy or emergency Removal of the tube has been advocated if there is any
tracheostomy should be performed. Difficulty doubt as to its position. Alternatively, disconnecting the
may be encountered, especially if the patient has a tube but leaving it in place may allow manual ventilation
fat neck. using a facemask placed over it.
See also, Intubation, awake; Intubation, difficult [Michael Wee, UK anaesthetist]

Intubation, fibreoptic. Usually refers to use of flexible Intubation, tracheal. Oro/nasal intubation was initially
fibreoptic instruments, although there are also rigid described for resuscitation (e.g. by Kite in 1788) and for
fibreoptic laryngoscopes available. May be used for laryngeal obstruction, although tracheal insufflation in
awake intubation or as an alternative to direct laryngos- animals had been described earlier. Macewen was the
copy in the anaesthetised patient, in both routine first to advocate tracheal intubation instead of tracheos-
and difficult cases. Oral intubation may be assisted by tomy for anaesthesia for head and neck surgery, in 1880.
passage of the scope via a specialised oral airway (see An intubating tube was described by ODwyer in 1885.
Airways), LMA or other device. Causes less trauma and Laryngoscopy was pioneered by Kirstein, Killian and
cardiovascular response than direct laryngoscopy and Jackson between 1895 and 1915. Modern endotracheal
intubation. anaesthesia and blind nasal intubation were developed
See also, Intubation, awake; Intubation, tracheal by Magill and Rowbotham after World War I. Tracheal
tubes and laryngoscopes are continually being devel-
Intubation, oesophageal. A potential complication of oped and adapted.
attempted tracheal intubation. If undetected, it may lead Indications for intubation:
to severe hypoxaemia, resulting in death or brain injury. anaesthetic:
Particularly likely if intubation is difficult or the practi- - restricted access to the patient, e.g. head and neck
tioner unskilled. Detection is often difficult, since obser- surgery, prone position.
vation of chest movement and auscultation over the - to protect against tracheal soiling by gastric con-
chest and stomach may wrongly suggest successful tra- tents and blood, e.g. dental, ENT and emergency
cheal intubation. The belching noise on manual inflation surgery.
that usually accompanies oesophageal intubation may - to secure the airway, e.g. in airway obstruction.
be absent. The reservoir bag may move convincingly - when muscle relaxation is required, e.g. abdomi-
during spontaneous ventilation. Condensation of water nal surgery.
vapour within the tube may occur in both oesophageal - when IPPV is required, e.g. respiratory disease,
and tracheal intubation. Preoxygenation may delay sub- thoracic or cardiac surgery, neurosurgery, pro-
sequent hypoxaemia and cyanosis. longed surgery.
Methods of detection: non-anaesthetic:
tactile test for tracheal tube placement: the index - CPR.
finger is passed along the tube into the pharynx, and - when IPPV is required, e.g. respiratory failure.
attempts made to palpate the interarytenoid groove - to secure/protect the airway, e.g. in airway obstruc-
at the back of the larynx, posterior to the tube. The tion, unconscious patients, impaired protective
larynx is moved cranially from the front of the neck, laryngeal reflexes.
using the other hand. - to allow aspiration of sputum/secretions.
sudden overdistension of the tracheal tube cuff Technique:
has been suggested, with palpation over the front of at least two laryngoscopes, a selection of tubes,
the trachea at the sternal notch. Tracheal trauma syringe for cuff inflation, suction apparatus, intuba-
may occur. tion aids, emergency equipment and drugs should
injection and withdrawal of air through the tube, always be available and checked before use.
using a large syringe or rubber bulb (oesophageal oral:
intubation detector device; Wee detector). Oesoph- - the patient is positioned with the neck flexed
ageal intubation is suggested by a belch on inflation, about 35 and head extended about 15 (sniffing
followed by absent or obstructed withdrawal of air. the morning air). A pillow is required.
Both components are silent and unobstructed if - with the lungs oxygenated and the patient
intubation is tracheal. either paralysed or adequately anaesthetised if
 Inverse ratio ventilation 327

- lidocaine spray 4% is sometimes applied to the

(a) larynx, to reduce stimulation by the tube. Lido-
caine gel is also available.
- size 89mm tubes are often used for men, 78mm
for women (smaller tubes are associated with a
lower incidence of sore throat and hoarseness);
average suitable length is 2225cm. The tube is
inserted under direct vision if possible, from the
right side of the mouth with conventional laryn-
goscopes. The view may be improved by back-
ward, upward and rightward pressure on the
larynx (BURP) from the front of the neck. If the
view is incomplete or insertion difficult, intuba-
tion aids (e.g. stylet, bougie) may help. If the
glottis is not seen, the bougie or tube may be
placed blindly, by careful advancement posterior
to the epiglottis or laryngoscope tip. Tracheal
rings may be felt if placement is successful;
(b) oesophageal intubation must be excluded.
- the tube cuff is inflated slowly until the
audible leak vanishes. Low-pressure inflators are
available.
- observation of the chest and auscultation of both
lungs (e.g. high in the axilla) are required to
exclude accidental intubation of the right main
bronchus. Auscultation over the stomach and in
the suprasternal notch has also been suggested to
help indicate gastric inflation and tracheal leak
respectively.
- the tube is tied or taped in position.
- other techniques include awake intubation, fibre-
optic intubation, use of the intubating LMA and
retrograde catheters. Intubation may also be per-
formed without instruments, by hooking the
fingers or thumb of one hand over the back of the
tongue, and guiding the tube by touch.
nasal:
Fig. 90Tracheal intubation using (a) curved and (b) straight
laryngoscope blades - cocaine paste/spray 10%, or xylometazoline 0.1%
is used to reduce epistaxis, which may be severe.
- tubes of diameter 1mm less than for oral intuba-
tion are usually employed; average suitable length
breathing spontaneously, the mouth is opened is 2528cm. The lubricated tube is gently inserted
with the right hand and the laryngoscope intro- directly backwards, twisting to ease its passage.
duced at the right side, using the left hand. The Intubation is achieved blindly, with fibreoptic
blades tip is passed back along the upper surface instruments or with laryngoscopy as above, using
of the tongue until the epiglottis is visible. forceps to position the tube if required.
- if a curved blade (e.g. Macintoshs) is used, the tip - checking/securing as above.
is placed between the epiglottis and the base of Special considerations apply for paediatric anaesthesia,
the tongue, and the laryngoscope lifted in the or when risk of aspiration is present (see Induction, rapid
direction of the handle, avoiding pivoting or pres- sequence).
sure on the upper teeth. The glottis is visible under In ICU, nasal intubation was previously preferred
the epiglottis as the latter is lifted forward (Fig. because of increased patient comfort, easier securing of
90a). This method is thought to be less stimulating the tube and mouth care. However, narrower, longer
than with a straight blade, because the dorsal tubes are required, and thus suction is more difficult and
surface of the epiglottis (innervated by the supe- occlusion more likely. The incidence of nasal sinusitis is
rior laryngeal branch of the vagus) is not touched. also increased. Early tracheostomy is now preferred.
- if a straight blade (e.g. Magills) is used, the tip is See also, Intubation, awake; Intubation, blind nasal; Intu-
placed posterior to the epiglottis and lifted as bation, complications of; Intubation, difficult; Intubation,
above. The glottis is visible beyond the tip (Fig. oesophageal
90b). Alternatively, the tip is passed into the
oesophagus and slowly withdrawn until the glottis Inverse ratio ventilation (IRV). Ventilatory mode used
appears. Epiglottic bruising is more likely with in neonatal IPPV and acute lung injury. Consists of a
this technique. In the paraglossal technique, the prolonged inspiratory phase of up to four times the dura-
straight blade is introduced to the (right) side of tion of the expiratory phase. Increases mean airway pres-
the tongue and angled so that the blades tip lifts sure and is thought to improve oxygenation by keeping
the epiglottis in the midline (a similar technique collapsible alveoli open for longer periods and by
is also possible using a curved blade). keeping alveoli distended through intrinsic PEEP
328 Investigations, preoperative

associated with shortened expiratory time. May require particles are relatively lipid-insoluble and therefore do
a few hours for alveolar recruitment to become appar- not cross easily. Once a drug has dissociated, passage
ent. Risk of barotrauma may be increased, and air trap- across the membrane depends on the concentration of
ping may occur if the expiratory phase is too short. It is the unionised form. Weak acids dissociate in alkaline
therefore contraindicated in obstructive lung disease environments; thus passage across membranes is
when hyperventilation may occur. Spontaneous ventila- favoured by acid environments. The opposite applies for
tion is prevented by most ventilators during the long weak bases.
inspiratory phase; thus it is unsuitable for weaning from Degree of ionisation is derived from the Henderson
ventilators. Usually requires neuromuscular blockade Hasselbalch equation:
and sedation. log [ionised drug]
acidic drug: pH pKa =
Investigations, preoperative. Aid clinical preoperative [unionised drug]
assessment of patients fitness for surgery and whether log [unionised drug]
improvement is possible, and provide a baseline for sub- basic drug: pH pKa =
[ionised drug]
sequent testing. Indications and requirements vary and
are sometimes controversial; history and examination At 50% ionisation, pH = pKa.
Examples of acidic drugs:
are generally considered more useful in routine preop-
phenytoin.
erative screening for disease. Unnecessary testing is
barbiturates, e.g. thiopental (pKa 7.6).
expensive, time-consuming and may be worrying for the
salicylates.
patient; it may be performed because of ignorance, sup-
penicillins.
posed medicolegal security and to avoid postponement
Examples of basic drugs:
of surgery if a test result is required later. Conversely,
diazepam (pKa 3.3).
anaesthetists are often pressed to proceed with anaes-
local anaesthetic agents, e.g. lidocaine (pKa 7.9),
thesia despite inadequate investigation.
Guidelines for investigation are related to:
bupivacaine (pKa 8.1).
opioid analgesic drugs, e.g. morphine (pKa 7.9),
cost of testing.
sensitivity and specificity of the test.
pethidine (pKa 8.5).
non-depolarising neuromuscular blocking drugs.
incidence of abnormality in the population
Examples of anaesthetic relevance:
concerned.
in acidosis, dissociation of thiopental is decreased;
clinical significance of the result if abnormal.
extent of planned surgery.
thus the concentration of unionised portion
Typical guidelines:
increases. The amount of drug entering the brain
CXR:
therefore increases; thus the effect per mg increases.
conversely, in infected tissues with a relatively acidic
- cardiovascular/respiratory disease unless recent
(under 612 months) films are available. pH, the dissociation of local anaesthetic agents is
- new respiratory symptoms. increased, rendering them less effective.
trapping of drugs in the ionised form in urine, by
- possible metastases.
- recent immigrant from an area where TB is manipulating urinary pH to aid excretion (forced
endemic, unless recent films are available. diuresis).
- as a preoperative baseline in major surgery. See also, Pharmacokinetics
- age > 60 years.
The first four indications are recommended by the Iontophoresis. Use of electric current to aid penetration
Royal College of Radiologists. of drug into the tissues. Suitable for drugs of low mw and
ECG: age over 4050 years, earlier in smokers or in high lipid solubility and potency, e.g. GTN, fentanyl. The
patients with cardiovascular disease. drug is applied to the skin in the ionised form using an
haemoglobin: age > 5060 years, evidence of electrode of the same charge as the drug; current is
anaemia, or major haemorrhage anticipated. applied using a nearby reference electrode to complete
Routine testing in all women and in all patients has the circuit. Drug is repelled from the electrode and
been suggested. passes into the skin and subcutaneous tissues.
biochemistry: age > 4050 years, metabolic diseases,
dehydration, drug therapy known to alter biochem- Ipecacuanha. Emetic drug, a mixture of plant alkaloids,
istry (e.g. diuretics) or whose actions are affected by formerly used in the treatment of poisoning and over-
abnormalities, e.g. digoxin. Creatinine has been sug- doses. Activates peripheral GIT sensory receptors and
gested as a better routine test than urea. Urine stimulates the chemoreceptor trigger zone. Produces
testing for glucose has been suggested if blood is not vomiting within 2030min, with effects lasting up to 2h.
tested. Its use is no longer advocated as there is no evidence
other investigations if suggested by history/ that it reduces absorption of poisons and it may increase
examination include testing for sickle cell anaemia, the risk of aspiration of gastric contents.
liver function tests, lung function tests, coagulation
studies, arterial blood gas interpretation, cervical
spine X-rays. IPPV, see Intermittent positive pressure ventilation
In 2004 NICE issued guidelines with more detailed rec-
ommendations for preoperative testing related to the Ipratropium bromide. Anticholinergic drug, used to
patients condition, age and proposed surgery. treat asthma and chronic bronchitis. Has a quaternary
amine structure. Of slower onset than salbutamol and
Ionisation of drugs. Important determinant of a drugs similar drugs; there may be synergy between them.
passage through membranes, since charged (ionised) Oxitropium (taken 812-hourly) and tiotropium (taken
 Ischaemic heart disease 329

once daily) are similar drugs; the latter has been associ- of high-density lipoproteins. Mortality and morbid-
ated with fewer exacerbations of COPD (but more dry ity are reduced by treating hypercholesterolaemia.
mouth) than ipratropium. hypertension, diabetes mellitus.
Dosage: obesity, lack of exercise, poverty, stress and alcohol
12 puffs aerosol (2040g) tds/qds. have been implicated in some studies.
0.10.5mg nebuliser solution (0.42.0ml 0.025% The main pathophysiological feature is a reduction
solution) tds/qds. Paradoxical bronchospasm in in coronary artery patency by lipid atheromatous
earlier preparations was caused by preservatives. plaques, that may be exacerbated by coronary spasm.
Systemic anticholinergic effects are rare, although This may lead to:
glaucoma has occurred in susceptible patients follow- myocardial ischaemia when O2 demand exceeds
ing delivery of nebulised ipratropium through poorly supply.
fitting masks. fissuring of plaques with thrombus formation; may
lead to acute coronary syndromes or sudden death.
IPSP, Inhibitory postsynaptic potential, see Synaptic Clinical features:
transmission angina (see Myocardial ischaemia).
dyspnoea, related to ischaemia, cardiac failure or
Iron lung, see Intermittent negative pressure ventilation smoking-related respiratory disease.
palpitations, syncope due to arrhythmias (including
Iron poisoning. Occurs almost exclusively in children heart block).
who accidentally consume iron tablets. Doses exceeding hypertension, cardiomegaly, peripheral or pulmo-
4060 mg/kg of elemental iron, or serum concentrations nary oedema.
exceeding 90 mol/l in children or 140 mol/l in adults fatty deposits due to hyperlipidaemia, e.g. around
represent severe poisoning. Early symptoms (within the eyes, arcus senilis in the cornea.
an hour) include nausea, vomiting, upper abdominal sudden death.
pain and GIT bleeding (caused by irons corrosive Investigations:
action on the gastric mucosa); later symptoms include resting ECG and exercise testing.
hypotension, hypoglycaemia, convulsions, acute kidney echocardiography.
injury and coma. Hepatic failure and pyloric stenosis nuclear cardiology gated scanning.
may occur. With intensive treatment, mortality is cardiac catheterisation.
about 1%. CT scanning and MRI.
Management: digital subtraction angiography: computerised sub-
general measures as for poisoning and overdose, e.g. traction of background signals in order to enhance
O2 therapy, iv fluids. vessel images. Allows iv contrast injection instead
in severe cases, desferrioxamine iv up to 15mg/kg/h of cardiac catheterisation.
to a maximum of 80mg/kg in 24h. With features of Management (see Acute coronary syndromes for
severe toxicity, treatment should be started without treatment of unstable disease):
waiting for the serum iron level. Instillation of 5g general measures: stopping smoking; treatment of
into the stomach has also been suggested to reduce hypertension and hypercholesterolaemia (e.g. with
absorption. Gastric lavage with sodium bicarbonate statins).
may convert iron to ferrous carbonate, which is first-line specific treatment is with nitrates (e.g.
less well absorbed. Whole bowel irrigation has been GTN, isosorbide), antiplatelet drugs, -adrenergic
performed after ingestion of enteric-coated prepa- receptor antagonists and calcium channel blocking
rations, although evidence of benefit is unclear. Gas- drugs. Oral/sublingual therapy is started first.
trostomy has been suggested to remove residual percutaneous coronary intervention is increasingly
tablets if abdominal X-ray suggests large quantities used to avoid surgery.
remaining despite emesis and lavage. coronary artery bypass graft.
treatment should be monitored by serial serum iron Anaesthetic management: the main aim is to prevent
measurements. perioperative myocardial ischaemia and infarction
(reinfarction rate is up to 6%, usually on the third
IRV, see Inverse ratio ventilation day; infarction rate if none previously is about
0.10.2%):
ISA, see Intrinsic sympathomimetic activity preoperatively:
- preoperative assessment of risk factors and sever-
Ischaemic heart disease. Most common cause of death ity of disease. Cardiac risk index is sometimes
in the developed world (2030%); its incidence is now used. Conditions are optimised before surgery
declining in many countries including the UK, due to if possible; e.g. treatment of cardiac failure,
improvements in treatment, secondary prevention and arrhythmias.
the reduction of preventable risk factors. - continuation of antianginal therapy up to and
Risk factors include: including the morning of surgery.
increasing age, male gender, postmenopausal - addition of further therapy if required; e.g. GTN
females. skin patch.
family history: incidence is increased if a person has - sedative premedication is often prescribed, to
a first-degree relative with angina or previous MI reduce anxiety and endogenous catecholamine
aged < 55 years. secretion.
smoking. perioperatively:
diet: associated with high plasma levels of low- - the main principle is the optimisation of myocar-
density lipoproteins and cholesterol, and low levels dial oxygen delivery while minimising demand.
330 Ischaemic preconditioning

The combination of tachycardia and hypotension

F H F
is particularly hazardous and should be avoided.
In general, drugs with minimal cardiovascular H C O C C F
effects are chosen, e.g. vecuronium, atracurium,
fentanyl. Pancuronium has traditionally been pre- F CI F
ferred because hypotension is less likely. Previous
concerns over isoflurane-induced coronary steal Fig. 91 Structure of isoflurane
have been refuted.
- direct arterial BP measurement is useful if disease
is severe or surgery extensive. Pulmonary artery Isoflurane. 1-Chloro-2,2,2-trifluoroethyl difluoromethyl
catheterisation is controversial. ether (Fig. 91). Inhalational anaesthetic agent, first syn-
- smooth induction of anaesthesia, using a minimal thesised in 1965 with its isomer enflurane, but not intro-
dose of iv anaesthetic agent given slowly, as the duced until 1980 because of earlier (erroneous) reports
armbrain circulation time may be prolonged. of hepatic carcinogenicity in mice.
Etomidate causes less myocardial depression Properties:
than other drugs, but others are often used. colourless liquid; pungent vapour, 7.5 times denser
Ketamine may increase cardiac work and is than air.
usually avoided. mw 184.5.
- spinal and epidural anaesthesia risk hypotension boiling point 49C.
and worsening of myocardial ischaemia, although SVP at 20C 33 kPa (250mmHg).
they may reduce myocardial work by reducing partition coefficients:
preload and afterload. - blood/gas 1.4.
- hypertensive response to intubation increases - oil/gas 97.
myocardial O2 demand with risk of myocardial MAC 1.05% (> 60 years) to 1.28% (young adults);
ischaemia (see Intubation, complications of). 1.61.8% in children.
- routine preoperative treatment with -blockers is non-flammable, non-corrosive. Dissolves certain
no longer advocated as it has been shown to plastics, e.g. some makes of syringe.
increase the incidence of CVA and death. supplied in liquid form with no additive.
- myocardial ischaemia may be demonstrated by Effects:
ECG or assessed by ratepressure product. CNS:
postoperatively: - smooth, rapid induction, but speed of uptake is
- admission to HDU/ICU if severe. Routine ICU limited by respiratory irritation. Recovery is
admission with aggressive maintenance of cardio- slower than with sevoflurane and desflurane.
vascular stability is controversial. - anticonvulsant properties, unlike enflurane.
- postoperative analgesia is particularly important, Causes more reduction of EEG activity than
to reduce sympathetic overactivity. other agents, producing an isoelectric EEG at
See also, Atherosclerosis greater than 2 MAC.
- reduces CMRO2.
Ischaemic preconditioning. Protective effect of short - increases cerebral blood flow and ICP.
non-lethal ischaemic periods on subsequent infarct size, - decreases intraocular pressure.
originally described in animal experiments and relating - has poor analgesic properties.
to myocardial ischaemia (although has also been applied RS:
to the brain and other tissue). Thought to be due to - irritant; more likely to cause coughing and laryn-
release of autocoids by ischaemic myocytes; the precise gospasm than sevoflurane.
mechanism is unknown but involves multiple second - respiratory depressant, with increased rate and
messenger systems resulting in inhibition of apoptosis decreased tidal volume.
and improved mitochondrial function. The effect is tran- - causes bronchodilatation.
sient, although some protective effect has been described CVS:
up to 72h later; improved ventricular function may also - myocardial depression is less than with halothane,
follow. Also seen when ischaemia is applied to tissue enflurane and sevoflurane, but vasodilatation and
away from the organ being preconditioned (e.g. with a hypotension commonly occur. Compensatory
tourniquet applied to the upper limb), termed remote tachycardia is common, especially in young
ischaemic preconditioning. Its importance in humans is patients.
uncertain but has been suggested by in vitro work, by - myocardial O2 demand decreases, but tachycardia
epidemiological surveys and studies in patients undergo- may reduce myocardial O2 supply.
ing cardiac surgery or angiography. - coronary steal is not thought to occur in humans.
Hausenloy DJ, Yellon DM (2011). Nat Rev Cardiol; 8: - arrhythmias are less common than with other
61929 agents. Little myocardial sensitisation to
catecholamines.
Isobestic point. A wavelength of light that is absorbed other:
by two substances to the same extent. In oximetry, the - dose-dependent uterine relaxation.
different absorption profiles of oxyhaemoglobin and - nausea/vomiting is uncommon.
deoxyhaemoglobin are utilised to quantify the percent- - skeletal muscle relaxation; non-depolarising neu-
age saturation of haemoglobin. Isobestic points occur at romuscular blockade may be potentiated.
590 and 805nm; these may be used as reference points - may precipitate MH.
where light absorption is independent of degree of satu- Less than 0.2% metabolised, the rest being excreted by
ration (see Fig. 124; Oximetry). the lungs. Widely used in neurosurgery, for the above
 Isoproterenol 331

properties. Fluoride ion production is minimal, even - different profiles of drug activity have been iden-
after prolonged surgery; higher levels have been reported tified as resulting from specific isomers, e.g. S(+)
after several days use on ICU. ketamine has greater anaesthetic and amnesic
12.5% is usually adequate for maintenance of potency than the R() isomer, with fewer emer-
anaesthesia, with higher concentrations for induction. gence phenomena and faster recovery. Similarly,
Tracheal intubation may be performed easily with spon- levobupivacaine is less cardiotoxic than the
taneous respiration, once the patient is adequately racemic bupivacaine preparation. Future drug
anaesthetised. development will be directed at production of
See also, Vaporisers single stereoisomers. Currently available drugs in
single stereoisomer form include d-tubocurarine,
Isolated forearm technique. Method for detecting l-hyoscine, etomidate, cisatracurium and ropiva-
awareness during anaesthesia. A tourniquet is inflated caine. Drugs administered as a mixture of two
on the upper arm to above systolic BP, before systemic isomers include ketamine, bupivacaine, atropine,
injection of neuromuscular blocking drug. Arm move- adrenaline, halothane and isoflurane. Mivacurium
ment, both spontaneous and in response to verbal and atracurium are presented as a mixture of
command, can be observed during anaesthesia. Patients more than two stereoisomers.
may respond to command without postoperative recall Cis-trans isomerism refers to the arrangements of paired
(wakefulness). atoms or groups around a double bond; cis refers to both
Tunstall ME (1977). Br Med J; 1: 1321 substituents being on the same side of the double bond,
whilst trans refers to one on each side.
Isomerism. Existence of two or more ions or com- Nau C, Strichartz GR (2002). Anesthesiology; 97:
pounds that have the same atomic composition but dif- 497503
ferent structural arrangement, often with different
properties. Isoniazid. Antituberculous drug, usually included in all
Two types exist:
anti-TB regimens.
structural: compounds have the same molecular Dosage: 300mg/day iv, im or orally in adults; 10mg/
formula but different chemical structures, that is, kg/day up to 300mg/day in children.
their atoms are arranged differently. Structural Side effects: peripheral neuropathy (especially in
isomers may have similar actions (e.g. isoflurane diabetes, alcoholism, malnutrition or chronic renal
[CF3CHClOCHF2] and enflurane [CHClFCF2O- failure, when concurrent treatment with pyridoxine
CHF2]) or different actions (e.g. promazine and 10mg/day should be given); nausea, hepatitis, agranu-
promethazine). Tautomerism (or dynamic isomer- locytosis, psychosis, convulsions, lupus-like syndrome
ism) refers to two structural isomers existing in equi- and erythema multiforme are rare.
librium. Following iv administration, pH changes
convert one isomer into the other, e.g. thiopental,
Isoprenaline hydrochloride/sulphate. Synthetic
ionised and water-soluble in the syringe but rapidly
catecholamine and inotropic drug. A non-selective
converted to the largely unionised, water-insoluble
-adrenergic receptor agonist, used for its effects on
form after injection. Midazolam undergoes similar
heart rate, vasomotor tone and bronchial muscle. Only
changes in lipid solubility after injection.
available in the UK on special order.
stereoisomerism: compounds have the same molec-
Actions:
ular formulae and chemical structure but have dif-
increased heart rate and force of myocardial con-
ferent spatial orientation. Two types exist:
traction (via 1 receptors).
- enantiomers: (optical isomers; chiral substances):
peripheral and pulmonary vasodilatation (via 2
the compounds are mirror images of each other,
receptors).
and have the ability to rotate the plane of polari-
systolic BP may therefore rise or fall; diastolic BP
sation of polarised light to the right (+, dextro, d
usually falls.
or D) or left (, laevo/levo, l or L). This classifica-
bronchodilatation (via 2 receptors).
tion has been largely superseded by the R/S Dosage:
system (standing for rectus and sinister, the Latin
0.020.2g/kg/min iv for complete heart block or
for right and left respectively), that describes
severe bradycardia. A bolus of 520g may also be
the configuration of the atoms around the chiral
given.
atom (around which the other components differ
may also be given orally, rectally or sublingually:
between the isomers) according to set rules
1030mg tds; absorption may be unreliable.
involving the mw of the other atoms. An R()
May cause tachycardia, tremor and ventricular arrhyth-
enantiomer thus has its atoms arranged in a clock-
mias. May worsen coronary perfusion in ischaemic heart
wise manner; an R(+) enantiomer also rotates
disease.
light to the right. Each enantiomer typically has
very different effects to those of its mirror image.
That such closely related isomers may have differ- Isoprostanes. Substances related to prostaglandins,
ent effects is one piece of evidence supporting formed by peroxidation of arachidonic acid by a reaction
receptor theory. A racemic mixture is one con- catalysed by free radicals (not involving cyclo-oxygenase).
taining equal amounts of the two enantiomers Have been studied as markers of oxidative stress,
and has no optical activity. e.g. occurring during reperfusion injury. Isoprostanes
- diastereomers: the compounds are not mirror themselves disrupt cell membranes and cause
images but have identical molecular formulae and vasoconstriction.
chemical structure. They generally have more
than one chiral centre. Isoproterenol, see Isoprenaline
332 Isosorbide di- and mononitrate

Isosorbide di- and mononitrate. Vasodilator drugs,

with similar actions to GTN but of longer duration (up
to 12h with sustained release preparations). IV infusion
of the dinitrate has been suggested in preference to infu- Liquid Gas
sion of GTN preparations because the latter contains
additives (e.g. propylene glycol). The mononitrate is a

Pressure (bar)
metabolite of the dinitrate. Used in ischaemic heart 72
disease, cardiac failure and as an antihypertensive drug
perioperatively. 52
Dosage: 40C
dinitrate: 36.5C
- 510mg sublingually.
20C
- up to 240mg/day orally; given 14 times daily. Liquid and vapour Vapour
- 210mg/h iv (0.52g/kg/min).
mononitrate: 20120mg/day orally in divided doses.
Side effects: as for GTN.
Volume

Isothermal change. Alteration in the state of a gas Fig. 92 Isotherms for N2O
while temperature remains constant, e.g. by removal of
heat produced during compression. Thus Boyles law
applies.
See also, Adiabatic change Dosage: 100400mg orally/iv daily.
Side effects: as for fluconazole, though hepatic impair-
Isotherms. Lines on a chart or graph denoting changes ment is more common. Heart failure has been
in volume or pressure with temperature remaining cons reported.
tant. The graph for an ideal gas would consist of rectan-
gular hyperbolas according to the gas laws. In fact, for ITU, Intensive therapy unit, see Intensive care unit
N2O (Fig. 92), the isotherms approach those of an ideal
gas at temperatures above its critical temperature Ivabridine hydrochloride. Antianginal drug, licensed
(36.5C). Compression of the N2O below its critical tem- for patients in normal sinus rhythm in whom -adrenergic
perature causes liquefaction, thus resisting an increase receptor antagonists are contraindicated or not toler-
in pressure. Once all the N2O is liquid, further compres- ated. Acts purely on the sinoatrial node, lowering heart
sion causes a large increase in pressure, since liquids are rate by selectively inhibiting the cardiac pacemaker If
less compressible than gases. (funny) current a mixed sodium/potassium inward
current that controls diastolic depolarisation.
Isoxane. Trade name for premixed Entonox with 0.25% Dosage: 2.57.5mg orally bd.
isoflurane. Has been used to provide analgesia during Side effects: bradycardia, first-degree heart block,
labour and minor surgery in a similar way to Entonox. ventricular ectopics, headache, dizziness, visual distur-
See also, Obstetric analgesia and anaesthesia bances; less commonly, GIT upset, supraventricular
ectopics.
ISS, see Injury severity score
IVOX, see Intravenous oxygenator
Itraconazole. Triazole antifungal drug, related to
fluconazole. IVRA, see Intravenous regional anaesthesia
 J
J receptors, see Juxtapulmonary capillary receptors (extrahepatic), primary biliary cirrhosis, drug-
induced, e.g. contraceptives. Conjugated bilirubin is
J wave, see Hypothermia raised, often markedly, and is excreted in the urine,
which is dark (but with reduced urobilinogen).
Faeces are pale and fatty. Itching is common.
Jackson, Charles T (18051880). US chemist, present at
The latter two types are frequently mixed and difficult
Wells unsuccessful demonstration of N2O in 1846; sug-
to distinguish.
gested diethyl ether to Morton for dental topical anaes-
Assessment should include questioning for a history
thesia instead. Applied for the patent rights to ether
of tattoos, drug abuse, sexual contacts, contacts with
jointly with Morton, the latter subsequently taking over
jaundiced people, travel abroad, drugs, blood transfu-
90% of Jacksons share. Jackson later claimed sole credit
sions, alcohol, acupuncture, abdominal symptoms and
for the discovery of anaesthesia.
recent anaesthetics.
Jaundice in ICU patients is often part of the present-
Jackson, Chevalier (18651958). Renowned US laryn- ing problem (e.g. in hepatic failure, biliary obstruction,
gologist. Perfected a direct-vision laryngoscope in the sepsis) or may result from drug therapy, the develop-
early 1900s, and wrote extensively on laryngoscopy and ment of acalculous cholecystitis, haemolysis of intra-
tracheal insufflation. abdominal haematoma, ischaemic hepatitis (in shocked
Boyd AD (1994). Ann Thorac Surg; 57: 5025 patients) or the administration of TPN. It may also be
part of multiple organ dysfunction syndrome.
Jaundice. Yellow discoloration of the skin caused by ICU management:
high plasma bilirubin concentration. Clinically detect- support of other organs, e.g. circulation,
able when total bilirubin exceeds 50mol/l (normally respiration.
under 17mol/l). treatment of cause, e.g. endoscopic retrograde
Normal formation and metabolism of bilirubin: cholangiopancreatography/surgery for obstructive
haemoglobin is broken down to amino acids and causes, cessation of drugs likely to cause jaundice.
haem in the reticuloendothelial system. Haem is treatment of associated clotting abnormalities, e.g.
further metabolised to lipid-soluble unconjugated with clotting factors, vitamin K.
bilirubin that is transported (bound to albumin) to early treatment of infection.
the liver. Anaesthetic management:
in the liver, unconjugated bilirubin is conjugated preoperative assessment as above, and for hepatic
with glucuronic acid, rendering it water-soluble. failure, depending on severity and cause.
conjugated bilirubin is stored in the gallbladder risk of perioperative acute kidney injury due to
with bile salts and acids, passing into the small acute tubular necrosis or hepatorenal syndrome:
bowel. - especially common with obstructive jaundice,
bilirubin is converted to urobilinogen and thence since bilirubin levels are often highest.
urobilin by gut bacteria. Reabsorbed from the gut, - more likely if dehydration or biliary sepsis is
with some urobilinogen passing back to the liver to present.
be re-excreted; a small amount is extracted by the - plasma urea/creatinine is monitored preop
kidneys. eratively.
Causes of jaundice: - preoperative iv hydration is instituted to maintain
increased bilirubin production, e.g. haemolysis. urine flow above 1ml/kg/h.
Usually mild. Unconjugated and conjugated biliru- - mannitol may be given if bilirubin is very high
bin levels are raised, with increased urinary or urine output inadequate despite hydration.
urobilinogen. Furosemide has also been used.
impaired conjugation of bilirubin, e.g. hepatitis, antibacterial therapy.
cirrhosis, drug-induced (e.g. -methyldopa, para anaesthetic drugs and techniques as for hepatic
cetamol), hepatic failure. Unconjugated bilirubin is failure.
raised; urinary urobilinogen may be raised because Postoperative jaundice may be due to:
the liver is unable to re-excrete it. Gilberts syndrome.
congenital abnormalities of bilirubin transport are underlying medical/surgical conditions.
rare, except for Gilberts syndrome (hepatic gluc- drugs, including halothane.
uronyltransferase deficiency causing mild unconju- haemolysis, e.g. due to blood transfusion reaction,
gated bilirubinaemia with otherwise normal liver or following extensive bruising and haematoma.
function tests and no urinary bilirubin). infection, e.g. transmitted via transfused blood/
obstruction of bile drainage, e.g. gallstones, needles, sepsis, pre-existing subclinical hepatitis
pancreatic carcinoma, cholangitis, cholecystitis becoming apparent postoperatively.

333
334 Jaw, fractured

hepatic injury due to severe hypoxia/hypotension. cylinder under pressure to a large space. The principle is
surgical iatrogenic biliary obstruction. employed in the cryoprobe. Conversely, temperature
Jaundice is particularly hazardous in neonates; the rises if gas within a small space is compressed.
immature bloodbrain barrier allows penetration of bili- See also, Adiabatic change
rubin into the basal ganglia of the brain, causing kernic-
terus (convulsions may occur, leading to brain damage).
Jugular bulb catheterisation. Performed to allow
[Nicolas Gilbert (18581927), French physician]
access to the blood draining the brain, and used to esti-
See also, Biliary tract
mate the balance between cerebral oxygen delivery and
utilisation. The jugular bulb is a dilatation of the internal
Jaw, fractured, see Facial trauma
jugular vein just below the base of the skull and may be
catheterised using a Seldinger technique with the needle
Jaw, nerve blocks, see Gasserian ganglion block; Man-
inserted lateral to the carotid pulsation at the level of
dibular nerve blocks; Maxillary nerve blocks
the thyroid cartilage and directed cranially towards the
external auditory meatus.
Jehovahs Witnesses. Religious group founded in the
Cerebral oxygenation can only be accurately moni-
USA in the 1870s. Believe that they alone will survive
tored if the dominant jugular bulb is used. The right side
the imminent destruction of the world, with a small pro-
is often chosen as it is usually dominant; more accurate
portion passing into Heaven to rule over the remainder
identification of dominance can be made by ultrasound
of worthy individuals who will reside in an earthly
examination of the internal jugular veins or by identify-
paradise. Since 1945, also believe that to receive blood
ing the larger increase in intracranial pressure that
products is against Gods will, thus causing potential
occurs during manual compression of each internal
difficulties perioperatively. Special consent forms are
jugular vein.
usually employed. For paediatric surgery, a court order
Blood may be sampled for PO2 and O2 saturation
is required in order to overrule parents wishes. Although
(SjO2), giving an indication of cerebral blood flow (lower
blood, plasma and autologous predonation are unac-
values reflecting greater uptake by the brain and there-
ceptable, cell salvage, cardiopulmonary bypass and
fore less blood flow, assuming O2 consumption remains
recombinant erythropoietin and factor VIIa are usually
constant), and concentrations of lactate and other sub-
permitted. Autologous blood transfusion is usually per-
stances. Indwelling fibreoptic sensors may also be placed
mitted only if contact of blood with the body is not
to give a continuous reading of global cerebral O2 satu-
broken. Other factors such as platelets, clotting factors,
ration; this has been used particularly during cardiopul-
albumin and intravenous immunoglobulin are matters
monary bypass, in neurosurgery and after head injury.
of conscience for individual Witnesses. Special measures
Desaturation (SjO2 < 55%) indicates impending cerebral
to reduce blood loss may be required, e.g. hypotensive
ischaemia, e.g. caused by hypotension, hypocapnia,
anaesthesia, recombinant factor VIIa.
increasing cerebral oedema.
[Jehovah (Old Testament); divine being]
Although supported by many enthusiasts, monitoring
Remmers PA, Speer AJ (2006). Am J Med; 119:
of jugular bulb O2 saturation gives information only
101318
about global cerebral function, not regional differences.
See also, Medicolegal aspects of anaesthesia
In addition, if cerebral blood flow and O2 consumption
both decrease, e.g. in severe brain injury, SjO2 may be
Jet mixing. Effect of a jet of gas (e.g. O2) delivered from
unchanged.
a nozzle into ambient gas, e.g. air. Energy is transferred
Schell RM, Cole DJ (2000). Anesth Analg; 90: 55966
from O2 molecules to adjacent air molecules; the latter
are entrained into the jet due to viscous shearing between
the gas layers. Employed in injector techniques for IPPV, Jugular veins. Include the internal, external and anterior
and in fixed performance O2 masks. In the latter, air is jugular veins (Fig. 93; see also Fig. 113; Neck, cross-
entrained to a fixed degree depending on O2 flow rate sectional anatomy).
and the size of side ports in the entrainment device. Internal jugular vein:
See also, Oxygen therapy; Venturi principle passes through the jugular foramen at the base of
the skull, draining the intracranial structures via the
Jet ventilators, see High-frequency ventilation; Injector sigmoid sinus.
techniques; Ventilators lies at first posterior, then lateral, to the internal
carotid artery. Contained within the carotid sheath
JG cells, see Juxtaglomerular cells with the carotid artery and vagus nerve; the cervical
sympathetic chain lies behind the sheath.
Jorgensen technique. Outmoded form of sedation for receives tributaries from the pharynx, face,
dental surgery, described in 1953, using pentobarbital, scalp, tongue and thyroid gland. Receives the tho-
pethidine and hyoscine iv. racic duct on the left and right lymph duct on
[Niels B Jorgensen (18941974), Danish-born Califor- the right.
nian dentist] has a dilatation at each end (jugular bulb), with
valves above the lower bulb.
Joule. SI unit of energy. 1 joule = work done when the terminates behind the sternoclavicular joint by
point of application of a force of 1 newton moves 1 metre joining with the subclavian vein to form the bra-
in the direction of the force (1J = 1N 1m). chiocephalic vein.
[James Joule (18181889), English physicist] External jugular vein:
drains the lateral parts of the head; passes over the
JouleThomson effect (JouleKelvin effect). Lowering sternomastoid muscle to join the subclavian vein
of temperature when a gas expands, e.g. passing from a behind the clavicle at its midpoint.
 Juxtapulmonary capillary receptors 335

Junctional arrhythmias (Nodal arrhythmias). Arrhyth

mias arising from the atrioventricular node. Com-
mon during anaesthesia, especially deep inhalational
anaesthesia.
May consist of:
ectopic beats.
Superficial bradycardia.
temporal v tachycardia.
On the ECG, inverted P waves may precede, follow or
Posterior be hidden by the (normal) QRS complexes. Usually of
Anterior auricular v little clinical significance, although cardiac output may
facial v be reduced. Cannon waves may be visible in the jugular
Internal venous waveform.
jugular v Atropine and ephedrine have been used to restore
Common
sinus rhythm in bradycardia; junctional tachycardias
facial v External may respond to lidocaine and similar drugs.
Anterior jugular v See also, Heart, conducting system
jugular v
Juxtaglomerular apparatus. System adjacent to renal
Clavicle glomeruli, composed of:
juxtaglomerular cells; epithelioid cells within the
Fig. 93Venous drainage of head and neck media of afferent arterioles entering the glomeruli.
Contain renin in granules.
macula densa; specialised tubular epithelial cells,
just before the start of the distal convoluted tubule.
Thought to be involved in the control of renin
secretion.

receives the anterior jugular vein (passing down granular cells within surrounding connective tissue;
from in front of the hyoid bone) behind the contain some renin granules.
clavicle. Responds to reductions in renal perfusion pressure
See also, Cerebral circulation; External jugular venous by secreting renin, although the exact mechanism is
cannulation; Internal jugular venous cannulation; Jugular unclear. Possibly renal vasodilatation is involved, since
bulb catheterisation -adrenergic receptor agonists, prostacyclin, bradykinin,
dopamine, furosemide and vasodilator drugs all increase
Jugular venous pressure (JVP). Assessed by observing renin secretion. Conversely, -adrenergic receptor
the height (in cm) of visible pulsation in the jugular veins agonists, vasopressin, and angiotensin reduce renin
above the sternal angle, with the patient reclining at 45. secretion.
The normal value is zero; i.e. the venous pulsations are Richly innervated with adrenergic nerve fibres;
not normally visible. The JVP falls during inspiration, -adrenergic activity increases secretion, and antago-
and rises during expiration and when pressure is applied nism reduces it, independently of vasodilatation.
to the abdomen (Q sign). Pulsations are usually non- See also, Nephron; Renin/angiotensin system
palpable. The venous waveform may be apparent. JVP
may be difficult to identify in obese patients. Juxtapulmonary capillary receptors (J receptors).
Useful as a clinical guide to right atrial pressure; Receptors present in alveolar walls near the pulmonary
raised in right-sided cardiac failure, hypervolaemia and capillaries. Thought to be responsible for the tachypnoea
mechanical obstruction, e.g. tricuspid stenosis or supe- seen in pulmonary oedema and interstitial lung disease,
rior vena caval obstruction. via vagal afferent fibres. Their role in normal lungs is
See also, Central venous pressure unknown.
 K
Kallikreins. Serine protease enzymes in tissue and type B: transverse lines, under 3cm long, seen at the
plasma, performing diverse physiological functions. lung bases, especially costophrenic angles. Repre-
Produce kinins from kininogens and may also catalyse sent thickened interlobular septa, e.g. due to fluid
formation of renin from prorenin. Plasma kallikrein is (e.g. pulmonary oedema), fibrosis or tumour.
produced from prekallikrein by various activating sub- type C: short reticular fine lines. Not commonly
stances, including part of activated coagulation factor seen.
XII. Plasmin, a fibrinolytic enzyme, catalyses the reac- [Peter Kerley (19001978), Irish radiologist]
tion, as does kallikrein itself. Inhibited by aprotinin.
Prostate-specific antigen (PSA) is a kallikrein used as a Ketamine hydrochloride. Phencyclidine derivative
biomarker for prostatic cancer. (Fig. 94), first used as an iv anaesthetic agent in 1965.
Increasingly used for postoperative analgesia and seda-
Katharometer. Device used for gas analysis, following tion on ICU. An antagonist at NMDA receptors; also
separation, e.g. by gas chromatography. A heated wire is interacts with opioid, monoamine and cholinergic recep-
placed in the gas flow; different gases have different tors. Recently described anti-inflammatory effects may
thermal conductive properties and therefore produce be via reduced expression of cytokines (e.g. interleukin-6)
different changes in electrical resistance of the wire. Par- by activated macrophages.
ticularly useful in detecting inorganic gases, e.g. helium, Uses include:

CO2, N2O and O2. Used to quantify the amount of a induction of anaesthesia, traditionally in shocked
known gas, not to identify unknown ones. patients. Produces a state of dissociative anaesthe-
sia: intense analgesia with light sleep. Increased
Kawasaki disease (Musculocutaneous lymph node syn- thalamic and limbic activity occurs, with dissocia-
drome). Autoimmune systemic vasculitis of unknown tion from higher centres.
maintenance of anaesthesia as the sole agent, espe-
aetiology, usually affecting children < 5 years old. Inci-
dence is 3.4 per 100 000 in the UK; three and 30 times cially in burns and trauma, or short procedures
more common in the USA and Japan respectively. (e.g. radiotherapy and radiological investigations).
Important because arteritis can lead to formation of Widely used in battlefield and pre-hospital anaes-
coronary artery aneurysms in 15% of cases if untreated, thesia due to its relative preservation of upper
with mortality of up to 4%. May present with fever (typi- airway reflexes. Its routine use at anaesthetic doses
cally for more than 5 days), conjunctivitis, reddened in adults is limited by psychomimetic emergence
lips, mouth and tongue, desquamating rash, peripheral phenomena (see below).
perioperative analgesia: when given perioperatively,
oedema and cervical lymphadenopathy. Diagnosis may
be difficult because not all these features may be present has a potent opioid-sparing effect, with reduced
at once, other non-specific symptoms may be present PONV and minimal side effects.
treatment of acute (e.g. postamputation) and
(e.g. cough, abdominal pain, vomiting, arthralgia) and
there is no diagnostic test. Treatment is with iv immuno- chronic neuropathic pain.
adjunct in regional anaesthesia: has local anaes-
globulin 2g/kg over 10h and aspirin 30mg/kg/day in
34 divided doses. thetic properties, and has been used for spinal and
[Tomisaku Kawasaki, Japanese paediatrician] epidural anaesthesia within clinical trials; concerns
Harnden A, Takahashi M, Burgner D (2009). Br Med J over direct neurotoxicity have restricted its use
2009; 338: 11338 beyond the trial setting.
possible neuroprotective effects via its NMDA
See also, Vasculitides
receptor antagonism.
abuse as a recreational drug (K, Special K),
KCT, Kaolin cephalin time, see Coagulation studies leading to its classification as a Class C drug under
the Misuse of Drugs Act in 2006.
Kelvin. SI unit of temperature. One kelvin (K) = 1/273.16
of the thermodynamic scale temperature of the triple
point of water (point at which solid, liquid and gaseous
water are at equilibrium). nK = (n 273.16)C.
[William Thomson (18241907), Irish-born Scottish CI
physicist; became Lord Kelvin in 1892] CH3 N

Kerleys lines. Opaque markings seen on the CXR: H

type A: thin 26cm unbranched lines, radiating
O
from the hila. Probably represent anastomoses
between central and peripheral lymphatic vessels. Fig. 94 Structure of ketamine

337
338 Ketanserin

Ketamine is commercially available as a racemic mixture > 2h, the last dose is given at least 60min
of two isomers or as the pure S(+) enantiomer. The latter before the end of surgery, to prevent prolonged
is 24 times as potent as the R() enantiomer and less recovery).
psychoactive, with a higher clearance and thus more to treat severe asthma: 0.52.5mg/kg/h infusion.
rapid recovery. Himmelseher S, Durieux ME (2005). Anesthesiology;
Presented in 10, 50 and 100mg/ml solutions, con 102: 21120
taining benzethonium chloride (the 10mg/ml solution See also, Isomerism
since 1997). pH is 3.55.5; pKa 7.5. 12% bound to plasma
albumin. Elimination half-life is about 3h. Metabolised Ketanserin. 5-HT antagonist, and weak 1-adrenergic
in the liver to weakly active metabolites, excreted receptor antagonist. Also has class III antiarrhythmic
in urine. properties. Has been used to prevent vasoconstriction
Effects: and bronchospasm in carcinoid syndrome, and also to
iv induction: smooth, but slower than thiopental provide vasodilatation and hypotension in cardiac
(about 30 s). surgery.
CVS/RS:
- BP and heart rate usually increase; cardiac Ketoacidosis. Metabolic acidosis due to accumulation of
output is maintained. Changes are probably ketone bodies in plasma. Occurs when there is reduced
via direct myocardial and central sympathetic availability of glucose (e.g. starvation, commonly seen in
stimulation, and blockade of noradrenaline chronic alcoholism) or reduced ability to utilise glucose
uptake by sympathetic nerve endings. Contraindi- (e.g. diabetic ketoacidosis). The latter is associated with
cated in severe ischaemic heart disease and hyperglycaemia; the former is not.
hypertension. Features:
- respiratory depression after rapid iv injection, but of acidosis, including hyperventilation and
less than with other agents. hyperkalaemia.
- relative preservation of laryngeal and pharyngeal characteristic sweet smell on the patients breath
reflexes, although increased salivation is common. due to ketosis.
Airway obstruction, laryngospasm and aspiration nausea and vomiting, dehydration.
may still occur. Treatment includes rehydration, correction of electro-
- bronchodilatation via a direct action and sympa- lyte imbalance and hypoglycaemia if present. Diabetic
thomimetic effects. ketoacidosis is treated with insulin.
CNS:
- analgesia at subanaesthetic doses. Ketobemidone hydrochloride. Opioid analgesic drug,
- increased muscle tone, twitching, blinking and with similar potency and properties to morphine. Mainly
nystagmus. used in Scandinavia.
- increased cerebral blood flow and ICP; contrain-
dicated in pre-eclampsia and severe intracranial Ketoconazole. Imidazole antifungal drug, active against
pathology. a wide range of fungi and yeasts. Should not be given
- anterograde amnesia in some cases. for superficial infections because of the risk of fatal
- at anaesthetic doses may cause vivid dreams and hepatotoxicity. Suppresses synthesis of glucocorticoids
emergence phenomena, e.g. unpleasant hallucina- and thus has been used for treatment of Cushings
tions. Usually less distressing in patients < 15 or > disease.
65 years. Hallucinations may be reduced by ben- Dosage: 200400mg orally od, usually for less than 14
zodiazepines, and delirium by butyrophenones. days (3mg/kg daily in children).
Physostigmine has also been used. Preoperative Side effects include hepatic impairment (occurs com-
counselling, opioid/hyoscine premedication and monly; liver function must be monitored), GIT distur-
recovery in a quiet, darkened room may also bances, gynaecomastia, rashes.
reduce their incidence.
other: Ketone bodies. Acetone, acetoacetic acid and hydroxy-
- may cause nausea and vomiting. Salivation is butyric acid; formed from hepatic metabolism of free
increased. fatty acids released from adipose tissue. Normally
- may increase uterine tone. utilised by brain, heart and other tissues as an energy
- increases intraocular pressure; contraindicated in source, keeping blood levels low. Levels increase when
open eye operations. fat metabolism increases, especially when intracellular
- does not cause histamine release. glucose is deficient, e.g. in diabetes mellitus, chronic alco-
Dosage (for racemic ketamine; dosages for S-ketamine holism, starvation, and high fat/low carbohydrate diet.
are approximately 50% lower): Increased levels may lead to ketoacidosis.
iv induction: 12mg/kg. Effects last for 510min.
Supplementary doses 0.5mg/kg. Ketoprofen. NSAID, similar to ibuprofen but with
im induction; 10mg/kg. Acts in 35min, lasting greater incidence of GIT side effects.
2030min. Dosage: 50100mg bdqds up to 200mg/day; may be
sedation (e.g. whilst performing regional techniques given orally, pr or by deep gluteal im injection (the
or on ICU): 2mg/kg im, 10mg increments iv, or latter for up to 3 days). A modified release prepara-
12mg/kg/h infusion. tion (100200mg orally od) and a topical gel are also
as an adjunct to general anaesthesia and post available.
operative opioid analgesia: 0.5mg/kg slow iv bolus
before skin incision, followed by 0.1250.25mg/kg Ketorolac trometamol/tromethamine. NSAID,
iv boluses at 30-min intervals (in operations lasting licensed for short-term postoperative analgesia. Has a
 Kirstein, Alfred 339

marked analgesic effect with little anti-inflammatory L1. Blood supply is from the renal arteries that arise
effect. Maximal plasma levels occur within 60min of im from the descending aorta, and venous drainage is via
injection and 5min of iv injection, with half-life of 56h. the renal veins into the inferior vena cava. Renal blood
Pain relief may not occur until 30min after injection. flow is 1200ml/min (22% of cardiac output), about
Over 99% protein-bound, with hepatic metabolism 400ml/100g/min. O2 consumption is 20ml/min, or
(reduced in the elderly). Over 95% of metabolites are 6ml/100g/min.
excreted in urine, with ~6% in the faeces. Recommended Composed of outer cortex and inner medulla, forming
parenteral doses have been reduced from those origi- pyramids. Functional unit is the nephron, with accompa-
nally proposed, following adverse events, including nying arterioles and capillaries.
death from GIT perforation/haemorrhage, asthma, Functions:
anaphylaxis and renal failure. The datasheet specifies filtration of plasma and excretion of waste products
intraoperative and prophylactic use before surgery of metabolism, whilst maintaining water, osmolality,
as contraindications because of the increased risk of electrolyte and acidbase homeostasis.
bleeding. secretion of renin.
Dosage: 10mg im/iv (the latter over at least 15 s) secretion of erythropoietin.
46-hourly, up to 90mg/day (60mg in elderly or formation of 1,25-dihydroxycholecalciferol (impor-
patients < 50kg) for up to 2 days. May also be given tant in calcium homeostasis).
orally: 10mg 46-hourly, up to 40mg/day for up to metabolism and excretion of drugs.
7 days. May be affected by anaesthesia/surgery:
Side effects: as for NSAIDs. CNS effects, including drug effects, e.g. methoxyflurane, diuretics.
drowsiness, dizziness, psychological changes and alteration of renal blood flow, e.g. hypotension,
convulsions. Contraindications include peptic ulcer aortic aneurysm repair.
disease, coagulation abnormalities/anticoagulant renal impairment following incompatible blood
drugs (including low-dose heparin), asthma, concur- transfusion, severe jaundice, sepsis, obstetric emer-
rent treatment with or allergy to any other NSAID, gencies or crush syndrome.
renal impairment, hypovolaemia, CVA, pregnancy See also, Acidbase balance; Fluid balance; Renal failure;
and lactation. Renal transplantation; Renin/angiotensin system

KetySchmidt technique. Method of measuring cere- Killian, Gustav (18601921). German laryngologist;
bral blood flow using the Fick principle, using N2O. published extensively on the structure and function
10% N2O is inhaled for 1015min, and the jugular of the larynx. A former student of Kirstein, he helped
venous concentration is assumed to be equal to the popularise direct laryngoscopy. Also performed the
brain concentration. Cerebral N2O uptake is therefore first translaryngeal removal of a foreign body from the
calculated. right main bronchus in 1897, using a rigid oesophago-
[Seymour S Kety (19152000) and Carl F Schmidt scope and cocaine local anaesthesia, thus pioneering
(18931988), US neuroscientists] bronchoscopy.

Key filling system. System for filling modern vaporis- Kilogram. SI unit of mass. The standard kilogram is the
ers with volatile anaesthetic agent, preventing filling mass of a cylindrical piece of platinumiridium alloy
with incorrect agent and supposedly reducing spillage kept at Svres, France.
and pollution by using closely fitting interlocking
components. Kilogram weight. Weight of a mass of 1 kilogram sub-
Composed of:
jected to standard Earth gravity. Also called kilogram
filler tube: a base at one end screws on to the bottle;
force.
the other end bears a plastic block that only fits into
the correct vaporiser filling port. 1 kg wt (or kgf ) due to gravity = 1 kg 9.81 m/s2
collar around the neck of the bottle of volatile = 9.81 newton
agent; protruding pegs slot into corresponding slots
in the filler tube base. Position of pegs and slots is Kinins. Vasodilator peptides derived from precursor
specific for each agent. molecules (kininogens) by the action of kallikreins.
Collar, filler tube base and block are colour-coded for Involved in many inflammatory and immune reactions,
the particular agent (halothane red; enflurane orange; and possibly in shock. Also thought to be involved in the
isoflurane purple; trichloroethylene blue; methoxy- carcinoid syndrome. Bradykinin is the main plasma
flurane green) and the name of the agent is written on kinin, causing vasodilatation and increased vascular per-
the filler tube base. meability. Glucocorticoids inhibit their release. Broken
Vaporisers for desflurane and sevoflurane do not down by angiotensin converting enzyme, mainly in the
utilise the key filling system, their bottles fitting to the lung. Elimination half-life is less than 15 s.
vaporiser by an agent-specific attachment already on
the bottle (desflurane) or fitted to it (sevoflurane). Kirstein, Alfred (18631922). German laryngologist;
See also, COSHH regulations; Environmental safety of described the first direct laryngoscopy in 1895. His laryn-
anaesthetists goscopes could be placed anterior or posterior to the
epiglottis. Stressed the importance of the sniffing the
Kidney. Situated on the posterior abdominal wall, with morning air position for laryngoscopy. Also suggested
the diaphragm and 11th and 12th ribs posteriorly. The translaryngeal removal of bronchial foreign bodies as
renal hila are approximately level with the pylorus. Each being easier than via tracheostomy.
kidney is about 10cm long, 5cm wide and 3cm thick. Hirsch NP, Smith GB, Hirsch PO (1986). Anaesthesia;
Nerve supply is via the coeliac ganglion from T12 and 41: 425
340 Kite, Charles

Kite, Charles (17681811). English doctor, practising in

Gravesend, Kent. Awarded the silver medal by the
Humane Society (now Royal Humane Society) in 1787
for his Essay on the Recovery of the Apparently Dead,
later published as a book. Described oro- and nasotra-
cheal catheterisation for lung inflation, and suggested
90
laryngospasm as a cause for hypoxia in drowning. Also
described successful resuscitation of a young girl by
passing an electric current across her thorax.

KlippelFeil syndrome. Inherited condition character-

ised by congenitally fused cervical vertebrae; subdivided Measured
according to the extent of vertebral involvement: angle
type I: several vertebrae (cervical and upper tho-
racic) form a single unit.
type II: one or two cervical vertebrae affected only.
type III: types I or II with thoracic or lumbar abnor-
malities too. 90
Most commonly restricted to C23 and C56. Scoliosis,
other skeletal malformations and cardiovascular and
genitourinary abnormalities may also occur. Typically,
the patient has a short neck with limited movement and Fig. 95 Measurement of the angle of curvature in scoliosis
a low posterior hairline. Both autosomal dominant and
recessive inheritance has been suggested for different
subtypes.
Anaesthetic considerations:
cervical instability.
the medial border of the tibial tuberosity to the
difficult intubation.
posterior edge of the tibia (taking care to avoid the
epidural and spinal anaesthesia may be technically
saphenous vein).
difficult.
related to abnormalities of other systems.
Koller, Carl (18571944). Austrian ophthalmologist; first
[Maurice Klippel (18581942) and Andre Feil (1884
described the use of local anaesthetic agent (cocaine) for
1955), French neurologists]
a surgical operation (for glaucoma) in Vienna in 1884,
Naguib M, Farag H, Ibrahim AEW (1986). Can Anesth
having previously investigated the drug with Freud. This
Soc J; 33: 6670
was reported by a colleague at an ophthalmological con-
gress in Heidelberg on the following day. Disappointed
Knee, nerve blocks. Blockade of nerves at or near the with his subsequent career progress, he emigrated to
knee joint, performed for surgery to the lower leg and New York in 1888.
foot. Blocks may be performed using ultrasound guid-
ance or nerve stimulator techniques. Korotkoff sounds. Sounds heard during auscultation
Nerves that may be blocked (see Fig. 66; Femoral over the brachial artery, whilst a proximal cuff is slowly
nerve block): deflated from above systolic pressure. Thought to
tibial nerve (L4S3): terminal branch of the sciatic result from turbulent flow within the artery, causing
nerve; supplies the anteromedial part of the sole vessel wall vibration and resonance. Used in arterial BP
of the foot via plantar branches. In the popliteal measurement. Three phases were originally described by
fossa, the nerve lies superficial and lateral to the Korotkoff; these were subsequently increased to five:
popliteal vessels, with vein medially and artery most phase I: intermittent tapping sound, corresponding
medial. to the heartbeat. Represents systolic pressure.
With patient prone and knee extended, a needle is phase II: sounds quieten or even disappear (auscul-
inserted in the midline of the popliteal fossa, level with tatory gap).
the femoral condyles. 510ml local anaesthetic agent is phase III: sounds become louder again.
injected at a depth of 23cm. phase IV: sounds suddenly become muffled.
common peroneal (L4S2): terminal branch of the phase V: sounds disappear.
sciatic nerve; supplies the dorsum of the foot via its Argument over whether diastolic pressure is best
superficial peroneal branch, and the area between recorded at phase IV or V continues; traditionally phase
the first and second toes via the deep peroneal IV is used in the UK, phase V in the USA. Recording of
branch. The region posterior to the head of the both has been suggested, e.g. 120/80/75.
fibula is infiltrated with 5ml solution. [Nicolai Korotkoff (18741920), Russian physician]
sciatic (L4S3): may be blocked before it divides into
tibial and common peroneal nerves above the pop- Krebs cycle, see Tricarboxylic acid cycle
liteal fossa, at a point 7cm cranial to the skin crease
behind the knee, and 1cm lateral to the midline. Kuhn, Franz (18661929). German physician; wrote
510ml solution is injected at a depth of 35cm. extensively on tracheal intubation for anaesthesia.
saphenous (L45): a continuation of the femoral Described tracheal insufflation in 1900 and nasotracheal
nerve; supplies the medial part of the lower leg, intubation in 1902.
ankle and foot. May be blocked by infiltration from Sweeney B (1985). Anaesthesia; 40: 10005
 Kyphoscoliosis 341

Kussmaul breathing (Air hunger). Hyperventilation mandatory; lung function tests and arterial blood
originally described in diabetic hyperglycaemic ketoaci- gas interpretation are useful.
dosis. Caused by stimulation of central chemoreceptors - chronic hypoxaemia may lead to pulmonary
by hydrogen ions. Occurs in severe metabolic acidosis hypertension and cor pulmonale.
from any cause. - preoperative physiotherapy and antibiotics may
[Adolf Kussmaul (18221909), German physician] be required.
perioperatively:
Kussmauls sign, see Cardiac tamponade - tracheal intubation may be difficult, especially if
the patient is unable to lie flat.
Kyphoscoliosis - surgery may be prolonged, with risk of major
Definitions: blood loss and hypothermia.
kyphosis: posterior curvature of spine. - transthoracic surgery may involve anterior or pos-
scoliosis: lateral curvature. terior approaches.
There may also be rotational deformity. - hypotensive anaesthesia is advocated by some, to
May be associated with congenital skeletal, muscular reduce blood loss and ease surgery. Others argue
or neurological abnormalities and diseases. Idiopathic that the risk of spinal cord ischaemia precludes
scoliosis develops in childhood and is the most common this. Careful positioning of the patient is required
form. The angle of curvature is measured from X-rays of to prevent pressure on the abdominal inferior
the spine (Fig. 95) and an angle > 10 is abnormal. There vena cava.
may be rotation of the vertebrae, with the spinous pro- - risk of cord damage during distraction of verte-
cesses turned inward towards the concavity of the curve. brae may be assessed by the wake-up test or
Thoracic, rib and chest wall deformity may cause restric- monitoring of evoked potentials.
tion of ventilation, especially if the curve exceeds 65. - access to the patient may be restricted.
Surgical fixation is increasingly performed early using postoperatively: ventilatory failure is possible; close
metal Harrington rods which allow progressive distrac- monitoring is required. CXR is usual to exclude
tion of the vertebrae as the child grows. pneumothorax. An epidural catheter may be placed
Anaesthetic management: by the surgeon for postoperative analgesia.
preoperatively: Central neural blockade (e.g. for labour) may be difficult
- assessment for associated disease. in scoliotic patients. The incidence of accidental dural
- MH may be commoner in this group. puncture during epidural anaesthesia may be increased,
- assessment of RS: lung volumes and compliance and its efficacy may be reduced following prior surgery.
are reduced; the main defect is restrictive. V/Q [Paul R Harrington (19111980), Texas surgeon]
mismatch may be present. Repeated aspiration Raw DA, Beattie JK, Hunter JM (2003); Br J Anaesth;
may occur in neuromuscular disease. CXR is 91: 886904
 L
Labat, Gaston (18771934). Anaesthetist, born in the secondary arrest: normal progress to 78cm, then
Seychelles; worked in Paris and at the Mayo Clinic and delay. Commonly due to malposition. Instrumental
New York University, USA. Pioneer of regional anaes- rate is 23%, CS rate 12%.
thesia, writing a classic text on the subject in 1922. Cephalopelvic disproportion may cause delay at any
Founded the American Society of Regional Anaesthesia stage, but especially secondary arrest. Most other causes
in 1923. are treated successfully with oxytocic drugs (with con-
Brown DL, Winnie AP (1992). Reg Anesth; 17: 24962 tinuous fetal monitoring).
Epidural blockade is often instituted to provide anal-
Labetalol hydrochloride. Combined - and -adrenergic gesia for augmented contractions, possibly to restore
receptor antagonist, with ratio of activities usually coordinated uterine activity, and in case of operative
quoted between 2:1 and 5:1 respectively. Selective for delivery.
1-receptors, but non-selective at -receptors, with some
intrinsic sympathomimetic activity. Used to treat severe
Lack breathing system, see Coaxial anaesthetic breath-
hypertension and pre-eclampsia, and in hypotensive
ing systems
anaesthesia. 90% protein-bound. Half-life is 4h. Metab-
olised in the liver and excreted in urine and faeces.
Undergoes extensive first-pass metabolism when given Lacosamide. Functionalised amino acid anticonvulsant
orally. drug, introduced in 2008. Used as adjunctive therapy
Dosage: to treat partial epilepsy with or without secondary gen-
550mg iv by slow injection, up to 200mg. Effects eralised seizures. Has also been used to treat non-
occur usually within 5min, lasting 618h. convulsive status epilepticus and pain due to diabetic
10200mg/h infusion. neuropathy. Acts by slow inactivation of neuronal
50100mg orally bd; increased up to a maximum voltage-gated sodium channels.
2.4g/24h. Dosage:
Side effects: initially 50mg orally bd, increasing to maintenance
as for -adrenergic receptor antagonists. Liver dose of 200mg bd after 4 weeks.
damage and jaundice may occur rarely. for status epilepticus: 200400mg iv bolus over
5min.
Labour, active management of. Term referring to a Side effects: visual disturbance, dizziness, drowsiness,
collection of medical interventions and management, nausea and vomiting, confusion, worsening of cardiac
including strict diagnostic criteria for the onset and conduction abnormalities.
course of labour, artificial rupture of membranes, early
use of oxytocic drugs and continuous obstetric input so
-Lactams. Group of substances containing the 4-atom
that the duration of labour is limited. Despite claims of
-lactam ring (Fig. 96). Include the penicillins, cephalo-
improved outcome, evidence is at best conflicting.
sporins, the monobactam aztreonam and the carbapen-
Medical intervention depends on the plot of cervical
ems. The -lactam ring is a site of breakdown by bacterial
dilatation and descent of the fetal head against time,
-lactamase, leading to bacterial resistance.
usually starting from presentation in labour. The curve
obtained is compared with curves derived from studies
of normal labours, primiparous or multiparous as appro- Lactate. Byproduct of anaerobic metabolism of the
priate (partograms). The normal curve is composed of products of glycolysis. Hypoxia prevents aerobic metab-
latent (up to 34cm cervical dilatation) and active (until olism of pyruvate to CO2 and water (via the tricarboxylic
10cm dilatation) phases. Delay in progress is repre- acid cycle); instead lactate is formed, with consequent
sented by a lag of more than 2h to the right of the increases in plasma lactate/pyruvate ratio (normally 10)
expected curve. and plasma lactate (normally 0.31.3mmol/l). The liver
Different patterns of delay may occur: removes 70% of lactate and the rest is converted to
prolonged latent phase: its relevance is disputed
by some obstetricians, since the onset of labour is
variable and difficult to define. Others claim up to
30% instrumental rate and up to 15% caesarean C C
section (CS) rate. More common in primiparous
women.
primary delay: i.e. slow progress of the active phase, C N
e.g. due to ineffective uterine contraction. Instru-
O
mental rate is 78%, CS rate 45%. More common
in primiparous women. Fig. 96 Structure of -lactam ring

343
344 Lactic acidosis

pyruvate by mitochondria-rich skeletal and cardiac but decreased by drugs causing enzyme induction
muscle. (e.g. other anticonvulsants). It also induces its own
Causes of increased levels: metabolism.
Type A: tissue hypoxia results in faster production Dosage: depends on the drug combination used; gen-
than normal: hypoxaemia, anaemia, tissue hypoper- erally starts at 25mg/day increased up to 500mg/day,
fusion, shock, CO poisoning, severe exercise, orally.
impaired hepatic flow. Side effects: rash and serious skin reactions, fever,
Type B: hypoxia is not a feature: increased catechol- malaise, blood dyscrasias, hepatic impairment, visual
amine levels, thiamine deficiency, decreased gluco- disturbances, GIT upset.
neogenesis (e.g. biguanide therapy).
Lanreotide. Long-acting somatostatin analogue; actions
Lactic acidosis. Metabolic acidosis accompanied by and effects are similar to those of octreotide. Used
raised plasma lactate levels. mainly in long-term management of acromegaly, by
Causes are divided into:
deep sc or im injection.
those with overt tissue hypoxia and anaerobic res-
piration (type A): Lansoprazole. Proton pump inhibitor; actions and
- severe hypoxaemia. effects are similar to those of omeprazole.
- severe anaemia. Dosage: 1530mg orally od.
- shock/haemorrhage/hypotension. Side effects: as for omeprazole.
- cardiac failure.
- severe exercise. LAP, see Left atrial pressure
- carbon monoxide poisoning.
- mesenteric ischaemia. Laparoscopy. A form of minimally invasive surgery in
those without apparent initial tissue hypoxia (type which an endoscope (laparoscope) is inserted into the
B), further subdivided into: abdominal cavity via a small incision, allowing the
- hepatic failure/renal failure (delayed clearance of abdominal and pelvic organs to be seen. Originally used
lactate). for diagnostic gynaecological procedures, now com-
- severe infection, thiamine deficiency, alcoholic monly performed for more extensive procedures (e.g.
and diabetic ketoacidosis (pyruvate dehydroge- hysterectomy) and other types of surgery, e.g. cholecys-
nase dysfunction). tectomy, gastric banding. Although benefits include
- cyanide poisoning, biguanides, salicylates, faster recovery, reduced morbidity and postoperative
sodium valproate (uncoupling of oxidative pain and wound infection, patients may be exposed to
phosphorylation). prolonged operating times. Requires induction of a
- exercise, severe infection, seizures, -adrenergic pneumoperitoneum, usually with CO2. Specific compli-
receptor agonists, fructose and sorbitol in TPN, cations are related to:
malignancies (increased glycolysis such that the gas insufflation:
aerobic pathway is overwhelmed). - trauma to intra-abdominal viscera (including
- glycogen storage disorders, inborn errors of stomach if previously distended with air during
metabolism. IPPV via facemask) and great vessels when the
In critical illness, type A and B causes frequently coexist trocar is introduced or gas insufflated.
(e.g. hypoxaemia with severe infection and increased - gas embolus if gas is accidentally insufflated into
glycolysis). blood vessels. CO2 is rapidly absorbed from the
Treatment:
blood, reducing the size of embolus.
directed at the underlying cause (with supportive - subcutaneous/mediastinal emphysema and
therapy). pneumothorax.
minimisation of drugs that may exacerbate the - bradycardia or asystole due to vagal stimulation.
problem (e.g. adrenaline). - caval compression reducing venous return if
cautious use of bicarbonate (increased lactate levels intraperitoneal pressure exceeds 34kPa. Higher
have followed its use). pressures may compress the aorta.
amine buffers, insulin and glucose infusions, and - gas may splint the diaphragm and reduce lung
stimulation of pyruvate dehydrogenase with sodium expansion.
dichloroacetate have also been tried. - raised intra-abdominal pressure may increase risk
Morris CG, Low J (2008). Anaesthesia; 63: 396411 of regurgitation and aspiration of gastric contents.
High incidence of PONV.
Laevobupivacaine, see Bupivacaine
- ICP is increased.
LambertBeer law, see BeerLambert law - CO2 may be extensively absorbed across the peri-
toneum, requiring increased alveolar ventilation
Lamotrigine. Anticonvulsant drug, blocks voltage-gated to maintain normocapnia.
sodium channels and thus inhibits the presynaptic - postoperative pain or discomfort, typically
release of glutamate and other excitatory neurotrans- referred to the shoulder tip, due to presence
mitters. Used for partial or secondary generalised sei- of peritoneal gas; incidence reduced if gas is
zures, either alone or in combination with other expelled from abdominal cavity at the end of the
anticonvulsants. Has also been used for the treatment of procedure.
bipolar disorders and in chronic pain management. - explosion through ignition of intestinal methane
Rapidly absorbed after oral administration with peak by diathermy has been reported.
plasma concentrations at 2.5h; half-life is 2436h. patients position: for upper GIT procedures
Plasma concentration is increased by sodium valproate patients are positioned head-up, which may
 Laryngeal mask airway 345

encourage venous pooling in the legs and further spheres:

hinder venous return. For gynaecological proce- - ventricular cardiac muscle must generate greater
dures the semi-lithotomy position is used, which tension when the heart is dilated than when of
may be associated with: normal size, in order to produce the same intra-
- reduced FRC and diaphragmatic splinting, ventricular pressure. Thus an enlarged failing
with risk of atelectasis, hypoxaemia and heart must contract more forcibly to sustain BP,
hypoventilation. hence the benefit of reducing preload.
- increased risk of regurgitation. - in the lungs, alveoli would tend to collapse as they
- increased venous return when the legs are raised. became smaller, were it not for surfactant, which
Pooling of blood in the legs may occur when reduces surface tension.
they are lowered afterwards, with resultant - if the outlet of an anaesthetic breathing system is
hypotension. obstructed, the reservoir bag distends, thus limit-
surgical procedure: ing the dangerous build-up of pressure that would
- bleeding may go unnoticed if not in the immedi- occur within a non-distensible bag.
ate area being worked on. [Pierre-Simon Laplace (17491827), French scientist]
- large amounts of irrigating fluid may be used, with
the risk of hypothermia if not warmed. Larrey, Baron Dominique Jean (17661842). French
- sudden coughing during upper GIT surgery may surgeon-in-chief to Napoleon. Employed refrigeration
risk damage to vital structures (e.g. bile ducts, anaesthesia in 1807, and again in 1812 during the Russian
vessels). campaign to allow painless amputations in half-frozen
- may involve laser surgery. soldiers. Also employed triage. Supported Hickman
Other considerations include patient co-morbidity; e.g. when the latter presented his experiments on suspended
obesity in patients for gastric banding. The above com- animation to the French Academy in 1828.
plications lead many anaesthetists to choose tracheal [Napoleon Bonaparte (17691821), French Emperor]
intubation and IPPV as the technique of choice, although Baker D, Cazala J-B, Carli P (2005). Resuscitation; 66:
the LMA is also commonly used for short gynaecologi- 25962
cal procedures in suitable patients.
Recommended maximal safe limits for insufflation: Laryngeal mask airway (LMA). Device invented by
4l/min. Brain and introduced into practice in 1988 for support-
35 litres total gas volume. ing and maintaining the airway without tracheal intuba-
3kPa maximal intraperitoneal pressure. tion. Consists of an oval head attached to a connecting
3040min total duration. tube (Fig. 97a). The head is inserted blindly into the
Gynaecological laparoscopy may also be performed pharynx to lie against the back of the larynx, and
using local anaesthesia, with infiltration of the abdomi- the circumferential cuff inflated to form a seal. Pressing
nal puncture site. Discomfort may result from peritoneal the junction of the head and tube backward and upward
stretching and pneumoperitoneum. Use of epidural/ against the palate during insertion has been recom-
spinal anaesthesia has been described but is rarely mended by the inventor; alternative methods include
attempted because of the above considerations. insertion with the bowl facing upwards and rotating it
Gerges FJ, Kanazi GE, Jabbour-Khoury SI (2006). J Clin 180 once inserted. Tolerated at lighter levels of anaes-
Anesth; 18: 6778 thesia than a tracheal tube. Insertion is easier following
propofol induction of anaesthesia than thiopental induc-
tion, because of the formers greater suppression of
Laplaces law. For a hollow distensible structure: laryngeal reflexes.
T T Has been used for spontaneous or controlled ventila-
P= + tion, the latter using inflation pressures of up to 10
R1 R2 25cmH2O. Does not protect against aspiration of gastric
where P = transmural pressure contents. May be removed before the patient wakes, or
T = tension in the wall left in position. A bite block is required to prevent
R1 = radius of curvature in one direction obstruction or damage by the teeth.
R2 = radius of curvature in the other direction Available in several sizes from 1 (neonates < 5kg) to
T 6 (adults >100kg), each with its own recommended
For a cylinder, one radius = infinity, therefore P =
R volume of air for cuff inflation, although a maximum cuff
pressure of 60cmH2O has been suggested as more
T logical than maximal volumes.
For a sphere, both radii are equal, therefore P = 2
R Used for:
Physiological/clinical importance: routine inhalational anaesthesia.
cylinders: inhalational anaesthesia where holding a facemask
- arteriolar smooth muscle response to fluctuating may be difficult, e.g. due to the patients positioning
intraluminal pressure: wall tension varies in order or site of surgery.
to maintain constant radius and blood flow (one airway maintenance in difficult intubation, in both
theory of the mechanism of autoregulation). previously unsuspected and known cases.
- as intraluminal pressure in arterioles or airways emergency management of failed intubation.
falls, or external pressure rises, there is a critical CPR.
closing pressure across the wall at which col- Also available with reinforced tubes to prevent kinking.
lapse may occur. In the lungs, this may occur More recent developments include: the ProSeal LMA,
during forced expiration, limiting expiratory which features a larger cuff (providing a better seal
air flow. against the glottis), and a gastric drainage port that
346 Laryngeal nerve blocks

(a) (b) (c)

Fig. 97 LMAs: (a) standard; (b) ProSeal; (c) intubating

opens at the tip of the cuff (Fig. 97b); and the intubating and ascends in the neck (see Fig. 113; Neck, cross-
LMA, in which the tube is shorter and rigid with a sharp sectional anatomy).
angle. In the latter, the bars covering the laryngeal aper- - on the right, given off at the right subclavian
ture are replaced by a single flap that lifts the epiglottis artery, passing below and behind it and ascending
when a tracheal tube (a soft silicone one specifically in the neck.
provided for the purpose) is passed blindly through it - in the neck, ascends in the groove between the
(Fig. 97c). The intubating and standard LMAs have been oesophagus posteriorly and trachea anteriorly.
used (with or without a fibreoptic scope) in known and - enters the larynx posterior to the thyrocricoid
unsuspected cases of difficult intubation. A version of joints, deep to the inferior constrictor. Supplies all
the intubating LMA has also been introduced that incor- the intrinsic laryngeal muscles except cricothy-
porates a small display screen mounted at the proximal roid, and the mucous membrane of the larynx
end of the airway so that intubation can be observed in below the vocal cords.
real time. afferent pathways also pass within the above nerves.
Washed and autoclaved between uses; a maximum Sympathetic branches pass with the arterial supply.
of 40 uses is recommended by the manufacturer. The Effects of nerve damage:
standard LMA and the intubating and ProSeal versions superior laryngeal: slack cord and weak voice.
are also available in disposable single-use versions, as are recurrent laryngeal (partial): cord held in the
many other similar-looking devices based on the same midline because the abductors are affected more
concept but produced by other manufacturers. than the adductors (Semons law). The voice is
[Archie Brain, British anaesthetist] hoarse. If bilateral, severe airway obstruction may
occur.
recurrent laryngeal (complete): cord held midway
Laryngeal nerve blocks, see Intubation, awake
between the midline and abducted position. If bilat-
eral, the cords may be snapped shut during inspira-
Laryngeal nerves. Derived from the vagus nerves: tion, causing stridor. The voice is lost.
superior laryngeal nerve: if one side only is affected, the contralateral cord
- arises at the base of the skull and passes deep to may move across and restore the voice.
the carotid arteries. Branches may be damaged during surgery (e.g. thyroid-
- divides into internal and external branches below ectomy) and tracheal intubation, especially if undue
and anterior to the greater cornua of the hyoid force is used or the cuff is inflated within the larynx. The
bone. recurrent laryngeal nerve may be involved by lesions in
- the internal laryngeal nerve pierces the thyrohy- the neck, thorax or mediastinum (on the left).
oid membrane with the superior laryngeal vessels, The superior laryngeal nerve may be blocked to allow
supplying the mucous membrane of the larynx awake tracheal intubation.
down to the vocal cords. [Sir Felix Semon (18491921), German-born English
- the external laryngeal nerve passes deep to the laryngologist]
superior thyroid artery, supplying cricothyroid See also, Intubation, awake
muscle and the inferior constrictor muscle of the
pharynx. Laryngeal reflex. Laryngospasm in response to stimula-
recurrent laryngeal nerve: tion of the laryngeal/hypopharyngeal mucosa. Afferent
- on the left, arises anterior to the ligamentum arte- pathway is via the laryngeal nerves, vagus and
riosus, passes below and behind it and the aorta brainstem.
 Laryngoscope 347

(a) (b)

(c) (d)

(e)

Fig. 98 Rigid laryngoscopes that convey the distal image via viewing channels to an eyepiece: (a) Bullard; (b) Upsher; (c) Airtraq; (d) TruView;
(e) Bonfils; or via a screen;

Laryngeal tube, see Airways laryngoscopy using only the thumb and index
finger whilst the other fingers of the left hand
Laryngoscope. Instrument used to perform laryngos- are free to apply pressure over the front of the
copy. The first direct-vision laryngoscope was invented infants larynx.
by Kirstein and later developed by Jackson; the principle blade:
was later modified by Magill, Macintosh and others. - usually set at right angles to the handle.
Most consist of: - many different laryngoscope blades have been
handle: described, most of them interchangeable when
- contains a battery power source (originally con- standard attachments are used.
nected to mains electricity). - older type of attachment: secured by screwing a
- fibreoptic laryngoscopes have batteries and bulb pin through the handle and blade seatings (Long-
in the handle, with transmission of light along a worth fitting). Newer forms employ a hook-on
fibreoptic bundle set in the blade. attachment at the base of the blade, locked on to
- short or adjustable handles are available; smaller the handle by a spring-loaded ball-bearing.
lighter handles are usually used for paediatric Devices incorporating viewing channels or with
anaesthesia. The Anderson laryngoscope handle video chips at the distal end allow either placement of
bears a hook for the left index finger, allowing the device in the trachea under visual control, with
348 Laryngoscope blades

(f) (g)

(h)

Fig. 98 Continued. (f) Airway Scope; (g) McGrath; (h) GlideScope (N.B. various similar devices and versions exist)

advancement of the tracheal tube over it, or identifica- Laryngoscope blades. Parts of laryngoscopes inserted
tion of the glottis and observation of the tubes passage into the mouth.
through the vocal cords. The image may be viewed by Consist of:
looking through an eyepiece, attachment to a camera/ base for attachment to handle.
video system or via a screen incorporated into the device tongue: straight or curved; the former is designed
itself (Fig. 98). Flexible fibreoptic instruments are also for placement posterior to the epiglottis, the latter
available. for anterior placement. The tip is usually blunt and
Surgical (suspension) laryngoscopes resemble Jack- thickened to reduce trauma.
sons more closely; they are composed of a viewing tube web: forms a shelf along one edge of the tongue,
with a right-angled handle, the two components together connecting the latter to the flange. Incorporates
forming three sides of a rectangle. They are illuminated electric connections and bulb (or fibreoptic bundle).
by an external light source attached to the proximal end Connection channels are completely removable in
of the tube. older models, and fixed to the web in newer ones.
Concerns over cross-infection, especially transmis- flange: parallel to the tongue; usually only present
sion of variant CreutzfeldtJakob disease, have led to for the proximal one- to two-thirds of the blade.
widespread use of disposable laryngoscope blades, laryn- Most are designed for use with the laryngoscope handle
goscopes or blade covers/sheaths. held in the left hand; i.e. the tongue is pushed to the left
[Sheila M Anderson (?1986), London anaesthetist; side of the patients mouth by the flange and web.
Longworth Scientific Instrument Co. Ltd, original name Common varieties (Fig. 99a):
for Penlon Ltd; Roger Bullard, Australian anaesthetist; Macintosh (1943): tongue, web and flange form a
Michael Upsher, US anaesthetist; Matt McGrath, reverse Z shape in cross-section. The most com-
Scottish designer; Pierre Bonfils, Swiss anaesthetist]. monly used blade in the UK; also popular in the
 Laryngoscope blades 349

(a)
(i) (vi)

(ii) (vii)

(iii) (viii)

(iv)

(v)

(b)
(i) (iii)

(ii)

Fig. 99 Laryngoscope blades (not to scale). (a) Adult/paediatric: (i) Macintosh; (ii) polio Macintosh; (iii) Magill; (iv) Miller; (v) Wisconsin; (vi) Soper;
(vii) Bellhouse; (viii) McCoy. (b) paediatric only: (i) Robertshaw; (ii) Seward; (iii) Oxford infant
350 Laryngoscopy

USA. Available in large adult, adult, child and baby

sizes; the latter size was not designed by Macintosh Epiglottic tubercle Epiglottis
and was criticised by him as being anatomically Vallecula
incorrect. A left-handed version is available, for
use when anatomical features of the airway require
insertion of the tracheal tube from the left side of
the mouth instead of the right. The McCoy blade
(1993) is hinged at the tip, and is controlled by a
lever on the laryngoscope handle. It allows eleva- Vestibular fold
Aryepiglottic
tion of the epiglottis whilst reducing the amount of Vocal cord
fold
force required during laryngoscopy. Although it
may make a difficult laryngoscopy easier, it may Cuneiform
also make an easy one more difficult. Another blade cartilage
with a similar function to the McCoy is actually Glottic opening Corniculate cartilage
flexible throughout its length; its curvature is
increased by a lever on the handle. Fig. 100View obtained during direct laryngoscopy
polio Macintosh (1950s): mounted at 135 to the
handle, to allow intubation in patients confined to
iron lung ventilators (e.g. in the Scandinavian polio [Robert L Soper (19081973), RAF anaesthetist;
epidemics of the 1950s). Useful when insertion of Eamon P McCoy, Belfast anaesthetist; Paul Bellhouse,
the blade into the mouth is hindered, e.g. by barrel Australian anaesthetist; Frank L Robertshaw (1918
chest, enlarged breasts, especially in obstetrics. 1991), Manchester anaesthetist; Edgar H Seward (1917
Magill (1926): U-shaped in cross-section. 1995), Oxford anaesthetist; Ronald A Bowen (19131999)
Miller (1941): similar to Magills, but with a curved and Ian Jackson, London anaesthetists; Paluel Flagg
tip and flatter flange and web, requiring less (18861970), Robert A Miller (19061976), Ephraim S
mouth opening for insertion. Available in 45 sizes Siker, Dante V Bizzarri (19141994) and Joseph G Giuf-
from premature baby to large adult. Popular in frida (?1993), US anaesthetists]
the USA. See also, Intubation aids; Intubation, tracheal
Wisconsin (1941): bigger than Magills, with the
bulb nearer the tip. Available in similar sizes to Laryngoscopy. Act of viewing the larynx. Indirect laryn-
Millers blade. Popular in the USA. goscopy was first described in 1855 in London by Garcia
Soper (1947): straight version of the Macintosh using a mirror. Direct laryngoscopy was pioneered by
blade. The small transverse slot near the tip was Kirstein, Killian and Jackson in the late 1800s/early
designed to prevent the epiglottis slipping off the 1900s, and is now the technique most commonly used for
blade. Available in adult, child and baby sizes. tracheal intubation. The view of the larynx during direct
Bellhouse (1988): angled along its length to give the laryngoscopy is shown in Fig. 100.
advantage of a straight blade, whilst the end nearest Anaesthesia for diagnostic or therapeutic laryngos-
the anaesthetist is brought anteriorly to avoid copy must provide relaxation of the jaw and vocal cords,
obstruction of the anaesthetists view. May be fitted with rapid recovery of laryngeal reflexes without laryn-
with an optical prism to enable an indirect view of gospasm. Problems include sharing of the airway, the
the glottis when a direct view is impossible. hypertensive response to laryngoscopy and contamina-
Specific paediatric blades (Fig. 99b): tion of the airway with blood and debris. Usually per-
Robertshaw (1962): straight tongue with gently formed under general anaesthesia, with IPPV through a
curving tip; the flange is folded inwards over the special 56mm microlaryngoscopy cuffed tracheal
tongue. Available in infant and neonatal sizes. tube (resistance is too high for spontaneous ventilation).
Seward (1957): similar to Robertshaws but with Other methods include injector and insufflation tech-
the flange folded outwards. Available in child and niques as for bronchoscopy. Spraying the cords with
baby sizes. lidocaine reduces postoperative laryngospasm but at the
Oxford infant (1952): straight tongue with slightly expense of diminished laryngeal reflexes.
curved tip. Available in one size. Useful for intuba- [Manuel Garcia (18051906), Spanish singing teacher]
tion in children with cleft palate. See also, Intubation, complications of; Intubation, diffi-
Others: cult; Intubation, tracheal
Guedel and Flagg (1928): similar to Magills, but
with the bulb at the tip. Guedels is set at an acute Laryngospasm. Reflex closure of the glottis by adduc-
angle to the handle. tion of the true and/or false cords. May persist after
BowenJackson (1952): similar to Macintoshs but cessation of its stimulus. The precise mechanism is con-
with a cleft tip, designed to straddle the glossoepi- troversial; the lateral cricoarytenoid muscles are thought
glottic fold. to be most important in adducting the cords whilst cri-
Siker (1956): angled blade incorporating a mirror at cothyroid tenses them. The extrinsic muscles of the
the angle. larynx may also have a role.
BizzarriGiuffrida (1958): similar to Macintoshs Caused by:
but with virtually no web and a very small flange; local stimulation of the larynx by saliva, blood,
designed for patients with little mouth opening. vomitus or foreign body (including laryngoscope,
Disposable blades (both plastic and metal) and blade airway or tracheal tube).
covers are available but concern has been raised that, response to other stimulation, e.g. surgery, move-
although they may reduce the risk of cross-contamination, ment, stimulation of anus, cervix (BrewerLuckhardt
they may make laryngoscopy more difficult. reflex).
 Larynx 351

The reflex is abolished in planes 24 of anaesthesia; thus

its occurrence may indicate insufficient depth of anaes- (a)
thesia. Occurs in about 1% of the general population
during general anaesthesia, up to 3% in infants and up
to 10% in patients with recent upper respiratory tract
infections or smokers.
May cause complete or partial airway obstruction, the
Thyroid cartilage
latter often presenting as inspiratory stridor. Causes
hypoxaemia and hypoventilation; pulmonary oedema
has been reported. Cricothyroid membrane
Management: Cricoid cartilage
cessation of stimulus.
administration of 100% O2. Positive airway pressure
may be applied by tightening the expiratory valve
of the breathing system, thus increasing the intake
of O2 with each breath.
when laryngospasm has subsided, depth of anaes- (b)
thesia may be deepened.
laryngeal muscle relaxation may be achieved with Epiglottis
suxamethonium (as little as 810mg may suffice) or Aryepiglottic
propofol, followed by ventilation with O2 and tra- fold
cheal intubation if necessary. Valleculla
Prevented by:
Cuneiform
achieving adequate depth of anaesthesia before
Corniculate cartilage
attempting laryngoscopy, insertion of airway, cartilage Piriform fossa
surgery, etc. Vocal cords
local anaesthetic spray to the larynx and laryngeal
Arytenoid
cartilage Thyroid cartilage
nerve blocks.
use of neuromuscular blocking drugs and tracheal
intubation. Cricoid cartilage

Larynx
Functions:
protects the tracheobronchial tree and lungs, e.g.
during swallowing.
allows coughing. (c)
allows speech.
allows straining, e.g. during defecation.
Extends from the root of the tongue to the cricoid Thyroid cartilage
cartilage, i.e. level with C36 (at higher level in Cricothyroid
children). muscle
Vocal cord
Dimensions:
length: 45mm (men); 35mm (women). Lateral
anteroposterior: 35mm (men); 25mm (women). Arytenoid cricoarytenoids
transverse: 45mm (men); 40mm (women). cartilage
Composed of hyoid bone, and epiglottic, thyroid,
cricoid, arytenoid, corniculate and cuneiform carti- Posterior Thyroarytenoid
lages, joined by several muscles and ligaments cricoarytenoid
(Fig. 101): Oblique arytenoid Transverse arytenoid
hyoid bone:
- level with C3. Fig. 101 Anatomy of the larynx: (a) lateral view; (b) posterior view;
- U-shaped, with horizontal body and bilateral (c) superior view with intrinsic muscles
greater and lesser horns, which pass backwards
and upwards respectively.
- attached superiorly to the mandible and tongue
(by hyoglossus, mylohyoid, geniohyoid and digas- cartilage above the vocal cords. The depression on
tric muscles) and styloid process (by stylohyoid either side of the midline glossoepiglottic fold is
ligament and muscle). the vallecula, with the pharyngoepiglottic folds
- attached inferiorly to the thyroid cartilage laterally.
(by thyrohyoid membrane and muscle), sternum - attached to the arytenoid laterally by the ary
(by sternohyoid muscle) and clavicle (by omohy- epiglottic membrane.
oid muscle). thyroid cartilage:
- attached posteriorly to the pharynx by the middle - formed from two quadrilateral halves, meeting
constrictor muscle. anteriorly to form the thyroid notch level with C4.
epiglottis: The posterior edge forms superior and inferior
- leaf-shaped, attached anteriorly to the base of the horns on each side, the latter articulating with the
tongue, body of the hyoid and back of the thyroid cricoid cartilage.
352 Laser surgery

- attached superiorly to the hyoid bone by the thy- the aryepiglottic folds and posteriorly by the arytenoid
rohyoid membrane and muscle. cartilages. The piriform fossa is the recess on each side,
- attached posteriorly to the pharynx (by inferior between the aryepiglottic folds medially and thyroid car-
constrictor muscle, palatopharyngeus and salpin- tilage and thyrohyoid membrane laterally. The rima glot-
gopharyngeus muscles) and styloid process (by tidis is the narrowest part of the airway in adults; the
stylothyroid muscle). cricoid is the narrowest in children.
- attached inferiorly to the cricoid (by cricothyroid Epithelium: squamous above the cords, columnar
membrane and muscle) and sternum (by sterno- below. Mucosa of the cords is closely adherent.
thyroid muscle). Muscle actions (Fig. 101c):
- attached inferomedially to the arytenoids by thy- the cords are tensed by cricothyroid and relaxed by
roarytenoid muscle; part of it attaches to the free thyroarytenoid and vocalis muscles.
border of cricothyroid, forming vocalis muscle, the cords are abducted by the posterior cricoaryte-
and part attaches to the lateral epiglottis, forming noids, causing outward rotation and movement of
thyroepiglottic muscle. the arytenoids.
cricoid cartilage: the cords are adducted by the lateral cricoaryte-
- signet ring-shaped, broadest posteriorly. Level noids (causing inward rotation of the arytenoids)
with C6. The lateral surface articulates with and transverse arytenoid muscle (causing the aryte-
the inferior horn of the thyroid cartilage; its noids to move together).
upper surface posteriorly articulates with the the inlet is opened by the thyroepiglottic muscle
arytenoids. and closed by the aryepiglottic muscle.
- attached via its superior surface to the thyroid the larynx is elevated by muscles from the pharynx
cartilage by the cricothyroid membrane. and those above the hyoid, and depressed by
- attached via its lateral surface to the thyroid sternothyroid.
cartilage (by cricothyroid muscle) and arytenoids Nerve supply:
(by lateral cricoarytenoid muscles). recurrent laryngeal nerve: all muscles except crico-
- attached via its posterior surface to the arytenoids thyroid, and sensation below vocal cords.
by the posterior cricoarytenoid muscles. superior laryngeal nerve: cricothyroid muscle, and
- attached inferiorly to the trachea by the cricotra- sensation above vocal cords.
cheal membrane. Blood supply: branches of superior and inferior
arytenoid cartilages: thyroid arteries and accompanying veins.
- pyramid-shaped, the bases articulating with the Lymphatic drainage:
back of the cricoid. above cords: to upper deep cervical nodes.
- also attached to the cricoid by posterior and below cords: to lower deep cervical nodes.
lateral cricoarytenoid muscles. See also, Laryngoscopy
- the vocal cords pass from the vocal processes
anteriorly to the back of the thyroid cartilage. Laser surgery. Use of laser (light amplification by stim-
- attached to the epiglottis superomedially via the ulated emission of radiation) radiation to cause tissue
aryepiglottic folds and muscles. destruction by producing intense local heat. Involves
- attached anterolaterally to the back of the thyroid stimulation of atoms, ions or molecules within a tube
cartilages by the thyroarytenoid muscles. using high voltage. Energy is absorbed and emitted by
- attached to each other by the transverse aryte- the particles; the emitted energy is amplified and allowed
noid muscle. to escape as a parallel beam of coherent light, of precise
corniculate cartilages: form tubercles in the wavelength and in phase.
posterior aryepiglottic folds, at the apex of the Effects of the laser beam on tissues depend on its
arytenoids. wavelength:
cuneiform cartilages: lie anterior to the corniculate CO2 laser (wavelength 10600nm): used for precise
cartilages, in the aryepiglottic folds. surgical cutting and coagulation, e.g. in ENT surgery,
Membranes and areas of the larynx: neurosurgery, general and gynaecological surgery
aryepiglottic membrane: and dermatology.
- passes from the anterior arytenoid to lateral neodymium yttriumaluminiumgarnet (Nd:YAG)
epiglottis. laser (1060nm): used for photocoagulation and
- forms the vestibular fold at the lower border. The debulking of tumours, e.g. bronchial carcinoma.
area between vestibular folds is termed the rima argon or krypton (400700nm): used for photoco-
vestibuli; that between the aryepiglottic fold and agulation in ophthalmology and dermatology.
vestibular fold is the vestibule; the recess between Risks to patient and operating staff:
the vocal and vestibular cords is the laryngeal ocular (corneal and retinal) damage: prevented by
sinus (saccule). containment of the laser beam, and by wearing pro-
cricothyroid membrane: free upper border forms tective glasses. Most glasses will absorb energy from
the vocal cord (level with C5) between the back of the CO2 laser; specifically tinted goggles are required
the thyroid cartilage and vocal process of the aryte- for the other types.
noid; it contains the vocal ligament beneath its skin damage: prevented by appropriate draping of
mucosa. The area between vocal cords is the rima the patient.
glottidis (glottis). explosions and fires: particularly problematic during
thyrohyoid membrane: lateral borders are thick- upper airway surgery, when the high-energy beams
ened to form the lateral thyrohyoid ligaments. may cause ignition of anaesthetic vapours, rubber,
The entrance to the larynx slopes downwards and back- PVC or silicone tracheal tubes or drapes. The fol-
wards, bounded anteriorly by the epiglottis, laterally by lowing precautions are available:
 Laxatives 353

- flexible metal tracheal tubes without cuffs. May present as cardiovascular collapse during surgery,
- metallic-coated tubes: expensive, and may still be when the cause may not be easily apparent. A history of
susceptible to damage. Cuff inflation is with saline allergy to rubber (e.g. rubber gloves, condoms) may be
instead of air. obtained. Typically associated with allergy to bananas,
- protection of the tube by wrapping in metallic avocados and chestnuts.
tape: no longer recommended now that coated or Evaluation includes skin-testing, in vitro leucocyte
metal tubes are available. studies and testing for anti-latex IgE antibodies. Peri
- avoidance of tracheal intubation, e.g. use of insuf- operative management includes avoidance of all latex-
flation or injector techniques, including high- containing equipment including facemasks, gloves,
frequency ventilation. airways/tubes, rebreathing bags/bellows, bungs, drains
- use of non-explosive mixtures of gases, e.g. under and catheters. Drug vials with rubber tops and iv tubing
30% O2 in nitrogen or helium. Intermittent flush- with rubber injection ports should be avoided. Protec-
ing with 100% nitrogen or helium has been used. tion of the arm with gauze before application of a rubber
- limitation of laser power and duration of bursts. BP cuff has been suggested, although cuffs and other
Vigilance should be high. If ignition occurs, the O2 equipment are increasingly manufactured without latex.
source should be disconnected and the operative Pretreatment with antihistamine drugs, H2 antagonist
site doused with water. drugs and corticosteroids has been used but may not be
gas embolism if the probes tip is gas-cooled. necessary if proper precautions have been taken. Since
production of noxious/potentially infective fumes: airborne latex particles have triggered allergic reactions,
adequate suction is required. no latex-containing equipment should be used in the
operating room before a known case; scheduling surgery
Latent heat. Energy released or absorbed when a sub- for the beginning of the operating list has been advo-
stance undergoes a change of state, without a change in cated. A high index of suspicion and availability of resus-
its temperature, e.g.: citative drugs are important; management of a reaction
liquid to gas or vice versa (latent heat of should follow standard lines as for adverse drug
vaporisation). reactions.
solid to liquid or vice versa (latent heat of fusion). Hepner DL, Castells MC (2003). Anesth Analg; 96:
Heat is required to change liquid to a gas, in order to 121929
overcome the attraction between molecules and expand
the substance; heat is given out when the reverse occurs, Laudanosine. Tertiary amine, a product of atracurium
e.g. when steam condenses. metabolism via Hofmann degradation. Half-life is about
Specific latent heat is the energy required to alter the 23h, i.e. considerably longer than for atracurium;
state of unit mass of substance at specified temperature; approximately doubled in renal failure. In anaesthetised
e.g. specific latent heat of vaporisation of water = dogs, causes epileptiform EEG changes at blood levels
2.26MJ/kg at 100C. It is greater at lower temperatures, over 17g/ml. Blood levels in humans, even after several
and falls at higher temperatures until it reaches zero at days infusion of atracurium in patients with renal and
the critical temperature. hepatic failure, rarely rise above 5g/ml, although fears
have been expressed about central stimulation in patients
at risk, e.g. those with an impaired bloodbrain barrier.
Lateral cutaneous nerve of the forearm, block, see
Cisatracurium at equipotent doses produces one-fifth of
Elbow, nerve blocks
the level of laudanosine. Has recently been found to
have analgesic effects in animals, and to interact with
Lateral cutaneous nerve of the thigh, block. Provides central GABA, opioid and acetylcholine receptors.
analgesia of the lateral thigh (e.g. for hip surgery), fol- Fodale V, Santamaria LB (2002). Eur J Anaesthesiol; 19:
lowing skin harvesting, and to reduce leg tourniquet 46673
pain. Has also been used in pain states and to diagnose
entrapment neuropathy of the nerve caused by the Lavoisier, Antoine Laurent (17421794). French
latters piercing the inguinal ligament instead of passing chemist. Disproved the phlogiston theory, showing that
under it (meralgia paraesthetica), before surgical the gain in weight of sulphur or phosphorus on combus-
treatment. tion was due to combination with air. Concluded that air
The nerve (L23) arises from the lumbar plexus consists of two elastic fluids: one necessary for combus-
(may arise from the femoral nerve), passing under the tion and respiration, and one that would support neither.
inguinal ligament just medial to the anterior superior Renamed the former (previously called dephlogisticated
iliac spine to supply the skin of the lateral side of the air) oxygne, estimating its concentration in air to be
thigh (see Fig. 67; Femoral triangle). A needle is inserted about 25%.
2cm medial and inferior to the iliac spine, at right angles
to the skin. A click is felt as the fascia lata is pierced. Lawen, Arthur (18761958). German surgeon, the first
1015ml local anaesthetic agent is injected fanwise, to perform caudal analgesia for abdominal surgery, using
mediolaterally. large volumes of procaine. Also described paravertebral
May also be blocked via femoral nerve block (three- block, and helped popularise regional anaesthesia.
in-one block). Described the use of curare to produce relaxation during
surgery in 1912.
Latex allergy. Typically occurs in individuals repeatedly
exposed to latex, e.g. healthcare workers and patients Laxatives
undergoing repeated urinary catheterisation (e.g. those Perioperative/ICU usage:
with spina bifida) or surgery. Thought to be true anaphy- to prepare the lower GIT before surgery.
laxis to various soluble proteins in latex. to reduce pain following rectal or anal surgery.
354 LBBB

to treat constipation, e.g. on ICU or 12mmHg) may reflect increased blood volume, reduced
postoperatively. myocardial contractility, reduced ventricular compliance
to treat poisoning and overdoses, e.g. whole bowel and increased venous return. May be measured directly
irrigation, especially in children. via a ventricular cannula or arterial cannulation, or
Divided into: inferred via pulmonary artery catheterisation.
bulk-forming laxatives: increase faecal mass and
stimulate peristalsis. Useful in patients with enter- Left ventricular end-diastolic volume. Nearest physi-
ostomies and colonic disease. Include bran, methyl- ological variable to left ventricular preload, as described
cellulose, ispaghula and sterculia. by Starlings law. May be assessed using echocardiogra-
stimulants: increase GIT motility. Include senna, phy or radiology, but indicators of left ventricular end-
bisacodyl, dantron, docusate sodium, glycerol (also diastolic pressure are easier to measure. Normally
acts as an osmotic laxative and faecal softener) and 7095ml/m2.
sodium picosulfate.
faecal softeners: liquid paraffin is rarely used since, Left ventricular failure, see Cardiac failure
if aspirated, may cause severe pneumonitis. Arachis
oil enemas may be useful for impacted faeces. Left ventricular fractional shortening. Indicator
osmotic laxatives: cause retention of water within of left ventricular function derived from M-mode
the bowel. Include lactulose (broken down by gut echocardiography.
bacteria to osmotically active compounds; also Equals:

(internal dimension ) ( internal dimension )

reduce ammonia production, hence its use in hepatic end-diastolic end-systolic
failure), polyethylene glycols and rectal citrate or
phosphates (caution in renal impairment since
hyperphosphataemia may result). Magnesium salts end-diastolic internal dimension
act within 24h but should not be used in renal Normally 3444%; often easier to estimate during echo-
impairment because of systemic absorption. cardiography than doing a formal evaluation of ejection
bowel cleansers: usually mixtures of agents; should fraction.
not be used in constipation. In frail patients, preop-
erative use may result in significant dehydration. Left ventricular stroke work, see Stroke work
Used in whole bowel irrigation.
Dosage depends on the particular preparation used. Legionnaires disease. Caused by Legionella pneu-
Complications include dehydration and electrolyte dis- mophila, Gram-negative aerobic bacteria. First came to
turbances. Stimulants may cause abdominal cramps; prominence when it killed 29 delegates at an American
osmotic laxatives may cause bloating. Laxatives (espe- Legion convention in 1976. More likely to affect elderly
cially stimulants) are contraindicated in intestinal patients. Acquired by inhaling contaminated water par-
obstruction. ticles, especially derived from cooling towers; typically
occurs in epidemics involving a single building. Presents
LBBB, Left bundle branch block, see Bundle branch as an acute febrile chest infection, typically with myalgia,
block fatigue and GIT upset before respiratory symptoms
develop. Pleuritic chest pain and confusion may occur.
LD50, see Therapeutic index/ratio Widespread infiltrates may be present on CXR. Diagno-
sis is via sputum culture serological testing. Treatment
Le Fort classification, see Facial trauma is with erythromycin or clarithromycin; 4-quinolones
have also been used. The disease lasts for 710 days.
Left atrial pressure (LAP). Mean pressure approxi- Mortality rates of 1030% have been reported.
mates to left ventricular end-diastolic pressure, unless
the mitral valve is abnormal. Pressure wave abnormali- Lenograstim, see Granulocyte colony-stimulating factor
ties are similar to the venous waveform, but with refer-
ence to mitral and aortic valves and systemic circulation, Lepirudin. Recombinant hirudin, used as an alter
instead of tricuspid and pulmonary valves and pulmo- native to heparin if the latter induces immune
nary circulation. thrombocytopenia.
May be measured via a catheter inserted directly into Dosage: 400g/kg slowly iv followed by 150g/kg/h
the left atrium, or indirectly via pulmonary artery cath- up to 16.5mg/h, adjusted according to coagulation
eterisation, which measures pulmonary capillary wedge studies.
pressure. Usually measured from mid-axilla or sternal Side effects: bleeding; hypersensitivity.
angle. Normal value is 210mmHg.
Leptospirosis (Weils disease). Caused by species
Left ventricular ejection time, see Systolic time of leptospira, Gram-negative aerobic bacteria. Passed
intervals from asymptomatic animals (dogs, rodents, livestock and
wild animals) via their urine to water, where it may
Left ventricular end-diastolic pressure (LVEDP). survive for many months. Typically affects sewage
Reflects the preload of the left ventricle. Provided ven- workers. Acquired via mucous membranes and broken
tricular compliance is constant, a constant relationship skin; it causes widespread vasculitis affecting the kidney,
(exponential rather than linear) exists between LVEDP liver, lungs and heart. Clinical features include fever,
and left ventricular end-diastolic volume. Normal myalgia, headache/neck stiffness, cough, chest pain, con-
LVEDP does not ensure normal ventricular function, fusion, rash and occasionally renal and hepatic failure.
and abnormal LVEDP may not indicate degree of Diagnosed retrospectively by increases in antibody
dysfunction. Elevations of LVEDP (normally under titre. Treatment is with benzylpenicillin, erythromycin or
 Levosimendan 355

tetracyclines. Normal organ function returns usually [Jacob Churg (19102005; Polish-born) and Lotte Strauss
within 12 months. Mortality is up to 11% if hepatic (19131985; German-born), US pathologists]
failure occurs.
[H Adolph Weil (18481916), German physician] Leukotrienes. Inflammatory mediators derived from
arachidonic acid by the action of lipoxygenases. Released
LES, see Lower oesophageal sphincter from mast cells, platelets and some leucocytes following
various stimuli (e.g. mechanical, thermal, infective and
Letheon. Name given to diethyl ether by Morton in 1846 immunological). Actions include bronchoconstriction,
when he patented his discovery. Despite this patent, vasoconstriction, increased vascular permeability and
ether was widely used without acknowledgement of chemotaxis of other inflammatory cells.
Mortons claim. His attempts to enforce the patent and They have been implicated in the pathophysiology of
payments of royalties included approaching the govern- sepsis, acute lung injury and asthma. Leukotriene
ments of the USA and France, but were unsuccessful. pathway inhibitors and leukotriene receptor antagonists
[Lethe (Greek mythology), river in Hades whose waters have been developed for use in asthma.
induced forgetfulness in those who drank them] Peters-Golden M, Henderson WR (2007). N Engl J Med;
357: 184154
Leucocytes. White blood cells; normal total count in
peripheral blood is 410 109/l. Levallorphan tartrate. Opioid receptor antagonist with
Exist as three morphologically different types: partial agonist properties, the n-allyl derivative of levor-
granulocytes: derived from common bone marrow phanol. Synthesised in 1950. 1.25mg levallorphan has
precursor stem cells: been combined with 100mg pethidine as pethilorphan,
- neutrophils (6070%; 2.57 109/l): phagocytic but hopes of analgesia without respiratory depression
with high enzyme content. were not realised. Its use has been superseded by
- eosinophils (14%; 0.010.4 109/l): contain his- naloxone.
tamine and are involved in cell-mediated hyper-
sensitivity reactions. Levetiracetam. Anticonvulsant drug used as monother-
- basophils (01%; 00.2 109/l): contain histamine apy or as an adjunct in the treatment of partial or gen-
and heparin; non-phagocytic. eralised epilepsy and for myoclonic seizures. Mechanism
lymphocytes (2335%: 13.5 10 /l): derived from
9
of action is unknown.
lymphoid stem cells throughout the body, including Dosage: 250mg1.5g bd orally or iv, titrated to
bone marrow. Mainly concerned with immune response.
mechanisms: B (bursa) cells with immunoglobulin Side effects: GIT upset, cough, ataxia, visual distur-
production and T (thymus) cells with immune bance, thrombocytopenia.
system regulation and killing of infected cells.
monocytes (48%; 0.20.8 10 /l): formed in spleen,
9
Levobupivacaine, see Bupivacaine
lymphoid tissue and marrow. Differentiate into
phagocytic tissue macrophages.
Leucocytosis may be caused by almost any acute illness Levofloxacin.Antibacterial drug, one of the 4-quinolones
as part of the inflammatory response. Other causes related to ciprofloxacin but more active against
include strenuous exercise, trauma, surgery, burns, and pneumococci.
glucocorticoid therapy. Leucopenia may be caused Dosage: 250500mg od/bd orally or iv.

by reduced production (e.g. drugs, radiation, inflamma- Side effects: as for ciprofloxacin. Hypotension and

tion, infection, infiltration of bone marrow by malig- thrombophlebitis may occur on iv administration.
nancy, fibrosis) or increased utilisation (e.g. sequestration
into the tissues). Thus, in severe illness, white cell Levorphanol tartrate. Synthetic opioid analgesic drug,
count may be increased or decreased. A low count synthesised in 1949. Similar to morphine but less sedat-
appears to be prognostic of increased mortality in ing. Onset of action is under 30min, lasting for up to 8h.
ICU patients. No longer available in the UK.
Bellingan G (2000). Intensive Care Med; 26: S11118
See also, Erythrocytes; Platelets Levosimendan. One of the calcium sensitisers, used as
an inotropic drug in the treatment of decompensated
Leukotriene pathway inhibitors. Group of drugs that congestive cardiac failure. Shown to improve survival
block the synthesis of all leukotrienes; have been used and cardiac function compared with placebo and dobu-
in asthma along with the leukotriene receptor antago- tamine; unlike the latter, levosimendan has no pro-
nists. Zileuton is an example, and inhibits the action of arrhythmic side effects.
5-lipoxygenase. Acts by binding to cardiac troponin C, increasing its
sensitivity to calcium; thus increases myocardial contrac-
Leukotriene receptor antagonists. Group of drugs tility without increasing myocardial O2 consumption.
that block the action of cysteinyl leukotrienes at their Also causes vasodilatation by opening ATP-sensitive K+
receptors, especially on bronchial smooth muscle. Have channels in smooth muscle; hence sometimes referred to
been used orally in mild/moderate asthma but not indi- as an ino-dilator. Reductions in arterial (systemic and
cated for treatment of acute attacks. ChurgStrauss pulmonary) and venous tone decrease afterload (both
syndrome (eosinophilia, systemic vasculitis and worsen- right and left ventricular) and preload respectively.
ing pulmonary symptoms) has been reported following Haemodynamic effects are seen within 5min of
their use. Examples include montelukast, zafirlukast and loading dose administration; peak effect is at 1030min.
pranlukast. 98% protein-bound with an elimination half-life of 1h.
356 Lidocaine hydrochloride

Dosage: 612g/kg iv loading dose over 10min, this concentration has been implicated in causing tran-
followed by infusion of 0.050.2g/kg/min titrated sient symptoms). Maximal recommended dose: 3mg/kg
to effect. without adrenaline, 7mg/kg with adrenaline. Toxic
Side effects: related to vasodilatation (e.g. hypoten- plasma levels: above about 10g/ml.
sion, headache).
Life support, see Cardiopulmonary resuscitation
Lidocaine hydrochloride (Lignocaine). Amide local
anaesthetic agent, introduced in 1947 (revolutionising Lightwand. Device used to place a tracheal tube without
regional anaesthesia because of its superior safety to requiring laryngoscopy. Consists of a flexible malleable
previous agents). The standard drug against which other stylet incorporating a light bulb at the distal end, with
local anaesthetics are compared. pKa is 7.9. 65% protein- the battery and handle at the proximal end. Placed inside
bound; 95% of an injected dose undergoes hepatic a tracheal tube with the bulb at the tubes tip, the tube/
metabolism and is excreted renally. Onset is rapid by all lightwand combination is bent into a J shape and
routes; usual duration of action for 1% solution is about manoeuvred into the larynx, with successful placement
1h, increased to 1.52h if adrenaline is added. indicated by a glow at the anterior neck below the
Uses: thyroid prominence. The tracheal tube is then passed
local anaesthesia. Often combined with adrenaline, into the trachea and the lightwand removed. Oesopha-
since lidocaine tends to produce local vasodilata- geal placement is suggested by a more diffuse glow
tion; 1:200000 and 1:80000 solutions are commonly above the prominence.
available, the latter usually restricted to dental use. Several different types exist. The technique has been
iv administration: used for both routine and difficult intubations.
- depression of laryngeal and tracheal reflexes Agro F, Hung OR, Cataldo R, etal (2001). Can J Anesth;
(e.g. during tracheal intubation/extubation). Com- 48: 5929
monly used to reduce the increase in ICP caused
by laryngoscopy. Possibly reduces muscle pains Lignocaine, see Lidocaine
and potassium increase after suxamethonium. It
has been used to produce analgesia and general Likelihood ratio. Method of quantifying the relative
anaesthesia (although its therapeutic ratio is low). probabilities of two complementary hypotheses. For
410% lidocaine has been used instead of air to a predictive test, it equals the probability that a
inflate the tracheal tube cuff, thereby reducing person with the condition has a positive test, over the
postoperative sore throat and hoarseness. probability that a person without the condition has a
- class I antiarrhythmic drug in ventricular positive test. Also equals sensitivity divided by (1 minus
tachyarrhythmias. specificity).
- may be useful in treatment of chronic pain.
Many preparations are available, including: Limbic system. Part of the brain, formerly termed the
0.250.5% solutions for infiltration anaesthesia and rhinencephalon. Composed of left and right lobes, each
IVRA. consisting of:
12% solutions for nerve blocks and epidural rim of cortical tissue around the hilum of the cere-
anaesthesia. bral hemisphere.
4% solution for topical anaesthesia of the mucous associated deep structures: hippocampus and gyrus,
membranes of the mouth, pharynx and respiratory uncus, amygdala, cingulate gyrus, part of insula,
tract. septal area, isthmus, Brocas olfactory area and
10% spray for topical anaesthesia as above. Avail- orbital surface of the frontal lobe. Also includes the
able in metered dose delivery systems (10mg/ hippocampal formation and thus associated with
spray). memory.
also available in 12% gel for urethral instillation, Responsible for olfaction, feeding behaviour, motiva-
and 5% ointment for skin, rectum and other mucous tion, sexual behaviour and generation of emotions.
membranes. A constituent of EMLA cream. In Damage to the amygdala is associated with rage
other countries (especially the USA), 5% hyper- reactions, hyperphagia and increased sexual activity;
baric solution has been used in spinal anaesthesia lesions in the uncus with olfactory and gustatory
(but see below). hallucinations.
Dosage: Thought to be one site of action of benzodiazepines
depends on the block. and possibly other anaesthetic drugs.
12mg/kg iv 25min before intubation/extubation. [Pierre P Broca (18241880), French surgeon]
for ventricular arrhythmias: 1mg/kg iv initially, then
4mg/kg/min for 30min, 2mg/kg/min for 2h and LiMON. Commercial non-invasive monitor of liver
1mg/kg/min thereafter. function and blood volume. Requires peripheral or
Adverse effects are as for local anaesthetic agents. Lido- central venous access and uses a four-wavelength near
caine is thought to be more toxic to nerve tissue when infrared finger sensor. Measures the plasma disappear-
directly applied than other local anaesthetics, hence the ance rate and the 15-min retention rate of an intrave-
increased incidence of transient radicular irritation syn- nous marker, indocyanine green. Knowledge of the
drome following its use for spinal anaesthesia than with cardiac output permits estimation of circulating blood
other drugs (hyperbaricity of the solution and use of volume and indocyanine green clearance within minutes.
very thin needles/catheters are also thought to contrib- As the elimination of indocyanine green is dependent
ute by encouraging pooling of drug around spinal on both liver blood flow and hepatocellular function,
nerves). This has led to revision of the drugs data sheet the system cannot differentiate the cause of a reduced
to specify dilution to 2.5% before administration (even clearance of indocyanine green. However, any sudden
 Lithium poisoning 357

reduction in clearance will reflect a fall in liver blood solutions. Has been used in neonatal respiratory distress
flow. Up to 10 measurements are possible in any 24-h syndrome and ARDS, mostly in animal models, but
period. human studies have been and are currently being
See also, Liver function tests performed.
In total liquid ventilation, the entire lung volume and
Linear analogue scale (Visual analogue scale). Method ventilator circuit are filled, requiring a specialised venti-
of evaluating pain, nausea, anxiety and other symptoms, lator. The liquid is oxygenated to a PO2 of 5090kPa
e.g. for statistical analysis. For example, for pain evalua- (350675mmHg) by either bubbling O2 through it or by
tion, a horizontal 10cm line is drawn on plain paper, using a standard extracorporeal device. Tidal volumes of
with no pain written at the left-hand end, and worst 1520ml/kg are given at a rate of about 5 breaths/min.
possible pain at the right-hand end. The patient marks In partial liquid ventilation (perfluorocarbon-associated
his or her position on the line. Thought to be more reli- gas exchange; PAGE) a volume approximating to FRC
able than assessments where patients choose the most is instilled and standard IPPV continued. Results in
appropriate number or word from a list, which may be improved oxygenation and increased compliance,
influenced by personal preference for certain words or thought to be via increased recruitment of non-aerated
numbers and limited by the number of choices offered. alveoli and redistribution of perfusion. A protective
Thought to be consistent for any individual; however, effect against further lung injury has been suggested.
because patients may interpret the analogue scale differ- Kaisers U, Kelly KP, Busch T (2003). Br J Anaesth; 91:
ently, comparison between patients may be unreliable. 14351
Also, patients tend to avoid the extremes of the scale,
clustering their scores around the middle; the scale is Lissive anaesthesia. Obsolete technique of anaesthesia
thus not truly linear. in which small doses of non-depolarising neuromuscular
blocking drugs (originally tubocurarine) were used to
Linezolid. Oxazolidinone antibacterial drug active produce muscle relaxation without causing complete
against Gram-positive bacteria, including multiresistant paralysis, allowing spontaneous respiration diaphrag-
staphylococci and enterococci, but poorly active against matic sparing.
Gram-negative organisms.
Dosage: 600mg bd orally or iv over 30120min, for Liston, Robert (17941847). Scottish-born surgeon; per-
a maximum of 28 days. formed the first operation under diethyl ether anaesthe-
Side effects: GIT disturbance, headache, dry mouth, sia in England on 21 December 1846, at University
blood dyscrasias (full blood count must be monitored College Hospital, London, having been told about ether
weekly). Has weak MAOI properties. by Boott. William Squire administered the anaesthetic
from a glass inhaler made by his uncle, Peter, whilst
Lingual nerve block, see Mandibular nerve blocks Frederick Churchill had an above-knee amputation. The
operation allegedly lasted 25s.
Lipid emulsion. Fat emulsion for iv administration com- [William Squire (18251899), London medical student,
posed of soya bean oil, glycerol and egg phospholipids. later physician; Peter Squire (17981884), London
Available in 10%, 20% and 30% concentration (of soya chemist; Frederick Churchill (1810?), English butler]
oil) for parenteral nutrition. 20% emulsion is the recom-
mended treatment for circulatory arrest due to local Lithium carbonate/citrate. Salts used for manic-
anaesthetic agents (and should also be considered for depressive disease. Lithium mimics sodium in the
severe toxicity without loss of circulation). Animal body, entering excitable cells during depolarisation. It
studies and case reports also support its use in the decreases release of central and peripheral neuro
treatment of poisoning with other lipophilic drugs, transmitters and may prolong depolarising and non-
including: -adrenergic receptor antagonists; calcium neuromuscular blockade and decrease requirements for
channel blocking drugs; tricyclic antidepressant drugs; anaesthetic agents. Termination 24h before anaesthesia
and neuroleptic drugs (e.g. haloperidol). Few adverse has been suggested but this is disputed. Has low thera-
effects have been associated with its use in acute poison- peutic ratio, with optimal plasma concentration of
ing, although pancreatitis may occur with acute 0.41.0mmol/l and toxicity occurring at > 1.5mmol/l.
hyperlipidaemia. Distributed slowly within the tissues (2436h with slow-
Dosage: for local anaesthetic toxicity: 1.5ml/kg of release preparations). Almost entirely excreted by the
20% emulsion over 60s, followed by an infusion of kidneys, with half-life 612h initially but > 24h if the
15ml/kg/h; maximum of two repeat boluses every tissue compartment contains significant amounts of
5min if circulation not restored (infusion rate should drug. Lithium poisoning may occur acutely and deliber-
also be doubled), up to a maximum of 12ml/kg total ately, or insidiously during chronic treatment as a result
dose. Similar regimens have been used for poisoning of dehydration, impaired renal function, infection and
with other agents. use of drugs, e.g. NSAIDs, diuretics.
Turner-Lawrence DE, Kerns Li W (2008). J Med Toxicol; Dosage: 200mg2.0g/day depending on the prepara-
4: 10914 tion, indication, plasma level and clinical response.
Side effects: as for lithium poisoning.
Lipopolysaccharide, see Endotoxins
Lithium poisoning. Toxic effects of lithium may be seen
Liquid ventilation. Technique of partially or totally at plasma concentrations of < 1.0mmol/l but are common
filling the lungs with perfluorocarbons (especially per- at > 1.5mmol/l; severe toxicity is usual at levels >
fluorooctylbromide) and ventilating with this liquid 2.0mmol/l, although acute poisoning may produce high
instead of O2-enriched air. First done experimentally in concentrations before the onset of symptoms. Features
animals in the early 1960s, using pressurised crystalloid include lethargy or restlessness initially; then tremor,
358 Litre

ataxia, GIT upset, weakness and muscle twitching; finally, stimulation of the livers autonomic innervation.
hypokalaemia, arrhythmias, renal failure, convulsions Kupffer cells phagocytose antigens and bacteria
and coma. absorbed from the GIT, and destroy old red cells.
Management consists of increasing urine output if drug metabolism: achieved by transforming lipid-
symptoms have not yet developed; general treatment is soluble compounds into water-soluble ones via
supportive with control of electrolyte imbalance and enzymes located in the hepatocyte microsomes.
convulsions, and haemodialysis (that may need repeat- Several processes are involved, including oxidation,
ing as lithium redistributes from the tissues to the circu- conjugation, reduction, hydrolysis, methylation and
lation) if neurological symptoms are present or if plasma acetylation. Most drugs are metabolised by a com-
concentration is > 7.5mmol/l after acute overdose (or > bination of oxidation by cytochromes and conjuga-
4mmol/l in chronic overdose). The possibility of pro- tion (see Pharmacokinetics).
longed absorption of lithium from slow-release prepara- Effects of anaesthetic agents:
tions should be remembered. Activated charcoal is both hepatic artery and portal vein blood flow are
relatively ineffective at preventing further absorption; reduced by most agents, probably as a consequence
whole bowel irrigation has been used but is not standard of reduced cardiac output. The effect is opposed by
therapy. hypercapnia and exacerbated by hypocapnia and
IPPV, although this is rarely significant.
Litre. SI unit of volume. Originally defined as the volume drug metabolism may be reduced in the presence of
of 1kg pure water at 4C, but redefined as equal to volatile agents, although whether due to alterations
1000cm3 in 1964, because of an error in the standard in hepatic blood flow or a direct inhibitory effect is
kilogram constructed in 1889. unclear.
enzyme induction by volatile agents has been
Liver. Largest body organ, weighing about 12001500g, reported but is controversial.
lying in the right upper abdominal quadrant. Two major toxic effects: e.g. halothane hepatitis.
lobes, right and left, are divided into lobules based on a [Karl W von Kupffer (18291902), German anatomist]
central vein connected by a network of sinusoids to
peripheral portal tracts. Central veins are tributaries of Liver dialysis. Term used to describe various techniques
hepatic veins; portal tracts contain branches of the for extracorporeal detoxification of blood in hepatic
hepatic artery, portal vein, lymphatics and bile ducts. failure. Includes the molecular adsorbents recirculation
Blood from the hepatic arterial and portal venous system (MARS) in which a dialysis circuit containing
systems is conveyed to the central veins via the sinusoids, albumin is separated from the patients blood by a semi-
lined with endothelial and phagocytic (Kupffer) cells permeable membrane, the albumin filtered in a second
and separated by hepatocytes. Bile canaliculi form net- circuit before being reused. Single-pass albumin dialysis
works between the hepatocytes, conveying bile towards (SPAD) uses a single disposable circuit containing
the biliary tract. albumin. Continuous venovenous haemodiafiltration
Blood flow is about 2030% of cardiac output (70% and other variants of haemoperfusion and haemodialy-
via the portal vein). sis have also been investigated. Few are in routine use,
Functions:
although MARS was approved in the USA in 2005 for
carbohydrate metabolism: glycogen storage and
patients awaiting liver transplantation.
breakdown.
protein metabolism: synthesises many, including
albumin, globulins, coagulation factors, complement Liver failure, see Hepatic failure
proteins, transferrin, haptoglobulins, caeruloplas-
min, plasma cholinesterase and 1-antitrypsin. Liver function tests. Most commonly measured:
Important site of amino acid deamination before bilirubin (see Jaundice).
interconversion and oxidation. Ammonia produced liver enzymes:
by deamination is converted to urea. - aspartate aminotransferase (AST) and alanine
fat metabolism: breakdown of dietary triglycerides aminotransferase (ALT): released by damaged
and fatty acids, and synthesis of triglycerides, phos- hepatocytes. Very high levels suggest hepatitis.
pholipid and cholesterol, released into the blood- Normally 540iu/l.
stream as lipoproteins. Cholesterol is also used to - alkaline phosphatase (ALP): highly raised in cho-
make bile acids. lestasis, both intra- and extrahepatic. Isoenzyme
bilirubin metabolism: unconjugated fat-soluble bili- analysis differentiates between hepatic and other
rubin is transported to the liver bound to albumin; sources, e.g. bone. Normally 40110iu/l.
it is conjugated with glucuronide to the water- - -glutamyl transferase (GT): non-specific, but
soluble form (see Jaundice). often raised following drug ingestion, e.g. alcohol.
formation of bile acids: cholic and chenodeoxy Normally 1050iu/l.
cholic acids are produced from cholesterol and plasma proteins:
secreted in the bile. Reabsorbed via enterohepatic - albumin: reduced in chronic liver disease after a
circulation. few weeks. Normally 3555g/l.
vitamin storage: A, D, K, B12 and folate. - globulins: increased to varying extents, depending
hormone metabolism and inactivation: include on the underlying cause. Normally 2535g/l.
cortisol, oestrogens, aldosterone, vasopressin and coagulation studies.
thyroxine. others, including:
haematological role: site of haemopoiesis during - bromosulfothalein excretion: rate of excretion
fetal and early neonatal life. Also acts as a reservoir depends on hepatic function.
for blood that can be redistributed to the body by - 1-fetoprotein, increased in hepatoma.
 Local anaesthetic agents 359

- cholinesterase. postoperatively. IPPV is usually maintained for

- 5 nucleotidase, increased in biliary obstruction. 2448h. Postoperative problems include infection,
Limdi JK, Hyde GM (2003). Postgrad Med J; 79: atelectasis and pleural effusion, graft failure, hepatic
30712 artery thrombosis, biliary leaks or obstruction, neu-
rological impairment and renal failure.
Liver transplantation. First performed in 1963. Indi- Hannaman MJ, Hevesi ZG (2011). Transplant Rev; 25:
cated for end-stage hepatic failure, e.g. due to inherited 3643
disease, chronic hepatitis, acute toxic hepatitis, primary See also, Organ donation; Transplantation
biliary cirrhosis and some cases of liver tumour. Scoring
systems are commonly used to prioritise potential recipi- Living will, see Advance decision
ents, based on the likelihood of death whilst waiting for
transplantation. Surgery involves vascular and biliary Local anaesthesia, see Infiltration anaesthesia; Local
isolation of the diseased organ (pre-anhepatic and anhe- anaesthetic agents; Regional anaesthesia; Topical anaes-
patic phases) with re-anastomosis of a donor cadaveric thesia; specific blocks
organ (reperfusion phase); partial donation by live
donors is also performed. The recipients liver is dis- Local anaesthetic agents. Cocaine was introduced
sected to its vascular pedicle, the portal vein, hepatic in 1884 by Freud and Koller; less toxic agents subse-
artery and inferior vena cava above and below the liver quently introduced include procaine and stovaine (1904),
are clamped, and the diseased organ is removed. Veno- cinchocaine (1925), tetracaine (amethocaine) (1931) and
venous bypass is often employed from the portal and lidocaine (lignocaine) (1947). Lidocaine is particularly
femoral veins to the axillary or internal jugular veins, non-toxic. Later drugs include chloroprocaine (1952),
although practice varies between centres. Donor liver mepivacaine (1956), prilocaine (1959), bupivacaine
viability is up to 8h from harvesting. It is flushed with (1963), etidocaine (1972), articaine (1974), ropivacaine
crystalloid solution via the portal vein to remove the and levobupivacaine (both 1997). Others are used only
transport infusate and air bubbles. Anastomosis of the for topical anaesthesia, e.g. benzocaine.
portal vein and hepatic artery is followed by release of General properties (Table 28):
vascular clamps, incorporating the donor liver into the poorly water-soluble weak bases with pKa > 7.4.
recipients circulation. composed of hydrophilic and hydrophobic portions
Anaesthesia: separated by an alkyl chain. The hydrophilic part is
as for hepatic failure. Preoperative assessment usually a tertiary amine; the lipophilic part (essen-
includes evaluation of cardiovascular status and tial for local anaesthetic action) is usually an unsat-
other co-morbidity. Opioid, volatile agent, neuro- urated aromatic ring, e.g. para-aminobenzoic acid.
muscular blockade and IPPV are usual; N2O is modification of chemical structure (lengthening the
avoided to reduce bowel distension and risk of air alkyl chain or increasing the number of carbon
embolism during re-anastomosis. Aseptic tech- atoms in the aromatic ring or tertiary amine) may
niques are used to reduce infection. Ciclosporin and alter lipid solubility, potency, rate of metabolism
corticosteroids are given. and duration of action.
monitoring and vascular lines include direct BP and classified according to the nature of linkage between
CVP measurement, pulmonary artery catheterisa- the amine and aromatic parts into ester or amide
tion (or a non-invasive method of cardiac output drugs:
measurement), several large iv cannulae, tempera- - esters:
ture probes and urinary catheter. - allergic reactions are common.
frequent measurement of plasma electrolytes, - rapidly metabolised by plasma and liver cholin-
glucose, haemoglobin, platelets, arterial blood gases esterase. One metabolite, para-aminobenzoic
and coagulation studies is required. Thromboelas-
tography is useful.
blood loss is usually 810 units but may be up to 200
units. Cell salvage is often used. Rapid blood trans-
fusion devices are required to keep up with losses; Table 28 Properties of local anaesthetic agents
they include a reservoir of several units of blood,
driven by a pump. Venous return may also be Equivalent Recommended
reduced by surgical manipulation. % Protein concentration maximal safe
SVR and cardiac rhythm/output may change fre- Agent pKa binding (%) dose (mg/kg)
quently. Myocardial depression may be caused by
hypocalcaemia, hypothermia and acidosis. Acidosis Esters
is common but treated cautiously, as postoperative Amethocaine 8.5 76 0.25 1.5
metabolic alkalosis is also common, due to metabo- Chloroprocaine 8.7 1 15
Cocaine 8.7 1 3
lism of lactate and citrate. Inotropic drugs are often
Procaine 8.9 6 2 12
required. Amides
hypoglycaemia and hyperglycaemia may occur, Bupivacaine 8.1 96 0.25 2
especially during the anhepatic phase. Cinchocaine 7.9 0.25 2
potassium levels fluctuate due to acidbase changes, Etidocaine 7.7 94 0.5 2
flushing out of liver perfusate and uptake by the Lidocaine 7.9 64 1 37
transplanted liver. Mepivacaine 7.6 78 1 5
surgery usually lasts 810h but may be up to Prilocaine 7.9 55 1 58
24h, with major biochemical, haematological Ropivacaine 8.1 94 1 3.5
and temperature disturbances that may persist
360 LODS

acid, is thought to be responsible for allergic doubtful; thus rarely used now except in eye
reactions. Metabolism may be prolonged when blocks.
plasma cholinesterase level is low, e.g. liver - dextrose to increase baricity for spinal anaesthe-
disease, pregnancy or atypical enzymes. sia: affects spread.
- amides: Toxicity:
- allergic reactions are rare; they may be associ- may follow accidental iv injection, or systemic
ated with the preservative vehicle. absorption, the latter affected by:
- metabolised by liver microsomal enzymes, - total dose administered. Recommended maximal
initially to aminocarboxylic acid and a safe doses are useful as a guide but are rough
cyclic aniline derivative, subsequently via estimations only, since other factors are involved
N-dealkylation and hydroxylation respectively. (see Table 28).
Dependent on liver blood flow and function. - site of injection: e.g. absorption is large after
presented in solution as acidic hydrochloride salts. topical anaesthesia and intercostal block and slow
Mechanism of action: after brachial plexus block and infiltration anaes-
produce reversible blockade of peripheral and thesia. Affected by blood flow and tissue
central neural transmission in autonomic, sensory vascularity.
and motor nerve fibres, depending on the concen- - vasoconstrictor additives.
tration of drug applied. - individual drug: e.g. lidocaine causes vasodilata-
bind to fast sodium channels in the axon membrane tion; bupivacaine binds extensively to tissues.
from within, preventing sodium entry during depo- Ropivacaine and levobupivacaine are less toxic
larisation. The threshold potential is thus not than bupivacaine.
reached and the action potential of the nerve not due to membrane-stabilising effects on other cells,
propagated (membrane-stabilising effect). especially heart and CNS. Features:
fate of injected drug: - tingling, typically around the mouth and tongue.
- diffuses to axons; thus more effective if depos- - lightheadedness, agitation and tremor.
ited close to the nerve (see Minimal blocking - unconsciousness and/or convulsions.
concentration). - hypotension may be caused by hypoxaemia fol-
- crosses the membrane in the unionised form; lowing central apnoea, direct myocardial depres-
thus activity depends on extracellular pH, since sion or vasodilatation. Arrhythmias and cardiac
the degree of ionisation and thus lipid insolubility arrest may occur; resistant ventricular arrhyth-
is increased by acidosis. The pH of infected tissue mias are particularly likely with bupivacaine.
is lower than normal, hence the effectiveness of treatment:
local anaesthetics is reduced. - supportive, with oxygenation/cardiovascular sup-
- dissociates within the axon to the ionised form; port as for CPR.
thus dependent on intracellular pH. - lipid emulsion 20%: 1.5ml/kg bolus over 1min,
- binds to sodium channels in their open state. repeated up to two times, followed by 15ml/kg/h
smallest nerve fibres are blocked first. increased to 30ml/kg/h if the CVS is stable. Pro-
Features of block are affected by: pofol is not a viable alternative because of the
patient variables, e.g. age, fitness, pregnancy. drugs haemodynamic effects and low concentra-
individual drug characteristics. tion of intralipid.
concentration and dose used: e.g. higher concentra- - thiopental or diazepam/midazolam may be used
tions and doses reduce onset time, and increase for convulsions, although hypotension may be
density and duration of block. exacerbated.
site of injection, e.g. rapid onset of spinal anaesthe- other complications may be related to:
sia but slow onset of brachial plexus block. - vasoconstrictors, e.g. tachycardia, arrhythmias,
additives: pallor, agitation, caused by adrenaline.
- vasoconstrictors, e.g. adrenaline, felypressin, - regional technique, e.g. intraneural injection,
phenylephrine: reduce systemic absorption and hypotension following spinal anaesthesia.
prolong the block. Intensity and onset may be - preservatives, e.g. allergic reactions (e.g. to
improved. Effects are greatest with local anaes- methylparaben), neurological damage and
thetics that cause vasodilatation, e.g. lidocaine, arachnoiditis.
and less with prilocaine and bupivacaine. Cocaine See also, Ionisation of drugs; Regional anaesthesia; spe-
itself causes vasoconstriction. Noradrenaline is cific blocks
less effective than adrenaline.
- CO2 dissolved under pressure (carbonated solu- LODS, see Logistic organ dysfunction system
tions): passes into axons, lowering pH; intracellu-
lar dissociation is thus favoured, with faster block. Lofentanil cis-oxalate. Opioid analgesic drug derived
- sodium hydroxide: remains extracellular, raising from fentanyl; developed in 1975. 20 times as potent as
pH and increasing the unionised fraction of drug; fentanyl and 6000 times as potent as morphine in animal
uptake into the axon is thus favoured. studies. Of similar pKa to fentanyl, highly lipophilic and
- potassium: has been shown to increase duration with a particularly long duration of action due to persis-
of block. tent binding to opioid receptors (about 10h). Has been
- dextrans: used to prolong blocks, perhaps by com- used via the epidural route to provide long-lasting anal-
bining with local anaesthetic and trapping it gesia, but not generally available.
within the tissues. Results are inconsistent.
- hyaluronidase: formerly used to increase spread Logistic organ dysfunction system (LODS). Scoring
by breaking down tissue stroma. Benefits are system developed to predict hospital mortality from 11
 Luer connectors 361

variables measured on the first day of admission to ICU opioid analgesic drugs, volatile anaesthetic agents
(Glasgow coma scale, heart rate, systolic BP, urea, creati- and most iv anaesthetic agents.
nine, urine output, PaO2/FIO2 ratio, white cell count, plate- ganglion blocking drugs.
lets, bilirubin and international normalised ratio). The Tone is increased by:
total score ranges from zero (normal) to 22. metoclopramide, domperidone and prochlor
Has been modified by adding infection as a 12th item perazine.
(organ dysfunction and/or infection; ODIN). neostigmine.
Keegan MT, Gajic O, Afessa B (2011). Crit Care Med; pancuronium.
39: 1639 No change is found with H2 receptor antagonists.
See also, Mortality/survival prediction on intensive Although suxamethonium may increase intragastric
care unit pressure, the corresponding increase in lower oesopha-
geal sphincter tone maintains barrier pressure.
Long, Crawford Williamson (18151878). US general Sphincter incompetence may result in gastro-
practitioner; administered diethyl ether several times for oesophageal reflux. It becomes less competent in hiatus
minor surgery from 1842 in Georgia, but did not report hernia, particularly if intra-abdominal pressure increases,
it until after Mortons demonstration. e.g. in the head-down position.
Hammonds WD, Steinhaus JE (1993). J Clin Anesth;
5: 1637 LownGanongLevine syndrome. Tendency to SVT
caused by an accessory conducting pathway bypassing
Long QT syndromes, see Prolonged QT syndromes the atrioventricular node. Impulses may pass directly
from the atria to the distal heart conducting system,
Lorazepam. Benzodiazepine, used for insomnia, epi- without the usual delay at the node.
lepsy, sedation and premedication. Now the initial drug Characterised by a normal P wave, short PR
of choice in status epilepticus. Half-life is approximately interval and normal QRS complex on the ECG. Anaes-
12h with prolonged duration of action. Said to produce thetic management is as for WolffParkinsonWhite
more amnesia than other benzodiazepines. Similar rates syndrome.
of absorption follow im and oral administration. [Samuel A Levine (18911966) and Bernard Lown,
Metabolised to a non-active metabolite. US cardiologists; William F Ganong (19242007), US
Dosage: physiologist]
14mg orally. If given the night before surgery, a
further 12mg may be given 12h preoperatively. LPS, Lipopolysaccharide, see Endotoxins
2530g/kg iv (50100g/kg in status epilepticus).
Lucid interval. Period of apparently normal function
LOS, see Lower oesophageal sphincter and behaviour following head injury, during which blood
is accumulating inside the skull from a slowly bleeding
Lower oesophageal sphincter. 25cm portion of vessel. Classically occurring with extradural haemor-
oesophagus of increased intraluminal pressure, extend- rhage, features only become apparent when the collec-
ing above and below the diaphragm. Opens reflexly tion causes compression of intracranial structures;
during swallowing, and helps to prevent retrograde because this may occur up to several hours after injury,
passage of gastric contents into the oesophagus via: diagnosis may be delayed and significant impairment
increased muscle tone: muscle of the sphincter zone, may result.
especially the inner circular layer, has higher resting
tone than other oesophageal muscle, possibly via Ludwigs angina. Cellulitis of the floor of the mouth
increased calcium ion uptake and utilisation. and submandibular region, with massive swelling. Often
neural input: due to anaerobic infection. May progress to laryngeal
- vagal: muscle tone reflexively increases as gastric obstruction and death unless treated with antibiotics ini-
pressure increases, thus maintaining barrier pres- tially, or by deep incision of the tissues under the
sure (normally about 20cmH2O). The reflex is mandible.
abolished by atropine. Anaesthetic management is as for airway obstruction;
- sympathetic: tone is increased by -stimulation antibiotic therapy may reduce the swelling and improve
and -blockade, and decreased by -stimulation obstruction preoperatively. Local anaesthesia may be
and -blockade. preferable in extreme cases.
mechanical factors: [Wilhelm von Ludwig (17901865), German surgeon]
- oesophageal compression by the diaphragm.
- acute angle of entry of the oesophagus into the Luer connectors. Worldwide system of standard fittings
stomach. designed to provide leak-free (for air and fluid) connec-
- mucosal flap or rosette at the oesophageal tions between syringes, hypodermic needles and three-
opening. way taps. The two standard types are Luer-Lok (ends
Muscle tone is decreased by: joined securely via a screw thread and matching hub on
anticholinergic drugs given iv; possibly less with the male and female connections, respectively) and
glycopyrronium. Atropine im does not affect Luer-Slip (tapered male and female connections held in
sphincter pressure, but inhibits the action of place by friction). Although originally designed for iv
metoclopramide. equipment, Luer connections are now present on many
gut hormones, e.g. vasoactive intestinal hormone, others, e.g. nasogastric tubes, airway monitoring tubing,
glucagon and gastric inhibitory peptide. Gastrin and equipment for spinal and epidural anaesthesia. Fatal
may increase tone at very high levels. wrong-route errors involving the latter (e.g. iv adminis-
progesterone. tration of local anaesthetic agents or intrathecal/epidural
362 Lumbar epidural anaesthesia

administration of iv cytotoxic drugs) have led to repeated

T12
calls for the development and adoption of non-Luer con-
nector systems, but their introduction has been beset by
enormous logistical problems. In 2009, the NPSA called
L1 Iliohypogastric n
for all spinal equipment to be non-Luer by April 2011 Ilioinguinal n
(revised in 2010 to April 2012), but adherence in the Genitofemoral n
NHS has been inconsistent, partly due to difficulties over Lateral
L2
proper evaluation of the new equipment. cutaneous
[Hermann W. Luer (18361910), German medical instru- n of thigh
ment maker] L3
Cook TM (2012). Anaesthesia; 67; 7: 784-92

Lumbar epidural anaesthesia, see Epidural L4

anaesthesia Femoral n Obturator n

Lumbar plexus. Formed in front of the transverse pro- Fig. 102 Plan of the lumbar plexus
cesses of the lumbar vertebrae from the anterior primary
rami of the first four lumbar nerves, occasionally with a
contribution from T12 (Fig. 102).
bodies in the lateral view, and should overlie their lateral
May be blocked via paravertebral, psoas compart-
edge in the anteroposterior view. Further confirmation
ment, fascia iliaca compartment and three-in-one
of positioning is made by injecting contrast medium.
femoral nerve blocks. Individual nerves may also be
2530ml local anaesthetic solution (e.g. 0.5% lidocaine
blocked. Block is useful for hip surgery and operations
or prilocaine) is injected at L2, or 15ml at L2 and L4.
on the thigh and anterior gluteal region, together with
Catheters may be inserted for repeated injection. Phenol
adjacent perineal and suprapubic areas.
or absolute alcohol is used for chemical sympatholysis,
See also, Inguinal hernia field block
3ml at each of L1, L2 and L3. The block may also be
performed with patient prone.
Lumbar puncture. Procedure for removing CSF either Complications include hypotension, genitofemoral
for diagnostic purposes (e.g. meningitis) or treatment neuritis, bleeding into psoas and epidural, subarachnoid
(e.g. benign intracranial hypertension, intrathecal injec- or iv injection.
tion of chemotherapy, CSF filtration). First performed by Similar blocks have been performed in the thoracic
Quincke for the treatment of hydrocephalus. Forms part region but with risk of pneumothorax.
of the procedure of spinal anaesthesia. May be required
in the ICU for diagnosis of neurological conditions.
Technique, contraindications and complications are as Lundberg waves, see Intracranial pressure monitoring
for spinal anaesthesia but without the drug effects; CSF
opening pressure may also be measured, using a simple Lundy, John Silus (18941973). US anaesthetist; he
manometer. Neurologists, general physicians and radi- became head of department at the Mayo Clinic in 1924.
ologists are more likely to use larger needles with cutting Co-founder of the American Board of Anesthesiology.
points than anaesthetists; whether subsequent post- An advocate and developer of regional techniques,
dural puncture headache (PDPH) is masked by the pre- balanced anaesthesia, thiopental and post-anaesthetic
senting symptoms is uncertain. The incidence of PDPH recovery rooms. Established the first blood bank in
may be decreased if the stylet is reinserted after aspira- the USA.
tion before removal of the needle, presumably by pre-
venting avulsion of dural strands sucked into the needles Lung. Organ of respiration. Continues to develop after
shaft during removal of CSF. birth, with alveolar proliferation complete at about
8 years.
Lumbar sympathetic block. Performed for periph- Anatomy:
eral vascular disease, including incipient gangrene, and cone-shaped, with bases applied to the diaphragm.
in chronic pain management (e.g. post-traumatic enveloped in pleura, attached to the mediastinum
dystrophies). at the hila.
The lumbar sympathetic chain lies on the anterolat- the right lung is larger than the left and divided into
eral aspect of the lumbar vertebral bodies within a three lobes separated by the oblique and transverse
fascial compartment formed by the vertebral column, fissures.
psoas sheath and posterior peritoneum. the left lung is divided into two lobes by the oblique
With the patient in the lateral position and with a fissure. The lingula is the anteroinferior portion of
soft pillow between the iliac crest and costal margin to the upper lobe.
curve the spine laterally, skin wheals are raised 58cm lobes are divided into segments (see Tracheobron-
lateral to the upper borders of the spinous processes of chial tree).
L24. A 1218cm long needle is directed medially, to surface anatomy:
strike the transverse process at about 35cm. The lateral - as for pleura, except for the lower border,
aspect of the vertebral body is contacted usually 46cm which lies two ribs cranial to the caudal pleural
deeper, and the needle advanced a further 12cm. limit.
Correct positioning is confirmed by negative aspiration - on the left side, the medial anterior border lies
for CSF or blood, and radiographic imaging: the needles 23cm lateral to the sternum at the fifth and sixth
should barely reach the anterior borders of the vertebral costal cartilages (cardiac notch).
 Lung transplantation 363

- the oblique fissure follows a line from the spine - distribution of ventilation and perfusion as for
of T4 downwards and outwards to the sixth costal V /Q
 mismatch.
cartilage. pulmonary circulation: assessment is difficult.
- the transverse fissure follows a horizontal line Radioisotope scanning may be used as for V /Q 
from the fourth costal cartilage until it hits the mismatch.
previous line. control of breathing: CO2 response curve or
Blood supply: via bronchial and pulmonary arteries response to hypoxia may be used.
(see Pulmonary circulation). response to exercise, using the above tests.
Nerve supply: sympathetic and vagal plexuses; sensory See also, Body plethysmograph; Nitrogen washout
pathways are mainly via the latter.
Lymph drainage: via bronchopulmonary, tracheo- Lung protection strategies. Principles of mechanical
bronchial and paratracheal nodes to mediastinal ventilation demonstrated to improve outcomes in acute
lymph trunks and thence brachiocephalic veins. lung injury. Components include:
Functions: avoidance of overdistension of alveoli.
gas exchange. permissive hypercapnia.
synthesis of associated phospholipids, e.g. surfac- maintenance of alveolar volume.
tant, carbohydrates (e.g. mucopolysaccharides) and prevention of radial stress associated with cyclical
proteins (e.g. collagen). end-expiratory collapse and re-expansion at low
metabolism and deactivation of certain compounds, lung volumes.
e.g. angiotensin, bradykinin and 5-HT. Takes up Inspiratory plateau pressure is usually limited to <
amide local anaesthetic agents. 35cmH2O. Pressurevolume curves may be used to
synthesis and release of compounds, e.g. prostaglan- identify an upper inflection point (UIP), thought to rep-
dins and histamine. resent the point of alveolar overdistension, and a lower
involvement in the immune system and possibly inflection point (LIP), thought to represent the point of
coagulation. alveolar recruitment during inflation. PEEP levels are
acts as a reservoir for blood; the pulmonary circula- set at or above LIP; maximum inspiratory plateau pres-
tion contains 500900ml blood. sure is set below UIP. Extracorporeal CO2 removal
See also, Alveolus; Lung ; Pulmonary has also been used to reduce the minute ventilation
requirement.
Lung function tests. Used to determine the nature and Yilmaz M, Gajic O (2008). Eur J Anaesthesiol; 25:
extent of pulmonary disorders. Clinical assessment, e.g. 8996
ability to walk up stairs, breath-hold for > 30s, or blow
out a lighted match held 15cm (6 inches) away, are Lung transplantation. First performed in 1963; includes
imprecise and non-specific indicators. transplantation of a single lung, both lungs (rarely per-
Include tests of: formed now), or sequential single lungs during the same
ventilation mechanics: operation. Most commonly performed for COPD and
- measurement of static lung volumes: cumbersome idiopathic pulmonary fibrosis, but also for cystic fibrosis
apparatus is required. Dead space and closing and other causes of end-stage lung disease. Similar con-
capacity may be measured. siderations apply as to heartlung transplantation:
- assessment of forced expiration and derived vari- Donor:
ables (e.g. FEV1, FVC, forced expiratory flow as for heartlung transplantation; those with signifi-
rate), e.g. using a spirometer. The FEV1/FVC ratio cant respiratory disease are excluded. HLA mis-
typically is reduced in obstructive lung disease, matching is not associated with reduced long-term
and is normal or high in restrictive disease. Peak rejection, although matching of size is important.
expiratory flow rate is another simple bedside test up to 9h is thought to be acceptable before trans-
for obstructive disease. Reversibility of obstruc- plantation, although up to 3h is best. Preservative
tive disease is assessed using inhaled broncho techniques may include iv heparin and prostacyclin
dilator drugs. Airway reactivity is assessed by (the latter into the pulmonary artery) before
challenging with histamine or methacholine whilst removal from the donor. A left atrial cuff, pulmo-
measuring FEV1. nary veins, main bronchi and pulmonary artery are
- flowvolume loops require more sophisticated taken in addition to the lungs.
apparatus, with instantaneous flow rate Recipient:
measurement. immunosuppression and antibiotic therapy as for
- airway resistance itself may be measured, and heartlung transplantation.
lung compliance. a double-lumen endobronchial tube or single-lumen
- maximal voluntary ventilation is non-specific and tube with bronchial blocker is used. Initial problems
related to effort as well as pulmonary function. are those of thoracic surgery in general, especially
- respiratory muscle function may be assessed, one-lung ventilation.
e.g. maximal mouth or nasal sniff pressures monitoring may include pulmonary artery catheter-
when breathing against a closed valve. Work of isation (the catheter usually flows to the better per-
breathing and O2 consumption may also be fused lung; it may require withdrawal before the
measured. lung is removed).
gas exchange: control of pulmonary vascular resistance may be
- blood gas interpretation and pulse oximetry. difficult; options include milrinone and inhaled
- diffusing capacity for carbon monoxide (transfer nitric oxide or prostacyclin. If the patient remains
factor); now thought to be related more to V/Q markedly unstable, cardiopulmonary bypass may
mismatch than to diffusion impairment. be used.
364 Lung volumes

Inspiratory reserve volume

Inspiratory capacity

Tidal volume Vital capacity

3.5

Total lung capacity

Litres

Expiratory reserve volume

Functional residual capacity

1.5

Residual volume

Fig. 103 Lung volumes

postoperative problems include non-cardiogenic LVEDV, see Left ventricular end-diastolic volume
pulmonary oedema (pulmonary reimplantation
response), hypoxaemia, disrupted anastomosis, LVET, Left ventricular ejection time, see Systolic time
infection and rejection. Obliterative bronchiolitis intervals
may occur.
Anaesthetic management of patients with transplanted LVF, Left ventricular failure, see Cardiac failure
lungs is as standard, remembering the risks of infection
and graft rejection, pulmonary hypertension and
LVH, Left ventricular hypertrophy, see Cardiac failure
impaired lung function (lung protection strategies are
employed).
Castillo M (2011). Curr Opin Anesthesiol; 24: 326 Lyme disease. Tick-borne disease caused by the
spirochaete Borrelia burgdorferi. First recognised as a
Lung volumes. Functional, not anatomical, volumes of cause of paediatric arthropathy in Lyme, Connecticut,
the lungs, usually expressed as if both lungs comprise USA, in 1975. Widespread in the USA and parts of
one unit. May be derived from a spirometer tracing of Europe and Asia, becoming more common in the UK.
inhaled/exhaled volumes, with maximal inspiration and Causes characteristic expanding skin lesions (erythema
expiration following normal tidal breathing (Fig. 103). migrans) at the site of the ticks bite, associated with
Approximate normal values for a 70-kg man: systemic flu-like symptoms. Weeks to months later, neu-
tidal volume: 0.5 litres
rological features (meningitis, encephalitis, cranial neu-
inspiratory reserve volume: 2.5 litres
ritis) lasting for months occur in 15% of cases whilst
inspiratory capacity: 3.0 litres
8% develop cardiac features (heart block, myocarditis)
vital capacity: 4.5 litres
lasting a few days. Arthritis occurs up to 2 years later in
expiratory reserve volume: 1.5 litres
60% of cases. Diagnosis is on clinical grounds, aided by
residual volume: 1.5 litres
serological testing. Treatment is with penicillins, tetracy-
FRC: 3.0 litres
clines, cephalosporins or macrolides depending on the
total lung capacity: 6.0 litres.
presentation and stage of illness. Outcome is usually
Capacities are sums of volumes. favourable, although late neurological complications
Tidal volume, inspiratory reserve volume, expiratory may persist.
reserve volume and capacities derived from them may [Willy A Burgdorfer, Swiss-born US entomologist]
be measured using a wet spirometer. Residual volume
may be measured using helium dilution or the body Lypressin, see Vasopressin
plethysmograph.
Other lung volumes measured include dead space Lytic cocktail. Obsolete mixture of chlorpromazine,
and closing capacity. Differential spirometry is used to promethazine and pethidine, described in the 1940s as a
examine function of single lungs. means of sedation, e.g. for premedication and labour.
See also, Lung function tests Produced a state of drowsiness and apathy (artificial
hibernation) but effects were long-lasting and accompa-
LVEDP, see Left ventricular end-diastolic pressure nied by hypotension.
 M
MAC, see Minimal alveolar concentration some Gram-negative bacteria, mycoplasma, rickettsia
and toxoplasma) but varying properties otherwise; thus
Macewen, William (18471924). Eminent Scottish the latter three drugs have longer durations of action
surgeon; Professor at Glasgow University, knighted in than erythromycin and cause less nausea and vomiting.
1902. Advocated and practised tracheal intubation,
usually oral, for laryngeal obstruction, e.g. due to diph- Macrophage colony-stimulating factor, see Granulo-
theria; he performed this by touch without anaesthetic. cyte colony-stimulating factor
Was the first to advocate tracheal intubation instead of
tracheotomy for head and neck surgery, in 1880. The Magill breathing system, see Anaesthetic breathing
tube was inserted before introduction of chloroform, systems
and the patient allowed to breathe spontaneously.
Packing around the tube achieved a seal. Magill, Ivan Whiteside (18881986). Irish-born anaes-
James CDT (1974). Anaesthesia; 29: 74353 thetist, responsible for much of the innovation in, and
development of, modern anaesthesia. With Rowbotham
Macintosh, Robert Reynolds (18971989). New in Sidcup after World War I, he developed endotracheal
Zealand-born anaesthetist, he became the first British anaesthesia as an alternative to insufflation techniques,
Professor of Anaesthetics in Oxford in 1937. Lord Nuff- originally for facial plastic surgery. Introduced his own
ield, a friend of Macintosh, had insisted that such a chair anaesthetic breathing system, forceps, laryngoscope and
be set up as a precondition for endowing further chairs connectors, and developed blind nasal intubation. A
in Medicine, Surgery and Obstetrics and Gynaecology. pioneer of anaesthesia for thoracic surgery, he devel-
Established Oxford as a centre for anaesthesia, and oped one-lung anaesthesia, endobronchial tubes and
helped to establish anaesthesia as a medical specialty. bronchial blockers. Also introduced bobbin flowmeters,
Wrote books and articles about many aspects of local portable anaesthetic apparatus and other equipment.
and general anaesthesia, and designed many pieces of Co-founder of the Association of Anaesthetists of
equipment, including his laryngoscope, spray, endobron- Great Britain and Ireland, he also helped establish the
chial tube, vaporisers and devices for locating the epidu- DA examination, the Faculty of Anaesthetists and the
ral space. Also helped research the hazards of aviation FFARCS examination. Worked at the Westminster and
and seafaring. Knighted in 1955, and received many Brompton Hospitals, London. Knighted in 1960, and
other medals and awards. received many other medals and awards.
[William Morris (18771963), English automobile indus- Edridge AW (1987). Anaesthesia; 42: 2313
trialist and philanthropist became Lord Nuffield in
1934] Magnesium. Largely intracellular ion, present mainly in
Mushin WW (1989). Anaesthesia; 44: 9502 bone (over 50%) and skeletal muscle (20%); the remain-
der is found in the heart, liver and other organs. 1% is
McKesson, Elmer Isaac (18811935). US anaesthetist, in the ECF. Normal plasma levels: 0.751.05mmol/l
practising in Toledo, Ohio. Founder and member of (although the value of measurement has been ques-
many US and international anaesthetic bodies. Also tioned, since most magnesium is intracellular). Defi-
inventor and manufacturer of expiratory valves, pressure ciency is common in critical illness. Required for protein
regulators, flowmeters, suction equipment, vaporisers and nucleic acid synthesis, regulation of intracellular
and intermittent flow anaesthetic machines. A major calcium and potassium, and many enzymatic reactions,
proponent of the use of N2O in modern anaesthesia. including all those involving ATP synthesis/hydrolysis.
Inhibits voltage-gated calcium channels, acting as a phys-
McMechan, Francis Hoeffer (18791939). US anaesthe- iological antagonist; also an antagonist at NMDA
tist, practising in Cincinnati. A pioneer of the develop- receptors.
ment of anaesthesia in the USA. Founded the American Herroeder S, Schonnher ME, De Hert SG, Hollman MW
Association of Anesthetists in 1912, and instrumental in (2011). Anesthesiology; 114: 97193
founding the National Anesthetic Research Society See also, Hypermagnesaemia; Hypomagnesaemia.
(subsequently the International Anesthesia Research
Society) whose publication (which became Anesthesia Magnesium sulphate. Drug with varied clinical indica-
and Analgesia) he edited. tions, reflecting its numerous sites of action, e.g. non-
competitive inhibition of phospholipase C-mediated
Macrolides. Group of antibacterial drugs containing a calcium release; antagonism of NMDA receptors; inhibi-
lactam ring but distinct from -lactams. Interfere with tion of voltage-gated calcium channels and sodium/
RNA-dependent protein synthesis. Includes erythromy- potassium pumps; and attenuation of catecholamine
cin, azithromycin, clarithromycin and telithromycin. All release from the adrenal glands. Its actions thus
have similar antibacterial activities (Gram-positive and include neuronal/myocardial membrane stabilisation

365
366 Magnesium trisilicate

and bronchial and vascular smooth muscle relaxation. within the MRI suite to allow scanning during operative
Magnesium chloride is also used. procedures.
Clinical indications: Problems and anaesthetic considerations:
as an anticonvulsant drug in pre-eclampsia and magnets used are very powerful but not considered
eclampsia. Thought to act by reducing cerebral directly harmful; however, the maximal safe level
vasospasm seen in the condition. Also causes for occupational exposure to static magnetic fields
systemic vasodilatation, helping to lower BP. Supe- is set at 200 mT over a single 8-h period. Indirect
rior to diazepam and phenytoin in preventing problems:
primary eclampsia, as well as preventing recurrence - metal objects may become dangerous projec-
of seizures. tiles if they are placed near the magnet. All
as a tocolytic drug. ferromagnetic metal equipment, including cylin-
severe asthma resistant to conventional bronchodi- ders, needles and laryngoscope batteries, must
lator therapy. be kept away from the machine. Intracranial
perioperative management of phaeochromocy- clips, pacemakers and heart valves may also be
toma. affected. Non-ferromagnetic anaesthetic equip-
cardiac arrhythmias (e.g torsade de pointes), ment is increasingly available.
especially those caused by hypokalaemia. - monitoring may be difficult because of poor
Dosage: 24g (816mmol) iv over 515min, fol- access to the patient and the need for special
lowed by 12g/h. equipment. Remote monitoring from outside the
Side effects: scanning room requires a window and protective
cardiac conduction defects, drowsiness, reduced brass tubes (waveguides) for cables passing
tendon reflexes, muscle weakness, hypoventilation between the scanning and observation rooms,
and cardiac arrest may occur with increasing with the ability to communicate with the patient.
hypermagnesaemia. Audible alarms may not be heard because of the
augments non-depolarising and depolarising neuro- background noise of the scanner and the need for
muscular blockade. Neonatal hypotonia may also ear protection. Automatic BP devices using plastic
occur. connectors, capnography, oesophageal stetho-
Overdosage may be treated with iv calcium. scopes and non-magnetic oximeters using fibreop-
Therapeutic plasma levels: 2.03.5mmol/l; side effects tic cabling are used. ECG artefacts (especially in
may occur above 45mmol/l, with cardiac arrest the ST region) may be caused by currents
above 12mmol/l. Loss of deep tendon reflexes (e.g. induced by aortic blood flow within the magnetic
knee jerk) may indicate impending toxicity. field. The length of capnography tubing (in side-
Herroeder S, Schonnher ME, De Hert SG, Hollman MW stream analysers) introduces a long delay before
(2011). Anesthesiology; 114: 97193 the CO2 signal is obtained.
- some magnets may be switched off in emergen-
cies, but may require lengthy and expensive
Magnesium trisilicate. Particulate antacid, used in dys-
restarting procedures. Rapid sudden shutdown
pepsia. Has been used to increase gastric pH preopera-
may result in the liquid coolant of the magnet
tively in patients at risk from aspiration of gastric
(cryogen; usually helium in modern devices)
contents, but may itself cause pneumonitis if inhaled.
boiling off and flooding the immediate area if not
Has also been used to reduce risk of peptic ulceration
properly vented (quenching). This may cause a
on ICU, e.g. by hourly nasogastric administration to
dangerous reduction in available O2 with the risk
keep pH above 34.
of asphyxia; proper procedures and O2 sensors are
therefore required.
Magnetic resonance imaging (MRI; Nuclear magnetic radiofrequency pulses may cause heating effects,
resonance, NMR). Imaging technique, particularly thought to be relatively insignificant. These effects
useful for investigating CNS, pelvic and musculoskeletal may be increased with metal prostheses.
pathology, where tissue movement is minimal. By using sedation/anaesthesia may be required, especially in
gating techniques it can also be used in other parts of children or nervous adults, since the subject has to
the body, including the chest; accurate measurements lie within a very small space and the scans are
of the hearts dimensions and movement have been accompanied by loud knocking noises. Problems
obtained. include those of radiology in general, in addition to
Involves placement of the patient within a powerful the above. Scans originally took up to 23h but are
magnetic field, causing alignment of atoms with an odd shorter with newer machines.
number of protons or neutrons, e.g. hydrogen. Radiofre-
quency pulses are then applied, causing deflection of the Malaria. Tropical disease caused by the protozoan plas-
atoms with absorption of energy. When each pulse stops, modium (P. vivax, P. ovale or P. falciparum), and spread
the atoms return to their aligned position, emitting by the anopheles mosquito, which carries infected blood
energy as radiofrequency waves. Computer analysis between individuals. Although not endemic in the UK,
of the emitted waves provides information about individual cases occur not uncommonly because of wide-
the chemical make-up of the tissue studied. MRI can spread air travel. Usual presentation is within 4 weeks
provide graphic tissue slices in any plane, or may be used of travel from an infected area, although onset may be
to analyse metabolic processes, e.g. distribution and delayed by many months. In milder forms, periodic
alterations of intracellular phosphate (spectroscopy). release of the organism from the liver and reticuloendo-
So-called functional MRI (fMRI) techniques demon- thelial system into the bloodstream causes relapsing
strate regional differences in tissue oxygenation and fever, rigors and malaise (typically cycles of pyrexia
cerebral blood flow. Interventional MRI involves surgery lasting 3 days [tertian] or 4 days [quartan], or having no
 Malignant hyperthermia 367

pattern [subtertian], depending on the infecting possible effects of anaesthesia on the immune
organism). system and cancer, e.g. administration of blood
Severe illness and death are more likely with Pl. fal- during bowel cancer resection may decrease
ciparum, particularly common in tropical Africa and survival.
South-East Asia. Incubation period is 714 days. Many anxiety, depression.
features are thought to result from sludging of damaged pain management.
infected red blood cells within capillaries, with resultant
ischaemia of organs. Malignant hyperthermia (MH). Condition first
Features include: described by Denborough in 1961, consisting of increased
rigors, fever, vomiting, headache. temperature and rigidity during anaesthesia. Incidence
confusion, convulsions, coma. 80% of deaths result is reported between 1:5000 and 1:200000. Results from
from cerebral malaria. abnormal skeletal muscle contraction and increased
acute kidney injury. metabolism affecting muscle and other tissues. Suscepti-
hypoglycaemia; thought to be caused by increased bility shows autosomal dominant inheritance; in 5070%
insulin secretion; it may also result from quinine of affected families the predisposing genetic loci are
therapy. found on the long arm of chromosome 19, coding for
bronchopneumonia, acute lung injury, pulmonary the ryanodine/dihydropyridine receptor complex at the
oedema. T-tubule/sarcoplasmic reticulum complex of striated
diarrhoea, endotoxaemia from bowel bacteria. muscle. This receptor regulates calcium flux in and out
anaemia, thrombocytopenia, intravascular hae of the sarcoplasmic reticulum; this control is lost in MH,
molysis, DIC. Diagnosis is made by examining resulting in a massive influx of calcium leading to uncon-
blood films, or rarely, bone marrow, for parasites. trolled muscle contraction. MH susceptibility is also
Prevention: genetically related to central core disease, a rare muscu-
use of insect repellents, mosquito nets over beds, etc. lar dystrophy. Several other gene mutations have been
drug prophylaxis, e.g. mefloquine, doxycycline or implicated, thus reducing the sensitivity of genetic analy-
malarone. sis as a test for MH.
vaccination: a vaccine has been developed that can MH follows exposure to triggering agents, particu-
halve the infection rate. larly the volatile anaesthetic agents and suxamethonium,
Treatment: although it is thought that a single dose of the latter by
chloroquine and primaquine for mild infections. itself will not cause the syndrome. It may occur in
quinine; usually reserved for resistant organisms or patients who have had previously uneventful anaesthet-
severe falciparum infection. ics. MH may also be triggered by stress and strenuous
severe infection: quinine salt 20mg/kg iv over 4h, exercise. Thus patients sensitivity to triggering agents
then 10mg/kg over 4h repeated 812-hourly until may vary at different times. Reactions have been
able to swallow (reduced by a third after 72h if reported up to 11h postoperatively.
unable to swallow). Oral therapy (10mg/kg) is con- Most common in young patients undergoing muscu-
tinued until 7 days treatment is completed. It is loskeletal surgery, including trauma surgery. Whether
then followed by a course of either pyrimethamine/ this reflects an underlying abnormality of muscle predis-
sulfadoxime combination or doxycycline. posing to trauma is unknown. Operations in the young
Malaria may be transmitted by blood transfusion; those are commonly for squints and orthopaedic problems,
with known infection or recent travel to an endemic area and increased incidence in this group may simply repre-
are therefore excluded from being donors. sent the first exposure to anaesthesia in susceptible
Greenwood BM, Bojang K, Whitty CJM, Targett GAT patients.
(2005). Lancet; 365: 148798 All patients should be questioned for family history
of anaesthetic problems, since many susceptible patients
Malignancy. Second commonest cause of death in the give a positive family history. Susceptible patients should
UK after cardiovascular disease. Patients may present to wear Medic Alert bracelets.
anaesthetists for investigative, therapeutic or unrelated Features are related to muscle abnormality and
procedures. ICU management may be required after hypermetabolism, but not all may be present:
major surgery related to the malignancy or for incidental sustained muscle contraction; results from break-
conditions. Considerable ethical issues surround ICU age of the normal impulse/contraction sequence
provision for patients with terminal disease. (excitation/contraction uncoupling) relating to
General considerations: abnormal calcium ion mobilisation, and is unre-
effects of malignancy itself: lieved by neuromuscular blocking drugs. Masseter
- primary: spasm may be an early sign.
- local, e.g. pressure effects, ulceration, muscle breakdown with release of potassium,
haemorrhage. myoglobin and muscle enzymes, e.g. cre-
- systemic, e.g. anaemia, cachexia, susceptibility atine kinase. Hyperkalaemia may cause cardiac
to infection, electrolyte disturbances (e.g. hyper- arrhythmias.
calcaemia), endocrine effects (e.g. Cushings increased O2 consumption, leading to cyanosis.
syndrome caused by bronchial carcinoma, car- increased CO2 production and hypercapnia.
cinoid syndrome, myasthenic syndrome). Hyperventilation may occur in the spontaneously
- metastatic, e.g. lung, liver, bone. breathing patient.
effects of previous treatment: rapidly increasing body temperature (e.g. > 0.5C
- surgery/radiotherapy, e.g. scarring, deformities. every 10min) and sweating.
- cytotoxic drugs, corticosteroids, opioid analgesic tachycardia and unstable BP.
drugs and antidepressant drugs. metabolic acidosis.
368 Mallampati score

Management: each other. Some would avoid phenothiazines and

discontinuation of the triggering agent, and aban- butyrophenones because of the neuroleptic malig-
donment of surgery if feasible. Changing the anaes- nant syndrome, but there is no evidence that the
thetic machine, tubing and soda lime has been two conditions are related.
suggested if possible. If not, since the modern vola- formerly, use of an anaesthetic machine not previ-
tile agents are hardly adsorbed on to modern plastic ously exposed to volatile agents was considered
breathing tubing, simply removing the vaporisers mandatory, but a new breathing system, flushed
and emptying the reservoir bag (or flushing the ven- with fresh gas for 1020min, has been suggested as
tilator bellows) may be sufficient. being adequate.
dantrolene is the only available specific treatment. routine monitoring should include core tempera-
1mg/kg is given iv, repeated as required up to ture. Some would consider arterial cannulation
10mg/kg. mandatory. Close monitoring should continue
supportive treatment: postoperatively.
- hyperventilation with 100% O2. Anaesthesia is dantrolene and supportive treatments should be
maintained with TIVA. readily available.
- correction of acidosis with bicarbonate, according reactions have been reported following apparently
to the results of blood gas interpretation. trigger-free anaesthetics, but these have not been
- cooling with cold iv fluids, fans, sponging and irri- severe.
gation of body cavities. Other causes of hyper- [Michael Denborough, Australian physician]
thermia should be considered. Wappler F (2010). Curr Opin Anesthesiol; 23: 41722
- treatment of hyperkalaemia if severe.
- diuretic therapy (mannitol or furosemide) and Mallampati score, see Intubation, difficult
urinary alkalinisation to reduce renal damage
caused by myoglobin.
- treatment of any arrhythmias as they occur. Malnutrition. Nutrient deficiency, usually of several
- corticosteroids (e.g. dexamethasone 4mg) have dietary components. Protein depletion with near-normal
been advocated. energy supply may lead to kwashiorkor, with hypopro-
- close monitoring in an ICU for 3648h postop- teinaemia and oedema. Protein and energy depletion
eratively. Creatine kinase levels should be mea- may lead to marasmus, with normal plasma protein
sured 12-hourly for 3648h, and the urine concentration.
Body reserves during total starvation under basal
analysed for myoglobin.
- acute kidney injury and DIC are treated as conditions:
carbohydrate: about 0.5kg, mainly as liver and
necessary.
Treatment with dantrolene should be instituted as soon muscle glycogen; lasts < 1 day.
protein: 46kg, mainly as muscle; lasts 1012 days.
as the diagnosis is suspected. Arterial blood gas interpre-
fat: 1215kg, as adipose tissue; lasts 2025 days.
tation and measurement of plasma potassium should be
performed early to detect acidosis and hyperkalaemia. Protein breakdown is reduced by even small amounts of
Prognosis is good if treated appropriately and early; glucose, possibly via resultant insulin secretion, inhibit-
mortality was 80% before dantrolene became available ing protein catabolism.
Malnutrition is common to some degree in hospital
but is < 5% today.
Investigation: patients. It may be associated with:
decreased intake, e.g. vomiting, malabsorption,
serum creatine kinase elevation and myoglobinuria
are suggestive, but not diagnostic. The former is not anorexia, poor diet, nil-by-mouth orders.
decreased utilisation, e.g. renal failure.
reliable as a screening test. Creatine kinase and
increased basal metabolic rate, e.g. trauma, burns,
myoglobin may both increase after suxamethonium
administration in normal patients. severe illness, pyrexia.
muscle biopsy may appear normal histologically.
Thus common perioperatively, especially in severe
caffeine and halothane contracture tests are the
chronic illness, GIT disease/surgery, alcoholics, the
investigations of choice. Biopsied muscle is exposed elderly and the mentally ill. May result in impaired
to caffeine and halothane, and tension in the muscle wound healing, bedsores, increased susceptibility to
measured. Contractures are induced in susceptible infection, weakness, anaemia, hypoproteinaemia, elec-
muscle. Results are divided into positive, negative trolyte disturbances and dehydration, vitamin deficiency
or equivocal. False-positive results may occur. All disorders and predisposition to hypothermia. Respira-
suspected cases and immediate relatives should be tory muscle weakness may predispose to respiratory
tested for susceptibility. complications.
Management of known cases: Long-term nutrition, via enteral or parenteral routes,
pretreatment with oral dantrolene is now thought
is thought to be beneficial preoperatively (at least 14
to be unnecessary. days). The place of short-term feeding is less certain.
sedative premedication is sometimes given to
Progress may be monitored by weight or skin thickness
reduce stress, but this is controversial. measurements.
avoidance of known triggering agents: volatile
agents and suxamethonium. N2O is considered safe. Managing Obstetric Emergencies and Trauma course
Many other drugs have been implicated at some (MOET course). Training programme, devised in 1998,
time, but the above are the only definite triggers. designed for medical staff working within obstetrics,
TIVA is a useful technique. Local anaesthetic tech- obstetric anaesthesia, and accident and emergency medi-
niques may be used, but MH may still occur. All cine. Similar to other acute life support courses in its
local anaesthetic agents are considered as safe as systematic approach and structure.
 Mannitol 369

Mandatory minute ventilation (MMV). Ventilatory mental/incisive branches of the inferior alveolar
mode used to assist weaning from ventilators. The nerve (supplying from the incisors to the first
required mandatory minute ventilation is preset, and the premolar): 0.51.0ml is injected at the mental
patient allowed to breathe spontaneously, with the ven- foramen from behind the second molar intraorally,
tilator making up any shortfall in minute volume. Thus or extraorally.
with the patient breathing adequately, the ventilator is buccal nerve: 0.51.0ml is injected lateral and pos-
not required. However, a minute ventilation made up of terior to the last molar, by the anterior border of
rapid shallow breaths will also satisfy the ventilator, the mandibular ramus.
despite alveolar ventilation being inadequate. In addi- submucous infiltration on both sides of individual
tion, not all ventilators allow spontaneous minute venti- teeth, directed along its long axis, may also be used.
lation to exceed the preset one (extended mandatory auriculotemporal nerve: 1.52.0ml is injected in the
minute ventilation; EMMV). Thus MMV is less popular anterior wall of the ear canal, at the junction of its
than IMV. bony and cartilaginous parts. Allows myringotomy
to be performed.
Mandibular nerve blocks. Performed for facial and 12% lidocaine or prilocaine with adrenaline is most
intraoral procedures. commonly used. Systemic absorption of adrenaline may
Anatomy: the mandibular division (V3) of the tri- cause symptoms, especially if high concentrations are
geminal nerve passes from the Gasserian ganglion used, e.g. 1:80000. Immediate collapse following dental
through the foramen ovale. nerve blocks is thought to result from retrograde flow of
Divisions: solution via branches of the external carotid artery,
motor nerves to the muscles of mastication and reaching the internal carotid; perineural spread to the
tensor muscles of the palate and eardrum. medulla has also been suggested.
sensory nerves (see Fig. 76; Gasserian ganglion See also, Gasserian ganglion block; Maxillary nerve
block): blocks; Nose; Ophthalmic nerve blocks
- meningeal branch: passes through the foramen
spinosum and supplies the adjacent dura. Mandragora (Mandrake). Plant, supposedly human-
- buccal nerve: supplies the skin and mucosa of the shaped, thought to hold magic powers, including the
cheek. ability to induce sleep and relieve pain. Contains hyo-
- auriculotemporal nerve; supplies the anterior scine and similar alkaloids. According to legend, its
eardrum, ear canal, temporomandibular joint, scream on uprooting killed all who heard it, hence the
cheek, temple, temporal scalp and parotid gland. supposedly safe method of collection: a dog is tied to
- inferior alveolar nerve: enters the mandible at its the plant at midnight, whilst its owner retreats to a safe
ramus, supplying the lower teeth and gums; the distance with ears stopped with wax. The dog is enticed
central incisors are innervated bilaterally. Emerges to run after food, pulling out the mandrake and dying in
through the mental foramen to supply the mucosa the process.
and skin of the lower lip, chin and gum. Carter AJ (2003). J R Soc Med; 96: 1447
- lingual nerve: passes alongside the tongue to
supply its anterior two-thirds, the floor of the Mannitol. Plant-derived alcohol. An osmotic diuretic; it
mouth and lingual gum. draws water from the extracellular and intracellular
The supraorbital foramen, pupil, infraorbital notch, spaces into the vascular compartment, expanding the
infraorbital foramen, buccal surface of the second pre- latter transiently. Not reabsorbed once filtered in the
molar and mental foramen all lie along a straight line. kidneys, it continues to be osmotically active in the urine,
Blocks: causing diuresis. Used mainly to reduce the risk of peri-
mandibular: a needle is inserted at right angles to operative renal failure (e.g. during vascular surgery,
the skin between the coronoid and condylar pro- surgery in obstructive jaundice) and to treat cerebral
cesses, just above the bone. After contacting the oedema. Efficacy in the latter depends on integrity of the
pterygoid plate, it is redirected posteriorly until bloodbrain barrier that may be altered in neurological
paraesthesiae are obtained, and 5ml local anaes- disease, although some benefit is derived from the sys-
thetic agent injected (N.B. the pharynx lies 5mm temic dehydration produced. Has also been used to
internally). lower intraocular pressure. It may also act as a free
inferior alveolar/lingual: with the mouth wide open, radical scavenger. Oral mannitol has been used (together
a needle is inserted parallel to the teeth and 1cm with activated charcoal) as an osmotic agent to increase
above their occlusal surface, medial to the oblique intestinal removal of poisons.
line of the mandibular ramus. It is advanced 1.5 Temporarily increases cerebral blood flow; ICP may
2.0cm and the syringe barrel swung across to the rise slightly before falling, especially after rapid injec-
opposite side. 11.5ml solution is injected with a tion. Excessive brain shrinkage in the elderly may
further 0.5ml on withdrawal (to block the lingual rupture fragile subdural veins. A rebound increase in
nerve). ICP may occur if treatment is prolonged, due to eventual
May also be performed extraorally, by injecting passage of mannitol into cerebral cells; the effect is small
1.52.0ml between the mandibular ramus and max- after a single dose. A transient increase in vascular
illa, level with the upper teeth gingival margins; volume and CVP may cause cardiac failure in suscepti-
the needle is inserted from the front with the ble patients.
mouth shut. Dosage: 0.252g/kg by iv infusion of 1020% solution
Buccal infiltration is required for surgery to the over 2030min. Effects occur within 30min, lasting
molar teeth; 0.51.0ml is injected into the cheek 6h. 0.250.5g/kg may follow 6-hourly for 24h, unless
mucosa opposite the third molar. The incisors diuresis has not occurred, cardiovascular instability
receive bilateral innervation. ensues or plasma osmolality exceeds 315 mosmol/kg.
370 MannWhitney rank sum test

Available as 10% and 20% solutions with osmolality 550 von Kodolitsch Y, Robinson PN (2007). Heart; 93:
and 1100 mosmol/kg respectively. 75560

MannWhitney rank sum test, see Statistical tests MARS, Molecular adsorbents recirculation system, see
Liver dialysis
Manslaughter. Unlawful killing of another person; a
criminal charge (as opposed to the civil charge of negli- Masks, see Facemasks; Oxygen therapy
gence) that has been applied to anaesthetists in cases
where the care provided was so poor as to constitute a Mass. Precise definitions vary, but include: the inertial
reckless or grossly negligent act or omission. Examples resistance to movement of a body, and the amount of
have included fatal cardiac arrest following disconnec- matter contained in a body. Under conditions of differ-
tion of the breathing system and inadequate immediate ing gravity, mass remains constant, whereas weight
postoperative care. varies. SI unit is the kilogram.
The charge of corporate manslaughter exists in
common law but actions against large organisations have Mass spectrometer. Device used to analyse mixtures of
often been unsuccessful because of difficulties identify- substances according to mw. The sample passes through
ing the person(s) responsible for the decisions that led an ionising chamber, and becomes charged by electrons
to death. The Corporate Manslaughter and Corporate arising from a cathode. The charged sample particles are
Homicide Act 2007 raises the possibility of senior man- then accelerated by an electric field that imparts a certain
agers, including clinicians (i.e. not just directors and velocity. When they subsequently pass through a strong
executives), facing charges if they are implicated in magnetic field, the particles are deflected to varying
playing a significant role that leads to a breach in deci- degrees depending on their mass and momentum. The
sion making related to operational processes within the electrical charge arriving at certain distances from the
organisation that subsequently results in the death of a accelerating chamber is measured, and corresponds to
person. the amount of differently sized particles present in the
Ferner RE (2000). Br Med J; 321: 121216 original sample. Different ranges of particle size may be
See also, Medicolegal aspects of anaesthesia analysed by altering accelerator characteristics. Com-
pounds of identical mw may be distinguished by identi-
MAO, see Monoamine oxidase fying breakdown products.
Alternatively, in the quadrupole mass spectrometer,
MAOIs, see Monoamine oxidase inhibitors the accelerated beam passes longitudinally between four
rods, of variable potential. Particles are removed from
MAP, see Mean arterial pressure the beam unless of a certain mass, depending on the
rods potential.
Mapleson classification of breathing systems, see Mass spectrometers may be used for on-line gas
Anaesthetic breathing systems analysis during anaesthesia.

Mareys law. Increased pressure in the aortic arch and Masseter spasm. Increase in jaw tone occurring after
carotid sinus causes bradycardia; decreased pressure suxamethonium. More common in children and after
causes tachycardia. halothane induction, although the incidence is hard to
[Etienne Jules Marey (18301904), French physiologist] determine because of diagnostic variability. A 1:100
See also, Baroreceptor reflex 1:3000 incidence has been reported, but is controversial.
A protective effect of thiopental has been suggested.
Marfans syndrome. Connective tissue disease, inher- Spasm may represent a normal dose-related response to
ited as an autosomal dominant gene. Prevalence is suxamethonium, but has been associated with MH sus-
1:20000. ceptibility, especially if spasm is severe and prolonged,
Features: and associated with markedly raised serum creatine
tall stature, with long thin extremities. High arched kinase and myoglobinuria. May also be seen in dystro-
palate. Joint dislocations, kyphoscoliosis, pes exca- phia myotonica following suxamethonium and acetyl-
vatum, inguinal and diaphragmatic herniae are cholinesterase inhibitors.
common. Management of spasm is controversial: termination
cataracts and subluxation of the ocular lens (50%). of anaesthesia and referral for muscle biopsy, treatment
cardiovascular: with dantrolene, and proceeding with caution have all
- aortic regurgitation (< 90%). been recommended.
- ascending aortic aneurysm.
- mitral valve prolapse. MAST, Military antishock trousers, see Antigravity suit
- conduction defects.
respiratory: Mast cells. Basophilic cells in connective and subcutane-
- kyphoscoliosis. ous tissues, involved in inflammatory reactions and
- emphysema. immune responses. Storage granules contain lytic
- pneumothorax. enzymes (e.g. tryptase) and inflammatory mediators, e.g.
- tracheal intubation may be difficult (high arched histamine, kinins, heparin, 5-HT, hyaluronidase, leuko
palate). trienes, platelet aggregating and leucocyte chemotactic
Death usually results from aortic dilatation and its com- factors. Release is caused by: tissue injury; complement
plications. Careful preoperative assessment for congeni- activation; drugs (e.g. atracurium); and cross-linkage of
tal heart disease and its sequelae is required. surface IgE molecules by antigen (i.e. true anaphylaxis).
[Bernard J Marfan (18581942), French paediatrician] Also involved in presentation of antigen to lymphocytes.
 Mean arterial pressure 371

Occur in excess in mastocytosis, either in the circulation superior alveolar nerve branches to individual teeth
or as tissue infiltrates. may be blocked by submucous infiltration above
each tooth.
for the CadwellLuc approach, the mucosa and
Maternal mortality, see Confidential Enquiries into
Maternal Deaths periosteum above the upper premolars may be
infiltrated with 510ml solution, to block branches
of the anterior superior alveolar nerve. Topical
Maxillofacial surgery. Anaesthesia may be required for application of, e.g. lidocaine may assist the block.
elective surgery (e.g. for facial deformities, tumours) or Further solution may be injected into the mucosa
because of facial trauma, infection or airway obstruction. of the maxillary sinus once opened. Alternatively,
General considerations are as for ENT, plastic and maxillary or infraorbital nerve blocks may be
dental surgery, in particular problems of access, protec- performed.
tion of the airway and the potential for long and bloody 12% lidocaine or prilocaine with adrenaline is most
surgery. Bradycardia may occur during procedures commonly used. Systemic absorption of adrenaline may
around the face (see Oculocardiac reflex). cause symptoms, especially if high concentrations are
used, e.g. 1:80000.
Maxillary nerve blocks. Performed for facial and intra- Immediate collapse following dental nerve blocks is
oral procedures. thought to result from retrograde flow of solution via
Anatomy: the maxillary division (V2) of the trigemi- branches of the external carotid artery, reaching the
nal nerve passes from the Gasserian ganglion through internal carotid; perineural spread to the medulla has
the foramen rotundum into the pterygopalatine fossa, also been suggested.
dividing into sensory branches and continuing as the [George Caldwell (18341918), US ENT surgeon; Henri
infraorbital nerve (see Fig. 76; Gasserian ganglion Luc (18551925), French ENT surgeon]
block). Branches: See also, Mandibular nerve blocks; Ophthalmic nerve
via the pterygopalatine ganglion to the nose, naso- blocks
pharynx and palate via nasal, nasopalatine, greater
and lesser palatine and pharyngeal nerves. Maximal breathing capacity, see Maximal voluntary
nasopalatine nerve: supplies the anterior third of
ventilation
the hard palate and palatal gingiva of the upper
incisors.
greater palatine: supplies the posterior hard palate
Maximal voluntary ventilation (Maximal breathing
and palatal gingiva of adjacent teeth. capacity). Maximal minute volume of air able to be
zygomatic nerve: supplies the temple, cheek and
breathed, measured over 15s. Normally about 120150
lateral eye. l/min. Equals approximately 35 FEV1. Rarely used,
posterior superior alveolar nerve: supplies the
since very tiring to perform.
molar/premolar teeth. See also, Lung function tests
infraorbital nerve: supplies the lower eyelid, con-
junctiva, side of the nose, upper lip, cheek, and via MCH/MCHC/MCV, Mean cell haemoglobin/Mean
its anterior superior alveolar branch, the upper cell haemoglobin concentration/Mean cell volume, see
canines and incisors, maxillary sinus and cheek Erythrocytes
mucosa.
The supraorbital foramen, pupil, infraorbital notch, MDEA, Methylenedioxyethylamfetamine, see Methyl-
infraorbital foramen, buccal surface of the second pre- enedioxymethylamfetamine
molar and mental foramen all lie along a straight line.
Blocks:
maxillary nerve: a needle is inserted extraorally
MDMA, see Methylenedioxymethylamfetamine
0.5cm below the midpoint of the zygoma and
directed medially until bone is contacted. It is redi- MEA syndrome, see Multiple endocrine adenomatosis
rected anteriorly and advanced a further 1cm, ante-
rior to the lateral pterygoid plate. 34ml local Mean (Average). Expression of the central tendency of
anaesthetic agent is injected. May also be blocked a set of observations or measurements. Equals the sum
via the intraoral route: the needle is inserted of all the observations divided by the number of obser-
behind the posterior border of the zygoma and vations (n), i.e.
directed upwards, medially and posteriorly 3cm.
Up to 5ml solution is injected within the pterygo-
x=
x
palatine fossa. n
nasopalatine nerve: 0.51.0ml is injected at the inci-
sive foramen, 0.51.0cm posterior to the upper inci- Population mean is denoted by ; sample mean by x.
sors in the midline. Means of more than one sample group may be com-
greater palatine nerve: 0.51.0ml is injected at the
pared using statistical tests.
greater palatine foramen, marked by a depression See also, Median; Mode; Standard error of mean; Statisti-
in the palate opposite the second/third molar 1cm cal frequency distributions; Statistics
above the gingival margin.
infraorbital nerve: 12ml is injected at the infraor- Mean arterial pressure (MAP). Average arterial BP
bital foramen, 0.51.0cm below the infraorbital throughout the cardiac cycle. The area contained within
notch. Injection may be performed intraorally or the arterial waveform pressure trace above MAP equals
extraorally. the area below it.
372 Mechanocardiography

(2 diastolic) + systolic
equals approximately (a)
3
(systolic diastolic)
or diastolic +
3 Recurrent Superior vena
Preferred by some clinicians to measures of systolic laryngeal nerve cava
or diastolic pressures, since it is less liable to errors Left phrenic Right phrenic
or differences due to measuring techniques. Also nerve nerve
represents the mean pressure available for perfusion of Aortic arch Trachea
tissues.
Left vagus Right vagus
nerve nerve
Mechanocardiography. Recording of the mechanical Thoracic duct Oesophagus
pulsations of the CVS; includes tracings of the JVP and
venous waveform, arterial waveform and recordings at Vertebral body
the apex using an externally applied transducer. Has
been used to investigate cardiovascular disease, espe-
cially valvular disease, and to determine systolic time
intervals.

Median. Expression of the central tendency of a set of (b)

measurements or observations.
Oesophagus
(n + 1)th
equals the measurement.
2 Trachea
Half the population lies above it, half below. Equals the
mean for a normal distribution.
See also, Statistical frequency distributions; Statistics
Aorta Pulmonary trunk
Median nerve (C6T1). Arises from the medial and
lateral cords of the brachial plexus in the lower axilla,
lateral to the axillary artery. Passes down the front of the
arm to the antecubital fossa, first lateral to the brachial
artery, then crossing it anteriorly at mid/upper arm to lie
medially. Entering the forearm, it crosses the ulnar
artery anteriorly, separated from it by pronator teress
deep head. Passes between flexor digitorum superficialis
and profundus; at the wrist it lies between the tendons
Oesophagus
of palmaris longus (medially) and flexor carpi radialis
(laterally).
Apart from branches to the joints of the wrist and
hand, it supplies: (c)
superficial flexor muscles (except flexor carpi
ulnaris), abductor pollicis brevis, flexor pollicis
brevis and opponens pollicis. Superior vena cava
radial side of the palm and the palmar surface of
the radial 3 1 2 digits, extending to their dorsal surface
at their tips. Aorta
via the anterior interosseus branch arising at the Right pulmonary Left pulmonary
distal antecubital fossa: flexor pollicis longus, radial arteries arteries
part of flexor digitorum profundus and pronator
quadratus.
May be blocked at the brachial plexus, elbow, forearm
and wrist. Left ventricle
See also, Brachial plexus block; Elbow, nerve blocks;
Wrist, nerve blocks.

Mediastinum. Region of the thorax between the two Diaphragm

pleural sacs. It is in contact with the diaphragm inferiorly,
Inferior vena cava Right ventricle
and continuous with the tissues of the neck superiorly.
Lies between the vertebral column posteriorly and
sternum anteriorly. Contains the heart, great vessels,
trachea, oesophagus, thoracic duct, vagi, phrenic and Fig. 104 Anatomy of the mediastinum: (a) transverse section through
recurrent laryngeal nerves, sympathetic trunk, thymus T4; (b) trachea and relations; (c) heart and great vessels
and lymph nodes (Fig. 104).
 Melatonin 373

Divided into: to balance of probabilities. Criminal law is involved less

superior mediastinum: above a horizontal line level commonly, e.g. involving murder or manslaughter due to
with T4/5 and the angle of Louis. criminal neglect or reckless disregard of clinical duties;
inferior mediastinum: below this line. Composed of proof must be beyond reasonable doubt.
anterior (between heart and sternum), middle (con- Usually related to:
taining pericardium and contents) and posterior negligence: harm resulting from a failure in the duty
(between heart and vertebrae) portions. of care. In the National Health Service (NHS),
Thus mediastinal enlargement may be caused by: employing Trusts are legally liable for the negligent
enlargement of any of the above constituent struc- acts/omissions of their employees during their
tures (central). employment (the principle of vicarious liability),
spinal and vertebral masses (posterior). providing indemnity for NHS work since 1990.
thymic, thyroid, teratoma and dermoid tumours Anaesthesia is considered a high-risk specialty
(anterior). Tumours (e.g. bronchial carcinoma) may because of common minor claims (e.g. damage to
involve local structures within the mediastinum, e.g. teeth) and very expensive major claims.
recurrent laryngeal or phrenic nerves, pericardium. perioperative deaths: those occurring within 24h of
Bleeding from the aorta following chest trauma or anaesthesia are reported to the coroner, who may
dissection may cause widening of the superior order an inquiry or inquest, although the time inter-
mediastinum. val is not specified by law. Once reported, organs
Patients with mediastinal enlargement may present may not be harvested for transplantation without
for biopsy (e.g. via mediastinoscopy through a the coroners permission.
suprasternal incision) or resection. Misuse of Drugs Act.
Main anaesthetic considerations: fitness to practise: investigated by a committee
preoperative state, e.g. related to the primary malig- of the General Medical Council (GMC) that regu-
nancy. Tracheal compression and airway obstruc- lates licensing to practise medicine in the UK;
tion, superior vena caval obstruction, phrenic and although not a civil court, the process may be
recurrent laryngeal nerve involvement and drug/ broadly similar.
radiotherapy effects may be present. More than one process may follow a single incident; thus
classically, induction of anaesthesia is inhalational, a serious error that results in a patients death may result
but some advocate iv induction. Reinforced in an inquest, a claim of negligence, a charge of man-
tracheal/bronchial tubes are often preferable. slaughter and/or a referral to the GMC.
severe haemorrhage may occur. Fluid replacement Similar considerations apply to ICU, although claims
via the femoral vein may be required if the superior arising from ICU itself are less common; however ICU
vena cava and its tributaries are involved. may be required for critical illness arising from negligent
one-lung anaesthesia and even extracorporeal cir- practice. Specific ICU issues with medicolegal implica-
culation may be required during resection. tions include competence (whether the patients are able
[Antoine Louis (17231792), French surgeon] to make their own decisions), non-provision of life-
See also, Chest X-ray sustaining treatment or withdrawal of treatment (justi-
fied if it is in the patients best interests to be allowed to
Medical emergency team (MET). Team consisting of die) and brainstem death. The need for attention to
medical and nursing staff skilled in resuscitation (in its detail and proper record-keeping is just as important as
broadest sense) responding to standardised calling crite- in general anaesthetic practice.
ria, including abnormal physiological variables (e.g. sys- In general, risks are reduced by: checking of anaes-
tolic BP < 90mmHg), specific conditions or any time thetic equipment; use of the WHO Surgical Safety
urgent medical assistance is required. May replace exist- Checklist; adequate preoperative assessment and prepa-
ing cardiac arrest teams on the basis that prevention of ration (including warning patients of risks); consultation
cardiac arrest or severe physiological deterioration is with senior colleagues when appropriate; adherence to
likely to have a better outcome than treatment applied generally accepted techniques, including adequate moni-
after cardiac arrest. Its effect on preventing cardiac toring; careful writing of clinical notes and anaesthetic
arrest, decreasing ICU admission and improving mortal- record-keeping, with copies kept for later use; and full
ity has not been proven. and honest explanation with patients and/or relatives
Lee A, Bishop G, Hillman KM, Daffurn K (1995). when anything goes wrong.
Anaesth Intens Care; 23: 1836 See also, Abuse of anaesthetic agents; Anaesthetic mor-
See also, Acute life-threatening events recognition and bidity and mortality; Ethics; Sick doctor scheme
treatment; Outreach team; Postoperative care team
Meglitinides. Oral hypoglycaemic drugs used in the
Medicines and Healthcare products Regulatory management of diabetes mellitus. Stimulate insulin
Agency (MHRA). UK government agency formed in release from the functioning cells of the pancreas.
2003 from the Medicines Control Agency and Medical Taken just before meals. Two available agents are nateg-
Devices Agency. Responsible for regulating medicines linide and repaglinide; the former is only licensed for
and medical devices and ensuring their safety, via use in combination with metformin. Common side
approval/regulation/monitoring of clinical trials, effects include headache and upper respiratory tract
reporting/investigating adverse drug reactions and infections.
licensing/testing medicinal products and devices.
Melatonin. Hormone synthesised and released by the
Medicolegal aspects of anaesthesia. In the UK, these pineal gland. Formed from the amino acid tryptophan,
usually concern matters of civil law, e.g. negligence, its formation is promoted by darkness and inhibited by
breach of contract or battery; proof must be according light. Actions include control of circadian rhythms,
374 Membrane potential

modulation of seasonal changes in physiology, timing of and semantic (concepts about the world and linguistic
puberty and thermoregulation. Its function of regulating meaning). The hippocampus, amygdala, frontal lobes,
sleep has resulted in its use in combating sleep depriva- and thalamic and hypothalamic nuclei are thought to be
tion in ICU patients. concerned with memory storage and retrieval.
Bellapart J, Boots R (2012). Br J Anaesth; 108: 57280 Anaesthetic agents are thought mainly to impair
acquisition of short-term memory, although transfer into
Membrane potential. Electrical potential difference intermediate and long-term memory may also be
across a cell membrane, present in almost all living affected.
eukaryotic cells. Results from the differential distribu- Wang DS, Orser BA (2011). Can J Anesth; 58: 16777
tion of charged particles across cell membranes. The See also, Amnesia; Postoperative cognitive dysfunction
distribution of each particle is determined by its perme-
ability across the membrane, the distribution of other Mendelsons syndrome, see Aspiration pneumonitis
particles (e.g. Donnan effect) and active transport
systems, e.g. sodium/potassium pump. Membranes Meninges. Tissue layers surrounding the brain and
are impermeable to proteins (negatively charged), spinal cord, composed of:
which thus remain intracellular; membranes are poorly pia mater: delicate vascular layer, closely adherent
permeable to sodium ions and moderately permeable to to the brain and cord, following their surfaces into
chloride and potassium ions. clefts, sulci, etc. Surrounded by CSF within the
Electrochemical gradients exist across the cell mem- arachnoid. Thin projections of the latter cross the
brane for each ion; the membrane potential at equilib- subarachnoid space to the pia. Blood vessels lie
rium for each is calculated by the Nernst equation. within the space.
Membrane potentials at given intracellular/extracellular Within the vertebral canal, the denticulate liga-
concentrations of sodium, chloride and potassium ions ment passes laterally from the pia along its length
together are calculated by the Goldman constant-field and attaches at intervals to the dura. The subarach-
equation. noid septum lies posteriorly, attaching to the arach-
Potential is conventionally written as negative; i.e. the noid intermittently. The pia terminates as the filum
inside is negative relative to the outside. The potentials terminale, which passes through the caudal end of
magnitude varies between tissues, e.g. 70 mV for nerves the dural sac and attaches to the coccyx.
and 90 mV for muscle. arachnoid mater: delicate membrane, containing
Changes in membrane permeability may alter, or CSF internally. Does not project into clefts and
be altered by, membrane potential, e.g. during action sulci, apart from the longitudinal fissure. Applied to
potentials. the dura externally; the potential subdural space lies
between them, containing vessels. Fuses with the
Membranes. Biological membranes share certain dura at S2. Arachnoid granulations project into the
features: venous sinuses, for drainage of CSF.
phospholipid bilayer; the hydrophilic end of each dura mater: composed of two fibrous layers: the
phospholipid molecule faces the membrane surface outer is adherent to the periosteal lining of the skull;
and the hydrophobic end lies within the membrane the inner attaches to the outer but is separated by
substance. venous sinuses. The inner layer forms sheets within
protein molecules at intervals within the membrane; the skull:
they may traverse it or project on one side only, - vertical: falx cerebri and falx cerebelli between
according to the water/lipid solubility of the protein the cerebral and cerebellar hemispheres
subunits. Proteins are able to float within the lipid respectively.
molecules. - horizontal: tentorium cerebelli above the cerebel-
proteins may function as enzymes, receptors, pumps lum and the diaphragma sellae above the pitu-
or channels for ions. They also have antigenic itary gland.
properties. The dura also forms two layers within the vertebral
resting membrane potential is created by differen- canal: the external adherent to the inner periostium
tial permeability for certain ions, together with of the vertebrae and the internal lying against the
active transport pumps. Most membranes are rela- outer surface of the arachnoid. The space between
tively permeable to chloride and potassium ions, the two dura layers is the epidural space. Projec-
less so to sodium ions, and relatively impermeable tions and fibrous bands are present within the epi-
to proteins and anions. Non-charged substances dural space, especially in the midline. Dura projects
(e.g. CO2 and non-ionised drugs) are able to cross intermittently to the posterior longitudinal ligament
freely, as is water. of the vertebrae, especially lumbar. Dura ends at
function of cells is dependent on the features of about S2.
their membrane proteins, which may be altered by All layers donate a thin covering sleeve to cranial
electrical signals or chemicals, e.g. drugs, hormones, nerves and spinal nerves as they leave the CNS. These
neurotransmitters. The action of anaesthetic agents dural cuffs, which contain CSF, may accompany spinal
is thought to involve alteration of membrane con- nerves through the intravertebral foramina.
figuration within the nervous system. Blood supply:
See also, Action potential; Anaesthesia, mechanisms of intracranial:
- from ascending pharyngeal, occipital and maxil-
Memory. Classically divided into explicit and implicit lary branches of the external carotid artery. The
memory; the latter not requiring conscious retrieval (e.g. maxillary artery gives rise to the middle menin-
driving a car), the former subdivided into episodic geal artery, which enters the skull through the
(information regarding specific events, places and times) foramen spinosum.
 Mental Capacity Act 2005 375

- from branches of the internal carotid and verte- Important because of its innocuous early course, rapid
bral arteries. progression and potentially disastrous outcome; the
spinal: as for the spinal cord. latter is thought to be related to the extremely toxic
See also, Meningitis; Vertebral ligaments endotoxin present in the outer wall of the organism. An
important cause of morbidity and mortality in children
and young adults; epidemics (e.g. in schools/colleges)
Meningitis. Inflammation of the meninges. Usually
occur periodically. Asplenia and complement deficiency
infective:
are specific risk factors. Shows seasonal variation
viral: usually coxsackie, echo, herpes and mumps
(approximately 40% of cases occurring between January
viruses. Usually has good prognosis, unless associ-
and March). The organism is present in the nasopharynx
ated with generalised encephalitis.
of about 5% of otherwise healthy subjects, increasing to
bacterial: Neisseria meningitidis (meningococcal
about 30% during epidemics. Case mortality is 1012%
meningitis), Streptococcus pneumoniae (pneumo-
in the UK.
coccal meningitis) and Haemophilus influenzae are Features:
the most common organisms. Mortalilty is high
non-specific (especially initially), e.g. cough, sore
unless treated; adhesions, hydrocephalus and cranial
throat, fever, vomiting, headache.
nerve damage are still possible after treatment.
signs and symptoms of meningitis: may develop in
others, e.g. TB, listeria, fungi.
about 85% of cases but bacteraemia and severe
Aseptic meningitis may also occur; it may be caused by
SIRS may occur without overt meningitis being
malignant infiltration, chemical irritation (e.g. alcoholic
present, and has a higher mortality.
solutions used to clean the skin before lumbar puncture)
petechial rash: present in up to 80% of patients,
and occasionally drugs (e.g. NSAIDs, H2 receptor
although sometimes limited to the mucous mem-
antagonists).
Features:
branes. May become maculopapular. DIC is
common. Vasculitic lesions or extensive skin digit or
fever, nausea, vomiting, headache, photophobia,
limb necrosis (purpura fulminans) may also occur.
convulsions, coma.
MODS and septic shock may occur.
neck stiffness, with muscle resistance to passive
adrenocortical insufficiency due to sepsis or adrenal
knee extension from the flexed position with the
haemorrhage.
thigh flexed (caused by stretching of inflamed sciatic
Diagnosis is often suggested by the history and clinical
nerve roots [Kernigs sign]).
examination, although similar rashes can occur with
cranial nerve lesions or signs of cerebral oedema
staphylococcal, streptococcal or Haemophilus influenzae
may be present.
infections. Blood cultures reveal the meningococcus in
may be associated with systemic involvement, e.g.
up to 80% of untreated cases. The organism may also be
effects of severe sepsis in meningococcal disease.
isolated from the skin lesions or CSF. Polymerase chain
CT scan is usually required to exclude space-
reaction (PCR) is increasingly used to identify the
occupying lesions and raised ICP before lumbar
organism.
puncture. Treatment:
CSF: Typical findings include:
iv antibiotic therapy as for meningitis.
- viral: increased lymphocytes, slightly raised
supportive: includes management of meningitis
protein and normal glucose.
(depressed consciousness, etc.), coagulopathy and
- bacterial: increased polymorphs and protein, and
septic shock.
reduced glucose. Bacteria may be visible on
limb fasciotomies or amputation may be
staining.
necessary.
- aseptic: increased polymorphs and protein, and
others: specific anti-endotoxin antibodies and anti-
normal glucose. The CSF may appear cloudy but
cytokine therapies, corticosteroids and other treat-
no organisms are seen or grown.
ments of severe sepsis have been studied but their
Recovery may be complete or there may be neurological
place is uncertain.
deficit, especially in bacterial meningitis and especially
If exposed before the patient has received appropriate
if treatment is delayed. Aseptic chemical meningitis is
antibiotics, close contacts (including ICU staff) should
characterised by its short and benign course.
receive prophylaxis, e.g. with rifampicin or ciprofloxacin.
Treatment is directed at the underlying organism.
At-risk subjects may be protected by immunisation with
Recent UK guidelines suggest cefotaxime or ceftriaxone
a polysaccharide vaccine against types A and C menin-
(both 2g iv) as soon as possible (i.e. before definitive
gococci; the B serogroup has a number of subtypes and
microbiological diagnosis). Ampicillin 2g is added if >
an effective vaccine against it has not yet been devel-
55 years, to cover listeria or vancomycin rifampicin if
oped. Public health officials should be contacted (it is a
penicillin-resistant pneumococcus is suspected. Dexa-
notifiable disease) to organise contact tracing and
methasone (e.g. 0.15mg/kg iv qds for 4 days) reduces
prophylaxis.
mortality and neurological morbidity.
Other forms of meningococcal disease are often
[Vladimir M Kernig (18401917), Russian neurologist]
trivial (e.g. conjunctivitis, pharyngitis, otitis media) but
some may be severe (e.g. pericarditis, endocarditis, myo-
Meningococcal disease. Strictly, refers to any illness carditis, septic arthritis).
caused by Neisseria meningitidis, although the term is Stephens DS, Greenwood B, Brandtzaeg P (2007).
often used to describe the severe systemic illness that Lancet; 369: 2196210
often results in admission to an ICU. Most infections in
the UK are caused by the B serotype, although the C Mental Capacity Act 2005. Act providing a framework
serotype more frequently causes outbreaks. The A sero- for decision making on behalf of adults without capacity;
type may also cause clinical infection. came into force in England and Wales in April 2007.
376 MEOWS

Largely building on pre-existing common law, the Act derived from the ubiquitous magnetic fluid that per-
confers formal statutory status on advance directives vaded the universe. Named after Mesmer, who originally
(termed advance decisions) and creates new lasting passed magnets over his patients bodies to treat them.
powers of attorney and court-appointed deputies with He later used only his touch, and then speech, to achieve
the ability to make medical decisions on behalf of adults the same effects. Investigated in Paris by a French Royal
> 16 years who lack capacity. Commission in 1784, which included Benjamin Franklin
Based on the following principles: and Lavoisier; mesmerism was declared to have no sci-
capacity must be presumed unless proven entific foundation, relying on suggestion alone. It contin-
otherwise. ued to be popular until the 1840s, when the importance
everything practicable must be done to support of psychological suggestion by the therapist was empha-
individuals to make their own decisions, before sised, leading to the concept of hypnotism.
deciding they lack capacity. [Franz A Mesmer (17341815), Swiss-born French physi-
individuals may make unwise or irrational decisions cian; Benjamin Franklin (17061790), US statesman and
and doing so is not evidence of incapacity. scientist]
any decision made on behalf of another person See also, Hypnosis
must be in their best interests (not necessarily their
best medical interests). MET, see Medical emergency team
if a decision is made on anothers behalf, it should
be the least restrictive option; i.e. the one that inter- Meta-analysis (Systematic review). Technique for deter-
feres least with the individuals freedoms in order mining the efficacy of a treatment by combining trials
to achieve the required aim. that may individually have been too small to show
Requires providers of healthcare to consider advance a statistically significant difference. Requires careful
decisions and to assess capacity before initiating, with- inclusion of all randomised controlled trials (RCTs) of
holding or withdrawing treatment. The new Court of the particular treatment, some of which may not have
Protection, created by the Act, has ultimate responsibil- been published. The RCTs are then scored according
ity for the Acts proper functioning, including deciding to their methodology, excluding any that are inade-
on individual cases. quately randomised or blinded. The results of the
White SM, Baldwin TJ (2006). Anaesthesia; 61: 3819 remaining RCTs are then pooled to increase the overall
number of subjects and power; the outcome of each RCT
MEOWS, see Modified Early Obstetric Warning Score is expressed in a standard format (e.g. odds ratio, number
needed to treat, absolute or relative risk reduction) and
Meperidine, see Pethidine the value for the combined data given. Typically, each
separate RCTs result is shown on a graph, with hori
Mepivacaine hydrochloride. Amide local anaesthetic zontal lines representing confidence intervals; the size of
agent, first used in 1956. Similar to lidocaine, but more the central mark represents the sample size (forest plot;
protein-bound. Does not cause vasodilatation. Not avail- Fig. 105). The combined result therefore has smaller con-
able in the UK. Used in 12% solutions for epidural fidence intervals and larger central mark than the con-
anaesthesia and 4% solution for spinal anaesthesia, in stituent RCTs, representing the greater certainty of the
the same doses as lidocaine. Maximal safe dose is 5mg/ combined result and the larger number of subjects.
kg; toxic plasma level is about 6g/ml. Rarely used in Those trials whose confidence intervals cross the line of
obstetrics because of greater fetal protein-binding and equivalence (for odds ratio, a value of one) are statisti-
longer fetal half-life than alternative drugs. cally non-significant whilst those that do not are sig-
nificant. In the example given, the overall conclusion is
MEPP, Miniature end-plate potential, see End-plate that there is a statistically significant difference, as dem-
potentials onstrated by the combined confidence intervals not
crossing the line.
Meptazinol hydrochloride. Synthetic opioid analgesic
drug, first investigated in 1971. Has partial agonist prop-
erties, and therefore antagonises respiratory depression
caused by morphine. Causes less respiratory depression
or sedation than morphine. Analgesic effects are almost
completely reversed by naloxone. 100mg is equivalent
to 10mg morphine or 100mg pethidine.
Dosage: 50100mg iv/im 24-hourly as required;
200mg orally, 36-hourly. (a)

Meropenem. Broad-spectrum carbapenem and antibac-

terial drug, similar to imipenem but not broken down by
renal enzymatic action. Less likely to cause convulsions
than imipenem, thus more useful in CNS infections.
(b)
Dosage: 500mg1g iv over 5min tds (2g in menin-
gitis or infection in cystic fibrosis).
Side effects: as for imipenem. 0.5 1 2
Odds ratio
Mesmerism. Treatment of various maladies (including
postoperative pain relief) by animal magnetism, the Fig. 105 Meta-analysis (forest plot): nine small trials (a) are pooled to
transmission between individuals of healing force give a combined result (b)
 Methionine and methionine synthase 377

Although meta-analysis has the ability to demon- in severe hypotension or shock: 0.55mg iv,
strate true treatment effects and thus represents the best titrated to effect; acts within 12min, lasting for
evidence on which to base clinical practice, the tech- 2030min.
nique may not always be valid because of:
bias in the identification of RCTs included (e.g. Methadone hydrochloride. Synthetic opioid analgesic
positive studies have traditionally been more drug, formulated in 1947. Due to its long duration of
likely to be published than negative ones). action (up to 24h), used for chronic pain management,
differing definitions of selection criteria for RCTs. maintenance in opioid addicts and cough suppression in
use of different outcomes in the component palliative care. Has similar actions and side effects to
studies. morphine, but is generally milder with less sedation.
the ability for single RCTs to influence unduly the Elimination half-life exceeds 18h. Accumulation may be
overall result in certain circumstances. problematic.
uncertainty in applying the result to a particular Dosage: 510mg orally/im/sc, tds/qds (bd in chronic
patient (e.g. man aged 45 years) when the RCTs use).
included all refer to a specific patient population See also, Spinal opioids
(e.g. men aged 6070 years).
Thus there have been some famous examples of treat- Methaemoglobinaemia. Increased circulating haemo-
ment effects apparently demonstrated by meta-analysis globin in which the iron atom of haem is in the ferric
that have not been supported by subsequent huge RCTs, (Fe3+) state (normally < 1%). Levels determined by
e.g. the beneficial effect of magnesium sulphate follow- co-oximetry.
ing MI. However, meta-analysis has had notable suc- May be:
cesses too, e.g. by demonstrating clearly the reduction in congenital:
mortality when -adrenergic receptor antagonists are - deficiency of reducing enzymes (especially
given following MI despite conflicting results of the cytochrome b5 oxidase), that normally convert
many small RCTs that previously existed. endogenously formed methaemoglobin to hae-
Akobeng AK (2005). Arch Dis Child; 90: 8458 moglobin. Usually autosomal recessive inheri-
tance; heterozygotes may be at risk of acute
Metabolism. Physical and chemical reactions occurring acquired methaemoglobinaemia.
in an organism in order to sustain life. Involves anabo- - abnormal haemoglobin chains, with fixation
lism (building up; i.e. incorporation of substrate into of iron in Fe3+ state; autosomal dominant
living cells) and catabolism (breaking down; usually con- inheritance.
cerned with energy liberation). Metabolic pathways are - glucose 6-phosphate dehydrogenase deficiency.
mediated by enzymes, subject to various control mecha- acquired: drugs and chemicals, e.g. prilocaine, chlo-
nisms (e.g. hormonal). Basic pathways may be discussed rate, quinones, nitrites, phenacetin, sulphonamides,
in terms of dietary substrate: aniline dyes.
carbohydrates: digested to monosaccharides, Effects:
absorbed and passed to liver and muscle. Glucose because methaemoglobin is dark (brownish),
is converted to glycogen for storage or broken down patients appear to have cyanosis when levels exceed
via glycolysis, tricarboxylic acid cycle and cyto- 1012% (at normal haemoglobin concentrations).
chrome oxidase system to CO2 and water with lib- Inaccurate readings of haemoglobin saturation may
eration of energy that is stored in ATP and other occur with pulse oximetry (as the level of methae-
compounds. moglobin increases, measured arterial O2 saturation
fats: digested to fatty acids and glycerol, which pass tends towards 85% since both oxygenated and
to the liver. Stored as adipose tissue or oxidised to deoxygenated forms absorb light equally at 660nm
CO2, water and energy. and 940nm).
proteins: digested to amino acids; form new the oxyhaemoglobin dissociation curve of the unaf-
proteins, e.g. enzymes, secretions, cellular compo- fected haem is shifted to the left, reducing O2 deliv-
nents such as muscle. Subsequently broken down ery to tissues. Patients already anaemic are more at
to urea. risk. Dyspnoea and headache are common at > 20%
Carbohydrate, fat and protein subunits are interchange- methaemoglobin, although rate of formation is also
able via many pathways, and are interlinked with other important.
substances, e.g. purines, nucleic acids. Treatment: reducing agents (e.g. iv methylthioninium
See also, Basal metabolic rate; Inborn errors of chloride [methylene blue]) if acute and severe:
metabolism 12mg/kg over 5min, repeated as necessary. Oral
therapy with methylthioninium chloride or ascorbic
Metaraminol tartrate/bitartrate. Vasopressor drug, acid may suffice in chronic methaemoglobinaemia. In
acting directly via -adrenergic receptors, and indirectly acute severe cases, blood or exchange transfusion
via adrenaline and noradrenaline release. Increases may be required.
cardiac output and SVR, and thus arterial BP. Used to Johnson D (2005). Can J Anesth; 52: 6658
raise BP following epidural/spinal anaesthesia and car- See also, Sulphaemoglobinaemia
diogenic shock. May cause excessive hypertension in
hyperthyroidism and monoamine oxidase inhibitor Methanol poisoning, see Alcohol poisoning
therapy, and myocardial ischaemia in ischaemic heart
disease. Methionine and methionine synthase. Methionine (an
Dosage: amino acid) is the main source of methyl groups in the
210mg sc or im; acts within 10min and lasts body, and is involved in many biochemical reactions,
11.5h. including myelination. It is also the precursor of
378 Methohexital sodium

glutathione, depleted in the liver by toxins, e.g. potent (MAC 0.2) and a powerful analgesic. Formerly
paracetamol poisoning, hence its use in the latter. For- used for general anaesthesia and draw-over analgesia,
mation from homocysteine by methionine synthase is e.g. during labour, using the Cardiff fixed output (0.35%)
involved in folate metabolism, and thymidine and DNA inhaler. Still available for use in Australia and New
synthesis. Zealand for pre-hospital analgesia.
Methionine synthase containing vitamin B12 as a
cofactor is inhibited by N2O, which interacts directly N-Methyl-D-aspartate receptors (NMDA receptors).
with the vitamin. Prolonged exposure to N2O may Receptors in the CNS activated by glutamate (but
result in features of folate/vitamin B12 deficiency, e.g. requiring glycine as a co-agonist) and to a lesser extent
subacute combined degeneration of the cord and mega- aspartate; involved in the plasticity of the CNS to affer-
loblastic anaemia. Myelination may also be affected. ent impulses, especially pain. Activation by sustained or
Significant effects are thought to be minimal up to 8h repeated C-fibre stimulation leads to intracellular phos-
normal anaesthetic use, but biochemical changes have phorylation of proteins and causes opening of specific
been found after a few hours. Megaloblastic changes membrane ion channels (opposed by magnesium). This
have been found in dentists who use N2O. Effects on leads to an increase in intracellular calcium concentra-
DNA synthesis may mediate teratogenesis after pro- tion and increased response to glutamate by a positive
longed exposure in animal models, but teratogenicity feedback mechanism. Thus input via NMDA receptors
in humans during routine anaesthesia is considered is thought to lead to a hyperexcitable state (wind-up)
negligible. whereby repeated stimuli cause increasing degrees of
pain sensation and expansion of the receptive field of
Methohexital sodium (Methohexitone). IV anaesthetic individual sensory neurones involved in pain pathways.
drug, first used in 1957 and discontinued in the UK in NMDA receptor antagonists are thought to prevent
2000. A methyl barbiturate, presented as a white powder these phenomena and may thus have a role in pre-
with 6% anhydrous sodium carbonate. pH of 1% solu- emptive analgesia. Also has a major role in long-term
tion: 1011. pKa is 7.9; thus a greater proportion remains neuronal potentiation and depression involved in
unionised in plasma than with thiopental. Used mainly memory and learning. The only NMDA antagonist avail-
for day-case surgery and short procedures, including able for use in the UK is ketamine, which is used in low
electroconvulsive therapy (because of its pro-convulsant doses (e.g. 0.10.2mg/kg) before skin incision to reduce
properties). postoperative pain.
Properties are similar to those of thiopental but pain NMDA receptor-mediated calcium influx is also
on injection, involuntary movement, hiccup and laryngo- thought to contribute to neuronal cell death following
spasm are more likely. Adverse effects of intra-arterial cerebral ischaemia and in neurodegenerative disorders.
injection are less than with thiopental, due to the more An autoimmune encephalitis due to antibodies directed
dilute solution. Recovery is within 34min of a single at NMDA receptors has been described.
dose of 1.01.5mg/kg, with half-life 24h. Petrenko AB, Yamakura T, Baba H, Shimoji K (2003).
Anesth Analg; 97: 110816
Methotrexate. Antimetabolite cytotoxic drug; inhibits
-Methyldopa. Antihypertensive drug, originally
dihydrofolate reductase, thus blocking purine and
thought to act via uptake into catecholamine synthetic
pyrimidine synthesis and preventing cell division. Used
pathways and formation of a false transmitter,
in the treatment of various malignancies, including acute
-methylnoradrenaline. The latter is now thought to
lymphoblastic leukaemia; also used in severe psoriasis
have a direct antihypertensive action of its own, possibly
and rheumatoid arthritis. May accumulate in pleural or
via stimulation of central inhibitory -adrenergic recep-
ascitic fluid, producing systemic toxicity subsequently.
tors, or reduction of plasma renin activity. Superseded
Excreted renally; thus NSAIDs are contraindicated
by newer drugs, but it is still occasionally used, e.g. in
since reduced renal function may increase toxicity.
Dosage varies widely according to the condition and
pre-eclampsia (shown to be non-teratogenic).
Dosage:
route; usual range is 7.5100mg every 27 days. May
250mg orally bd/tds, titrated to response (maximum
be given orally, iv, im or intrathecally.
Side effects: myelosuppression, mucositis, pneumoni-
3g/day).
250500mg iv over 3060min (as methyldopate
tis (especially likely in rheumatoid arthritis), GIT
hydrochloride). Onset of action is 46h, lasting up
disturbance, hepatic impairment.
to 16h.
Side effects:
Methoxamine hydrochloride. Vasopressor drug, acting leucopenia, hepatitis, haemolytic anaemia. 1020%
via selective 1-adrenergic receptor stimulation. Used of patients have a positive direct Coombs test
(12mg iv) to raise BP (e.g. during epidural or spinal that may interfere with blood compatibility testing
anaesthesia) and to treat SVT. Causes a reflex bradycar- (see Haemolysis). A SLE-like syndrome has been
dia via the baroreceptor reflex. Discontinued in 2001 reported.
because of falling global demand. sedation, confusion.
bradycardia, hypotension, oedema.
Methoxyflurane. CHCl3CF2OCH3. Inhalational anaes- GIT disturbances.
thetic drug, first used in 1960. Cheap and non-explosive, paradoxical hypertension has occurred after iv use.
but withdrawn from practice because of high-output [Robin RA Coombs (19212006), Cambridge
renal failure caused by fluoride ion production. Has high immunologist]
boiling point (105C) and therefore difficult to vaporise.
Very soluble in blood (blood/gas partition coefficient of Methylenedioxyethylamfetamine, see Methylenedioxy-
13); induction and recovery are therefore slow. Extremely methylamfetamine
 Metronidazole 379

Methylenedioxymethylamfetamine (MDMA; Ecs Dosage: 24g/day orally.

tasy). Synthetic amfetamine-like stimulant drug, abused Side effects include sedation, extrapyramidal move-
recreationally, especially in association with prolonged ments, renal stones and diarrhoea.
dancing. Psychological effects include feelings of eupho-
ria and increased intimacy with others. Toxicity has been Meticillin-resistant Staphylococcus aureus, see Infec-
associated with collapse and sudden death, particularly tion control; Staphylococcal infections
when combined with extreme physical exertion and
dehydration. Has been associated with hyperthermia
(thought to involve central 5-HT pathways and not Metoclopramide hydrochloride. Antiemetic drug,
peripheral mechanisms as in MH), arrhythmias and acting via dopamine receptor antagonism at the chemo-
hepatic failure. With increasing awareness that concur- receptor trigger zone. Also a prokinetic drug, increasing
rent dehydration may be harmful, cases of hyponatrae- gastric emptying and lower oesophageal sphincter pres-
mia caused by excessive water intake have been reported. sure via a peripheral cholinergic action, but will not
Degeneration of central neurones has also been reported reverse the effects of opioid analgesic drugs in this
after prolonged exposure. Most cases of acute critical respect unless given iv. It also decreases the sensitivity
illness involve hyperthermia that may be associated with of visceral afferent nerves to local emetics and irritants.
severe acidosis, DIC and rhabdomyolysis. Has little effect on PONV if 10mg is given iv on induc-
Management of acute toxicity is mainly supportive. tion of anaesthesia, but significantly reduces PONV if
Hyperthermia is treated with active cooling; dantrolene 20mg is given towards the end of surgery. Half-life is
has been used. about 46h.
Dosage:
Similar concerns exist for the related drug methylene-
10mg iv, im or orally tds as required. Total daily
dioxyethylamfetamine (Eve), which is less commonly
used. dose: 0.5mg/kg.
has been used in very high doses (up to 5mg/kg iv)
Hall AP, Henry JA (2006). Br J Anaesth; 96: 67885
to treat vomiting caused by cytotoxic therapy;
thought to antagonise central 5-HT3 receptors.
Methylmethacrylate. Acrylic cement used in orthopae- Side effects: extrapyramidal effects and dystonic
dic surgery for fixation of prostheses. Thought to be the reactions (particularly affecting the face), especially
cause of hypotension, hypoxaemia or cardiovascular col- following iv administration in children or young
lapse upon prosthesis insertion, although the mechanism adults. Hypotension and tachy- or bradycardia may
is unclear. occur after rapid injection. Has been associated with
Possible mechanisms:
methaemoglobinaemia and sulphaemoglobinaemia if
direct cardiotoxicity of the monomer.
taken chronically or in high dosage.
allergic reaction.
peripheral vasodilatation.
activation of the coagulation cascade within the pul- Metocurine, see Dimethyl tubocurarine chloride/
monary vasculature. bromide
fat or air embolism resulting from insertion of lipid-
soluble cement into the bone cavity under Metoprolol tartrate. -Adrenergic receptor antagonist,
pressure. available for oral and iv administration. Relatively selec-
combination of the above, exacerbated by the high tive for 1-receptors. Uses and side effects are as for
temperatures generated (over 90C) as the cement -adrenergic receptor antagonists in general.
hardens. Dosage:
Risks are reduced by washing out the bone cavity with hypertension, migraine: 100200mg orally od/bd;
saline before cement insertion, and retrograde insertion, arrhythmias, angina: 50100mg bd/tds; thyrotoxico-
avoiding air trapping within the cavity. sis: 50mg qds.
Donaldson AJ, Thomson HE, Harper NJ, Kenny NW acute administration: 24mg slowly iv, repeated up
(2009). Br J Anaesth; 102: 1222 to 10mg.
acute coronary syndromes: 5mg iv every 2min up
Methylnaltrexone bromide. Peripherally acting mu to 15mg if haemodynamically tolerated; then
opioid receptor antagonist licensed as a treatment for 15min later 50mg orally qds for 48h.
opioid-induced constipation in patients receiving pallia-
tive care. Does not cross the bloodbrain barrier, thus Metre. SI unit of length. Originally defined according to
devoid of central effects. the length of a platinumiridium bar kept at Svres,
Dosage: 812mg sc on alternate days. France, but redefined in 1960 according to the speed of
Side effects include abdominal pain, diarrhoea, light in a vacuum, following doubts as to the bars con-
nausea. stant length over time: 1 metre = the distance occupied
by 1650763.73 wavelengths of a specified orange-red
Methylprednisolone, see Corticosteroids light from gaseous krypton-86.

-Methyl-p-tyrosine (Metirosine). Antihypertensive Metronidazole. Antibacterial drug, active against a

drug; inhibits conversion of tyrosine to dopa, thus wide range of anaerobic bacteria and protozoa. Used in
blocking catecholamine synthesis. Available on a named many infections, especially gastrointestinal and gynaeco-
patient basis in the UK. Has been used to reduce the logical. Undergoes hepatic metabolism and renal excre-
incidence and severity of hypertensive episodes in tion, with a half-life of 8.5h. Tinidazole has similar
phaeochromocytoma, e.g. before or instead of surgery. actions but a longer duration of action and is given
Should not be used in essential hypertension. once daily.
380 MEWS

Dosage: MichaelisMenten kinetics. Refers to the reaction

200800mg orally/iv tds. between a single substrate S and an enzyme E, via an
1g pr tds for 3 days, then bd. intermediate complex ES to give a single product P:
Side effects: disulfiram-like reaction, nausea, vomit-
S + E  ES  P
ing, urticaria; rarely drowsiness, ataxia; on prolonged
dosage peripheral neuropathy, convulsions, leucope- As the concentration of S ([S]) increases from zero, rate
nia, urine discoloration. of reaction increases, until the enzyme binding sites
become saturated, and maximal rate of reaction is
MEWS, see Modified early warning score reached. Thus, initially, velocity of reaction (V) is propor-
tional to [S]; i.e. first-order kinetics apply. Eventually, V
MEOWS, Modified early obstetric warning score, see does not increase as [S] increases; i.e. zero-order kinetics
Modified early warning score apply (Fig. 107).
V [S]
Michaelis Menten equation: V = max
Mexiletine hydrochloride. Class Ib antiarrhythmic Km + [S]
drug; reduces fast sodium entry and shortens the refrac-
tory period. Chemically related to lidocaine, but active where Vmax = maximal reaction velocity
orally. Half-life is 10h. Used to treat ventricular Km = Michaelis constant, the concentration of S
arrhythmias. at which V = 1 2 Vmax
Dosage: Vmax and Km are found by plotting 1/V against 1/[S] to
400mg orally, followed by 200250mg tds/qds. obtain a straight line; the x-intercept is 1/Km, the
100250mg iv over 10min, followed by 250mg y-intercept is 1/Vmax and the slope is Km/Vmax.
over 1h, then 250mg over 2h, then 30mg/h May also be applied to pharmacology, to describe
thereafter. absorption, distribution and elimination of drugs.
Side effects: [Leonor Michaelis (18751945), German-born US
hypotension, bradycardia. chemist; Maud Menten (18791960), US physician]
confusion, ataxia, nystagmus, tremor, convulsions. See also, Pharmacokinetics
hepatitis, jaundice, GIT disturbances.
Miconazole. Imidazole antifungal drug, active against a
MeyerOverton rule. Describes the positive correla- wide range of fungi and yeasts. Used for local treatment,
tion between anaesthetic potency of inhalational anaes- or by mouth (as tablets or oral gel) for intestinal
thetic agents and lipid solubility. Can be seen if MAC is infection.
plotted against oil/gas partition coefficients at 37C for Dosage: tablets: 250mg qds for 10 days; gel: 510ml
various agents, using logarithmic scales (Fig. 106). qds.
[Hans Meyer (18531939), German pharmacologist; Side effects include GIT disturbances and rash.
Charles Ernest Overton (18651933), English-born Should be avoided in porphyria.
German pharmacologist]
See also, Anaesthesia, mechanism of Microshock, see Electrocution and electrical burns

MH, see Malignant hyperthermia Midazolam hydrochloride. Benzodiazepine, used for

sedation, premedication and induction of anaesthesia.
MHRA, see Medicines and Healthcare products Regula- Has also been used for status epilepticus. Water-soluble
tory Agency at pH < 4 due to its open imidazole ring (five-membered
ring containing carbon and nitrogen atoms); it becomes
MI, see Myocardial infarction highly lipid-soluble at body pH due to ring closure (an
example of structural isomerism), resulting in rapid
onset of action following iv administration. Also rapidly
1000

Carbon tetrachloride
10 V max
Sulphur hexafluoride
MAC (atmospheres)

N2O
Xenon 1.0
Velocity

Vmax
Cyclopropane
0.1 2
Fluroxene
Diethyl ether
Enflurane
Halothane 0.01
Chloroform
Methoxyflurane
0.001
10000 1000 100 10 1.0 0.1 [S] = Km
Oil/gas partition coefficient [S]

Fig. 106 MeyerOverton rule Fig. 107 MichaelisMenten kinetics

 Minimal alveolar concentration 381

absorbed after im injection. Elimination half-life is 1.5 Management is divided into:

2.5h. Undergoes hepatic metabolism to an active com- prophylactic: includes -adrenergic receptor antag-
pound (alpha-hydroxymidazolam) that is excreted onists, 5-HT receptor antagonists (e.g. pizotifen,
renally. Anterograde amnesia is marked. methysergide), amitriptyline.
Has relatively slow onset when used for induction, therapeutic: includes simple analgesic/antiemetic
with prolonged recovery. Effects are antagonised by combinations, 5-HTID receptor agonists, ergota-
flumazenil. mine.
Dosage: Anaesthetic management of a migraine sufferer is along
premedication: 0.070.1mg/kg im, 3060min pre- standard lines. Management in the presence of an actual
operatively. Paediatric oral dosage: 0.50.75mg/kg migraine attack is uncertain; if severe it may be wiser to
30min preoperatively. postpone surgery, although there is no evidence to
sedation: 0.52mg increments iv. By infusion: 0.05 support this.
0.2mg/kg/h. Silberstein SD (2004). Lancet; 363: 38191
induction: up to 0.3mg/kg.
Respiratory and cardiovascular depression may occur, Military antishock trousers, see Antigravity suit
especially in elderly and sick patients, in whom reduced
dosage is required. Milrinone lactate. Phosphodiesterase inhibitor, used as
See also, Intravenous anaesthetic agents an inotropic drug in severe congestive cardiac failure.
Increases cardiac output and reduces SVR without
MID-CM, see Minimally invasive direct cardiac increasing heart rate or myocardial O2 demand, although
massage rate of atrioventricular conduction may increase slightly.
Elimination half-life is about 22.5h. Excreted mainly
Midwives, prescription of drugs by. Approved hospital via urine.
midwives in the UK are usually permitted to administer Dosage: 50g/kg over 10min iv, followed by 0.3
certain drugs on the labour ward without individual pre- 0.75g/kg/min up to 1.1mg/kg/day; doses should be
scription by doctors, according to agreement with the reduced in renal impairment.
local health authority and obstetricians. Specified drugs Side effects: hypotension, ventricular and supraven-
thus vary between hospitals, but usually include: tricular arrhythmias, angina, headache.
opioid analgesic drugs, usually pethidine 100
150mg im, repeated once. Minaxolone. Water-soluble corticosteroid iv anaesthetic
Entonox and O2. agent derived from Althesin, investigated in the late
oxytocics, e.g. oxytocin and ergometrine separately 1970s/early 1980s. Causes rapid induction with involun-
or combined. tary muscle movement, anaesthesia lasting up to 20min.
antiemetic drugs/H2 receptor antagonists, e.g. Development was terminated because of reported
metoclopramide/ranitidine. toxicity in rats.
lidocaine 0.5% 1020ml for local perineal
infiltration. Mineralocorticoids. Group of corticosteroids; typically
vitamin K and naloxone for the neonate. comprise aldosterone physiologically and fludrocorti-
Others include hypnotics, traditionally chloral hydrate sone therapeutically. Chief function is to regulate the
or trichlofos. Temazepam and alternative opioids (e.g. transport of sodium and potassium ions in the kidney
pentazocine) are sometimes given. Community mid- and other organs; hence they cause renal sodium reab-
wives usually have freedom to prescribe iron, antacids, sorption and loss of potassium. Hydrocortisone and
etc., in addition. other corticosteroids have some mineralocorticoid
Midwives may give epidural solutions (but not the effects but these are generally too weak to make hydro-
first injection) according to written instructions; respon- cortisone a useful therapeutic mineralocorticoid
sibility for administration lies with the prescribing (although they may limit its usefulness as a long-term
doctor. They may also administer TENS. glucocorticoid when used for disease suppression).
See also, Nurses, prescription of drugs by
Miniature end-plate potential, see End-plate
Migraine. Episodic form of headache; classified into potentials
migraine without aura (75% of cases; headache is typi-
cally unilateral and throbbing; there may be nausea and Minimal alveolar concentration (MAC). Minimal
photophobia) and migraine with aura (25% of cases; alveolar concentration of inhalational anaesthetic agent
headache is preceded by visual disturbances, numbness, that prevents movement in response to a standard skin
etc.). May be difficult to distinguish from tension head- incision in 50% of subjects studied, when breathed in
aches (caused by muscular contraction), headache oxygen in the absence of any other analgesic or
caused by cervical spondylosis, temporal arteritis, tri- anaesthetic/depressant drugs. Thus inversely related to
geminal neuralgia/other facial pain syndromes and anaesthetic potency. Useful as a means of comparing
headache caused by drugs. Subarachnoid haemorrhage, different agents, and may be used to guide clinical dosage
meningitis and post-dural puncture headache may also if end-tidal concentration of agent is monitored. Defined
pose diagnostic difficulties. Neurological features may in terms of percentage of one atmosphere; therefore not
occasionally be severe and mimic CVA. Typically pro- influenced by altitude.
voked by triggers such as stress, alcohol and certain MAC is reduced by:
foods. The pathophysiology is uncertain but altered cere- other depressant drugs (e.g. opioids, sedatives, other
bral blood flow, cerebral vasoconstriction/dilatation, cor- inhalational agents).
tical hyperexcitability and nitric oxide pathways have all CNS depletion of catecholamines, e.g. by
been implicated. -methyldopa, reserpine.
382 Minimal blocking concentration

hypothermia. the arbitrariness of the defined outcomes. However, it

hypoxaemia/hypotension. has been useful for examining the effects of local anaes-
pregnancy, possibly due to increased progesterone thetic dosage, concentration and volume independently,
levels. and of the addition of adjuncts, e.g. opioids.
extremes of age. Graf BM, Zausiq Y, Zink W (2005). Curr Opin Anesthe-
MAC is increased in: siol; 18: 2415
children.
hyperthermia. Minimally invasive direct cardiac massage (MID-
hyperthyroidism. CM). Variant of open chest cardiac massage that does
chronic alcoholism. not require thoracotomy. Uses a hand-held device intro-
It is unaffected by duration of anaesthesia, sex, acidaemia/ duced via a small thoracostomy. The device consists of a
alkalaemia, hypercapnia or hypocapnia. 40 FG introducer and a flat umbrella-shaped plunger
The term MAC-BAR (blocks adrenergic response) that is collapsed and retracted during insertion. Once in
has also been studied; it refers to the minimum alveolar the chest, the umbrella is opened, expanding to a diam-
concentration of agent at which the increase in heart rate eter of 7.5cm, and used to pump the heart rhythmically
or BP (or both) provoked by skin incision is prevented from outside the pericardium.
in 50% of subjects. Rozenberg A, Incagnoli P, Delpech P, etal (2001). Resus-
The term MAC awake has been used to describe the citation; 50: 25762
alveolar concentration of agent at which 50% of subjects See also, Cardiac arrest; Cardiopulmonary resuscitation
no longer respond appropriately to command. The term
has also been applied to the alveolar concentration at Minitracheotomy. Commercially available device,
which 50% of subjects respond appropriately when enabling emergency cricothyrotomy. Also useful as a
recovering from anaesthesia, in the absence of other route for tracheobronchial suction when sputum reten-
depressant drugs. It is often presented as the ratio of tion is a problem, e.g. respiratory infection, impaired
MAC awake/MAC; in general this ratio is in the order coughing or postoperatively. May thus avoid tracheal
of 0.30.5 for the commonly used volatile agents. It has intubation or formal tracheostomy, e.g. in ICU.
been suggested that MAC awake is the minimum alveo- The pack originally included a blade, 4mm internal
lar concentration required to prevent awareness during diameter tube and introducer, standard 15mm connec-
anaesthesia, although this is disputed. tor, suction catheter and securing tapes. Because of dif-
For values of MAC, see Table 24; Inhalational anaes- ficulties inserting the device without a guide-wire, one
thetic agents was subsequently introduced into the pack along with a
syringe, short 16G needle and dilator. The needle and
Minimal blocking concentration (Cm). Lowest concen- syringe are used to locate the trachea through a small
tration of local anaesthetic agent that will block a nerve vertical incision in the cricothyroid membrane and the
in vitro within (usually) 10min. Temperature, pH and guide-wire inserted into the trachea. The rest of the
electrolyte composition are specified. Higher concentra- insertion proceeds using the Seldinger technique. Com-
tions are required clinically, in order to achieve Cm at the plications include haemorrhage, subcutaneous emphy-
axons. Dependent on the size of axon, not the site sema and misplacement.
(although important clinically because of diffusion
across membranes, drug absorption, etc.). Minoxidil. Antihypertensive drug causing peripheral
vasodilatation. Reserved as third-line treatment after
Minimal infusion rate (MIR). Application of the MAC diuretics and -adrenergic receptor antagonists, because
concept to infusions of iv anaesthetic agents, e.g. in of tachycardia and water and salt retention. Also causes
TIVA. Equals the minimal infusion rate of agent that increased hair growth. Taken orally, 2.525mg od/bd.
prevents movement in response to skin incision in 50%
of subjects studied. More complex than MAC of inhala- Minute ventilation (Minute volume). Volume of air
tional agents, because of the influence of pharmacoki- breathed per minute. Equals tidal volume respiratory
netic factors associated with the use of iv infusions. rate; i.e. includes alveolar ventilation and dead space
ventilation. Normally 57 litres.
Minimal local anaesthetic concentration/dose/
volume (MLAC/MLAD/MLAV). Measurement used to Minute volume dividers, see Ventilators
compare the effects of different local anaesthetic solu-
tions and/or dosing regimens, typically for epidural or MIR, see Minimal infusion rate
spinal anaesthesia. For example, for MLAD, it requires
a series of patients to receive a standard concentration Misoprostol. Analogue of naturally occurring prosta-
of local anaesthetic, the response of each patient accord- glandin E1, licensed for gastric protection and healing of
ing to a defined outcome (e.g. for labour analgesia, ulcers in patients taking NSAIDs. Has been used to
whether pain scores reach a target reduction within a increase uterine contractions (e.g. in therapeutic abor-
set time) affecting the dose that the subsequent patient tion) and to prevent and treat postpartum haemorrhage,
receives (e.g. failed analgesia results in the next patient for which doses of 200800g have been given orally,
receiving a 20% higher dose; successful analgesia vaginally and rectally. Serious side effects are rare,
results in a 20% lower dose). Analysis of the fluctuating although shivering is common.
dosage requirements over a set number of patients
allows calculation of the ED50 for that concentration and Misuse of Drugs Act 1971. Introduced in the UK as a
outcome. Thus akin to MAC for inhalational anaesthetic replacement for the obsolete Dangerous Drugs Act.
agents. Criticisms include the lack of usefulness of Defined three classes of drugs, according to the penalties
knowing the ED50 (ED90 or ED95 being more useful) and for offences:
 Mitral stenosis 383

Class A: cardiac enlargement, particularly of the left atrium,

- opioid analgesic drugs, e.g. morphine, pethidine, and pulmonary oedema. Echocardiography and
fentanyl, alfentanil, diamorphine, methadone. cardiac catheterisation are useful.
- cocaine, methylenedioxymethamfetamine, methyl- Anaesthetic management:
amfetamine, lysergide (LSD), phencyclidine. main principles are as for congenital and ischaemic
- parenteral forms of class B drugs. heart disease. Drugs taken may include diuretics,
Class B: digoxin and anticoagulant drugs. The following
- opioids, e.g. codeine, pentazocine. should be avoided: myocardial depression, hypovo-
- amfetamines, barbiturates. laemia, bradycardia (which increases regurgitation;
- others, e.g. glutethimide (sedative/hypnotic), mild tachycardia is preferable), vasoconstriction,
phenmetrazine (appetite suppressant). e.g. due to sympathetic stimulation (pain, light
Class C: includes benzodiazepines, anabolic steroids anaesthesia), cold. If pulmonary artery catheterisa-
and certain amfetamine-related drugs. Cannabis tion is done, large V waves are typically seen in the
was reclassified as a Class C drug in 2004 (previ- pulmonary venous waveform.
ously Class B) but this was reversed in 2008. Ket- Foster E (2010). N Engl J Med; 363: 15665
amine (previously unclassified) was classified as a See also, Heart murmurs; Valvular heart disease
Class C drug in 2006.
Misuse of Drugs Regulations 2001: specifies the Mitral stenosis. Rheumatic fever is by far the most
requirements for handling, storage, record-keeping, common cause; others include congenital, infective
etc.: and inflammatory causes. Symptoms are usually present
Schedule 1: drugs not used therapeutically, e.g. can- if the valve area is reduced from the normal 45cm2
nabis, lysergide. to < 1.5cm2, although concurrent anaemia or atrial
Schedule 2: opioids, including codeine, morphine, fibrillation may precipitate symptoms with less severe
etc., and cocaine (controlled drugs). To be kept in stenosis.
locked cupboards (but not necessarily double- Effects:
locked); details of patients are recorded in registers reduced left ventricular filling, with left atrial hyper-
with practitioners signatures and kept for trophy and dilatation.
2 years. increased pulmonary vascular pressures, with pul-
Schedule 3: barbiturates, buprenorphine, pentazo- monary congestion and reduced pulmonary compli-
cine, temazepam (from 1996). Registers and locked ance. Work of breathing is increased.
cupboards are not required but special prescription if prolonged, it may cause pulmonary hypertension,
requirements are (except for buprenorphine and with right ventricular overload and/or tricuspid or
temazepam). pulmonary regurgitation. Progression may be rapid
Schedule 4: benzodiazepines, ketamine, anabolic in 2530%; the reason is unknown.
steroids. AF occurs in up to 50%; ventricular filling is reliant
Schedule 5: products containing low concentrations on atrial contraction, thus AF may lead to pulmo-
of substances otherwise in Schedule 2. Exempt from nary oedema.
virtually all controlled drug requirements. Features:
cardiac failure and dyspnoea. Haemoptysis may be
Mitral regurgitation. Most commonly due to degenera- caused by recurrent chest infection, pulmonary
tive disease associated with mitral valve prolapse; previ- oedema or infarction, or blood vessel rupture.
ously, most cases were due to rheumatic fever, when AF and systemic embolism.
mitral stenosis usually coexisted. May also be due to malar flush (mitral facies), parasternal heave and
papillary muscle dysfunction secondary to MI or degen- features of tricuspid valve regurgitation may be
eration; rare causes include left ventricular dilatation in present.
cardiac failure, cardiomyopathy, bacterial endocarditis tapping apex (palpable first heart sound). The first
and ruptured chordae tendinae. sound is loud, with opening snap following the
Effects: second sound. A low-pitched rumbling diastolic
left atrial dilatation; pulmonary oedema, especially murmur follows, heard best at the apex on expira-
if acute. Regurgitant fraction increases if SVR tion with the stethoscope bell, leaning forward and
rises. to the left. Presystolic accentuation is heard before
left ventricular hypertrophy and increased stroke the first heart sound, due to atrial contraction; it
volume. disappears in AF. The opening snap may disappear
AF if severe. Ventricular filling is less reliant on if the valve is calcified.
atrial contraction than in mitral stenosis; thus ECG may reveal P mitrale (a widened, notched P
cardiac output is usually maintained. wave), AF and right ventricular hypertrophy. CXR
Features: features may include cardiac enlargement, particu-
left ventricular hypertrophy, with pansystolic larly of the left atrium, and pulmonary oedema.
murmur loudest at the apex on expiration and Mitral calcification and features of pulmonary
leaning forward, and radiating to the axilla. A thrill, hypertension may be present. Echocardiography
third heart sound and diastolic flow murmur may be and cardiac catheterisation are especially useful. In
present. AF, left and later right ventricular failure moderate and severe stenosis the area is reduced to
may be present. < 2 and < 1cm2 respectively.
systemic embolism. Anaesthetic management:
endocarditis. main principles are as for congenital and ischaemic
ECG may reveal P mitrale, ventricular hypertrophy, heart disease. Drugs taken may include diuretics,
and ventricular ectopics. CXR features may include digoxin, anticoagulant drugs. The following should
384 Mitral valve prolapse

be avoided: myocardial depression; atrial fibrilla- in composition, and mixes during passage through
tion; tachycardia (reduces left ventricular filling the heart.
time); hypovolaemia and vasodilatation (reduce Mixed venous O2 saturation (Sv O 2 ) is related to arte-
atrial and thus ventricular filling); and increased rial O2 content, O2 consumption and cardiac output; it
pulmonary vascular resistance, e.g. due to hypox may be monitored continuously via a fibreoptic bundle
aemia. In pulmonary artery catheterisation, left on a pulmonary artery catheter. (Sv O 2 ) has been used as
ventricular end-diastolic pressure estimation is an indicator of O2 supply/demand in critically ill patients,
inaccurate due to stenosis. Due to lower cost and and as an early indicator of imminent haemodynamic
morbidity, percutaneous catheter balloon valvulo- failure; tissue O2 delivery is considered critical at (Sv O 2 )
plasty has become the treatment of choice in of under 50% (normally 75%). The measurement is non-
patients with suitable valve anatomy and/or high specific, however, and is increased by peripheral shunt-
surgical risk. ing, e.g. in septic shock.
postoperative IPPV may be required. See also, Arteriovenous oxygen difference
Chandrashekar Y, Westaby S, Narula J (2009). Lancet;
374: 127483 MLAC/MLAD/MLAV, see Minimal local anaesthetic
See also, Heart murmurs; Tricuspid valve lesions; Valvu- concentration/dose/volume
lar heart disease
MMV, see Mandatory minute ventilation
Mitral valve prolapse. Superior displacement of mitral
valve leaflet tissue into the left atrium, above the mitral MOC-etomidate, see Etomidate
annular plane. Thought to occur in up to 15% of the
population, sometimes associated with autosomal domi- Mode. Expression of the central tendency of a set of
nant inheritance. Also associated with Marfans syn- observations or measurements. Equals that observation,
drome and other collagen disorders (e.g. EhlersDanlos or group of observations, that occurs the most often.
syndrome). Acquired causes are as for mitral regurgita- Equals the mean for a normal distribution.
tion. Often asymptomatic, but may lead to mitral regur- See also, Median; Statistical frequency distributions;
gitation, cardiac failure, bacterial endocarditis and Statistics
systemic emboli.
Signs: Modified early warning score (MEWS). Scoring
mid-systolic click, occurring at the onset of the
system used to aid identification of critically ill patients
carotid pulsation. or those at risk of clinical deterioration. Uses six vari-
late systolic heart murmur, not always present.
ables (systolic BP, heart rate, respiratory rate, tempera-
Diagnosis is usually aided by echocardiography or ture, neurological status and urine output) to score the
angiography. degree of abnormality of a patients physiology, with a
Perioperative complications are unlikely unless possible composite score of 0 (normal) to 17. Used to
mitral regurgitation is severe or left ventricular dysfunc- trigger calls for assistance from the patients primary
tion is present. team, a medical emergency team, an outreach team or
[Edvard Ehlers (18631927, Danish dermatologist; others.
Henri-Alexandre Danlos (18441912), French A similar concept (modified early obstetric warning
physician] score; MEOWS) has been applied to obstetric patients
Shah PM (2010). J Cardiol; 56: 12533 since analyses of maternal deaths and near-misses typi-
See also, Heart sounds cally find that the severity of the mothers condition is
not appreciated until late in the illness.
Goldhill DR (2001). Q J Med; 94: 50710
Mivacurium chloride. Non-depolarising neuromuscular See also, Acute life-threatening events recognition and
blocking drug, a benzylisoquinolinium ester (as is atra- treatment; Early warning scores
curium). Tracheal intubation is possible approximately
2min after a dose of 0.070.25mg/kg (doses above MODS, see Multiple organ dysfunction syndrome
0.15mg/kg should be given over 30s more slowly in
patients with asthma or CVS disease). Effects last 10 MOET, see Managing Obstetric Emergencies and Trauma
20min. Supplementary dose: 0.1mg/kg. May be given by course
iv infusion at 0.20.5mg/kg/h. Causes little or no cardio-
vascular instability, although histamine release (with Moffets solution, see Nose
bronchospasm, urticaria and hypotension) may accom-
pany high doses, especially if given rapidly. Metabolised Molality. Number of moles of solute per kilogram of
by plasma cholinesterase (thus its action may be mark- solvent. A molal solution contains 1 mole/kg.
edly prolonged in cholinesterase deficiency) to highly
water-soluble metabolites, excreted rapidly via the Molarity. Number of moles of solute per litre of solu-
urine; half-life is 25min. Also undergoes some hepatic tion. A molar solution contains 1 mole/l.
metabolism. More easily reversed than atracurium or
vecuronium. Has been suggested as an alternative to Mole. SI unit of amount of substance. Defined as that
suxamethonium, especially in children, in whom onset quantity containing the same number of particles as
and recovery are faster than in adults. there are atoms in 12g of carbon-12. This number (Avo-
gadros number) equals 6.022 1023.
Mixed venous blood. True mixed venous blood is
obtained from the right ventricle or pulmonary artery, Molecular adsorbents recirculation system, see Liver
since superior and inferior vena caval blood is different dialysis
 Monoamine oxidase 385

Molecular weight (mw). Mass of a molecule, equal to UK recommendations (Association of Anaes

the sum of atomic weights of its constituent atoms. thetists):
presence of the anaesthetist is mandatory during
Molgramostim, see Granulocyte colony-stimulating the whole procedure, with adequate record-keeping
factor and hand-over.
monitoring is instituted before induction and con-
Monitoring. Adequate monitoring during anaesthesia tinued until recovery.
and recovery is now generally acknowledged to improve equipment monitoring: O2 failure warning device,
patient safety, reducing anaesthetic morbidity and mor- output and delivery O2 analyser, and disconnection
tality. Standards of minimal monitoring have been pub- detection by expired tidal volume measurement,
lished in many countries, e.g. in the USA since 1986 and capnography and airway pressure measurement.
the UK since 1988. Failure to employ appropriate moni- Monitoring of volatile agent. All alarms set at
toring equipment is increasingly considered negligent. appropriate values and enabled. Infusion devices
Devices should warn of adverse changes in the state of checked and alarms set.
the patient, and of altered functioning of anaesthetic patient monitoring: clinical observation of colour,
equipment. pupils, respiration, pulse and response to surgery,
Most monitors involve electrical equipment. Techni- chest auscultation, urine output and blood loss
cal considerations: when appropriate, plus:
signal from patients may be: - for induction and maintenance: ECG, arterial
- primary electrical signals, e.g. ECG, EEG, power BP measurement, pulse oximetry, capnography,
spectral analysis. oxygen and volatile agent analyser, a nerve stimu-
- electrical signals derived from other energy forms, lator whenever neuromuscular blocking drugs are
e.g. via pressure transducers. used, and a means of temperature measurement
- evoked signals, e.g. neuromuscular blockade mon- available.
itoring, evoked potentials. - for recovery: oximetry and BP measurement
skin electrodes are usually made of silver/silver (ECG, nerve stimulator, temperature measure-
chloride to reduce alterations in impedance, and to ment and capnography immediately available).
reduce the creation of interfering potentials within - heart rate and BP recorded at regular intervals
the electrode. as appropriate. Waveforms are preferable to
amplification/processing of the signal via inter numeric displays. Trend displays/printouts
mediate components. Accuracy of reproduction is recommended.
related to: - direct BP measurement, CVP measurement, pul-
- signal:noise ratio: improved by filtering, and aver- monary artery pressures, arterial blood gas inter-
aging the signal so that background noise is can- pretation and blood tests as appropriate.
celled out. Recording between two recording - for sedation, regional anaesthesia: at least ECG,
leads (differential input) also cancels out back- oximetry and BP measurement.
ground noise, since the noise is in phase in both - adequate monitoring (including easily accessible
the leads. and visible displays) required for transfer of
- baseline drift: may be random or due to the effect patients.
of temperature on semiconductors. Buhre W, Rossaint R (2003). Lancet; 362: 183946
- sensitivity of the amplifier: related to the voltage See also, Anaesthesia, depth of; Blood flow; Carbon
of the original signal (i.e. appropriate gain). dioxide measurement; Cardiac output measurement;
- linearity of the response: distortion causes non- Echocardiography; Gas analysis; Oxygen measurement;
linear response characteristics and hysteresis. Pulmonary artery catheterisation; Pulmonary wedge
- damping. pressure; Respirometer
- frequency range: related to the harmonics of the
measured signal.
- matched output/input voltage, current, etc., of Monoamine oxidase (MAO). Enzyme present in mito-
components. chondria of most tissues, especially liver, intestinal
- interference; may be caused by: mucosa, lung, kidney and catecholamine-secreting nerve
- capacitance between the patient and electrical endings. Catalyses oxidative deamination of amines to
equipment. aldehyde derivatives, e.g. RCH2NH2 RCHO. Inac-
- inductance of current in the patient and monitor tivates active amines, including catecholamines, whether
wires by electrical equipment. circulating, absorbed from the gut, or at adrenergic/5-HT
- other electrical equipment, e.g. diathermy, other nerve endings. Many products are subsequently metabo-
monitors. lised by catechol-O-methyl transferase (COMT), and
display of the signal, as, e.g. a waveform on oscillo- many products of COMT metabolism are subsequently
scopes, numerical display, galvanometer and/or metabolised by MAO.
paper strip. Two distinct types have been identified: type A,
alarms are usually incorporated into monitors; mainly inactivating noradrenaline and 5-HT, and type B,
limits are set to minimise inappropriate warnings mainly inactivating tryptamine and phenylethylamine.
without compromising sensitivity. Alarms of differ- Dopamine and tyramine are inactivated by both. Both
ent devices are often of random pitch and are present in liver and brain; type B is thought to be
frequency; standardisation of alarms has been predominant in certain CNS regions, e.g. basal ganglia.
suggested. Non-specific and type A-specific MAO inhibitors are
risk of electrocution and electrical burns from elec- used to treat depression; MAO type B inhibitors are
trical equipment. used as antiparkinsonian drugs.
386 Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs). The term Moricizine hydrochloride. Class I antiarrhythmic drug,
usually refers to non-specific inhibitors of monoamine structurally related to phenothiazines. Available on a
oxidase, used as antidepressant drugs and developed in named patient basis in the UK. Used to treat ventricular
the 1950s from anti-TB drugs. Examples include phenel- arrhythmias. Half-life is 36h.
zine, isocarboxazid, tranylcypromine and moclobemide. Dosage: 200300mg orally tds or 400500mg fol-
Recently increasing in use following a period of unpopu- lowed by 200mg tds for rapid control.
larity. Inhibit monoamine oxidase irreversibly (except Side effects: GIT disturbances, dizziness, arrhythmias,
moclobemide), resynthesis of the enzyme taking at least jaundice, thrombocytopenia.
3 weeks.
Anaesthetic importance: Morbidity and mortality, see Anaesthetic morbidity
interaction with pethidine: may be: and mortality; Mortality/survival prediction on intensive
- excitatory: agitation, hypertension, tachycardia, care unit
hyperreflexia, hypertonus, pyrexia, convulsions,
coma. Thought to be caused by excessive central Morphine hydrochloride/sulphate/tartrate. Opioid
5-HT activity, due to reduced 5-HT uptake. Treat- analgesic drug, in use for thousands of years as opium
ment includes -adrenergic receptor antagonists, derived from poppy seeds. Isolated in 1803, and synthe-
vasodilator drugs and chlorpromazine. Steroids sised in 1952, although still obtained from poppies.
have been used. The standard drug with which other opioids are
- depressive: may cause hypoventilation, hypoten- compared.
sion, coma. Thought to be caused by impaired Used for premedication and as an analgesic drug.
hepatic metabolism of opioid. Naloxone and Also useful in pulmonary oedema. Peak effect occurs
directly acting vasopressors, e.g. noradrenaline, 1520min after iv, and 6090min after im injection;
have been used for treatment. action lasts 45h. Undergoes significant first-pass
Morphine has been suggested as the opioid of metabolism when given orally. Undergoes hepatic deal-
choice, titrated to effect. Although fentanyl is kylation, oxidation and conjugation to morphine 3-
related to pethidine, it has been safely used; and 6-glucuronide, excreted in urine. The latter is a
however experience is limited. Pentazocine has highly active metabolite, and may be responsible for
also been used safely. prolonged action, e.g. in renal impairment or chronic
sympathomimetic drugs may produce exaggerated administration.
hypertensive responses, especially those acting indi- Actions:
rectly via catecholamine release, e.g. ephedrine, CNS:
metaraminol. Directly acting drugs (e.g. noradrena- - depression of:
line, adrenaline and isoprenaline) should be used in - respiratory centre; rate is reduced more than
small amounts if required. Catecholamines and tidal volume. Neonates and the elderly are par-
drugs increasing catecholamine levels should be ticularly susceptible.
avoided, e.g. pancuronium, ketamine, cocaine and - cough reflex.
adrenaline in local anaesthetic solutions (the last is - pain sensation, especially dull continuous pain.
controversial). Most effective if given before the painful stimu-
other iv and inhalational agents, benzodiazepines lus. Perception of painful stimuli is altered as
and non-depolarising neuromuscular blocking well as pain sensation itself.
drugs are considered safe; doxapram is considered - anxiety; morphine causes sedation and
unsafe. euphoria.
phenelzine may decrease plasma cholinesterase - ACTH and prolactin secretion.
levels. - metabolic rate.
Crises may also follow oral ingestion of active amines - vasomotor centre; depression is now thought to
or precursors (e.g. in tyramine-rich food such as cheese be minimal, if it occurs at all.
and red wine) because of inhibition of the enzyme in the - stimulation of:
gut wall. - chemoreceptor trigger zone.
Traditional advice, to stop taking MAOIs 23 weeks - parasympathetic nucleus of the third cranial
preoperatively, is rarely given now, because of risks of nerve, causing miosis.
worsening depression, and possible inadequacy of this - vasopressin release.
interval. Moclobemide is a reversible inhibitor of MAO - vagus nerve, causing bradycardia.
type A (or RIMA), said to be less likely to interact with - higher centres causing euphoria or, less com-
amines and drugs. No treatment-free period is required monly, dysphoria.
after stopping therapy. Selegiline is a MAO type B inhib- - muscle rigidity following high doses; may be
itor used in Parkinsons disease; it increases central caused by central interference with motor func-
dopamine levels without exhibiting an exaggerated tion, although the mechanism is unclear.
response to dietary amines. - may cause addiction.
peripheral:
MonroKellie doctrine. The cranial cavity is a rigid - histamine release; may cause vasodilatation, bron-
closed container; thus any change in intracranial blood choconstriction, itching (typically of the nose),
volume is accompanied by the opposite change in CSF flushing. Hypotension may occur (partly a central
volume, if ICP remains constant. effect).
[Alexander Monro (17331817) and George Kellie - constipation, delayed gastric emptying and
(17581829), Scottish anatomists] reduced lower oesophageal sphincter tone.
Increases the tone of biliary and genitourinary
Montelukast, see Leukotriene receptor antagonists smooth muscle, including sphincters.
 Motor neurone, lower 387

- increases catecholamine release from the adrenal None of the general systems has been shown to be supe-
medulla. rior to the others, although updated systems generally
Dosage: perform better than the original ones.
standard im, iv or sc dose: 0.10.15mg/kg. Breslow MJ, Badawi O (2012); Chest 141: 24552,
orally: adults: 1020mg increased slowly up to 51827
200mg, 4-hourly; sustained release preparation: See also, Intensive care, outcome of
from 10mg bd.
has been given via buccal and rectal routes. Morton, William Thomas Green (18191868). US
Doses and/or frequency of administration should be dentist, considered the founder of anaesthesia, despite
reduced at the extremes of age and in renal or hepatic being predated by Clarke, Long and Wells. Briefly prac-
failure. tised with Wells in Boston in 18423, before entering
[Morpheus, Greek god of dreams] Harvard Medical School in 1844, although he never com-
See also, Opioid receptors; Spinal opioids pleted his medical studies. Present at Wells unsuccessful
demonstration of N2O at Harvard in 1844. Morton
Mortality and morbidity, see Anaesthetic morbidity approached Jackson for advice on supplies of N2O for
and mortality; Mortality/survival prediction on intensive further experiments. Jacksons suggestion of diethyl
care unit ether as a topical analgesic led to Mortons use of ether
for inhalational anaesthesia for dental extraction on 30
September 1846. At the Massachusetts General Hospital
Mortality probability models (MPM). Scoring systems, on 16 October, he successfully anaesthetised Edward
similar to APACHE and simplified acute physiology Gilbert Abbott, whilst Warren excised a mass from
score, for predicting outcome of ICU patients. The latest the latters jaw. Became demoralised by subsequent
version (MPM III) is based on multiple regression analy- battles against Jacksons claim to the discovery, and
sis applied to data from 125000 patients at the time of against widespread infringement of his patent (which he
admission to ICU and reflects changes in clinical man- named Letheon). His contribution was recognised only
agement since the MPM II system was introduced. posthumously.
Scores are derived from weighting of variables related [Edward Gilbert Abbott (18251855), US printer]
to physiology, acute and chronic disease, reason for See also, Letheon
admission, age and therapeutic interventions. A proba-
bility of hospital mortality can be calculated at 0, 24, 48 Motor neurone disease. Progressive degenerative dis-
and 72h after ICU admission. Individual versions of the order characterised by degeneration of motor neurones
MPM system are termed MPM0 (calculation of risk of in the brainstem nuclei of the cranial nerves and anterior
hospital death on entry to ICU), MPM24, MPM48 and horn cells of the spinal cord. Prevalence is 5 per 100000;
MPM72 (calculated after 24, 48 and 72h of ICU care mainly affects men aged 5070. Death usually occurs
respectively). within 35 years.
Higgins TL, Teres D, Copes WS, etal (2007). Crit Care Types:
Med; 35: 82735 amyotrophic lateral sclerosis: upper motor neurone
See also Intensive care, outcome of; Mortality/survival lesions with spastic limb weakness.
prediction on intensive care unit progressive bulbar palsy: lower motor neurone
lesions of the brainstem nuclei, causing dysarthria
Mortality/survival prediction on intensive care unit. and dysphagia.
Many attempts have been made to develop methods of progressive muscular atrophy: lower motor neurone
predicting outcomes in critically ill patients, to allow: lesions of the anterior horn cells.
estimation of prognoses for individual patients. Anaesthetic problems are related to:
comparison between different treatments, e.g. in possible laryngeal incompetence leading to aspira-
clinical studies. tion of gastric contents.
comparison between different units (e.g. using the respiratory muscle weakness, with greater sensitiv-
standardised mortality ratio: observed mortality ity to respiratory depressant drugs.
divided by predicted mortality). increased sensitivity to neuromuscular blocking
allocation of resources. drugs. An exaggerated hyperkalaemic response to
Scoring systems may be based on a single set of data suxamethonium is theoretically possible but has not
(static) or on repeated collections over time (dynamic). been reported.
Many different systems exist, including: ICU concerns include the above and also the ethical
simple five-point scale according to clinical judge- issues surrounding ventilatory support when respiratory
ment, e.g. certain to die; likely to die, etc. failure occurs.
therapeutic intervention scoring system (TISS):
based primarily on treatment interventions. Motor neurone, lower. Term used to describe motor
acute physiology score (APS), simplified acute neurones that directly innervate muscle, i.e. without
physiology score (SAPS), APACHE scoring other neurones interposed. Lower motor neurone
systems, mortality probability models (MPM), lesions therefore result in complete cessation of neural
logistic organ dysfunction system (LODS): based input to the muscle, resulting in characteristic clinical
mainly on the patients physiological state thera- features:
peutic interventions. flaccid paralysis.
specific systems for certain conditions, e.g. coma visible fasciculations, thought to be caused by spon-
scales such as the Glasgow coma scale (GCS), taneous firing of neighbouring motor units that
trauma scales, scoring systems for sepsis, burns, sub- have taken over the affected muscle.
arachnoid haemorrhage, hepatic failure. absent reflexes.
388 Motor neurone, upper

muscular atrophy. commonly refers only to the former. Upper motor

denervation hypersensitivity. Thought to be the neurone lesions may thus occur at any level above the
cause of invisible fibrillation of muscle fibres. An lower neurone cell bodies, producing characteristic fea-
increased hyperkalaemic response to suxametho- tures, after initial flaccid paralysis:
nium may occur from 4 days to 7 months after increased tone and spastic paralysis. Typically,
injury. muscle exhibits clasp-knife rigidity, possibly due to
See also, Motor neurone, upper activity of muscle spindles without inhibitory higher
input.
Motor neurone, upper. Term used to describe neurones increased reflexes and up-going plantar responses
of the motor pathways, excluding lower motor neurones. (Babinski reflex).
Thus includes neurones of the motor cortex, cerebellar no fasciculation.
and extrapyramidal pathways, although the term no atrophy.

Leg

Face

Head of caudate nucleus Internal capsule

Cerebrum Putamen

Globus pallidus

Thalamus

Medulla

Pyramid

Decussation

Spinal cord

Lateral corticospinal tract Anterior corticospinal tract

Spinal cord

Fig. 108 Pyramidal (corticospinal) motor system

 Moxifloxacin hydrochloride 389

an increased hyperkalaemic response to suxame-

thonium may occur from 10 days to 7 months after (a)
injury, although the mechanism is unclear.
[Joseph Babinski (18571932), French neurologist]
See also, Motor neurone, lower

Motor pathways. Consist of the following systems:

pyramidal pathways (Fig. 108): fibres arise from
pyramidal cells of the motor cortex of the precen-
tral gyrus and premotor area. Legs are represented
uppermost, with the head at the lower part of the
(b)
gyrus. Regions of densest innervation (e.g. face,
hands) have a disproportionately greater represen-
tation. Fibres then pass via the internal capsule (legs
represented behind, face anteriorly), and via the
cerebral peduncle and pons to the medulla, forming
the pyramids. Most of the fibres decussate in the
lower medulla and pass within the lateral cortico-
spinal tract of the spinal cord. Some pass within the
anterior corticospinal tract without decussating;
these cross within the spinal cord at their spinal
levels. Some fibres pass to cranial nerve motor
nuclei. Most of the fibres synapse with intermediate (c)
neurones.
extrapyramidal pathways: less well defined than the
above system. Fibres arise from the premotor area
and corpus striatum, and pass via the basal ganglia,
substantia nigra and nuclear masses of the midbrain
and hindbrain. They descend within the rubrore-
ticulospinal and vestibulospinal tracts. Other path-
ways pass from the tectum of the midbrain and
olives of the medulla. Concerned with control of
movement.
cerebellar pathways: involve the thalamus, red
nucleus, pons, medulla and cerebral cortex.
pathways of the autonomic nervous system.
See also, Motor neurone, lower; Motor neurone, upper;
Spinal cord lesions Fig. 109 Examples of mouth gags: (a) Fergusson; (b) Mason; (c) Doyen

Motor unit. One lower motor neurone and the muscle

fibres it innervates. In muscles for fine movement (e.g. of
the eye and hand) motor units are small, i.e. < 10 fibres Mouth gags. Devices used to hold open the patients
per neurone. Muscles involved in posture may have up mouth, e.g. during dental surgery (Fig. 109). The blade
to 1000 fibres per neurone. All fibres of a motor unit are tips are usually covered with plastic or rubber to prevent
of the same type, i.e. fast or slow; the type is thought to dental damage, and are placed at the molars.
be determined by characteristics of the nerve itself. [Eugene L Doyen (18591916), French surgeon;
Sir William Fergusson (18081877), Scottish-born
Mountain sickness, see Altitude, high London surgeon; Francis Mason (18371886), London
surgeon]
Mouth, see Larynx; Pharynx; Teeth; Tongue
Moxifloxacin hydrochloride. Broad-spectrum 4-
Mouth care. Important aspect of care of the uncon- quinolone type antibacterial drug; acts by inhibiting bac-
scious patient. Involves regular inspection of the oral terial DNA replication. More active against Gram-positive
mucosa, tongue, gums and teeth and their thorough organisms than ciprofloxacin, but is ineffective against
cleansing. The teeth, tongue and palate are cleansed with pseudomonas infections. Due to potentially severe side
toothpaste using a toothbrush or sponge-tipped swab. effects, its use is restricted to specific infections (severe
The mouth should be rinsed with water or a mouthwash chest infections, complicated skin and soft tissue infec-
solution. Meticulous mouth care reduces incidence of tions and pelvic inflammatory disease) that have failed
ventilator-associated pneumonia. Regular suction of the to respond to other agents.
mouth is important to improve comfort and reduce the Dosage: 400mg orally or iv od.
risk of aspiration. Immunocompromised patients or Side effects:
those receiving broad-spectrum antibiotics may develop prolonged QT syndromes (contraindicated
oral candidiasis. in patients with other risk factors for QT pro
Tracheal or gastric tubes may exert pressure, leading longation); fulminant hepatitis; renal failure;
to ulceration, unless they are adequately supported and tendon inflammation/rupture; muscle weakness/
moved to different parts of the mouth at regular myoglobinuria; and convulsions.
intervals. may enhance the effects of warfarin.
390 Moxonidine

Moxonidine. The first selective imidazoline receptor Marsh DJ, Gimm O (2011). Adv Otorhinolaryngol; 70:
agonist, introduced as a centrally acting antihypertensive 8490
drug. Acts by stimulating imidazoline type 1 (I1) recep- See also, Apudomas; Hyperparathyroidism
tors in the medulla, thereby reducing central and periph-
eral sympathetic activity. May also stimulate renal I1 Multiple organ dysfunction score. Scoring system for
receptors, causing increased sodium and water excretion. evaluating dysfunction of six organ systems: respiratory,
Has minimal affinity for 2-adrenergic receptors and renal, hepatic, cardiovascular, central nervous and hae-
thus causes fewer side effects than other centrally acting matological. Weighted scores (04 points) are given for
drugs. Peak plasma levels occur within 1h of oral admin- increasing degrees of abnormality of six variables (arte-
istration, with half-life of about 2h. 90% is excreted rial PO2:FIO2 ratio, serum creatinine, serum bilirubin,
unchanged in the urine. platelet count, pressure-adjusted heart rate [heart rate
Dosage: 200g orally od, increased to 300g bd if CVP:mean arterial BP ratio] and Glasgow coma score).
required. Raw data are collected daily; the value recorded is a
Side effects: sedation, dry mouth, headache, dizziness, representative value for the day (i.e. at a particular time
sleep disturbance. and not necessarily the worst value).
Marshall JC, Cook DJ, Christou NV, etal (1995). Crit
MPM, see Mortality probability models Care Med; 23: 163852

MRI, see Magnetic resonance imaging Multiple organ dysfunction syndrome (MODS). Syn-
drome of organ dysfunction affecting two or more
MRSA, Meticillin-resistant Staphylococcus aureus, see organs, remote from the site of primary tissue injury or
Infection control; Staphylococcal infections infection. Previously termed multiple organ failure.
Thought to be caused by dysregulation of the innate
Mucolytic drugs. Used to reduce sputum viscosity (e.g. inflammatory response, causing systemic inflammation,
in COPD, asthma) via cleaving of disulphide bonds hypoperfusion and tissue injury. Causes include: sepsis,
in mucus glycoprotein. Their use is controversial since burns, surgery and massive blood transfusion. Predomi-
no clear benefit has been shown when administered nantly affects the respiratory, renal, hepatic, neurologi-
orally. Include carbocisteine, erdosteine and mecysteine. cal, gastrointestinal, haematological and cardiovascular
Inhaled dornase alfa, a genetically engineered DNA-ase systems. A major cause of death in ICU; mortality
(DNase), is indicated in cystic fibrosis but has been increases as more organs are involved. The degree of
used in other lung conditions. N-acetylcysteine is used organ dysfunction may be described by the multiple
orally and by nebuliser in ICU, but the latter may cause organ dysfunction score.
severe bronchospasm. Other strategies to reduce sputum Johnson D, Mayers I (2001). Can J Anesth; 48: 5029
viscosity include instillation of saline or bicarbonate
solutions. Multiple sclerosis, see Demyelinating diseases

MUGA, see Multigated acquisition imaging Murphy eye, see Tracheal tubes

Multigated acquisition imaging (MUGA imaging). Muscarine. Alkaloid extracted from certain mushrooms;
Technique of nuclear cardiology in which information mimics certain actions of acetylcholine (hence it is a
from each of many cardiac cycles is combined to parasympathomimetic drug) and was used to investigate
assess regional ventricular wall function and ejection the physiology of the autonomic nervous system. It stim-
fraction. The subjects red blood cells are labelled with ulates postganglionic acetylcholine receptors (musca-
technetium-99m in vivo and time allowed for complete rinic receptors) at effector organs of the parasympathetic
mixing of the marker throughout the circulating volume. nervous system, and at sweat glands of the sympathetic
Scanning then takes place over several cycles. Advan- nervous system. It also causes parkinsonian tremor,
tages over single-pass cardiographic techniques include ataxia and rigidity; thus muscarinic receptors are thought
less reliability on the injection technique (crucial in the to exist in the CNS. Other receptors may be involved in
single-pass method) and the ability to scan before and an inhibitory role at adrenergic nerve endings, e.g. in the
after exercise or drug administration. Disadvantages heart and autonomic ganglia.
include the overlap of the heart chambers on the image
and the inability to follow a tracer bolus through the Muscle. Contractile tissue; may be:
chambers of the heart. skeletal (striated; voluntary):
- the most abundant form.
Multiple endocrine adenomatosis (MEA; Multiple - normally contracts only when stimulated.
endocrine neoplasia, MEN). Term encompassing - no connections between individual fibres.
three distinct syndromes of multiple endocrine tumours, - composed of elongated cylindrical fibres, each
all of which are inherited by autosomal dominant surrounded by its sarcolemma (muscle cell mem-
transmission: brane). Each fibre contains myofibrils, containing
type I: parathyroid adenoma, pancreatic adenoma actin and myosin filaments and surrounded by
or carcinoma and anterior pituitary adenoma. sarcoplasmic reticulum and mitochondria. The
type IIa: medullary thyroid carcinoma, phaeochro- T-tubule system invaginates from the sarcolemma
mocytoma and parathyroid adenoma. to connect all myofibrils with the extracellular
type IIb: medullary thyroid carcinoma, phaeochro- space.
mocytoma and mucosal neuromas. - microscopically visible striations are due to
Patients presenting for endocrine surgery may thus have myosin and actin arrangements, labelled for his-
other tumours and associated syndromes. torical reasons (Fig. 110). The sarcomere (portion
 Muscular dystrophies 391

between adjacent Z lines) shortens during muscle further hydrolysis of ATP allows sequestration of
contraction. calcium and muscle relaxation. ATP is derived from
- different types of fibre: glycolysis and from dephosphorylation of phos-
- type I: red muscle; responds slowly with slow phorylcreatine, stored during rest.
metabolism and high oxidative capacity (high A single twitch caused by an action potential of 1 ms
myoglobin, mitochondria and capillary content). lasts up to 200 ms. Contraction may be isometric (force
Suitable for prolonged contraction, e.g. postural increases but muscle length remains constant) or iso-
muscles. tonic (force is constant and muscle shortens). Repeated
- type IIB: white muscle, short contraction with fast stimulation results in summation of contraction,
low oxidative capacity. Suitable for rapid fine since there is inadequate time for relaxation between
movements, e.g. eye and hand muscles. stimuli. Above a certain frequency, tetanic contraction
- type IIA: as for IIB but with high oxidative occurs.
capacity, i.e. red. Uncommon in humans.
cardiac:
Muscle relaxants, see Neuromuscular blocking drugs
- similar to slow striated muscle, but fibres are
branched, and joined end to end by intercalated
discs; also connected to adjacent fibres by gap Muscle spindles. Encapsulated structures present in and
junctions (i.e. forms a functional syncytium). parallel to skeletal muscle. Contain up to 10 specialised
- has spontaneous pacemaker activity, due to slow muscle (intrafusal) fibres, attached to the ordinary
depolarisation between action potentials. muscle (extrafusal) fibres or to their tendons. Muscle
- cannot exhibit tetanic contraction, due to a pro- contraction thus results in shortening of the spindles.
longed refractory period. Sensory nerve fibres from the spindles end on the motor
smooth:
neurones supplying the extrafusal muscle fibres of that
- no striations; actin and myosin filaments arranged muscle. They transmit impulses when stretched; thus
randomly. passive muscle stretching causes reflex contraction, e.g.
- occurs in sheets of interconnecting cells (e.g. vis- knee jerk reflex arc. Discharge in some afferent fibres is
ceral) or multiunits (e.g. iris). proportional to degree of stretch; discharge in others is
- exhibits slow spontaneous activity; also respon- also proportional to speed of stretch. Muscle contraction
sive to stimulation of the autonomic nervous reduces tension within the spindle, reducing the afferent
system. Visceral muscle contracts if stretched. discharge. Activation of the reflex also inhibits contrac-
See also, Motor unit; Muscle spindles; Neuromuscular tion of opposing muscle groups (reciprocal innervation)
junction via an inhibitory spinal interneurone.
Small -motor fibres innervate the ends of the intra-
Muscle contraction. Involves the following steps: fusal fibres, causing them to contract. This stretches the
depolarisation of the postsynaptic membrane at the
central portions, with reflex extrafusal fibre contraction
neuromuscular junction. as before, and increases the sensitivity of the spindles to
area of depolarisation spreads across the muscle
passive stretching. -Motor activity is controlled by
membrane and into the muscle bulk via the T-tubule descending pathways in the spinal cord; thus muscle tone
system. and posture are controlled at both spinal and supraspi-
depolarisation causes release and mobilisation of
nal levels. Increased muscle tone and clonus seen in
intracellular calcium ions from sarcoplasmic upper motor neurone lesions may result from overactive
reticulum. -activity due to interruption of inhibitory descending
calcium ions bind to the troponin component of the
pathways. -Activity is also increased in anxiety, resulting
actin complex, causing displacement of the tropo- in exaggerated tremor.
myosin component from myosin binding sites. Increased passive stretching of a muscle eventually
myosin can now bind to actin, with hydrolysis of
causes sudden relaxation, due to stimulation of Golgi
ATP, structural alteration of myosin and shortening tendon organs within the muscle tendons. This inverse
of muscle fibres. ATPase is present on myosin mol- stretch reflex is exaggerated in upper motor neurone
ecule heads. The process repeats with further muscle lesions (clasp-knife effect).
shortening. Histologically, contraction leads to [Camillo Golgi (18431926), Italian physician]
shortening of the I band and H band (Fig. 110).
Muscular dystrophies. Hereditary disorders of muscle,
involving progressive destruction of mainly skeletal, but
also cardiac, muscle. Result from mutation of the gene
A band I band for dystrophin, a cytoskeletal protein involved in the
interaction between the sarcomeres and the extracellu-
lar matrix (via dystrophin-associated protein, DAP).
Deficiency of dystrophin (and DAP) results in weaken-
ing of the muscle membrane with calcium influx and
necrosis of muscle fibres; in Duchennes dystrophy defi-
ciency is severe whilst in Beckers a reduced amount
of normal dystrophin still results in some activity. Plasma
creatine kinase levels may be markedly increased.
Classified according to inheritance: may be sex-linked
Z line Myosin H band Actin Z line (e.g. Duchennes, Beckers), autosomal dominant (e.g.
facioscapulohumeral, oculopharyngeal) or recessive (e.g.
Fig. 110 Microscopic appearance of myofibril limb girdle):
392 MVV

Duchennes: most common (1 in 3500 live male ocular muscles, causing ptosis and diplopia.
births) and severe. Usually presents at 35 years of bulbar muscles, causing dysarthria and predisposing
age; although death from respiratory failure previ- to aspiration of gastric contents.
ously occurred in late teens, life expectancy has respiratory muscles.
improved with non-invasive positive pressure venti- limb muscles.
lation (NIV). Myasthenic crises (suddenly worsening and spreading
Beckers, facioscapulohumeral, limb girdle: less weakness requiring IPPV) may be provoked by drug
severe, with later onset and death. Cardiac involve- omission, infection, stress, pregnancy or drugs (e.g.
ment is less common. aminoglycosides).
Orthopaedic surgery is common for limb contrac- Classified according to severity:
tures, etc. Severe forms may present significant anaes- grade I: confined to eye muscles (15% of cases).
thetic risk: grade IIa: generalised mild muscle weakness.
weak respiratory muscles and kyphoscoliosis: grade IIb: generalised moderate weakness and/or
impaired ventilation and sputum clearance. Pre- bulbar weakness.
existing and postoperative chest infection is more grade III: acute fulminating: rapid and progressive
likely. Respiratory failure postoperatively is and/or respiratory involvement.
common and elective NIV is advocated. grade IV: myasthenic crisis requiring IPPV.
rhabdomyolysis may follow suxamethonium or Diagnosis:
volatile anaesthetic agents, typically following marked improvement following iv edrophonium
prolonged exposure to the latter. Severe hyperka- 2 + 8mg (Tensilon test).
laemia and myoglobinuria may result. An MH- EMG shows reduced response to single twitch,
like picture may develop as muscle metabolism fade on tetanic stimulation and post-tetanic
increases (in the absence of true inherited MH). potentiation.
Total intravenous anaesthesia is the technique of detection of anti-acetylcholine receptor antibodies.
choice. Treatment:
cardiac involvement is common in Duchennes; emergency intubation and IPPV for impending/
characteristically the ECG shows tachycardia, short actual respiratory failure or bulbar dysfunction.
PR interval, deep Q waves laterally and tall R Blood gas interpretation is rarely useful in myasthe-
waves in V1. Cardiomyopathy may be more common nia for determining the need for IPPV; clinical indi-
in Beckers but both may lead to heart block and cators are best.
arrhythmias (VF has occurred on induction of acetylcholinesterase inhibitors, e.g. pyridostigmine
anaesthesia). Bradycardia is common in facioscapu- 3090mg 6-hourly, neostigmine 1530mg 4-
lohumeral dystrophy. hourly. Muscarinic side effects include miosis,
delayed gastric emptying and impaired swallowing colic, lacrimation, diarrhoea, salivation; atropine
predispose to aspiration of gastric contents. may be given to reduce these. May cause cholinergic
Plans for anaesthesia must take account of the above crisis in overdosage; distinguished from myasthenic
considerations. Regional techniques are popular when crises by injection of edrophonium 2mg. Myas-
feasible. ICU concerns include the above and also the thenic crises improve transiently, cholinergic crises
ethical issues surrounding respiratory support should do not.
respiratory failure occur. immunosuppressive therapy includes corticoste-
Birnkrant DJ, Panchitch HB, Benditt JO etal (2007). roids (e.g. prednisolone 1mg/kg on alternate days;
Chest; 96: 197786 usually started in hospital because of possible
[Guillaume Duchenne (18061875), French neurologist; deterioration), azathioprine, cyclophosphamide,
Peter Becker (19082000), German geneticist] ciclosporin, mycophenolate.
treatment of any coexistent electrolyte abnor
malities, especially hypokalaemia, hypocalcaemia,
MVV, Maximal voluntary ventilation, see Lung function
hypermagnesaemia.
tests
plasmapheresis and iv immunoglobulin, especially
combined with immunosuppressive therapy, are
Myasthenia gravis. Autoimmune disease characterised used for short-term remission in severe cases.
by weakness and increased fatigability of skeletal muscle. thymectomy: benefit most myasthenic patients
Prevalence is 50100 per million. More common in between 16 and 60 years old producing either full
young women and older men. May also occur transiently remission or reduction in immunosuppressive
in neonates born to affected mothers, and may be caused therapy. Anaesthetic management:
by drugs, e.g. penicillamine. - preoperatively: assessment of respiratory function
Caused by an immune response in which IgG is important. Pyridostigmine is usually withheld
autoantibodies are produced against the acetylcholine on the morning of surgery. Preoperative plasma-
receptors of the neuromuscular junction postsynaptic pheresis or iv immunoglobulin has been used.
membrane. The autoantibodies (detectable in 90% of Potassium abnormalities increase muscle weak-
patients) occupy receptors, leading to their destruction ness and should be corrected.
and reduction in receptor density. The thymus gland is - perioperatively: there is increased sensitivity to
abnormal (either hyperplasia or thymoma) in 75% of non-depolarising neuromuscular blocking drugs
cases and is thought to be the site of production of the and relative resistance to suxamethonium with
autoantibodies. Often associated with other autoim- increased tendency to develop dual block. Tra-
mune conditions, e.g. thyroid disease. cheal intubation and IPPV are usually performed
Characterised by muscle weakness (typically worse without neuromuscular blocking drugs, using e.g.
on exertion and improving with rest); may affect: propofol and/or a volatile agent. Atracurium in
 Myocardial contractility 393

reduced doses (5060% of usual) has been sug- (one type of atypical pneumonia), caused by M.
gested over other drugs. Surgery is performed pneumoniae:
via a suprasternal or trans-sternal route. Haemor- typically associated with initial headache, sore
rhage and pneumothorax may occur. The tracheal throat, fever, malaise and cough; the cough becomes
tube may be left in situ and ventilation monitored productive and patchy chest signs may develop,
on ICU or HDU, although tracheal extubation is although classic signs of consolidation are rare.
usually possible immediately postoperatively. Usually affects a single lower lobe only, although
- postoperatively: pyridostigmine may be restarted, the clinical course is variable. CXR signs (patchy
usually in reduced dosage. Close respiratory mon- shadowing) often precede clinical features and
itoring and physiotherapy are required. Postop- persist after clinical recovery.
erative atelectasis and infection are common. extrapulmonary features include haemolytic
Anaesthetic management of patients with myasthenia anaemia, GIT upset, including hepatic and pancre-
gravis for other surgery should follow the above atic involvement, rash, arthritis, CNS (meningitis,
guidelines. Where feasible, regional techniques may encephalitis, ascending paralysis, transverse myeli-
be safer. tis, cranial nerve palsy) and cardiac (myocarditis,
Blichfeldt-Lauridsen L, Hansen BD (2012). Acta Anaes- pericarditis) involvement.
thesiol Scand; 56: 1722 diagnosed by demonstration of a rising antibody
See also, Myasthenic syndrome titre, since culture of organisms is slow and difficult.
Cold agglutinins may also be identified in blood.
Myasthenic syndrome (EatonLambert syndrome). treatment with clarithromycin, erythromycin or tet-
Acquired disorder of the neuromuscular junction racycline. Death is rare.
in which there is decreased quantal release of acetylcho- Other infections include GIT and genitourinary ones,
line from the presynaptic nerve terminal. Caused by such as non-specific urethritis, pelvic inflammatory
IgG autoantibodies interfering with the voltage-gated disease, vaginitis and pyelonephritis. Most are caused by
calcium channels necessary for acetylcholine mobilisa- M. hominis or U. urealyticum.
tion and release. Usually associated with small cell bron-
chial carcinoma or, rarely, autoimmune disease (e.g. Myelin. Lipoprotein derived from multiple layers of cell
polyarteritis nodosa). membranes, encasing the axons of myelinated neurones.
Distinguished from myasthenia gravis thus: Arises from Schwann cells in the peripheral nervous
classically improves on exercise (EMG shows an system (one cell to one axon portion), and from oligo-
increase in power on tetanic stimulation). dendrocytes in the CNS (one cell to up to 40 axon por-
usually affects proximal limb muscles. tions). Deficient at 1mm intervals (nodes of Ranvier).
autonomic nervous system involvement is common. Unmyelinated peripheral nerves are merely encased in
tendon reflexes are depressed or absent. Schwann cell cytoplasm. Acts as an insulating sheath,
power is only slightly improved by neostig- increasing speed of nerve conduction in myelinated
mine, despite possible improvement following nerves by restricting membrane depolarisation to the
edrophonium. nodes of Ranvier; depolarisation jumps from node to
caused by defective release of acetylcholine from node (saltatory conduction) instead of slower, smooth
presynaptic nerve endings, with normal postsynap- progression along unmyelinated nerves. Conditions
tic receptors. affecting the myelin sheath include the demyelinating
May improve with oral guanidine hydrochloride 30 diseases and Guillain-Barr syndrome.
50mg/kg tds or aminopyridine; corticosteroids, iv immu- [Theodor Schwann (18101882), German physiologist;
noglobulins and plasmapheresis have been used. Louis Ranvier (18351922), French physician and
General anaesthetic considerations are as for myas- pathologist]
thenia gravis. There is increased sensitivity to non-
depolarising and depolarising neuromuscular blocking Myocardial contractility. Ability of the myocardial
drugs. Atracurium has been suggested as the drug of muscle to contract at a particular length of fibre (i.e.
choice. Postoperative respiratory complications are independent of loading factors), thus a major determi-
more likely with severe weakness. nant of stroke volume, cardiac output and myocardial
[LM Eaton (19051958), US neurologist; Edward H O2 demand.
Lambert (19152003), US neurophysiologist] Increased by:
Titulaer MJ, Lang B, Verschuuren JJGM (2011). Lancet intrinsic mechanisms:
Neurol; 10: 1098107 - Anrep effect.
- Bowditch effect.
Mycophenolate mofetil. Cytotoxic immunosuppressive extrinsic factors:
drug used in organ transplantation, especially in combi- - sympathetic nervous system activity.
nation with ciclosporin and corticosteroids. Has also - catecholamines via 1-adrenergic receptors.
been used in myasthenia gravis. Metabolised to myco- - inotropic drugs.
phenolic acid. Decreased by:
Dosage: 15mg/kg orally or iv od. parasympathetic nervous system (slight effect).
Side effects: hypersensitivity reactions, myelosuppres- hypoxaemia and hypercapnia (via direct effects;
sion, liver toxicity. also cause increased sympathetic activity).
acidosis and alkalosis.
Mycoplasma infections. Caused by various species of cardiac disease, e.g. ischaemic heart disease, cardio-
mycoplasma, small bacteria that lack a cell wall (thus myopathy, myocarditis.
resistant to antibiotics that target cell wall synthesis). electrolyte disturbances, e.g. hyperkalaemia,
The most important infection is mycoplasma pneumonia hypocalcaemia.
394 Myocardial infarction

drugs, e.g. most iv and inhalational anaesthetic PE.

agents, antiarrhythmic drugs. Dresslers syndrome: pericarditis, pleurisy and
Assessment is difficult; indirect methods include mea- pneumonitis, typically 46 weeks later.
surement of: Perioperative MI has been investigated by several
stroke volume and stroke work. studies. Summary of findings:
speed of contraction. postoperative MI is most common within the first
cardiac output. 12 days, according to troponin levels.
ratio of left ventricular end-diastolic pressure to left with previous MI, overall reinfarction rate is 67%
ventricular end-diastolic volume. (if no previous MI, infarction rate is 0.10.2%).
peak left ventricular pressure. quoted reinfarction rates are related to the time
ejection fraction. since the MI:
See also, Starlings law - within 3 months of surgery: 2030%.
- within 46 months: 1020%.
Myocardial infarction (MI). Myocardial necrosis caused - greater than 6 months: 45%.
by unrelieved myocardial ischaemia, forming part of the aggressive management (e.g. pulmonary artery
spectrum of acute coronary syndromes (see Acute coro- catheterisation, use of inotropic and vasodilator
nary syndromes for pathophysiology, classification, clini- drugs, admission to ICU) has been reported to
cal features, investigations, differential diagnosis and lower the overall infarction rate to 2%, and the
management of MI). Usually starts at the endocardium, reinfarction rates as follows:
spreading outwards. Commonly affects the left ventricle, - MI within 3 months: under 6%.
but may involve the right ventricle or atria. Classified - within 46 months: 23%.
according to ECG criteria into ST segment elevation - greater than 6 months: 12%.
MI (STEMI) and non-ST segment elevation MI However, the statistical analysis used has been criti-
(NSTEMI). cised, and the value of routine intensive monitoring
ECG changes in STEMI: and treatment remains controversial, especially
sequentially occurring T wave changes, ST segment when the increased cost is considered.
elevation and pathological Q waves in leads overly- perioperative reinfarction carries increased mortal-
ing the infarct are typical. Lead groupings and their ity (up to 70%).
corresponding cardiac territories: incidence of silent MI may be higher.
- II, III and aVF: inferior (diaphragmatic) surface. risk factors include: unstable angina, periopera-
- V13: interventricular septum. tive hypotension, prolonged surgery and upper
- V34: anterior surface of the left ventricle. abdominal/thoracic or vascular surgery.
- V56, I and aVL: lateral surface of the left risk is not increased by previous cardiac surgery.
ventricle. risk is not associated with the type of anaesthetic or
- V12: posterior surface. drugs used.
tall, widened (hyperacute) T waves often precede cardiac risk index has been developed for assess-
ST elevation. ST elevation usually resolves in ment of risk of death or severe perioperative car-
< 2 weeks and T wave inversion after several diovascular complications. Presence of cardiac
months, with Q waves often lasting for several years failure is the most important risk factor. Other
(Fig. 111). factors are related to arrhythmias, age and general
persistent ST elevation may indicate ventricular condition of the patient.
aneurysm or an area of dyskinetic myocardium. Q reinfarction is often associated with perioperative
waves may be absent in subendocardial infarction. myocardial ischaemia detected by ST depression.
other changes include abnormalities of the P wave It is not always associated with hypertension or
and PR interval in atrial infarction, conduction hypotension.
defects, e.g. bundle branch block and heart block Risk of perioperative MI is thus reduced by:
and arrhythmias. postponement of elective surgery until > 6 months
Delayed complications include: after MI.
ventricular rupture, usually 58 days later. treatment of preoperative risk factors where
ventricular aneurysm. possible.
interventricular septum rupture, usually 46 days avoidance of myocardial ischaemia as for ischaemic
later. heart disease.
papillary muscle damage and mitral regurgitation. Landesberg G, Beattie WS, Mosseri M, Jaffe AS, Alpert
mural thrombus formation and systemic JS (2009). Circulation; 114: 293444
embolism. [William Dressler (18901969), US cardiologist]

Myocardial ischaemia. Inadequate blood supply to

(a) (b) (c) (d) the myocardium. Effects are related to myocardial O2
supply/demand balance; largely dependent on:
supply:
- coronary blood flow:
- aortic end-diastolic pressure minus left ventric-
ular end-diastolic pressure.
- duration of diastole.
Fig. 111Typical changes in ECG following MI: (a) normal; - coronary vessels: calibre is usually maintained
(b) immediate: (c) few weeks; (d) few months by autoregulation. Stenosis may be caused by
 Myoglobin 395

atheroma, thrombosis and spasm. The subendo- glucose, pyruvate and lactate. Utilisation of the latter
cardial region is most at risk of ischaemia. compounds increases in ischaemia.
- blood viscosity. O2 requirements are reduced by volatile anaesthetic
- O2 content. agents and other negative inotropes, e.g. -adrenergic
demand: receptor antagonists. Etomidate and propofol may
- myocardial contractility and wall tension. decrease demand; other iv agents may increase it if
- heart rate. tachycardia occurs.
Effects:
reversible increases in hydrogen ion, potassium, Myocardial preconditioning, see Ischaemic
phosphate, lactate and adenosine concentrations. preconditioning
Unless ischaemia is corrected within about 30min,
MI ensues, with release of cardiac enzymes and Myocarditis. Inflammation of the cardiac muscle; the
myoglobin. definition is difficult because clinical diagnosis (acute
ECG changes: thought to be caused by ion leakage cardiac failure, arrhythmias or ECG changes in a person
across the ischaemic myocardial membrane, alter- with a previously normal heart) is often not supported
ing membrane potentials and causing current flow by the results of biopsy or post-mortem histology (i.e.
between normal and ischaemic areas. ST segment with lymphocytic infiltration).
changes are most common; depression is due to Caused by:
subendocardial ischaemia, elevation due to trans- infective invasion of cardiac muscle, e.g. viruses
mural ischaemia. Arrhythmias may occur. (especially coxsackie B and echovirus), bacteria,
impaired myocardial contractility: first depressed, rickettsia, fungi, trypanosomiasis. Myocarditis is
then absent, then myocardial lengthening with thought to be a common feature of apparently mild
worsening ischaemia. viral upper respiratory tract infections. Features
pain (angina): possibly due to increased potassium may be prompted by vigorous exercise or anaesthe-
or substance P. Pain is typically constant, crushing sia and especially if the diagnosis is unsuspected.
and mid-sternal, radiating across the chest, to the post-infective inflammation: thought to represent a
neck or arms. Related to exertion, cold or emotion different mechanism to the above and includes
and relieved by rest, it may be absent (silent post-viral, HIV infection, rheumatic fever, diph
ischaemia). Dyspnoea and sweating may occur. Cre- theria. In the last, bacterial toxins are thought to be
scendo angina is characterised by increasing fre- responsible.
quency of attacks with diminishing levels of exertion; primary autoimmune processes: rheumatic fever,
unstable angina occurs at rest (diagnosed when MI connective tissue diseases, sarcoidosis, thyroid dis-
has been excluded). Repeated small thromboses orders, diabetes mellitus (microangiopathy may
may be responsible; both types may herald immi- also be involved), amyloidosis.
nent MI. other allergic processes, e.g. drug-induced (e.g. peni-
Detection: cillin, sulphonamides), rejection of cardiac trans-
symptoms and signs as above. plants, serum sickness.
detection of reduced supply/increased demand. direct drug toxicity, e.g. lithium, cyclophosphamide,
Indices of supply include diastolic pressure time alcoholism.
index. Indices of demand include ratepressure physical trauma, e.g. radiation.
product and tension time index. Endocardial viabil- other infiltration or inflammation, e.g. diabetic,
ity ratio has been used to indicate the ratio between myxoedema, haemochromatosis, connective tissue
supply and demand. disease, drug-induced (e.g. cytotoxic drugs).
ECG. Preoperative silent ischaemia (i.e. without Treatment includes corticosteroids, antiviral drugs and
symptoms) has been found in up to 15% of patients supportive therapy.
over 40 years old; the significance of this in terms of Medical and anaesthetic management is as for cardiac
outcome is unknown. The figure is higher for disease in general; in acute disease surgery should be
patients presenting for vascular surgery. Similar epi- deferred if feasible, and as cardiostable an anaesthetic
sodes of silent ischaemia have been found postop- provided as possible. General treatment is supportive
eratively, especially in those with risk factors. It has according to the presenting features.
been suggested that patients who exhibit this are Sagar S, Liu PP, Cooper LT (2012). Lancet; 379: 73847
more likely to suffer postoperative MI.
pulmonary capillary wedge pressure monitoring. Myofascial pain syndromes. Dysfunction and usually
echocardiography. pain in one or more muscles/muscle groups, associated
nuclear cardiography. with trigger point activity. May follow acute strain or
coronary sinus catheterisation. repeated use. Typically associated with patterns of
Management: as for ischaemic heart disease. referred pain, e.g. trigger points in the neck with facial
See also, Monitoring; Myocardial metabolism pain, trigger points in the shoulder with arm pain. Identi-
fied trigger points may be injected with local anaesthetic,
Myocardial metabolism. Myocardial O2 consumption is treated with acupuncture, ultrasound and pressure, or
normally about 30ml/min (10ml/100g/min). Coronary the muscles passively stretched using a cold spray to
blood flow is directly proportional; the mechanism is allow adequate relaxation.
unclear but may involve adenosine, CO2, potassium ions,
prostaglandins, hydrogen ions and lactate. O2 extraction Myoglobin. Iron-containing molecule with mw 17000.
from blood is about 70%; thus increased demands are Similar to haemoglobin, but binds only one molecule of
met mainly by increasing blood flow. The main energy O2 per molecule. Its O2 dissociation curve is to the left
substrate is free fatty acids; other substrates include of that of haemoglobin, being a rectangular hyperbola
396 Myoglobinuria

Table 29 Segmental innervation of limb muscles

Movement Muscle(s) Level

100
Arterial blood Shoulder
Abduction Supraspinatus C45
75 Venous blood External rotation Infraspinatus C45
% Saturation

Adduction Pectoralis C68

Elbow
50 P50 P50
Flexion/supination Biceps C56
Pronation Pronators C67
Extension Triceps C78
Wrist
Extension/radial flexion C67
Ulnar flexion C78
0 Fingers
0 2 4 6 8 10 12 14 (kPa) Extension Long extensors C7
Flexion Long flexors C8
25 50 75 100 (mmHg) Spreading and closing All short muscles of the hand T1
Po2 Hip
Flexion Iliopsoas L13
Fig. 112 Oxymyoglobin dissociation curve (dotted line) with Extension Gluteal L5S2
oxyhaemoglobin dissociation curve (solid line) for comparison Knee
Extension Quadriceps L34
Flexion Hamstrings L5S2
Ankle
with a steep rise to a plateau (Fig. 112). The Bohr effect Extension Anterior tibial L45
does not occur. 95% saturated at PO2 of 5.3 kPa Flexion Calf muscles S12
(40mmHg), falling below 65% saturation only at PO2
below 1 kPa (7.5mmHg). The P50 is 0.13kPa (1mmHg).
Found in skeletal and heart muscle, where it binds O2
from arterial haemoglobin, releasing it at O2 tensions Myosin. Muscle protein (mw 520kDa), consisting of two
close to zero. Thus it acts as an O2 transporter and res- heavy and four light chains. Globular portions of the
ervoir for contracting muscle. molecules contain ATPase and actin binding sites, and
See also, Oxyhaemoglobin dissociation curve project sideways from myosin filaments.
See also, Muscle contraction

Myoglobinuria. Presence of myoglobin in the urine, Myotomes. Inner parts of embryonic somites, differen-
colouring it red. Results from skeletal muscle break- tiating into skeletal muscle and related to their corre-
down (rhabdomyolysis) due to: sponding dermatomes. Although the origins of certain
crush injury (crush syndrome). skeletal muscle groups are controversial, they tend to
prolonged immobility/hypothermia from any cause, retain their original somatic nerve supply; thus particular
especially poisoning and overdoses (particularly spinal nerves may be assessed clinically by testing
opioid, alcohol and cocaine overdose). specific muscles or groups (Table 29). Used to assess
extreme exertion. neurological lesions and the extent of spinal/epidural
polymyositis, myopathies, e.g. alcoholic, deficiency anaesthesia.
states, congenital conditions or associated with viral
infections. Myotonia congenita. Autosomal dominant disorder of
toxins, e.g. of sea snakes, multiple wasp stings. skeletal muscle. No systemic symptoms occur other than
MH. myotonia (involuntary sustained muscle contraction fol-
neuroleptic malignant syndrome. lowing stimulation), exacerbated by cold and rest, and
carbon monoxide poisoning. relieved by exercise. A more common, milder form is
heatstroke. inherited as autosomal recessive. Anaesthetic manage-
paroxysmal myoglobinuria: rare disorder of muscle ment is as for dystrophia myotonica. Hypothermia
pain, weakness, paralysis and myoglobinuria. Most should be avoided. An association with MH has been
common in young men/children. Affected muscles suggested, although there are difficulties in interpreting
are classically painful and oedematous. Creatine the caffeinehalothane contracture test in myotonic
kinase levels may be markedly raised. patients.
Myoglobin is readily filtered by the kidneys because of
its small size. May be associated with renal failure, Myotonic syndromes. Group of inherited muscle dis-
thought to be caused by ferrihemate, a nephrotoxic eases including dystrophia myotonica and myotonia con-
breakdown product of myoglobin in acid conditions genita characterised by an increase in muscle tone
(myoglobin itself is not thought to be directly nephro- (myotonia) following muscular contraction. Myotonia
toxic). Tubular obstruction may also be involved. Main- may also be present in hyperkalaemic periodic paralysis.
tenance of good hydration and urine output is thought Anaesthetic considerations are related to systemic mani-
to prevent renal impairment. Administration of bicar- festations of the disease and the effects of certain anaes-
bonate helps to increase urinary pH and reduce forma- thetic drugs worsening myotonia, e.g. suxamethonium.
tion of ferrihemate.
David WS (2000). Neurol Clin; 18: 21543 Myxoedema, see Hypothyroidism
 N
Nabilone. Cannabinoid antiemetic drug, acting on CB1 Dosage:
and CB2 cannabis receptors, used in chemotherapy- opioid poisoning: 0.42.0mg iv/im/sc, repeated after
induced nausea and vomiting. Has also been used in 23min to a total of 10mg. Administration by infu-
palliative care. sion (310g/kg/h) may be required.
Dosage: 12mg orally bd/tds. postoperatively: 1.53g/kg iv, followed by 1.5g/
Side effects: drowsiness, ataxia, visual disturbances, kg repeated every 2min as required. Infusion or im
sleep disturbances, hypotension, tachycardia. injection may be used to prevent later resedation.
neonatal resuscitation: 10g/kg im, iv or sc repeated
Nalbuphine hydrochloride. Opioid analgesic drug and every 23min or 60g/kg im as a single injection.
opioid receptor antagonist, synthesised in 1968. Partial Side effects: hypertension, arrhythmias, pulmonary
agonist at kappa and sigma opioid receptors, and partial oedema and cardiac arrest have followed rapid iv
antagonist at mu receptors. Used for premedication, injection, possibly due to sudden catecholamine
anaesthesia and treatment of pain. Active within 23min release secondary to reversal of sedation and
of iv, or 15min of im injection. Half-life is about 5h. analgesia.
Undergoes hepatic metabolism and excreted renally. Acute withdrawal may be precipitated in patients
Side effects such as vomiting are thought to be less than dependent on opioids.
with morphine, although maximal analgesia attainable is
also less. Psychomimetic effects are less problematic NALS, Neonatal Advanced Life Support, see Neonatal
than with pentazocine. Withdrawn from the UK market Resuscitation Program
in 2003.
Dosage: 0.10.3mg/kg iv/im/sc. Up to 1.0mg/kg iv
Naltrexone hydrochloride. Opioid receptor antagonist,
has been used during anaesthesia. synthesised in 1965. Derived from naloxone, with
similar actions but longer duration (24h after a single
Nalmefene hydrochloride. Opioid receptor antagonist, dose). Used in the treatment of opioid and alcohol
introduced in the USA in 1995. Longer half-life (10.8h) dependence.
than naloxone, thus less likely for opioid effects to recur Dosage: 2550mg/day orally. Has also been given via
following reversal. subcutaneous implants.
Nalorphine hydrochloride/hydrobromide. Opioid
analgesic drug and opioid receptor antagonist, synthe- Naproxen. NSAID derived from propionic acid. Has a
sised in 1941. Partial agonist at kappa and sigma opioid favourable side-effect profile among NSAIDs (although
receptors, and antagonist at mu receptors. Psychomi- not as potent as ibuprofen), and can be given just twice
metic effects are common at analgesic doses (510mg). daily.
Dosage: 250500mg orally bd or 500mg pr od/bd.
No longer available.
Side effects: as for NSAIDs.

Naloxone hydrochloride. Opioid receptor antagonist,

synthesised in 1961. N-Allyl derivative of oxymorphone. Narcotic drugs. Strictly, drugs which induce sleep,
Although it has a high affinity for the mu receptor, it but the term usually refers to morphine-like drugs. Pre-
has no intrinsic activity. Used to reverse unwanted ferred terms include opiates, opioids and opioid analge-
effects of opioid analgesic drugs, e.g. sedation, respira- sic drugs.
tory depression, spasm of the biliary sphincter. Also
reverses opioid-mediated analgesia. Reverses the effects Nasal inhalers. Used instead of facemasks for dental
of pentazocine but not buprenorphine. Used to reverse anaesthesia. Designed to fit over the nose, leaving the
ventilatory depression and pruritus following spinal mouth free. During induction of anaesthesia, the patient
opioids, without reversing analgesia. Also used in poi- is instructed to breathe through the nose. During anaes-
soning and overdoses due to other depressant drugs, e.g. thesia, a mouth pack prevents mouth breathing. Now
alcohols, benzodiazepines, barbiturates, although its rarely used.
efficacy is disputed. Reportedly useful in septic shock, Different types:
increasing BP and cardiac output; the mechanism is Goldmans: black rubber, with an inflatable rim as
unclear but may involve increase of endogenous cate- for facemasks. Incorporates an adjustable pressure-
cholamine release or antagonism of increased levels of limiting valve, and attaches to the breathing system
endorphins that occur in sepsis. Effective within 12min over the patients forehead. It should be held from
of iv injection, with a half-life of 12h; thus depressant behind the patients head using both thumbs whilst
effects of opioid analgesic drugs may recur after a few the other fingers support the jaw. May also be held
hours. Metabolised in the liver and excreted mainly with a head harness using two studs incorporated
renally. into the sides.

397
398 Nasal positive pressure ventilation

McKessons: made of malleable black rubber, thus General findings and recommendations:
adjustable. Connected to the breathing system via most deaths occur in elderly and/or the sickest
two tubes which pass around the sides of the head patients.
to meet behind, helping to hold the inhaler in place. overall care is good but there are identifiable
Incorporates an expiratory valve. deficiencies:
newer types are made of plastic, and may incorpo- - inadequate consultation between trainees and
rate unidirectional gas flow, e.g. through inspiratory their seniors and between anaesthetists and
and expiratory tubes passing around the head. Scav- surgeons.
enging of exhaled gases is thus aided. - inadequate supervision and training of locum and
[Victor Goldman (19031993), London anaesthetist] trainee (and in later reports, of non-consultant
career grade) anaesthetists and surgeons. Also,
Nasal positive pressure ventilation, see Non-invasive inappropriate vetting of locum staff.
positive pressure ventilation - inappropriate decisions to operate in futile cases.
- operating outside the surgeons subspecialty.
Nasogastric intubation. Performed for enteral nutri- - inadequate prophylaxis against DVT.
tion, or gastric drainage. Fine-bore tubes are used for the - insufficient appreciation of the importance of pre-
former, usually inserted using a wire stylet, which is operative resuscitation, especially in the elderly
removed after placement. Larger tubes (e.g. 1016 Ch) and non-elective surgery.
are used for gastric drainage, e.g. following abdominal - inappropriate operating at night.
surgery or in intestinal obstruction. They may be placed - insufficient emergency operating theatre, ICU
in the awake patient (who aids placement by swallowing and HDU facilities.
or sipping water) or unconscious patient (e.g. after - lack of involvement of senior staff in emergency
induction of anaesthesia, either before or after tracheal lists and paediatric cases.
intubation). Placement can often be performed blindly, - non-availability of fibreoptic intubating
and may be aided by passage through a plain nasal tra- equipment.
cheal tube placed into the pharynx or by prior transient - sending inappropriate staff with critically ill
inflation of the upper oesophagus via a tightly fitting patients during transfer.
facemask. Placement may require direct vision using a - poor quality and unavailability of medical records.
laryngoscope and forceps (the oesophagus lies posterior the need for post-mortem examination, audit and
to the larynx and to the left of the midline). Correct morbidity/mortality assessments has been repeat-
placement is confirmed by aspiration of gastric contents edly stressed.
(should be tested for acidity), auscultation over the left
hypochondrium during injection of air, abdominal X-ray National Halothane Study, see Hepatitis
or palpation by the surgeon during surgery. If already
in place, withdrawal of the tube before induction of National Institute of Academic Anaesthesia (NIAA).
anaesthesia has been suggested, to avoid increasing Established in 2008 by the Royal College of Anaesthe-
gastro-oesophageal reflux or rendering cricoid pressure tists, Association of Anaesthetists of Great Britain and
inefficient. However, this is rarely done. Ireland, British Journal of Anaesthesia and Anaesthe-
sia, to further the academic profile of the specialty of
National Confidential Enquiry into Patient Outcome anaesthesia and promote high-quality research. Coordi-
and Death (NCEPOD). Ongoing study originally nates the assessment and awarding of anaesthetic
commissioned by the Association of Anaesthetists research grants within the UK, and houses the Health
of Great Britain and Ireland, together with the Associa- Services Research Centre (HSRC) which coordinates
tion of Surgeons of Great Britain and Ireland, and national, outcome-based projects.
published in 1987 as the Confidential Enquiry into Peri- Mahajan RP, Reilly CS (2012). Br J Anaesth; 108: 13
operative Deaths (CEPOD). The first UK study to
involve both anaesthetists and surgeons, it analysed all National Institute for Health and Clinical Excellence
4000 NHS deaths occurring within 30 days of surgery (NICE). NHS Special Health Authority for England
(excluding obstetric and cardiac surgery) in three regions and Wales, established in 1999 (as the National Institute
during 1986. The first national Report (NCEPOD; 1989) for Clinical Excellence) to provide authoritative,
focused on children under 10 years; subsequent Reports evidence-based and reliable guidance on current best
have focused on particular aspects, e.g. deaths following practice. Its guidance is derived from independent
specific surgical or interventional procedures or in spe- assessments of clinical evidence combined with cost-
cific age groups, out-of-hours operating, acute kidney effectiveness analyses, and covers both individual health
injury. technologies (including medicines, medical devices, diag-
The scheme now includes independent hospitals and nostic techniques and procedures) and the clinical man-
also involves the Royal Colleges of Anaesthetists, Obste- agement of specific conditions. In 2005, NICE took on
tricians and Gynaecologists, Ophthalmologists, Patholo- the functions of the Health Development Agency to
gists, Physicians, Radiologists and Surgeons, and the become the National Institute for Health and Clinical
Faculties of Dental Surgery and Public Health Medicine Excellence (though still known as NICE). Is thus respon-
of the Royal Colleges of Surgeons and Physicians respec- sible for providing national guidance on the promotion
tively. The name changed in 2002 to the National Confi- of good health and the prevention and treatment of
dential Enquiry into Patient Outcome and Death, ill health.
reflecting extension of NCEPODs remit to include phy-
sicians and primary care and to review near misses as National Patient Safety Agency (NPSA). NHS Special
well as deaths. Although an independent body, NCEPOD Health Authority, formed in 2001 to coordinate reports
is funded mainly by the Department of Health. of adverse events or near misses and their analysis.
 Neck, cross-sectional anatomy 399

Operated three main services until its abolishment Szpilman D, Bierens JJLM, Handley AJ, Orlowski JP
in 2012: (2012). N Engl J Med; 366: 210210.
National Reporting and Learning Service (NRLS;
collecting and analysing patient safety incidents in Near infrared oximetry/spectroscopy (NIRS). Moni-
the NHS) and commissioning of the national confi- toring technique based on the principle that light in the
dential enquiries (into maternal and child health, near infrared spectrum (650900nm wavelength) trans-
patient outcome and death, and suicide and homi- mits through biological tissues. Increasingly used to
cide). These roles transferred to the NHS Commis- image biological events in the cerebral cortex. Photons
sioning Board. produced by a laser photodiode are directed into the
National Clinical Assessment Service (NCAS), pro-
skull; whilst many are reflected and dispersed, a propor-
viding advice and support to the NHS regarding tion is transmitted. Coloured compounds within the
concerns about individual doctors, dentists and tissues (chromophores), especially oxyhaemoglobin,
pharmacists performance. This role transferred to deoxyhaemoglobin and oxidised cytochrome oxidase,
NICE. have characteristic absorption spectra. The emergent
National Research Ethics Service (NRES), oversee-
light intensity is detected and a computer converts the
ing ethical review of research across the UK. NRES changes in light intensity into changes in chromophore
moved to the new Health Research Authority. concentration. Clinical applications include monitoring
See also, Confidential Enquiry into Maternal Deaths; of cerebral oxygenation and cerebral blood flow and
National Confidential Enquiry into Patient Outcome volume, e.g. in neurosurgery, cardiac surgery and head
and Death injury.
Murkin JM, Arango M (2009). Br J Anaesth; 103 (suppl
Natriuretic hormone, see Atrial natriuretic peptide 1); i313
See also, Functional imaging
Nausea, see Postoperative nausea and vomiting;
Vomiting
Nebulisers. Devices used to provide a suspension of
NCEPOD, see National Confidential Enquiry into droplets in a gas, for administration of inhaled drugs or
Patient Outcome and Death humidification. Droplets of 5 m are deposited in the
trachea and bronchi; those of 1 m pass to alveoli and
Near-drowning. Defined as initial survival following may impair gas exchange. Thus the ideal droplet size is
immersion in liquid, usually water; death at the time of between 1 and 5 m.
Nebulisers may be:
immersion may be due to anoxia (drowning) or cardiac
gas-driven: water is entrained by the gas flow
arrest caused by sudden extreme lowering of tempera-
ture (immersion syndrome). Secondary drowning refers (Venturi principle) and broken into a spray; this
to death following near-drowning after a period of rela- may be directed against an anvil which breaks up
tive wellbeing and is usually due to ARDS/acute lung the drops into smaller droplets. May be combined
injury. with a heater.
ultrasonic: droplets are formed from water lying on
Autopsy following drowning reveals little or no lung
water in 15% of cases (dry drowning); laryngospasm a vibrating plate, or from water dropped on to the
following initial laryngeal contamination has been sug- plate. Water overload may occur, since the droplets
gested. In 85% of cases, pulmonary aspiration of water are very small and the water content of the gas is
occurs (wet drowning); this may involve: high.
mechanical: water is dispersed into a mist by a spin-
fresh water: systemic absorption may cause
haemolysis, haemodilution and electrolyte ning disc.
disturbances. Gas-driven devices are used for drug delivery; all
salt water: draws water into the lungs.
types may be used for humidification.
Both types cause pulmonary oedema and hypoxaemia.
Haemodynamic changes due to fluid shifts are rare; thus Neck, cross-sectional anatomy. At the level of C6,
in practice the type of water may have little clinical major anatomical structures within the layer of skin, fat
significance. and subcutaneous tissue may be described in terms of
Other adverse factors include hypothermia, aspira- fascial layers (Fig. 113):
tion of gastric contents and predisposing conditions, e.g. superficial fascia: encloses platysma muscle and
alcoholism or drug abuse, trauma, epilepsy, MI, CVA. deep fascial layers.
Complications include ARDS, cerebral oedema, deep fascia: composed of three layers:
acute kidney injury, pneumonia, pancreatitis, acidosis - investing fascia: lies posterior to the anterior and
and shock. Sepsis is especially likely if the water is external jugular veins. Splits to enclose sternohy-
contaminated. oid, sternothyroid, omohyoid, sternomastoid and
Management: trapezius muscles.
CPR. - prevertebral fascia: extends laterally on scalenus
treatment of complications as appropriate. anterior and medius to form the floor of the pos-
rewarming. terior triangle of the neck, and passes downwards
antibiotics as appropriate. Use of corticosteroids is to form the axillary sheath. Separated from the
controversial and declining. oesophageal/pharyngeal junction in the midline
nasogastric aspiration to remove gastric water. by the retropharyngeal space.
Recovery has been reported after up to 60min immer- pretracheal fascia: contains the trachea, oesophagus
sion followed by prolonged CPR, especially in children and thyroid gland.
and if hypothermic. Hypoxic brain injury may occur. See also, Carotid arteries; Tracheobronchial tree
400 Necrotising enterocolitis

Cricoid cartilage

Anterior jugular vein

Sternomastoid muscle

Thyroid gland
Pretracheal fascia
Recurrent laryngeal
nerve
Carotid sheath Sympathetic chain
(contains internal External jugular vein
jugular vein, carotid
artery and vagus C6
nerve) Superficial fascia

Investing fascia
Prevertebral fascia

Brachial plexus Vertebral artery Oesophagus Scalene muscles

Fig. 113 Cross-section of neck at C6

Necrotising enterocolitis (NEC). Necrosis of GIT Management:

mucosa (especially terminal ileum, caecum and ascend- prompt diagnosis; made on clinical grounds,
ing colon) seen in neonates, usually within the first week although MRI and biopsy may help distinguish it
of life. Prevalence is up to 8% in premature and low- from acute cellulitis.
birth-weight babies; predisposing factors include early surgical debridement (the diagnosis is usually
asphyxia, hypotension and umbilical catheterisation. confirmed at surgery), with fasciotomy to prevent
Mucosal damage follows hypoperfusion and ischaemia, compartment syndrome.
leading to abdominal distension, vomiting and faecal antibacterial drug therapy and general supportive
blood and mucus, although the onset may be insidious. care; hyperbaric oxygen has been used.
Pallor, bradycardia, jaundice, intestinal perforation and [Jean A Fournier (18321914), Paris dermatologist]
DIC may occur. Plain abdominal X-ray shows dilated Ustin JS, Malangoni MA (2011). Crit Care Med; 39:
loops of bowel and intramural gas bubbles. 215662
Management is largely supportive, with iv fluids,
IPPV, correction of anaemia, antibacterial drugs (includ- Needles. Christopher Wren described injection via a
ing anaerobic cover), probiotic agents and TPN. Surgery quill and bladder in 1659. Metal tubes and stylets were
may be required if perforation occurs or there is no subsequently used, but the hypodermic cannula and
improvement despite medical therapy. Quoted mortality trocar were first described by Rynd in 1845. Different
ranges from 10% to 50%. Survivors commonly exhibit sizes and types are available for different uses, e.g. for iv/
impaired psychomotor development. hypodermic use, epidural and spinal anaesthesia. Short-
Wu SF, Caplan M, Lin HC (2012). Pediatr Neonatol; bevelled needles are traditionally preferred for regional
53:15863 anaesthesia. Hollow needles are not required for acu-
puncture or electrical stimulation/recording.
Needle size is described by a wire gauge classifica-
Necrotising fasciitis. Uncommon deep-seated infection tion (G; Stubs gauge; Birmingham gauge), which origi-
of subcutaneous tissue, resulting in destruction of fat and nally referred to the number of times the wire was
fascia. Predisposing factors include immunosuppression, drawn through the draw plate (Table 30). It differs
alcoholism, diabetes, peripheral vascular disease, surgery, slightly from the American and Standard wire gauges.
penetrating injuries (which may be minor) and varicella Internal diameter varies according to different materi-
infection, although it may affect young healthy individu- als and needle strengths. The system is also used for iv
als. Systemic upset is thought to result from bacterial cannulae. For hypodermic needles, colour-coding is
toxins, endogenous cytokines and other inflammatory mandatory in the UK for certain sizes: 26 G brown;
mediators. May be rapidly fatal unless aggressively 25 G orange; 23 G blue; 22 G black; 21 G green; 20 G
treated. May be caused by: yellow; 19 G cream.
Gram-negative bacilli, enterococci and mixed [Sir Christopher Wren (16331723), English scientist
anaerobes. Infection involves fat and fascia, although and architect; Francis Rynd (18011861), Irish surgeon;
the skin is usually spared. Includes Fourniers gan- Peter Stubs (17561806), English toolmaker and
grene of the perineum. innkeeper]
group A streptococci. Features include systemic
toxicity, pain, necrosis of subcutaneous tissue and Needlestick injury, see Environmental safety of
skin, gangrene, shock and MODS. anaesthetists
 Neonate 401

lack thereof) is judged against that of a reasonable

Table 30 Diameter of needles of different gauge number
body of medical opinion, even if that body is a minority
Gauge number (G) Outside diameter (mm)
(Bolam test); traditionally the fact that such a body of
opinion exists has usually been enough for a successful
36 0.10 defence against a charge of negligence in the UK. More
30 0.30 recently the courts have scrutinised the reasoning and
29 0.33 evidence behind such opinion before accepting that it is
28 0.36 reasonable. In the UK, since negligence must be proved
27 0.41 in order for compensation to be paid, inability to estab-
26 0.46 lish this link will result in no compensation. Thus there
25 0.51 have been calls for no-fault compensation schemes
24 0.56
similar to that in New Zealand, in which the fact that
23 0.64
harm has occurred is enough to result in compensation
22 0.71
21 0.81
without having to prove negligence.
20 0.90 [John Hector Bolam, UK shipping assistant and psychi-
19 1.08 atric patient; suffered fractures in 1954 during electro-
18 1.27 convulsive therapy administered without paralysis or
17 1.50 restraint, then claimed negligence by the hospital. The
16 1.65 claim was dismissed because withholding of anaesthesia
15 1.83 was accepted medical practice at the time.]
14 2.11
13 2.41
Neisserial infections. Mostly caused by two species of
12 2.77
11 3.05
the Gram-positive cocci genus:
Neisseria gonorrhoeae: may cause acute endo
10 3.40
9 3.76 carditis, urethritis, pelvic inflammatory disease and
8 4.19 pelvic abscesses.
7 4.57 N. meningitidis (meningococcus): causes meningo-
6 5.16 coccal disease, including meningitis. The organism
1 7.62 may be carried in the nasopharynx of about 5% of
otherwise healthy subjects, increasing to about 30%
during epidemics.
Neisserial infection is common in complement
deficiency.
NEEP, see Negative end-expiratory pressure [Albert Neisser (18551916), German physician]

Nefopam hydrochloride. Centrally acting analgesic Neomycin sulphate. Aminoglycoside and antibacterial
drug, unrelated to opioid analgesic drugs and NSAIDs. drug, used orally for selective decontamination of the
Inhibits reuptake of 5-HT, noradrenaline and dopamine. digestive tract, specifically in hepatic failure and before
Has similar analgesic potency to NSAIDs. Peak action bowel surgery. Also used topically for skin or mucous
occurs 12h after im injection. Drowsiness and respira- membrane infections.
tory depression may occur, but less than with opioids. Dosage: 1g orally, 4-hourly.
Dosage: 3090mg orally tds. Side effects: as for aminoglycosides. May be absorbed
Side effects: nausea, headache, confusion, anti systemically in hepatic failure, resulting in toxicity.
cholinergic effects. Should be avoided in patients
with epilepsy and those taking monoamine oxidase Neonatal resuscitation, see Cardiopulmonary resusci-
inhibitors. tation, neonatal
Evans MS, Lysakowski C, Tramr MR (2008). Br J
Anaesth; 101: 61017 Neonatal Resuscitation Program (NRP). Programme
of training in neonatal CPR, established in 1988 in the
Negative end-expiratory pressure (NEEP). Adjunct USA and administered by the American Heart Associa-
to IPPV, popular in the 1960s70s as a method of tion and American Academy of Pediatrics. Similar in
reducing the adverse cardiovascular effects of IPPV by concept to the ATLS and related courses. Has been
maintaining a subatmospheric airway pressure at end- referred to as NALS (Neonatal Advanced Life
expiration. However, NEEP increases airway collapse, Support), but the term is not an official one.
alveolararterial O2 difference and dead space, whilst
reducing FRC. Thus no longer used. Neonate. Child within 28 days of birth. Normally weighs
34kg, with body surface area approximately 0.19m2.
Negligence. Civil charge in which the following must be Major changes at birth include the following:
established: change from fetal circulation to adult circulation
duty of care owed to the patient by the doctor, other via transitional circulation. The fibrous left ventri-
professional or institution. cle, which is of similar size to the right ventricle
failure in that duty. at birth, gradually increases in compliance and
harm suffered as a result of that failure. contractility.
Although the duty of care and failure in that duty may expansion of fluid-filled alveoli; requires negative
be easy to demonstrate, establishing according to the intrapleural pressures exceeding 70 cmH2O. Increas-
balance of probabilities that harm is a direct result of ing numbers of alveoli are expanded in successive
that failure is usually more difficult. A doctors action (or breaths. Most fluid is rapidly expelled via the upper
402 Neostigmine methylsulphate/bromide

(a) (b)
Bowman's capsule Glomerulus Interlobular artery
Distal convoluted Afferent arteriole Interlobular vein
tubule
Arcuate artery

Proximal Efferent arteriole Arcuate vein

convoluted
tubule
Descending Ascending
vasa recta vasa recta

Collecting Loop of Henle

duct

Fig. 114 Structure of nephron: (a) glomerulotubular system; (b) vascular system

airway, with the remainder drained via capillary and given with atropine or glycopyrronium when adminis-
lymphatic vessels over 13 days. tered iv to prevent muscarinic side effects. Active within
Anatomical and physiological features and principles 1min of iv injection, with action lasting 2030min.
of anaesthesia are as for paediatric anaesthesia. Periop- Active for up to 4h after oral administration. Excreted
erative risks are higher than for older children, especially mainly renally, mostly unchanged. Elimination half-life
in premature neonates; surgery is usually deferred if is 5090min. May be administered parenterally (as
possible. methylsulphate) or orally (as bromide). Has also been
See also, Cardiopulmonary resuscitation, neonatal; Fetal given intrathecally; produces analgesia but with increased
haemoglobin; Fetal monitoring; Neurobehavioural testing nausea and vomiting.
of neonates; Obstetric analgesia and anaesthesia; Paedi- Dosage:
atric advanced life support; Paediatric intensive care; reversal of non-depolarising blockade: 0.04
Surfactant 0.08mg/kg iv with 0.020.04mg/kg atropine or
1020g/kg glycopyrronium.
Neostigmine methylsulphate/bromide. Acetylcholin- myasthenia gravis: 1530mg orally or 1.02.5mg sc/
esterase inhibitor, first synthesised in 1931. Used to im, 24-hourly.
increase acetylcholine concentrations at the neuromus- other uses: as for myasthenia gravis.
cular junction, e.g. reversal of non-depolarising neuro- Side effects: as above. Cholinergic crisis may occur in
muscular blockade and myasthenia gravis. Also has a overdosage.
direct stimulatory effect on skeletal muscle acetylcho-
line receptors; in addition, it is thought to have signifi-
Neosynephrine, see Phenylephrine
cant presynaptic action, increasing the amount of
acetylcholine released. May cause depolarising neuro-
muscular blockade in overdosage. Other effects are Nephritic syndrome. Acute glomerulonephritis charac-
those of muscarinic stimulation, e.g. bradycardia, terised by reduction of glomerular filtration rate, haema-
increased GIT motility and bladder contractility, sweat- turia, proteinuria, salt and water retention, increased
ing, salivation, miosis, bronchospasm. Has been used to intravascular volume and hypertension. Most commonly
treat urinary retention and ileus, e.g. postoperatively. a post-infectious condition, it is also seen in SLE. Usually
Effects on autonomic ganglia are small, consisting of mild; severe cases may result in acute kidney injury.
stimulation at low doses and depression at high doses. A Distinction between it and nephrotic syndrome has
quaternary ammonium compound, it crosses the blood been overplayed in the past and both share common
brain barrier poorly and has few CNS effects. Routinely aetiologies.
 Nerve conduction 403

Nephron. Basic renal unit; each kidney contains about peritubular capillaries and ascending vasa recta
1.3 million. drain into interlobular veins.
Structure (Fig. 114a): [Sir William P Bowman (18161892), English
glomerulus: formed by a 200m diameter invagina- surgeon; Friedrich GJ Henle (18091885), German
tion of capillaries into the blind end of the nephron anatomist]
(Bowmans capsule). Water is filtered from the See also, Acidbase balance; Clearance; Diuretics; Renin/
blood across the glomerular membrane, together angiotensin system
with substances under 48nm in diameter. GFR
equals about 120ml/min (180 1/day). Nephrotic syndrome. Defined by daily urinary protein
tubule: 4565mm long. The site of reabsorption/ excretion exceeding 3.5g/1.73m2 body surface area.
secretion of substances from/into the filtrate, May be caused by primary or secondary (e.g. to diabetes
giving rise to the eventual composition of urine. mellitus, pre-eclampsia, connective tissue disease, post-
Consists of: viral hepatitis or streptococcal infection, drugs such as
- proximal convoluted tubule: 15mm long. Lies NSAIDs or captopril) glomerular disease. Features
within the renal cortex. Lined by a brush border. include generalised oedema, susceptibility to infection
Site of active reabsorption of sodium and potas- and thromboembolism (especially renal vein thrombosis
sium ions, bicarbonate, phosphate, glucose, uric and DVT) and hyperlipidaemia. Hypoalbuminaemia
acid and amino acids. Water moves passively from may lead to altered drug binding.
the tubule by osmosis. Up to 80% of filtered water Treatment includes a low-sodium diet and diuretic
and solutes is reabsorbed. therapy to reduce oedema, and a low-protein diet and
- loop of Henle: about 1525cm long; length angiotensin converting enzyme inhibitors to reduce pro-
depends on whether the glomerulus lies within teinuria. Other treatment is directed against the cause,
the outer or inner renal cortex (short in the e.g. corticosteroids in glomerulonephritis.
former, long in the latter). A further 15% of fil- See also, Renal failure
tered water is reabsorbed. 15% of loops extend
into the medulla, where interstitial osmolarity is
Nernst equation. Equation for calculating the mem-
very high (up to 1200 mosmol/l). Water moves out
brane potential at which an individual ion is at equilib-
of the descending limb, followed by sodium ions
rium across the membrane (assuming complete
along a concentration gradient as the tubular fluid
permeability to that ion). For ion X:
becomes more concentrated. In the ascending
limb, which is impermeable to both water and RT [X]o
E= ln
sodium ions, sodium and chloride ions are actively FZ [X]i
co-transported from the tubule. The fluid thus
where E = equilibrium potential
becomes more dilute as it ascends. Urea is rela-
R = universal gas constant
tively free to pass across the tubular membranes.
T = absolute temperature
The solutes remain in the region of the medulla
F = Faraday constant (coulombs per mole of
because of the countercurrent multiplier mecha-
charge)
nism whereby the blood vessels supplying the
Z = valence of the ion
loop pass close to those draining it. Solutes pass
[X]o = extracellular concentration of X
down concentration gradients from ascending
[X]i = intracellular concentration of X.
vessels to descending vessels, and thus recirculate
at the tip of the loop. Water passes from the For chloride, potassium and sodium, E = 70mV, 94mV
descending vessels to the ascending vessels, and is and +60 mV respectively. Since the normal resting mem-
thus removed from the area. This maintains the brane potential is about 70 mV, other factors must
high osmolarity in the medullary region. The thick affect potassium and especially sodium distribution (e.g.
ascending segment forms part of the juxtaglo- relative permeability and the sodium/potassium pump).
merular apparatus where it passes near the [Hermann W Nernst (18641941), German physicist;
glomerulus. Michael Faraday (17911867), English scientist]
- distal convoluted tubule: 5mm long. A further See also, Goldman constant field equation
5% of filtered water is reabsorbed. Sodium
ions are reabsorbed in exchange for potassium Nerve. Excitable tissue whose function is the transmis-
or hydrogen ions, under the influence of sion of nerve impulses. Typical peripheral nerves consist
aldosterone. of several groups of fascicles. Each fascicle is surrounded
collecting ducts: 20mm long. Each receives several by the perineurium and contains a group of neurones,
tubules. Pass through the cortex and medulla, the axons of which are encased in the endoneurium
opening into the renal pelvis at the medullary (Fig. 115).
pyramids. Some sodium/potassium/hydrogen ion Peripheral nerves originate in the spinal cord, and
exchange occurs at the cortical part. Water is reab- may be sensory, motor or mixed. Some also carry auto-
sorbed depending on the amount of vasopressin nomic nervous system fibres.
present, which increases tubular permeability to See also, Motor pathways; Sensory pathways
water and thus increases urine concentration.
Blood supply (Fig. 114b): Nerve conduction. Passage of an action potential
afferent and efferent arterioles supply and drain the along neurones; involves waves of depolarisation and
capillaries to the glomerulus respectively. repolarisation that move longitudinally across the nerve
efferent arterioles subsequently divide to form peri- membrane.
tubular capillaries or vasa recta (long loops which In unmyelinated nerves, impulses spread at up to
accompany the loop of Henle). 2m/s. Positive charge flows into the depolarised area
404 Nerve growth factor

- cauda equina syndrome following use of spinal

Perineurium Artery
catheters for continuous spinal anaesthesia.
- infection.
Vein - haematoma formation.
- chemical contamination of local anaesthetic, or
injection of the wrong solution.
- poor positioning of the anaesthetised limb with
ischaemia as above.
other:
- central venous cannulation.
- tracheal intubation.
Fascicle Axon Classic division of nerve injuries:
surrounded by neurapraxia: caused by compression. Typically
endoneurium incomplete, affecting motor more than sensory
components (when present, touch and propriocep-
Epineurium
tion predominate). Usually recovers within 6 weeks.
Damage during general anaesthesia is usually of
Fig. 115 Cross-section of a typical nerve this nature, and associated with positioning.
axonotmesis: axonal and myelin loss within the
intact connective tissue sheath. Typically there is
from the membrane just distally, altering the distal per- complete motor and sensory loss, with slow recov-
meability to ions (especially sodium and potassium) as ery due to nerve regeneration from proximal to
for action potential generation. When the threshold distal nerve.
potential is reached, depolarisation occurs. Retrograde neurotmesis: partial or complete severance. Recov-
conduction is prevented by the refractory period of the ery is rare.
membrane proximally. Electromyographic and nerve conduction studies
The myelin sheath of myelinated nerves acts as an may aid differentiation between types of injury, and
insulator that prevents the flow of ions across the nerve are most useful 13 weeks after the event. Baseline
membrane. Breaks in the myelin (nodes of Ranvier), studies performed immediately after the injury are
approximately 1mm apart, allow ions to flow freely also useful to identify or exclude pre-existing deficit.
between the neurone and the ECF at these points. Depo- Many specific neuropathies have been described,
larisation jumps from node to node (saltatory conduc- including lesions of the following:
tion), a process that increases conduction velocity (up to brachial plexus: usually stretched, typically by
120m/s) and conserves energy. shoulder abduction and extension, with supination.
[Louis A Ranvier (18351922), French pathologist and Stretch is exacerbated by bilateral abduction. Upper
physician] roots are usually affected; weakness lasts up to
several months, although recovery usually occurs
Nerve growth factor (NGF). Protein produced within 23 months. Lower roots may be damaged
by many cell types; taken up by small sensory and sym- during sternal retraction in cardiac surgery. Com-
pathetic nerve fibres via specific receptors and retro- pression may be caused by shoulder rests in the steep
gradely transported to the cell body. Required for growth head-down position, resulting in temporary palsy.
and survival of neurones in the fetus and neonate; ulnar nerve (most common nerve injury reported):
released from connective tissue and inflammatory cells may be compressed between the humeral epicon-
following tissue injury in response to cytokine stimula- dyle and the operating table or arm supports, or
tion. Causes hyperalgesia via both central and peripheral injured by poles during transfer of the patient.
effects; thus thought to be important in acute and chronic radial nerve: caused by the patients arm hanging
pain states. over the side of the operating table.
Sofroniew MV, Howe CL, Mobley WC (2001). Ann Rev median nerve: may be damaged by direct needle
Neurosci; 24: 121781 trauma, or drug extravasation in the antecubital
fossa.
Nerve injury during anaesthesia. May occur during facial nerve: compressed between the anaesthetists
general, local or regional anaesthesia. fingers and the patients mandible during mask
Causes of neuronal injury include: anaesthesia.
general anaesthesia: abducens nerve: temporary lesions may follow
- poor positioning of the patient; thought to cause spinal or epidural anaesthesia.
local nerve ischaemia. trigeminal nerve: typically damaged by the
- ischaemia caused by hypotension or use of trichloroethylene/soda lime interaction.
tourniquets. supraorbital nerve: compressed by the tracheal tube
- hypothermia. connector, catheter mount, head harness or ventila-
- extravasation of drugs into perineural tissue. tor tubing.
- toxicity of degradation products of anaesthetic common peroneal nerve: compressed between
agents, classically trichloroethylene with soda lithotomy pole and fibular head.
lime. saphenous nerve: compressed between lithotomy
local/regional anaesthesia: positioning/ischaemia/ pole and medial tibial condyle.
hypothermia as above plus: sciatic nerve: damaged by im injections or com-
- direct trauma from a needle or catheter. pressed against the operating table in emaciated
- intraneural injection of local anaesthetic agent. patients.
 Neuroleptic malignant syndrome 405

pudendal nerve: compressed between a poorly locus at chromosome 17, with an incidence of
padded perineal post and the ischial tuberosity. 1:3000. Flat, brown caf au lait spots occur in all
Nerve injury may also be caused by surgical trauma/ sufferers, six or more spots larger than 1.5cm being
compression. diagnostic. Neurofibromata may be subcutaneous/
Similar concerns exist for patients undergoing pro- cutaneous, or may occur in deeper peripheral nerves
longed treatment on ICU. or autonomic nerves supplying viscera. They may
See also, Cranial nerves; Critical illness polyneuropathy also occur at the foramen magnum or within the
theca, causing nerve root or spinal cord compres-
Nerve stimulator, see Neuromuscular blockade moni- sion. Pulmonary fibrosis occurs in 20% of cases;
toring; Regional anaesthesia; Transcutaneous electrical hypertension is present in 6% of patients and may
nerve stimulation be associated with phaeochromocytoma (in 1%) or
renal artery stenosis. Intracranial tumours occur in
Netilmicin. Aminoglycoside and antibacterial drug with 510% of cases, and skeletal abnormalities (includ-
similar activity to gentamicin but less active against ing kyphoscoliosis) in 10%. Potential anaesthetic
pseudomonas. Less ototoxic than gentamicin. problems result from the distribution of neurofibro-
Dosage: 46mg/kg im/iv daily or up to 2.5mg/kg im/ mata and may include difficulty with tracheal intu-
iv bd/tds. Blood concentrations: 1h post-dose < bation or regional blocks. Despite earlier reports,
12mg/l; pre-dose < 2mg/l. patients exhibit normal sensitivity to neuromuscu-
Side effects: as for aminoglycosides. lar blocking drugs.
neurofibromatosis 2 (NF-2): very rare condition in
Neuralgia. Pain in the distribution of a defined nerve or which bilateral acoustic neuromas are present.
group of nerves. Gene has been mapped to chromosome 22.
[Friedrich D von Recklinghausen (18331910), German
Neuritis. Inflammation of nerve(s). pathologist]
Hirsch NP, Murphy A, Radcliffe JJ (2001). Br J
Neurobehavioural testing of neonates. Investigation Anaesth; 86: 55564
of the effects of obstetric analgesia and anaesthesia on
the neonate is difficult because of many variables, e.g.
Neurokinin-1 receptor antagonists. Antiemetic drugs,
obstetric details, fetal distress, method of delivery, type
acting via inhibition at neurokinin-1 (NK1) receptors
and route of drugs administered, methods of analysis of
present in the GIT and CNS. Aprepitant is currently
data. In many early studies, aortocaval compression was
licensed for nausea and vomiting induced by cancer che-
not avoided.
Tests used:
motherapy. Have also been studied in PONV.
Diemunsch P, Joshi GP, Brichant J-F (2009). Br J
neonatal behavioural assessment scale (NBAS):
Anaesth; 103: 713
very detailed, taking up to 1h to perform. More
See also, Tachykinins
sensitive than the others.
early neonatal neurobehavioural scale (ENNS):
directed more towards disorders of tone. Quicker Neurolepsis, see Neuroleptanaesthesia and analgesia
and easier to perform.
neurological and adaptive capacity score (NACS):
Neuroleptanaesthesia and analgesia. Use of very
even more directed towards tone. Takes a few
potent opioid analgesic drugs (e.g. fentanyl and pheno-
minutes to perform. The least sensitive test for
peridine) combined with butyrophenones (e.g. droperi-
subtle effects.
Summary of results:
dol and haloperidol) to produce a state of reduced motor
activity and passivity (neurolepsis). Introduced in 1959.
pethidine: reduces alertness and responsiveness
The term neuroleptanaesthesia is usually restricted to
before respiratory depression is evident. Greatest
the combination of opioid, butyrophenone and N2O.
effect is at 2 days. Rapid placental transfer follows
Characterised by profound analgesia, sedation and anti-
maternal iv injection.
emesis, with cardiovascular stability (although mild
anaesthetic agents: thiopental causes more neonatal
hypotension may occur). Has been used for premedica-
depression than ketamine (but tone is increased by
tion, sedation and as the sole anaesthetic technique,
ketamine, giving higher scores). Low concentrations
with/without neuromuscular blocking drugs, for surgical
of volatile inhalational anaesthetic agents produce
procedures (now rarely employed for the latter use
little, if any, effects. Regional techniques consis-
because of prolonged recovery).
tently produce higher scores.
See also, Lytic cocktail
local anaesthetic agents: initial fears of hypotonia
following lidocaine have now been dispelled. All
local anaesthetic drugs have similar effects, lower- Neuroleptic malignant syndrome (NMS). Rare condi-
ing scores only when very sensitive testing is tion first described in 1960, characterised by altered con-
employed. The significance of this is unknown. sciousness, hyperthermia, autonomic dysfunction and
muscle rigidity. Usually triggered by drugs (e.g. butyro-
Neurofibromatosis. Group of neurocutaneous diseases phenones, phenothiazines, metoclopramide, lithium,
characterised by multiple tumours derived from the reserpine), although it has been reported during with-
neurilemma sheath of cranial and peripheral nerves/ drawal of L-dopa in patients with Parkinsons disease.
nerve roots. The mechanism is thought to involve dopamine receptor
Classified into: blockade in the basal ganglia and hypothalamus. Occurs
neurofibromatosis 1 (NF-1; von Recklinghausens mostly in young males. Incidence is increased with dehy-
disease). Autosomal dominant disease with gene dration, CNS disease and exhaustion.
406 Neuromuscular blockade monitoring

Features develop over 13 days: between 20 and 60mA, and is minimised by placing
hyperthermia and tachycardia (thought to be caused the positive electrode proximally.
mostly by increased muscle metabolism, although a direct stimulation of the muscle should be avoided,
central component may be present). since any response will be independent of neuro-
extrapyramidal dysfunction: rigidity, dystonia, muscular blockade.
tremor. commonly used sites:
autonomic dysfunction: labile BP, sweating, saliva- - ulnar nerve: electrodes are placed along the ulnar
tion, urinary incontinence. border of the forearm, with assessment of thumb
increased creatine kinase (> 1000 units/l) and white adduction. More sensitive than the diaphragm
cell count. and vocal cords to neuromuscular blocking drugs.
Differential diagnosis is as for hyperthermia (in particu- - facial nerve: electrodes are placed anterior to the
lar MH), Parkinsons disease, catatonia, central anticho- tragus of the ear, with assessment of facial muscle
linergic syndrome, monoamine oxidase inhibitor reaction contraction. Underestimation of the degree of
and infection, e.g. tetanus. Although similar to MH, NMS blockade is common, because of direct muscle
is generally considered an entirely separate entity. stimulation and relative insensitivity of the facial
Management: muscles to neuromuscular blocking drugs.
supportive: O2, cooling, hydration, DVT - accessory nerve: one electrode is placed behind
prophylaxis. the mastoid process and the other at the posterior
increased central dopaminergic activity, e.g. with border of sternomastoid. Stimulation causes con-
bromocriptine (dopamine agonist) 2.520mg tds traction of sternomastoid and trapezius muscles
(orally only). Amantidine and L-dopa have also and is easier to see than following stimulation of
been used. the facial nerve. Asystole has followed tetanic
dantrolene and non-depolarising neuromuscular stimulation when the upper electrode was placed
blocking drugs have been used to treat the periph- anterior to the ear, attributed to stimulation of the
eral muscle effects, reducing fever, rigidity and vagus via the cranial root of the accessory nerve.
tachycardia. The latter drugs are effective in NMS, - tibial nerve: electrodes are placed behind the
in contrast to MH. medial malleolus, with assessment of big toe
anticholinergic drugs have also been used. plantar flexion.
Mortality is 2030%, from renal failure, arrhythmias, PE - common peroneal nerve: electrodes are placed
or aspiration pneumonitis. lateral to the neck of the fibula, with assessment
Adnet P, Lestovel P, Krivosic-Horber R (2000). Br J of foot dorsiflexion.
Anaesth; 85: 12935 patterns of stimulation:
- single pulses (0.11.0Hz).
Neuromuscular blockade monitoring. Ideally, this - tetanic stimulation (50100Hz) for 35s. Painful
should be undertaken whenever non-depolarising in the awake patient. May be repeated every
neuromuscular blocking drugs are used since residual 510min.
block is common in the recovery room, even after the - post-tetanic stimulation using single pulses.
use of intermediate-acting drugs such as atracurium and - train-of-four (TOF; four pulses at 2Hz). TOF
vecuronium. A nerve stimulator is used to stimulate a count is the number of palpable muscle twitches;
peripheral nerve via surface or needle electrodes; the TOF ratio is force of the fourth twitch divided by
muscle response is then assessed. force of the first. May be repeated every 1015s.
Assessment may be: - post-tetanic count: used to assess intense block-
visual. ade. Following 5s tetanus at 50Hz, the number
tactile. of twitches produced by single pulses at 1Hz is
mechanical: reflects both neuromuscular transmis- counted. Should not be performed more than
sion and muscle contractility. Assessed by: once in 5min.
- measurement of tension developed in a muscle - double-burst stimulation: used to assess recovery
with a strain gauge or pressure transducer. from non-depolarising blockade. Two short tetanic
- accelerometry: the transducer consists of a piezo- stimulations (e.g. 50Hz for 60 ms) are applied 750
electric ceramic wafer with electrodes on both ms apart. The second response is weaker than the
sides. Following changes in velocity, an electrical first in non-depolarising blockade. More sensitive
voltage proportional to the acceleration is gener- at detecting fade than TOF.
ated between the electrodes. Force = mass accel- Observed responses:
eration; thus the muscle tension response may be normal neuromuscular function:
evaluated. - equal twitches in response to single pulses
electrical: registers the EMG response via two (Fig. 116a).
surface/needle electrodes. Only monitors transmis- - sustained tetanic contraction, with post-tetanic
sion across the neuromuscular junction, and thus is potentiation (PTP) revealed by mechanical
more specific than mechanical assessment. assessment only.
Stimulation: depolarising neuromuscular blockade:
unipolar square waveform lasting 0.20.3 ms - equal but reduced twitches in response to single
(ensures constant current during stimulation). pulses and TOF (Fig. 116b). TOF ratio thus equals
supramaximal stimulation is required in order to unity.
eliminate variation in muscle response caused by - sustained but reduced tetanic contraction, with
partial depolarisation of the nerve; this results in neither fade nor PTP.
simultaneous depolarisation of all nerve fibres - dual block may supervene if large amounts of
within the nerve. Required current may vary suxamethonium are administered.
 Neuromuscular junction 407

ionised at body pH, containing two quaternary

(a) ammonium groups (tubocurarine and vecuronium
contain one each, but acquire a second following
injection). Poorly lipid-soluble with variable protein
binding. Following injection, the drugs are rapidly
redistributed from blood to the ECF and other
tissues, e.g. kidney, liver. The clinical effect depends
(b) on individual drug characteristics and drug con
centration at the neuromuscular junction, which
depends on the drugs pharmacokinetics.
depolarising: cause depolarisation by mimicking the
(c) action of ACh at ACh receptors, but without rapid
hydrolysis by acetylcholinesterase. An area of depo-
larisation around the ACh receptordrug complex
results in local currents which open sodium chan-
Fig. 116 EMG response to peripheral nerve stimulation in a train-of- nels before the continuing current flow inactivates
four, tetanus, train-of-four pattern: (a) normal; (b) partial depolarising them. Propagation of an action potential is pre-
block; (c) partial non-depolarising block vented by the area of inexcitability that develops
around the ACh receptors. Thus fasciculations occur
before paralysis. Examples are suxamethonium
non-depolarising neuromuscular blockade.
(1951) and decamethonium (1948); only the former
- progressively decreasing twitches in response is available for clinical use in the UK.
to single pulses (Fig. 116c), with eventual Apart from the presence or absence of fasciculation,
disappearance. non-depolarising and depolarising neuromuscular block
- tetanic contraction exhibits fade and PTP. ade may be distinguished by neuromuscular blockade
- TOF: successive decrease in the four responses, monitoring.
with eventual disappearance of the fourth, third, In general, suxamethonium is used for paralysis of
second and first twitches at 75%, 80%, 90% and rapid onset and short duration, e.g. to allow rapid tra-
100% blockade respectively. During recovery, the cheal intubation. The slower-acting non-depolarising
twitches reappear in the reverse order. Suggested drugs were traditionally used for prolonged paralysis
suitable values during anaesthesia: when rapid intubation was not required, although
- TOF count of 1 for tracheal intubation. rocuronium, atracurium and vecuronium have bridged
- TOF count of 12 for maintenance; deeper the gap between these drugs and suxamethonium
levels may be required for complete diaphrag- (Table 31).
matic paralysis. See also, Interonium distance; Nicotine and nicotinic
- TOF count of 34 before attempting reversal of receptors
blockade, especially with long-acting drugs.
- TOF ratio (at the thumb) of 0.9 for adequate Neuromuscular junction. Synapse between the pre-
maintenance of spontaneous ventilation. synaptic motor neurone and the postsynaptic muscle
- post-tetanic count and double-burst stimulation membrane. On approaching the junction, the axon
as above. divides into terminal buttons that invaginate into the
- sustained head lift for 5s is the most useful clini- muscle fibre. The synaptic cleft is 5070 nm wide and
cal indicator of adequate neuromuscular function filled with ECF and a basement membrane containing
(under 30% blockade). Other suggested indica- high concentrations of acetylcholinesterase. The muscle
tors include the ability to open the mouth, pro- membrane is folded into longitudinal gutters, whose
trude the tongue, cough, maintain sustained hand ridges conceal orifices to secondary clefts. The orifices
grip, and achieve adequate tidal volume, vital lie opposite the release points for acetylcholine (ACh)
capacity (15ml/kg) and inspiratory pressure (Fig. 117).
(20cm H2O). However, these may all be possible Three types of acetylcholine receptor have been iden-
at 5080% blockade. tified at the neuromuscular junction:
Fuchs-Buder T, Schreiber JU, Meistelman C (2009). postjunctional: involved in traditional neuromuscu-
Anaesthesia; 64 (Suppl 1): 829 lar transmission. Following activation of both sub-
units, sodium and calcium move into the myocyte
Neuromuscular blocking drugs. Drugs used to impair and potassium exits through specific ion channels
neuromuscular transmission and provide skeletal muscle (see also Fig. 2b; Acetylcholine receptors).
relaxation during anaesthesia or critical care. prejunctional: control an ion channel specific for
May be one of two types: sodium and respond to released ACh by mobilising
non-depolarising: include tubocurarine (first used further ACh storage vesicles to the active zone of
as curare in 1912), gallamine (1948), dimethyl tubo- the junction, ready for release. Blockade of these
curarine (1948), alcuronium (1961), pancuronium receptors is thought to underlie the phenomenon of
(1967), fazadinium (1972), atracurium (1980), fade in non-depolarising neuromuscular blockade;
vecuronium (1983), pipecuronium (1990), doxacu- activation during tetanic stimulation results in post-
rium (1991), mivacurium (1993), rocuronium (1994), tetanic potentiation.
cisatracurium (1995), and rapacuronium (1999). extrajunctional: normally present in small numbers,
Non-depolarising agents are competitive antago- but proliferate over the muscle membrane in dener-
nists at postsynaptic acetylcholine (ACh) receptors vation hypersensitivity, burns and certain muscle
of the neuromuscular junction. They are highly diseases.
408 Neuromuscular transmission

Table 31 Properties of neuromuscular blocking drugs

Vol. of Clinical
Onset time Half-life distribution Clearance duration of Histamine
Drug (min) (min) (l/kg) (ml/kg/min) action (min) Route of elimination release Autonomic effects

Alcuronium 35 180200 0.10.3 1.5 2040 Renal

Atracurium 1.52 20 0.160.18 5.56.0 2030 Hofmann degradation +
+ plasma hydrolysis
Cisatracurium 11.5 100 0.23 3.9 3040 As for atracurium
Dimethyl tubocurarine 35 345 0.5 1.0 90120 Renal + Weak ganglion blockade
(metocurine)
Doxacurium 45 85100 0.2 2.22.6 100200 Renal + hepatic
Fazadinium 0.51.5 4080 0.2 4.0 4060 Renal Muscarinic + ganglion
blockade
Gallamine 12 160 0.25 1.2 2030 Renal Muscarinic blockade
Mivacurium 1.52 25 1015 Plasma cholinesterase
+ hepatic
Pancuronium 23 120140 0.250.3 1.8 4060 Renal + hepatic Weak muscarinic blockade
+ sympathomimetic
action
Pipecuronium 2.53 140 0.3 2.5 90120 Renal + hepatic
Rapacuronium 0.53.5 28 0.29 611 630 Renal + hepatic ++
Rocuronium 2 2229 0.120.16 4.75.7 30 Hepatic
Tubocurarine 35 150190 0.50.6 23 3050 Renal + hepatic ++ Ganglion blockade
Vecuronium 1.52 5570 0.27 5.2 2030 Renal + hepatic
Suxamethonium 0.51.5 2.5 25 Plasma cholinesterase + Muscarinic + ganglionic
stimulation

Nerve

Myelin
Mitochondrion

Microtubule
Schwann cell
Nerve terminal

Basement membrane containing

Active zone
acetylcholinesterase or release site
Synaptic space Acetylcholine receptors

Muscle Secondary cleft

Primary cleft

Actinmyosin complex

Fig. 117 Structure of neuromuscular junction

Martyn JAJ, Jonsson Fagerlund M, Eriksson LI (2009). opening of presynaptic voltage-gated calcium chan-
Anaesthesia; 64 (Suppl 1): 19 nels. Resultant increase in intracellular calcium
See also, Neuromuscular blocking drugs causes mobilisation of acetylcholine (ACh) vesicles
to the active zone and subsequent release into the
Neuromuscular transmission. Stages of transmission: synapse.
depolarisation of the motor nerve leading to action binding of ACh to postsynaptic nicotinic ACh
potential propagation to the nerve endings at the receptors, allowing sodium and calcium ion influx
neuromuscular junction. and causing an end-plate potential. If the latter is
 Neurosurgery 409

large enough, depolarisation of the muscle mem- sedation or anaesthesia may be required in children,
brane occurs. uncooperative or neurologically impaired patients or
resultant action potential causing muscle for prolonged procedures. Principles are as for radiology
contraction. and neurosurgery.
hydrolysis of ACh by acetylcholinesterase within Specific techniques:
1 ms. myelography: injection of contrast into the thecal
Transmission may be impaired by: sac to examine the spinal cord. Usually performed
inhibition of ACh synthesis, storage or release, e.g. via lumbar puncture but occasionally via a cervical
by hemicholinium, -bungarotoxin and botulinum approach. Steep tilting is often required to aid
toxins respectively. Aminoglycosides are also spread of the contrast. Complications include head-
thought to impair ACh release, as does the myas- ache, convulsions and arachnoiditis.
thenic syndrome. CT scanning.
blockade of ACh receptors, e.g. by neuromuscular MRI.
blocking drugs, -bungarotoxin, receptor destruc- positron emission tomography.
tion in myasthenia gravis. cerebral angiography: injection of radiological con-
acetylcholinesterase inhibitors. trast media via femoral or carotid puncture. Hyper-
Naguib M, Flood P, McArdle JJ, Brenner HR (2002). ventilation improves the arteriogram quality by
Anesthesiology; 96: 20231 increasing cerebrovascular resistance. Complica-
See also, Synapse tions include CVA (1% of patients), haemorrhage,
haematoma, thrombosis, arterial spasm and brady-
Neurone. Basic unit of the nervous system. Consists of: cardia (especially during vertebral angiography).
ventriculography and pneumoencephalography:
cell body: contains the nucleus and most of the cyto-
plasm. Usually at the dendritic end of the neurone. injection of gas (usually air) into the ventricular
The dendritic zone is the site of integration of system, with imaging in different positions. N2O is
incoming impulses via dendrites, and of initiation of usually avoided. Bradycardia may occur. Rarely
the action potential. performed now.
therapeutic interventions:
axon: may exceed 1 metre in length. May be myelin-
ated or unmyelinated (see Myelin; Nerve conduc- - embolisation: e.g. of cerebral and spinal arteriove-
tion). Anterograde and retrograde flow of organelles nous malformations and cerebral aneurysms.
and proteins occurs along the axon. Usually requires anticoagulation. Control of BP
terminal buttons (nerve endings): situated near the
is essential to avoid rupture.
cell body or dendrites of other neurones and contain - balloon angioplasty and stenting: e.g. of occlusive
neurotransmitters. cerebral disease and vasospasm secondary to sub-
Divided into classes in 1924 according to the com- arachnoid haemorrhage. Deliberate hypertension
pound action potential obtained when a mixed nerve may be required to maintain cerebral perfusion
is stimulated: pressure and avoid ischaemia.
A: 120 m diameter myelinated fibres. Subdivided
- carotid artery stenting for stenosis.
into: - thrombolysis of acute thromboembolic
- : 70120m/s conduction; somatic motor and pro- stroke. Cerebral haemorrhage may occur
prioception sensation. postoperatively.
- : 5070m/s; touch and pressure sensation. Schulenburg E, Matta B (2011). Curr Opin Anesthesiol;
- : 3050m/s; motor fibres to muscle spindles. 24: 42632
- : < 30m/s; pain, cold, touch sensation.
B: 13 m diameter; < 15m/s conduction: myelin-
Neurosurgery. Encompasses procedures involving the
ated preganglionic autonomic fibres. cranium, brain, meninges, cranial nerves, spinal cord and
C: < 1 m diameter; < 2m/s conduction: unmyelin-
vertebral column, and those performed for pain manage-
ated postganglionic autonomic fibres, and pain and ment. Basic principles for intracranial surgery are related
temperature sensation. to maintenance of normal cerebral perfusion pressure
Local anaesthetic agents block C fibres first, then B, and cerebral blood flow, with avoidance of cerebral isch-
then A fibres. Pressure blocks A, B and C fibres in aemia, cerebral steal and increased ICP. Cerebral pro-
order, and hypoxia B, A and C fibres. tection has been employed.
Main considerations:
An alternative classification has been suggested:
preoperatively:
I:
- a: muscle spindles. - preoperative assessment of neurological status,
- b: Golgi tendon organ. hydrocephalus, etc. Endocrine abnormalities may
II: muscle spindles, touch, pressure.
be present (e.g. pituitary gland surgery).
III: pain, cold, touch.
- fluid and electrolyte imbalance may be present,
IV: pain, temperature, others.
especially if associated with reduced oral intake
[Camillo Golgi (18431926), Italian physician] and vomiting.
See also, Nociception - hypertension may be present, especially in asso-
ciation with subarachnoid haemorrhage.
- drug therapy may include anticonvulsant drugs
Neuropathy of critical illness, see Critical illness and corticosteroids.
polyneuropathy - other injuries may accompany head injury.
- sedative premedication is usually avoided because
Neuroradiology. Most neuroradiological procedures of possible perioperative respiratory depression
are painless and do not require anaesthetic intervention; and decreased conscious level.
410 Neurotransmitters

perioperatively: and the patients neurological state is easily

- iv induction of anaesthesia is usual; most iv anaes- monitored.
thetic agents are suitable apart from ketamine. postoperatively:
Smooth induction avoiding hypoxaemia, hyper- - tracheal extubation is usually possible at the end
capnia, hypertension and tachycardia is required. of surgery and is performed under deep anaesthe-
Hyperkalaemia has followed suxamethonium in sia; coughing or straining should be avoided.
certain upper and lower motor neurone lesions. Elective IPPV may be required, e.g. following
-Adrenergic receptor antagonists may be given prolonged operations and when ICP is critically
to reduce the hypertensive response to laryngos- raised. Airway obstruction caused by acute swell-
copy, whilst lidocaine 0.51.5mg/kg may be given ing of the tongue has been reported following
iv to reduce the increase in ICP. Adequate time posterior fossa surgery.
should be allowed for full paralysis before tra- - close observation is required, in case of bleeding,
cheal intubation is attempted. Lidocaine spray vasospasm, increased ICP, convulsions, hypoten-
may be employed during laryngoscopy. Use of a sion or hypertension. The Glasgow coma scale is
reinforced tracheal tube is usual, with thorough employed for monitoring progress. ICP monitor-
fixation. The eyes and face should be protected ing may be used.
with padding. - the patient should be kept normothermic to
- a large-bore iv cannula is necessary, since blood prevent postoperative shivering.
loss may be considerable. CVP measurement may - morphine is a suitable choice for postoperative
be required, especially if the patient is to be posi- analgesia.
tioned sitting. Arterial cannulation is usual. End- - diabetes insipidus or the syndrome of inappropri-
tidal CO2 measurement, pulse oximetry, ECG and ate antidiuretic hormone secretion may occur.
temperature measurement are mandatory. Neuro- - increased risk of DVT has been associated with
muscular blockade monitoring is especially useful, neurosurgery. In the immediate postoperative
since inadequate paralysis may have disastrous period mechanical methods of prophylaxis
results. ICP monitoring, evoked potentials and are usually preferred to heparin due to the
EEG derivatives are sometimes employed. potentially catastrophic effects of postoperative
- permissive hypothermia (to 35C) is increasingly bleeding.
popular in an attempt to reduce cerebral Dinsmore J (2007). Br J Anaesth; 99: 6874
metabolism. See also, Spinal surgery
- perioperative problems include:
- those related to positioning of the patient. The
supine position is common; others include: Neurotransmitters. Substances secreted from presyn-
- lateral/prone: vena caval obstruction and aptic nerve endings, which act at the postsynaptic mem-
damage to the face, eyes, etc., may occur. brane to cause excitatory or inhibitory effects. Act via
- sitting (for posterior fossa lesions): air embo- specific receptors that elicit intracellular effects (e.g. by
lism, hypotension and obstruction of neck opening membrane ion channels, activating intracellular
veins may occur. The first two may be reduced enzymes or altering DNA transcription). The same neu-
by the antigravity suit, PEEP and administra- rotransmitter may be excitatory at one synapse, and
tion of iv fluids. inhibitory at another.
Examples:
- inaccessibility of the airway.
amines, e.g. noradrenaline, adrenaline, dopamine,
- those of prolonged surgery, e.g. heat loss, fluid
balance. 5-HT, histamine.
amino acids, e.g. glycine, glutamate, GABA,
- acute control of ICP.
- arrhythmias and cardiovascular instability aspartate.
polypeptides, e.g. substance P, enkephalins. Sub-
during manipulation of brainstem structures
(posterior fossa lesions). stances active as circulating hormones may also
- maintenance is usually with air/O2 mixture with a function as neurotransmitters, e.g. vasopressin,
volatile inhalational anaesthetic agent (e.g. isoflu- oxytocin, vasoactive intestinal peptide, glucagon,
rane or sevoflurane) with or without a short- somatostatin.
others, e.g. acetylcholine, nitric oxide.
acting opioid, e.g. fentanyl, remifentanil. N2O is
usually avoided because it increases cerebral In general, acetylcholine and the amino acids are
blood flow and ICP and because of the risk of involved with fast point-to-point signalling whereas the
expansion of a pneumoencephalocoele. TIVA is polypeptides, amines and nitric oxide have a slower,
also used. An arterial PCO2 of 4.55.0 (35 more diffuse regulatory function. More than one neu-
40mmHg) is considered optimal. rotransmitter may be secreted by one neurone, e.g. vaso-
- hypotensive anaesthesia is sometimes employed, active intestinal peptide is often secreted with
especially for vascular lesions. acetylcholine, and is thought to potentiate the latters
- bradycardia may follow application of suction to actions. Amines are often secreted with peptide
intracranial and extracranial drains. neurotransmitters.
- some procedures involving CT scanning (e.g. ste- See also, Neuromuscular junction; Receptor theory; Syn-
reotactic surgery) require moving the anaesthe- aptic transmission
tised patient between operating and imaging
rooms. Neutral thermal range, see Thermoneutral range
- local anaesthetic techniques may also be used
(e.g. for awake craniotomy). Once the skull and
dura are opened, there is usually little discomfort New injury severity score, see Injury severity score
 Nitric oxide 411

New York Heart Association classification. Method of Has no antiarrhythmic action. Used in hypertension,
assessment of cardiac disease (originally cardiac failure), ischaemic heart disease and Raynauds phenomenon.
e.g. in preoperative assessment: Active within 2030min of oral administration, but a
class I: no functional limitation. faster response follows sublingual retention of the cap-
class II: slight functional limitation. Fatigue, palpita- sules contents (though not licensed for sublingual use).
tions, dyspnoea or angina on ordinary physical May thus be administered sublingually during anaesthe-
activity, but asymptomatic at rest. sia. 95% protein-bound. Half-life is 35h. Metabolised
class III: marked functional limitation. Symptoms in the liver and excreted renally.
on less than ordinary activity, but asymptomatic Dosage:
at rest. 520mg orally bd/tds. Long-acting formulations are
class IV: inability to perform any physical activity, also available: 1090mg od.
with or without symptoms at rest. 100200g may be infused into the coronary arter-
ies, e.g. for spasm during coronary angiography.
Newton. Unit of force. 1 N is the force required to Side effects: headache, flushing, dizziness, GIT distur-
accelerate a mass of 1kg by 1m/s2. bance, peripheral oedema. Has been implicated in
[Sir Isaac Newton (16431727), English physicist] increasing risk of MI in patients with hypertension,
although this has been disputed.
Newtonian fluids, see Fluids [Maurice Raynaud (18341881), French physician]

NGF, see Nerve growth factor Nimodipine. Dihydropyridine calcium channel blocking
drug, preferentially affecting cerebral vascular smooth
NIAA, see National Institute of Academic Anaesthesia muscle. Increases cerebral blood flow, especially to
poorly perfused areas, e.g. those affected by arterial
Nicardipine hydrochloride. Calcium channel blocking spasm following subarachnoid haemorrhage (SAH).
drug. Used in the UK for treatment of hypertension and Dosage:
ischaemic heart disease; also available parenterally in prophylactically following SAH: 60mg orally
the USA for short-term reduction of BP, e.g. periopera- 4-hourly for 21 days.
tively. IV preparation is incompatible with bicarbonate in established vasospasm: 15g/kg/h iv, doubled
and Hartmanns solutions. after 2h if BP is stable. Continued for 514 days.
Reacts with PVC infusion tubing; polypropylene and
NICE, see National Institute for Health and Clinical polyethylene are suitable. May be degraded by light.
Excellence Side effects: hypotension, flushing. Should be used
with care in raised ICP.
NiCO. Commercial non-invasive cardiac output mea-
surement system that employs partial CO2 rebreathing NIPPV, see Non-invasive positive pressure ventilation
and the Fick principle to estimate cardiac output. A
small rebreathing loop is inserted into the patients NIRS, see Near infrared spectroscopy
breathing circuit and intermittently increases the volume
of the circuit. Concentration and flow of CO2 are mea- NISS, New injury severity score, see Injury severity
sured by a sensor placed between the patient and the score
rebreathing loop. The change in cardiac output is pro-
portional to the ratio of the change in CO2 elimination Nitrazepam. Benzodiazepine widely used as a hypnotic
and the resulting change in end-expiratory CO2. drug. Has also been used as an anticonvulsant in child-
hood myoclonic epilepsy. Onset of sleep occurs within
Nicorandil. Potassium channel activator with a nitrate an hour; duration of action is 48h. Extensively protein-
component, used to prevent and treat angina. Causes bound; elimination half-life is up to 30h, resulting in
arterial and venous vasodilatation. Peak plasma levels hangover effects during the day.
occur within 3060min of administration. Only slightly Dosage: 510mg orally at night.
protein-bound. Side effects: disorientation, confusion, drowsiness.
Dosage: 530mg orally bd. Dependence may occur.
Side effects: headache, vomiting, dizziness,
hypotension. Nitric oxide (NO). Oxide of nitrogen, active as a bio-
logical mediator throughout the body but especially in:
Nicotine. Toxic alkaloid derived from tobacco, mimics vascular endothelium: responsible for vascular
certain actions of acetylcholine, and was used to investi- relaxation. Reduced production has been impli-
gate the physiology of the autonomic nervous system. At cated in vasospasm associated with various disease
low doses, it stimulates postsynaptic nicotinic acetylcho- states, e.g. diabetes mellitus, hypertension and fol-
line receptors of the neuromuscular junction, autonomic lowing subarachnoid haemorrhage. NO is thought
ganglia and adrenal medulla; at high doses, it blocks to be the effector molecule for all nitrate vasodila-
them. Also causes CNS stimulation, followed by tor drugs.
depression. brain tissue: acts as a neurotransmitter.
macrophages: involved in the response to
Nifedipine. Dihydropyridine calcium channel blocking infection.
drug, affecting coronary and peripheral vascular smooth platelets: involved in aggregation and adhesion.
muscle more than myocardial muscle. Negative inotropic Synthesised in endothelial cells during the oxidation of
effect is usually insignificant because of baroreceptor- L-arginine to L-citrulline, the reaction being catalysed by
mediated tachycardia. NO synthase (NOS). The NO thus produced diffuses
412 Nitrogen

into vascular smooth muscle and converts inactive gua-

nylate cyclase into the active form; the latter converts
Vascular lumen
guanosine triphosphate into cyclic guanosine mono-
phosphate, which causes vascular relaxation (Fig. 118).
Vascular endothelium
Two forms of NOS exist: the constitutive (endothelial) NOS L-Citrulline
form, present in vascular and brain tissue, which pro- L-Arginine
duces small quantities of NO continuously (eNOS); and NO
the inducible form, present in macrophages (iNOS).
In sepsis, NO production is thought to be increased Vascular smooth GTP Inactive
by endotoxin, the action of cytokines, e.g. tumour necro- muscle Active
guanylate
sis factor and certain interleukins. The amount of the Relaxation cGMP
g-cyclase
cyclase
inducible form of NOS increases, resulting in overpro-
duction of NO with resultant excessive vasodilatation. NOS, nitric oxide synthase
NOS inhibitors have been investigated experimentally GTP, guanosine triphosphate
in the treatment of sepsis. cGMP, cyclic guanosine monophosphate
In neonatal, paediatric or adult pulmonary hyperten-
sion, inhaled NO (1150ppm) has been used to produce Fig. 118 Synthesis and action of nitric oxide (NO)
selective pulmonary vasodilatation without systemic
effects. A clear effect on outcome in ARDS has not been
conclusively demonstrated.
NO has a biological half-life of < 5s, its action being - from other routes of loss, e.g. proteinuria: nitrogen
terminated by combining with haemoglobin to form loss (g/24h) = protein loss (g/24h)
methaemoglobin. 1/6.25 since 6.25g protein contains 1g nitrogen.
Measured in gaseous form using a chemilumines- Other losses occur from sweat and faeces (e.g. 24g per
cence reaction (NO + ozone O2 + NO2 + light) or l GIT fistula fluid lost per 24h).
electroanalysis using a specific electrode. Levels in Calculation is a useful guide to appropriate nutrition
tissues are measured using electron paramagnetic reso- in critical illness. A normal adult requires about 0.15g
nance or fluorescence spectroscopy. N/kg/day; this may double in severe sepsis.
See also, Energy balance
Nitrogen. Non-metallic element existing in the atmos
phere as a colourless, odourless inert gas (isolated in Nitrogen, higher oxides of. Nitric oxide (NO), nitrogen
1772). Forms 78.03% of atmospheric air. Atomic weight dioxide (NO2) and nitrogen trioxide (N2O3); the latter
is 14; boiling point is 195C. Obtained by fractional decomposes to form NO and NO2. NO reacts with O2,
distillation of air. Reacts poorly with other substances. forming NO2, which dissolves in water to form nitrous
Blood/gas solubility coefficient is 0.014. Has anaesthetic and nitric acids. The gases are produced during some
properties at hyperbaric pressures (see Inert gas narco- fires, during manufacture of N2O, and in the metal indus-
sis). Converted into organic compounds by nitrifying try. Irritant if inhaled, they cause mild upper airway
bacteria and plants, and present throughout the body in symptoms initially but pulmonary oedema several hours
amino acids and proteins. after initial recovery. Severe pulmonary fibrotic destruc-
See also, Nitrogen balance; Nitrogen washout tion may follow 23 weeks later. Formation of nitrates
in the body may result in vasodilatation and hypoten-
Nitrogen balance. Difference between the amount of sion, and cause methaemoglobinaemia. Treatment is
nitrogen ingested (as amino acids or proteins) and the supportive. Contamination of some N2O cylinders in
amount of nitrogen excreted (mainly urinary). Usually 1967 in the UK led to their widespread recall. May be
measured within a 24-h period. Negative if losses exceed tested for using moistened starch iodide paper, which
intake, e.g. catabolism, starvation; positive if intake turns blue on exposure. NO is involved in intercellular
exceeds losses, e.g. during recovery from severe illness. communication and control of vascular tone.
Estimated thus: See also, Smoke inhalation
intake = the nitrogen content of all foods/fluids
taken. Nitrogen narcosis, see Inert gas narcosis
output = the sum of nitrogen losses calculated from
the following three components: Nitrogen washout. Elimination of nitrogen from the
- from urinary urea: nitrogen (g/24h) = urea lungs whilst breathing non-nitrogen-containing gas.
(mmol/24h) 6/5 because 1/6 is excreted as sub- During successive breaths, the concentration of nitrogen
stances other than urea exhaled falls as an exponential process, falling to about
1/1000 to convert mmol to mol 2.5% after 7min in normal patients. During anaesthesia
60 to convert mol urea to g using circle systems, 710min high fresh gas flow is
28/60 to convert g urea to g nitrogen required to remove most body nitrogen. Elimination is
i.e. urea (mmol/24h) 0.0336. prolonged if ventilation is distributed unevenly (see
- from blood urea: nitrogen (g/24h) = change in below).
urea (mmol/l/24h) 1/1000 Tests employing nitrogen washout:
60 measure of FRC.
28/60 as above single-breath nitrogen washout (Fowlers method).
60% body weight (kg) since urea is distributed multiple-breath nitrogen washout: the patient
amongst total body water breathes 100% O2, with nitrogen measurement at
i.e. change in urea (mmol/l/24h) 0.0168 body the lips. Log nitrogen concentration is plotted
weight against number of breaths. If lung ventilation is
 NMDA receptors 413

uniform, expired nitrogen concentration decreases

by the same fraction with each breath, as demon-
strated by a straight line on the graph. A curved line
is obtained if ventilation is uneven, as nitrogen is
quickly washed out from well-ventilated alveoli but

Log end-tidal N2 concentration

only slowly from poorly ventilated ones (Fig. 119).

Nitroglycerin, see Glyceryl trinitrate

Nitroprusside, see Sodium nitroprusside

Nitrous oxide (N2O). Inhalational anaesthetic agent,

first isolated by Priestley in 1772. Suggested as being a
useful analgesic by Davy in 1799; first used for dental
extraction by Wells in 1844 but superseded by diethyl
ether. Reintroduced by Colton in 1863.
Manufactured by heating ammonium nitrate to 240C
and removing impurities (e.g. higher oxides of nitrogen,
ammonia and nitric acid) by passage through scrubbers
and washers. Water vapour is also removed. Number of breaths
Properties: Uniform ventilation
colourless, slightly sweet-smelling gas, 1.53 times Uneven ventilation
denser than air.
mw 44. Fig. 119 Multiple-breath nitrogen washout
boiling point 88C.
critical temperature 36.5C.
partition coefficients:
- blood/gas 0.47.
- oil/gas 1.4.
MAC 105%. - expands air-filled cavities because it is over 40
non-flammable but supports combustion, breaking times as soluble as nitrogen; thus passes from the
down to O2 and nitrogen at high temperatures. blood into the cavity faster than the nitrogen can
supplied as a liquid/gas in French blue cylinders diffuse out. Can double the size of a pneumotho-
with pin index positions 3 and 5: pressure is 40 bar rax in 10min at 70%. Also expands air embolism
at 15C and 54 bar at room temperature. Ice often and may cause pneumoencephalocoele following
forms on the cylinder during use because of latent neurosurgery.
heat of vaporisation. Also supplied as gaseous Excreted unchanged from the lungs; a small amount dif-
Entonox. fuses through the skin.
Effects: Commonly used for analgesia (above 20%) and as a
CNS: carrier gas for other inhalational agents and O2, usually
- fast onset and recovery; strongly analgesic but in concentrations of 5066%. Although weakly anaes-
weakly anaesthetic. thetic and rarely adequate alone, it reduces the require-
- increases cerebral metabolism, cerebral blood ment for other agents. Its adverse effects and concern
flow and ICP slightly. about its effects on the environment have led to a reduc-
- has inhibitory effects on NMDA receptors; stimu- tion in its use and replacement by air. Recent evidence
latory on opioid and adrenergic receptors. suggests an increased incidence of major cardiovascular
RS: and respiratory complications after major surgery if N2O
- non-irritant. Depresses respiration slightly. is used, though the findings are controversial and may
- may cause diffusion hypoxia (Fink effect) at the be related to differences in FIO2 rather than to N2O itself.
end of surgery. Also used in the cryoprobe.
CVS: little effect on heart rate and BP usually, See also, Environmental safety of anaesthetists; Nitrogen,
although it decreases myocardial contractility, espe- higher oxides of; Pollution; Relative analgesia
cially when combined with volatile agents or opioids.
GIT: associated with PONV; possible causes include NIV, Non-invasive ventilation, see Nasal positive pres-
expansion of gas-containing bowel or inner ear sure ventilation
cavities or a direct central effect (possibly via opioid
receptors). Nizatidine. H2 receptor antagonist used in peptic ulcer
other: disease; similar to cimetidine but does not cause enzyme
- does not affect hepatic or renal function, nor inhibition. Well absorbed orally, it is 40% protein-bound,
uterine or skeletal muscle tone. with 90% excreted by the kidneys.
- interacts with methionine synthase; prolonged Dosage:
use may cause bone marrow depression, megalo- 150300mg orally od/bd.
blastic anaemia and peripheral neuropathy. 100mg iv over 15min tds, or 10mg/h iv up to
Implicated in causing fetal abnormalities and 480mg/day.
spontaneous abortion, but no direct evidence Side effects: as for ranitidine.
exists. Generally considered as being safe during
pregnancy. NMDA receptors, see N-Methyl-D-aspartate receptors
414 NMJ

NMJ, see Neuromuscular junction Features:

absence of fasciculation following administration of
NMR, Nuclear magnetic resonance, see Magnetic reso- drug.
nance imaging exhibits fade and post-tetanic potentiation.
antagonised by acetylcholinesterase inhibitors.

NO, see Nitric oxide potentiated by aminoglycosides, volatile inhala-

tional anaesthetic agents, acidosis, electrolyte
No reflow phenomenon. Reduction in organ blood disturbances (especially hypokalaemia, hypermag-
flow following a period of ischaemia or infarction, nesaemia, hypocalcaemia), myasthenia gravis,
without mechanical vessel obstruction. Has been myasthenic syndrome.
observed affecting the heart and brain, e.g. after MI/ Blockade may also be potentiated by excess drug at the
myocardial ischaemia and CVA/cerebral ischaemia neuromuscular junction, e.g. caused by overdose, or
respectively. The aetiology is unclear but small vessel reduced metabolism, excretion or muscle blood flow.
vasospasm, endothelial oedema or extrinsic compression See also, Neuromuscular blockade monitoring; Priming
by tissue oedema, increased blood viscosity, platelet principle
aggregation and venous congestion have all been sug-
gested. Treatment has been aimed at all these factors, Non-invasive positive pressure ventilation. An alter-
with varying degrees of success. native to IPPV via tracheal tube, positive pressure ven-
Rezkalla SH, Kloner RA (2002). Circulation; 105: tilation may be applied via a tightly fitting nasal mask,
65662 facial mask, nasal pillows that fit into the nostrils, or
a helmet that encloses the whole head. Ventilators
may deliver a set volume or, more commonly, a set
Nociceptin, see Orphanin FQ pressure. Uses include: ventilatory support in acute
respiratory failure (especially exacerbations of COPD
Nociception. Sensation of noxious stimuli, i.e. associ- and cardiogenic pulmonary oedema); facilitation of
ated with injury or threatened injury. extubation/weaning from ventilators; support for patients
Occurs via specialised nerve endings (nociceptors) of
requiring nocturnal IPPV (e.g. central sleep apnoea,
certain neurones: neuromuscular disorders); and palliation in end-stage
C-fibres: respond to heat, mechanical and chemical respiratory disease.
stimuli, giving rise to pain. Action potentials gener- Indications for use in the acute setting:
ated by these stimuli are thought to be generated increased dyspnoea, tachypnoea and work of
via the transient receptor potential vanilloid breathing.
receptor-1 (TRPV1) receptor channels. acute respiratory acidosis.
They also respond to endogenous pain-producing hypoxaemia despite conventional oxygen therapy.
substances, e.g. bradykinin, histamine and potas- Contraindications:
sium ions. Because of their responsiveness to many inadequate mask fit, uncooperative patient.
stimuli, they are also known as polymodal haemodynamic instability, ongoing myocardial
nociceptors. ischaemia.
A-fibres: inability to protect airway (e.g. reduced conscious
- type I: respond to heat and mechanical stimuli, level, bulbar failure).
with high threshold. Thought to give rise to pain recent upper GIT/respiratory tract surgery.
from long-standing stimuli. BIPAP (bi-level positive airway pressure) refers to a
- type II: respond to heat and mechanical stimuli, technique in which two levels of positive pressure are
with fast response and low threshold. Thought to provided during inspiration and expiration. Airflow in
give rise to initial pain sensation. the patient circuit is sensed by a transducer and aug-
- receptors responding to cold and mechanical mented with a preset level of positive pressure. Cycling
stimuli, thought to give rise to pain associated between inspiratory and expiratory modes may be trig-
with cold. gered by the patients spontaneous breaths or according
Other types may also exist. Although initially described to a preset rate (cycling either fully automatically or only
and most abundant in skin, they also exist in other if the patient fails to take a spontaneous breath within a
tissues, e.g. muscle, joints, teeth. Injury increases their certain time period). CPAP may also be delivered in
response and sensitivity. either mode. BIPAP may also be administered via an
See also, Pain; Pain pathways oral mask.
Disadvantages and complications include discomfort,
Nodal arrhythmias, see Junctional arrhythmias gastric distension, vomiting and aspiration of gastric
contents, and pressure necrosis, e.g. to the bridge of
Non-depolarising neuromuscular blockade. Caused the nose.
by competitive antagonism of acetylcholine (ACh) by Nava S, Hill N (2009). Lancet; 374: 2509
non-depolarising neuromuscular blocking drugs at the
ACh receptors of the neuromuscular junction. The Non-parametric tests, see Data; Statistical tests
end-plate potential produced by ACh diminishes as
receptor occupancy by the neuromuscular blocking drug Non-rebreathing valves. Prevent exhaled gas from
increases; when it fails to reach the threshold for depo- passing upstream from the patient in anaesthetic breath-
larisation, neuromuscular transmission fails. This only ing systems, thus almost eliminating rebreathing (but
occurs when >8090% of ACh receptors are blocked, reducing efficiency because dead space gas is wasted).
demonstrating the wide margin of safety of neuromus- Most commonly used in draw-over techniques and for
cular transmission. CPR with self-inflating bags. Also used in demand
 Non-steroidal anti-inflammatory drugs 415

(a) (b) (c)

Mushroom valves For anaesthetic use FGF Bobbin

FGF FGF
Rubber

Expiratory Rubber
valve
Patient Patient Patient

Fig. 120 Examples of non-rebreathing valves: (a) Ambu-E; (b) Laerdal; (c) Ruben. FGF, fresh gas flow

valves. For use with a fixed fresh gas supply, a reservoir Effects are via inhibition of cyclo-oxygenase, resulting in
bag is required unless fresh gas flow rate exceeds peak reduced prostaglandin, prostacyclin and thromboxane
inspiratory flow rate. Should be placed as near to the production (see Fig. 15; Arachidonic acid). Inhibitors of
patient as possible, e.g. attached directly to the facemask/ cyclo-oxygenase-2 (COX-2) (e.g. parecoxib, celecoxib)
tracheal tube. have been produced for their relative lack of GIT side
Valves may be designed for either spontaneous ven- effects.
tilation or IPPV; commonly used ones may be used Side effects:
for both, and include: GIT disturbance, e.g. nausea, discomfort, diarrhoea,
Ambu-E valve (Fig. 120a): contains silicone rubber bleeding and ulceration (for the non-selective
flaps (mushroom valves) within a clear plastic NSAIDs, the risks are greatest with azapropazone
housing. Those designed for CPR contain one and least with ibuprofen; piroxicam, ketorolac,
mushroom valve; those for anaesthetic use contain naproxen, indometacin and diclofenac are interme-
a second distal one to prevent in-drawing of diate. The selective COX-2 inhibitors are associated
room air. with a lower risk than non-selective NSAIDs).
Laerdal valve (Fig. 120b): contains a circular sili- renal impairment (may occur with both selective
cone rubber internal valve and a ring-shaped rubber and non-selective NSAIDs); may arise from:
expiratory valve. - renal hypoperfusion: especially common in
Ruben valve (Fig. 120c): contains a bobbin which is patients with sodium depletion (e.g. those taking
held against the upstream port by a spring at rest diuretics), hypovolaemia or pre-existing renal
and moved downstream by gas flow during disease. Results from inhibition of protective
inspiration. prostaglandin-mediated renal vasodilatation;
Malfunction (e.g. due to condensation of water vapour) usually occurs soon after administration of the
may cause sticking of the valve or rebreathing. Baro- NSAID, in most cases with recovery following
trauma may occur if high internal pressure holds the discontinuation. May progress to acute tubular
expiratory port closed, e.g. during apnoea with high fresh necrosis.
gas flow. - acute interstitial nephritis: typically occurs after
[Ambu: from ambulant, Danish for movable; Asmund S chronic administration, with slow recovery in
Laerdal (19131981), Norwegian businessman and most cases after discontinuation. Has also been
manufacturer; Henning M Ruben (19142004), Danish reported after acute perioperative use. Acute
anaesthetist] kidney injury may result, usually associated with
severe proteinuria. Corticosteroids have been
Non-steroidal anti-inflammatory drugs (NSAIDs). suggested as being helpful.
Group of chemically dissimilar compounds with anti- - systemic vasculitis (rare) leading to glomerulone-
inflammatory, antipyretic and analgesic actions. Widely phritis and papillary necrosis.
used for mild pain (e.g. musculoskeletal disease, head- decreased platelet function and impaired coagula-
ache, dysmenorrhoea), inflammatory disorders (espe- tion. Although platelet dysfunction has been shown
cially musculoskeletal) and postoperative analgesia. after perioperative use, bleeding problems are rare,
Individual responses to NSAIDs are variable and many although care is required if other drugs with antico-
drugs may have to be tried before achieving optimal agulant actions are co-prescribed, e.g. prophylactic
benefit. heparin. The selective COX-2 inhibitor rofecoxib
Classified into: was withdrawn in 2004 because it was associated
salicylic acids: e.g. aspirin, benorilate, diflunisal. with an increased incidence of cardiovascular side
propionic acids: e.g. fenbufen, ibuprofen, naproxen. effects, particularly MI, that was originally attrib-
acetic acids: e.g. diclofenac, indometacin. uted in early studies to a cardioprotective effect of
fenamates: mefenamic acid, flufenamic acid. naproxen in the control group. The mechanism is
pyrazolones: e.g. phenylbutazone, azapropazone. thought to be unequal inhibition of prostacyclin and
oxicams: e.g. piroxicam, tenoxicam, meloxicam. thromboxane synthesis.
pyrroles: e.g. ketorolac. may exacerbate asthma.
416 Noradrenaline

adverse drug reactions are common (cross- mucous lining which traps particles larger than 46 m,
sensitivity may occur between different drugs). sweeping them back to the pharynx. Sneezing also rids
others, e.g. fluid retention, hyperkalaemia and meta- the nose of irritants.
bolic acidosis (via inhibition of renin secretion with Divided into:
resultant hypoaldosteronism), rarely hepatotoxicity. external nose:
NSAIDs have been implicated in reducing bone - bones:
healing after fractures, leading some orthopaedic - nasal part of frontal bones.
surgeons to suggest they should be avoided periop- - frontal process of maxillae.
eratively, but the evidence is weak and they con- - nasal bones.
tinue to be used widely. - cartilages (lower part and septum).
Evidence suggests that NSAIDs reduce opioid require- - fibrofatty tissue (ala).
ments when used intra-/postoperatively. Should be used nasal cavity: subdivided by the septum into two
cautiously if there is a risk of increased perioperative separate compartments, opening anteriorly by the
bleeding or renal impairment (the latter, for instance, in nares and posteriorly by the choanae. The small
the elderly, diabetics, and after cardiac, hepatobiliary, dilatation immediately within the nares (vestibule)
renal or major vascular surgery) or sensitivity to aspirin. is lined with stratified squamous epithelium bearing
Postoperative renal dysfunction and GIT ulceration/ hairs and sebaceous and sweat glands. The remain-
bleeding should lead to cessation of therapy. der is lined with columnar ciliated cells and mucus-
secreting goblet cells. Subdivided into:
Noradrenaline (Norepinephrine). Catecholamine, the - roof: slopes upwards and backwards forming the
immediate precursor of adrenaline (differing by one bridge of the nose; it then has a horizontal part
methyl group on the terminal amine). A neurotransmit- (cribriform plate of the ethmoid bone) and finally
ter in the sympathetic nervous system, ascending reticu- a downward sloping part (palatine bone).
lar activating system and hypothalamus. Also a hormone, - floor: composed of the palatine process of the
forming about 20% of the catecholamines released from maxilla and horizontal plate of the palatine bone.
the adrenal medulla. A tissue flap (soft palate) extends into the naso-
Predominantly stimulates -adrenergic receptors pharynx, closing off the nasal passages during
(non-selectively), although with some 1-receptor swallowing.
stimulation. After secretion, 80% is taken up by post - medial wall: nasal septum.
ganglionic sympathetic nerve endings for reuse - lateral wall: ethmoidal labyrinth, nasal surface of
(uptake1); the remainder is metabolised by catechol-O- the maxilla and perpendicular plate of the pala-
methyltransferase and monoamine oxidase or taken up tine bone. The three scroll-like conchae hang
by other cells, e.g. vascular smooth muscle (uptake2). down over the nasal meatus. The olfactory organ
Used as an inotropic drug when SVR is low, e.g. in of the first cranial nerve lies above and beside
sepsis. An extremely potent vasopressor drug, it increases the upper concha. The orifices of the maxillary,
both systolic and diastolic arterial BP via arterial and sphenoid, frontal and ethmoidal sinuses open on
venous vasoconstriction. There may be compensatory to the lateral nasal wall.
bradycardia caused by baroreceptor reflex activation. Blood supply:
Coronary perfusion is increased but with increased myo- upper: anterior and posterior ethmoidal branches
cardial O2 demand. Cardiac output may increase or of the ophthalmic artery.
decrease depending on clinical circumstances. Cerebral lower: sphenopalatine branch of the maxillary
blood flow and O2 demand may fall. Although hypoten- artery.
sion may be corrected, renal and mesenteric vasocon- anteroinferior septum: septal branch of the superior
striction may reduce renal blood flow. labial branch of the facial artery.
Supplied commercially as noradrenaline tartrate. Venous drainage is via a submucous plexus which
Dosage: 0.030.2g/kg/min via a central vein, drains into the sphenopalatine, facial and ophthalmic
although higher doses may be needed in sepsis. veins.
Tachyphylaxis may occur. Tissue necrosis may follow Nerve supply is from branches of the ophthalmic (V1)
extravasation. and maxillary (V2) divisions of the trigeminal nerve:
skin:
Norepinephrine, see Noradrenaline - supratrochlear branch of the frontal nerve (V1).
- anterior ethmoidal branch of the nasociliary
Normal distribution, see Statistical frequency nerve (V1).
distributions - infraorbital branch of V2.
maxillary antrum: V2 via sphenopalatine ganglion.
Normal solution. One containing 1 gram equivalent frontal sinus: frontal nerve (V1).
weight of substance per litre. So-called normal saline ethmoid region: anterior and posterior branches of
solution (0.9%) is incorrectly described, being less than the nasociliary nerve (V1).
1/6 normal. nasal cavities:
See also, Equivalence - anterior: anterior ethmoidal branch of the naso-
ciliary nerve (V1).
Noscapine, see Papaveretum - posterior: short sphenopalatine and posterior
nasal branches of V2 (septum); long sphenopala-
Nose. Entrance to the pharynx and thence larynx and tine branch (lateral wall).
lungs. Apart from its olfactory role, it filters, humidifies Trauma to the nose may result from passage of a
and warms inspired air with its extensive vascular sur- tracheal or nasogastric tube, or nasal airway. Resultant
faces (turbinates and septum). Filtering relies on the epistaxis may be severe, and may be reduced by prior
 Notifiable diseases 417

administration of cocaine spray or paste, or other vaso- other patients.

pressor solutions, e.g. xylometazoline 0.1%. hospital staff (inadequate hygiene).
For topical anaesthesia of the nose, many techniques Other contributing factors include:
have been described. Moffetts method is one of the patients age and general medical condition.
best known: drugs (e.g. antacids, corticosteroids, H2 receptor
solution consists of 2ml 8% cocaine, 2ml 1% antagonists, sedatives, broad-spectrum antibiotics).
sodium bicarbonate and 1ml 1:1000 adrenaline. supine position.
one-sixth of the solution is instilled into each nostril aspiration of gastric contents.
and retained for 10min in each of the following reintubation.
positions: right lateral head-down, face-down, and Typical pathogens include:
left lateral head-down. Streptococcus pneumoniae.
Other techniques involve application of 810% Haemophilus influenzae.
cocaine or other agent plus 1:200000 adrenaline swabs Staphylococcus aureus.
to the anterior septum and posterior nasal cavity. Gram-negative bacilli.
Maxillary and ophthalmic nerve blocks may be used for Often more than one organism is involved.
operations on or around the nose. Approaches to clinical diagnosis vary but criteria
[Arthur J Moffett (19041995), Birmingham include new, progressive or persistent CXR abnormali-
otolaryngologist] ties, with evidence of infection (e.g. purulent sputum,
See also, Choanal atresia; Ear, nose and throat surgery hypo- or hyperthermia, and a low [< 5000/mm3] or raised
[> 10000/mm3] white cell count). Isolation of the respon-
Nosocomial infection. Infection acquired as a result sible organism(s) is best undertaken using bronchoal-
of a patients admission to hospital. Occurs in up to 10% veolar lavage, either blind or via fibreoptic bronchoscopy.
of patients, with mortality of up to 5%. More common Therapy should be organism-specific when possible, but
in the acutely ill (e.g. on ICU). broad-spectrum antibiotics are frequently necessary
Aetiology may be related to: until the organism is identified.
hospital factors: widespread presence of pathogens, Prevention is assisted by:
poor general hygiene and transfer between staff vaccination, e.g. against Haemophilus influenzae,
and patients. pneumococcus and influenza virus.
patient factors: increasingly elderly population with hygiene, e.g. hand-washing policies, removal of
reduced resistance, immunodeficiency states, diabe- wrist-watches, use of gloves.
tes, smoking, malnutrition, alcoholism, trauma and control of gastric pH (avoidance of alkaline pH
drug therapy. reduces bacterial overgrowth).
interventions: surgery, tracheal intubation, catheter- control of gastric volume and motility (distension
related sepsis, bladder catheterisation, use of broad- risks reflux and aspiration).
spectrum antibacterial drugs resulting in resistant rotational therapy.
organisms, blood transfusion, TPN or stress ulcer good airway protocols, e.g. avoiding nasal intuba-
prophylaxis. tion (risks sinusitis) and the supine position (patients
Sites of infection in order of decreasing frequency: should be nursed 30 head-up), regular aspiration
urinary tract infection, surgical wound infection, noso of subglottic secretions.
comial pneumonia and bacteraemia. Organisms most selective decontamination of the digestive tract,
commonly involved in order of decreasing frequen although this remains controversial except in
cy: Staphylococcus aureus, pseudomonas, coagulase- trauma.
negative staphylococci, candida species and Escherichia Torres A, Ferrer M, Badia JR (2010). Clin Infect Dis; 51
coli. Fungal infection is especially common in immuno- Suppl 1:S4853
suppressed patients. See also Infection control; Nosocomial infection; Sepsis;
Management: Ventilator-associated pneumonia
prevention:
- effective infection control. Use of care bundles. Notifiable diseases. Diseases that an attending doctor
- selective decontamination of the digestive tract is required by law to report to the local authority proper
may be appropriate in certain circumstances. officers, usually via the consultant in communicable
source control (e.g. debridement of infected wounds,
disease or chief environmental health officer. The scheme
removal of infected catheters). allows epidemiological surveillance and early identifica-
treatment with appropriate anti-infective agents by
tion of potential epidemics (Table 32). Failure to send
the use of antimicrobial stewardship programmes.
Vincent JL (2003). Lancet; 361: 206877 Table 32 Notifiable diseases in the UK
See also, Ventilator-associated pneumonia
Acute encephalitis Measles Scarlet fever
Acute poliomyelitis Meningitis Smallpox
Nosocomial pneumonia. Hospital-acquired chest
Anthrax Meningococcal TB
infection occurring > 48h after hospital admission; Cholera septicaemia Tetanus
excludes infections incubating on admission. May occur Diphtheria Mumps Typhoid fever
in up to 25% of ICU patients and increases hospital Dysentery Ophthalmia neonatorum Typhus
mortality, length of stay and costs. Food poisoning Paratyphoid fever Viral haemorrhagic
Originates from: Leprosy Plague fever
micro-aspiration of oropharyngeal flora. Leptospirosis Rabies Viral hepatitis
environment (air, water, food, etc.). Malaria Relapsing fever Whooping cough
equipment (tracheal tubes, suction catheters, bron- Rubella Yellow fever
choscopes, etc.).
418 Novoseven

details of the case on a certificate may result in convic- patients needed to receive a drug before one suffers a
tion and a fine. complication.
See also, Meta-analysis; Odds ratio; Relative risk
Novoseven, see Eptacog alfa reduction

NPSA, see National Patient Safety Agency Nurses, prescription of drugs by. In the UK, specially
trained nurses have been able to prescribe from a limited
NRP, see Neonatal Resuscitation Program formulary since 1998; from 2006, regulations allowed
certain nurses (and pharmacists) to prescribe any
NSAIDs, see Non-steroidal anti-inflammatory drugs licensed drug (including opioids) so long as it is within
their specific competence and local clinical governance
NSTEACS, non-ST segment elevation acute coronary frameworks. Other nurses and pharmacists are able to
syndromes, see Acute coronary syndromes prescribe within specific management plans drawn up by
a doctor for individual cases. Likely to have most rele-
NSTEMI. non-ST segment elevation myocardial vance to acute and chronic pain management, premedi-
infarction, see Acute coronary syndromes; Myocardial cation and intensive care.
infarction See also, Midwives, prescription of drugs by

Nuclear cardiology. Assessment of cardiac function Nutrition. An adequately balanced daily supply of
using gamma cameras to trace radioisotopes.Technetium- carbohydrates, fats, proteins, vitamins, electrolytes,
99m-labelled blood may be followed through the heart trace elements and water is essential to maintain
during first pass of a bolus, or over many cardiac cycles normal health.
linked to the ECG (multigated acquisition imaging; Average normal adult daily requirements:
MUGA). Individual chamber movement and valve func- water: 3040ml/kg.
tion may be observed, and ejection fraction calculated nitrogen: 0.2g/kg.
by recording the number of counts in systole and dias- energy: 3040 Cal/kg.
tole. Alternatively, the uptake of thallium-201 by cardiac electrolytes:
tissue may be observed (uptake by normal myocardium - sodium: 1mmol/kg.
is proportional to blood flow). Thallium scanning may - potassium: 1mmol/kg.
be enhanced by giving intravenous dipyridamole to pre- - chloride: 1.5mmol/kg.
cipitate ischaemia by causing coronary steal. Recently - phosphate: 0.20.5mmol/kg.
infarcted myocardium may be labelled with technetium- - calcium: 0.10.2mmol/kg.
99m pyrophosphate. Other tracers used to identify areas - magnesium: 0.10.2mmol/kg.
of infarction, necrosis or inflammation include indium- trace elements:
111, gallium-67 citrate, and radiolabelled myosin-specific - iron: 0.2mg/kg.
antibodies. - zinc: 0.2mg/kg.
- selenium: ~ 1g/kg.
Nuclear magnetic resonance, see Magnetic resonance vitamins: vary from under 0.1g/kg to 1.0mg/kg (see
imaging Table 43; Vitamins).
Energy requirements depend on the particular circum-
Null hypothesis. In statistics, the assumption that the stances for each individual, e.g. they increase after
observed frequency of an event equals the expected trauma and burns (see Catabolism), and with pyrexia (by
frequency. It may state that any observations are due about 10% for every C above normal). Patients should
to chance alone, or that the groups studied come from be fed via the oral route if possible, preferably with
the same population; statistical tests aid the acceptance normal food.
or rejection of this hypothesis (and whether an alterna- For critically ill patients, more precise estimation of
tive hypothesis, e.g. that observed differences are caused energy balance is necessary, whatever the route of
by treatment, can be accepted). In traditional hypothe- administration. Once energy requirements have been
sis testing, results are expressed in terms of the proba- determined, it is divided into carbohydrate (4 Cal/g) and
bility that the null hypothesis is true for the case fat (9 Cal/g) components to accompany nitrogen (150
concerned. 200 Cal/g nitrogen). Carbohydrate should comprise 40
See also, Confidence intervals; Statistical significance 50% of energy requirements. Appropriate enteral or
parenteral solutions are then selected from commer-
Number needed to treat (NNT). Indicator of treat- cially available products (some pharmacies make up
ment effect in clinical trials. The inverse of absolute their own solutions), satisfying requirements for energy,
risk reduction, it gives the number of patients that fluid and electrolytes. Vitamins may be added as required.
need to be treated in order to prevent a specified unde- Bistrian BR, McCowen KC (2006). Crit Care Med; 34:
sirable outcome (e.g. PONV). For example, for an anti- 152531
emetic with NNT for PONV of 5, one needs to treat five See also, Malnutrition; Metabolism; Nitrogen balance;
patients with the drug in order to prevent one patient Nutrition, enteral; Nutrition, total parenteral
suffering PONV. Combines both the efficacy of the drug
and the incidence of the condition treated; for example, Nutrition, enteral. Feeding via the GIT. Ideal route is
an antiemetic that is effective in 100% of patients will by mouth using normal or liquidised food and calorific/
have a NNT of 5 if the incidence of PONV is 1:5, but if protein supplements, if necessary. Commonly performed
it is only 50% effective (or the incidence of PONV falls via fine-bore nasogastric tubes on ICU. Alternatives
to 1:10) the NNT will be 10. Number needed to harm include a nasojejunal feeding tube (using a weighted
(NNH) is a similar concept, indicating the number of tube or passed via endoscopy), percutaneous endoscopic
 Nystatin 419

gastrostomy or a jejunostomy tube placed at the time of 1050%, and requires central venous infusion to avoid
surgery. venous thrombosis. Other energy sources have also been
In patients with adequate GIT function, it is prefer- used, e.g. sorbitol, xylitol and ethanol. Insulin is usually
able to TPN as it is more physiological, provides protec- required to control hyperglycaemia associated with
tion against stress ulcers, maintains intestinal barrier glucose-rich infusions. Tight glycaemic control is no
integrity (thus reducing bacterial translocation) and pro- longer recommended as it is associated with greater
motes biliary flow, preventing the cholestasis commonly morbidity secondary to hypoglycaemia. Fat is usually
seen with TPN. administered as 10 or 20% soya bean oil emulsions;
Principles are those of nutrition generally. Carbohy- allergic reactions may occur rarely with the 20% prepa-
drate is the usual energy source in most enteral feeds, ration. Trace elements and vitamins must be added.
but high concentrations increase osmolality, causing Most solutions are administered from one large bag
diarrhoea. The protein source is usually whole protein, via a pump and a single dedicated central venous
although preparations containing oligopeptides or cannula, although a peripheral line is acceptable for tem-
amino acids are useful in pancreatic disease and malab- porary infusion of fat emulsion.
sorption syndromes. Medium chain triglycerides are the The patient should be encouraged to mobilise to
usual source of fat. Most feeds also contain fibre. prevent muscle breakdown.
Complications: Complications:
mechanical, e.g. tube blockage, passage of the tube those associated with central venous cannulation.
into the trachea, regurgitation. sepsis.
nausea and vomiting: occur in 10% of cases; may metabolic disorders:
require antiemetic drugs or prokinetic drugs. - hyperglycaemia.
diarrhoea: occurs in up to 60% of cases; may be - refeeding syndrome with hypophosphataemia,
caused by intolerance of high osmotic load, underly- hypokalaemia and hypomagnesaemia.
ing bowel disorder, contaminated feed or concur- - metabolic acidosis.
rent antibacterial drug therapy. Administration of - hypernatraemia.
pre- and probiotic supplements may be beneficial. - lipaemia.
refeeding syndrome. - trace element or vitamin deficiency.
electrolyte and liver function test abnormalities. cholestasis resulting in acute cholecystitis.
Zaloga GP (2006). Lancet; 367: 110111 Routine monitoring should include:
See also, Energy balance; Nutrition, total parenteral clinical signs, weight and fluid balance daily.
Skinfold thickness and arm circumference have
Nutrition, total parenteral (TPN). Administration of been used.
total nutritional requirements by iv infusion; it may be plasma urea, creatinine, electrolytes and osmolarity
required in patients who are hypercatabolic and/or have daily. Glucose should be measured more frequently.
an abnormal GIT. Commonly required in critically ill Liver function and plasma calcium, phosphate and
patients on ICU with abdominal pathology or multior- magnesium should be assessed at least twice a week.
gan failure. Only indicated if enteral nutrition fails to urine urea and osmolarity daily.
deliver requirements or is impossible to use. May also be full blood count every 13 days; prothrombin time
used to support enteral nutrition. once a week. Iron, folate and vitamin B12 should be
Principles are those of nutrition generally, i.e. measured at least weekly.
calculation of nitrogen balance, energy and fluid require- Blackburn GL, Wollner S, Bistrian BR (2010). Arch
ments. Nitrogen and the energy source should be given Surg; 145: 5338
together, preferably continuously. 56mmol potassium See also, Energy balance; Nutrition, enteral
and 12mmol magnesium are required per gram of
nitrogen. Nystatin. Polyene antifungal drug, principally used for
The nitrogen component is given as mixtures of treatment of Candida albicans infections of skin, mucous
essential and non-essential amino acids (the nitrogen membranes and GIT. Not absorbed when administered
content varies considerably between different solutions). by mouth and too toxic for parenteral use. Available as
Some amino acid solutions contain electrolytes and most tablets, oral suspension, cream or pessaries.
are hypertonic. Some contain energy sources, e.g. glucose Dosage (adults and children): 100000 units orally qds.
and fructose. Carbohydrate is usually given as glucose Side effects: GIT upset, rash.
 O
Obesity. Common and increasing problem in the Anaesthetic considerations:
Western world. Usually defined according to body mass preoperatively:
index (see Table 12; p 79). Approximately 20% of UK - preoperative assessment for the above complica-
adults are obese by this definition and this number has tions and appropriate management. Patients
trebled in the last 20 years. Morbid obesity is defined as may be taking amfetamines or other drugs for
twice ideal body weight and affects 1% of the popula- weight loss.
tion; general mortality in this group is twice that of - low-mw heparin prophylaxis is routine, because
normal. Distribution of fat is thought to be more impor- patients are less mobile and risk of DVT is
tant than weight per se, with abdominal deposition par- increased. The ideal prophylactic dose is not
ticularly detrimental. Thus for a BMI 25kg/m2, a waist certain in morbidly obese patients, but suggested
(just above the navel) circumference of 94cm indi- regimens include enoxaparin 40mg sc bd or
cates increased risk and 102cm substantially increased 0.5mg/kg od. Intermittent pneumatic calf com-
risk for men; corresponding values for women are 80cm pression should be used if possible.
and 88cm respectively. - im injection may be difficult because of subcuta-
Effects: neous fat, while anti-DVT stockings may not fit.
RS: perioperatively:
- increased body O2 demand and CO2 production, - veins may be difficult to find and cannulate.
because of increased tissue mass. Minute ven - hiatus hernia is common, with risk of aspiration
tilation required to maintain normocapnia is of gastric contents. Volume and acidity of gastric
thus increased, which further increases O2 contents may be increased. In addition, tracheal
demand. intubation may be difficult: insertion of the laryn-
- reduced FRC because of the weight of the chest goscope blade into the mouth may be hindered,
wall. FRC is especially reduced in the supine posi- the neck may be short and movement reduced.
tion, due to the weight of the abdominal wall and - hypoxaemia may occur rapidly during apnoea,
contents. Thoracic compliance is thus reduced, since FRC (hence O2 reserve) is reduced, and O2
increasing work of breathing and O2 demand. consumption increased. FRC is increased if the
V/Q mismatch results in hypoxaemia. patient is positioned head-up before induction of
- hypoxic pulmonary vasoconstriction increases anaesthesia.
work of the right ventricle and may lead to pul- - airway maintenance is often difficult, because of
monary hypertension and right-sided cardiac increased soft tissue mass in the upper airway.
failure. Spontaneous ventilation is often inadequate
- obstructive sleep apnoea and alveolar hypoventi- because of respiratory impairment, which worsens
lation syndrome may occur. in the supine position (especially in the head-
CVS: down position or with legs in the lithotomy posi-
- cardiac output and blood volume increase, to tion). Thus IPPV is usually employed; high
increase O2 flux. inflation pressures may be required.
- hypertension occurs in 60%; thus left ventricular - transferring and positioning the patient may be
work is increased. Left ventricular hypertrophy difficult. The typical maximum weight limit for
and ischaemia may occur, with resultant left-sided manual operating tables is 135kg, and for electri-
cardiac failure. Arrhythmias are common. cal operating tables is 250300kg. Two operating
- ischaemic heart disease is common due to hyper- tables placed side by side may be necessary if the
cholesterolaemia, hypertension, diabetes mellitus patient is too wide for a single table.
and physical inactivity. - monitoring may be difficult, e.g. BP cuff too small,
other diseases are more likely, e.g. non-insulin- small ECG complexes.
dependent diabetes mellitus (caused by insulin - surgery is more likely to be difficult and pro-
resistance and inadequate insulin production, the longed, with increased blood loss.
latter worsening with age), hypercholesterolaemia, - drug use:
gout and arthritis, gallbladder disease, hepatic - appropriate dosage may be difficult; e.g. neuro-
impairment due to fatty liver and cirrhosis, CVA, muscular blocking drugs are given according to
breast and endometrial malignancies. lean body weight. Factors affecting drug phar-
Patients may present for bariatric surgery or other macokinetics include: changes in the volume of
procedures. The former is usually done laparascopically distribution due to decreased fraction of total
and includes gastric banding, partial gastrectomy and body water, increased fatty tissue and increased
gastric bypass, as single procedures or in combination. lean body mass; increased drug clearance due to

421
422 Obesity hypoventilation syndrome

increased renal blood flow, increased GFR and administered the first obstetric anaesthetic in 1847,
tubular secretion; changes in plasma protein using diethyl ether. He used chloroform later that year,
drug binding. subsequently preferring it to ether. Moral and religious
- increased metabolism of inhalational anaes- objections to anaesthesia in childbirth declined after
thetic agents is thought to occur, e.g. increased Snows administration of chloroform to Queen Victoria
fluoride ion concentrations after prolonged use in 1853. Regional techniques were introduced from the
of enflurane. early 1900s, and have become increasingly popular since
- although regional techniques may have potential the 1960s.
advantages over general anaesthesia, they are Choice of technique is related to the physiological
often technically difficult. effects of pregnancy (especially risk of aortocaval com-
postoperatively: pression and aspiration pneumonitis), and effects of
- atelectasis and hypoventilation are common, with drugs and complications on the fetus, neonate and
increased risk of infection, hypoxaemia and respi- course of labour. Anaesthesia has until the last 2030
ratory failure. Patients are often best nursed years been a major cause of maternal death, as revealed
sitting. Elective non-invasive positive pressure in the Reports on Confidential Enquiries into Maternal
ventilation may be beneficial. Difficulty mobilis- Deaths.
ing may be a problem. Methods used:
- postoperative analgesia, O2 therapy and physio- non-drug methods, e.g. TENS, acupuncture, hypno-
therapy are especially important. CPAP therapy sis, psychoprophylaxis, audioanaesthesia (white
for obstructive sleep apnoea should be restarted noise; high-frequency sound played through
in the immediate postoperative period. HDU or headphones), abdominal decompression (applica-
ICU admission is often required. tion of negative pressure to the abdomen): gener-
Similar considerations apply to admission of obese ally safe for mother and fetus, but of variable
patients to ICU for non-surgical reasons. efficacy and thus rarely used, except for TENS and
Cheah MH, Kam PCA (2005). Anaesthesia; 60: psychoprophylaxis.
100921 systemic opioid analgesic drugs:
- morphine was used with hyoscine to provide
Obesity hypoventilation syndrome (Pickwickian syn- twilight sleep in the early 1900s. However, it
drome, after a character from Dickens Pickwick Papers). readily crosses the placenta to cause neonatal
Obesity, daytime hypersomnolence, hypoxaemia and respiratory depression. Pethidine was first used in
hypercapnia, often in the presence of right ventricular 1940 and approved for use by UK midwives in
failure. Causes are multifactorial: 1950; it is the most commonly used opioid (e.g.
most patients have restrictive lung disease, resulting 50150mg im up to two doses), but some units
in poor compliance, increased work of breathing, prefer diamorphine. 3075% of women gain no
alveolar hypoventilation and increased CO2 pro- benefit from pethidine and there is little evidence
duction. Pulmonary hypertension is present in 60% that opioids actually reduce pain scores. Nausea,
of patients. vomiting, delayed gastric emptying and sedation
patients often have coexisting V/Q mismatch. may occur, with neonatal respiratory depression
Cyanosis and plethora are common, due to polycy- especially likely 24hafter im injection. Neona-
thaemia secondary to hypoxia. tal respiratory depression is marked after iv
severe obstructive sleep apnoea is almost invari- injection. Subtle changes may be detected on
able. In addition there is a disordered central control neurobehavioural testing of the neonate.
of breathing, possibly due to leptin deficiency or - other opioids have been used with similar effects.
resistance. Control is especially poor during sleep A lower incidence of neonatal depression has
and sudden nocturnal death is common. been claimed for partial agonists and agonist/
General and anaesthetic management is as for obesity antagonists (e.g. nalbuphine, pentazocine, mep-
and cor pulmonale. The FIO2 should be increased cau- tazinol), but they are not commonly used.
tiously to avoid depression of the hypoxic ventilatory - patient-controlled analgesia has been used, e.g.
drive. CPAP may be useful to reduce hypercapnia and pethidine 1020mg iv or nalbuphine 23mg iv
normalise O2 saturations. Respiratory depressant drugs (10min lockout), or fentanyl 1025g following
should also be used cautiously; postoperative respiratory 2575g loading dose (35min lockout). More
failure may occur. recently, remifentanil has been used (e.g. 3040g
[Charles Dickens (18121870), English author] bolus, 23min lockout), though severe respira-
Piper AJ, Grunstein RR (2011). Am J Respir Crit Care tory depression has been reported.
Med; 183: 2828 - opioid receptor antagonists, e.g. naloxone, may be
required if neonatal respiratory depression is
Obstetric analgesia and anaesthesia. Strictly, analge- marked.
sia refers to removal of pain during labour and anaes- sedative drugs: rarely used nowadays; promazine,
thesia is provided for operative delivery and other promethazine, benzodiazepines, chloral hydrate,
procedures. Pain during the first stage of labour is clomethiazole and chlordiazepoxide have been
thought to be caused by cervical dilatation, and is usually used. All may cause neonatal depression.
felt in the T11L1 dermatomes. Back and rectal pain inhalational anaesthetic agents:
may also occur. Pain often worsens at the end of the - ether and chloroform were first used in 1847.
first stage. Pain during the second stage is caused by Trichloroethylene was used in the 1940s, and
stretching of the birth canal and perineum. methoxyflurane in 1970; formerly approved for
Early attempts at pain relief included the use midwives use with draw-over techniques, their
of abdominal pressure, opium and alcohol. Simpson use in the UK ceased in 1984.
 Obstetric analgesia and anaesthesia 423

- N2O was first used in 1880. Intermittent-flow - motor block may be distressing, and if extensive
anaesthetic machines were developed from the may be associated with delayed descent of the
1930s, using N2O with air or O2. Entonox was used fetal head.
in 1962 by Tunstall, and approved for use by mid- - requires iv cannulation (although the need for
wives in 1965. It is usually self-administered using routine administration of iv fluids has been
a face-piece or mouthpiece and demand valve. questioned if low-dose techniques are used.
Slow deep inhalation should start just before a - requires 24-h dedicated anaesthetic cover.
contraction begins, in order to achieve adequate - increased incidence of backache has been
blood levels at peak pain. May cause nausea and reported, but this has been shown to reflect
dizziness; it is otherwise relatively safe with selection of patients prone to backache (e.g.
minimal side effects, although maternal arterial complicated labour, lower pain threshold), plus
desaturation has been reported, especially in the tendency of patients to link back pain with
combination with pethidine. Useful in 50% of any procedure performed on the back, rather
women but of no help in 30% and, like opioids, than a result of regional analgesia or anaesthe-
there is little evidence that it reduces pain scores. sia itself.
Isoflurane has been added with good effect - effect on labour:
(Isoxane). - temporary reduction in uterine activity has
- enflurane, isoflurane, desflurane and, more been reported following injection of solution,
recently, sevoflurane have been used with draw- though this may be caused by the bolus of
over inhalation. crystalloid traditionally given concurrently.
general anaesthesia: no longer used for normal - incoordinate uterine activity may improve.
vaginal delivery. Problems are as for caesarean - ventouse/forceps rate is increased; thought
section. to occur because:
regional techniques: involve blockade of the nerve - patients likely to require forceps delivery
supply of: are more likely to receive epidural
- uterus: analgesia.
- via sympathetic pathways in paracervical tissues - muscle tone is reduced, as above.
and broad ligament to the spinal cord at T1112, The relative importance of these two factors
sometimes T10 and L1 also. is hotly disputed, with non-anaesthetists
- the cervix is possibly innervated via separate claiming that epidurals cause an increase in
S24 pathways in addition. instrumental delivery rates whilst anaesthe-
- birth canal and perineum: via pudendal nerves tists claim that epidural analgesia is merely a
(S24), genitofemoral and ilioinguinal nerves and marker of abnormal and/or high-risk labours.
sacral nerves. Randomised clinical trials are few and suffer
Regional techniques used: from practical problems such as lack of obstet-
epidural anaesthesia/analgesia: ric blinding and non-compliance with the allo-
- caudal analgesia was first used in obstetrics in cated treatment. The argument is therefore
1909 by Stoeckel; a continuous technique was likely to continue, although studies suggest
introduced in the USA in 1942. that low-dose techniques are more likely to
- continuous lumbar techniques were first used in result in spontaneous delivery than the older,
1946; they have become popular in the UK since higher-dose methods (though even with the
the 1960s, with most units now providing a 24-h latter, normal vaginal delivery rates are
service. Uptake varies widely, with up to 7080% thought to occur if adequate time is allowed
for primiparae in some centres. The overall epidu- for the second stage). Perineal tears may
ral rate in the UK is around 2030%. occur if the second stage is very prolonged.
- advantages: - technique:
- reduces maternal exhaustion, hyperventilation, - standard techniques are used, but low doses of
ketosis and plasma catecholamine levels. local anaesthetic agent are used to minimise
- avoids adverse effects of parenteral opioids. motor block and risk of adverse effects. If higher
- reduces fetal acidosis and maintains or increases doses are used, smaller volumes are required
uteroplacental blood flow if hypotension is because venous engorgement reduces the
avoided. volume of the epidural space. Hypotension is
- may improve contractions in incoordinate common with higher doses of local anaesthetic,
uterine activity. especially in the presence of hypovolaemia; it is
- thought to reduce morbidity and mortality in reduced by preloading with iv fluid, usually crys-
breech delivery, multiple delivery, premature talloid (e.g. 0.9% saline/Hartmanns solution,
labour, pre-eclampsia, maternal cardiovascular 500ml). L23 or L34 interspaces are usually
or respiratory disease, diabetes mellitus, forceps chosen, although, because identification of the
delivery and caesarean section. lumber interspaces by palpation is not reliable
- disadvantages: (especially in pregnancy when the pelvis tilts),
- risk of hypotension, extensive blockade, iv anaesthetists often place the catheter at a higher
injection and other complications. Post-dural interspace than that intended.
puncture headache is more common than in - bupivacaine is traditionally preferred, since
non-pregnant subjects following accidental fetal transfer is least. Others have been used, e.g.
dural tap (the maximum acceptable incidence lidocaine, chloroprocaine. Prilocaine is rarely
of the latter has been set at about 1% in the used because of the risk of methaemoglobinae-
UK). Shivering and urinary retention may occur. mia. Ropivacaine is claimed to cause less motor
424 Obstetric analgesia and anaesthesia

block than bupivacaine when higher concentra- blocks should be regularly assessed and an
tions are used. Levobupivacaine has a better anaesthetist should be readily available, with
safety profile, but with low-dose regimens this resuscitative drugs and equipment. Maximal
difference becomes less relevant. doses of local anaesthetic agents should not
- use of a test dose is controversial. With low-dose be exceeded in a 4-h period.
regimens, the first dose is also the test dose. Backache and neurological damage may
- suitable dose regimens: be caused by labour itself, although epidural
- bupivacaine 0.1% 1015ml with fentanyl analgesia is often blamed by the patient and
12g/ml as boluses. More concentrated solu- non-anaesthetic staff.
tions provide analgesia lasting slightly longer, spinal anaesthesia was first used in 1900. Popular in
but with more motor blockade. 0.75% solu- the USA in the 1920s, it only increased in popularity
tion is contraindicated in obstetrics. Manual in the UK towards the end of the 1900s. Technique
top-up injections are usually given by mid- and management are as standard, but with more
wives. Aspiration through the catheter should rapid onset of hypotension and greater incidence of
precede top-ups, which should be given in post-dural puncture headache and variable blocks
divided doses except for low-dose solutions. A (especially using plain bupivacaine) than in non-
maximum of 25mg bupivacaine has been sug- pregnant subjects. Dose requirements are reduced,
gested for any single injection. Ropivacaine possibly due to altered CSF dynamics, although
0.2% is an alternative. changes in CSF pH, proteins and volume have been
- infusions: provide more consistent analgesia, suggested. Effects are as for epidural anaesthesia.
with less motor block and hypotension Mostly used for caesarean section, forceps and ven-
than high-dose top-ups, and reduce the risk touse delivery and removal of retained placenta.
from accidental iv or subarachnoid injection. Doses for vaginal procedures: 1.01.6ml heavy
Bupivacaine 1020mg/h is usually employed, bupivacaine 0.5%; lower doses with opioids have
usually as a 0.10.2% solution, and often com- also been used.
bined with fentanyl 12g/ml. Large volumes CSE has been advocated because of its rapid onset
of more dilute solutions have been used, sup- and intense quality of analgesia (from the spinal
porting the concept of an extended sleeve component), with subsequent management as for
of anaesthetic solution over the appropriate epidural analgesia. Its routine place in labour is
segments. The height of the block must be controversial because of its increased cost, the
regularly assessed, and the infusion adjusted increased risk of post-dural puncture headache,
accordingly. damage to the conus medullaris and (theoretical)
- patient-controlled epidural analgesia is also concerns over increased risk of infection. In addi-
used, e.g. with 0.10.125% bupivacaine with tion, the unreliability of identifying the lumbar
fentanyl 13g/ml, and boluses of 812ml interspaces by palpation may result in insertion of
without a background infusion, or of 36ml the needle at a higher vertebral level than intended.
with a background infusion of 36ml/min, The lowest easily palpable interspace should there-
and a lockout time of 1020min. fore be chosen, and an epidural-only technique used
- epidural opioids have been used alone, but above L34.
rarely in the UK (see Spinal opioids). Fen- A widely used starting intrathecal dose is 1ml
tanyl is usually added to weak solutions of plain bupivacaine 0.25% mixed with fentanyl 25g,
bupivacaine as above. In the USA, sufentanil made up to 2ml with saline. 35ml boluses of the
is often used. Epidural pethidine has also low-dose epidural mixture above are also used.
been used. Continuous spinal analgesia has been described,
- inadequate blockade includes: missed using the same low-dose solution.
segment (commonly in one groin, the cause paravertebral block: bilateral blocks are required
is unclear); backache (especially with occipi- at either L2 (for sympathetic block) or T1112
toposterior presentation); rectal or perineal (somatic block).
pain; and unilateral blocks. Remedial mea- paracervical block: rarely performed because of
sures include further injection of solution, fetal arrhythmias.
with the unblocked part dependent. Use of a pudendal nerve block and perineal infiltration/
stronger solution, a different local anaesthetic, spraying with local anaesthetic: only of use for the
or fentanyl 5075g, may be helpful. The second stage. Pudendal block is used for forceps and
catheter should be withdrawn 12cm if uni- ventouse delivery.
lateral block occurs. Resiting of the catheter local infiltration of the abdomen for caesarean
may be required. Suprapubic pain may result section.
from a full bladder, and may be relieved by Particular problems in obstetric anaesthetic practice:
urinary catheterisation. Breakthrough pain in obstetric conditions, e.g. pre-eclampsia, placenta
the presence of a uterine scar may indicate praevia, placental abruption, postpartum haemor-
uterine rupture. Overall about 10% of epidur- rhage. Haemorrhage may follow any delivery, and
als require adjustment or extra doses. facilities for urgent transfusion should be available,
- contraindications, complications and manage- including a cut-down set and O-negative uncross-
ment are as for epidural analgesia/anaesthesia. matched blood. DIC may also occur in septic
Care should be taken in antepartum haemor- abortion, intrauterine death, hydatidiform mole
rhage (see below). Extensive blockade and and severe shock.
accidental iv injection of local anaesthetic are maternal disease, e.g. cardiovascular, respiratory,
possible following catheter migration. All diabetes. Epidural blockade is usually preferred.
 Oculocardiac reflex 425

fluid overload associated with oxytocin administra- Breast milk may be unsuitable for use because of mater-
tion; pulmonary oedema associated with tocolytic nal drugs; if required, lactation can be suppressed with
drugs. bromocriptine (although hypertension, CVA and MI
specific procedures/presentations: have followed its use, hence it should be avoided in
- premature labour: spinal/epidural analgesia/ hypertensive disorders).
anaesthesia is usually preferred, since it allows Price LC, Slack A, Nelson-Piercy C (2008). Best Pract
smooth controlled delivery with or without Res Clin Obstet Gynaecol; 5: 77599
forceps. The immature fetus may be especially See also, Placenta praevia; Placental abruption; Postpar-
susceptible to drug-induced depression. Tocolytic tum haemorrhage
drugs may have been used.
- twin delivery: epidural analgesia is usually Obstructive sleep apnoea, see Sleep apnoea/hypopnoea
employed. Caesarean section is required for
delivery of the second twin in up to 10% of cases. Obturator nerve block. Performed to accompany
Blood loss at delivery is greater than with a single sciatic nerve block or femoral nerve block, or in the
fetus. The enlarged uterus is more likely to cause diagnosis and treatment of hip pain. The obturator nerve
aortocaval compression. (L24), a branch of the lumbar plexus, passes down
- breech presentation: most deliver by caesarean within the pelvis and through the obturator canal into
section nowadays because of evidence that neo- the thigh, to supply the hip joint, anterior adductor
natal outcome is better. muscles and skin of medial lower thigh/knee.
- manual removal of placenta: spinal/epidural With the patient supine and the leg slightly abducted,
anaesthesia is usually considered preferable to an 8cm needle is inserted 12cm caudal and lateral to
general anaesthesia, since the latter risks aspira- the pubic tubercle, and directed slightly medially to
tion of gastric contents, and inhalational agents encounter the pubic ramus. It is then withdrawn and
cause uterine relaxation. redirected laterally to enter the obturator canal, and
collapse on labour ward: advanced 23cm. If a nerve stimulator is used, twitches
- causes include: shock associated with abruption in the adductor muscles are sought. After careful aspira-
and DIC, postpartum haemorrhage, total spinal tion to exclude intravascular placement, 1015ml local
blockade, overdosage or iv injection of local anaesthetic agent is injected.
anaesthetic, amniotic fluid embolism, PE, eclamp- In an alternative approach, the leg is externally
sia, inversion of the uterus and pre-existing rotated and abducted and an 810cm needle inserted
disease. behind the adductor longus tendon near its pubic inser-
- CPR is hindered by aortocaval compression, tion, and directed posteriorly and slightly cranially and
relieved by tilting the patient to one side or laterally. 510ml solution is injected at a depth of
manually displacing the uterus laterally. Caesar- 23cm.
ean section should be undertaken within 5min if
there is no improvement in the mothers Occipital nerve blocks, see Scalp, nerve blocks
condition.
[Walter Stoeckel (18711961), German obstetrician; Octreotide. Long-acting somatostatin analogue, used in
Michael E Tunstall (19282011), Aberdeen carcinoid syndrome and related GIT tumours and acro-
anaesthetist] megaly. Also licensed for use in treating complications
See also, Cardiopulmonary resuscitation, neonatal; Ergo- of pancreatic surgery. Has also been used in bleeding
metrine; Fetal monitoring; Flying squad, obstetric; Labour, oesophageal varices, and to reduce vomiting in palliative
active management of; Midwives, prescription of drugs care. Plasma levels peak within an hour of sc administra-
by; Obstetric intensive care tion, and within a few minutes of iv injection. Half-life is
12h. Lanreotide is a similar agent.
Obstetric intensive care. Required in 0.29 cases per Dosage:
1000 deliveries, depending on the population served and 50g sc od/bd, increased to 200g tds if required
the ICU admission criteria used. Most common reasons (rarely up to 500g tds in carcinoid syndrome).
for admission are haemorrhage, pre-eclampsia and 50100g iv in carcinoid crisis, diluted to 1050%
HELLP syndrome; a mortality of 34% is reported in in 0.9% saline.
UK series but up to 20% has been reported elsewhere. 50g iv followed by 50g/h in bleeding varices.
Main problems are related to the risks to the fetus and Side effects: GIT upset, glucose intolerance, hepatic
the physiological changes of pregnancy: obstetric patients impairment.
have increased oxygen demands and reduced respira-
tory reserves, and are more susceptible to aspiration of Oculocardiac reflex. Bradycardia following traction on
gastric contents, aortocaval compression, acute lung the extraocular muscles, especially medial rectus. Affer-
injury, DVT and DIC. ent pathways are via the occipital branch of the trigemi-
General management is along standard lines, with nal nerve; efferents are via the vagus. The reflex is
attention to the above complications. Excessive fluid particularly active in children. Bradycardia may be
administration should be avoided, since ARDS is a severe, and may lead to asystole. Other arrhythmias may
common feature of obstetric critical illness. Fetal moni- occur, e.g. ventricular ectopics or junctional rhythm. Bra-
toring should be ensured if antepartum, although the dycardia may also follow pressure on or around the eye,
needs of the mother outweigh those of the fetus. Utero- fixation of facial fractures, etc. The reflex has been used
placental blood flow may be impaired by vasopressors to stop SVT with eyeball massage. Reduced by anticho-
and the mother may be too sick to receive tocolytic linergic drugs administered as premedication or on
drugs should premature labour occur. Caesarean section induction of anaesthesia. If it occurs, surgery should stop,
may be required to improve the mothers condition. and atropine or glycopyrronium should be administered.
426 Oculogyric crises

Retrobulbar block does not reliably prevent it; local reduces this in chronic oedema. Generalised
infiltration of the muscles has been used instead. oedema occurs in dependent parts of the body, e.g.
See also, Ophthalmic surgery ankles if ambulant, sacrum if bed-bound. Treatment
is directed at the cause. If localised, the affected part
Oculogyric crises, see Dystonic reactions is raised above the heart.
See also, Cerebral oedema; Hereditary angioedema; Pul-
Oculorespiratory reflex. Hypoventilation following monary oedema; Starlings forces
traction on the external ocular muscles. Reduced respi-
ratory rate, reduced tidal volume or irregular ventilation Oesophageal contractility. Used as an indicator of
may occur. Thought to involve the same afferent path- anaesthetic depth and brainstem integrity. Skeletal
ways as the oculocardiac reflex, but with efferents via the muscle is present in the upper third of the oesophagus,
respiratory centres. Heart rate may be unchanged, and smooth muscle in the lower third, and both types in the
the reflex is unaffected by atropine. middle third. Afferent and efferent nerve supply is
mainly vagal via oesophageal plexuses, but also via sym-
ODAs/ODPs, see Operating department assistants/ pathetic nerves.
practitioners Normal pattern of contractions:
primary: continuation of the swallowing process;
Odds ratio. Ratio of the odds of an events occurrence propels the food bolus down the oesophagus.
in one group to its odds in another, used as an indicator secondary (provoked): caused by presence of food,
of treatment effect in clinical trials. For example, if a etc., within the oesophageal lumen. Unrelated to
disease is suspected to be caused by exposure to a certain swallowing.
factor, a 2 2 table may be drawn for proportions of tertiary (spontaneous): non-peristaltic; function is
patients in the following groups: uncertain.
Measured by passing a double-ballooned probe into the
With disease Without disease lower oesophagus. The distal balloon is filled with water
Exposed a c and connected to a pressure transducer; the other
Not exposed b d balloon (just proximal) may be inflated intermittently to
study provoked contractions.
Odds ratio = the ratio of a/b to c/d Altered by:
= ad/bc. anaesthesia: provoked contractions diminish in
amplitude as depth increases, and spontaneous con-
Harder to understand (but more useful mathematically) tractions become less frequent. Oesophageal con-
than other indices of risk commonly used. tractility index ([70 spontaneous rate] + provoked
See also, Absolute risk reduction; Meta-analysis; Number amplitude) is used as an overall measure of activity.
needed to treat; Relative risk reduction Thought to be analogous to BP, heart rate, lacrima-
tion and sweating during anaesthesia; i.e. suggestive
ODIN, Organ dysfunction and/or infection, see Logistic of anaesthetic depth, but not reliable. Activity may
organ dysfunction system be decreased by atropine and smooth muscle relax-
ants (e.g. sodium nitroprusside) and increased by
ODwyer, Joseph (18411898). US physician; regarded neostigmine.
as the introducer of the first practical intubation tube in brainstem death: spontaneous contractions disap-
1885, although the technique had been described previ- pear, and provoked contractions show a low ampli-
ously by others, e.g. Kite. His short metal tube, used as tude pattern. Has been used to indicate the presence
an alternative to tracheostomy in diphtheria, was or absence of brainstem activity in ICU, but its role
inserted blindly into the larynx on an introducer; the is controversial. Presently not included in UK brain-
flanged upper end rested on the vocal cords. He mounted stem death criteria.
his tube on a handle for use with Fells resuscitation See also, Anaesthesia, depth of
bellows in 1888; the FellODwyer apparatus could be
used for CPR or anaesthesia. Later modifications Oesophageal obturators and airways. Devices inserted
included addition of a cuff. blindly into the oesophagus of unconscious patients to
[George Fell (18501918), US ENT surgeon] secure the airway and allow IPPV when tracheal intuba-
Baskett TF (2007). Resuscitation; 74: 21114. tion is not possible, e.g. by untrained personnel. They
have been used in failed intubation. Consist of a cuffed
Oedema. Generalised or local excess ECF. Caused by: oesophageal tube, often attached to a facemask for
hypoproteinaemia and decreased plasma oncotic sealing the mouth and nose and preventing air leaks. The
pressure. cuff reduces gastric insufflation and regurgitation but
increased hydrostatic pressure, e.g. cardiac failure, may not prevent it.
venous or lymphatic obstruction; salt and water The epiglottis is pushed anteriorly, creating an air
retention (e.g. renal impairment, drugs, e.g. NSAIDs, passage for ventilation. An ordinary tracheal tube may
oestrogens, corticosteroids). be used to isolate the stomach and improve the airway
leaky capillary endothelium, e.g. inflammation, in a similar way.
allergic reactions, toxins. Two main types are described:
direct instillation, e.g. extravasated iv fluids, infiltra- blind-ended cuffed tube, perforated level with the
tion. Several causes often coexist, e.g. hypoprotein- hypopharynx for passage of air. Inflation is through
aemia, portal hypertension and fluid retention in the tube and via the perforations to the lungs.
hepatic failure. Characterised by pitting when pro- open-ended tube, to allow gastric aspiration. Infla-
longed digital pressure is applied, although fibrosis tion is through a separate port of the facemask. If
 Oliguria 427

causes variceal thrombosis and fibrosis) and ligation

(e.g. with rubber bands) are also used. Portocaval
shunt procedures, e.g. distal splenorenal shunts
B A (requiring surgery) or transjugular intrahepatic por-
tosystemic shunts (TIPS; performed under radio-
logical control) decompress the portal circulation
but at the expense of hepatic encephalopathy (pos-
sibly less common after TIPS). The effect of all
these procedures on survival is disputed.
if bleeding occurs:
- resuscitation as for acute hypovolaemia. Airway
management is complicated by haematemesis
and steps to avoid aspiration of blood and gastric
contents must be taken.
- pharmacological reduction of portal venous
pressure:
- vasopressin 20U over 15min iv or its analogue
terlipressin 2mg iv followed by 12mg 46-
hourly up to 72h. Controls bleeding in 6070%
of cases.
- somatostatin 250g followed by 250g/h or its
C
analogue octreotide 50g followed by 50g/h.
- endoscopic sclerotherapy or ligation may be per-
formed acutely.
- radiological procedures include embolisation
D or TIPS.
- acute surgical shunt procedures.
Fig. 121The Combitube (see text) - balloon tamponade using a Sengstaken
Blakemore tube.
accidental tracheal placement occurs, IPPV may be Garcia-Tsao G, Bosch J (2010). N Engl J Med; 362:
performed through the tube. 82332
The above features have been combined in a
double-lumen device (Combitube), which may be Off-pump coronary artery bypass graft, see Coro-
placed in either the oesophagus or trachea (Fig. nary artery bypass graft
121). A distal cuff (15ml) seals the oesophagus or
trachea, whilst a proximal balloon (100ml) seals the Ofloxacin. Antibacterial drug, one of the 4-quinolones
oral and nasal airways. IPPV may be performed related to ciprofloxacin. Used for respiratory and geni-
through either tube depending on the devices posi- tourinary tract infections.
tion; it enters the oesophagus in over 95% of cases Dosage: 200400mg orally or iv od/bd.
initially and ventilation via the longer proximal Side effects: as for ciprofloxacin. Hypotension and
tube (A) will result in pulmonary ventilation via the thrombophlebitis may occur on iv administration.
proximal openings (C). The shorter distal tube (B)
may then be used for gastric suction via the distal Ohms law. Current passing through a conductor is pro-
opening (D). If the device is tracheal, IPPV may be portional to the potential difference across it, at constant
achieved via tube B and opening D. Has been sug- temperature. Thus: voltage = current resistance. (i.e.
gested as a suitable device for non-medical person- V = IR). An analogous form exists for flow of a fluid:
nel (e.g. for CPR), although trauma is more common pressure = flow resistance.
than with alternative devices, such as the LMA. [Georg S Ohm (17871854), German physicist]

Oesophageal sphincter, see Lower oesophageal Old age, see Elderly, anaesthesia for
sphincter
Oliguria. Reduced urine output; definition is controver-
Oesophageal stethoscope, see Stethoscope sial but usually described as under 0.5ml/kg/h. Common
after major surgery or in ICU.
Oesophageal varices. Dilated oesophagogastric veins Caused by:
occurring in portal hypertension, e.g. in hepatic cirrhosis; urinary retention, blocked catheter, etc.
the veins represent one of the connections between the poor renal perfusion, e.g. hypotension, hypovolae-
systemic and portal circulations. Account for up to a mia, low cardiac output. Urine formation usually
third of cases of massive upper GIT haemorrhage. Mor- requires MAP of 6070mmHg in normotensive
tality is up to 30% if bleeding occurs, partly related to subjects.
the underlying severity of liver disease. effect of drugs, e.g. morphine causes vasopressin
Management: secretion.
prevention of haemorrhage: -adrenergic receptor increased intra-abdominal pressure (e.g. abdominal
antagonists, e.g. propranolol, have been used to compartment syndrome): the mechanism is unknown
reduce portal BP if hepatic function is not too but ureteric stents do not prevent it, suggesting
impaired. Endoscopic sclerotherapy (e.g. with etha- mechanisms other than ureteric compression.
nolamine oleate or sodium tetradecyl sulphate; renal failure.
428 Omeprazole

Management: surgery (classically to medulla/high cervical spine).

exclusion of retention or blocked catheter. Despite being awake, victims may breathe only on
urinary and plasma chemical analysis (e.g. sodium, command, with apnoea when asleep. The term has
osmolality) is useful in distinguishing renal from also been applied to a congenital form of hypoventila-
prerenal causes (see Renal failure). Management is tion and to respiratory depression caused by opioid anal-
according to the underlying cause. gesic drugs.
[Ondine, German mythological sea nymph; the curse of
Omeprazole. Proton pump inhibitor used to reduce having to remember when to breathe, and thus being
gastric acidity. A prodrug converted to its active form by unable to sleep for fear of dying, was inflicted on her
the acidic conditions of gastric parietal cell canaliculi. unfaithful husband by her father, King of the Sea]
Effects last for up to 24hafter single dosage. Nannapaneni R, Behari S, Todd NV, Mendelow AD
Dosage: 1040mg orally od. For reduction of risk (2006). Neurosurg; 57: 35463
from aspiration of gastric contents, 40mg orally the
night before, and 40mg on the morning of surgery. One-lung anaesthesia. Deliberate perioperative col-
May also be given iv: 4080mg. lapse of one lung to allow or facilitate thoracic surgery,
Side effects: uncommon and usually mild: diarrhoea, whilst maintaining ventilation and gas exchange on the
rash, headache, rarely dizziness, hepatic enzyme and other side. Requires the use of endobronchial tubes
haematological changes. or blockers. Commonly performed for surgery to the
lungs, oesophagus, aorta and mediastinum, but most
Omphalocele, see Gastroschisis and exomphalos operations are possible without it (sleeve resection of
the bronchus being a notable exception). Its main
Oncotic pressure (Colloid osmotic pressure). Osmotic problem is related to hypoxaemia caused by the V/Q
pressure exerted by plasma proteins, usually about mismatch produced, exacerbated by the lateral position
3.3kPa (25mmHg). Important in the balance of Starling used for most thoracic surgery. Perioperative hypoxae-
forces, and movement of water across capillary walls, e.g. mia increases postoperative risk of cognitive dysfunc-
in oedema. Although related to plasma protein concen- tion, atrial fibrillation, renal failure and pulmonary
tration, the relationship is thought to be non-linear hypertension.
because of molecular interactions and effects of charge. Effects of lateral positioning on gas exchange:
See also, Intravenous fluids awake:
- ventilation: FRC of the upper lung exceeds that
Ondansetron hydrochloride. 5-HT3 receptor antago- of the lower lung, because of mediastinal move-
nist, introduced in 1990 as an antiemetic drug following ment to the dependent side, and pushing up of the
anaesthesia and chemotherapy. Although claimed to be lower hemidiaphragm by abdominal viscera. Thus
superior to alternative antiemetics for PONV, convinc- the upper lung lies on a flatter part of the compli-
ing evidence for this is lacking. However, it does not ance curve (i.e. is less compliant) whilst the lower
affect dopamine receptors and unwanted central effects lung lies on the steep part of curve, i.e. is more
are rare. Evidence suggests greater efficacy for treat- compliant (Fig. 122a). In addition, the raised
ment of PONV, than for its prophylaxis. Has also hemidiaphragm on the dependent side contracts
been used to treat intractable pruritus following spinal more effectively. Thus most ventilation is of the
opioids, although evidence for its effectiveness is weak. lower lung.
Decreases the incidence of postoperative shivering. - perfusion: mainly of the lower lung because of
Only 7075% protein-bound. Undergoes hepatic metab- gravity; i.e. is matched with ventilation.
olism and renal excretion. Half-life is 3h. anaesthetised:
Dosage: - FRC of both lungs is reduced; the upper lung now
PONV: lies on the steep part of the curve and the lower
- prophylaxis: 4mg slowly iv/im on induction, or lung on the flatter part (Fig. 122b). Thus the upper
16mg orally 1hpreoperatively, or 8mg orally (more compliant) lung is ventilated in preference
preoperatively repeated twice 8-hourly postop- to the lower (less compliant) lung.
eratively. In children > 1 month, 0.1mg/kg slowly - perfusion is still mainly of the lower lung, i.e. V /Q

iv up to 4mg. mismatch occurs (usually of minor importance
- treatment: 14mg slowly iv/im. in normal patients, since both blood flow and
nausea following radiotherapy or chemotherapy:
8mg orally/iv/im or 16mg pr, followed by further
doses up to 16mg/day for up to 5 days. In severe
cases, a single loading dose of 16mg pr or iv over
15min may be given before treatment. In children, (a) (b)
5mg/m2 iv before treatment followed by 24mg Upper lung
orally 12-hourly.
Side effects: headache, constipation, flushing sensa-
Upper lung
Volume

Volume

tion, hiccups, occasionally hepatic impairment, visual Lower lung

disturbances, rarely convulsions. Prolongation of
ECG intervals, including heart block, has been Lower lung
reported. May reduce the analgesic efficacy of trama-
dol hydrochloride.
Pressure Pressure
Ondines curse. Hypoventilation caused by reduced Fig. 122 Compliance curve for upper and lower lungs in the lateral
ventilatory drive, originally described following CNS position: (a) awake; (b) anaesthetised
 Operating department assistants/practitioners 429

ventilation usually differ by up to 10% between - performing an alveolar recruitment manoeuvre

the two sides). on the dependent lung.
one-lung anaesthesia: all ventilation is of the lower - altering the ventilation strategy (i.e. changing
lung, whereas considerable perfusion is still of tidal volume and/or PEEP).
the upper lung. Thus significant shunt occurs in the suction is applied to the collapsed lung before rein-
upper lung, with V /Q  mismatch usual in the flation, to remove accumulated secretions.
lower lung. slow manual inflation is performed at the end of the
- CO2 exchange increases via the lower lung; thus procedure, to encourage expansion. The surgeon
CO2 elimination is thought to be maintained if may request sustained pressures (e.g. 3040 cmH2O)
minute ventilation is unchanged. to test the integrity of the bronchial suturing.
- degree of hypoxaemia is affected by: Karzai W, Schwarzkopf K (2009). Anesthesiology; 110:
- side of operation: as the right lung is larger than 140211
the left, oxygenation is often better during left
thoracotomy. Open-drop techniques. Common and convenient tech-
- pre-existing state of the lungs: decrease in oxy- niques for administering inhalational anaesthetic agents
genation is greatest in normal lungs, e.g. during in the 1800s/early 1900s. The volatile anaesthetic agent
non-pulmonary surgery. Conversely, contribu- (e.g. chloroform, diethyl ether, ethyl chloride) was
tion to oxygenation by the diseased, operative dripped on to a cloth (originally a folded handkerchief)
lung is usually reduced; thus the drop in arterial on the patients face from a dropper bottle. Concentra-
PO2 is smaller when it is collapsed. tion of agent depended on the rate of drop administra-
- FIO2: increases above 0.5 may not improve oxy- tion. Specially designed bottles and masks were later
genation, since pure shunt is not corrected by developed; the best-known mask is that of Schimmel-
raising FIO2. busch, although this was adapted from Skinners earlier
- cardiac output: hypoxaemia worsens if cardiac model. Some incorporated channels for O2 insufflation,
output falls because of a decrease in the PO2 of or gutters around the edge to catch liquid anaesthetic.
mixed venous blood passing through the shunt. [Curt Schimmelbusch (18601895), German surgeon;
The situation is complicated by altered distribu- Thomas Skinner (18251906), Liverpool obstetrician]
tion of pulmonary blood flow caused by changes
in cardiac output. Operant conditioning. Type of learning in which volun-
- hypoxic pulmonary vasoconstriction: whether it tary behaviour is strengthened or weakened by rewards
is attenuated by use of anaesthetic agents, or or punishments respectively. May be involved in the
whether it contributes any protection against development of certain behavioural aspects of pain syn-
shunt, is unclear. dromes. Has been used in chronic pain management,
- ventilation strategy: the optimum tidal volume with several weeks admission to hospital, involving
and level of PEEP are controversial. In order reduction in drug therapy and encouragement of activity
to prevent atelectasis in the dependent lung, and independence. Thus concentrates on behaviour sec-
some advocate using large tidal volumes (e.g. ondary to pain instead of pain itself.
12ml/kg) without PEEP (as PEEP may reduce See also, Cognitive behavioural therapy
cardiac output or increase shunt through the
uppermost lung, exacerbating hypoxaemia). An Operating department assistants/practitioners
increasingly common strategy is to use low tidal (ODAs/ODPs). Non-medical anaesthetic support staff;
volumes (e.g. 67ml/kg) with moderate PEEP the role arose from the requirements of military sur-
to prevent atelectasis while reducing the risk of geons and anaesthetists for specialist non-nursing assis-
causing volutrauma and acute lung injury. tance during World War II, although box carriers (so
- content of the collapsed lung: hypoxaemia called because they carried the surgeons instruments in
worsens after about 10min as contained O2 is a box) were in use in the UK in the early 1800s. City &
absorbed. Arterial PO2 is increased by applica- Guilds of London Institute training for ODAs was intro-
tion of 57cmH2O CPAP using O2, or by inter- duced in 1976, offering specific training in the areas of
mittent inflation, e.g. every 1015min. anaesthesia and surgery without passage through the
- surgery: e.g. leaning on mediastinum, reduction nursing training system, whilst the term ODP was intro-
of venous return. Tying the uppermost pulmo- duced in 1989 to further the concept that adequately
nary artery stops shunt to the uppermost lung. trained staff could equally come from nursing or
Practical management: traditional ODA backgrounds. A National Vocational
preoperative assessment as for thoracic surgery; Qualification (NVQ) in Operating Department Practice
patients particularly at risk during one-lung anaes- was introduced in 1991. Repeated attempts to bring the
thesia may be identified. two ODP career structures (i.e. ODA and non-ODA)
close monitoring using oximetry and/or arterial closer together was hampered for many years by (1)
blood gas interpretation. different pay scales and (2) lack of central registration
FIO2 is usually set to 0.40.5. of ODAs compared with nurse ODPs statutory require-
surgical ligation of the pulmonary artery is per- ment to be registered with the nursing authorities. A
formed early. voluntary register of ODAs was established in the late
management of acute desaturation includes: 1980s/early 1990s and compulsory registration of all
- increasing FIO2 to 1.0. ODPs was established in 2004. The professional body for
- use of fibreoptic bronchoscopy to check tube posi- ODPs is the College (formerly Association) of ODPs,
tion and clear secretions. which has almost 5000 members and publishes the
- administration of O2 to the uppermost lung, e.g. bi-monthly Technic: The Journal of Operating Depart-
with CPAP or intermittent inflation. ment Practice.
430 Ophthalmic nerve blocks

ODPs have an invaluable role in supporting most Local anaesthesia:

anaesthetic activity, e.g. preparing and ordering drugs cornea and conjunctiva: 4% lidocaine (with or
and equipment, setting up the operating theatre for without adrenaline) or 24% cocaine is instilled
cases, helping to organise operating lists. They may into the conjunctival sac. Cocaine is not used in
also assist the surgical staff (including scrubbing) and glaucoma, as it dilates the pupil.
the concept of multi-skilling supports their activity retrobulbar block, peribulbar block or sub-Tenons
in various roles within the operating theatre suite block: retrobulbar block is less commonly per-
and beyond, e.g. ICU, trauma teams. More extended formed now because of associated complications.
practical roles are supported in some units (e.g. assisting prevention of blepharospasm: infiltration between
at cardiac arrests, placing iv cannulae), although this is the muscles and bone parallel to the lower and
controversial. lateral orbital margins from a point 1cm behind the
orbits lower lateral corner; alternatively, local
Ophthalmic nerve blocks. Performed for procedures anaesthetic may be injected above the condyloid
around the eye, nose and forehead, and certain intraoral process of the mandible. These injections are
procedures. rarely required with large-volume modern regional
Anatomy (see Fig. 76; Gasserian ganglion block): techniques.
ophthalmic division of the trigeminal nerve (V1) is sedation may be used. Close monitoring is required
entirely sensory and passes from the Gasserian gan- as the patients head is covered by drapes. Supple-
glion, where it divides into branches which pass mentary O2 should be delivered.
through the superior orbital fissure: General anaesthesia:
- lacrimal nerve: supplies the lateral upper eyelid preoperatively:
and conjunctiva, lacrimal gland and skin of the - preoperative assessment of children with strabis-
lateral angle of the mouth. mus for muscle disorders and MH susceptibility.
- frontal nerve: supplies the upper eyelid, frontal Cataracts may occur in dystrophia myotonica,
sinuses and anterior scalp via the supraorbital inborn errors of metabolism, chromosomal abnor-
branch; upper eyelid and medial forehead via the malities, diabetes mellitus, corticosteroids therapy
supratrochlear branch. or following trauma. Lens subluxation may occur
- nasociliary nerve: supplies the anterior dura, ante- in Marfans syndrome and inborn errors, e.g.
rior ethmoidal air cells, upper anterior nasal homocystinuria. The elderly should be assessed
cavity and skin of the external nose via the ante- for other diseases, e.g. diabetes, hypertension (see
rior ethmoidal branch; posterior ethmoidal and Elderly, anaesthesia for).
sphenoid sinuses via the posterior ethmoidal - drugs used in eye drops may be absorbed and
branch; medial upper eyelid, conjunctiva and active systemically, e.g. ecothiopate, timolol.
adjacent nose via the infratrochlear branch; - opioid premedication is usually avoided because
cornea, iris, ciliary body and dilator/sphincter of its emetic properties. Benzodiazepines are
pupillae via the long and short ciliary branches. popular.
Sympathetic fibres carried in short ciliary branches perioperatively:
synapse in the ciliary ganglion - procedures include the above operations, repair
supraorbital foramen, pupil, infraorbital notch, of retinal detachment, vitrectomy, repair of eye
infraorbital foramen, buccal surface of the second injuries (see Eye, penetrating injury) and opera-
premolar and mental foramen all lie along a tions on the lacrimal system.
straight line. - the airway is usually not easily accessible to the
Blocks: anaesthetist.
supraorbital nerve: 13ml local anaesthetic agent is - for children, considerations include those for
injected at the supraorbital notch. paediatric anaesthesia, the very active oculocar-
supratrochlear nerve: 13ml is injected at the diac and oculorespiratory reflexes, and the
superomedial part of the opening of the orbit. increased incidence of PONV after strabismus
both the above nerves may be blocked by subcuta- repair (thought also to be associated with traction
neous infiltration above the eyebrow. on extraocular muscles). Atropine or glycopyr-
frontal nerve: 1ml is injected at the central part of ronium should be available; some advocate
the roof of the orbit. routine administration to all patients preopera-
anterior ethmoidal nerve: 2ml is injected at the tively or on induction of anaesthesia. Standard
superomedial side of the orbit, at a depth of 34cm. techniques are employed, with tracheal intuba-
See also, Mandibular nerve blocks; Maxillary nerve tion or LMA and spontaneous or controlled
blocks ventilation.
- for adults, standard agents and techniques are
Ophthalmic surgery. Historically, first performed used. Control of IOP is usually achieved by iv
without anaesthesia and then under topical anaesthesia induction, IPPV and hyperventilation, and use of
(e.g. by Koller), because of the eyes accessibility and the a volatile inhalational anaesthetic agent (for
disastrous effects of coughing during general anaesthe- effects of specific drugs, use of sulphahexafluoride,
sia. Subsequently, increasingly performed under general etc., see Intraocular pressure). Administration of
anaesthesia because of patients expectations and the iv acetazolamide may be required. Spontaneous
ability to control intraocular pressure (IOP). More ventilation may be suitable for extraocular proce-
recently local anaesthesia has been favoured again, espe- dures. The LMA is often used, since coughing and
cially in the elderly. Children (for strabismus repair) and straining are less pronounced than with tracheal
the elderly (for cataract extraction) form the largest intubation. The oculocardiac reflex may still occur
groups of patients. in adults.
 Opioid receptors 431

- systemic absorption of topical solutions, e.g. depression due to buprenorphine may not be
adrenaline, cocaine, may occur. responsive.
- coughing, straining and vomiting may increase
IOP, especially undesirable if the globe is open. Opioid receptor antagonists. Different types:
postoperatively: avoidance of straining and pure antagonists, e.g. naloxone, naltrexone: antago-
vomiting is desirable. Postoperative pain tends nists at all opioid receptor subtypes. Methylnaltrex-
to be mild. one is a peripherally acting mu antagonist, currently
under investigation as a treatment for postopera-
tive ileus.
Opiates. Strictly, substances derived from opium. For-
agonistantagonists: agonists at some receptors but
merly used to describe agonist drugs at opioid receptors;
antagonists at others, e.g.:
the terms opioids and opioid analgesic drugs are now
- pentazocine: agonist at kappa and sigma, antago-
preferred.
nist at mu receptors.
- nalorphine: partial agonist at kappa and sigma,
Opioid analgesic drugs. Opium and morphine have antagonist at mu receptors.
been used for thousands of years; morphine was isolated - nalbuphine: as for nalorphine, but a less potent
in 1803 and codeine in 1832. Diamorphine was intro- sigma agonist.
duced in 1898, papaveretum in 1909. Other commonly partial agonists, e.g. buprenorphine, meptazinol
used drugs include: pethidine (1939); methadone (1947); (mu receptors); may antagonise mu effects of other
phenoperidine (1957); fentanyl (1960); alfentanil (1976); opioids (e.g. morphine).
tramadol (1977); sufentanil (1984) and remifentanil Their main clinical use is to reverse effects of opioid
(1997). Drugs with opioid receptor antagonist properties analgesic drugs, e.g. in opioid poisoning. Those with
include pentazocine (1962), nalbuphine (1968), mep- agonist properties are also used as analgesic drugs; some
tazinol (1971) and buprenorphine (1968). have been used to reverse unwanted effects of other
May be divided into naturally occurring alkaloids opioids (e.g. respiratory depression) whilst still main-
(e.g. morphine, codeine), semisynthetic drugs (slightly taining analgesia. In practice, this is very difficult to
modified natural molecules, e.g. diamorphine, dihydro- achieve. Also used in diagnosis and treatment of opioid
codeine) and synthetic opioids (e.g. pethidine, fentanyl, addiction. Receptor-specific compounds have been
alfentanil, remifentanil). May also be classified accord- developed for research and identification of receptor
ing to their opioid receptor specificity and actions, or subtypes.
according to their onset and duration of action. Many result from modification or substitution of the
Each drug has slightly different effects on the bodys side chain on the nitrogen atom of parent analgesic
systems, but their general effects are those of morphine. drugs, e.g. N-allyl group substitution for the N-methyl
The purer drugs, e.g. fentanyl, alfentanil, sufentanil, do group (hence the name, nal ).
not cause histamine release, and may be used in very
high doses with relative cardiostability, e.g. for cardiac Opioid receptors. Naturally occurring receptors to
surgery. In lower doses, they are used to provide intra- morphine and related drugs, isolated in the 1970s. All are
and postoperative analgesia, and to prevent the haemo- G protein-coupled receptors and activation results in
dynamic consequences of tracheal intubation and opening of potassium channels and closure of voltage-
surgical stimulation. Also used as general analgesic gated calcium channels; this leads to membrane hyper-
drugs and for premedication, anxiolysis, cough suppres- polarisation, reduced neuronal excitability and thus
sion and treatment of chronic diarrhoea. reduced nociceptive transmission. This effect is enhanced
See also, Opioid ; Spinal opioids by reduction of cAMP by inhibition of adenylate cyclase.
Found mainly in the CNS but also GIT; thought to be
involved in central mechanisms involving pain and
Opioid detoxification, see Rapid opioid detoxification
emotion. Three primary subgroups are now recognised
(each subdivided into two or more putative subtypes),
Opioid poisoning. Presents with nausea and vomiting, although others have been suggested in the past. More
respiratory depression, hypotension, pinpoint pupils recently, data from transgenic mice lacking a single
and coma. Depressant effects are exacerbated by opioid receptor (e.g. MOP) have called into question the
alcohol ingestion. Hypothermia, hypoglycaemia and, validity of further subtype classification.
rarely, pulmonary oedema and rhabdomyolysis may Subgroups:
occur. Convulsions may occur with pethidine, codeine mu (MOP):
and dextropropoxyphene. Drug combinations con - activation causes analgesia, respiratory depres-
taining opioids include atropinediphenoxylate for diar- sion, euphoria, hypothermia, pruritus, reduced
rhoea and paracetamoldextropropoxyphene/codeine/ GIT motility, miosis, bradycardia, physical depen-
dihydrocodeine for pain. The former combination may dence; i.e. the classic effects of morphine.
cause convulsions, tachycardia and restlessness (hence it - responsible for supraspinal analgesia; i.e. drugs
has been withdrawn from US and UK markets); the act at brain level.
latter may cause delayed hepatic failure. - the putative mu1 receptor subtype is thought to
Management: be responsible for supraspinal analgesia; the mu2
supportive: includes gastric lavage, iv fluids, O2 for most of the other effects; and mu3 receptors
therapy and IPPV. Activated charcoal may be have been identified on immune cells.
helpful if oral opioids have been recently ingested. - agonists: all opioid analgesic drugs.
naloxone 0.42.0mg iv repeated after 23min as - partial agonists: buprenorphine, meptazinol
required to a total of 10mg; infusion may be neces- (thought to be specific at mu1 receptors).
sary as its duration of action is short. Respiratory - antagonists: nalorphine, nalbuphine, pentazocine.
432 Opioids

delta (DOP):
Superior orbital Superior rectus
- distributed throughout the CNS. Located pre
fissure Optic canal
synaptically, they inhibit the release of
neurotransmitters. Lateral rectus Superior oblique
- activation has been experimentally shown to
produce analgesia and cardioprotection.
- agonists: enkephalins.
kappa (KOP):
- activation causes analgesia, miosis, sedation, dif-
ferent sort of dependence.
- responsible for spinal analgesia; i.e. drugs
thought to act at spinal level.
- agonists: experimental agents spiradoline and
enadoline cause analgesia but adverse effects,
including diuresis, sedation and dysphoria, pre- Medial rectus
clude clinical use.
Sigma receptors, previously considered opioid receptors, Inferior orbital Inferior oblique Inferior rectus
are not considered so now because the effects of their fissure
stimulation are not reversed by naloxone. They bind to
phencyclidine and its derivatives, e.g. ketamine. All sub- Fig. 123 Frontal view of right orbital cavity
types are antagonised by naloxone and naltrexone (mu
and kappa more than delta).
The nociceptin/orphanin FQ peptide (NOP) receptor posteriorly, its roof is formed by the orbital plate of the
(previously termed the orphan receptor) is related to frontal bone (and lesser wing of the sphenoid posteri-
the above receptors but its lack of sensitivity to naloxone orly); its floor by the maxilla and zygoma; its medial wall
makes it difficult to classify in the original opioid tax- by the frontal process of the maxilla and lacrimal bone
onomy. It is found throughout the brain and spinal cord, anteriorly and orbital plate of the ethmoid and body of
binds endogenous orphanin FQ, and produces antanal- the sphenoid posteriorly; and its lateral wall by the
gesia supraspinally and analgesia at spinal level. zygoma and greater wing of the sphenoid (Fig. 123). Has
Dietis N, Rowbotham DJ, Lambert DG (2011). Br J three openings posteriorly:
Anaesth; 107: 818 superior orbital fissure: transmits the third, fourth
and fifth (the three branches of the ophthalmic
Opioids. Substances which bind to opioid receptors; division) cranial nerves. Also transmits branches of
include naturally occurring and synthetic drugs, and the middle meningeal and lacrimal arteries, oph-
endogenous compounds. thalmic veins and sympathetic fibres.
inferior orbital fissure: transmits the maxillary
Opium. Dried juice from the unripe seed capsules of the nerve.
opium poppy Papaver somniferum. Contains many dif- optic canal: transmits the optic nerve and ophthal-
ferent alkaloids, including morphine (920%), codeine mic artery. The extraocular muscles are supplied by
(up to 4%) and papaverine. Used for thousands of years the third, fourth and sixth cranial nerves and have
as a recreational drug and for analgesia, especially in the the following actions on the pupil:
Far East. Use as a therapeutic drug is rare now, purer - superior rectus: elevates.
drugs and extracts being preferred. - inferior rectus: lowers.
- medial and lateral rectus: moves medially and
Oral rehydration therapy. Method of treating dehydra- laterally respectively.
tion when mild or where facilities for iv fluid administra- - superior oblique: moves downwards and
tion are lacking, e.g. in the community or developing laterally.
countries. Particularly useful in gastroenteritis and in - inferior oblique: moves upwards and laterally.
children; it has also been used in less serious burns. The rectus muscles attach posteriorly to a common ten-
Various commercial mixtures exist; all contain glucose, dinous ring surrounding the optic canal and part of the
the presence of which in the intestinal lumen facilitates superior orbital fissure; they attach anteriorly to the
the reabsorption of sodium ions and thus water. A simple sclera of the eyeball in front of the equator. The superior
version can be made by adding 20g glucose (or 40g oblique muscle attaches posteriorly above the tendinous
sucrose since only half becomes available as glucose ring, hooking round the pulley-like trochlea before
after ingestion), 3.5g sodium chloride, 2.5g sodium attaching posterolaterally to the eyeball, behind the
bicarbonate and 1.5g potassium chloride per litre of equator. The inferior oblique attaches posteriorly to the
water. Suitable solutions have been made by taking floor of the orbit and attaches to the posterolateral
three 300ml soft drink bottles of water and adding a surface of the eyeball, behind the equator.
level bottle capful of salt and eight capfuls of sugar. See also, Peribulbar block; Retrobulbar block; Skull;
Sub-Tenons block
Orbeli effect. Increase in strength of contraction of
fatigued muscle following sympathetic nerve Or, Pierre-Cyprien (18281889). French physician;
stimulation. Professor of Physiology at Bordeaux. Investigated blood
[Leon A Orbeli (18821958), Russian physiologist] transfusion and the effects of iv injection of drugs. Pro-
duced general anaesthesia with iv chloral hydrate in
Orbital cavity. Cavity containing the eye and extraor- 1872, thus becoming the first to employ TIVA. Also
bital structures. Roughly pyramidal with the apex treated tetanus with the drug.
 Orthopaedic surgery 433

Orexins (Hypocretins). Excitatory neuropeptides to hours, with metabolism by oxidation, ester hydrolysis
derived from an amino acid precursor, prepro-orexin. and combination with glutathione, and excretion in
Postulated as playing an important role in arousal, main- faeces or urine.
tenance of the waking state, neural control of food Toxic effects:
intake and neuroendocrine function, including energy peripheral enzyme inhibition:
metabolism and reproduction. May be involved in the - phosphorylation of acetylcholinesterase: may
pathophysiology of neurodegeneration and head injury. be irreversible depending on the compound
involved. Features are those of cholinergic crisis
Organ donation. Organs for transplantation may be and include muscarinic effects (bronchospasm,
donated by living subjects, e.g. kidney and bone marrow. sweating, increased secretions, abdominal cramps,
The main issue concerns the undertaking of anaesthesia bradycardia, miosis) and nicotinic effects (muscle
and surgery (with their attendant risks) by a healthy twitching, weakness, hypertension and tachycar-
patient for altruistic reasons. dia). Enzyme reactivation may be induced by
Many organs may be obtained from patients follow- pralidoxime if administered within 2436h.
ing diagnosis of brainstem death. They include kidney, - phosphorylation of other enzymes, e.g. lipases,
heart, lung, liver, small bowel, pancreas, skin and cornea. GIT enzymes.
Demand for organs outstrips supply. At present in the myopathic effects: weakness may occur within
UK, members of the public identify themselves as poten- 24hof poisoning, with recovery taking up to 3
tial donors by joining a national registry (an opt-in weeks. Muscle paralysis in humans may occur after
system); in some countries (e.g. Spain, Austria, Belgium), recovery from the initial cholinergic crisis, 24
an opt-out system operates in which permission is 96hafter poisoning. Mainly affecting proximal
assumed unless specified otherwise, and this has been muscles, it is thought to involve postsynaptic dys-
proposed in the UK amongst considerable controversy. function at the neuromuscular junction.
Even more controversial is donation after circulatory delayed polyneuropathy: usually follows poisoning
death (DCD), e.g. patients who arrive in hospital dead, with non-insecticide compounds. Develops 24
patients in whom CPR is unsuccessful, those in whom weeks after the cholinergic crisis, with weakness and
cardiac arrest occurs after brainstem death and those in paraesthesiae. Pyramidal signs may be present.
whom treatment has been withdrawn but in whom Recovery is variable.
formal brainstem death testing cannot be done because CNS effects: anxiety, tremor, confusion, coma and
of sedation, metabolic abnormalities, etc. In the latter convulsions may occur, with EEG abnormalities.
group, treatment may be withdrawn once the surgical Respiratory failure may result from peripheral
team is ready; death is pronounced 2min after asystole weakness, central depression and increased tra-
and surgery to retrieve organs begins 510min after cheobronchial secretions.
asystole. Diagnosis is based on history, tolerance to atropine
Non-living patients have traditionally been consid- therapy, acetylcholine assay and measurement of blood
ered unsuitable for donation for a number of relative and urine organophosphorus and metabolite levels.
reasons (e.g. systemic infection, age); with the relative Treatment:
shortage of organs, only HIV infection or Creutzfeldt supportive measures as for poisoning and over-
Jakob disease is considered an absolute contraindication doses in general. Care should be taken to avoid
and DCD now represents 35% of all donors in the UK. self-contamination.
Maintenance of tissue oxygenation, organ function drug therapy:
and metabolic and cardiovascular stability should be - atropine 2mg (20g/ml in children) iv each
pursued as for critically ill patients, until and during 510min until dry flushed skin, dilated pupils and
organ removal. Endocrine therapy with methylpredniso- tachycardia.
lone, triiodothyronine and control of blood sugar with - pralidoxime 30mg/kg diluted in 1015ml water,
insulin may improve donor organ function. iv over 510min. May be repeated up to twice if
Thompson JP, Murphy PG, Bodenham AR (2012). Br J no improvement is seen within 30min, up to a
Anaesth; 108 (suppl 1): i1i119 usual maximum of 12g/24h. Rarely, iv infusion of
up to 500mg/h may be required. For children, a
Organe, Geoffrey Stephen William (19081989). bolus dose of 2060mg/kg.
English anaesthetist, born in India. A major influence on Roberts DM, Aaron CK (2007). Br Med J; 334: 62934
the development of anaesthesia in the UK and abroad,
and involved in much research, particularly into the Orphanin FQ (OFQ; nociceptin), See Opioid receptors
newly introduced neuromuscular blocking drugs. Profes-
sor of Anaesthesia at Westminster Hospital, London, Orthopaedic surgery. Anaesthetic considerations may
and knighted in 1968. be related to:
indication for surgery:
Organophosphorus poisoning. An important world- - trauma: presence of other injuries, risks of emer-
wide cause of death due to acute poisoning, organophos- gency surgery (e.g. aspiration of gastric contents).
phorus compounds are acetylcholinesterase inhibitors, Adequate resuscitation is important preopera-
commonly used as insecticides but also manufactured as tively, especially in the elderly, e.g. following frac-
chemical weapons. One, ecothiopate, is used in glau- tured neck of femur (NOF). Cases with risk of
coma. Those used in insecticides are usually ester, amide infection, ischaemia or nerve damage are particu-
or thiol derivatives of phosphoric or phosphonic acids, larly urgent.
or their mixtures. They may be absorbed via the GIT, - musculoskeletal disease, e.g. rheumatoid arthritis,
lungs or skin, and are rapidly distributed to all tissues, connective tissue diseases, muscular abnormali-
especially liver and kidney. Half-lives vary from minutes ties. There is a higher than normal incidence of
434 Oscilloscope

MH susceptibility in young patients with muscu- osmolality = the number of osmoles per kilogram
loskeletal abnormalities. solvent.
- congenital malformations: may be accompanied osmolarity = the number of osmoles per litre
by other system involvement, e.g. cardiac lesions. solution.
- risk of massive hyperkalaemia following suxame- osmoles = the mw of a substance divided by the
thonium if neurological or muscle lesions are number of freely moving particles liberated in
present. solution.
surgical procedure: Thus 1mmol of a salt that dissociates completely into
- may involve repeated anaesthesia. two ions provides 2mosmol. In the body, the solvent is
- use of tourniquets. water, with density 1kg/l; thus osmolality and osmolarity
- use of methylmethacrylate cement. are often used interchangeably, although proteins and
- problems of specific procedures, e.g. fats in plasma give rise to a small difference.
kyphoscoliosis. Osmolality of plasma is maintained at 280
- regional techniques are particularly useful, e.g. hip 305mosmol/kg. Regulatory mechanisms include stimu-
surgery (arthroplasty, fractured NOF). Epidural lation of thirst by osmoreceptors, baroreceptors and the
and spinal anaesthesia are associated with fewer renin/angiotensin system. Osmoreceptors also stimulate
postoperative complications (including DVT) vasopressin release. Most contribution to plasma osmo-
than after general anaesthesia, although mortality lality arises from sodium and its anions, glucose and urea;
after fractured NOF is the same at 1 year. thus plasma osmolality may be estimated thus:
- DVT and PE are common, especially after hip mosmol/kg = [glucose] + [urea]
surgery; prophylactic measures should be taken. + (2 [Na + ]) (all in mmol/l ).
Fat embolism may occur after long bone
fractures. Alcohols, proteins, triglycerides and mannitol are not
accounted for. Proteins usually contribute little since,
Oscilloscope. Device for displaying recorded signals, despite their high concentration, few particles are liber-
particularly those of high frequency and when analysis ated in solution because of their high mw.
of their shape is required, e.g. ECG or arterial waveform. Osmolality/osmolarity is determined by measuring
May also be used without the time-base to plot two ionic concentration with a flame photometer, measuring
signals with respect to each other, e.g. flowvolume osmotic pressure or by employing the colligative proper-
loops. ties of solutions (e.g. depression of freezing point, lower-
The earliest oscilloscopes utilised a cathode ray tube ing of vapour pressure).
to generate, accelerate and focus an electron beam on to Urinary and plasma osmolality measurement is
a fluorescent screen, the beam visible as a bright dot. The useful in investigating oliguria and renal failure.
signal potential was applied vertically across the beam, See also, Fluid balance; Hyperosmolality; Hypo-
causing vertical deflection; a spatial reconstruction of the osmolality; Osmolar gap; Tonicity
signal against time was then seen on the screen. The
pattern could be made to persist by altering the charac- Osmolar gap (Osmolality gap). Difference between cal-
teristics of the fluorescent material, or by using a second culated and measured plasma osmolality. Normally
cathode system. These are now termed analogue oscil- 1015 mosmol/kg; increased in the presence of low-
loscopes, to distinguish them from the modern digital molecular-weight substances not included in the formula
devices that have replaced them in medical practice. for calculating plasma osmolality, e.g. alcohols, mannitol,
These utilise an analogue-to-digital converter to trans- glycine (in the TURP syndrome). May also be applied
late measured voltages (sampled at close, regular to urine osmolality, e.g. to indicate the presence of
time intervals) into digital information that is then dis- osmotically active substances such as ammonium ions.
played on liquid crystal or light-emitting diode panels.
Digital devices benefit from greater portability and Osmoreceptors. Cells in the anterior hypothalamus,
the option to apply processing algorithms to recorded outside the bloodbrain barrier; respond to changes in
signals (e.g. for ST segment analysis and detection of plasma osmolality. Control thirst and secretion of vaso-
arrhythmias). pressin, possibly via separate groups of osmoreceptors.

Oscillotonometer. Obsolete device for indirect arterial Osmosis. Movement of solvent molecules across a semi-
BP measurement, using one (upper) cuff for occluding permeable membrane from a dilute solution to a con-
the brachial artery and a second (lower) cuff for detect- centrated one, tending to equalise the concentrations on
ing pulsations, often incorporated into a double cuff. both sides. Thus water moves across cell membranes
Both cuffs are inflated by hand to above systolic BP and from the ECF following dextrose infusion, once the dex-
then allowed to deflate slowly, using a lever to switch the trose has been metabolised. Similarly, water in very
dial to a sensitive indicator mode by which increased hypotonic iv fluids may move into red blood cells after
and then decreased oscillations of the dial needle indi- infusion, causing haemolysis.
cate systolic and then diastolic pressures respectively. At
each of these points, the lever is used to return the indi-
cator dial to a recording mode to allow actual cuff Osmotic clearance, see Clearance, osmotic
pressure to be displayed. Has been replaced by auto-
mated devices, which employ similar principles but are Osmotic diuretics, see Diuretics
more accurate, more reliable and easier to use.
Osmotic pressure. Pressure required to prevent move-
Osmolality and osmolarity. Expressions of concentra- ment of solvent molecules by osmosis across a semiper-
tion of osmotically active particles in solution: meable membrane.
 Oxycodone hydrochloride 435

nRT
equals as for the ideal gas law,
V
where n = number of particles,
R = universal gas constant,
T = absolute temperature, A
V = volume.
Thus proportional to the number of osmotically active

Absorbance
particles per unit volume, not mw. Ideal ionic solutions B
dissociate completely in solution, whereas in the body
incomplete dissociation and interactions between ions
result in lower osmotic pressure than predicted. Plasma
osmotic pressure is approximately 7.3 atmospheres.
See also, Oncotic pressure; Osmolality and osmolarity;
Tonicity

Ouabain. Cardiac glycoside, poorly absorbed from the 400 500 600 700 800 900
GIT and administered iv. Faster acting than digoxin; thus Wavelength (nm)
used when rapid action is required. 5% protein-bound,
with half-life about 24h, and excreted via kidneys and HbO
liver. Hb
Dosage: 100250g by iv infusion.
Not commercially available in the UK. Fig. 124 Absorbance of light by oxygenated (HbO) and deoxygenated
(Hb) haemoglobin: A and B are isobestic points. The vertical dashed
lines indicate the wavelengths (660nm and 940nm) most often used
Outreach team. Concept similar to the medical emer- by modern pulse oximeters
gency team, for improving identification and care of
acutely ill patients throughout hospitals but especially
on general wards. Usually nurse-led, but may also contain
experienced medical and physiotherapy staff, often from
ICUs, who may provide the following services: rapid in 1940 using ear/hand probes, but the technique was
response to acutely ill patients in general ward areas, cumbersome and difficult to perform. Modern pulse
critical care education for ward clinicians, facilitation of oximeters became widespread from the 1980s following
early admission to ICU/HDU, early recognition of advances in microchip technology, allowing manipula-
patients for whom CPR and/or ICU admission is inap- tion of the recorded signal. Included in the UK/Ireland
propriate and early post-ICU follow-up. Referral criteria minimal monitoring standard for anaesthesia since 1987.
include specific clinical scenarios or the results of early Relies on the principle that absorbance of light
warning scores. energy by haemoglobin varies with its level of oxygen-
Goldhill DR (2005). Br J Anaesth; 95: 8894 ation. Oxygenated and deoxygenated haemoglobin
See also, Acute life-threatening events recognition and (HbO and Hb respectively) have different absorbance
treatment spectra (Fig. 124). Isobestic points occur where the lines
cross. Thus comparison of absorbance at different wave-
Ovarian hyperstimulation syndrome. Condition lengths allows estimation of the relative concentrations
caused by pharmacological stimulation of the ovaries in of HbO and Hb (i.e. SaO2). Earlier machines used two
assisted conception programmes. Characterised by wavelengths, including one isobestic point as a reference;
ovarian enlargement, pleural effusion and ascites; the modern pulse oximeters may use two or more wave-
latter in particular may be massive and unrelenting. lengths, not necessarily including an isobestic point.
Clinical features range from abdominal discomfort and Blood gas machines estimate SaO2 from arterial
swelling to hypovolaemic shock, hepatic impairment, samples, whereas pulse oximeters read from ear or finger
acute kidney injury and acute lung injury. DVT may also probes measuring light passing through tissue. Analysis
occur. Mild symptoms occur in up to a quarter of cases of reflected light has also been used to determine SaO2;
of induced ovulation, whilst the severe form occurs surface probes have been developed which may be stuck
in 12%. on to skin at any site, e.g. the head of a fetus. All oxim-
Treatment is mainly supportive, with correction of eters are calibrated using data measured from human
hypovolaemia, careful attention to fluid balance and cor- volunteers; saturations < 80% are therefore estimated
rection of metabolic disturbances. DVT prophylaxis is from extrapolated data, and may be inaccurate.
recommended. Abdominal paracentesis and pleural Mannheimer PD (2007). Anesth Analg; 105: S1017
drainage are usually performed in severe cases; ultrafil- See also, BeerLambert law
tration and re-infusion of the ascitic fluid iv have been
used to replace the protein-rich fluid otherwise lost. Oxpentifylline, see Pentoxifylline
Sansone P, Aurilio C, Pace MC, etal (2011). Ann N Y
Acad Sci; 1221: 10918 Oxycodone hydrochloride. Opioid analgesic drug,
described in 1916. Oral preparations are twice as potent
Overdoses, see Poisoning and overdoses as oral morphine due to higher oral bioavailability.
Intravenous oxycodone is roughly equivalent to iv
Oximetry. Determination of arterial O2 saturation of morphine.
haemoglobin (SaO2) by measuring absorbance of light by Dosage: initially 5mg 46-hourly, increased to a
blood. Described in 1934 using open blood vessels, and maximum of 400mg/day. Slow-release oral
436 Oxygen

preparations are available, allowing bd dosing. May  O2 = cardiac output (CO) arterial O2 content
D
also be given sc/slowly iv: 110mg 4-hourly. = 850 1200 ml/min (500 700 ml/min/m 2 )
Also available as suppositories (as the pectinate) by
special order. V O2 = CO (arterial O2 content
mixed venous O2 content)
= 240 2770 ml/min (120 160 ml/min/m 2 )
Oxygen. Non-metallic element existing as a colourless
May be used to supplement other measured cardiovas-
odourless diatomic gas (O2) in the lower atmosphere,  O2 falls, a critical
cular variables, e.g. BP, CVP, CO. As D
and as triatomic oxygen (O3, ozone) and monatomic
point is reached, after which V O2 also falls, representing
oxygen (O) in the upper atmosphere. The most plentiful  O2 above
tissue anaerobic respiration. Maintenance of D
element in the Earths crust (as opposed to nitrogen, the
600ml/min/m2, and V O2 above 170ml/min/m2, was pre-
most plentiful in the atmosphere), it makes up 21% of
viously suggested to increase survival in critical illness,
air by volume. Discovered independently in 1771 by
but this is no longer considered to be the case.
Scheele and Priestley, the latter calling it dephlogisti-
O2 extraction ratio has also been used (normally
cated air. Recognised as a gas by Lavoisier, who named
2230%):
it and explained the process of combustion. Combines
with many other elements and molecules, and most arterial mixed venous O2 contents
abundant as water. arterial O2 content
Essential for cellular respiration in animals and lower
Vincent JL (1991). Can J Anaesth; 38: R447
plants; higher plants take in CO2 and release O2 during
See also, Oxygen extraction ratio; Oxygen, tissue tension;
photosynthesis. Boiling point is 183C; melting point is
Regional tissue oxygenation; Shock
218C; critical temperature is 118C. Atomic weight
is 16; specific gravity is 1.1 for liquid O2 and 1.4 for
Oxygen extraction ratio. Ratio of oxygen uptake
gaseous O2.
(V O2) to oxygen delivery ( D
 O2), expressed as a percent-
Commercial O2 is supplied in liquid form, manufac-
age. Normally about 25%, it increases during periods of
tured by the fractional distillation of air. Available in
increased tissue demand, e.g. exercise. Also varies
hospitals by piped gas supply, O2 concentrators or in
according to the tissue involved; thus myocardial extrac-
cylinders at 137 bar.
tion ratio is about 70%.
[Carl W Scheele (17421786), Swedish chemist]
See also, Oxygen ; Phlogiston; Vacuum-insulated
Oxygen failure warning device. Device attached to (or
evaporator
incorporated into) the anaesthetic machine; designed to
alert anaesthetists to failure of the O2 supply. Earlier
Oxygen cascade. Series of steps of PO2 from atmo- models were often unreliable, e.g. Bosun device (required
spheric air to mitochondria in cells: batteries to power a warning light, which could be
dry atmospheric gas: 21kPa (160mmHg): influ- switched off, and only operated when the N2O supply
enced by barometric pressure and inspired O2 was connected).
concentration. Ideal features of mechanical devices:
humidified tracheal gas: 19.8kPa (150mmHg). audible warning activated when O2 pressure falls
alveolar gas: 14kPa (106mmHg): influenced by below a certain value; powered by O2 itself.
alveolar ventilation and O2 consumption. warning continues when O2 is exhausted; powered
arterial blood: 13.3kPa (100mmHg): influenced by by N2O.
V/Q mismatch. delivery of N2O turned off.
capillary blood: 67kPa (4555mmHg): influenced breathing system opened to atmosphere, allowing
by blood flow and haemoglobin concentration. inhalation of air.
mitochondria: 15kPa (7.540mmHg). cannot be switched off.
Reduction in PO2 at any stage, e.g. due to hypoventila- Most consist of a spindle, kept at one end of its casing
tion, lung disease, causes reduction in subsequent steps, by the normal working O2 pressure; a spring moves the
risking inadequate mitochondrial PO2 for aerobic metab- spindle towards the other end as O2 pressure falls, allow-
olism (below the Pasteur point). ing O2 to pass to a whistle via a port previously blocked
See also, Hypoxia; Oxygen, tissue tension; Oxygen by the spindle. Further movement as O2 pressure contin-
transport ues to fall allows N2O to flow to a whistle, stops N2O
delivery to the patient and opens the system to air. Many
have a visual indicator too, e.g. producing a colour
Oxygen concentrator. Device for extracting O2 from
change.
atmospheric air. Air is passed under pressure through a
More recent devices are electronic rather than
column of zeolite which acts as a molecular sieve, trap-
gas-powered.
ping nitrogen and water vapour whilst leaving O2 and
trace gases. Nitrogen is removed by depressurising the
column. Two columns are used, each alternatively Oxygen flux. Amount of O2 delivered to the tissues per
adsorbing or expelling nitrogen. Produces a continuous unit time.
supply of over 90% O2, suitable for most medical uses. Equals:
Range in size from small units for home use to large ones CO arterial O2 content
supplying whole hospitals. = (CO O2 bound to haemoglobin
+ O2 dissolved in plasma)
 O2 ). Calculated O2 flux. Used with = CO [(10 Hb Sa O2 1.34) + (10 Pa O2 0.0225)]
Oxygen delivery ( D
O2 consumption (V O2) to optimise treatment in critical where CO = cardiac output in l/min
illness. Hb = haemoglobin concentration in g/dl
 Oxygen saturation 437

SaO2 = arterial O2 saturation of haemoglobin and gold mesh cathode within potassium
1.34 = Hfners constant hydroxide solution. Hydroxide ions are pro-
PaO2 = arterial PO2 in kPa duced at the cathode as above; they combine
0.0225 = ml of O2 dissolved per 100ml plasma with lead at the anode to form lead oxide and
per kPa (0.003ml per mmHg) give up electrons. Thus current flows, propor-
tional to the number of O2 molecules diffusing
Normally 8501200ml/min, or 500700ml/min/m2 if
through the plastic membrane. No external
cardiac index is used.
power source is required, but lifespan is limited.
The tissues cannot utilise all of the transported O2:
May be affected by N2O unless special cells
the last 2025% remains bound to haemoglobin. Tissue
are used.
O2 supply can increase during times of extra demand via
- paramagnetic cell: most gases are diamagnetic,
increases in cardiac output, e.g. during exercise. If the O2
i.e. repelled by magnetic fields. O2 and nitric
carrying capacity of blood is reduced (e.g. in anaemia)
oxide are paramagnetic, i.e. attracted. The cell
cardiac output must increase at rest in order to maintain
contains two nitrogen-filled glass spheres joined
O2 flux, and reserves are less. Myocardial depression
by a bar which is suspended on a vertical wire
during anaesthesia in this situation is thus particularly
within a magnetic field. O2 introduced into the
hazardous.
cell is attracted into the magnetic field, displac-
See also, Oxygen delivery; Oxygen extraction ratio;
ing the spheres and rotating the bar against the
Oxygen, tissue tension; Oxygen transport
torque of the wire. Degree of rotation is propor-
tional to the number of O2 molecules. It may be
Oxygen, hyperbaric. O2 therapy at greater than atmo- measured by observing the deflection of a beam
spheric pressure, usually 23 atmospheres. Increases the of light reflected by a mirror mounted on the
amount of dissolved O2 in blood, according to Henrys wire, or by measuring the current required to
law. In 100ml blood, 0.3ml O2 dissolves at PO2 of prevent rotation when passing through a coil
13.3kPa (100mmHg). Thus for 100% O2 at 3 atmo- mounted on the bar. A rapid response paramag-
spheres, dissolved O2 = 5.7ml. Since haemoglobin is netic device employs an alternating magnetic
always saturated, even in venous blood, its binding field applied to two streams of gas, one sample
capacity for CO2 and buffering capacity are reduced, and and the other reference; the O2 concentration in
pH falls. The resultant hyperventilation may result in the sample gas is represented by a difference in
hypocapnia. pressure between the two streams. Alterna-
Used in the treatment of carbon monoxide poisoning, tively, an alternating magnetic field is applied to
air embolism, gas gangrene, decompression sickness and the gas, producing a sound wave; its amplitude
chronic wounds, and has been investigated as an adjunct is proportional to the concentration of O2 (mag-
to radiotherapy and in multiple sclerosis. Single-patient netoacoustic technique). Accuracy of these
chambers filled with 100% O2 may be used, or large techniques is high.
pressurised chambers containing patient and attendants, - non-specific methods, e.g. mass spectrometer,
with a tightly fitting mask applied to the patient. ultraviolet light absorption.
Gill AL, Bell CNA (2004). QJM; 97: 38595 measurement of arterial PO2:
See also, Oxygen transport - O2 electrode as above. Tiny intravascular probes
have been developed for continuous arterial
Oxygen measurement. Methods include: measurement.
gas analysis: - transcutaneous electrode: similar to the O2 elec-
- chemical, e.g. conversion to non-gaseous com- trode, but with a heating coil to cause vasodilata-
pounds, with reduction in overall volume of gas tion, increase rate of O2 diffusion, and reduce the
mixture (Haldane apparatus). difference between arterial and skin PO2. Inac-
- physical: curate, especially in adults, and with slow response
- O2 electrode (Clark electrode; polarographic time; they may also cause burns.
cell): silver/silver chloride anode and platinum - fibreoptic sensor placed intravascularly; measures
cathode in potassium chloride solution inside a intensity or wavelength of reflected light.
cylinder, with a gas-permeable plastic mem- measurement of arterial O2 content: e.g. liberation

brane covering its end. 0.6 V potential is applied of gas from blood with chemical analysis (van Slyke
across the electrodes. O2 diffuses to the cathode, apparatus) or use of an O2 electrode.
reacting with electrons and water to form measurement of oxygen saturation of
hydroxide ions and causing current flow propor- haemoglobin.
tional to the O2 concentration. Thus: [Leland C Clark (19182005), US biochemist]
O2 + 2 H 2O + 4e 4OH
The following reactions occur at the anode: Oxygen radicals, see Free radicals
4 Ag 4 Ag + + 4e
Oxygen saturation. Refers to percentage saturation of
4 Ag + + 4Cl 4 AgCl haemoglobin with O2; equals
May be used with gas or liquid samples. Main- O2 content of haemoglobin
tained at 37C. Falsely high readings caused by
halothane are prevented by using a membrane O2 capacity of haemoglobin
impermeable to halothane. May be calculated for whole blood, and the dissolved O2
- fuel cell: similar to the O2 electrode but pro- component subtracted, or measured using oximetry.
duces its own potential. Consists of lead anode Normal range in arterial blood at 37C, pH 7.40 and
438 Oxygen therapy

- All perform similarly, delivering approximately

Table 33 Effects of breathing air or 100% O2
2530% O2 at 2l/min O2 flow, and 3040% at
Air 100% O2
4l/min flow.
other means of administration include IPPV and its

Alveolar PO2 (kPa [mmHg]) 14 (106) 88 (667) variations, CPAP, apnoeic oxygenation and hyper-
Arterial blood baric therapy. Transtracheal administration has also
PO2 (kPa [mmHg]) 13.3 (100) 84 (638) been used in chronic lung disease requiring continu-
O2 saturation (%) 99 100 ous O2 therapy, via a narrow-bore catheter inserted
O2 content (ml/100ml blood): above the sternal notch.
bound to haemoglobin 19.7 20.1 Problems of O2 therapy:
dissolved 0.3 1.9 reduction of hypoxic ventilatory drive in a small
Venous blood
group of patients who have chronic CO2 retention,
PO2 (kPa [mmHg]) 5.3 (40) 7 (53.2)
e.g. COPD. Apnoea may result if chronic hypoxae-
O2 saturation (%) 75 85
O2 content (ml/100ml blood):
mia is reversed, thus necessitating controlled O2
bound to haemoglobin 14.9 17.2 therapy. 24% O2 is administered initially; if arterial
dissolved 0.1 0.2 PCO2 has not risen by more than 11.5kPa (7.5
10mmHg), and PO2 has not improved adequately,
28% O2 is administered, then 30%, etc., until satis-
factory PO2 and PCO2 have been achieved. It has
normal barometric pressure is 97100%. Reduced in recently been suggested that this phenomenon is
cardiac or respiratory disease. related to an acute decrease in pulmonary vascular
resistance following O2 administration, rather than
Oxygen therapy. Used to: a reduction in hypoxic ventilatory drive itself.
correct hypoxaemia due to V/Q mismatch, hypo pulmonary and CNS O2 toxicity.
ventilation or impaired alveolar gas diffusion. Only absorption atelectasis.
partially corrects hypoxaemia due to shunt. increased risk of explosions and fires.
increase pulmonary O2 reserves, e.g. in case of retinopathy of prematurity.
apnoea, hypoventilation. [MC: Mary Catterall (19392009), London physician]
increase the amount of dissolved oxygen, e.g. in
anaemia, cyanide poisoning and carbon monoxide Oxygen, tissue tension (PTO2). Partial pressure of O2 in
poisoning (also increases rate of carboxyhaemoglo- tissues; represents the balance between local supply and
bin dissociation). consumption of O2. Most often measured in subcutane-
other uses include reduction of pulmonary hyper- ous tissue because of its ease of measurement and rela-
tension, reduction of air-filled cavities (e.g. subcuta- tive stability (normally 1ml/kg/min). Measured using an
neous emphysema, pneumothorax, air embolism, O2 electrode mounted on a microcatheter or a fibreoptic
intestinal distension), and special uses of hyperbaric probe placed under the skin. Has been used to indicate
O2 (see Oxygen, hyperbaric). tissue perfusion; thought to be important in wound
The effects of breathing 100% O2 compared with air are healing and susceptibility to infection.
shown in Table 33. Ragheb J, Buggy DJ (2004). Br J Anaesth; 92: 4648
Methods of administration:
fixed performance devices; i.e. FIO2 is constant, Oxygen toxicity. May be:
despite changes in inspiratory flow rate: respiratory: pulmonary toxicity is related to
- O2 tent. actual PO2, not concentration. Tracheobronchial
- anaesthetic breathing system. irritation and substernal discomfort are noticed by
- Venturi devices or high air flow O2 enrichers healthy volunteers after 1224hbreathing 100%
(HAFOE): the facemask feed connector incorpo- O2. Reduced vital capacity, compliance and diffus-
rates holes designed to allow entrainment of ing capacity, and increased arteriovenous shunt and
atmospheric air into the O2 stream by jet mixing. dead space may occur after 2436h. Changes
Specific connectors produce set FIO2 values at include endothelial damage, reduced mucus clear-
certain O2 flow rates, assuming the patients peak ance and infiltration by inflammatory cells. Surfac-
inspiratory flow rate does not exceed the total gas tant levels may decrease and capillary permeability
flow rate (if this occurs, air will be entrained via increase. Eventually fibrosis may occur, although
the side-holes in the facemask, and the FIO2 maximal safe concentrations and duration of O2
will fall). Devices that deliver lower FIO2 entrain therapy are unclear. Up to 48hbreathing 100% O2
more air and deliver higher total gas flow, and is thought not to be associated with permanent
so deliver the stated FIO2 more reliably; e.g. the damage; up to 50% is considered safe for any
0.28 FIO2 device delivers a total flow of 45l/min period. Certain cytotoxic drugs increase the inci-
to the patient, while the 0.6 FIO2 delivers 30l/min dence and severity of fibrosis, e.g. bleomycin. Free
total flow. radical formation is the most likely mechanism.
variable performance devices; i.e. FIO2 depends on Free radical scavengers, surfactant and leukotriene
inspiratory flow rates: blocking drugs have been investigated as protective
- nasal cannulae. A nasal catheter, with a foam cuff or therapeutic agents, but prevention is considered
to aid placement in the nostril, is also available. more effective. The lowest FIO2 that produces an
- plastic masks, e.g.: acceptable arterial PO2 should be used whenever O2
- moulded hard plastic. is administered.
- Edinburgh: soft plastic. neurological: at above 23 atmospheres, convulsions
- MC: soft plastic with foam-padded edges. may occur (Bert effect).
 Oxytocin 439

ocular: exposure to high arterial PO2 for long periods

may lead to retinopathy of prematurity. (a)

Arterial blood
Oxygen transport. In a normal person with a haemo- 100
globin concentration of 15g/dl breathing air, arterial
blood carries approximately 20ml O2 per 100ml: Venous blood
19.7ml combined with haemoglobin.
75

% Saturation
0.3ml dissolved in plasma.
In venous blood, 15ml is carried per 100ml blood: 50
P50
14.9ml combined with haemoglobin.
0.1ml dissolved.
Normally, the amount carried by haemoglobin is only
slightly increased with O2 therapy, since haemoglobin is
already over 97% saturated; the dissolved O2 is increased
in proportion to the arterial PO2: 0.0226ml per kPa per 0
100ml blood (0.3ml per 100mmHg). 0 2 4 6 8 10 12 14 (kPa)
See also, Oxygen flux 25 50 75 100 (mmHg)
Po2
Oxygenation index. Indicator of the degree of impair-
ment of oxygenation, often used in studies of neonatal (b)
respiratory support as a means of assessing severity of
respiratory failure when comparing different respiratory 100
therapies:
F O (%) mean airway pressure (cmH 2O)
equals I 2 % Saturation
PO2 (mmHg)
Values above 40 are associated with about 80% mortal- 50
ity with conventional treatment.

Oxygenators, see Cardiopulmonary bypass

Oxyhaemoglobin dissociation curve. Plot of oxygen

saturation of haemoglobin against PO2, for normal Po2
haemoglobin and PCO2 at 37C (Fig. 125a). The curve
is sigmoid-shaped because of the increasing affinity Fig. 125 Oxyhaemoglobin dissociation curve: (a) normal; (b) shift to
of haemoglobin for successive O2 molecules after right or left
the first.
Important points on the curve:
P50: PO2 at which saturation is 50%; normally about
3.5kPa (27mmHg).
venous blood: normally corresponds to 75% satura-
Developed in 1955. Available in the USA for parenteral
tion and PO2 of 5.3kPa (40mmHg). and rectal use. Action lasts 45h.
arterial blood: normally corresponds to 97% satura-
tion and PO2 of 13.3kPa (100mmHg). Oxytocin. Hormone secreted by the posterior pituitary
Thus a small drop in PO2 from normal levels causes gland, causing smooth muscle contraction in the uterus
only slight reduction in arterial saturation, because the and milk ducts. Used to stimulate uterine contraction,
curve is flat at this point. If PO2 is already reduced, e.g. e.g. during labour, postpartum or postabortion. Less
in lung disease, the same small drop may cause signifi- effective in early pregnancy. Acts within 23min of iv
cant desaturation, corresponding to the steep part of injection. Synthetic preparation (Syntocinon) is free of
the curve. vasopressin, and thus preferable to pituitary extract.
The curve is shifted to the right (i.e. P50 > 3.5kPa) by Causes less nausea/vomiting than ergometrine and
acidosis, hyperthermia, hypercapnia (Bohr effect) and does not cause hypertension (but see below). Available
increased 2,3-DPG levels (Fig. 125b). Saturation as 5U and 10U, and as 5U in combination with ergo-
becomes lower for any given PO2; i.e. O2 is bound less metrine 500g.
avidly. Thus O2 unloading to the tissues is favoured. Dosage:
The curve is shifted to the left (i.e. P50 < 3.5kPa) in to stimulate labour: 14mU/min iv, increased in at
the opposite situations, and in fetal haemoglobin, met least 20-min steps up to 20mU/min.
haemoglobinaemia and carbon monoxide poisoning. at caesarean section or after vaginal delivery: 2.5
Saturation becomes greater for any given PO2; i.e. O2 is 5U slowly iv (may also be given im, although not
bound more avidly. Thus fetal haemoglobin can bind O2 licensed by this route). Often given as an infusion
from maternal haemoglobin. after caesarean section (typically 40U/500ml,
See also, Myoglobin given over 4h).
to treat postpartum haemorrhage: 510U slowly iv
Oxymorphone hydrochloride. Opioid analgesic drug, followed by 540U/500ml crystalloid, infused as
derived from morphine and 68 times as potent. required.
440 Oxytocin

Side effects: given rapidly, in doses > 5U and following ephed-

uterine hyperstimulation and fetal distress. rine administration. Severe hypotension may occur
reduction in SVR and BP and increased cardiac when oxytocin is given to patients with cardiac
output results from vasodilatation (thought to be disease.
due at least partly to the preservative/vehicle rather severe hyponatraemia has followed prolonged
than to the drug itself), together with autotransfu- infusion if diluted in dextrose solutions, exacer-
sion from the uterus to the systemic circulation. bated by a direct antidiuretic effect of the hormone
Tachycardia may also occur. These changes may be itself.
severe, especially when a single bolus of oxytocin is rashes, nausea, allergic reactions.
 P
P50, see Oxyhaemoglobin dissociation curve pacemakers are checked and adjusted via radiofre-
quency programming without requiring removal, and
P value, see Probability recorded data downloaded for analysis of cardiac
function.
Indicated if an arrhythmia is associated with
P wave. Component of the ECG representing atrial
syncope, dizziness and cardiac failure, e.g. in sick sinus
depolarisation. Normally positive (i.e. upwards) in lead
syndrome, heart block or post-MI. Prophylactic use is
I, and best seen in leads II and V1 (see Fig. 59b; Electro-
controversial.
cardiography). Maximal amplitude is normally 2.5mm
A generic pacemaker code identifies function (Table
in lead II, and its duration 0.12 s (three small squares).
34), the first three positions indicating basic pacing func-
In right atrial enlargement, the P wave is tall and peaked
tion. Thus VVI denotes ventricular pacing and sensing,
(P pulmonale); in left atrial enlargement, it is wide and
with inhibition of pacing if any spontaneous ventricular
notched (P mitrale).
complex occurs (e.g. as would apply in temporary trans-
See also, PR interval
venous pacing). DDD denotes pacing and sensing of
both chambers, with inhibition or triggering to maintain
Pacemaker cells. Cardiac muscle cells that undergo sequential atrial and ventricular contraction, allowing
slow spontaneous depolarisation to initiate action poten- spontaneous activity if it occurs. Rate modulation implies
tials. Their activity results from a slow decrease in mem- the ability to alter the heart rate in response to the
brane potassium ion permeability, resulting in gradual patients level of activity; rate-adaptive devices respond
increase in intracellular potassium concentration. Rate to physiological parameters normally associated with
of discharge depends on the slope of phase 4 depolarisa- changes in heart rate (e.g. body movement, QT interval,
tion, resting membrane potential and threshold poten- respiration, temperature, pH, myocardial contractility,
tial. Pacemaker cells exist in the sinoatrial (SA) node, haemoglobin saturation) by increasing the pacing rate.
atrioventricular (AV) node, bundle of His and ventricu- The fifth position is allocated to multisite pacing, which
lar cells. Spontaneous rates of discharge for the different refers to stimulation of different sites either within one
sites: SA node 7080/min, AV node 60/min, His bundles chamber (e.g. right ventricle) or within two chambers of
50/min and ventricular cells 40/min. Impulses from the same type (e.g. both ventricles). With the develop-
the faster SA node usually reach and excite the slower ment of implantable cardioverter defibrillators, much of
pacemaker cells before the latter can discharge the latter functions are covered within the defibrillator
spontaneously. codes (see Defibrillators, implantable cardioverter).
See also, Heart, conducting system Anaesthesia for patients with pacemakers:
preoperatively:
Pacemakers. Devices implanted subcutaneously, usually - preoperative assessment is particularly directed
outside the thorax, that provide permanent cardiac towards the CVS.
pacing (to distinguish them from temporary pacing - pacemaker type and indication are ascertained.
devices). Pacemakers are usually checked regularly (e.g.
Modern devices consist of a titanium casing, contain- every 3 months).
ing the pulse generator and lithium iodide battery (the - ECG:
latter lasting > 10 years). Electrodes are usually unipolar; - if pacing spikes occur before all or most beats,
i.e. one intracardiac electrode, with current returning heart rate is pacemaker-dependent.
to the pacemaker via the body. The heart electrode is - although traditional advice was to convert
usually endocardial, passed via a central vein; epicardial older demand pacemakers to fixed rate by
electrodes have been used. Leads may be steroid-eluting placing a magnet over the pulse generator, this
to reduce inflammation at the site of contact. Modern is no longer recommended outside specialist

Table 34 North American Society of Pacing and Electrophysiology/British Pacing and Electrophysiology Group generic pacemaker code

Position 1: chamber paced Position 2: chamber sensed Position 3: response Position 4: rate modulation Position 5: multisite pacing

0 = None 0 = None 0 = None 0 = None 0 = None

A = Atrium A = Atrium T = Triggered A = Atrium R = Rate modulation
V = Dual V = Ventricle I = Inhibited V = Ventricle
D = Dual D = Dual D = Dual D = Dual

441
442 Packed cell volume

cardiac pacing units since the effect on the Paediatric anaesthesia. Main considerations are related
devices programming is unpredictable. to the anatomical and physiological differences between
- CXR: pulse generator and lead position may be adults and children, especially neonates (defined as < 1
identified. month old; infants are < 1 year old).
perioperatively: Thus in children compared with adults:
- potential electrical interference or pacemaker RS:
damage by diathermy is more likely if the latter - the tongue is large and the larynx situated more
is applied near the device. Sensing may be trig- anteriorly and cephalad (C34). The epiglottis is
gered, with resultant chamber inhibition, or large and U-shaped. A straight laryngoscope
arrhythmias induced. Diathermy may also repro- blade is thus often preferred for tracheal intu
gramme the pacemaker to a different mode. bation, and the head should be in the neutral posi-
- if avoidance of diathermy is not possible, risks are tion (as opposed to the sniffing position in
reduced by using bipolar diathermy, or placing the adults).
plate distant from the pacemaker if unipolar dia- - the cricoid cartilage is the narrowest part of the
thermy is used. Current should not be applied upper airway up to 810 years of age (cf. glottis in
across the chest, and its strength and duration of adults). A small decrease in diameter (e.g. caused
use should be minimal. by oedema or stricture formation following pro-
- care should be taken with CVP/pulmonary artery longed tracheal intubation) may lead to airway
catheters since they may dislodge the electrodes. obstruction.
- temporary pacing facilities (or non-invasive trans- - the left and right main bronchi arise at equal
thoracic pacing) and an external defibrillator angles from the trachea. At birth, the tracheo-
should be available. bronchial tree is developed as far as the terminal
- isoprenaline may be required if pacemaker failure bronchioles. Alveoli number 20 million, increas-
occurs. ing to 300 million by 68 years.
- alteration of pacemaker sensitivity by halothane - respiration is predominantly diaphragmatic, and
has been described in older pacemaker models. sinusoidal and continuous instead of periodic.
- avoidance of suxamethonium has been suggested Neonates are obligatory nose breathers. Respira-
in case fasciculations are sensed as arrhythmias. tory rate is increased. Tidal volume is about
- MRI may be hazardous since the pacemaker may 7ml/kg as in adults. The infant lung is more sus-
be switched to asynchronous mode, may fail alto- ceptible to atelectasis because the chest wall is
gether or may move within the chest. more compliant and therefore pulled inwards by
postoperative pacemaker checking may be the lungs, decreasing FRC. Closing capacity may
required. exceed FRC during normal respiration in neo-
American Society of Anesthesiologists (2011). Anesthe- nates and infants. Surfactant may be deficient in
siology; 114: 24761 premature babies.
- response to CO2 is reduced at birth, and irregular
Packed cell volume, see Haematocrit breathing may also occur. Premature babies may
suffer from apnoeic episodes; they are at risk of
PADP, Pulmonary artery diastolic pressure, see Pulmo- postoperative apnoea up to about 50 weeks post-
nary artery pressure conceptual age. Gasp and HeringBreuer reflexes
are active.
Paediatric Advanced Life Support (PALS). Course set - basal metabolic rate and O2 consumption are high
up in the USA by the American Heart Association and (the latter is 56ml/kg/min, compared with about
the American Academy of Pediatrics. Intended for 34ml/kg/min in adults). Hypoxaemia thus occurs
healthcare professionals caring for acutely ill children more rapidly than in adults.
(e.g. those working in paediatric, anaesthetic, intensive - the oxyhaemoglobin dissociation curve of fetal
care and emergency departments). Course objectives haemoglobin is shifted to the left (P50 of 2.4kPa
include: [18mmHg]). Haemoglobin concentration falls
recognition of the infant or child at risk of cardio- from 18g/dl (12 weeks of age) to 11g/dl (6
pulmonary arrest and the application of strategies months6 years).
for its prevention. CVS:
identification of the cognitive and psychomotor - cardiac output is 3050% higher than in adults,
skills necessary for resuscitating and stabilising the largely due to increased heart rate. Arterial BP is
neonate, infant or child in respiratory failure, shock lower (Table 35).
or cardiopulmonary arrest (e.g. drug dosages, airway
and ventilation techniques, identification of normal
and abnormal cardiac rhythms, defibrillation, vascu-
lar access).
The course is predominantly practical with an emphasis Table 35 Normal heart rate and BP at different ages
on hands-on training. Technical skills and cognitive pro-
cesses are first taught separately in small group sessions. Age Heart rate (beats/min) BP (mmHg)
Practical application of these skills and knowledge in
critical situations is then emphasised by using case 06 months 120180 80/45
presentations. 3 years 95120 95/65
Kleinman ME, Chameides L, Schexnayder SM, et al 5 years 90110 100/65
(2010). Circulation; 122 (suppl 3): S876908 10 years 80100 110/70
See also, Advanced Paediatric Life Support
 Paediatric anaesthesia 443

- left and right ventricles are similar at birth, the blocking drugs, probably due to altered pharmaco-
former fibrous and non-compliant, making stroke kinetics. They may be resistant to suxamethonium,
volume relatively fixed. requiring up to twice the adult dose.
- blood volume at birth is up to 90ml/kg (or 50 + Practical conduct of anaesthesia:
haematocrit). It falls to 80ml/kg for children and children are placed first on the operating list, to
70ml/kg by 14 years. allow as short a fasting time as possible.
- veins are more difficult to cannulate. most standard drugs are used, administered
- reversion to fetal circulation may occur in severe according to weight. As a rough guide the following
hypoxaemia. scheme may be useful:
CNS: - 14 years: adult dose.
- the spinal cord ends at L3 at birth, receding to - 7 years: 1 2 adult dose.
L12 by adolescence. - 4 years: 1 3 adult dose.
- the immature bloodbrain barrier results in - 1 year: 1 4 adult dose.
increased sensitivity to centrally depressant drugs, - newborn: 1 8 adult dose.
particularly opioid analgesic drugs. - premature: 1 10 adult dose.
- vagal reflexes are particularly active in children. premedication is often given orally, to avoid injec-
Bradycardia readily occurs in hypoxaemia. tions, but standard im drugs are also given. Rectal
- subependymal vessels are fragile in premature administration has also been used. Atropine may
neonates, with risk of rupture if BP and ICP be given to reduce excessive secretions and vagal
increase. reflexes.
temperature regulation is impaired. Ratio of body induction of anaesthesia:
surface area to body weight is greater than in adults - cyclopropane was popular but is no longer avail-
and there is less body fat. Thus heat loss is rapid, able in the UK. Halothane has been replaced by
compounded by impaired shivering and increased sevoflurane. Inhalational induction is rapid
metabolic rate. Brown fat is metabolised to main- because of increased alveolar ventilation, a low
tain body temperature. Insensible water loss is FRC and a high cerebral blood flow.
increased in premature babies. - standard iv anaesthetic agents are suitable.
prolonged fasting may cause hypoglycaemia in Administration im (e.g. ketamine) is also used.
small children, and oral clear fluids are usually EMLA or topical tetracaine (amethocaine) is
allowed up to 2h preoperatively (4h for milk). IV routinely used before iv induction.
administration of dextrose may be required. The presence of parents at induction is usually
fluid balance is delicate, since a greater proportion allowed, depending on the circumstances.
of body water is exchanged each day. Total body appropriately sized laryngoscope handles and
water is normally increased, with a higher ratio of blades are employed. Uncuffed tracheal tubes are
ECF to intracellular fluid (ECF exceeds intracellular commonly used (usually until ~10 years), with a
fluid in premature babies). The kidneys are less able small air leak at 1525 cmH2O airway pressure, to
to handle a water or solute load, or to conserve water avoid subglottic stenosis. The approximate size may
or solutes. Thus dehydration readily occurs in illness. be calculated thus:
Appropriate maintenance fluid requirements - diameter = (age/4) + 4.5mm.
(using dextrose/saline) have traditionally been cal- For neonates:
culated thus: - under 750g/26 weeks gestation: 2.02.5mm.
- 7502000g/2634 weeks: 2.53.0mm.
4ml/kg/h for each of the first 10kg, plus
- over 2000g/34 weeks: 3.03.5mm.
2ml/kg/h for each of the next 10kg, plus
- length = (age/12) + 12cm.
1ml/kg/h for each kg thereafter.
More recently, cuffed tubes have been used in term
More recently, because of the risk of perioperative neonates and children, on the basis that a smaller
hyponatraemia (children being at particular risk tube with a low-pressure, high-volume cuff is better
from resultant encephalopathy), and because peri- able to provide an adequate conduit for ventilation
operative hypoglycaemia is less of a problem than whilst minimising pressure on the cricoid cartilage
traditionally thought, there has been a move away (from the tube itself) and the trachea (from the
from hypotonic solutions such as dextrose/saline, cuff). A formula for cuffed tubes has been sug-
with maintenance fluids given as 0.450.9% saline gested: diameter = (age/4) + 3.0mm.
or Hartmanns solution, and isotonic fluids avoided dead space and resistance should be minimal in
if plasma sodium concentration is under 140mmol/l. anaesthetic breathing systems; adult forms are suit-
Blood is traditionally given above 10% of blood able if the child weighs over 2025kg but the Bain
volume loss, but larger blood losses are increasingly system is often avoided because of increased resis-
allowed if starting haemoglobin concentration is tance to expiration. Ayres T-piece is suitable up
high. In hypovolaemia, 10ml/kg colloid is a suitable to 25kg. Spontaneous ventilation via a facemask
starting regimen. or LMA is usually suitable for short procedures in
actions of drugs may be affected by the above children older than 3 months. Below this, tracheal
factors, or by lower plasma albumin levels (up to intubation and IPPV are traditionally performed,
1 year of age), resulting in greater amounts of free although the LMA is preferred by some.
drug. Renal and hepatic immaturity may contribute for IPPV using a T-piece, the following fresh
to reduced clearance. MAC of inhalational anaes- gas flows have been suggested, producing slight
thetic agents is increased in neonates, but may hypocapnia:
be reduced in premature babies. Neonates are - 1030kg: 1000ml + 100ml/kg per min.
more sensitive to non-depolarising neuromuscular - > 30kg: 2000ml + 50ml/kg per min.
444 Paediatric intensive care

Set minute volume should equal twice fresh gas congenital abnormalities). Non-accidental injury
flow. must always be considered.
routine monitoring, including temperature - head injury occurs in 50% of cases of blunt
measurement. trauma. A modified Glasgow coma scale is used
anaesthetic rooms and operating theatres should be for assessment; otherwise, management is along
warmed. Warming blankets and reflective coverings similar lines to that of adults.
should also be used, with humidification of inspired - spinal cord injury and thoracic/abdominal trauma
gases. is usually caused by road traffic accidents.
tracheal extubation may be performed with the poisoning and overdoses.
child awake or anaesthetised, depending on the Specific attention must be paid to:
clinical context. smaller equipment, drug doses and fluid volumes;
regional techniques are effective for peri- and post- specialised equipment.
operative analgesia, e.g. caudal analgesia, inguinal nutrition and electrolyte/fluid balance.
field block, penile block. Local wound infiltration is temperature regulation.
also effective. Spinal and epidural anaesthesia have sedation and analgesia.
also been used. educational and psychological needs.
paracetamol and codeine are often used for postop- the risk of retinopathy of prematurity in neonates.
erative analgesia, with morphine for severe pain. In 1997, the Department of Health recommended that
Antiemetic drugs are given as required; ondanse- level 3 paediatric intensive care should be primarily
tron and cyclizine are commonly used. delivered in lead centres supported by district general
Other problems are related to the procedure per- hospitals (capable of initiating intensive care), major
formed, e.g.: acute general hospitals (large adult ICUs already man-
repair of congenital defects, e.g. tracheo-oesophageal aging critically ill children at level 2 or 3) and specialist
fistula, pyloric stenosis, gastroschisis, diaphragmatic hospitals (e.g. those caring for children with burns or
hernia, congenital heart disease. requiring cardiac or neurosurgery). Each centre must
related to trauma. comply with specific standards relating to training,
ENT, dental and ophthalmic surgery. equipment, the experience of medical and nursing staff,
The National Confidential Enquiry into Patient Outcome access to specialist services and advice, treatment proto-
and Death (as NCEPOD) focused for its first year on cols, facilities for families and audit. Regional paediatric
paediatric anaesthesia. It concluded that general care retrieval teams have also been established.
was good, although outcome was related to clinicians Overall mortality ranges from 5 to 10% depending
experience. on admission criteria. Scoring systems such as the pae-
diatric trauma score, injury severity score and paediatric
Paediatric intensive care. Classified into levels 1, 2 risk of mortality score attempt to predict outcome and
and 3, primarily on the basis of interventions under- allow audit of care within and between units.
taken. Level 1 is high dependency care; level 3 is almost Frey B, Argent A (2004). Intensive Care Med; 30: 10416,
always provided in tertiary paediatric centres. In general, 12927
differs from adult intensive care by virtue of anatomical See also, Brainstem death; Cardiopulmonary resuscita-
and physiological differences between adults and chil- tion, neonatal; Cardiopulmonary resuscitation, paediat-
dren (see Paediatric anaesthesia) and the range of condi- ric; Necrotising enterocolitis
tions seen.
Main clinical problems encountered include:
Paediatric logistic organ dysfunction score (PELOD).
acute respiratory failure:
Scoring system for the severity of multiple organ
- upper airway obstruction: dysfunction in paediatric intensive care. Based on 12
- neonates: choanal atresia, congenital facial variables relating to six organ systems (neurological,
deformities, laryngeal/tracheal abnormalities. cardiovascular, renal, respiratory, haematological and
- infants/children: inhaled foreign body, tonsillar/ hepatic). Has been used as daily indicator of organ
adenoidal hypertrophy, croup, epiglottitis and dysfunction.
angioedema. Leteurtre S, Martinot A, Duhamel A, et al (2003). Lancet;
- lung disorders: 362: 1927
- neonates: meconium aspiration, respiratory
distress syndrome, diaphragmatic hernia, pneu-
mothorax, chest infection. Paediatric risk of mortality score (PRISM). Scoring
- infants/children: pneumonia, asthma, bronchio system used in paediatric intensive care to help predict
litis, cystic fibrosis, congenital heart disease, mortality. Originally used weighted scores for 14 vari-
trauma, near-drowning, burns. ables related to acute physiological status; the latest
- in neonates, respiratory impairment may result version (PRISM III) has 17 and includes additional risk
in the development of a persistent fetal factors, including acute and chronic diagnosis. Has been
circulation. validated for most categories of paediatric ICU.
neurological disease:
Pollack MM, Patel KM, Ruttimann UE (1996). Crit Care
- neonates: birth asphyxia, central apnoea, Med; 24: 74352
convulsions.
- infants/children: meningitis, encephalitis, status Paediatric trauma score. Trauma scale designed to
epilepticus, GuillainBarr syndrome. allow triage of paediatric patients. Six variables (weight,
trauma: the leading cause of death in children under patency of airway, systolic BP, conscious level, presence
a year old and the third leading cause in older of skeletal injury and skin injuries) attract scores of 2
children (after sudden infant death syndrome and (normal), 1 or 1 (severely compromised); scores under
 Pain management 445

8 indicate increased morbidity and mortality and require questionnaires for analysis of personality and pain
referral to a paediatric trauma centre. (e.g. Minnesota multiphasic personality inventory,
Tepas JJ, Ramenofsky ML, Mollitt DL, et al (1988). J McGill questionnaire) have been used.
Trauma; 28: 4259
Pain, intractable, see Pain; Pain clinic; Pain manage-
PAF, see Platelet-activating factor ment; individual conditions

Pain. Classically defined as an unpleasant sensory and Pain management. Acute pain, e.g. postoperative, is
emotional experience resulting from a stimulus causing, usually treated with systemic analgesics and regional
or likely to cause, tissue damage (nociception), or techniques (see Postoperative analgesia).
expressed in terms of that damage. Thus affected by Chronic pain management may involve the following,
subjective emotional factors, making pain evaluation dif- after pain evaluation:
ficult. Chronic pain may arise from nervous system dys- simple measures, e.g. rest, exercise, heat and cold
function rather than tissue damage and may be associated treatment, vibration.
with damage to pain pathways (neurogenic pain, e.g. systemic drug therapy:
trigeminal neuralgia, postherpetic neuralgia, complex - analgesic drugs: different drugs, dosage regimens
regional pain syndrome type 2, phantom limb pain, and routes of administration may be chosen,
central pain). Substances released from damaged tissues, depending on the severity and temporal pattern
and/or reorganisation of somatic and sympathetic of the pain, and efficacy and side effects of the
spinal reflex pathways, are thought to be involved in drugs. Drugs used range from mild NSAIDs to
the aetiology of chronic pain. Chronic pain is usually opioid analgesic drugs. The latter are usually
more difficult to diagnose and treat than acute pain, reserved for severe pain of short duration, or pain
and psychological and emotional factors are more associated with malignancy; they may require
important. concurrent antiemetic and aperient therapy.
See also, Allodynia; Dysaesthesia; Hyperaesthesia; Implantable devices may be used for intermittent
Hyperalgesia; Hyperpathia; Hypoalgesia; Myofascial iv, epidural or subarachnoid injection or continu-
pain syndromes; Pain clinic; Pain management; Postop- ous infusion of opioids.
erative analgesia - other drugs used include:
- psychoactive drugs, e.g. antidepressant drugs,
Pain clinic. Outpatient clinic run by consultants (usually anticonvulsant drugs (e.g. pregabalin, gabapen-
anaesthetists) with a special interest in the management tin, carbamazepine). Of these, amitryptiline,
of chronic pain. Its role includes diagnosis of the under- pregabalin and duloxetine are suitable first-line
lying condition and management directed at reducing agents for chronic/neuropathic pain.
subjective pain experiences, reducing drug consumption, - corticosteroids, either by local injection or oral
increasing levels of normal activity and restoring a therapy. Particularly useful in neuralgia or pain
normal quality of life. Requires appropriate facilities for associated with oedema, e.g. malignancy. Often
consultation, and performance of nerve blocks and sur- injected with local anaesthetic agents, e.g.
gical procedures. Anaesthetists, physicians, psychologists epidurally for back pain.
and neurologists may be involved. Primary referrals to - muscle relaxants, e.g. baclofen, dantrolene, ben-
the clinic are usually from general practitioners or hos- zodiazepines; may be useful if muscle spasm is
pital consultants. problematic.
See also, Pain management - others, e.g. antimitotic drugs, calcitonin in
bony pain, -adrenergic receptor antagonists,
Pain evaluation. Difficult to perform, because pain is a clonidine.
subjective experience. local anaesthetic nerve blocks: may be diagnostic,
Methods used depend on the setting and whether the prognostic (to allow assessment before destructive
pain is acute or chronic: lesions) or therapeutic. Include:
experimental methods (e.g. assessing analgesic - injection of trigger points in myofascial pain
effects of new drugs): syndromes.
- animals: tail-flick response to heat; pedal with- - facet joint injection.
drawal response to pinching the foot; head- - caudal analgesia, epidural anaesthesia, spinal
shaking response to ear pinching. anaesthesia.
- humans: degree of tolerated digital pressure; tol- - paravertebral nerve blocks.
erated duration of immersion of the forearm into - sympathetic nerve blocks, e.g. stellate ganglion,
icy water. coeliac plexus and lumbar sympathetic blocks, iv
acute pain, e.g. postoperative: linear analogue scale; guanethidine block.
using numbers or words to rate the degree of pain neurolytic procedures: usually reserved for severe
(patient and observer assessment may be used); pain associated with malignancy, since relief may
demand for analgesia. Babies have been studied by not be permanent and severe side effects may occur,
recording and analysing their cries. e.g. anaesthesia dolorosa. X-ray guidance is usually
chronic pain: the pain is characterised by noting its employed to aid percutaneous neurolysis. Methods
type, duration, location, quality, intensity, modifying include:
factors (e.g. food, exercise), time relations, and asso- - regional techniques as above, using phenol or
ciated symptoms and mental changes. Clinical absolute alcohol. The former is hyperbaric com-
examination and investigations are performed as pared with CSF, the latter hypobaric. Thus for
appropriate. Linear analogue and rating scales may intrathecal neurolysis the required posterior
be used as above. More complicated psychological sensory roots may be selectively destroyed with
446 Pain pathways

appropriate positioning of the patient. Pituitary DMello R, Dickenson AH (2008). Br J Anaesth; 101:
ablation has also been used. 816
- extremes of temperature, e.g. cryoprobe, radiofre- See also, Nerves; Nociception; Sensory pathways
quency probe. The latter delivers a high-frequency
alternating current, producing up to 80C heat. It Pain, postoperative, see Postoperative analgesia
is used at peripheral nerves, facet joints, dorsal
root ganglia and trigeminal ganglion, and for per-
cutaneous cordotomy. Palliative care. General approach to care of patients
- surgery: includes peripheral neurectomy, dorsal with terminal illness (often malignancy but also neuro-
rhizotomy or lesions in the dorsal root entry logical, inflammatory, etc.). Recognised as a separate
zones (DREZ), commissurotomy (sagittal divi- specialty in the UK since 1987. Includes not only
sion of the spinal cord), mesencephalotomy and symptom control but also psychological, spiritual and
thalamotomy. social support. Requires a multidisciplinary approach,
electrical stimulation: including the expertise of general physicians, oncologists,
- TENS and electroacupuncture. surgeons, nursing staff, physiotherapists and religious
- dorsal column stimulation. advisers. Anaesthetists are increasingly involved as they
- stimulation of deep brain structures has also been have expertise in controlling symptoms such as pain,
used, e.g. via electrodes implanted in the periven- anxiety, nausea and vomiting; they also care for patients
tricular grey matter or thalamus. with terminal disease in the ICU.
acupuncture. See also, Ethics; Euthanasia; Withdrawal of treatment
psychological techniques, e.g. psychotherapy, cogni- in ICU
tive behavioural therapy, operant conditioning,
hypnosis, biofeedback, relaxation techniques. Palonosetron. 5-HT3 receptor antagonist licensed as an
The World Health Organization has suggested a pain antiemetic drug in chemotherapy-induced nausea and
ladder in which mild pain is treated by a non-opioid vomiting.
adjuvant; moderate pain by a mild opioid non-opioid Dosage: single dose only of 250g iv 30min before
adjuvant; and severe pain with a strong opioid non- chemotherapy treatment.
opioid adjuvant. Side effects include GIT upset, arrhythmias, angina
and peripheral neuropathy.
Pain pathways. Most pain arises in pain receptors (noci-
ceptors) widely distributed in the skin and musculoskel-
etal system. Those responding to pinprick and sudden PALS, see Paediatric advanced life support
heat (thermomechanoreceptors) are associated with
myelinated A fibres, convey sharp pain sensation and Pancreatitis. Acute pancreatitis is an autodigestive
are responsible for rapid pain transmission and reflex process caused by unregulated activation of trypsin in
withdrawal. Receptors responding to pressure, heat, pancreatic acinar cells; this in turn leads to release of
chemical substances (e.g. histamine, prostaglandins, ace- other enzymes and activation of complement and kinin
tylcholine) and tissue damage (polymodal receptors) are pathways. Inflammatory processes also occur with the
associated with unmyelinated C-fibre endings, and are release of other harmful enzymes. Ischaemic changes,
responsible for dull pain sensation and immobilisation together with generation of free radicals, cause isch-
of the affected part. aemia and haemorrhagic necrosis of the pancreatic
Afferent impulses pass centrally thus: parenchyma. Although the condition is mild in 80% of
first-order neurones have cell bodies within the patients, mortality is high in the remainder because of
dorsal root ganglia of the spinal cord. A fibres resulting sepsis, respiratory failure, shock and acute
synapse with cells in laminae I and V of the cord, kidney injury.
whilst C fibres synapse with cells in laminae II and Associated with biliary tract disease or alcoholism in
III (substantia gelatinosa). about 80% of cases. May occasionally follow upper
most second-order neurones synapse with A fibres abdominal surgery, pancreatic ductal obstruction (e.g. by
in the posterior horn, crossing to the opposite side carcinoma), trauma, mumps, hepatitis, cystic fibrosis,
immediately or within a few segments. They ascend hypothermia, hypercalcaemia, hyperlipidaemia, diuret-
within the anterolateral columns (spinothalamic ics or corticosteroids.
tract) to the ventroposterior nucleus of the thala- Features:
mus and periaqueductal grey matter. severe epigastric pain (typically radiating through
The substantia gelatinosa does not project directly to the back), nausea and vomiting, fever, occasion-
to higher levels, but contains many interneurones ally mild jaundice.
involved in pain modulation (e.g. described by the epigastric tenderness on palpation, progressing to
gate control theory of pain). Some fibres project to features of peritonitis.
deeper layers of the spinal grey matter, giving rise to discoloration in flanks caused by tracking of blood
the spinoreticular tract which projects to the ascend- from the retroperitoneal space (Grey Turners
ing reticular activating system (ARAS). Fibres are sign) or via the falciform ligament to the umbilicus
then relayed to the thalamus and hypothalamus (Cullens sign).
(some fibres reach the thalamus without passing to hypotension, oliguria, respiratory failure.
the ARAS, via the palaeospinothalamic tract). Investigations reveal raised serum and urinary amylase
third-order neurones transmit from the thalamus to (secondary to leakage from the pancreas), leucocytosis,
the somatosensory cortex. hyperglycaemia, hypocalcaemia (secondary to calcium
Pain sensation may thus be modified by ascending or sequestration in areas of fat necrosis), hypoproteinaemia
descending pathways at many levels. and hyperlipidaemia. Since many other disorders also
 Paracervical block 447

result in increased amylase levels, measurement of the Pandemic. Outbreak of an infectious disease affecting
more specific marker serum lipase is increasingly used human populations across a wide region (e.g. multiple
for diagnosis. Abdominal X-ray may reveal a sentinel continents or worldwide).
loop of small bowel overlying the pancreas. CXR may See also, Influenza
show a raised hemidiaphragm, pleural effusion, atelecta-
sis or acute lung injury. Abdominal CT scanning may be Pantoprazole sodium. Proton pump inhibitor; actions
helpful in confirming the diagnosis and assessing the and effects are similar to those of omeprazole.
severity of pancreatic damage. Dosage: 4080mg orally or iv od.
Poor prognosis may be indicated by: age > 55 years; Side effects: as for omeprazole.
systolic BP < 90mmHg; white cell count > 15 109/l;
temperature > 39C; blood glucose > 10mmol/l; arterial Papaveretum. Opioid analgesic drug, first prepared in
PO2 < 8kPa (60mmHg); plasma urea > 15mmol/l; serum 1909 and consisting of opium alkaloids: morphine 47.5
calcium < 2mmol/l; haematocrit reduced by over 10%; 52.5%, codeine 2.55.0%, noscapine (narcotine) 16
abnormal liver function tests. 22%, papaverine 2.57.0% and others, e.g. thebaine <
Management: 1.5%. Widely popular for many years, especially as pre-
supportive, e.g. O2 therapy, iv fluid administration, medication. In response to a warning issued by the Com-
electrolyte replacement (especially calcium and mittee on Safety of Medicines that noscapine may be
magnesium), analgesia, insulin therapy and nutri- genotoxic, a new formulation was made available in
tion (via nasogastric or nasojejunal routes). MODS 1993, consisting of morphine, papaverine and codeine
is treated along conventional lines. alone. Confusion over dosage regimens has led to many
aprotinin, peritoneal lavage, glucagon, calcitonin anaesthetists abandoning papaveretum in favour of
and somatostatin have been used, but with little morphine.
evidence of efficacy. Dosage: 7.715.4mg sc, im or iv 4-hourly as required.
prophylactic antibacterial agents to prevent infec- Also available in combination with hyoscine.
tion of the necrotic pancreas are advocated but the
benefit is debatable. Papaverine. Benzylisoquinoline opium alkaloid, without
evidence of necrosis on CT imaging may merit fine- CNS activity. Used for its relaxant effect on smooth
needle aspiration to diagnose localised infection muscle, e.g. GIT and vascular. Has been used to treat
and guide antibiotic therapy. cerebral and coronary vasospasm. May be injected iv or
early endoscopic retrograde cholangiopancreatog- applied directly during surgery. Its use has been advo-
raphy (ERCP) with sphincterotomy is recom- cated following intra-arterial injection of thiopental.
mended in patients with biliary obstruction/sepsis. Dosage: up to 30mg slowly iv (may cause histamine
surgery may be required for drainage of an release). Also used in combination oral preparations
abscess or pseudocyst or for relief of biliary obstruc- to relieve GIT spasm.
tion. Resection of necrotic pancreas has been per-
formed but mortality from surgery in early disease Paracelsus (14931541). Swiss philosopher and physi-
is high. cian; his real name was Theophrastus Bambastus von
Chronic pancreatitis usually occurs in alcoholics, and is Hohenheim. Lectured at the University of Basle. Revo-
characterised by pancreatic calcification and impaired lutionised the theory of medicine, encouraging the
enzyme secretion with malabsorption, and repeated science of research and experimentation. Described the
episodes of pain. Surgery may be required; anaesthetic effects of diethyl ether on chickens in 1540 and advo-
considerations are related to alcohol abuse, and the cated its use in epilepsy. He is also credited with intro-
consequences of malabsorption and malnutrition. ducing the use of bellows for ventilating the lungs.
[George Grey Turner (18771951), English surgeon; Davis A (1993). J R Soc Med; 86: 6536
Thomas S Cullen (18681953), Canadian-born US
gynaecologist] Paracentesis. Puncture of any hollow organ or cavity
Frossard JL, Steer ML, Pastor CM (2008). Lancet; 371: for removal or instillation of material; however the term
14352 usually refers to drainage of ascites from the perito-
neum, e.g. in hepatic failure. Removal of large volumes
Pancuronium bromide. Synthetic non-depolarising improves cardiac output and respiratory function,
neuromuscular blocking drug, first used in 1967. Bisqua- decreasing portal venous pressure. It also reduces weight,
ternary amino-steroid, but with no steroid activity. Initial improving comfort and mobility. However, rapid aspira-
dose is 0.050.1mg/kg, with tracheal intubation possible tion may be followed by cardiovascular collapse and
after 23min. Effects last 4060min. Supplementary oliguria, possibly due to sudden release of the splinting
dose: 0.010.02mg/kg. Histamine release is extremely effect of the intra-abdominal fluid.
rare. May cause increases in heart rate, BP and cardiac With the patient supine and with the bladder emptied,
output, caused by vagolytic and sympathomimetic a needle is inserted through the abdominal wall, usually
actions. The latter may be due to release of noradrena- in the left and right upper and lower quadrants, after
line from sympathetic nerve endings or blockade of its infiltration with local anaesthetic. The avascular linea
uptake. Pancuronium is strongly bound to plasma gam- alba below the umbilicus is also commonly used. Inser-
maglobulin after iv injection, and metabolised mainly by tion of the needle along a Z-shaped path through the
the kidney but also by the liver. Elimination is delayed layers has been suggested, to reduce subsequent persis-
in renal and hepatic impairment. tent leakage.
Traditionally used in shocked patients requiring See also, Peritoneal lavage
anaesthesia, because of its cardiovascular effects. For-
merly commonly used in ICU, but superseded by atra- Paracervical block. Used to provide analgesia during
curium and vecuronium. the first stage of labour, or for gynaecological
448 Paracetamol

procedures, e.g. dilatation and curettage. First performed on phenytoin, barbiturates, carbamazepine or rifampicin
in 1926. therapy), or in malnourished, alcoholic or HIV-positive
With the patients legs apart, a special sheathed needle patients.
(with tip protected) is directed into the lateral vaginal Patients may be asymptomatic for 24h after inges-
fornix by the operators fingers. The needle tip is advanced tion. Early features include nausea and vomiting,
0.51cm to point cranially, laterally and dorsally, and anorexia and right upper quadrant pain. Early impaired
510ml local anaesthetic agent injected into the parame- consciousness suggests concurrent depressive drug
trial tissue on either side, blocking the uterine nerves that ingestion, e.g. alcohol, opioid analgesic drugs. Liver func-
form a plexus at the base of the broad ligament. Vaginal, tion tests become abnormal after about 18h, with pro-
vulval and perineal sensation is unaffected. longed prothrombin time and raised bilirubin at 3648h.
Seldom used in modern obstetrics, because of the Hepatotoxicity peaks at about 34 days, with hepatic
high incidence of fetal arrhythmias (especially bradycar- failure if severe. Lactic acidosis, hypoglycaemia and
dia), thought to be caused by alterations in uteroplacen- acute kidney injury may also occur. Prognostic factors
tal blood flow or absorption of local anaesthetic. include the presence of acidaemia (mortality ~95% if pH
See also, Obstetric analgesia and anaesthesia < 7.3), renal impairment, severe hepatic encephalopathy
and a factor V level < 10% (~90% mortality).
Paracetamol (Acetaminophen). Analgesic drug, Treatment:
derived from para-aminophenol; introduced in the 1950s. as for poisoning and overdoses. Activated charcoal
Inhibits central prostaglandin synthesis and has a central is given if > 150mg/kg has been ingested and if the
antipyretic action. Purported to have minimal peripheral patient presents within 1h of the overdose. Gastric
anti-inflammatory effects, although this has been dis- lavage and ipecacuanha are no longer recom-
puted. Also inhibits cyclo-oxygenase pathways in the mended. Ingestion of opioid/paracetamol combina-
brain, but less so peripherally. Does not cause gastric tions (e.g. containing codeine, dextropropoxyphene)
irritation or affect platelet adhesion. Used in isolation to should be considered if level of consciousness is
treat minor pain, and as part of a multimodal strategy depressed on presentation, and naloxone given.
for postoperative analgesia. replenishment of hepatic glutathione stores with
Rapidly absorbed after oral administration, with peak glutathione precursors:
plasma levels within 60min. Minimally protein-bound in - N-acetylcysteine: first-line antidote, previously
plasma. Conjugated with glucuronide and sulphate in thought to be effective only within 16h of poison-
the liver; < 10% is oxidised by the hepatic P450 system to ing, but evidence now also supports later admin-
form N-acetyl-p-benzoquinoneimine, a potential cellular istration. 150mg/kg is given in 200ml 5% dextrose
toxin. Normally, this is safely conjugated with glutathi- iv over 15min, followed by 50mg/kg in 500ml
one, but it may cause hepatic necrosis in paracetamol dextrose over 4h, then 100mg/kg in 1 litre dex-
poisoning, when the glucuronide and sulphate pathways trose over 16h.
are saturated and glutathione stores are depleted. Half- - methionine: animal studies suggest lower efficacy
life is about 2h, but its effects last longer. than N-acetylcysteine. Can be given within 10
Dosage: 12h of poisoning if the patient is not vomiting.
0.51.0g orally/rectally 4-hourly, up to 4g maximum 2.5g is given orally, followed by 2.5g 4-hourly for
daily. 12h. Nausea and vomiting are common side
in children, traditionally recommended dosage of effects.
1015mg/kg 4-hourly 4/day has been challenged liver transplantation may be required (see Hepatic
based on pharmacokinetic data; an initial loading failure).
dose of 20 (oral) or 40 (rectal) mg/kg may be fol- A single measurement of plasma paracetamol concen-
lowed by doses of 1015mg/kg 46-hourly up to 40 tration taken more than 4h after ingestion (earlier mea-
(premature), 60 (< 3 months old) or 90 (> 3 months) surements are unreliable) identifies patients at risk of
mg/kg/day for up to 48h (72h if > 3 months). hepatic damage and thus requiring treatment. Previ-
an iv preparation was introduced in the UK in 2004: ously, treatment was initiated at different blood levels
- adult/child > 50kg: 1g 46-hourly up to 4g daily. according to risk factors (Fig. 126); in 2012 the Commis-
- adult/child 1050kg: 15mg/kg 46-hourly up to sion on Human Medicines advised that treatment should
60mg/kg daily. be given regardless of risk factors (and if there was
- adult/child < 10kg: 7.5mg/kg 46-hourly up to doubt over the timing of ingestion).
30mg/kg daily. Ferner RE, Dear JW, Bateman DN (2011). Br Med J;
Side effects: nausea, vomiting, rashes. 342: d2218
Available in combination with other analgesics, e.g.
Paradoxical pain. Type of chronic pain that does not
codeine. Over-the-counter sale of 500mg tablets/
respond to opioid analgesic drugs in the usual way.
capsules in the UK is limited to packs of 32 (packs of
Usually associated with cancer pain. Increasing the dose
100 tablets/capsules may be purchased from pharmacists
may increase side effects without apparent reduction in
in special circumstances).
pain. Altered drug metabolism has been suggested (e.g.
Oscier CD, Milner QJW (2009). Anaesthesia; 64: 6572
for morphine, production of 6-glucuronide [analgesic]
reduced in comparison to 3-glucuronide [antanalgesic]),
Paracetamol poisoning. The commonest cause of acute
but this has been disputed. Management includes giving
hepatic failure in the UK and USA. Hepatocellular
the drug by an alternative route, using a different opioid
necrosis may occur if >150mg/kg is taken, due to satura-
or combination with adjunct drugs such as tricyclic anti-
tion of the normal metabolic pathways for paracetamol
depressant drugs.
and exhaustion of hepatic glutathione stores. Lower
doses may also be toxic, especially in the presence of Paraesthesia. Abnormal positive sensation similar to
pre-existing hepatic enzyme induction (e.g. in patients pins and needles, occurring when neural tissue
 Paramagnetic oxygen analysis 449

is irritated (e.g. peripheral nerve, spinal cord, sensory - inflammatory, e.g. transverse myelitis, multiple
cerebral cortex). May be produced accidentally or inten- sclerosis.
tionally during regional anaesthesia. Elicitation of par- - infectious, e.g. viral myelitis (e.g. herpes, polio-
aesthesia may increase the chances of successful nerve myelitis, HIV infection), epidural abscess,
block but also of neurological damage. syphilis, TB.
- degenerative, e.g. motor neurone disease, bone
Paraldehyde. Obsolete hypnotic and anticonvulsant disease affecting the spinal column.
drug, introduced in 1882. Has an offensive smell, and is - nutritional, e.g. vitamin B12 and E deficiency.
irritant and flammable. Decomposes with heat and light - hereditary, e.g. Friedreichs ataxia.
to acetic acid, and dissolves plastic. Has been used in the peripheral nerve:
treatment of psychiatric disturbance, status epilepticus - inflammatory, e.g. GuillainBarr syndrome,
and for premedication. diphtheria.
- metabolic, e.g. acute intermittent porphyria.
Paralysis, acute. May result in paraplegia (diplegia) - poisoning, e.g. heavy metal poisoning.
with paralysis of the legs and lower part of the trunk or neuromuscular junction:
quadriplegia (tetraplegia) with paralysis of all four limbs - poisoning, e.g. botulism, organophosphorus poi-
and trunk. The suffix plegia denotes complete paralysis; soning, aquatic toxins (e.g. tetrodotoxin).
paresis denotes partial paralysis. Hemiplegia refers to - bites and stings, e.g. snakes.
unilateral paralysis, e.g. associated with CVA and other - immunological, e.g. myasthenia gravis, myasthenic
neurovascular conditions including migraine. syndrome.
May be caused by lesions affecting the: muscle:
cerebrum/brainstem: - inflammatory, e.g. polymyositis.
- neoplastic, e.g. frontal lobe or brainstem tumours. - congenital, e.g. periodic paralysis.
- vascular, e.g. bilateral carotid or basilar artery - electrolyte imbalance, e.g. hypo/hyperkalaemia,
thrombosis. hypercalcaemia, hypermagnesaemia, hypophos-
- demyelinating disease, e.g. multiple sclerosis, phataemia.
central pontine myelinosis. Diagnosis is based largely on history, examination and
- hydrocephalus, cerebral palsy. investigations (e.g. MRI, CSF examination, nerve con-
spinal cord: duction studies). The commonest cause of acute paraly-
- spinal cord injury. sis is GuillainBarr syndrome followed by spinal cord
- neoplastic (primary or metastatic). injury caused by fracture dislocation of the cervical
- vascular, e.g. arteriovenous malformations, spine. Thoracic and lumbar spine damage is less common
anterior spinal artery thrombosis, epidural but may also cause paraplegia. In the absence of trauma,
haematoma. vascular insult to the spinal cord may produce paralysis
that may be sudden or evolve over several hours. This
200
usually follows thrombosis of a spinal segmental artery
1.3 and results in the anterior spinal artery syndrome. Spinal
190
subarachnoid haemorrhage similarly causes rapid paral-
180 1.2
ysis, as will basilar thrombosis causing pontine infarction.
170
1.1 Peripheral causes usually produce subacute paralysis,
160 with the exception of periodic paralysis (may occur
150 1.0 over minutes).
Paracetamol concentration (mmol/l)
Paracetamol concentration (mg/l)

Anaesthetic/ICU implications:
140
0.9 respiratory failure requiring ventilatory support,
130
e.g. IPPV; this may be exacerbated by aspiration of
120 0.8
gastric contents if the pharyngeal and laryngeal
110 muscles are affected. Support is likely to be required
0.7
100 for a long time since most conditions resolve slowly.
90 0.6 control of the airway: suxamethonium may cause

80 severe hyperkalaemia depending on the age of

0.5 the lesion or whether the process is ongoing.
70
Normal treatment line Alternative methods include use of rapidly acting
60 0.4
non-depolarising drugs, e.g. rocuronium, awake
50 intubation, tracheostomy. The latter is often used in
0.3
40 the long term.
30 0.2 there may also be autonomic disturbance depend-
20 High-risk treatment line ing on the cause.
0.1 other features of the primary disease.
10
long-term supportive care includes nutrition and
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 fluid balance, regular turning and prevention of
decubitus ulcers, prophylaxis against DVT and nos-
Time (h) ocomial infection, prompt treatment of infection
Fig. 126Treatment lines for normal and high-risk patients after
and psychological support.
paracetamol poisoning; recent (2012) guidance has dispensed with this See also, Intubation, awake
distinction and advises treatment with acetylcysteine for blood levels
above a line joining 100mg/L at 4 hours and 15mg/L at 15 hours Paramagnetic oxygen analysis, see Oxygen
(approximating to the dotted line) measurement
450 Paramedic training

Paramedic training. Extended skills training for ambu- bronchoconstriction and increased secretions.
lance personnel in the UK was introduced in certain increased GIT motility, relaxation of sphincters and
areas in the early 1970s, with a national training pro- increased secretions (profuse watery secretion from
gramme adopted in 1984. Currently, the only route to salivary glands). Increased insulin and glucagon
becoming registered as a paramedic is either via a secretion.
student paramedic position with an ambulance service bladder contraction and relaxation of sphincter.
trust, or passing an approved university course in variable effect on the uterus.
paramedic science. Trainee paramedics attend local hos- penile erection.
pitals and are required to perform tracheal intubations Acetylcholine is the neurotransmitter at all synapses.
and iv cannulations under supervision, often involving Its actions are divided into nicotinic (at ganglia) and
anaesthetists. muscarinic (at postganglionic synapses).
See also, Acetylcholine receptors; Muscarine; Nicotine
Parametric tests, see Data; Statistical tests
Parasympathomimetic drugs. Drugs producing the
Paraplegia, see Paralysis, acute effects of stimulation of the parasympathetic nervous
system. Include:
Paraquat poisoning. A common domestic herbicide, drugs that stimulate acetylcholine receptors:
paraquat is rapidly absorbed when ingested orally, peak - acetylcholine: has widespread actions, therefore
plasma levels occurring in 12h. Can also be absorbed not used therapeutically.
through the skin. Industrial preparations contain 10 - synthetic choline esters, e.g. carbachol, methacho-
20% paraquat; those for home use contain 2.5%. Lethal line: the former has nicotinic and muscarinic
dose is 35g; mortality is up to 75%. actions, the latter mainly muscarinic. Both are
Features: resistant to hydrolysis by cholinesterases. Carba-
corrosive burns to mouth, pharynx and chol is used in glaucoma and urinary retention.
oesophagus. Bethanechol is a similar drug, and used in urinary
dyspnoea, pulmonary oedema, acute lung injury, retention and as a laxative.
rapidly progressive pulmonary fibrosis. Lung - cholinomimetic alkaloids, e.g. pilocarpine: used in
damage is exacerbated by high inspired O2 glaucoma.
concentrations. acetylcholinesterase inhibitors.
cardiac, hepatic and renal impairment.
Management: Paravertebral block. Blocks nerves as they pass
general support as for poisoning and overdoses. through the intervertebral foramina into the paraverte-
oral administration or gastric instillation of an bral space; may be performed in the thoracic or lumbar
adsorbent such as activated charcoal 100g followed region, e.g. for breast or abdominal surgery respectively.
by 50g 4-hourly, or fullers earth 1000ml 15% Solution may track medially through the foramina into
aqueous suspension (or 500ml 30%) 2-hourly, the epidural space, or laterally into the intercostal
together with 200ml 20% mannitol or magnesium space.
sulphate as a laxative; administration is repeated With the patient sitting or in the lateral position, a
until the charcoal or fullers earth is seen in the skin wheal is raised 35cm lateral to the most cephalad
stool. Gastric lavage is not recommended. aspect of the appropriate spinous processes. An 8cm
haemoperfusion has been advocated but paraquats needle is inserted approximately 34cm perpendicular
large volume of distribution limits its usefulness. to the skin until the transverse process is encountered,
Paraquat concentrations can be measured in the serum then walked off the cephalad border and advanced a
or (more easily) in the urine. further 12cm. 5ml local anaesthetic agent is then
Garawammana IB, Buckley NA (2011). Br J Clin Phar- injected. May be performed bilaterally.
macol; 72: 74557 A loss-of-resistance technique may be used to confirm
correct needle placement, as for epidural anaesthesia. A
Parasympathetic nervous system. Part of the auto- catheter may be passed into the paravertebral space for
nomic nervous system. Myelinated preganglionic effer- prolonged analgesia. Complications include epidural,
ent fibres emerge with cranial nerves III, VII, IX and X, subarachnoid and iv injection.
and spinal nerves S24. They pass to their target organs, Thavaneswaran P, Rudkin GE, Cooter RD, et al. (2010).
where they synapse with short non-myelinated postgan- Anesth Analg; 110: 17404
glionic fibres (cf. sympathetic nervous system). The vagus
nerves carry about 75% of all parasympathetic fibres Parecoxib. NSAID acting preferentially on cyclo-
and innervate the heart, lungs, oesophagus, stomach, oxygenase-2, licensed for short-term (< 2 days) treat-
other viscera and GIT as far as the splenic flexure. The ment of postoperative pain. Onset of action is 713min,
sacral nerves run as the pelvic splanchnic nerves to the with effects lasting up to 12h. A prodrug of valdecoxib,
pelvic viscera (see Fig. 21; Autonomic nervous system). to which it is rapidly converted (half-life 22min); valde-
Afferent fibres travel in cranial nerves IX and X and in coxib itself has a half-life of 8h.
the sacral nerves. Dosage: 40mg iv/deep im injection followed by 20
Effects of parasympathetic stimulation: 40mg bd/qds up to 80mg/day.
pupillary and ciliary muscle contraction, increased Side effects: as for NSAIDs. Hyper- or hypotension
lacrimal secretion. and peripheral oedema may also occur. Has been
bradycardia, reduced velocity of cardiac conduc- associated with severe hypersensitivity reactions,
tion. Vasodilatation occurs in skeletal muscle, especially in patients allergic to sulphonamides.
abdominal viscera, and coronary, pulmonary and
renal circulations. Parenteral nutrition, see Nutrition, total parenteral
 Patient-controlled analgesia 451

Parkinsonism, see Parkinsons disease Paroxysmal nocturnal haemoglobinuria. Rare

acquired chronic haemolytic anaemia, resulting from
blood cell membrane abnormality and increased sensi-
Parkinsons disease. Idiopathic degenerative disorder tivity to lysis by complement. Haemoglobinuria is clas-
of the CNS involving the basal ganglia and extrapyrami- sically noticed on waking.
dal motor system, with loss of dopamine leading to an Haemolysis may be precipitated by infection, hypox-
imbalance between acetylcholine and dopamine in the aemia, hypercapnia, acidosis and hypoperfusion, all of
substantia nigra. Secondary causes include carbon mon- which should be avoided during anaesthesia. Steroids
oxide poisoning, encephalitis, CVA, heavy metal poison- may help reduce haemolysis. Platelet destruction may
ing, or drugs that antagonise dopamine receptors (e.g. lead to bleeding, or abnormal function may lead to
phenothiazines); secondary disease is termed parkin- venous thrombosis. Renal impairment is common. Drugs
sonism. Affects 3% of the population > 65 years old; the causing complement activation should be avoided, and
aetiology is in most cases unknown but may include red blood cells washed before blood transfusion.
genetic, toxic and environmental factors. Kathirvel S, Prakash A, Lokesh N, Sujatha P (2000).
Features: Anesth Analg; 91: 102931
bradykinesia, rigidity (lead-pipe or cogwheel),
rest tremor (46Hz). Initiation, speed, strength and PART team, Patient-at-risk team, see Outreach team
precision of movement are impaired. The face is
typically expressionless and the gait shuffling. Partial liquid ventilation, see Liquid ventilation
upper airway and vocal cord dysfunction can result
in laryngospasm. Partial pressure. Pressure exerted by each component
in so-called parkinson plus syndromes, features of of a gas mixture. For a gas dissolved in a liquid (e.g.
parkinsonism are accompanied by those of other blood) the term tension is used, although denoted by
multisystem degeneration, e.g. certain forms of the same symbol (P).
dementia and autonomic failure. See also, Daltons law; Respiratory symbols
a restrictive ventilatory defect may occur.
Treatment is aimed at restoring the dopaminergic/
Partial thromboplastin time, see Coagulation studies
cholinergic balance, and includes:
increasing brain levels of dopamine by administer-
Partition coefficient. Ratio of the amount of substance
ing its precursor levodopa (dopamine does not
in one phase to the amount in another phase at stated
cross the bloodbrain barrier). Conversion of
temperature, with the two phases being of equal volume
levodopa to dopamine outside the CNS with resul-
and in equilibrium with each other. Depends on the rela-
tant side effects is prevented by concurrent admin-
tive solubility of the substance in the two phases. May
istration of carbidopa or benserazide. These inhibit
refer to solids, liquids or gases; when the phases are
dopa decarboxylase peripherally, as they do not
liquid and gas it equals the Ostwald solubility coefficient.
cross into the brain. Bradykinesia and rigidity are
Blood/gas and oil/gas partition coefficients of inhala-
improved more than tremor. Side effects include
tional anaesthetic agents are related to speed of uptake
involuntary movements, nausea, vomiting, and
and potency respectively.
psychiatric disturbances. Improvement may be
intermittent (onoff effect).
anticholinergic drugs: benzatropine, trihexypheni-
Pascal. SI unit of pressure. 1 pascal (Pa) = 1N/m2.
dyl (benzhexol), orphenadrine: improve tremor and [Blaise Pascal (16231662), French physicist]
rigidity more than bradykinesia.
other drugs: bromocriptine, apomorphine and
Pasteur point. Critical mitochondrial PO2 below which
lisuride (dopamine agonists), selegiline (type B aerobic metabolism cannot occur. Thought to be 0.15
monoamine oxidase inhibitor), amantadine, 0.3kPa (1.42.3mmHg).
pergolide. [Louis Pasteur (18221895), French scientist and
stereotactic surgery (especially stimulation of the
microbiologist]
globus pallidus and subthalamic nucleus) may be See also, Oxygen cascade
successful. Fetal tissue implantation has been per-
formed experimentally. Patent ductus arteriosus, see Ductus arteriosus, patent
Anaesthetic considerations:
pre-existing restrictive lung disorders and postural Patient-at-risk team, see Outreach team
hypotension. Excessive salivation and dysphagia
may result in tracheal aspiration of secretions. Patient-controlled analgesia (PCA). Technique
levodopa is continued up to surgery, since its half- whereby intermittent boluses of analgesic drugs (e.g.
life is short. It has been given iv. opioid analgesic drugs) are self-administered by patients
symptoms may be exacerbated by dopamine antag- according to their own requirements, used widely for
onists, e.g. phenothiazines and butyrophenones postoperative analgesia. Usually iv but other routes
(including antiemetic drugs). include epidural, sc and intranasal. Systems usually
the risk of hyperkalaemia following suxametho- consist of infusion devices that deliver on-demand bolus
nium is controversial. injections, with or without a continuous background
postoperative sleep apnoea has been reported, infusion. Bolus volume and rate and the minimum time
especially in the postencephalitic disease. between boluses (lockout interval) may be altered.
[James Parkinson (17551824), London physician] These controls must be inaccessible to the patient (or
Kalenka A, Schwarz A (2009). Curr Opin Anaesthesiol; relatives), and the infusion connected downstream from
22: 41924 a non-return valve if attached to another iv infusion (to
452 PAV

Peak flowmeters. Simple and inexpensive hand-held

Table 36 Dosage regimens for different opioids for iv
flowmeters for measuring peak expiratory flow rate
patient-controlled analgesia
(PEFR). The Wright peak flowmeter is a constant-
Drug Bolus dose (mg) Lock-out interval (min) pressure, variable orifice device, able to measure peak
flow rates of up to 1000 l/min. It has a flat circular
Diamorphine 0.51.5 35 body, with a handle and mouthpiece. Exhaled air is
Fentanyl 0.020.05 310 directed by a fixed baffle within the body on to a movable
Morphine 0.52.0 515 vane that is free to rotate around a central axle against
Nalbuphine 15 515 the force of a small spring. There is a circular slot in
Oxycodone 0.52.0 510 the base of the chamber, through which expired air
Pethidine 520 515 escapes. As the vane moves, the slot is uncovered,
thus increasing the effective orifice size. The vane reaches
its furthest excursion according to PEFR, and is held
there by a ratchet. PEFR is read from a dial on the
face of the meter, according to a pointer attached to
prevent retrograde flow into the second infusion set with the vane. It slightly underreads in comparison with a
subsequent overdosage when the latter is flushed). pneumotachograph.
Has been shown to provide more consistent plasma A simpler, cheaper version consists of a cylindrical
drug levels when compared with standard im techniques. tube, employing a piston that is blown along its length.
The usefulness of background infusions is controversial, As it does so, it uncovers a linear slot along the tube. A
the risk of overdosage balanced by possibly improved ratchet mechanism operates as before. PEFR is read
analgesia. Preoperative explanation of the technique is from a scale at the top of the cylinder.
desirable. [B Martin Wright (19122001), London engineer]
Drugs with relatively short half-lives are usually
employed. Widely varying dosage regimens have been PEEP, see Positive end-expiratory pressure
described; individual adjustment may be required (Table
36). Complications are related to incorrect programming PEFR, see Peak expiratory flow rate
and setting-up, patients misunderstanding of the tech-
nique, equipment malfunction and administration of PEG, see Percutaneous endoscopic gastrostomy
additional conventional on demand opioid analgesia
leading to overdose. Patients require adequate monitor- Pelvic trauma. Usually caused by blunt trauma (e.g.
ing, since respiratory depression may still occur. Nausea road accidents or falls) and often associated with abdom-
and vomiting may be a problem if regular antiemetics inal trauma, chest trauma and head injuries.
are not prescribed, firstly because drug levels remain Damage may involve:
constant, and secondly because the as required anti- pelvic ring: disruption causes pain on movement.
emetics that would be routinely given along with im Diagnosis is confirmed with X-ray or CT scanning.
opioids tend not to be given if as required opioids bladder: rupture occurs in 1015% of pelvic trauma
themselves are no longer being given. PCA is also used cases. Suggested by lower abdominal peritonism
(epidural and iv) for analgesia in labour (see Obstetric and inability to pass urine. IV urography (or cystog-
analgesia and anaesthesia). raphy if a urinary catheter is in place) shows extrav-
Grass JA (2005). Anesth Analg; 101 (Suppl): S4461 asation of contrast from the torn bladder wall.
urethra: damage is suggested by disruption of the
PAV, see Proportional assist ventilation pubis symphysis on X-ray, perineal bruising, blood
at the meatus, inability to pass urine and a high-
PCA, see Patient-controlled analgesia riding prostate on pr examination in males. IV
urography should be performed to exclude total
PCV, Packed cell volume, see Haematocrit disruption.
vaginal and bowel perforation from bony
PCWP, see Pulmonary capillary wedge pressure fragments.
pelvic blood vessels: arteriography may be neces-
PDA, Patent ductus arteriosus, see Ductus arteriosus, sary for diagnosis.
patent pelvic nerves.
Management:
PDPH, see Post-dural puncture headache resuscitation as for trauma generally.
simple pelvic fractures require bed rest only,
PE, see Pulmonary embolism whereas complicated fractures require early opera-
tive fixation. External fixation is now common.
PEA, see Pulseless electrical activity intraperitoneal bladder rupture requires laparot-
omy and drainage of the bladder with both supra-
Peak expiratory flow rate (PEFR). Maximal rate of air pubic and urethral catheters. Extraperitoneal
flow during a sudden forced expiration. Most conve- rupture requires drainage via a urethral catheter
niently measured with a peak flowmeter; may also be with subsequent confirmation of healing using
measured from a flowvolume loop, or with a pneumo- cystography. Broad-spectrum antibacterial drugs
tachograph. Highly dependent on patient effort. Reduced should be given.
by obstructive airways disease, e.g. asthma, COPD. urethral injuries generally should be treated by
Normal values: 450700 l/min (males), 250500 l/min suprapubic catheterisation and drainage; however,
(females). if pelvic X-ray shows no disruption of the symphysis
 Pentoxifylline 453

and there is no blood at the meatus, a urethral cath- the penis arises from the genital branch of the genito-
eter may be passed cautiously. femoral nerve.
pelvic vessels may require embolisation if haemor- A needle is introduced at right angles through a skin
rhage is severe. wheal in front of the symphysis, and passed below its
caudal edge. It is inserted up to 35mm deeper than the
Pendelluft. Phenomenon originally believed to cause symphysis (a click may be felt). After negative aspiration
the hypoxaemia occurring in flail chest. The theory sug- for blood, 12ml local anaesthetic agent is injected for
gested that air is drawn from the affected side into the children up to 3 years old, 35ml for older children and
unaffected lung during inspiration, due to disrupted 510ml for adults. Adrenaline may cause ischaemia and
chest wall integrity on the damaged side. During expira- necrosis and must not be used. Solution diffuses to block
tion, air passes from the normal lung back into the both sides following midline injection, but risk of hae-
affected lung; thus air moves to and fro between the two matoma is greater; therefore two injections may be per-
sides, instead of in and out of the chest via the trachea. formed, one either side of the midline. 15ml solution
Hypoventilation and V/Q mismatch due to pain, lung is also injected around the base of the penis.
contusion and sputum retention are now thought to be See also, Lumbar plexus; Sacral plexus
more important.
[German: oscillating breath] Pentamidine isetionate. Antiprotozoal agent used in
the treatment and prophylaxis of pneumocystis pneumo-
Penicillamine. Degradation product of penicillin used nia. Because of its side effects, used as a second-line drug
as a chelating agent, especially in copper, lead, gold, if infection is resistant to co-trimoxazole. Has also been
mercury and zinc poisoning. Also used in the treatment used to treat leishmaniasis and trypanosomiasis.
of rheumatoid arthritis and chronic active hepatitis. Dosage:
Dosage: from 125 to 250mg/day orally for chronic pneumocystis treatment: 4mg/kg/day slowly iv for
inflammatory conditions to 12g/day in divided doses at least 14 days or 600mg daily by inhalation of
for chronic copper overload or lead poisoning. nebulised solution, for 3 weeks.
Side effects: blood dyscrasias, convulsions, neuropa- pneumocystis prophylaxis: 300mg every 4 weeks
thy, nausea and vomiting, colitis, renal and hepatic (or 150mg every 2 weeks) by nebulised solution.
impairment, bronchospasm, myasthenia gravis, sys- other infections: 34mg/kg iv/im every 17 days.
temic lupus erythematosus-like syndrome, rashes. Side effects: severe, sometimes fatal hypotension,
Blood counts and urine testing for proteinuria should hypoglycaemia and ventricular arrhythmias, pancre-
be performed regularly. atitis, renal failure, blood dyscrasias, bronchospasm,
nausea, vomiting.
Penicillins. Group of natural and synthetic bactericidal
antibacterial drugs with a -lactam structure. Act by Pentastarch, see Hydroxyethyl starch
interfering with formation of peptidoglycan cross-links
within the bacterial cell wall, resulting in osmotic damage.
Penetrate body tissue and fluids well except for the Pentazocine hydrochloride/lactate. Agonistanta-
CNS (unless the meninges are inflamed). Excreted gonist opioid analgesic drug described in 1962. Benzo-
renally by active tubular secretion. Bacterial resistance morphan derivative, with agonist activity at kappa and
is caused by production of -lactamases that hydrolyse sigma opioid receptors, and antagonist activity at mu
the -lactam ring. receptors. Used for moderate to severe pain; has been
May be classified into:
used to reverse the respiratory depression caused by
benzylpenicillin and phenoxymethylpenicillin.
morphine or fentanyl whilst maintaining analgesia.
penicillinase-resistant penicillins: flucloxacillin, Undergoes extensive first-pass metabolism; conju-
temocillin. gated with glucuronides and excreted renally. Half-life is
broad-spectrum penicillins: ampicillin, amoxicillin,
about 23h.
Dosage: 0.51.0mg/kg, iv/im/sc. 50100mg orally,
co-amoxiclav, co-fluampicil.
antipseudomonal penicillins: piperacillin, ticarcillin.
34-hourly.
Side effects:
Problems include hypersensitivity (related to the basic
sedation, dizziness.
penicillin structure thus all penicillins may cross-
hallucinations and dysphoria, especially in the
react; only 723% of allergic patients are truly
allergic), cerebral irritation (causing encephalopathy), elderly.
sweating, hypertension, tachycardia.
especially in high dosage or renal failure, and excessive
precipitation of withdrawal reactions in opioid
administration of sodium or potassium in parenteral
preparations. addicts.
Its side effects have limited its popularity.
Penile block. Used to provide peri- and postoperative See also, Opioid receptor antagonists
analgesia for circumcision and other procedures on the
penis, especially in children. Pentolinium tartrate. Obsolete long-acting ganglion
The dorsal nerves of the penis (terminal branches blocking drug used to treat hypertension and in hypo-
of the pudendal nerves, S24) travel medial to the tensive anaesthesia.
ischiopubic rami into the deep perineal pouch, and
pierce the perineal membrane to pass to the penis. They Pentoxifylline (Oxpentifylline). Xanthine used in
may be blocked within a triangular space bounded peripheral vascular disease and vascular dementia.
by the symphysis pubis above, corpora cavernosa below Reduces blood viscosity. Also inhibits tumour necrosis
and superficial fascia anteriorly. The penile vessels lie in factor production by macrophages; has thus been studied
the midline. Some innervation of the skin at the base of as a potential therapeutic agent in sepsis.
454 PEP

Dosage: peripheral vascular disease: 400mg orally Percutaneous coronary intervention (PCI). Group of
bd/tds. percutaneous endovascular techniques for treating isch-
Side effects: nausea, headache, GIT disturbances, aemic heart disease. Considerably cheaper than surgical
thrombocytopenia. coronary artery bypass graft (CABG), with a similar risk
See also, Cytokines of death and MI in selected patients; CABG is more
effective at relieving angina and less likely to require
repeat intervention, but carries higher procedural risk
PEP, Pre-ejection period, see Systolic time intervals of CVA.
Techniques include:
balloon dilatation of stenosed coronary arteries
Peptic ulcer disease. Ulceration due to an imbalance
between the action of gastric acid and the normal protec- (coronary angioplasty).
rotational excision atherectomy.
tive mechanisms of the upper GIT mucosa. May occur
laser ablation atherectomy.
at any site exposed to gastric acid, e.g. oesophagus,
insertion of endoluminal stents.
stomach, duodenum. Abnormal gastric emptying, gastro-
oesophageal reflux, drugs (e.g. NSAIDs, corticosteroids), Due to a high restenosis rate (3050% within 6 months),
alcohol, psychological and epidemiological factors are balloon angioplasty has been replaced as the standard
thought to contribute. Infection with Helicobacter pylori of care by insertion of self-expanding mesh stents, the
has a fundamental role in the development of chronic latter either bare metal or drug-eluting. Bare metal
gastritis and peptic ulcer disease; the persistence of stents (BMS) still carry a 2025% risk of restenosis due
serum antibodies against the organism reflects the chro- to neointimal hyperplasia; drug-eluting stents (DES)
nicity of the infection. About 70% of patients with release an antiproliferative agent that inhibits stent
gastric ulcers have evidence of H. pylori infection that endothelialisation and reduces 1-year restenosis rate to
can be detected with the 13C-urea breath test. Infected 5%. However, drug-eluting stents carry a higher risk
patients have an increased rate of GIT bleeding in of potentially catastrophic late stent thrombosis (see
the ICU. below).
Indications:
Treatment:
elective revascularisation for patients with stable
neutralisation of existing acid with antacids.
increased surface protection (postulated angina.
urgent treatment for those with non ST elevation
mechanism):
- sucralfate. acute coronary syndromes.
emergency treatment for ST elevation MI if readily
- bismuth compounds.
- carbenoxolone. available.
reduction of acid production:
Patients are pretreated with antiplatelet drugs to prevent
- H2 receptor antagonists. in-stent thrombosis, and may also receive calcium
- proton pump inhibitors. channel blocking drugs to reduce coronary vasospasm.
- anticholinergic drugs, e.g. pirenzepine. Those with BMS require ongoing dual antiplatelet
- eradication of H. pylori infection. Recommended therapy (e.g. clopidogrel and aspirin) for 6 weeks; those
therapy includes PAC regimen (double dose with DES require two agents for 1 year (as the poorly
proton pump inhibitor, amoxicillin, clarithromy- endothelialised stent surface is highly thrombogenic).
cin) or PCM regimen (amoxicillin is replaced by All PCI patients should receive aspirin therapy for life.
Anaesthetic considerations (for non-cardiac surgery):
metronidazole) for 1 week. Effective in < 90%.
as for ischaemic heart disease generally.
surgery: indications include failed medical treat-
timing of surgery: risk of stent thrombosis is highest
ment, malignant change, or complications as
above. Surgery may involve highly selective vagot- within 30 days of PCI. Elective surgery should be
omy or vagotomy and drainage procedure (duode- postponed for > 6 weeks or > 12 months in those
nal ulcer), or partial gastrectomy (gastric ulcer). with BMS or DES respectively.
if surgery cannot be postponed, premature cessa-
Anaesthesia in chronic disease requires no special
precautions unless gastro-oesophageal reflux or tion of clopidogrel markedly increases risk of
anaemia is present. Acute haemorrhage or per adverse cardiovascular events, particularly in those
foration may present with vomiting, shock and with DES. Some therefore recommend that in most
hypovolaemia. cases these patients continue dual therapy periop-
eratively. For procedures where risks of bleeding
are very high (e.g. intracranial surgery), dual therapy
Percentile. Value that indicates the percentage of a dis- may be temporarily stopped and a rapidly revers-
tribution equal to or below it; e.g. 97% of measurements ible bridging therapy (e.g. tirofiban or heparin)
are equal or less than the 97th percentile. Often used in should be considered. These decisions should be
charts, e.g. of childrens height against age. The 3rd, 50th made in conjunction with a cardiologist.
and 97th percentiles plotted on the chart indicate the Barash P, Akhtar S (2010). Br J Anaesth; 105 (Suppl 1):
heights that include 3%, 50% and 97% of the population i315
respectively, at each age. May thus be used to follow
a childs growth, since height would be expected to Percutaneous endoscopic gastrostomy (PEG). Tech-
remain within the same percentile during normal devel- nique for establishing enteral nutrition that avoids the
opment. The 3rd and 97th percentiles approximate to discomfort and complications of long-term nasogastric
2 standard deviations from the mean, for normally dis- intubation. Useful for patients with neurological dyspha-
tributed data. gia. After passing a gastroscope into the stomach, the
Often used to indicate variability (scatter) around the stomach is inflated so that its anterior wall makes contact
median for ordinal data. with the anterior abdominal wall. Using the light from
 Pericarditis 455

the gastroscope, an appropriate site (usually 2cm below single injection through either the upper or lower lid. A
the left costal margin and 2cm from the midline) is mixture of lidocaine 2% and bupivacaine 0.50.75% in
marked on the skin. Under local anaesthesia, a trocar is equal proportions with or without adrenaline 1: 400 000
introduced into the stomach and a thread fed through it is suitable; alternatives include prilocaine 3% or ropiva-
into the stomach. This is grasped by the endoscope and caine. Hyaluronidase 5 units/ml promotes spread of
pulled out through the mouth; the PEG tube is attached solution.
to the thread and pulled through the mouth into the See also, Orbital cavity
stomach. The PEG is secured to the anterior abdominal
wall with a clip. In patients unable to lie flat due to dia- Pericardiocentesis. Removal of fluid from within the
phragmatic failure, a radiologically inserted gastrostomy pericardium. Usually performed to relieve acute cardiac
(RIG), in which the gastrostomy is inserted following a tamponade, although may also be used for diagnostic
barium meal, may be safer. purposes. If ultrasonography is available, needle aspira-
tion may be performed from any reasonable area on the
Percutaneous endoscopic jejunostomy (PEJ). Tech- chest wall. For blind pericardiocentesis, the subxiphoid
nique for enteral nutrition, similar to percutaneous approach is most commonly used:
endoscopic gastrostomy. Used to administer nutrition a long 1822 G needle attached to a syringe is
and drugs directly to the small bowel. introduced between the xiphisternum and the left
costal margin, and directed towards the left shoul-
Percutaneous tracheostomy, see Tracheostomy, der at 3540 to the skin. Aspiration is performed
percutaneous as the right ventricle is approached, until pericardial
fluid is obtained. A three-way tap is used. Pericar-
Percutaneous transluminal coronary angioplasty dial blood does not clot, whereas intracardiac
(PTCA), see Percutaneous coronary intervention blood does.
an ECG chest lead may be attached to the needle;
Perfluorocarbons (PFCs). Chemically inert organic ST elevation and ventricular ectopics may indicate
compounds in which all the hydrogen atoms have been contact with the ventricle.
replaced by fluorine. Clear liquids, they dissolve O2 and trauma to myocardium and coronary vessels is
CO2 to an extent directly proportional to the gas con- reduced by inserting a plastic iv cannula over the
centration to which they are exposed (i.e. according to needle into the pericardial space.
Henrys law), and have therefore been investigated as Alternative approaches:
artificial blood substitutes. Insoluble in water, they in the fifth intercostal space just lateral to the left
require emulsification (e.g. with egg phospholipids) for sternal edge (approaches the left ventricle).
use in the circulation. PFCs can dissolve about 20 times one intercostal space lower, and 12cm lateral to
as much O2, and four times as much CO2, as plasma. the apex beat, directed towards the right shoulder
Their use in humans has been limited by side effects, e.g. (approaches the apex).
CVA, thrombocytopenia, flu-like illness.
They have also been investigated as a suitable medium Pericarditis. Inflammation of the pericardium. May be:
for liquid ventilation, since their high density means they acute:
displace exudate from the airways and alveoli whilst - caused by infections, connective tissue diseases,
their low surface tension is thought to increase lung renal failure, hypothyroidism, MI, trauma, drugs,
compliance. Also used in eye surgery as a temporary radiation and tumours. Postviral pericarditis
replacement for vitreous humour. (often with cocksakie B virus) is the most common
Fabian TC (2011). J Trauma; 70 (Suppl): S424 form.
See also, Blood, artificial - features include sudden central chest pain, worse
lying down or on moving, often with fever and
Perfusion pressure. Represents the pressure head for tachycardia. Auscultation may reveal a pericardial
blood flow to an organ or tissues. Equals MAP minus friction rub. ECG may reveal ST segment eleva-
mean venous pressure; e.g. cerebral perfusion pressure tion, possibly with T wave inversion later.
equals MAP minus ICP. - NSAIDs are often effective in providing analge-
sia. Corticosteroids may be useful in pericarditis
Peribulbar block. Used in ophthalmic surgery as an secondary to autoimmune disease.
alternative to retrobulbar block, since risk of complica- - pericardial fluid may accumulate, with disappear-
tions (e.g. retrobulbar haemorrhage) is lower. Facial ance of the rub. Slow accumulation may cause
nerve block is not required. Involves injection of local little cardiovascular disturbance, whereas rapid
anaesthetic agent outside the muscle cone. accumulation may cause cardiac tamponade.
Several techniques have been described. In one, a chronic constrictive:
needle is inserted through the lid margin between the - the pericardium becomes fibrous or calcified, and
superior orbital notch and the medial canthus, and thus rigid.
directed upwards between the globe and orbital roof. - usually follows radiation, chronic renal failure,
34ml solution is injected at a depth of 2.02.5cm. The rheumatoid arthritis or TB, or is idiopathic.
needle is then inserted through the lid margin at the - resembles cardiac tamponade, with restriction of
junction of the outer one-third and inner two-thirds of diastolic cardiac filling. A sharp drop in right atrial
the lower orbital rim, and directed downwards between pressure (y descent) occurs just before right ven-
the globe and orbital floor. 45ml solution is injected at tricular filling, due to rapid blood flow across the
a depth of 2.02.5cm. Gentle pressure is applied to the tricuspid valve (cf. tamponade, where atrial pres-
eye for 10min. Alternatives include a more superficial sures remain high throughout diastole). The heart
injection (anterior peribulbar block) and the use of a sounds may be quiet, and ECG complexes small.
456 Pericardium

Pericardial calcification may be present on the autonomic involvement.

CXR. risk of severe hyperkalaemia following administra-
- management: as for cardiac tamponade. Surgery tion of suxamethonium in motor neuropathy.
may be required. difficulty weaning from ventilators.
Khandaker RH, Espinosa RE, Nishimura RA, et al Hughes R (2008). Pract Neurol; 8: 396405
(2010). Mayo Clin Proc; 85: 57293 See also, Critical illness polyneuropathy

Pericardium. Sac enclosing the heart and roots of the Peripheral vascular resistance, see Systemic vascular
great vessels. The outer fibrous pericardium fuses below resistance
with the central tendon of the diaphragm, and above and
superiorly with the adventitia of the great vessels. The Peritoneal dialysis (PD). Dialysis technique used pri-
inner serous pericardium has visceral and parietal layers, marily in chronic renal failure and less commonly in
enclosing the pericardial cavity. The visceral layer covers poisoning and overdose. Following insertion of an intra-
the heart and is termed the epicardium. peritoneal PD catheter through the lower anterior
See also, Mediastinum; Pericardiocentesis; Pericarditis abdominal wall (surgically or percutaneously), pre-
warmed dialysate fluid is introduced into the peritoneal
Peridural, see Epidural cavity. The peritoneum acts as a semipermeable mem-
brane between blood and dialysate; the latter is allowed
Periodic paralysis. Group of diseases, usually inherited to remain within the cavity for a period (dwell time) to
in an autosomal dominant pattern, characterised by epi- allow equilibration between the two compartments. The
sodic skeletal muscle weakness. speed and degree of equilibration depend on the fre-
Classified into different types: quency and volume of exchanges and dwell time (2 litres
hypokalaemic: caused by point mutations in skele- dialysate is usually exchanged over 1h), the permeabil-
tal muscle calcium channels. Weakness may be gen- ity and blood supply of the peritoneum and the tonicity
eralised and severe and is usually precipitated by of the dialysate (contains sodium, chloride, calcium,
stenuous exercise or a carbohydrate load. May magnesium, lactate and a variable amount of glucose
result in respiratory failure. Treatment of acute and potassium; osmolality is 346485 mosmol/kg depend-
attacks is with iv or oral potassium; prophylaxis is ing on the glucose content, that varies from 1.3 to 4.5%;
with acetazolamide. potassium-free solutions are also available).
hyperkalaemic/normokalaemic: caused by point Advantages of PD are its simplicity, lack of require-
mutations in muscle sodium channels. Occurs in first ment for vascular access and anticoagulation, and
decade of life and results in episodic mild weakness haemodynamic stability; disadvantages include its inef-
to total paralysis. May be precipitated by exercise, ficiency and slowness. Complications include pain, bleed-
cold or potassium ingestion. Treatment is with acet- ing, visceral perforation, peritonitis, hyperglycaemia,
azolamide or thiazide diuretics. Anaesthesia may hypoproteinaemia and respiratory embarrassment if
result in prolonged paralysis, especially if suxame- large volumes of dialysate are used. As with haemodialy-
thonium is used. sis, drugs are removed from the plasma during PD and
alterations in dosage may be required. Contraindications
Peripheral neuropathy. Term encompassing any disor- include previous abdominal surgery, drains, ileus and
der affecting the peripheral nerves (motor and/or adhesions. PD may be performed continuously (e.g. in
sensory). ICU) to improve its efficacy and reduce respiratory
Divided into: embarrassment.
polyneuropathy: generalised process characterised
by widespread and symmetrical degeneration Peritoneal lavage. Technique for diagnosis of intra-
of the: abdominal bleeding following blunt abdominal trauma.
- axon, e.g. drugs, metabolic disorders. Following bladder drainage and decompression of the
- myelin sheath, e.g. diphtheria, GuillainBarr stomach using a nasogastric tube, a peritoneal lavage
syndrome. catheter is introduced under local anaesthesia into the
- neurone cell body, e.g. motor neurone disease. abdominal cavity, 12cm below the umbilicus in the
focal and multifocal neuropathies: asymmetrical midline. A Seldinger or cut-down technique may be
involvement of one or more peripheral nerves, e.g. used. If no fluid is aspirated, 10ml/kg (up to 1000ml) of
by ischaemia, trauma (including nerve injury during warm saline is introduced into the cavity and then
anaesthesia), vasculitis, infiltration (e.g. by tumour). drained by gravity. The resultant aspirate is sent for
Diabetes mellitus is the most common cause of chronic analysis; the presence of significant numbers of white
peripheral neuropathy (causing both polyneuropathy (> 500/ml) or red cells (> 100 000/ml), or bacteria, indi-
and focal neuropathy), followed by carcinoma, vitamin cates the need for diagnostic laparoscopy or laparotomy.
B1 and B12 deficiency (e.g. in alcoholism) and drug Introduction of blood during the procedure itself may
therapy (e.g. isoniazid, amiodarone, cimetidine). Other lead to a false-positive result. Abdominal ultrasound is
causes include renal failure, hypothyroidism, connective used as a less invasive diagnostic method.
tissue diseases, HIV, leprosy, amyloidosis, porphyria and Continuous peritoneal lavage has been used in acute
heavy metal poisoning. pancreatitis, peritonitis and postoperatively in intra-
Clinical features include weakness and sensory dis- abdominal sepsis in an attempt to wash away bacteria
turbance, usually initially distal in polyneuropathies. and toxins.
Autonomic neuropathy may occur. See also, Paracentesis
Anaesthetic and ICU considerations:
underlying disease. Peritonitis. Inflammation or infection of the perito-
bulbar involvement. neum. Infection is usually with bacteria, most commonly
 pH measurement 457

involving mixed anaerobic and aerobic organisms, half-life of about 34h. Approximately 60% protein-
although spontaneous (primary) peritonitis is caused bound in plasma. 510% is excreted unchanged in urine,
by a single species (usually streptococci, pneumococci or more if the urine is acidic. 90% undergoes hepatic
haemophilus). metabolism to norpethidine, an active substance (half-
Caused by: life 2040h) which may cause hallucinations and
perforation of part of the GIT. convulsions.
penetrating trauma (including postoperative infec- Has similar effects to morphine, but also has local
tion from drains). anaesthetic and anticholinergic actions. May cause
direct spread from an infected organ, e.g. appendi- bronchodilatation, but may also cause histamine release.
citis, cholecystitis. May relax contracted GIT and urinary smooth muscle.
haematogenous spread in bacteraemia. High doses may cause convulsions and myocardial
Clinical features include fever (or hypothermia in severe depression.
sepsis), tachycardia, pain (worse on movement and Indications for use are as for morphine.
breathing), guarding and rigidity. Bowel sounds may be Dosage: 50150mg orally or 2550mg iv 4-hourly.
sparse or absent, with abdominal distension. Untreated, Also used in obstetric analgesia and anaesthesia (50
shock may occur. Diagnosis may be aided by paracente- 150mg im, max 400mg/day), and has been given by
sis; imaging may reveal an underlying cause. If the diag- subarachnoid injection (50100mg).
nosis remains in doubt, exploratory laparotomy may be Has been used as a component of the lytic cocktail.
indicated as for intra-abdominal sepsis. Should be avoided in patients taking monoamine
Treatment: oxidase inhibitors.
general resuscitative measures: iv fluids, inotropes,
respiratory support. PFA-100, see Coagulation studies
nasogastric tube.
broad-spectrum antibacterial drug therapy, e.g. a pH. Negative logarithm to base 10 of hydrogen ion con-
cephalosporin, metronidazole and aminoglycoside. centration (lower case p being the symbol for log10);
surgical correction of the underlying cause. i.e. pH = log [H+]. Used as an indication of acidity; the
peritoneal lavage with or without antibiotics has more acid a solution, the lower the pH (Table 37). pH of
been used, especially postoperatively. normal arterial blood is 7.347.46, corresponding to [H+]
Complications include MODS, GIT obstruction caused of 3446nmol/l.
by adhesions and persistent ileus. TPN may be required. See also, Acidbase balance
Overall mortality is approximately 10%, although post-
operative peritonitis and faecal peritonitis carry mortali- pH measurement. Relies on the principle that, when
ties of 50% and 70% respectively. two electrolyte solutions are separated by a semiperme-
able membrane, an electrical potential difference is gen-
Permissive hypercapnia. Acceptance of hypercapnia in erated across the membrane that is proportional to the
patients undergoing IPPV, e.g. for respiratory failure hydrogen ion concentration gradient across it.
especially asthma and acute lung injury. Used as part of The pH electrode uses H+-sensitive glass as the mem-
a lung protective strategy, when ventilation to a normal brane; this separates the sample solution (e.g. blood),
Pco2 may result in excessive airway pressure, baro- from the silver/silver chloride measuring electrode
trauma and volutrauma. immersed in an internal buffer solution of constant pH.
Laffey JG, OCroinin D, McLoughlin P, Kavanagh BP Thus, the potential difference across the glass is depen-
(2004); Intensive Care Med; 30: 34756 dent on the [H+] of the sample. A mercury/mercurous
chloride/potassium chloride electrode system also makes
Permissive hypotension, see Damage control contact with the blood (via a membrane to prevent con-
resuscitation tamination), acting as a reference electrode. The poten-
tial difference between the reference and measuring
Peroneal nerve block, see Ankle, nerve blocks; Knee, electrodes is amplified and displayed.
nerve blocks

Perphenazine. Phenothiazine, used as an antiemetic Table 37 Corresponding values for pH and hydrogen ion
drug and tranquilliser. More potent than chlorproma- concentrations
zine, with fewer side effects. Dystonic reactions are
common. pH units [H+] (nmol/l)
Dosage: 25mg orally/im tds/qds (to a maximum of
24mg). 6.8 158
6.9 126
Persistent vegetative state, see Vegetative state 7.0 100
7.1 79
7.2 63
PET, Pre-eclamptic toxaemia, see Pre-eclampsia 7.3 50
7.4 40
PET scanning, see Positron emission tomography 7.5 32
7.6 25
Pethicks test, see Checking of anaesthetic equipment 7.7 20
7.8 16
Pethidine hydrochloride. Synthetic opioid analgesic 7.9 13
drug, developed in Germany in 1939. One-tenth as 8.0 10
potent as morphine, with duration of action of 24h and
458 Phaeochromocytoma

The system is maintained at 37C; potential output is and magnesium sulphate have been used to
linear at approximately 60mV per pH unit. control perioperative hypertension. -Receptor
See also, Blood gas interpretation antagonists or other antiarrhythmic drugs may be
used to control tachycardia.
Phaeochromocytoma. Rare tumour secreting cate- - following the tumours removal, iv fluids and
cholamines, originating from chromaffin tissue. 90% occasionally phenylephrine or dopamine may be
occur in the adrenal gland, 10% at other sites within the required to maintain BP.
sympathetic nervous system. 10% are bilateral and 10% postoperatively:
malignant. May occur as part of multiple endocrine ade- - ICU care is required.
nomatosis or in association with neurofibromatosis. - hypoglycaemia, cardiovascular instability and
Usually presents with headache, psychosis, palpita- fluid imbalance may occur.
tions, sweating and hypertension (episodic or sustained). - bilateral adrenalectomy will require replacement
Tumours secreting mainly adrenaline cause tachyar- of corticosteroids.
rhythmias; those secreting noradrenaline cause vasocon- Rarely, phaeochromocytoma may present for the first
striction, ischaemia and hypertension. Some tumours time during incidental surgery, pregnancy or labour;
secrete both these catecholamines and also dopamine. morbidity and mortality are high in this context.
Glucose intolerance and cardiomyopathy may occur. Kinney MAO, Narr BJ, Warner MA (2002). J Cardiotho-
Diagnosis is confirmed by: rac Vasc Anesth; 16: 35969
measuring plasma catecholamines or urinary cate-
cholamine metabolites (e.g. metanephrine, hydroxy- Phantom limb. Sensation of the continued presence of
methylmandelic acid; HMMA). an amputated limb, occurring in up to 80% of patients.
suppression tests (e.g. using pentolinium, clonidine) More common after arm amputation, and when amputa-
with measurement of plasma catecholamines. tion is delayed after the original injury. Pain is severe in
provocation tests (e.g. using histamine, tyramine or 15% of cases and usually described as burning or throb-
glucagon). Rarely used now, since dangerous hyper- bing. The limb may be felt to be in an abnormal posi-
tension may occur. tion. Thought to be a state of central pain, due to
Tumours may be located using selective venous cathe- abnormal afferent activity in the interrupted intermedi-
terisation and catecholamine assays, arteriography (may ate neurones. Treatment has included phenytoin, carba-
provoke hypertensive crises), CT scanning, MRI mazepine, local somatic and sympathetic nerve blocks,
and radioactive meta-iodobenzyl guanidine (MIBG) injection of trigger points, TENS, dorsal column stimula-
scintigraphy. tion and cordotomy. Although spinal anaesthesia has
Anaesthetic considerations: been reported to exacerbate the pain, there have been
preoperatively: reports of successful treatment with intrathecal opioids.
- chronic hypertension may lead to hypertrophic or Pre-emptive analgesia with epidural anaesthesia has
dilated cardiomyopathy, the latter associated with been claimed to prevent the development of phantom
cardiac failure. Preparation includes several limb pain when instituted before surgical amputation,
weeks oral therapy with -adrenergic receptor but the evidence for this is weak.
antagonists (e.g. traditionally phentolamine or Nikolajsen L, Jensen TS (2001). Br J Anaesth; 87:
phenoxybenzamine but more recently with 1- 10716
selective antagonists, e.g. prazosin or doxazosin).
With the older non-selective -receptor antago- Pharmacodynamics. Describes the effects of drugs on
nists, -adrenergic receptor antagonists are admin- the body. Drugs may act by physical interactions (e.g.
istered when -receptor blockade is complete, but antacids, general anaesthetics), or by interacting with
doxazosin may be used without -receptor antag- receptors (receptor theory) or enzymes.
onists since it does not block presynaptic 2- See also, Doseresponse curves; Gender differences and
receptors and thus is not associated with increased anaesthesia; Pharmacogenetics; Pharmacokinetics
cardiac sympathetic activity (unless tumours are
predominantly adrenaline-secreting). Initiation of Pharmacogenetics (Pharmacogenomics). Describes the
-receptor blockade before -receptor blockade variability of drugs actions according to the genetic
is contraindicated as it may exacerbate hyperten- make-up of the individual. Examples include a prolonged
sion because of antagonism of 2-mediated vaso- action of suxamethonium due to variations of plasma
dilatation in muscle. Labetalol and atenolol are cholinesterase, and variation in metabolism of opioid
often used. -Methyl-p-tyrosine and calcium drugs, benzodiazepines, paracetamol and other NSAIDs
channel blocking drugs have also been used. due to genetic variation in the cytochrome P450 enzyme
- fluid therapy may be required; this may be aided system. May involve both pharmacodynamic and phar-
by central venous cannulation or possibly pulmo- macokinetic phenomena. Potential applications include
nary artery catheterisation. the tailoring of drug therapy to individual patients
perioperatively: based on their genotype, which could be analysed from
- drugs causing minimal cardiovascular disturbance a single blood sample. Current obstacles include the
are used for anaesthesia. incomplete understanding of many drugs mechanism of
- direct arterial BP measurement and CVP with or action, the involvement of multiple genes in a given
without pulmonary capillary wedge pressure response to a drug, and the difficulty in characterising
monitoring are required. actual patients responses in terms of their genotypes.
- catecholamines may be released in response to Blakey JD, Hall IP (2011). Br J Clin Pharmacol; 71:
surgical stress, anaesthetic drugs and handling of 82431
the tumour. Sodium nitroprusside, phentolamine, See also, Gender differences and anaesthesia; Genetics;
GTN, prazosin, calcium channel blocking drugs Pharmacodynamics; Pharmacokinetics
 Pharmacokinetics 459

Pharmacokinetics. Describes the absorption, distribu- Ct = C0 e kt

tion, metabolism and elimination of drugs, i.e. effects of
where Ct = concentration at time t
the body on drugs. These factors determine how the
C0 = concentration at time zero
effector site concentration of a drug varies over time.
k = a constant
Population differences in pharmacokinetic characteris-
e 2.718
tics may arise from general individual variations and
genetic factors (see Pharmacogenetics). A straight line is obtained when it is plotted using
Absorption: a semi-logarithmic scale (Fig. 127b).
may be via oral, sublingual, buccal, inhalational, iv,
im, sc, rectal or topical routes. k
The slope of the line =
rate of absorption affects the maximum concentra- 2.303
tion and duration of drug action. Most drugs are 0.693
absorbed by simple diffusion; i.e. rate depends on and half -life =
drug solubility, tissue permeability, surface area and k
vascularity of the absorption site. Lipid solubility Clearance = k volume of distribution
depends on the degree of ionisation of the drug, D
which depends on the pK of the drug in solution =
AUC
and body pH. Some drugs are absorbed by active
transport, e.g. L-dopa, -methyldopa. where AUC = area under the plasma
absorption from the GIT also depends on drug concentration/time curve
characteristics, gut motility, vomiting, destruction of D = dose of drug at time zero
drug by digestive enzymes, interaction with food or
other drugs, GIT disease and intestinal microflora. - two-compartment model: bi-exponential decline
First-pass metabolism reduces the bioavailability of in plasma level; an initial rapid distribution
many orally administered drugs, e.g. opioid analge- phase is followed by a slower elimination phase
sic drugs. Other routes of administration avoid this. (Fig. 127c). Each component of the curve may be
absorption occurs via the lungs for inhalational analysed separately.
anaesthetic agents. Drug is distributed from a central compart-
Distribution: ment (i.e. blood, brain, lungs) to a peripheral one
related to lipid solubility, pK, body fluid pH, protein- (e.g. ECF, tissues). The central compartment does
binding, regional blood flow, and specific properties not necessarily correspond to an anatomical
of the drug (e.g. iodine taken up by thyroid tissue). volume, but is defined in terms of its apparent
protein-binding limits both the amount of free drug volume. Elimination occurs from the central
and redistribution of drugs from the blood. Volume compartment.
of distribution and clearance of a drug are inversely - three-compartment distribution: one central and
proportional to its protein-binding. two peripheral compartments are assumed.
initial redistribution may reduce blood levels of a Metabolism:
drug with recovery from its effects, although the drug activity may be enhanced (e.g. morphine
total amount in the body has hardly changed, e.g. metabolised to morphine-6-glucuronide), de-
thiopental and other iv anaesthetic agents. creased (most drugs) or unaltered (e.g. certain
compartment models have been described to benzodiazepines).
explain the distribution of drugs in the body: usually occurs in two phases in the liver. Phase I
- one-compartment model: plasma concentration involves oxidation, reduction or hydrolysis, often
declines as a simple negative exponential process involving the cytochrome P450 enzyme system. Phase
after a bolus injection (first-order kinetics; Fig. II reactions involve conjugation with glucuronic
127a), i.e.: acid, glycine, glutamine and sulphate, increasing

(a) (b) (c)

Log10 concentration

Log10 concentration

Phase
Concentration

Phase

Time Time Time

Fig. 127 Drug concentration against time: (a) and (b) one-compartment model; (c) two-compartment model
460 Pharynx

water solubility. Rate of metabolism may be altered Their anterior borders are open to form the nasal, buccal
by enzyme induction/inhibition. and laryngeal cavities. Their posterior borders insert into
other sites may be involved, e.g. plasma cholinester- a median raphe along the length of the pharynx.
ase (suxamethonium), kidney (e.g. dopamine). Blood supply:
Elimination: arterial: via superior thyroid and ascending pharyn-
may occur via lungs, bile, urine, GIT, saliva or breast geal branches of the external carotid artery.
milk. Renal excretion depends on GFR, water solu- venous: via pharyngeal plexus to the internal jugular
bility and extent of active tubular secretion and vein.
reabsorption. Nerve supply: ninth and 10th cranial nerves, with
most drugs are eliminated by first-order kinetics, additional nasal innervation via the fifth nerve.
whereby rate of elimination is proportional to the [Bartolomeo Eustachio (15131574), Italian physician]
amount of drug in the body (i.e. simple exponential See also, Nose
decay).
in zero-order kinetics, a constant amount of drug is
Phase II block, see Dual block
eliminated per unit time (e.g. alcohol, phenytoin).
Zero-order kinetics may replace first-order kinetics
when elimination pathways are saturated, i.e. at Phase shift. Delay between the arrival of a signal at a
high drug concentrations. monitoring device (e.g. transducer) and the latters
These analyses allow prediction of drug kinetics for output. Distortion of the signal is minimised by applying
calculation of appropriate dosage regimens or incorpo- the same delay to all components of the waveform, thus
ration into the software of computer-controlled infusion maintaining the phase relationship between harmonics.
pumps. For a continuous drug infusion, 50% of steady- This is achieved by adjusting the damping of the system
state levels are reached after one half-life, 75% after two to about two-thirds critical damping, at which there is a
half-lives, 87.5% after three, 93.75% after four, 96.875% linear relationship between phase lag and the frequency
after five, etc. A loading dose achieves steady-state levels of the wave.
more quickly, but is limited by adverse effects if a large
dose is given, depending on the drugs therapeutic ratio/ Phenobarbital/Phenobarbital sodium (Phenobarbi-
index. At steady state, the infusion rate equals the rate tone). Long-acting barbiturate and anticonvulsant drug,
of elimination of drug for a one-compartment model, or introduced in 1912. Used as a secondary agent in all
the rate of transfer to a peripheral compartment for a types of epilepsy except absence attacks. Also used in
multi-compartment model. the treatment of status epilepticus. Although absorbed
Rigby-Jones AE, Sneyd JR (2012). Anaesthesia; 67: 511 slowly after oral administration, it has an oral bioavail-
See also, Drug interactions; Gender differences and ability of 90% with duration of action up to 16h. Elimi-
anaesthesia; Genetics; MichaelisMenten kinetics; Target- nation half-life is about 90h. 2045% protein-bound,
controlled infusions and 75% metabolised by hepatic microsomal enzymes;
25% is normally excreted unchanged in urine.
Pharynx. Common upper end of the respiratory and Dosage:
alimentary tracts, extending from the base of the skull to 60180mg orally od (58mg/kg/day in children).
the level of C6. for status epilepticus: 10mg/kg.
Divided into: Side effects include sedation and ataxia. Paradoxical
nasopharynx: lies behind the nasal cavities, above excitation may occur in children.
the soft palate. Contains the adenoids, and a Eusta- Hepatic enzyme induction may reduce the effective-
chian tube orifice on each lateral wall. ness of other drugs, e.g. warfarin, oral contraceptives,
oropharynx: lies behind the mouth and tongue, corticosteroids.
below the soft palate. Bounded anteriorly by the
anterior pillars of the fauces (with buccal cavity
anteriorly), superiorly by the palate and inferiorly Phenol. Organic compound with the chemical formula
by the tip of the epiglottis. Contains the tonsils, lying C6H5OH. Used as a neurolytic agent in chronic pain
between the anterior and posterior pillars (contain- management. Thought to spare large myelinated fibres
ing palatoglossus and palatopharyngeus muscles whilst damaging unmyelinated C pain fibres by protein
respectively). denaturation. Hyperbaric 5% solution in glycerin is
laryngopharynx: lies behind and around the larynx,
used for subarachnoid neurolysis of posterior nerve
extending from the level of the epiglottic tip to roots; 0.52.0ml has an effect lasting up to 14 weeks.
the C6 level. The larynx projects into the laryngo- 67% solution in water is used for sympathetic nerve
pharynx, leaving a deep recess (piriform fossa) on blocks.
each side. Also used for sclerotherapy of haemorrhoids, and as
Composed of mucosa (ciliated columnar type in the a throat gargle. 15% solution (carbolic acid) is also used
nasopharynx; stratified or squamous elsewhere), submu- for disinfection of equipment. Irritant to the skin. Used
cosa, muscle layer and loose areolar sheath. The muscles for surgical antisepsis by Lister in Glasgow in 1865.
(superior, middle and inferior constrictors) are arranged [Joseph Lister (18271912), English surgeon]
so that the upper parts of each overlap the lower fibres
of the muscle above. They arise thus: Phenoperidine hydrochloride. Obsolete synthetic
superior: from the pterygomandibular raphe, and opioid analgesic drug related to pethidine, discontinued
bony points at either end. in the UK in 1997. Used mainly for neuroleptanaesthesia
middle: from the hyoid bone and stylohyoid and analgesia, and sedation in ICU. Undesirable features
ligament. included vasodilatation, hypotension, increased ICP and
inferior: from the thyroid and cricoid cartilages. metabolism to pethidine and norpethidine.
 Phenytoin/phenytoin sodium 461

Phenothiazines. Group of sedative and antipsy- Dosage:

chotic drugs. Also have antimuscarinic, antiemetic, anti- 5001000mg orally bd/qds.
histamine, antidopaminergic and -adrenergic receptor for prophylaxis, 250mg (rheumatic fever) or 500mg
antagonist properties. Some may potentiate the effects (splenectomy, sickle cell) bd.
of opioid analgesic drugs. Different drugs have varying Side effects: as for benzylpenicillin.
degrees of these properties, depending on the side chains
of the molecule. Act mainly on the ascending reticular Phentolamine mesylate. Non-selective -adrenergic
activating system, limbic system, basal ganglia, hypo- receptor antagonist, with an additional direct relaxant
thalamus and chemoreceptor trigger zone. Cause seda- action on vascular smooth muscle. Used in hypotensive
tion, with reduced muscular, GIT and cardiovascular anaesthesia and to control hypertensive crises, e.g.
activity. Effect on respiration is variable. Central tem- caused by phaeochromocytoma, monoamine oxidase
perature regulatory mechanisms, shivering, and periph- inhibitor interactions and clonidine withdrawal. An oral
eral vasoconstriction are impaired, but metabolic rate is preparation is used for the treatment of erectile dysfunc-
unaffected. Highly lipid-soluble and extensively protein- tion. Previously used for diagnosing phaeochromocy-
bound. Metabolised in the liver to mostly inactive toma and in the assessment of complex regional pain
metabolites. syndromes. Its place in the management of phaeochro-
Side effects: mocytoma has now been superseded by prazosin and
extrapyramidal symptoms, e.g. tardive dyskinesia, doxazosin. Acts within 2min of iv injection, with dura-
dystonia, tremor, facial grimacing. tion of action 1015min.
drowsiness, insomnia, depression, hypothermia, pre- Dosage: 25mg iv repeated as required; 0.12.0mg/
vention of shivering. min by infusion.
anticholinergic effects, e.g. tachycardia, arrhythmias, Side effects: postural hypotension, tachycardia,
dry mouth, urinary retention, blurring of vision. abdominal pain, diarrhoea, nasal congestion.
galactorrhoea, menstrual irregularity, gynaecomas- See also, Vasodilator drugs
tia, weight gain.
blood dyscrasias, haemolysis. Phenylephrine hydrochloride. Synthetic selective 1-
photosensitivity, contact dermatitis, rash. adrenergic receptor agonist, used as a vasopressor drug,
obstructive jaundice. e.g. in spinal anaesthesia. Causes intense vasoconstric-
hypotension. tion and compensatory bradycardia. Popular in obstetric
neuroleptic malignant syndrome. regional anaesthesia, since it appears more effective
potentiation of other depressant drugs. than ephedrine, and fetal acidbase profile is better than
Chlorpromazine is the standard phenothiazine; others if large doses of ephedrine are used. Has been adminis-
include alimemazine (trimeprazine), promethazine, per- tered topically to the nasal mucosa and eye to cause
phenazine, promazine, thioridazine, fluphenazine and vasoconstriction and mydriasis respectively, and as a
trifluoperazine. vasoconstrictor agent for local anaesthesia. Has also
been used to treat SVT. Of similar structure to adrena-
Phenoxybenzamine hydrochloride. Irreversible non- line, lacking only the 4-hydroxyl group.
selective -adrenergic receptor antagonist, chemically Dosage:
related to the nitrogen mustards; forms covalent bonds 25mg im or sc.
with -adrenergic receptors. Used mainly to control 100500g iv (510g/kg in children); 30
hypertension caused by phaeochromocytoma. Has also 180g/min by infusion. Boluses of 25100g are
been used in complex regional pain syndrome type 1. used to treat hypotension in obstetric regional
More active at 1-receptors than at 2-receptors. Onset anaesthesia.
of action may be up to 1h after iv injection, due to con- 2.55mg added to 100ml local anaesthetic
version to an active form. Effects last for several days, solution.
although its elimination half-life is about 24h. Side effects: hypertension, bradycardia, vomiting.
Dosage:
10mg orally od, increased by 10mg/day as required. Phenytoin/phenytoin sodium. Hydantoin anticonvul-
1mg/kg in 200ml saline over 2h od (profound sant drug, introduced in the late 1930s. Used to treat all
hypotension may occur). types of epilepsy except petit mal, in chronic pain man-
Side effects: postural hypotension, tachycardia, retro- agement, and previously as a class Ib antiarrhythmic
grade ejaculation, nasal congestion, miosis, rarely drug (especially for digoxin-induced arrhythmias). Has
GIT disturbances. membrane-stabilising effects on all neuronal cells,
See also, Vasodilator drugs including peripheral nerves and cardiac muscle; acts by
blocking voltage-gated sodium channels.
Phenoxymethylpenicillin (Penicillin V). Natural peni- A poorly water-soluble weak acid, with pKa ~ 8.3.
cillin used especially in streptococcal infections and in Variably absorbed from the GIT, it may cause gastric
rheumatic fever prophylaxis. Also used for pneumo irritation. Erratically absorbed after im injection,
coccal prophylaxis after splenectomy or in sickle cell probably due to local precipitation. About 90% protein-
anaemia. Similar to benzylpenicillin but less active and bound, and metabolised in the liver to inactive metabo-
more acid-stable; thus suitable for oral administration, lites that are excreted renally. Elimination follows
following which peak serum levels occur in about 60min first-order kinetics at plasma levels below 10mg/l;
(although somewhat variably, hence the recommenda- zero-order kinetics occur above 10mg/l, due to satura-
tion that it not be used for severe infections). 80% of the tion of enzyme systems (see Pharmacokinetics). Elimina-
drug is protein-bound. Excreted in urine (the dose tion half-life is about 24h but varies. Susceptible to
should be reduced in renal impairment) and faeces. hepatic enzyme induction, and is itself an enzyme
Elimination half-life is 40min. inducer.
462 PHI

Dosage: phosphate intake. Decreased excretion occurs when

34mg/kg daily as one or two oral doses, increased intake is low or in response to thyroxine or growth
up to 600mg/day. hormone. Hyperphosphataemia causes no specific clini-
for status epilepticus: 20mg/kg iv slowly, with ECG cal sequelae but may disturb calcium metabolism. Hypo-
monitoring, followed by 100mg tds/qds. Plasma phosphataemia is uncommon but may occur during TPN
levels should be monitored. and ketoacidosis.
for arrhythmias: 3.55.0mg/kg iv slowly, repeated
once if required. Phosphodiesterase inhibitors. Substances that prevent
IV administration should be via a large vein at no conversion of 3,5-adenosine monophosphate (cAMP)
more than 50mg/min. Flushing with saline should to 5-adenosine monophosphate, or 3,5-guanosine
follow as the solution is strongly alkaline and irri- monophosphate (cGMP) to 5-guanosine monophos-
tant. Arrhythmias and hypotension may occur. phate by the enzyme phosphodiesterase (PDE; see Fig.
Plasma therapeutic range is 1020mg/l (40 5; Adenosine monophosphate, cyclic). Both cAMP and
80mol/l). cGMP are important intracellular messengers. Many iso-
Side effects: enzymes of PDE exist:
headache, vomiting, confusion, tremor. Ataxia, PDE I: stimulated by calcium/calmodulin.
nystagmus and blurred vision may indicate PDE II: stimulated by cGMP.
overdosage. PDE III: inhibited by cGMP.
skin eruptions, lymphadenopathy, hirsutism, fever, PDE IV: cAMP-specific.
hepatitis, gingival hyperplasia. The purple glove PDE V: cGMP-specific.
syndrome (blue/purple discoloration followed by PDE inhibitors have antithrombotic, anti-inflammatory,
oedema and necrosis) may occur around the site of vasodilator, inotropic and bronchodilator properties.
iv administration. Amrinone, milrinone, enoximone, piroximone and
osteomalacia. pimobendan are examples of PDE III inhibitors. Ami-
rarely, megaloblastic anaemia (due to impaired nophylline, papaverine and caffeine are non-specific
folate absorption and storage), other blood inhibitors and sildenafil and dipyridamole are PDE V
dyscrasias. inhibitors.
fetal abnormalities and neonatal bleeding may
follow its use in pregnancy. Phrenic nerve pacing. Intermittent electrical stimula-
Chronic usage may increase fluoride ion produc- tion of the phrenic nerves (usually bilaterally), to pace
tion from enflurane, and cause resistance to non- the diaphragm in chronic hypoventilation due to brain-
depolarising neuromuscular blocking drugs. stem, medulla or upper cervical cord lesions. Has also
Available as a prodrug, fosphenytoin. been used in COPD. Described in the 1960s, it requires
intact phrenic nerves and diaphragm function, thus
PHI, see Prehospital index excluding its use in lower motor neurone lesions and
myopathies.
Phlogiston. Imaginary substance proposed in the 1720s, Platinum electrodes are implanted around the nerves
thought to separate from combustible material during in the neck or thorax and connected to a subcutaneous
burning. Following experiments in the 1770s, Priestley radio receiver, which is triggered by an external power
concluded that dephlogisticated air (O2) and dephlo- source. Respiratory rate, inspiratory time and sighs may
gisticated nitrous air (N2O) were deficient in phlogiston be adjusted. Neck electrodes risk inadvertent stimula-
and could thus support combustion, whereas nitrous tion of the brachial plexus. Nerve trauma at surgery,
air (NO2) was saturated with it and was unable to do so. infection and poor contacts may cause failure. Diaphrag-
The phlogiston theory was subsequently disproved by matic fatigue may also occur. Obstructive apnoea may
Lavoisier. be precipitated in some cases of central alveolar
hypoventilation.
Phonocardiography. Technique employing contact Shehu I, Peli E (2008). Eur J Anaesthesiol; 25: 18691
microphones placed on the chest, for amplification and
recording of heart sounds. Used to obtain an objective Phrenic nerves. Originate from the ventral rami of
record of heart sounds and heart murmurs. May be per- C35 on each side, supplying the motor innervation of
formed simultaneously with ECG and arterial waveform the diaphragm. Also convey sensory fibres from the dia-
recording, allowing calculation of systolic time intervals. phragm, hence the shoulder-tip referred pain caused by
A similar technique is employed in fetal monitoring. diaphragmatic irritation. Sensory fibres from the medi-
See also, Cardiac cycle astinal pleura, fibrous pericardium and parietal serous
pericardium are also conveyed.
Phosphate. Total body content is about 25 000mmol, Descend vertically on the scalenus anterior muscles,
most of which is intracellular. 80% is in bone, 15% is in which they cross from lateral to medial sides. Each nerve
soft tissues and only 0.1% is in ECF. Most intracellular passes to the root of the neck beneath the sternomastoid
phosphate is in the organic form. Normal plasma inor- muscle, inferior belly of omohyoid, internal jugular vein
ganic phosphate levels: 0.81.45mmol/l. and (on the left) the thoracic duct. The right phrenic
Involved in cell membranes (phospholipids), enzyme nerve enters the thorax behind the subclavian/internal
regulation, energy storage (ATP), O2 transport (2,3- jugular venous junction, descending subpleurally next to
DPG) and acidbase buffering. the right brachiocephalic vein, superior and inferior
Levels are controlled by renal excretion; most of venae cavae and pericardium. Some of its branches pass
the filtered phosphate is reabsorbed in the proximal through the caval foramen of the diaphragm, spreading
tubule of the nephron. Excretion is increased by para- over its peritoneal surface. The remainder pierce the
thyroid hormone, calcitonin, adrenaline and increased diaphragm just lateral to the caval orifice. The left nerve
 Pin index system 463

enters the thorax between the subclavian artery and Techniques include:
vein. It passes superficially to the aortic arch, to pierce postural drainage: positioning according to the
the diaphragm anteriorly and to the left of the caval anatomy of the tracheobronchial tree, with or
opening. Some of the divisions of each nerve cross to the without breathing exercises.
other side. breathing exercises, e.g. incentive spirometry,
Local anaesthetic block has been advocated as a coughing. Forced expirations may be more effective
treatment for chronic hiccups. 10ml local anaesthetic than cough alone, especially if combined with pos-
agent is injected 12cm deep at a point 2cm above the tural drainage.
sternoclavicular joint and for 5cm laterally. intermittent lung inflations using ventilators, to
Phrenic paralysis may complicate brachial plexus increase lung expansion.
block, trauma, tumour, neurological disease and cardiac chest wall percussion and vibration: their efficacy
surgery. Clinically, paradoxical inward abdominal move- has also been questioned.
ment is seen on inspiration, with a raised hemidiaphragm upper airway suction: usually combined with the
on CXR. above.
See also, Phrenic nerve pacing Administration of nebulised bronchodilator drugs
before physiotherapy may produce a better sputum
yield. Nebulised saline, humidified O2 and mucolytics are
Physicians Assistants (Anaesthesia). Non-medically also commonly used.
qualified personnel able to deliver anaesthesia under May be painful, especially postoperatively, and ade-
supervision by a qualified anaesthetist. In the UK, the quate analgesia is essential.
term is specific to graduates of programmes approved by
the Royal College of Anaesthetists, set up as pilots ini-
Physostigmine salicylate/sulphate. Acetylcholinester-
tially in 2003, in response to predicted shortfalls in man-
ase inhibitor, derived from the West African Calabar
power. The scheme mirrors those introducing other
bean. Causes reversible inhibition of acetylcholinester-
support roles within the NHS, taking on some of the
ase by binding to its esteratic site, lasting 12h. Readily
activities and duties traditionally exclusive to qualified
crosses the bloodbrain barrier because of its tertiary
doctors. The original term Anaesthesia Practitioners
amine structure. Used to treat the central anticholinergic
was replaced by the new title in 2008 to bring it into line
syndrome, and topically in glaucoma. Has also been used
with Physicians Assistants in other specialties and to aid
in -hydroxybutyric acid poisoning. Formerly used as a
understanding of the role.
general CNS stimulant, e.g. in tricyclic antidepressant
drug poisoning and to reverse opioid-induced respira-
Physiological and operative severity score for the tory depression. No longer available in the UK.
enumeration of mortality and morbidity (POSSUM). Dosage: 0.04mg/kg slowly iv.

Scoring system described in 1991 as a method of predict- Side effects: nausea, hypertension, tachycardia. Large

ing outcome (morbidity and mortality) for surgical doses may result in cholinergic crisis.
patients. Patients are scored before operation (using
measures of physiological derangement) and at opera- PiCCO. Commercial non-invasive cardiac output mea-
tion (using an operative severity score) to give predic- surement system made available in 1997, combining the
tions of morbidity and hospital mortality. The original principles of transpulmonary thermodilution, in which
POSSUM model has been modified for specific subspe- the cold transverses the lungs after injection, and arte-
cialties to provide greater accuracy (e.g. P-POSSUM for rial pulse contour analysis. Requires injection of a single
general surgery, CR-POSSUM for colorectal cancer bolus injection of cold saline through a central venous
surgery, V-POSSUM for vascular surgery). catheter and its detection by a specially modified cannula
Prytherch DR, Whiteley MS, Higgins B, et al (1998). Br placed in a large artery (e.g. femoral/brachial). Permits
J Surg; 85: 121720 continuous estimation of cardiac output, intrathoracic
blood volume, left ventricular afterload, extravascular
lung water and stroke volume variation. Provides
Physiotherapy. Treatment and prevention of disease cardiac output measurements with similar accuracy to
using passive and active movement, vibration, massage that obtained from pulmonary artery catheterisation,
and application of heat. Used for neurological, musculo- although frequent calibration may be required in unsta-
skeletal and respiratory disorders. Has an important role ble patients (e.g. in sepsis or haemorrhage).
in the ICU in preventing stiffness of limbs and joints PiCCO 2 uses a more refined algorithm and was
during prolonged immobility, and in helping the patient released in 2008.
mobilise during recovery. Mayer J, Suttner S (2009). Curr Opin Anesthesiol; 22:
Chest physiotherapy aims to maintain clear airways, 8048
increase lung expansion and thus reduce atelectasis and
sputum retention. Often beneficial pre- and postopera-
tively in patients with respiratory disease, helping to Pickwickian syndrome, see Obesity hypoventilation
optimise respiratory function. It is also valuable in the syndrome
ICU management of patients with respiratory failure,
before, during and after IPPV. It is thought to be most Pierre Robin syndrome, see Facial deformities,
useful when excessive sputum is present; its place in congenital
uncomplicated COPD, chest infection without sputum
production, and routine postoperative management is Pin index system. International system introduced in
unclear. Thought to be of little benefit if disease is mainly 1952, preventing accidental connection of a gas cylinder
peripheral; thus it is most effective if secretions are to the wrong anaesthetic machine yoke. The cylinder
within the bronchi. valve block bears holes into which fit pins protruding
464 Pipecuronium bromide

secondary sources used alternately with a small

reserve supply. The primary source may be a mani-
fold of cylinders, vacuum insulated evaporator, air
compressor or O2 concentrator.
pipeline distribution network: made of phosphorus
deoxidised non-arsenical copper, greased and spe-
cially cleaned with steam, shot and medical air.
Joints are usually made with a silver alloy, although
some are threaded. They should be colour-coded
and marked with the name of the gas contained.
Isolation valves should be supplied.
terminal distribution system: includes self-closing
1 6 sockets, probes, flowmeters, and hoses and their
2 3 4 5
7 connections with anaesthetic machines. The probes
and sockets should be specific for the service sup-
plied, the probe of one gas fitting only the socket
for the same gas.
Some probes (e.g. for ward use) may incorporate
flowmeters. Connecting hoses to probes should only
be possible if specialised equipment is used, reduc-
ing the risk of misconnection. Hose connections to
anaesthetic machines are made specific for each
Fig. 128 Position of holes (17) in pin index system service by non-interchangeable screw-thread con-
nectors. UK colour coding of hoses:
- N2O: French blue.
from the yoke. A flush connection is only achieved if the - O2: white.
holes and pins align correctly. The positions of the holes - air: black/white.
on the valve block (and corresponding pins on the yoke) - Entonox: French blue/white.
are specified by an international standard (Fig. 128): - vacuum: yellow.
O2: positions 2 and 5. system failure alarms: predominantly low-pressure
N2O: positions 3 and 5. alarms, they sound when secondary and reserve
air: positions 1 and 5. systems are in use. Usually situated at hospital tele-
CO2: positions 1 and 6. phone switchboards.
Entonox: position 7. Howell RS (1980). Anaesthesia; 35: 67698
The system may be circumvented, e.g. by removing pins See also, Suction equipment
or using several Bodok seals. When piped gas supplies
were first introduced, pin-indexed fittings were attached Piperacillin. Semisynthetic penicillin derivative with
to the pipelines; these could be inserted upside-down broad-spectrum antibacterial activity; has greater
into the cylinder yokes, allowing incorrect gas connec- activity against Gram-negative organisms than narrow-
tion. The positions for cyclopropane were 3 and 6. spectrum penicillins, with slightly reduced effectiveness
against certain Gram-positive organisms (e.g. Strepto-
Pipecuronium bromide. Non-depolarising neuromus- coccus pneumoniae). Especially effective against pseu-
cular blocking drug, synthesised in Hungary in the late domonas infections, although bacterial resistance is a
1970s and made available in the USA in 1990. A more growing problem. Often given with an aminoglycoside
potent analogue of pancuronium, which it resembles in in severe pseudomonas infections since the combination
its clinical action but with fewer CVS side effects. 40% is synergistic (but the two drugs should not be mixed in
excreted by the kidneys, it accumulates in renal failure. the same syringe). Only available combined with the
Reversibly inhibits plasma cholinesterase, and does not -lactamase inhibitor tazobactam. Piperacillin is 20%
release histamine. A 0.070.08mg/kg intubating dose protein-bound with volume of distribution 1520 l.
acts within 1.52min, lasting for 1.52h. Excreted via urine and faeces. Elimination half-life is
approximately 1h.
Piped gas supply. Networks of pipes and socket outlets Dosage: 4.5g iv tds (qds in neutropenic patients).
that distribute medical gases from a central source to Side effects: as for benzylpenicillin. The high
points of use. In the UK, only O2, N2O, Entonox, CO2 sodium content of the preparation may result in
(rarely) and compressed air may be distributed by such hypernatraemia.
systems. All are supplied at 4 bar except air, which may
be required at 7 bar for surgical instruments. Medical Pirbuterol. -Adrenergic receptor agonist, available for
vacuum is also supplied by a pipeline system. the treatment of asthma but also investigated as an
Essential features include: orally active inotropic drug. Active at 1-adrenergic
indexing system to prevent cross-connection. receptors, with some activity at 2-receptors. Thus
prevention of contamination of gases. increases cardiac output and causes vasodilatation; BP
automatic function, especially when switching over may fall. Tachycardia is uncommon.
supplies.
anticombustion and anti-explosion controls. Piritramide. Opioid analgesic drug, developed in 1960
Systems consist of: and available in oral and iv forms. 20mg is equivalent to
central gas source: either a large primary source 15mg morphine. Of faster onset than morphine, with
and small reserve supply, or large primary and similar duration of action. Causes less hypotension,
 Placenta 465

nausea and vomiting, but with greater hypnotic effect. [A ]

Not available in the UK. Thus log [H + ] = log Ka + log
[HA]
Substituting pH for log [H+], and pKa for log Ka:
Pirogoff, Nicholai Ivanovich (18101881). Russian
[A ]
surgeon at St Petersburg, a pioneer of battlefield trauma pH = pKa + log
surgery, also known for introducing rectal diethyl ether [HA]
for surgery in 1847. Also studied the effects of ether, For a weak base (B):
designed apparatus for its rectal and inhalational admin-
[B]
istration, and published the first book on the subject pH = pK b + log
in 1847. [BH + ]
Secher O (1986). Anaesthesia; 41: 82937 The pK represents the pH value at which the solute is
50% dissociated; i.e. [A] = [HA] or [B] = [BH+].
Piroxicam. Oxicam NSAID, available for enteral and im Whilst pKa strictly refers to an acidic substance and
use. Rapidly absorbed after oral administration, it is 99% pKb to a basic one, by convention pKa is used to refer to
protein-bound and has a long (50h) half-life; thus can both acids and bases.
be given once daily. Due to a high incidence of cutaneous The stronger an acid, the lower its pKa, and the stron-
and GIT adverse reactions, its use is now restricted ger a base, the higher its pKa. Thus important when con-
to analgesia in chronic inflammatory or rheumatoid sidering ionisation of drugs and passage of drugs or
conditions. other substances across membranes.
Dosage: 1020mg orally, pr or by deep im injection
od/bd. Placenta. Structure dividing the fetal and maternal cir-
Side effects: as for NSAIDs, though associated culations. Approximately 56 days after conception the
with an increased risk of GIT upset and serious skin fertilised egg (now a mass of uniform cells) attaches to
reactions compared with most others. the endometrium. The endometrium is invaded by the
outer layer of the trophoblast of the egg, the syncytio-
trophoblast. Further proliferation of the trophoblast
Pituitary gland. Lies in the pituitary fossa of the sphe- forms finger-shaped masses of tissue, the chorionic villi,
noid bone, above the sphenoid air sinuses and below the between which spaces (lacunae) appear. The tips of the
optic chiasm. Composed of anterior and posterior lobes, villi erode the walls of the endometrial spiral arteries so
connected to the hypothalamus by the infundibular that the lacunae expand to form large spaces filled with
stalk, which contains nerve fibres and the hypophyseal maternal blood within which float the villi. Primitive
portal blood system. The infundibulum pierces the dia- blood vessels appear in the villi from about 18 days after
phragma sellae, a dural sheet, that covers the gland. fertilisation, eventually joining the fetal umbilical vessels.
Function:
Densely packed masses of fetal villi (fetal cotyledons)
anterior lobe: are supplied by branches of the umbilical arteries, dis-
- contains cells formerly classified by their staining tributed radially as end-arteries. Several cotyledons form
properties (chromophobe, eosinophil and acido- a single placental lobe. Thus the barrier between fetal
phil cells); now identified on an immunocyto- and maternal circulations is two cells thick, consisting of
chemical basis into five cell types: the fetal capillary endothelium and its covering of syn-
- somatotrophs: secrete growth hormone. cytial trophoblast.
- lactotrophs: secrete prolactin. Blood supply:
- corticotrophs: secrete ACTH. fetal: blood arrives via two umbilical arteries and
- thyrotrophs: secrete thyrotrophin. leaves by a single umbilical vein. Umbilical blood
- gonadotrophs: secrete luteinising and follicle- flow is up to 100ml/min at 22 weeks and 300ml/min
stimulating hormones. at term, of which about 20% does not participate in
- secretion is controlled by hypothalamic inhibitory exchange with maternal blood.
or releasing factors, carried to the anterior maternal: delivered via the uterine arteries. Uterine
pituitary by the portal blood system and by nega- blood flow (UBF) at term is 500700ml/min, 80%
tive feedback control by circulating end-organ of which passes to the placenta. There is no auto-
hormones. regulation in the placental circulation and therefore
posterior lobe: secretes vasopressin and oxytocin. flow is directly related to mean uterine perfusion
Pituitary gland disease may be associated with over- or pressure and inversely related to uterine vascular
under-secretion of hormones (usually the latter). resistance. UBF may be reduced by maternal hypo-
Enlargement may cause visual field defects, optic atrophy tension, hyperventilation and stress, and by vaso-
and raised ICP. pressor drugs.
Smith M, Hirsch NP (2000). Br J Anaesth; 85: 314 Placental function is related to its total surface area and
See also, Acromegaly; Cushings disease; Diabetes insipi- UBF. Impaired function causes fetal hypoxaemia and
dus; Hypopituitarism acidosis if acute, and may lead to delayed fetal growth if
chronic.
Functions:
pK. Negative logarithm (to base 10) of the dissociation
gas exchange: O2 and CO2 exchange is favoured by
constant for a weak acid or base in aqueous solution. The
law of mass action states that for a weak acid (HA) dis- fetal haemoglobin and the double Bohr effect
sociating in solution, HA H+ + A: respectively.
nutrient exchange: all energy substrates, water, min-
[H + ][A ] erals and electrolytes enter the fetus via the pla-
dissociation constant Ka =
[HA] centa by facilitated or active transport.
466 Placenta praevia

hormone synthesis and release: hormones include Allahdin S, Voigt S, Htwe TT (2011). J Obstet Gynaecol;
chorionic gonadotrophin, oestrogens, progesterone, 31: 16
prolactin, somatomammotrophin and renin. Several See also, Placental abruption
corticosteroid hormones are synthesised by the
fetoplacental unit, e.g. placental pregnenolone is
Placental abruption. Complete or partial separation of
metabolised by the fetus before further placental
the placenta before delivery, causing retroplacental
metabolism to form oestrogens.
haemorrhage; thought to occur to some degree in up to
See also, Fetus, effect of anaesthetic agents on; Obstetric
45% of all pregnancies, although only 1050% of these
analgesia and anaesthesia; Placenta praevia; Placental
present clinically. More common in smokers, pre-
abruption
eclampsia, multiparity, abdominal trauma, and those
with a previous history of placental abruption. May
Placenta praevia. Encroachment of the placenta upon
coexist with placenta praevia in 10% of cases. Has been
the cervical os. Overall risk is about 0.25%, increased if
classified into asymptomatic (grade 0); vaginal bleeding
there has been previous caesarean section (CS), e.g. up
without maternal or fetal distress (grade I); fetal distress
to 10% after four previous CS. May coexist with placen-
present (grade II); and fetal and maternal distress (grade
tal abruption in 10% of cases.
Classified into:
III), although this classification is not used as commonly
as that for placenta praevia.
grade I: the placenta is low-lying, i.e. within the
Problems:
lower uterine segment; the placenta does not reach
a cause of antepartum haemorrhage; presents with
the internal os.
abdominal pain and, usually, fetal distress. The
grade II: the placenta reaches the os.
amount of vaginal bleeding (if present) may under-
grade III: the placenta covers the whole of the os
estimate the extent of haemorrhage, which may be
but most of the placenta is positioned to one side.
visible on ultrasound as retroplacental clot.
grade IV: the placenta is placed squarely over
associated with DIC (in up to 10%) and renal corti-
the os.
Problems:
cal necrosis (although renal impairment more often
results from acute tubular necrosis caused by hypo-
may cause antepartum haemorrhage with cardio-
volaemia). The extent of DIC may be out of propor-
vascular collapse and fetal distress.
tion to the amount of bleeding; it may worsen (or
requires CS, especially in the higher grades, since
develop if not already present) if caesarean section
the presenting part will compress the placenta and
(CS) is delayed. Thus, urgent CS is required in sig-
obstruct blood flow during labour and vaginal deliv-
nificant abruption, although mild cases may be
ery. Malpresentation is more common.
managed expectantly.
associated with postpartum haemorrhage since the
Anaesthetic management:
lower uterine segment is unable to contract as effec-
standard techniques as for obstetric analgesia and
tively as the upper segment, being less muscular.
anaesthesia.
may be associated with placental invasion (placenta
general anaesthesia is usually preferred for CS
accreta) or even penetration of the uterine wall
because of the risk of hypovolaemia and DIC.
(placenta percreta); delivery of the placenta may be
Coagulation studies are mandatory before regional
accompanied by torrential haemorrhage that may
anaesthesia is performed, if chosen.
require hysterectomy, uterine artery embolisation
at least two large-bore iv cannulae (plus blood
or iliac artery ligation. Placenta accreta occurs in
warmer), cross-matched blood and appropriate
about 0.04% of all pregnancies, increased to 59%
senior staff should be arranged. Since coagulopathy
in mothers with placenta praevia and up to 4050%
may worsen unless delivery is achieved, CS should
if there have been 23 previous CS.
Anaesthetic management:
not be delayed.
Tikkanen M (2011). Acta Obstet Gynecol Scand; 90:
standard techniques, as for obstetric analgesia and
1409
anaesthesia.
choice of anaesthetic according to standard criteria;
in emergency CS general anaesthesia is usually pre- Plasma. Non-cellular portion of blood; represents the
ferred unless the amount of bleeding is small and ECF component within the vascular space. A clear, yel-
there is no cardiovascular instability. Traditionally, lowish fluid.
general anaesthesia has been preferred for elective Normal composition:
CS because of the impaired compensatory CVS water.
reflexes during extensive regional block and the dif- proteins:
ficulty managing an awake patient should severe - albumin (3550g/l).
haemorrhage occur. Recent opinion has shifted to - globulins, including immunoglobulins (2535g/l).
accept regional anaesthesia even in grades III and electrolytes:
IV placenta praevia, although many obstetric anaes- - main cations:
thetists would prefer general anaesthesia if there - sodium (135145mmol/l).
has been previous CS. - potassium (3.55.5mmol/l).
for grades III and IV cases, at least two large-bore - calcium (2.122.65mmol/l).
iv cannulae (plus blood warmer), immediately - magnesium (0.751.05mmol/l).
available cross-matched blood and appropriate - main anions:
senior staff should be ensured. Coagulopathy is - chloride (95105mmol/l).
uncommon unless massive transfusion is required; - bicarbonate (2433mmol/l).
thus CS should wait until these facilities and back-up - phosphate (0.81.45mmol/l).
are present. - lactate (0.61.8mmol/l).
 Plethysmography 467

others, e.g. urea (2.57.0mmol/l), creatinine (60 skin grafts may be taken from trunk or limbs, reduc-
130mol/l), fats, carbohydrates, e.g. glucose (4.0 ing sites of access to the patient.
6.0mmol/l), amino acids, enzymes, vitamins, regional techniques may be useful for graft donor
hormones, bilirubin. sites, e.g. femoral nerve block, lateral cutaneous
Osmolality is 280305 mosmol/kg. nerve of the thigh block.
Plasma clots on standing; the supernatant solution is a low haematocrit is thought to improve perfusion
termed serum. Plasma volume is about 3.5 litres in adults and healing of grafts. Dextran solutions may be
(5% of body weight), and measured by dye dilution tech- used to improve perfusion of grafted areas.
niques, using dyes or radioactive markers. tourniquets may be required.
Available for transfusion as fresh frozen plasma.
See also, Blood products; Coagulation Platelet-activating factor (PAF). Phospholipid auto-
coid produced by platelets, polymorphonuclear leuco-
Plasma exchange, see Plasmapheresis cytes and other blood cells. Thought to be a major
mediator (along with cytokines) in sepsis. Natural and
Plasma expanders. IV fluids that increase plasma synthetic PAF antagonists have been investigated as pos-
volume by an amount greater than that infused, because sible treatment for sepsis, with mixed results. PAF has
of indrawing of water from the extracellular and intra- also been shown to modulate CNS activity (e.g. neuronal
cellular spaces by osmosis. The term is usually reserved differentiation) and increased levels are associated with
for colloids, although hypertonic iv solutions act as neuronal injury.
short-term plasma expanders.
Platelet function analysers, see Coagulation studies
Plasma, fresh frozen, see Blood products
Platelets. Non-nucleated, smooth, disc-shaped blood
Plasma substitutes, see Colloids cells derived from cytoplasmic fragments of megakaryo-
cytes (bone marrow stem cells). Maturation of mega-
Plasmapheresis. Selective removal of small volumes karyocytes, and thus platelet production, is controlled by
(up to 600ml) of plasma from the body. Replacement a feedback mechanism involving the humoral agent
with iv fluids is not required. Removal of larger volumes thrombopoietin. Measure 24m in diameter and 58 fl
with fluid replacement is termed plasma exchange. Used in volume, with a circulatory life span of 814 days.
to remove plasma constituents associated with disease, Normal adult count is 150400 109/l blood; 1020% of
e.g. antibodies, antigens, immune complexes, drugs. Rate the total platelet population lies within the spleen. Plate-
of removal must exceed that of renewal. Usually reserved let deficiency and excess are termed thrombocytopenia
for disease resistant to other therapy. and thrombocytosis respectively.
Often beneficial in: Essential for normal coagulation, spontaneous
myasthenia gravis and myasthenic syndrome. haemorrhage occurring at counts below 2030 109/l.
GuillainBarr syndrome and other demyelinating Cytoplasmic granules within platelets contain many sub-
neuropathies. stances, including ATP, ADP, 5-HT, adrenaline, calcium,
multiple myeloma. fibronectin, fibrinogen, -thromboglobulin and throm-
Goodpastures syndrome. bospondin, which contribute to platelet aggregation,
thrombotic thrombocytopenic purpura. blood coagulation, local vasoconstriction, chemotaxis
poisoning with mushrooms and digoxin. and vessel repair.
May be beneficial in: Thromboxane synthetase is also present, and is
bullous pemphigoid. activated when platelets contact damaged vascular
rhesus haemolytic disease. endothelium. Release of thromboxane stimulates plate-
SLE. let aggregation via increased ADP levels, the ADP
rheumatoid arthritis. binding to specific receptors and activating the glycopro-
severe relapses of multiple sclerosis. tein IIb/IIIa complex (at which fibrinogen, von Wille-
Requires intermittent extracorporeal centrifugation or brand factor and adhesive proteins bind). Aggregation
continuous filtration. Removal of over 1000ml requires leads to further ADP release and release of the other
replacement with albumin to prevent a fall in plasma substances, eventually resulting in formation of a plug.
oncotic pressure. Partial substitution with colloids or During this process, the platelets become more spherical
crystalloids is often used. A single volume exchange and extend pseudopodia. Conversely, prostacyclin,
(40ml/kg) reduces plasma components by 5060%, present in the vascular endothelium, stimulates produc-
usually lasting 2448h. Usually, 1.5 plasma volumes are tion of platelet cAMP and reduces release of ADP,
exchanged during each session, repeated every 12 days inhibiting aggregation. Thus a fine balance exists between
according to clinical response. the two processes.
Practical considerations and complications are as for Apart from coagulation disorders arising from abnor-
extracorporeal circulation and iv fluid administration. mal platelet numbers, prolonged bleeding may arise
from abnormal function despite normal counts, e.g. renal
Plasmin and plasminogen, see Fibrinolysis failure, hepatic failure, pre-eclampsia and use of anti-
platelet drugs. Platelet function may be assessed using
Plastic surgery. Anaesthetic considerations: the bleeding time and thromboelastography.
related to the reason for surgery, e.g. burns, trauma, George JN (2000). Lancet; 355: 15319
facial deformities (see Ear, nose and throat surgery). See also, Coagulation studies; Platelet-activating factor
possible requirement for hypotensive anaesthesia.
problems of prolonged surgery, e.g. heat loss, blood Plethysmography. Recording of volume changes of an
loss, positioning of the patient. organ, part of the body or the whole body.
468 Pleura

Clinical applications: is confirmed by obtaining specimens, in most cases by

body plethysmograph. using bronchopulmonary lavage. The incidence has
non-invasive arterial BP measurement. decreased recently with more effective prophylaxis and
impedance plethysmography. treatment with co-trimoxazole and pentamidine. Corti-
measuring limb blood flow: costeroids are recommended in moderate-to-severe
- recording pressure changes in a circumferential disease, initiated at the same time as antimicrobial
cuff or strain gauges. therapy. Mortality is 2030% in patients with HIV infec-
- inflating a proximal cuff to between venous and tion, 50% in those without.
arterial pressures, and recording volume changes Huang L, Cattamanchi A, Davis JL, et al (2011). Proc
by immersing the limb in water. Am Thorac Soc; 8: 294300

Pleura. Double-layered sac enclosing the lungs. The Pneumonia, see Chest infection
outer parietal layer attaches to the diaphragm, mediasti-
num and chest wall. The inner visceral layer is closely Pneumonitis. Inflammation of the lung caused by physi-
applied to the lung surface and enters its fissures. The cal or chemical agents, e.g. inhalation of toxic or irritant
layers meet at the lung hila. They are held together by the substances and fumes, radiation. Clinical features vary
negative intrapleural pressure within the pleural cavity, from mild dyspnoea to those of severe acute lung
which normally contains a small amount of serous fluid. injury. Inflammation caused by infection is termed pneu-
Surface markings: monia; that caused by an allergic reaction is termed
apex: 3.5cm above the clavicular midpoint. alveolitis.
medial border: passes behind the sternoclavicular See also, Aspiration pneumonitis
joint, meeting the opposite pleura level with the
second costal cartilage. Descends to the costoxi- Pneumotachograph. Constant orifice, variable-pressure
phoid angle on the right; deflects laterally to the flowmeter, used widely in anaesthetic and respiratory
lateral sternal edge on the left. research. Measures the pressure gradient across a
inferior border: lies level with the eighth rib in the fixed resistance using pressure transducers; using the
midclavicular line, 10th rib in the midaxillary line, HagenPoiseuille equation, if flow is laminar, the pres-
and passes up to the spine of T12 posteriorly. sure difference is proportional to flow. In the Fleisch
pneumotachograph, the resistance is produced by an
Pleural effusion. Serous fluid between the parietal and array of tubes 12mm in diameter, the number of tubes
visceral layers of pleura (interpleural pus and blood being matched for the desired flow range. The resistor is
are called empyema and haemothorax, respectively). enclosed within an electrical coil to prevent condensa-
May be unilateral or bilateral. Divided according to the tion. In other devices, the resistance consists of a layer
protein content into: of metal or plastic gauze, the latter less likely to cause
transudates (< 30g/l), e.g. cardiac failure, condensation.
hypoproteinaemia. The instrument head should be appropriately sized to
exudates (> 30g/l), e.g. tumours, inflammatory avoid turbulence, and the gas flow spread evenly over
disease (e.g. connective tissue diseases), infection the resistance unit. The pressure gradient depends not
(e.g. TB), PE, abdominal disease (e.g. subphrenic only on the gas flow but also on its composition, viscosity
abscess, pancreatitis, ovarian carcinoma). and temperature; thus difficulties may arise if gas com-
Features include dyspnoea, usually related to the size of position varies between breaths.
the effusion. Chest wall movement and breath sounds [Alfred Fleisch (18921973), Swiss physiologist]
are reduced over the effusion, with percussion typically
stony dull. Large unilateral effusions may displace the Pneumothorax. Free gas, usually air, within the pleural
mediastinum (and thus the trachea) towards the oppo- cavity.
site side. Confirmed by CXR, ultrasound or CT scan- Has been classified as:
ning; examination of the fluid aids diagnosis. simple: the gas is not under tension. May be:
Treatment includes chest drainage and is otherwise - open: continuing communication between the
directed towards the cause. source of the gas and the pleural cavity. Intrapleu-
Large pleural effusions may hinder lung expansion ral and atmospheric pressures are equal and lung
and should be drained preoperatively. Other anaesthetic expansion is poor, causing marked hypoxaemia.
considerations are related to the underlying cause. Pendelluft may occur. Mediastinal shift may occur
in phase with respiration, causing cardiovascular
Pneumatics, see Fluidics collapse. Gas exchange may improve with IPPV,
which increases expansion of the collapsed lung
Pneumocystis pneumonia (PCP). Chest infection (but tension pneumothorax may develop if gas is
caused by the fungus Pneumocystis jiroveci (formerly P. forced into the pleural cavity and is unable to
carinii), particularly common in patients with immuno- escape).
deficiency associated with HIV infection, chemotherapy - closed: no continuing communication with the gas
or organ transplantation. The organism produces an source; lung collapse is proportional to the volume
acute interstitial pneumonitis that is rapidly followed by of gas introduced into the pleural cavity. Gas
pulmonary fibrosis and impaired pulmonary diffusion exchange is unaltered by IPPV, if there is no risk
and decreased lung compliance. Features include hypox- of further gas leakage.
aemia, dyspnoea and dry cough. Often, patients have an tension: gas flow into the pleural cavity is unidirec-
associated picture of systemic sepsis. The CXR typically tional and a valve mechanism prevents its escape.
shows subtle diffuse interstitial shadowing, but may be The pressure within the pleural cavity increases,
normal or occasionally grossly abnormal. The diagnosis with worsening pulmonary collapse, hypoxaemia,
 Poliomyelitis 469

hypercapnia, mediastinal shift and obstruction to Poiseuilles equation, see HagenPoiseuille equation
venous return. Tension is increased by IPPV.
May occur by three mechanisms: Poisoning and overdoses. May be deliberate, or may
intrapulmonary rupture: retrograde perivascular follow accidental exposure or ingestion. Substances
dissection of gas towards the lung hilum, which may responsible include those found in the home, industrial
result in mediastinal emphysema. May follow use of or agricultural chemicals, plant or animal toxins, and
high inflation pressures during IPPV, or severe therapeutic drugs.
cough or Valsalva manoeuvre. May also occur spon- Principles of management:
taneously if the alveolar septum is weakened by removal of the patient from the source of the toxic
infection or chronic lung disease. substance, e.g. from scene of a fire, chemical spillage.
injury to the visceral pleura: air escapes through the Medical staff should be adequately protected, since
hole into the pleural cavity; the lung collapses and absorption through skin and lungs may occur.
the hole may seal or act as a valve. Causes include CPR and standard management of the unconscious
spontaneous rupture of an emphysematous bulla, patient, including monitoring.
fractured ribs, regional anaesthetic techniques or blood analysis for drug, glucose and electrolyte
central venous cannulation, tracheostomy and levels, specific organ function tests, etc.
lung biopsy. prevention of further absorption of ingested
injury to the parietal pleura: gas enters from the substances, e.g. using activated charcoal (gastric
atmosphere (e.g. open chest wound, during central lavage and emetic drugs are no longer routinely
venous cannulation) or from adjoining structures: recommended). Whole bowel irrigation may be
- peritoneal cavity: gas passes upwards through the useful after poisoning with extended-release drug
retroperitoneal tissue and ruptures through the preparations.
mediastinal parietal pleura, or passes through specific antidotes and treatments, e.g. naloxone, flu-
defects in the diaphragm. mazenil, chelating agents, digoxin antibody frag-
- mediastinum: gas ruptures through the pleura as ments, thiosulphate in cyanide poisoning.
above; it may arise following oesophageal perfo- lipid emulsion has been used to treat overdose with
ration and procedures such as tracheostomy and a variety of lipid-soluble drugs.
thyroidectomy. increasing elimination of ingested substances, e.g.
Features: forced diuresis, haemoperfusion, dialysis, activated
range from mild dyspnoea and pleuritic chest pain charcoal.
to respiratory distress. If the pneumothorax is very Common problems include respiratory depression,
large or under tension, severe hypoxaemia and car- hypotension, arrhythmias, coma, convulsions and distur-
diovascular collapse may occur. bances of temperature regulation. Pulmonary oedema,
clinical signs may be absent in small pneumothora- ARDS, hepatic failure and renal failure may also occur.
ces (< 15% of the hemithorax), but there may be: Regional or national poisons units provide informa-
subcutaneous emphysema; ispilateral reduction of tion and advice.
chest wall movement and breath sounds; and Brooks DE, Levine M, OConnor AD, et al (2011).
increased resonance to percussion. There may be Chest; 140: 107285
audible wheezing, or a crunch caused by air in the Levine M, Brooks DE, Truitt CA, et al (2011). Chest; 140:
mediastinum (Hammans sign). Inflation pressures 795806
may rise during anaesthesia with IPPV. See also, Alcohol poisoning; Barbiturate poisoning;
erect CXR in expiration may reveal absent lung Carbon monoxide poisoning; Chemical weapons; Opioid
markings beyond the edge of the collapsed lung, poisoning; Organophosphorus poisoning; Paracetamol
with the characteristic lung edge usually visible. poisoning; Salicylate poisoning; Smoke inhalation; Tricy-
Diagnosis may be difficult from a supine film. clic antidepressant drug poisoning
Pleural gas under tension causes marked lung col-
lapse, hyperexpansion of the ipsilateral lung and Polarographic oxygen analysis, see Oxygen
mediastinal shift. measurement
Treatment depends on the size of the pneumothorax;
small ones often resolve spontaneously. If symptomatic, Poliomyelitis. Disease caused by one of three small
or if IPPV is planned, chest drainage should be per- RNA enteroviruses transmitted by the respiratory or
formed. A tension pneumothorax may be life-threatening faeco-oral routes. Now uncommon in developed coun-
and requires urgent relief, e.g. with a needle or iv cannula. tries following successful immunisation programmes.
N2O, being more soluble than atmospheric nitrogen, Following 714 days incubation period, an acute febrile
may rapidly expand a pneumothorax (by 100% in 10min illness occurs, with upper respiratory or GIT symptoms
at inspired concentration of 70%); it should therefore lasting a few days. Over 90% of cases of infection are
not be used unless a chest drain has been placed. subclinical. Pyrexia may recur with features of acute
[Louis Hamman (18771946), US physician] viral meningitis. Asymmetrical lower motor neurone
Haynes D, Baumann MH (2010). Semin Respir Crit Care weakness develops in 1% of cases of infection, caused
Med; 31: 76980 by destruction of the anterior horn cells of the spinal
See also, Chest trauma; Flail chest cord and cranial nerve nuclei. Ventilatory support is
required during the acute illness in approximately 30%
POCD, see Postoperative cognitive dysfunction of cases, because of intercostal or diaphragmatic involve-
ment. Bulbar involvement may impair swallowing, cough
Poise. Unit of viscosity in the cgs system of units. 1 P = reflexes and vocal cord function. Rarely, medullary
1 dyne s/cm2. involvement may cause cardiovascular instability or
[Jean Poiseuille (17971869), French physiologist] sleep apnoea.
470 Pollution

Most patients have residual disability, but improve- over 50 years. Features are caused mainly by
ment may continue for up to 2 years after the acute hypervolaemia and hyperviscosity (headaches,
episode. Progressive weakness may occur 2030 years plethora, pruritus, dyspnoea, visual disturbances,
later (postpolio syndrome). 1030% of those requiring reduced cardiac output, thrombotic and haemor-
ventilatory support acutely require long-term support. rhagic episodes) and a high metabolic rate (night
Lambert DA, Giannouli E, Schmidt BJ (2005). Anesthe- sweats, weight loss). Hepatosplenomegaly may
siology; 103: 63844 occur. White cell and platelet counts may also be
increased; platelet function may be abnormal.
Pollution. Traditionally, most attention has been paid to The main perioperative risks are haemorrhage
the effects of inhalational anaesthetic agents on the well- (caused by abnormal platelets) and thrombosis.
being of nearby staff, e.g. in the operating theatre. More Elective surgery should be delayed to allow treat-
recently the contribution of anaesthetic agents to atmo- ment; emergency surgery should proceed only
spheric ozone depletion and global warming has been a after venesection and volume replacement. Treat-
concern. Both N2O and volatile agents are degraded in ment is directed at keeping the haematocrit below
the atmosphere by ultraviolet light to form radicals and 0.5, usually with repeated venesection, radioactive
halogen atoms, respectively; these damage the ozone phosphorus or myelosuppressive drugs (busul-
layer. Both N2O and volatile agents also contribute to the fan). PRV progresses to myelosclerosis in 2030%
greenhouse effect. Anaesthetic use has been estimated to of cases.
contribute ~1% of atmospheric N2O. Recent interna- - secondary to raised erythropoietin levels, e.g. in
tional agreements on reduction of atmospheric pollutants response to chronic hypoxaemia (e.g. pulmonary
have included agents such as these, leading to renewed disease, cyanotic heart disease, high altitude) or
interest in alternative anaesthetic agents such as xenon. inappropriate secretion (e.g. renal carcinoma,
Other concerns include the effect of plasticisers (e.g. hepatocellular carcinoma, haemangioblastoma).
phthalates) in polyvinyl chloride (PVC) tubing and Risks are related to increased blood viscosity and
other equipment; they have been implicated in causing thrombosis as above.
multiple health issues, particularly involving the endo- Levine RL, Gilliland DG (2008). Blood; 112: 21908
crine system.
Shine KP (2010). Br J Anaesth; 105: 7313 Polymyositis. Group of idiopathic autoimmune inflam-
See also, COSHH regulations; Environmental safety of matory diseases, including dermatomyositis, affecting
anaesthetists; Scavenging muscle and skin. May involve multiple systems. Usually
presents with myalgia, muscle tenderness and weakness
Polyarteritis nodosa. Connective tissue disease charac- (mainly proximal). Bulbar weakness may lead to dys-
terised by a necrotising arteritis affecting small and phagia, dysphonia and regurgitation. Intercostal and dia-
medium-sized arteries causing aneurysm formation, phragmatic weakness may result in respiratory failure,
haemorrhage and infarction in major organs. Incidence exacerbated by interstitial pneumonitis that is also a
peaks at 4050 years, with men affected twice as com- feature of the disease. Cardiac manifestations include
monly as women. arrhythmias, conduction defects, myocarditis and cardio-
Features: myopathy. In dermatomyositis, there is a characteristic
malaise, fever, weight loss, myalgia. erythematous rash of the face and neck. Malignancy is
arthralgia, rash, peripheral neuropathy. Myasthenic common, especially in older men.
syndrome may occur rarely. Creatine kinase is raised; muscle biopsy is confirma-
GIT involvement including haemorrhage, pancre- tory. Treatment includes corticosteroids and other immu-
atitis, intestinal and gallbladder infarction. nosuppressive drugs.
renal impairment (may be part of a triad of haema- An abnormal sensitivity to neuromuscular blocking
turia, haemoptysis and asthma); includes nephritic drugs has been suggested but is unproven.
syndrome or nephrotic syndrome. Mammen AL (2010). Ann NY Acad Sci; 1184: 13453
CVS involvement: hypertension, ischaemic heart
disease, cardiac failure, pericarditis. Polymyxins. Group of antibacterial drugs that include
CNS involvement: cerebral ischaemia, blindness, polymyxin E (colistin) which is active against Gram-
subarachnoid haemorrhage, encephalopathy, negative organisms, including pseudomonas and poly-
seizures. myxin B, which is used in otitis externa. May enhance
Anaesthetic considerations include any pre-existing the action of non-depolarising neuromuscular blocking
organ damage as described above, plus possible drug drugs via their postsynaptic blocking action at the neu-
therapy that may include corticosteroids and immu- romuscular junction.
nosuppressive drugs.
See also, Vasculitides Polyneuropathy, acute post-infective, see Guillain
Barr syndrome
Polycythaemia. General term for a haemoglobin
concentration above 1617g/dl, red cell count above Polyneuropathy of critical illness, see Critical illness
5.66.4 1012/l, or haematocrit above 0.470.54 (all polyneuropathy
values femalemale respectively).
May be: Polystyrene sulphonate resins. Ion exchange resins
relative (reduced plasma volume, e.g. burns, used to treat mild or moderate hyperkalaemia. Available
dehydration). as calcium (calcium resonium) or sodium (resonium
absolute (increased red cell volume): A) preparations. Given orally, they remain in the
- primary (polycythaemia rubra vera, PRV): myelo- GIT without renal or hepatic excretion. Decrease in
proliferative disorder, occurring mainly in men plasma potassium occurs 224h after administration.
 Positioning of the patient 471

Electrolytes must be monitored closely during therapy. about drugs is obtained from case reports, animal studies
Contraindicated in hyperparathyroidism, multiple and analysis of drug effects on cell cultures.
myeloma, sarcoidosis, metastatic bone disease (calcium Effects of drugs:
resins) and cardiac failure (sodium resins). definite precipitants: include barbiturates, pheny
Dosage: toin and sulphonamides.
15g orally tds/qds; 30g rectally retained for 9h. implicated in laboratory or animal studies but not
0.51.0g/kg/day in children. in humans: etomidate, lidocaine, chlordiazepoxide.
Side effects: cardiac failure, headaches, encephalopa- considered safe to use: opioid analgesic drugs, N2O,
thy, metabolic alkalosis, fluid retention, nausea, vomit- diazepam, suxamethonium, tubocurarine, galla-
ing, constipation, colonic necrosis, GIT obstruction. mine, atropine, neostigmine, bupivacaine, prilo-
caine, procaine, propranolol, chlorphenamine,
Popliteal fossa. Diamond-shaped space behind the droperidol, chlorpromazine, chloral hydrate,
knee joint, bounded inferiorly by the two heads of gas- aspirin, paracetamol, insulin.
trocnemius muscle and superiorly by biceps femoris (lat- controversial: halothane, corticosteroids, ketamine,
erally) and semimembranosus/semitendinosus muscles propofol. All have been used safely despite conflict-
(medially). ing evidence.
Contents (medially to laterally): Kaupinnen R (2005). Lancet; 365: 24152
popliteal artery: continues from the femoral artery, See also, Inborn errors of metabolism
and divides into anterior and posterior tibial arter-
ies at or below the lower part of the fossa. The Poseiro effect. Decrease in arterial BP during uterine
popliteal vein lies superficially. contraction; thought to be caused by exacerbations of
tibial nerve: arises from the sciatic nerve, usually at aortocaval compression.
the upper pole of the fossa. Lies superficial to the [JJ Poseiro (described 1967), Uruguayan obstetrician]
popliteal vessels. The common peroneal nerve See also, Obstetric analgesia and anaesthesia
passes laterally around the fibular head, lateral to
the fossa. Positioning of the patient. Undertaken to:
fat pad. facilitate surgery, imaging, etc.
See also, Knee, nerve blocks encourage venous drainage (for surgery) or disten-
sion (for central venous cannulation).
Pop-off valve, see Adjustable pressure-limiting valve allow the performance of and control the extent of
regional anaesthesia.
Populations. In statistics, any group of similar objects, protect the airway (e.g. recovery position).
events or observations. Usually contains too many indi- improve oxygenation (prone ventilation).
viduals to be studied as a whole, thus samples are studied reduce ICP.
and any conclusions drawn are applied to the whole encourage drainage of sputum, e.g. postural
population. A population may be described by its: drainage.
shape, i.e. statistical distribution curve, e.g. normal, Often performed when the patient is anaesthetised;
binomial. damage to limbs, joints, pressure areas and nerves may
central tendency, e.g. mean, median, mode. occur unless care is taken. Tracheal tube, iv lines, etc.,
scatter, e.g. standard deviation, percentiles. may be displaced during movement.
Specific problems associated with certain positions:
Porphyria. Group of diseases characterised by overpro- supine: V/Q mismatch may occur, especially if
duction and excretion of porphyrins (intermediate com- closing capacity exceeds FRC. Regurgitation of
pounds produced during haemoprotein synthesis) and gastric contents may occur. The calves should be
their precursors. Caused by specific enzyme defects raised off the bed to reduce risk of DVT. In preg-
within the haem metabolic pathway. Several forms exist, nancy, aortocaval compression may occur.
divided into hepatic and erythropoietic varieties. Only prone: similar considerations to the supine position
three forms affect the conduct of anaesthesia, all of them apply. Chest wall and abdominal movement during
hepatic varieties transmitted by autosomal dominant respiration may be hindered. Supports should be
inheritance with incomplete penetrance: positioned under the iliac crests and shoulders,
acute intermittent porphyria (AIP): results in leaving the abdomen free. Venous return may be
increased amounts of urinary porphobilinogen and impeded if the abdomen is compressed. Acute
-aminolaevulinic acid (D-ALA) during attacks. hepatic failure has been reported in a small number
May present with acute abdominal pain, vomiting, of patients following prolonged surgery in the prone
acidbase disturbances, motor and sensory periph- position; intraoperative hepatic ischaemia related
eral neuropathy, autonomic dysfunction, cranial to positioning has been implicated, though not
nerve palsies, mental disturbances, convulsions and proven; nevertheless, monitoring of acidbase status
coma. Diagnosed by urinalysis. and plasma lactate concentration has been advised.
variegate porphyria: may present with similar The face and eyes should be carefully padded (see
features to AIP. Photosensitivity is common. Eye care). Particular care is required to prevent
Diagnosed by stool examination for copro- and undue extension or rotation of the neck; the fully
protoporphyrin. neutral position has been suggested, since neuro-
hereditary coproporphyria: photosensitivity may logical lesions have been reported, especially after
occur. long procedures.
Acute attacks may be precipitated by drugs, stress, infec- lateral: V /Q
 mismatch occurs (see One-lung anaes-
tion, alcohol ingestion, menstruation, pregnancy and thesia). The lower arm may be compressed and its
starvation, although not at every exposure. Information venous drainage impaired.
472 Positive end-expiratory pressure

Trendelenburg: originally described as supine with Post-dural puncture headache (PDPH). Headache
steep head-down tilt, with the knees flexed over the occurring after dural puncture, e.g. spinal anaesthesia or
broken end of the table. Diaphragmatic movement diagnostic lumbar puncture. First described by Bier in
is limited by the weight of the abdominal viscera, 1899. May rarely develop after epidural anaesthesia
reducing FRC and increasing atelectasis. Risk of without an obvious dural tap. More common in obstet-
regurgitation is increased. Venous engorgement of rics and in young patients. Reported incidence varies but
the head and neck may be accompanied by raised is < 1% with pencil-point 2529 G needles in non-
ICP and intraocular pressure. Brachial plexus injury pregnant patients, and up to 75% with 16 G epidural
may occur if shoulder supports are used. needles in obstetric analgesia and anaesthesia.
reversed Trendelenburg: hypotension may occur if Thought to be due to CSF leaking through the dural
the head-up tilt is achieved rapidly. hole, with caudal shift of the brain and stretching of
lithotomy position: similar considerations to the intracranial nerves, dura and blood vessels in the upright
Trendelenburg position. Injury to the lower back, position. The most likely cause is thought to be cerebral
hips and knees may occur. Common peroneal or venous dilation. The incidence is increased by using
saphenous nerves may be compressed against the large-gauge needles, especially if the longitudinal dural
lithotomy poles. Sciatic nerve injury has been fibres are cut transversely by the needle bevel instead of
reported after prolonged procedures. DVT may being split longitudinally, e.g. by non-cutting pencil-point
follow calf compression against the poles. spinal needles.
sitting: difficult to position the unconscious patient. Headaches usually occur within 13 days of dural
Hypotension and air embolus may occur (see Dental puncture, normally lasting for 12 weeks but occasion-
surgery; Neurosurgery). ally for months. They are classically severe, frontal or
Neurological lesions or those relating to tissue ischaemia occipital, and exacerbated by sudden movement, getting
(e.g. bald areas on the scalp, compartment syndrome) up from the supine position, and coughing and straining.
are thought to be more likely if there is prolonged hypo- Neck stiffness, visual disturbance and altered hearing
tension associated with long procedures. may occur. Diagnosis is from the history and on clinical
[Friedrich Trendelenburg (18441924), German surgeon] grounds. Typically, manual pressure over the right hypo-
See also, Nerve injury during anaesthesia gastrium causes lessening of the headache, possibly via
epidural venous congestion secondary to hepatic com-
Positive end-expiratory pressure (PEEP). Adjunct to pression. MRI and CT scanning have been used to
IPPV, introduced in 1967. Produced by maintaining a demonstrate CSF leaks. Rarely, cranial nerve palsies,
positive airway pressure during expiration: usually 520 convulsions and subdural or intracranial haemorrhage
cmH2O, although higher levels have been used (super- have been reported.
PEEP). Minimises airway and alveolar collapse and Treatment:
increases compliance, by increasing FRC. Thus improves avoidance of dehydration.
oxygenation and reduces pulmonary shunt. High levels simple analgesics, e.g. paracetamol, NSAIDs.
may increase dead space and exacerbate the adverse specific therapy: caffeine 150200mg orally tds/qds
effects of IPPV related to intrathoracic pressure; baro- has been shown to reduce the severity of headache.
trauma and reduced cardiac output are more likely. Sumatriptan 6mg sc od; caffeine/ergotamine
Urine output is reduced, and vasopressin secretion and mixture 100mg/1mg; ACTH 1.5U/kg iv in 12 l
ICP increased. saline over 1h or its synthetic analogue Synacthen
Used to reduce O2 requirement and improve oxygen- 1mg im have also been used, although the evidence
ation in respiratory failure, except where its adverse is relatively weak and the mechanisms of action are
effects are especially dangerous, e.g. asthma. The follow- unclear.
ing terms have been used to describe the adjustment epidural administration of fluids, e.g. saline, dextran,
of PEEP: blood: thought to displace CSF cranially and pos-
best PEEP: produces the least shunting without sig- sibly reduce further leakage across the dura. Epidu-
nificant reduction of cardiac output. ral blood patch is effective, but is generally reserved
optimum PEEP: produces maximal O2 delivery with for when headache is persistent.
the lowest dead space/tidal volume ratio. Prophylactic bed rest after dural puncture is no longer
appropriate PEEP: that with the least dead space. considered helpful.
Auto-PEEP (intrinsic PEEP) is the difference between Bezov D, Lipton RB, Ashina S (2010). Headache; 50:
alveolar pressure and airway pressure at end-expiration, 114452, 148298
and exists when expiration continues right up to inspira-
tion (i.e. no expiratory pause). It may occur in airway Posterior tibial artery. Arises (with the anterior artery)
obstruction, asthma, COPD, ARDS, and in forced from the popliteal artery at the lower border of the
expiration. popliteal fossa. Runs distally on the surface of the pos-
terior tibial muscle deep to soleus; lower down it becomes
Positron emission tomography (PET). Technique for superficial and lies medial to tendo calcaneus. Divides
imaging the distribution of inhaled or injected positron- into lateral and medial plantar arteries. The artery can
emitting radioisotopes, e.g. 15O, 13N, 11C and 18F. Tomo- be palpated between the medial malleolus and the
graphic techniques similar to those used for CT scanning prominence of the heel and may be used for arterial
are used. Usually restricted to brain imaging, providing cannulation.
information about cerebral blood flow, O2 and glucose
metabolism. Postherpetic neuralgia. Persistent pain in the distribu-
tion of one or more peripheral nerves following shingles
POSSUM, see Physiological and operative severity score (herpes zoster). Usually defined as pain lasting for over
for the enumeration of mortality and morbidity 1 month. Shingles is caused by reactivation of dormant
 Postoperative cognitive dysfunction 473

varicella-zoster virus seeded during an earlier episode of - rectal: drug absorption may be variable; the tech-
primary chickenpox. It usually affects adults and occurs nique is less common in the UK.
spontaneously, although predisposing factors include NSAIDs: popular as a method of reducing opioid
age > 55 years and immunodeficiency (especially associ- requirements, particularly after day-case surgery,
ated with HIV infection and leukaemia). The virus lies dental surgery and orthopaedic surgery. May be
dormant in the dorsal root ganglia but may multiply and given parenterally, orally or rectally. They may
invade the corresponding sensory nerves. The T5 and T6 cause GIT upset and impair renal and platelet func-
dermatomes are most commonly affected. Pain usually tion. Increased perioperative bleeding has been
precedes the appearance on an inflamed base of cutane- reported, but this is rarely clinically significant.
ous vesicles, that last 24 weeks. In 10% of cases, scarring other drugs: ketamine reduces opioid requirements
and pain persist; the latter may be severe and intractable, and may be particularly useful in postoperative
triggered by contact, draughts and stress. neuropathic pain (e.g. after limb amputation).
Treatment may be disappointing, but includes tricy- Clonidine and gabapentin may also be useful
clic antidepressant drugs, anticonvulsant drugs, local adjuncts, the former particularly if hypertension is
counter-irritants, TENS, acupuncture, local anaesthetic a problem.
agent creams, repeated epidural anaesthesia, peripheral local anaesthetic agents: provide excellent analgesia
or sympathetic nerve block and the dorsal root entry but with the risk of motor blockade and toxicity of
zone procedure. Modification with aciclovir or cortico- local anaesthetics, and variable duration of action
steroids is unproven. In most cases the pain is (depending on the technique and drug chosen).
self-limiting. Duration may be prolonged by the use of repeated
injections or infusions via catheters. Methods:
Postoperative analgesia. Increasingly managed by - infiltration or nerve block: performed before or
acute pain teams; duties include education of medical after surgery.
and nursing staff, audit, research, and visiting postopera- - caudal analgesia, epidural anaesthesia or spinal
tive patients specifically to monitor and adjust analgesia anaesthesia: limited by hypotension and motor
regimens. paralysis. May be combined with opioids.
Analgesic requirements vary according to the type of inhalational anaesthetic agents: some postoperative
surgery, fitness of the patient, psychological factors and benefit is derived from the agents used periopera-
interindividual differences. tively. Entonox is the only agent used postopera-
Techniques available: tively, e.g. for physiotherapy or changes of dressings,
opioid analgesic drugs: and is limited by its adverse effects on the haema-
- im: painful to administer, and result in variable tological system.
plasma drug levels. The time from the patients nerve destruction (e.g. cryoanalgesia) has been used
expressing pain to the drugs administration in thoracic surgery, but has limited application
depends on the patients persistence, the level of elsewhere.
nursing staffing and the procedures for obtaining other methods less widely used include TENS,
and checking controlled drugs. Commonly used, acupuncture and hypnosis.
however, because of its convenience and low cost. See also, Analgesic drugs; Pain; Pain evaluation; Pain
- iv: more reliable; methods include: management; Pre-emptive analgesia
- incremental small boluses titrated against effect;
reduces accidental overdosage but still may
Postoperative care team. Proposed system of compre-
allow periods of inadequate analgesia.
hensive postoperative care that includes regular rounds
- continuous infusion: may be adjusted to the
and a team of specialist postoperative care nurses who
minimal effective rate with minimal side effects.
are able to support ward nursing and medical staff by
Steady-state plasma levels may be slow to
providing additional expertise and equipment. An exten-
achieve, and overdosage may still occur.
sion of the concept of acute pain teams. Aims include
- patient-controlled analgesia: less demanding on
better maintenance of vital organ function, decreased
the nursing staff, and the patients sense of
postoperative complications, reduced postoperative
being in control may be beneficial.
mortality, greater comfort and satisfaction and a shorter
- spinal opioids: although analgesia is usually
hospital stay.
extremely good, large interpatient variability
Goldhill DR (1997). Br Med J; 314: 389
exists. Side effects include urinary retention,
See also, Care of the critically ill surgical patient; Medical
nausea, pruritus and respiratory depression;
emergency team; Outreach team; Safe transport and
careful monitoring is required to detect the latter.
retrieval team
- sc: useful if iv access is limited but confers no
advantage over iv administration.
- oral: use may be restricted by inability to drink, Postoperative cognitive dysfunction (POCD). Mild
nausea and vomiting, delayed gastric emptying cognitive fogginess following anaesthesia and surgery,
and first-pass metabolism. as distinct from florid postoperative confusion. Requires
- transdermal: slow-release patches are stuck to the neurocognitive testing for diagnosis. Occurs in up to
skin; does not require cannulae or catheters, but 50% of all patients in the first postoperative week. In
adjustment of the release rate is impossible. Fen- 1015% of elderly patients it persists for longer periods,
tanyl and buprenorphine are available in trans- especially in those with pre-existing cognitive problems.
dermal preparations. Possible factors include:
- sublingual/buccal: avoids injection but suffers poor control of postoperative delirium.
the disadvantages of intermittent administration. neuronal and synaptic loss due to sedative/
Buprenorphine is administered in this way. anaesthetic agents.
474 Postoperative nausea and vomiting

deposition of neurotoxic proteins (similar to those With prophylaxis the incidence is usually under 30% in
found in Alzheimers disease) in brain cells follow- high-risk cases. The most effective approach for prevent-
ing anaesthesia. ing PONV is thought to be the use of multiple strategies
neuroinflammatory changes due to surgical trauma. and different drugs.
It has been suggested that preoperative cognitive func- Habib AS, Gan TJ (2004). Can J Anaesth; 51: 32641
tion testing may identify those patients at risk. See also, Vomiting
[Alois Alzheimer (18641915), German neurologist and
pathologist] Postpartum haemorrhage (PPH). Defined as more
Crosby G, Culley DJ (2011). Anesth Analg; 112: than 500ml blood loss associated with vaginal delivery
9991001 and greater than 1000ml loss with caesarean section,
although accurate measurement is notoriously difficult
Postoperative nausea and vomiting (PONV). Consis- at this time. A common cause of maternal morbidity and
tently rated by patients as the most feared postoperative mortality, it is associated with a number of predisposing
symptom. Apart from its unpleasantness, it may also factors, including multiple pregnancy, multiparity, pre-
increase pain, disturb dressings/surgical repairs, increase eclampsia, placenta praevia and prolonged augmented
bleeding and increase the risk of aspiration of gastric labour. Problems include not identifying women at risk
contents. May lead to electrolyte imbalance and dehy- (even though risk factors are well known), not recognis-
dration if prolonged. ing significant hypovolaemia when it occurs and a lack
In the absence of prophylaxis, PONV occurs after up of an appropriate sense of urgency when resuscitating
to 90% of surgical procedures, the following increas- the patient. The problems of DIC and dilutional coagu-
ing the risk: lopathy may rapidly be superimposed upon the underly-
patient factors: ing condition.
- young age. Caused by:
- female gender. Incidence increases during men- obstetric factors, e.g. uterine atony, retained pla-
struation and decreases after the menopause, i.e. centa, uterine/vaginal tears, uterine inversion,
is presumably hormonally mediated. instrumentation or intrauterine manipulation.
- anxiety, especially in patients who always vomit. non-obstetric factors, e.g. coagulation disorders.
Increases in circulating catecholamine levels may Typically, PPH presents with tachycardia and other fea-
be important. tures of haemorrhage, although since most cases are fit
- previous history of PONV or motion sickness. young women, cardiovascular compensation is usually
- non-smoking. very effective until severe hypovolaemia occurs,
- early postoperative mobilisation, eating and when sudden collapse may ensue. Uterine inversion
drinking. may be associated with profound hypotension and
surgical factors: bradycardia.
- gynaecological/abdominal/ENT/squint surgery. Initial management consists of basic fluid resuscita-
- laparoscopic procedures. tion. Specific treatment is aimed at the underlying cause,
- severe pain. e.g. oxytocin and carboprost for uterine atony, evacua-
anaesthetic factors: tion of the uterus for retained products, surgical repair
- use of opioid analgesic drugs, including of tears, reduction of uterine inversion. Anaesthetic
premedication. management for obstetric intervention depends on the
- use of certain anaesthetic drugs, e.g. diethyl ether, state of the circulation, whether there is an epidural
trichloroethylene, cyclopropane, etomidate, N2O catheter already in situ and the possibility of coagulopa-
(the last via a direct central effect, GIT distension thy. The risks of regional anaesthesia must be weighed
and/or expansion of middle ear cavities). against the risks of general anaesthesia in each individ-
- possibly prolonged anaesthesia and the use of ual case.
neostigmine (though these are disputed). See also, Caesarean section; Obstetric analgesia and
- physical factors, e.g. gastric insufflation, pharyn- anaesthesia
geal stimulation.
other factors: Post-tetanic count, see Neuromuscular blockade
- hypoxaemia/hypotension. monitoring
- dehydration.
Various scores have been devised for predicting the like- Post-tetanic potentiation (PTP; Post-tetanic facilita-
lihood of PONV in a particular case, based on the pres- tion). Increased response to a single pulse stimulus fol-
ence or absence of the following factors: female gender; lowing tetanic contraction. Seen during non-depolarising
history of PONV/travel sickness; non-smoker; postop- neuromuscular blockade and in myasthenia gravis;
erative opioids; prolonged procedure. thought to be caused by increased presynaptic mobilisa-
Reduced by: tion and release of acetylcholine in response to increased
avoidance of triggers where possible, e.g. anxiety, frequency of action potentials. Absent in depolarising
opioids, N2O, vigorous pharyngeal suction, and pos- neuromuscular blockade. Mechanical PTP occurring in
sibly general anaesthesia altogether. normal subjects without neuromuscular blockade is
use of specific antiemetic drugs and procedures thought to be caused by calcium ion accumulation result-
(e.g. acupuncture at the wrist), especially in ing in increased muscle strength. EMG recording does
combination. not exhibit PTP in unblocked muscle.
use of drugs, techniques and procedures associated See also, Neuromuscular blockade monitoring
with low incidence of nausea and vomiting, e.g.
propofol. Post-traumatic stress disorder. Psychological disorder
administration of iv fluids. following a severe physical or mental trauma, e.g.
 Prasugrel hydrochloride 475

accident or natural disaster; has also been reported after representation of the distribution of frequencies within
awareness during anaesthesia or after an acute critical each epoch. The frequency distribution of successive
illness, e.g. requiring ICU care. In order to make the epochs may be plotted consecutively on continuous
diagnosis the following must exist: paper as a series of peaks and troughs (compressed spec-
the stressor is considered exceptional, e.g. severe tral array) representing frequencies of high and low
trauma or accident. activity respectively. Has been used to monitor depth of
onset within 6 months of the event. anaesthesia. The technique has also been applied to
prominent memories: often distressing, intrusive, beat-to-beat variability of heart rate and BP to deter-
recurrent and causing the sufferer to relive the mine the relative influence of sympathetic and parasym-
experience. pathetic activity, e.g. perioperatively.
avoidance behaviour, e.g. refusing to undergo More recently, the technique has been combined with
anaesthesia. analysis of the relationship between different frequency
hyperarousal, e.g. irritability or anxiety. components and the degree of burst suppression to give
Management includes psychological support and coun- the bispectral index.
selling, with specific psychological treatment according See also, Anaesthesia, depth of
to the individual requirements. Drug therapy may also
be required. The advice of a psychologist or psychiatrist Poynting effect. Dissolution of gaseous O2 when
with a specific interest is recommended. bubbled through liquid N2O, with vaporisation of the
liquid to form a gaseous O2/N2O mixture.
Potassium. Principal intracellular cation, present at [John H Poynting (18521914), English physicist]
135150mmol/l. Present in the plasma at 3.55.0mmol/l. See also, Entonox
Total body content is about 3200mmol, of which 90% is
intracellular, 7.5% within bone and dense connective PPF, Plasma protein fraction, see Blood products
tissue and 2.5% in interstitial fluid, transcellular fluid
and plasma. About 90% is exchangeable. Essential for PPH, see Postpartum haemorrhage
maintenance of the cell membrane potential and genera-
tion of action potentials. PR interval. Represents atrial depolarisation. Mea-
Filtered potassium is reabsorbed mainly at the proxi- sured from the beginning of the P wave to the beginning
mal convoluted tubule of the nephron. It is secreted at of the QRS complex of the ECG, irrespective of whether
the distal tubule, in effect in exchange for sodium and the QRS complex starts with a Q wave or an R wave (see
hydrogen ions under the influence of aldosterone. Fig. 59b; Electrocardiography). Normally 1.22.0ms.
Daily requirement: about 1mmol/kg/day. Shortened in junctional arrhythmias, WolffParkinson
White syndrome and LownGanongLevine syndrome.
Prolonged in heart block and hypothermia.
Potassium channel activators. Class of antianginal
drugs that act by opening potassium channels primarily Pralidoxime mesylate/chloride. Acetylcholinesterase
in smooth muscle but also in other excitable tissues, reactivator, used with atropine to treat organophospho-
causing arterial and venous dilatation. Result in rus poisoning. Has three main actions:
improved blood flow to poststenotic areas of myocar- converts the acetylcholinesterase inhibitor to a
dium. Nicorandil was the first to be developed. harmless compound.
protects acetylcholinesterase transiently against
Potency. Ability of a drug to produce a certain effect at further inhibition.
a given dose. Influenced by the drugs absorption, distri- reactivates the inhibited acetylcholinesterase.
bution, metabolism, excretion and affinity for its recep- Does not reverse the muscarinic effects of organophos-
tor. Very potent drugs are effective in very small doses. phorus compounds, but highly active at nicotinic
See also, Doseresponse curves sites. Must be given within 2436h of poisoning to be
effective. Its effects usually occur within 1040min of
Potentiation, post-tetanic, see Post-tetanic administration.
potentiation Dosage: 30mg/kg iv over 20min, followed by iv infu-
sion of 8mg/kg/h, up to a maximum of 12g/24h. For
Power (in Physics). Rate of performing work. SI unit is children, a bolus dose of 2060mg/kg.
Side effects: drowsiness, visual disturbances, nausea,
the watt: 1W = 1J/s.
tachycardia, muscle weakness.
Power (in Statistics). The ability of statistical tests to Prasugrel hydrochloride. Thienopyridine antiplatelet
reveal a difference of a certain magnitude. Power analy- drug, used in combination with aspirin in patients with
sis is performed before a clinical trial to determine the acute coronary syndromes undergoing percutaneous
sample size required to show a certain difference, or coronary intervention. More effective than clopidogrel
retrospectively when analysing a statistically insignifi- at reducing the risk of ischaemic events, coronary stent
cant result. Increased if groups are equally sized and thrombosis and all-cause mortality, but is associated with
large, and if the difference between them is large. Power a higher incidence of fatal haemorrhage. Like clopido-
equals 1 , where = type II error; power of 8090% grel, it is an inactive prodrug, rapidly converted to an
( = 0.10.2) is usually considered acceptable. active metabolite by the CYP3A4 subtype of the cyto-
Yentis SM (1996). Anaesthesia; 51: 41314 chrome P450 enzyme system; however, unlike clopidogrel,
there is no clinically relevant effect of pharmacogenetic
Power spectral analysis. Fourier analysis of 216 second variations in enzyme expression. Cessation 7 days before
sections (epochs) of the EEG, with graphical elective surgery is recommended.
476 Prazosin hydrochloride

Dosage: 60mg orally initially followed by 10mg od Pathogenesis is unclear but is thought to involve
(5mg od if body weight < 60kg or age > 75 years). impaired trophoblastic invasion of myometrial arteries,
Side effects: bleeding, rash, rarely thrombotic throm- with reduced placental perfusion and increased pla
bocytopenic purpura. cental oxidative stress. This leads to release of inflamma-
tory mediators from the placenta, resulting in a
Prazosin hydrochloride. -Adrenergic receptor antag- generalised inflammatory response with systemic endo-
onist, highly selective for 1-adrenergic receptors. Used thelial dysfunction.
as a vasodilator drug (e.g. in hypertension and cardiac Maternal features:
failure) and as a bladder smooth muscle relaxant in cardiovascular: thought to involve increased sensi-
outflow obstruction. Rarely causes compensatory tachy- tivity to angiotensin II (sensitivity is normally
cardia, presumably because of its 1-receptor specificity. decreased in pregnancy) and catecholamines, with
97% protein-bound, with a half-life of 23h. Excreted vasoconstriction, reduced plasma volume, oedema
mainly via bile and faeces. Doxazosin and terazosin are and increased arterial BP.
related drugs. renal: renal blood flow, GFR and urine output are
Dosage: 0.5g orally bdqds, increasing to 420mg/ decreased, with proteinuria.
day in divided doses. haematological: fibrinogen, fibrin and platelet turn-
Side effects: postural hypotension (especially after over is increased. HELLP syndrome (haemolysis,
the first dose), nausea, drowsiness, headache. elevated liver enzymes, low platelets) may occur.
Platelet function may be impaired.
Predictive value. In statistics, a test to predict or exclude neurological: hyperexcitability and hyperreflexia;
a condition. May be: visual symptoms and headache may forewarn of
positive: proportion of patients with positive test impending convulsions (eclampsia).
results who have the condition. Severe PET is heralded by BP > 160/110mmHg,
negative: proportion of patients with negative test severe proteinuria or oliguria < 500ml/24h, DIC, pul-
results who do not have the condition. monary oedema, neurological symptoms and epigastric
Incorporates the sensitivity and specificity of a test as (hepatic) pain.
well as how common the condition is; for example, a test Consistently one of the most common causes of mater-
for predicting failed intubation may have a reasonably nal mortality, especially in the developing world; death
high sensitivity and specificity, but because the condition may result from aspiration of gastric contents, CVA,
(failed intubation) is rare, the positive predictive value hepatorenal failure or cardiac failure. In the UK, most
will always tend to be low. deaths are now caused by CVA (previously by ARDS).
Altman DG, Bland JM (1994). Br Med J; 309: 102 Treatment includes bed rest, control of hypertension,
See also, Errors; Sensitivity; Specificity prevention of convulsions and delivery of the fetus if
possible:
Prednisolone. Corticosteroid with predominantly glu- antihypertensive drugs used include -methyldopa,
cocorticoid activity, used in the long-term suppression of labetalol, hydralazine and calcium channel blocking
allergic, autoimmune and inflammatory disease. Four drugs orally. Severe hypertension may require iv
times as potent as hydrocortisone. treatment with:
Dosage: initially 1060mg orally od, usually reduced - labetalol 510mg increments, or 10200mg/h
after a few days but occasionally longer. Maintenance infusion.
dose: 2.515mg daily. The acetate preparation may be - hydralazine 510mg increments, or 550mg/h
given im (25100mg once or twice weekly) or into infusion.
inflamed joints (525mg). - sodium nitroprusside or GTN 0.15.0g/kg/min.
Side effects: as for corticosteroids. Concurrent administration with iv fluids is impor-
tant since the intravascular compartment is gener-
Pre-eclampsia (Pre-eclamptic toxaemia, PET; ally depleted; central venous cannulation may be
Pregnancy-induced hypertension, PIH). Defined as the required (pulmonary artery catheterisation is now
following occurring after the 20th week of pregnancy: rarely performed as evidence of its benefit is
hypertension: systolic, mean or diastolic BP > 140, lacking). Administration of fluids (by consensus,
105 or 90mmHg respectively, or an increase in sys- preferably colloids) should begin before iv vasodila-
tolic or diastolic BP greater than 30 and 15mmHg tors to avoid precipitous falls in BP and/or placental
respectively. perfusion. Oliguria is common, and it is relatively
peripheral oedema. easy for inexperienced staff to overload the circula-
proteinuria > 0.3g/l. tion in an attempt to improve urine output. As oli-
Represents a multisystem disease with many other guria usually resolves spontaneously 12 days after
manifestations. Thus there has been a move in defini- delivery, many argue that tolerating a degree of
tion away from the classic triad of PET above, towards transient renal impairment is preferable to causing
the definition of PIH with or without other features. pulmonary oedema. If the latter does occur,
PIH occurs in 1012% of pregnancies whilst PET itself furosemide iv and CPAP may avoid the need for
has an incidence of 23%. More common in first preg- intubation and IPPV.
nancies with a particular partner (typically the features anticonvulsant drugs: magnesium sulphate reduces
are less severe or present later in subsequent pregnan- the incidence of eclampsia by almost 60%, although
cies), diabetes mellitus, polyhydramnios, obesity, black the number needed to treat is large (6090; even
race and multiple pregnancy. Perinatal mortality is higher in developed countries where the disease
increased. Usually improves rapidly following delivery tends to be less aggressive) and side effects are
of the fetus, although the clinical picture may first relatively common, albeit mild. Magnesium has
worsen before recovery. also been shown to be superior to diazepam and
 Pregnancy 477

phenytoin at preventing recurrent convulsions after Side effects: dry mouth, GIT upset, CNS impair-
eclampsia. ment, weight gain; rarely neutropenia, heart block,
Anaesthetic involvement may be required for analgesia pancreatitis.
during labour, caesarean section or assistance with man-
agement of fluids and BP. Pregnancy. Usually lasts 40 weeks. Most physiological
Anaesthetic techniques: changes occur in response to the increased metabolic
epidural anaesthesia: demands of the uterus, placenta and fetus, and include
- prevents the increases in catecholamines associ- alterations in the following systems:
ated with pain, thus increasing placental blood cardiovascular:
flow. - increased intravascular volume from the first tri-
- avoids the risks of general anaesthesia. mester, returning to normal within 2 weeks of
- contraindicated if there is a coagulopathy or low delivery. Plasma expansion (50%) exceeds red
platelet count (below 50 000 109/l constitutes an cell expansion (20%), resulting in the physiologi-
absolute contraindication; 50 000100 000 109/l cal anaemia of pregnancy. Haemoglobin concen-
has been suggested as acceptable if laboratory tration is usually about 12g/dl at term. White
coagulation studies are normal, depending on cell count increases throughout and peaks after
clinical circumstances). delivery.
- careful fluid management and local anaesthetic - increased heart rate, peaking at 2836 weeks,
administration are required to avoid cardiovascu- when it may exceed normal rate by 10
lar instability following blockade. Sensitivity to 15 beats/min.
sympathomimetic drugs is increased. - increased cardiac output from 10 weeks, reaching
- avoidance of adrenaline in local anaesthetic 140% of normal at term with further increases
solutions has been suggested but this is during labour. Stroke volume increases by 30%.
controversial. Ejection systolic heart murmurs are common, and
spinal anaesthesia has previously been avoided third or fourth heart sounds may occur.
because of the fear of sudden severe hypotension, - decreased SVR as a result of the smooth muscle
but this can be prevented if there is adequate relaxation caused by progesterone. Sites of venous
volume expansion and BP control. engorgement include cutaneous and epidural
general anaesthesia: vessels, the latter affecting height of block in epi-
- risks include difficult intubation (because of dural anaesthesia.
facial and laryngeal oedema), the hypertensive - reduced MAP, being lowest at the time of maximal
response to intubation and cardiovascular insta- cardiac output.
bility. Administration of antihypertensive drugs - aortocaval compression in the supine position.
or opioid analgesic drugs (e.g. alfentanil 7 - ECG changes caused by cephalad displacement
10g/kg or fentanyl 14g/kg, especially in com of the diaphragm by the uterus include left axis
bination with magnesium) before intubation has deviation and inverted T waves in leads V2 and V3.
been used. respiratory:
- the anticonvulsant effect of thiopental may be - increased minute ventilation (by 50% in the
beneficial. first trimester), mainly caused by increased
- magnesium sulphate may result in increased sen- tidal volume (thought to be a central effect of
sitivity to neuromuscular blocking drugs. progesterone).
Monitoring, BP control and eclampsia prophylaxis (if - reduced arterial PCO2 to about 4kPa (30mmHg)
appropriate) should continue after delivery. with resulting respiratory alkalosis by the 12th
Dennis AT (2012). Anaesthesia; 67: 100920 week of pregnancy; arterial PO2 increases by
See also, Obstetric analgesia and anaesthesia about 1.3kPa (10mmHg). Arterial pH remains
normal due to renal excretion of bicarbonate.
Pre-ejection period, see Systolic time intervals - reduced FRC (both expiratory reserve volume
and residual volume decrease) from the 20th
Pre-emptive analgesia. Concept that suppression of week onwards, caused by the upward displace-
dorsal horn neuronal activity involved in pain pathways, ment of the diaphragm by the uterus.
before a painful stimulus (e.g. surgery), results in reduced - increased O2 consumption throughout pregnancy,
analgesic requirements postoperatively. Techniques of but especially in the third trimester (up to 20%).
suppression include central neuraxial blockade (e.g. - increased risk of hypoxaemia during anaesthesia
epidural/spinal anaesthesia), local anaesthetic infiltra- results from reduced FRC and increased O2
tion of tissues, use of NSAIDs and opioid analgesic drugs demand.
and antagonism of NMDA receptors (e.g. with ket- - venous engorgement of the upper airway, that
amine) in order to manipulate CNS plasticity and reduce may lead to spontaneous epistaxis or haemor-
wind-up. Supported by animal and some human studies, rhage on instrumentation.
although the clinical relevance is uncertain. gastrointestinal: gastric emptying is probably
Dahl JB, Kehlet H (2011). Curr Opin Anaesthesiol; 24: normal apart from during labour, when it may be
3318 reduced (markedly if opioids are given). Gastric
acidity is probably normal. Gastro-oesophageal
Pregabalin. Anticonvulsant drug, related to gabapentin. reflux occurs in at least 80% of women, caused by
Licensed for adjunctive therapy of partial seizures and the effects of progesterone on the lower oesopha-
also treatment of neuropathic pain. geal sphincter, and the uterus pushing the stomach
Dosage: 150mg orally/day in 23 doses, increased into a horizontal position. The time after conception
after 12 weeks to 300600mg/day. at which the GIT effects occur, and the time after
478 Pregnanolone

delivery at which they revert to normal, are - aspiration pneumonitis.

unknown. 1620 weeks has been suggested as the - adverse drug reactions.
time of onset; progesterone levels fall to non- - bronchospasm.
pregnant levels by 24h of delivery, and reflux - DVT.
usually resolves by 36h. Drugs suitable for premedication include:
coagulation: increased levels of fibrinogen and all opioid analgesic drugs, e.g. morphine.
clotting factors except XI and XIII, predisposing benzodiazepines, e.g. diazepam, temazepam,
towards thromboembolism. Platelet count falls lorazepam.
slightly. Systemic fibrinolytic activity is depressed, barbiturates, e.g. pentobarbital.
but localised activity (i.e. ability to lyse clots from butyrophenones, e.g. droperidol.
within) is maintained. Thus the level of fibrin phenothiazines, e.g. alimemazine (trimeprazine),
degradation products increases as pregnancy pro- promethazine.
gresses. However, in normal pregnancy neither anticholinergic drugs, e.g. atropine, hyoscine,
bleeding nor clotting times are increased. glycopyrronium.
renal: dilatation of the renal pelvises and ureters other antiemetic drugs, e.g. metoclopramide.
from the end of the first trimester. Renal blood flow H2 receptor antagonists, e.g. ranitidine, cimetidine.
and GFR increase by 40%. Increased renin/ antacids, e.g. sodium citrate.
angiotensin system activity increases sodium and In addition, certain drugs already taken regularly by the
water retention, with falls in serum creatinine and patient are usually continued up to and including the day
urea; glycosuria may occur. of surgery, e.g. antiarrhythmic drugs, antihypertensive
endocrine: peripheral insulin resistance due to drugs, drugs used in ischaemic heart disease and asthma,
antagonism by hormones (e.g. human placental lac- anticonvulsant drugs.
togen) may aggravate or precipitate gestational Oral premedication (e.g. with benzodiazepines) is
diabetes. often used in place of traditional im injection of opioid
hepatic: blood flow is unaltered. Serum albumin and and anticholinergic drugs.
cholinesterase levels fall, whilst hepatic enzyme Many anaesthetists do not routinely prescribe pre-
levels may increase. medication because of disadvantages such as:
Non-urgent surgery is usually delayed until the second excessive sedation.
trimester, because of the possible risk (although never difficulty with timing of drug administration.
proven) of teratogenic effects on the fetus. Conditions pain from im injections.
requiring abdominal surgery are associated with nausea and vomiting (with opioids).
increased risk of miscarriage or premature labour. dry mouth with anticholinergic drugs.
See also, Fetus, effect of anaesthetic agents on; Obstetric unnecessary drug administration.
analgesia and anaesthesia antanalgesia and restlessness.
delayed recovery.

Pregnanolone, see Eltanolone

Preoperative assessment. Main objectives include
assessment of:
Prehospital index (PHI). Scoring system used to assess
the risks to the patient of suffering perioperative
trauma victims according to their BP, pulse rate, respira-
morbidity or death.
tory status, conscious level and mechanism of injury.
whether the patients condition may be improved
Now rarely used.
before surgery, e.g. by changing medication, treating
pre-existing disease, administering fluids.
Preload. End-diastolic ventricular wall tension. Usually how otherwise to minimise the perioperative
inferred from ventricular end-diastolic pressure, itself risk, e.g. by enlisting more experienced help,
approximating to pulmonary capillary wedge pressure rescheduling the time of surgery, using special
(left) or CVP (right). Related to myocardial contractility anaesthetic or analgesic techniques, booking a bed
and cardiac output by Starlings law. on ICU or HDU.
Also refers to prophylactic administration of iv fluids Preadmission clinics (involving assessment by an anaes-
to reduce hypotension, e.g. before spinal or epidural thetist, surgeon or nurse) attempt to reduce the rate of
anaesthesia. delay and cancellation of surgical procedures caused by
inadequate preparation of patients. Protocols may
Premedication. Administration of medication before support non-anaesthetic staff in assessing patients.
anaesthesia. Assessment is directed towards the individual
Aims: patients circumstances but in general is divided
anxiolysis. into:
analgesia. history:
smooth induction of anaesthesia and reduction of - medical and surgical history, including the nature
anaesthetic agent requirements. of the proposed surgery.
reduced upper airway and salivary secretions. - previous anaesthetic history, including adverse
reduced risk of awareness. reactions, PONV and other problems.
reduced PONV. - family history of medical or anaesthetic
reduced risks of specific complications associated problems.
with anaesthesia/surgery or the patients pre- - drug history (past and present).
existing condition, e.g.: - smoking and alcohol intake.
- bradycardia, e.g. in ophthalmic surgery. - known allergies and atopy.
- hypertensive response to tracheal intubation. - weight of the patient (especially children).
 Pressure regulators 479

- presence of capped, crowned, chipped or loose patients at risk from aspiration of gastric contents. Thus
teeth. a vital part of rapid sequence induction.
- anxiety. The optimal technique is uncertain; 3min administra-
- time of last oral intake. tion is thought to be as effective as 5min administration,
- systems review, in particular: or even four vital capacity breaths. A tightly fitting face-
- CVS: hypertension, features of ischaemic heart mask (to prevent entrainment of room air) and adequate
disease, cardiac failure, arrhythmias. flow of O2 are vital. Monitoring of end-expiratory O2
- RS: recent chest infection, features of COPD or concentration may be a useful guide during preoxygen-
asthma. ation; washout of nitrogen from the lungs is indicated by
- GIT: hiatus hernia or other risk factors for aspi- an increase in expired O2 concentration towards steady
ration of gastric contents. state (near 100% in ideal conditions with no gas leaks
- CNS: epilepsy, pre-existing neurological or mixing). More effective in obese patients if they are
lesions. positioned head-up.
examination: Tanoubi I, Drolet P, Donati F (2009). Can J Anaesth; 56:
- airway, teeth, cervical spine (including assessment 44966
for possible difficult tracheal intubation or mask See also, Induction, rapid sequence
ventilation).
- CVS: for hypovolaemia, dehydration, cyanosis Pressure. Force per unit area. SI unit is the pascal: 1Pa
and anaemia; pulse, BP, JVP, cardiac impulse, = 1N/m2.
heart sounds, lung bases, periphery (for oedema).
- RS: for clubbing and cyanosis, position of the Pressure generators, see Ventilators
trachea, chest expansion, air entry, respiratory
sounds.
- CNS: cranial nerves, spinal cord and peripheral Pressure measurement. May be:
direct:
nerves, including dermatomes and myotomes.
- suitable veins for cannulation. - liquid manometers that measure:
- suitability for regional techniques where intended. - absolute pressure, e.g. mercury barometer.
preoperative investigations.
- pressure relative to atmospheric pressure
Scoring systems may be used to classify patients accord- (gauge pressure), e.g. U tube. The sensitivity
ing to preoperative status, e.g. ASA physical status, may be increased by using liquid of low density,
cardiac risk index, New York Heart Association classifi- inclining the manometer tube or using a differ-
cation, Glasgow coma scale, subarachnoid haemorrhage ent non-miscible liquid in each of the limbs of
and hepatic failure scoring systems. the U tube (differential liquid manometer).
Cardiopulmonary exercise testing is increasingly used - aneroid gauge (one in which there is no liquid).
to predict outcome in high-risk surgical cases. The need In one form a sealed metal bellows changes size
for blood compatibility testing and premedication is also with changes in external or applied pressure,
assessed. moving a pointer on a scale (e.g. aneroid barom-
The assessment period is also an opportunity to eter). In the Bourdon gauge used in anaesthesia,
explain the forthcoming anaesthesia and confirm the a coiled tube of oval cross-section uncoils as it
patients consent. becomes circular on cross-section, due to the high
Garca-Miguel FJ, Serrano-Aguilar PG, Lpez-Bastida J pressure of the gas inside it, and this moves the
(2003). Lancet; 362: 174957 pointer.
See also, individual diseases and drugs; Emergency - pressure transducers.
indirect, e.g. in arterial BP measurement.
surgery
[Eugene Bourdon (18081884), French engineer]
Preoperative fasting, see Gastric emptying
Pressure-regulated volume control ventilation. Ven-
tilatory mode combining the benefits of pressure-
Preoperative optimisation. Technique of preopera- controlled IPPV with a decelerating inspiratory flow
tively improving physiological variables with iv fluids, pattern and a guaranteed tidal volume. The ventilator
inotropic and vasodilator drugs to produce supranormal automatically monitors the lungs properties and modi-
levels of oxygen delivery (goal-directed therapy) in fies the inspiratory pressure level to deliver a predeter-
patients undergoing major surgery. Has been claimed to mined volume. Maximum inspiratory pressure permitted
reduce morbidity and mortality in certain groups of is just below the preset upper pressure limit and, if the
patients, e.g. those undergoing major vascular surgery. tidal volume cannot be delivered with this pressure, the
Since it requires preoperative admission to the ICU and ventilator alarms, indicating that the breath has been
invasive monitoring, the process has huge implications pressure-limited. Useful mode where lung/chest compli-
in terms of costs and utilisation of ICU beds. ance alters during inspiration, e.g. atelectasis, broncho-
Tote SP, Grounds RM (2006). Br J Anaesth; 97: 411 spasm. Achieves a set tidal/minute volume with the
lowest possible inspiratory pressure. The maximum pres-
Preoxygenation. Administration of 100% O2 before sure change between two breaths is preset by the ventila-
induction of anaesthesia. Increases the O2 reserve in the tor (approximately 3 cmH2O).
lungs (by replacing N2 in the FRC) and thus the time to
hypoxaemia during subsequent apnoea, e.g. during tra- Pressure regulators. Formerly called reducing
cheal intubation. Also increases arterial PO2, although valves, devices for reducing the high pressures delivered
O2 content and saturation may not increase by much. by cylinders to anaesthetic machines, and maintaining
Particularly useful when difficulties are anticipated, or in the reduced pressure at a constant level that is easier to
480 Pressure sores

Pressure support, see Inspiratory pressure support

(a)
Priestley, Joseph (17331804). English scientist, best
known for his work on various gases. A major proponent
of the phlogiston theory, he isolated ammonia (as alka-
Main spring line air), sulphur dioxide (vitriolic acid air), O2
(dephlogisticated air), N2O (dephlogisticated nitrous
Diaphragm Reduced air), nitrogen dioxide (nitrous acid air) and methane.
pressure Also investigated electrical conduction. Emigrated to
p the USA in 1794.

Cylinder Prilocaine hydrochloride. Amide local anaesthetic

pressure agent, introduced in 1959. Slower in onset than lidocaine,
p but lasts about 1.5 times as long and less toxic. pKa is 7.9.
Sealing spring 55% protein-bound. Undergoes hepatic and renal
metabolism. Maximal safe dose: 5mg/kg alone, 8mg/kg
with adrenaline. Used as 0.51.0% solutions for infiltra-
(b) tion, 12% for nerve blocks and 0.5% for IVRA. Also
available as a 4% plain or 3% solution with felypressin
for dental infiltration, and in EMLA cream. May cause
methaemoglobinaemia in doses above about 600mg in
Main spring adults, due to its metabolite ortho-toluidine.
A preservative-free hyperbaric 2% solution (with 6%
Diaphragm glucose) for spinal anaesthesia was introduced in the UK
Reduced in 2011.
pressure
p
Priming principle. Shortening of the time of onset of
non-depolarising neuromuscular blockade by adminis-
Cylinder tration of a non-depolarising neuromuscular blocking
pressure drug in divided aliquots. The priming dose (1520% of
p Sealing spring the usual intubating dose) is followed by the remainder
of the intubating dose 48min later, depending on the
drug used.
Suggested explanatory theories:
Fig. 129 Diagram of pressure regulators: (a) direct; (b) indirect the priming dose occupies a proportion of post
synaptic receptors at the neuromuscular junction;
the main dose can thus occupy more rapidly the
use. Also reduce the requirement for high-pressure critical mass of receptors for neuromuscular
tubing. blockade.
May be: the priming dose occupies presynaptic receptors,
direct (Fig. 129a): cylinder pressure P tends to open reducing mobilisation and release of acetylcholine;
the valve. the main dose thus acts faster.
indirect (Fig. 129b): cylinder pressure P tends to Initially thought to answer the need for rapid tracheal
close the valve. intubation without using suxamethonium. However, the
The diaphragm moves according to p and the tension in priming dose itself may cause unpleasant symptoms (e.g.
the springs. As p falls, the diaphragm bulges into the regu- diplopia and weakness) and serious complications, e.g.
lator, allowing more gas flow into the upper half and thus hypoventilation and aspiration of gastric contents.
maintaining p. If p increases, the diaphragm is pushed Jones RM (1989). Br J Anaesth; 63: 13
upwards, decreasing gas flow and again maintaining p.
Thus pressure is maintained despite changes in demand. PRISM, see Paediatric risk of mortality score
If cylinder pressure P falls, p is likewise maintained.
The regulators are specific to each gas, and should be Proarrhythmias. Arrhythmias caused or exacerbated
labelled accordingly. Pressure relief valves are incorpo- by antiarrhythmic drugs. May occur even with standard
rated in case of excessive pressures. Pressure gauges may dosage and normally therapeutic plasma drug levels.
also be incorporated. Common examples include VT and torsade de pointes.
Two-stage regulators are often used, to reduce wear
and tear on the diaphragm and reduce pressure fluctua- Probability (P). In statistics, the likelihood that the
tions, especially if high gas flows are required. The output observed result is a chance occurrence. Analogous to,
of one stage is the input of the second. Demand valves but distinct from, the chance of a type I error. Statistical
may be based on this principle. significance is usually denoted by a P value < 0.05, indi-
Slave regulators are those whose output depends on cating that the observed result might be expected to
the output of another regulator. For example, the output occur by chance alone 5 times in 100 occasions.
of an O2 regulator may be applied above the diaphragm
of a N2O regulator, keeping the latters valve open. If the Probability limits, see Confidence intervals
O2 pressure fails, the N2O valve closes.
Procainamide hydrochloride. Class Ia antiarrhythmic
Pressure sores, see Decubitus ulcers drug, chemically related to procaine. Effective against
 Prone ventilation 481

ventricular and supraventricular arrhythmias. Has 85% Prokinetic drugs. Group of drugs that increase GIT
oral bioavailablity and 15% protein-bound. Under- activity. Include metoclopramide and domperidone,
goes hepatic metabolism (largely via acetylation to their prokinetic actions mediated via enhancement of
N-acetylprocainamide) and renal excretion, although GIT cholinergic activity (although dopamine antago-
4050% is excreted unchanged. Rarely used in the UK nism may contribute). Used in oesophageal reflux,
and available only via special order. gastric stasis and non-ulcer dyspepsia. Erythromycin has
Dosage: a powerful prokinetic effect via GIT motilin receptors
up to 50mg/kg/day orally in 48 doses. and has been used in ileus. General parasympathomi-
20mg/min slowly iv up to 17mg/kg, with ECG metic drugs also increase GIT motility but are rarely
monitoring for widened QRS complex or PR used for this purpose.
interval prolongation. 26mg/min may follow.
Side effects: hypotension with iv usage, GIT upset, Prolonged QT syndromes. Conditions in which the
rash, agranulocytosis, SLE-like syndrome (especially QT interval of the ECG exceeds 0.44 s.
in slow acetylators). May be:
congenital: due to mutation of genes coding for
Procaine hydrochloride. Ester local anaesthetic agent, cardiac sodium or potassium ion channels. The
introduced in 1904, now seldom used. The first synthetic autosomal recessive form is often associated with
local anaesthetic. Less lipid-soluble than lidocaine, with sensorineural deafness. Syncope may be provoked
slower onset of less intense anaesthesia, and shorter by physical exercise and stress.
duration of action. pKa is 8.9. 6% protein-bound. Poorly acquired:
absorbed from mucous membranes; thus not useful as - myocardial disease, e.g. MI, rheumatic fever,
a topical anaesthetic. Used in 0.251.0% solutions for third-degree heart block, cardiomyopathy.
infiltration anaesthesia, and 12% for nerve blocks, - electrolyte disturbance, e.g. hypocalcaemia,
usually with adrenaline 1:200 000. Maximal safe dose: hypokalaemia, hypomagnesaemia.
12mg/kg. - drugs, e.g. class Ia, Ic and III antiarrhythmic drugs,
phenothiazines, tricyclic antidepressant drugs,
Procalcitonin. Propeptide of calcitonin, produced by selective serotonin reuptake inhibitors and some
the C cells of the thyroid gland but not normally released antibacterial agents, e.g. erythromycin.
into the circulation (except in low concentrations) in - severe head injury.
health. Systemic procalcitonin levels rise significantly Both forms are associated with the development of
during severe infection or inflammation, hence interest ventricular arrhythmias, including torsade de pointes
in its use as a marker of infection and antibiotic and VT, causing recurrent syncope or sudden death.
treatment. This has been associated with anaesthesia. The risk may
Schuetz P, Albrich W, Mueller B (2011). BMC Med; be greater if there is also increased QTc dispersion.
9: 107 Avoidance of increased sympathetic tone and use of
-adrenergic receptor antagonists is generally recom-
mended; phenytoin and verapamil have been used to
Prochlorperazine maleate/mesylate. Piperazine phe- treat acute arrhythmias. Long-term treatment is with
nothiazine with antiemetic, -adrenergic agonist and -blockers or cardiac pacing.
weak sedative properties. Used mainly as an antipsy- Staikou C, Chondrogiannis K, Mani A (2012). Br J
chotic drug and antiemetic drug. Active within 1020min Anaesth; 108: 73044
of im administration and 3040min of oral administra-
tion. Action lasts 34h. Promethazine hydrochloride/theoclate. Phenothi-
Dosage:
azine and antihistamine drug, with sedative, anticholin-
12.5mg orally bd increased to up 100mg daily if
ergic and antiemetic properties. Used for antiemesis,
required, or 12.525mg im bd/tds. Not licensed for allergic reactions, sedation and premedication, especially
iv use in the UK, although it has been safely given in children. Also used topically to relieve pruritus. One
by that route. component of the lytic cocktail. Well absorbed orally but
Side effects: as for phenothiazines. Extrapyramidal
undergoes extensive first-pass metabolism. Excreted
reactions are more likely than following chlorproma- renally following hepatic metabolism.
zine, especially in children. Dosage:
1020mg orally bd/tds; 0.51.0mg/kg for paediatric
Procyclidine hydrochloride. Anticholinergic drug, used premedication.
in the treatment of Parkinsons disease and drug-induced 2550mg im or by slow iv injection.
extrapyramidal symptoms, e.g. acute dystonic reaction. Side effects are those of phenothiazines and anticho-
Acts by reducing the effect of acetylcholine in the basal linergic drugs.
ganglia.
Dosage: Prone ventilation. Technique in which patients are
2.510mg orally tds. turned prone whilst receiving IPPV, used in ARDS.
510mg im, repeated after 20min up to 20mg/day. Improves oxygenation in up to 80% of patients; although
5mg iv repeated as necessary; relief is usual after a initial studies failed to show survival benefits, recent
single dose and within 5min but may take 30min. meta-analysis suggests improved survival in those with
Side effects: dry mouth, GIT disturbance, urinary severe, but not moderate, hypoxaemia.
retention, dizziness, blurred vision. Proposed mechanisms for improved oxygenation
include increased FRC (via redistribution of secretions,
Prodrug. Inactive substance metabolised to active drug interstitial oedema and atelectasis away from the poste-
within the body, e.g. clopidogrel, diamorphine. rior areas), changes in regional diaphragmatic excursion
482 Propafenone hydrochloride

and redistribution of perfusion away from more oede- Effects:

matous lung regions. Patients may be turned regularly, induction:
e.g. for up to 8h every 24h. Disadvantages during - smooth and rapid, with only occasional move-
turning include accidental displacement of tubes and ments. It has been suggested that loss of response
catheters/cannulae, injury to eyes/face/limbs, stimulation to verbal command is a better indication of ade-
of coughing and cardiovascular instability; once turned, quate dosage than loss of eyelash reflex.
the main problems are inaccessibility and care of pres- - pain on injection is common; it may be reduced
sure areas. These problems may be reduced by using by prior administration of opioid analgesic drugs,
rotational therapy instead. injecting into a large vein, and prior injection of,
Raoof S, Goulet K, Esan A, Hess DR, Sessler CN (2010). or mixing with, lidocaine.
Chest; 137: 143748 CVS/RS:
- hypotension is common, although whether caused
by direct myocardial depression, reduced SVR, or
Propafenone hydrochloride. Class Ic antiarrhythmic
both is controversial. Normo- or bradycardia is
drug, affecting atria, conducting system and ventricles.
common; resetting of the baroreceptor reflex
Has slight -adrenergic antagonist properties. Used for
has been suggested. Reduces the hypertensive
preventing and treating SVT and VT. Undergoes hepatic
response to tracheal intubation.
metabolism and renal excretion.
Dosage: 150300mg orally tds.
- respiratory depression is marked.
Side effects are usually mild and include dizziness,
- tends to obtund upper airway reflexes, thus allow-
ing manipulation/instrumentation more readily
GIT disturbances, blurred vision and bradycardia.
than thiopental. Thus particularly useful when
placing the LMA. Tracheal intubation may be
Propofol. 2,6-Diisopropylphenol (Fig. 130). IV anaes- possible after propofol induction without neuro-
thetic agent, first used in 1977 and introduced into clini- muscular blocking drugs, especially if opioids are
cal practice in 1986. Thought to produce anaesthesia by also given.
binding to GABAA receptors and potentiating the action CNS:
of endogenous GABA. - antanalgesia has not been reported.
Originally formulated in Cremophor EL, but refor- - has an antiemetic effect. Increased appetite has
mulated before commercial release because of allergic been suggested but may reflect the excellent
reactions. Now presented as an oilwater emulsion: 1% quality of recovery rather than a direct effect.
(presented in 20ml ampoules, 50/100ml vials and 50ml - involuntary movements have been reported fol-
prefilled syringes) or 2% (for infusion only and pre- lowing propofol, but these are not thought to be
sented in 50ml vials and 50ml prefilled syringes), con- epileptiform convulsions. Has been used success-
taining 10% soya bean oil, 1.2% egg phosphatide and fully in intractable epilepsy.
2.25% glycerol. A new formulation containing medium- - reduces cerebral blood flow, ICP and intraocular
chain triglycerides causes less pain on injection; in addi- pressure.
tion some formulations contain either 0.005% EDTA or - dreams may occur. Claims by patients of sexual
sulphite as a preservative. Fospropofol is the phosphate assault whilst anaesthetised have been made.
prodrug of propofol and as such has a slower onset of other: allergic phenomena and delayed recovery
action; it is licensed in the USA for light sedation. have been reported to the Committee on Safety of
Aquafol is a newly developed emulsification of propofol Medicines.
in water, which has similar properties to the parent agent Dosage:
but causes more pain on injection. 1.52.5mg/kg for induction (increased to 2.55mg/
pKa is 11. Distribution and elimination half-lives are kg in children).
12min and 15h respectively; context-sensitive half- for maintenance, several regimens have been
life is approximately 20min after 2h infusion, 30min suggested, based on pharmacokinetic studies,
after 6h infusion and 50min after 9h infusion. 98% including the Bristol regimen (applies to concurrent
protein-bound after iv injection. Metabolised in the liver use of 66% N2O, or infusion of alfentanil 3050g/
and excreted renally. Extrahepatic metabolism is sug- kg/h):
gested by a plasma clearance (2530ml/kg/min) that - 10mg/kg/h for 10min.
exceeds hepatic blood flow. There are no active metabo- - 8mg/kg/h for 10min.
lites. Thus recovery is rapid with minimal residual effects, - 6mg/kg/h thereafter, adjusted if required accord-
making it a popular agent in short cases, e.g. in day-case ing to clinical response.
surgery. These properties also make it suitable for TIVA In modern practice, more precise anaesthesia is
and iv sedation. achieved by using target-controlled infusion (TCI)
pumps which automatically adjust infusion rates
according to the patients age, weight, volume
infused and target plasma propofol concentration
(in healthy patients, 48g/ml for induction of
anaesthesia and 36g/ml for maintenance).
OH 1.04.0mg/kg/h for sedation (licensed for up to 3
CH3 CH3 days).
CH CH
Contamination during preparation for infusion has led
CH3 CH3 to iatrogenic bacteraemia, and hence the development
of the EDTA preparation.
Contains the same energy content as 10% fat emul-
Fig. 130 Structure of propofol sion (900 Cal/l). Plasma lipid levels should be monitored
 Prostaglandins 483

in all patients receiving propofol infusions for longer arrhythmias, hypertrophic obstructive cardiomyop-
than 3 days. athy, anxiety, thyrotoxicosis: 1040mg orally bd/tds.
The 1% solution is licensed for induction/maintenance acute coronary syndromes: 40mg orally qds for 23
of anaesthesia and sedation for short procedures in chil- days, then 80160mg/day.
dren over 1 month (the 2% solution should not be used acute iv administration: 1mg over 1min, repeated
in children < 3 years). Not approved for sedation of as required up to 510mg.
children of any age in ICU (neurological, cardiac, renal
and hepatic impairment have been reported after its use Propylene glycol. Diol alcohol (CH3.CHOH.CH2OH),
in this setting). Myocardial failure and acidosis have used as a solvent in drugs, e.g. etomidate, GTN, loraze-
been reported after prolonged infusion of high doses in pam. Has been associated with hypotension, lactic aci-
adults, leading to the description of a distinct metabolic dosis, pulmonary hypertension and haemolysis; these
syndrome, the propofol infusion syndrome. effects are independent of the drug infused.

Propofol infusion syndrome. Progressive myocardial Prostacyclin. Prostaglandin PGI2 produced by the
failure (often with resistant bradycardia), metabolic aci- intima of blood vessels via the cyclo-oxygenase limb of
dosis, hyperkalaemia and evidence of muscle damage in the arachidonic acid metabolism pathway. The most
the absence of other causes, in children and adults potent inhibitor of platelet aggregation, acting via an
receiving infusions of propofol. Typically associated with increase in cAMP levels. At high doses, may disperse
hyperlipaemia and high infusion rates of propofol (> circulating platelet aggregates. Thought to have vital
4mg/kg/h) for prolonged periods (> 2 days), it is thought importance in preventing coagulation within normal
to be related to exacerbation of poor tissue oxygenation blood vessels. Also a potent vasodilator drug. Increases
and impaired cellular utilisation of glucose, perhaps renin production and blood glucose levels.
involving respiratory chain dysfunction. Treatment is Provided commercially as synthetic epoprostenol
supportive and includes withdrawal of propofol; haemo- sodium, which is reconstituted in saline and glycerine to
dialysis has been used successfully. Mortality is high. produce a clear colourless solution of pH 10.5. Used to
Wong JM (2010). Am J Ther; 17: 48791 prevent platelet aggregation during renal dialysis or
other forms of extracorporeal circulation; has also been
Proportional assist ventilation (PAV). Mode of partial used in pre-eclampsia, pulmonary hypertension, haemo-
ventilatory support in which the ventilator generates an lytic uraemic syndrome and septic shock. Half-life is
instantaneous inspiratory pressure in proportion to the 23min, with cessation of platelet effects within 30min
instantaneous effort of the patient (i.e. does not use of stopping an infusion. Its main metabolite is 6-keto-
preset pressure or volume targets). Intended to facilitate prostaglandin F1.
normal neuroventilatory coupling by allowing the Dosage: 235ng/kg/min iv.
patient to control all aspects of breathing (i.e. tidal Side effects: flushing, headache, hypotension.
volume, inspiratory and expiratory durations, and flow
patterns), whilst the ventilator functions as an extension Prostaglandins (PGs). Unsaturated fatty acids contain-
of the patients respiratory muscles. Changes in lung and ing 20 carbon atoms and a five-membered carbon ring
chest wall impedance may prevent PAV from being fully (cyclopentane ring) at one end. Derived from arachi-
effective. Has several potential benefits: donic acid, and thought to be synthesised in most tissues,
greater patient comfort and lower sedation although originally isolated from seminal fluid in the
requirements. 1930s. Named according to the configuration of the
reduced ventilator asynchrony and improved sleep cyclopentane ring (e.g. PGA, B, C, etc. to PGI [prostacy-
quality. clin]), with subscript numbers denoting the number of
reduction of peak airway pressures. side-chain double bonds.
preservation and enhancement of the patients own Functions include:
homeostatic control mechanisms. immune and inflammatory responses.
May have a non-invasive role in COPD. platelet aggregation.
Moerer O (2012). Curr Opin Crit Care; 18: 619 temperature regulation by action on the
hypothalamus.
Propranidid. IV anaesthetic agent, first used in 1956 and exocrine/endocrine and reproductive function.
withdrawn in 1984. Eugenol (oil of cloves) derivative, renal blood flow and renin production.
prepared in Cremophor EL or polyoxyethylated castor CNS neurotransmission.
oil. Hydrolysed by plasma and liver esterases. Rapidly pain perception and local sensitisation of tissues to
acting, with rapid recovery. Hypotension, apnoea follow- inflammatory mediators.
ing initial hyperventilation, venous thrombosis and Have varying effects on smooth muscle: PGE2, PGI2 and
adverse drug reactions were common. PGA2 cause arteriolar dilatation, whilst PGF2 causes
vasodilatation in some vascular beds and vasoconstric-
Propranolol. -Adrenergic receptor antagonist (the first tion in others. PGF2 and PGD2 cause bronchoconstric-
to be introduced, in 1964). Non-selective, and without tion, whereas PGE2 causes bronchodilatation. PGE2 and
intrinsic sympathomimetic activity. 9095% protein- PGF2 cause uterine contraction and are used to induce
bound. Its primary metabolite, 4-hydroxypropanolol, has abortion or labour, e.g. administered vaginally. Oral and
-blocking activity. Uses and side effects are as for iv administration is rarely used, the latter because of side
-adrenergic receptor antagonists in general. effects, including vomiting, diarrhoea, dizziness, pyrexia
Dosage: and rash.
hypertension, portal hypertension, angina, migraine, PGE1 is used iv to maintain patency of the ductus
phaeochromocytoma: 3080mg orally bd, increased arteriosus in congenital heart disease before corrective
up to 120320mg/day. surgery. Tachy- or bradycardia, hypotension, pyrexia,
484 Protamine sulphate

DIC and convulsions may occur. It has been studied in resistance (most commonly factor V Leiden), both of
the treatment of ARDS. An analogue is available for which predispose to venous thrombosis.
oral use, to prevent gastric ulcers associated with A recombinant form of activated protein C, drotre-
NSAIDs. cogin alfa, was previously recommended by NICE in the
Half-life is a few minutes, with local metabolism of treatment of severe sepsis; it was withdrawn from use
circulating PGs via the pulmonary, hepatic and renal worldwide in 2011 following a number of trials showing
circulations. no benefit compared with placebo.
Many of the effects of NSAIDs involve inhibition of [Leiden; city in Netherlands where the factor was first
PG synthesis. identified in 1993]
PGE2 and PGF2 are given as dinoprostone and car-
boprost respectively; PGE1 is given as alprostadil. Protein:creatinine ratio (PCR). Ratio of protein to
creatinine in a random urine sample, used as a more
Protamine sulphate. Mixture of low-molecular-weight, accurate quantitative indicator of proteinuria than
cationic, basic proteins prepared from the sperm of simple stick testing whilst not requiring a 24-h urine col-
salmon and other fish. Used as a heparin antagonist lection. Has been found to correlate reasonably well
(both unfractionated and low-molecular-weight heparin), with 24-h protein; e.g. PCRs < 1 and > 3 (or < 10 and >
and in the preparation of protamine zinc insulin. Has an 30mg/mmol, depending on the units of measurement)
anticoagulant effect when given alone in high doses, via are consistent with 24-h protein excretions of < 1g and
inhibition of formation and action of thromboplastin. > 3g respectively. Albumin:creatinine ratio has also
Binds and inactivates anionic, acidic heparin, forming a been used.
stable salt.
Dosage: 1mg iv neutralises 100U heparin if given Proteins. Polypeptide chains of amino acids (usually
within 15min of the latters administration; less is defined as over 50500). May incorporate carbohydrates
required after longer intervals. Dosage is usually or fats. Present in all cell protoplasm and required for
adjusted according to the patients coagulation status. growth and healing. Involved in:
cellular structure, e.g. collagen, myosin, actin,
Should be given slowly (i.e. less than 5mg/min); indi-
vidual doses should not exceed 50mg. membranes.
Side effects: myocardial depression, bradycardia, pul- enzymes.
hormones and precursors.
monary hypertension, histamine release, complement
blood components, e.g. immunoglobulins, haemo-
activation, anaphylaxis. These effects are more likely
following rapid administration. Chronic exposure in globin, albumin.
diabetics, previous vasectomy or allergy to fish may See also, Nitrogen balance; Nutrition
predispose to allergic reactions.
Prothrombin time, see Coagulation studies
Protein-binding. Occurs for many blood-borne sub- Proton pump inhibitors. Group of drugs that selec-
stances, e.g. bilirubin, mineral ions, hormones, and many tively inhibit the H+/K+-ATPase enzyme located on the
drugs. Important in drug pharmacokinetics because only luminal surface of the gastric parietal cells, thus virtually
the free unbound fraction is available to cross mem- abolishing gastric acid production. Used to treat peptic
branes, produce its effects, or be metabolised or excreted. ulcer disease and severe gastro-oesophageal reflux and
Free fraction of drug is affected by plasma protein levels, to decrease the risk from aspiration of gastric contents
drug concentration, pH and presence of other substances in high-risk patients. Should be used with caution in liver
or drugs that compete for the same binding sites. The disease. Include omeprazole, lansoprazole, pantoprazole
drugprotein complex may act as an antigen in adverse and rabeprazole.
drug reactions.
The main proteins involved are:
Pruritus. Itch-like sensation in the absence of a normal
albumin: binds certain ions (e.g. calcium) and
stimulus; can arise from cutaneous, neurological or psy-
acidic drugs, e.g. thiopental, phenytoin, warfarin, chological triggers. Afferent pathways involve a number
salicylates. of inflammatory mediators, e.g. histamine peripherally
1-acid glycoprotein: binds basic drugs, e.g. local
and 5-HT centrally.
anaesthetic agents, propranolol, quinidine. Causes may be:
globulins: bind e.g. tubocurarine.
cutaneous:
See also, Anaesthesia, mechanism of; Drug interactions; - release of histamine, e.g. due to drugs (morphine,
Hypoproteinaemia cyclizine, antibiotics, anaphylaxis) or other
cutaneous stimuli, including trauma, infections/
Protein C. Plasma protein that promotes fibrinolysis infestations, systemic inflammatory conditions.
and inhibits thrombosis and inflammation. The circulat- - deposition of other irritant substances, e.g. bile
ing inactive form is activated by the enzyme complex of salts, calcium.
thrombin coupled with thrombomodulin (an endothelial - other skin diseases.
surface membrane protein). Activated protein C blocks neurological:
the activated forms of coagulation factors V and VIII, - interaction with central neurotransmitters (e.g.
thereby inhibiting prothrombinase and factor X-ase epidural/spinal opioids).
complexes. Activation of protein C may be impaired - cerebral lesions.
during sepsis and protein C may also be consumed. - peripheral neuropathy.
Reduced levels of protein C are associated with an psychological.
increased mortality. Inherited protein C abnormalities Often seen after administration of anaesthetic or related
include protein C deficiency and activated protein C drugs. Although many drugs, especially propofol and
 Pulmonary artery catheterisation 485

ondansetron, have been studied as possible prophylactic compartment (usually at 1012cm) as for epidural
or therapeutic agents, there is little evidence to support anaesthesia. 3040ml local anaesthetic agent is injected.
the use of most. For systemic opioid-induced pruritus, Complications include subarachnoid, epidural and
antihistamine drugs may be used, while opioid receptor intravascular injection.
antagonists are effective following epidural/spinal
opioids. Psychological aspects of intensive care, see Confusion
Waxler B, Dadabhoy Z, Stojiljkovic L, Rabito S (2005). in the intensive care unit; ICU delirium; Intensive care
Anesthesiology; 103: 16878 follow-up; Post-traumatic stress disorder

Pseudocholinesterase, see Cholinesterase, plasma Psychoprophylaxis. Technique used in obstetric analge-

sia and anaesthesia to increase comfort and relaxation
Pseudocritical temperature. Temperature at which gas during labour. Requires antenatal education about preg-
mixtures separate into their component parts. Varies nancy and labour, and training in relaxation and breath-
with pressure: for Entonox, highest (5.5C) at 117 bar, ing techniques.
and decreases above and below this pressure. Thus
equals 7C for Entonox cylinders (135 bar) and 30C PT, Prothrombin time, see Coagulation studies
for pipelines (4 bar).
PTS, see Paediatric trauma score
Pseudomembranous colitis. Inflammation of the large PTT, Partial thromboplastin time, see Coagulation
bowel characterised by diarrhoea, abdominal pain, fever, studies
and blood and mucus in the stool; presentation ranges
from an asymptomatic carrier state to fulminant life- Pudendal nerve block. Used bilaterally to provide anal-
threatening colitis. Caused by toxins produced by gesia in obstetric analgesia and anaesthesia, especially
Clostridium difficile, usually associated with use of anti- for forceps and ventouse delivery. Has a high failure rate,
bacterial drugs (e.g. cephalosporins, clindamycin) and exacerbated by inadequate time between performance
immunosuppressive therapy. The use of proton pump of the block and attempted delivery.
inhibitors may be a risk factor. Diagnosis is confirmed The pudendal nerve (S24) arises from the sacral
by culture of the organism and detection of the toxin in plexus and leaves the pelvis through the greater sciatic
the faeces. Colonoscopy reveals pseudomembranes con- foramen, passing behind the ischial spine and sacrospi-
sisting of fibrin and leucocytes. Infection spreads between nal ligament to re-enter the pelvis through the lesser
patients by environmental contamination and direct sciatic foramen. It supplies the perineum, vulva and
cross-infection. lower vagina.
Management: Techniques:
withdrawal of antibacterial drugs if possible. transvaginal approach: with the patient in the lithot-
rehydration. omy position, two fingers palpate the ischial spine
metronidazole 400mg orally tds (or 500mg iv), or from within the vagina. A 12.5cm guarded needle
vancomycin 125250mg orally qds for 710 days. is introduced 1.2cm beyond the spine, into the
Bobo LD, Dubberke ER, Kollef M (2011). Chest; 140: sacrospinal ligament, and the needle point extended.
164353 After negative aspiration for blood, 10ml local
anaesthetic agent is injected.
Pseudomonas infections. Commonly seen in hospitals, transperineal approach: a needle is introduced
systemic effects occur via release of endo- and exotoxins. through a point midway between the anus and
Manifestations include catheter-related sepsis, severe ischial tuberosity, and directed as above by a finger
chest infection (especially in those receiving IPPV), in the vagina.
meningitis and general features of sepsis. Infection Local infiltration of the labia is required to block cutane-
typically results in a characteristic odour. Treatment ous branches of the genitofemoral and ilioinguinal
following culture and sensitivity testing consists of an nerves.
anti-pseudomonas penicillin (or third-generation cepha-
losporin) combined with an aminoglycoside. Pugh, Benjamin (17151798). Shropshire-born surgeon
See also, Nosocomial infection and apothecary; practised in Essex. Early advocate of
vaccination against smallpox and author of A Treatise of
Psoas compartment block. Regional anaesthesia tech- Midwifery in 1754. Advocated the use of an air pipe,
nique used to block components of the lumbar plexus inserted into the larynx, to maintain the airway of neo-
(specifically, femoral, obturator and lateral femoral cuta- nates during delayed breech extraction.
neous nerves) and part of the sacral plexus, which lie Baskett TF (2000). Resuscitation; 44: 1535
between psoas major anteriorly and quadratus lumbo- See also, Cardiopulmonary resuscitation, neonatal
rum posteriorly, e.g. for hip and femoral shaft surgery.
With the patient in the lateral position with the oper- Pulmonary artery catheterisation. Performed using
ative side uppermost and hips partly flexed, a skin wheal flow-directed balloon-tipped pulmonary artery cathe-
is raised 35cm lateral to the lower border of the spinous ters, introduced into clinical practice in the early 1970s
process of L4. A 1015cm needle is inserted perpendicu- by Swan and Ganz (after whom one commercial device
lar to the skin until it contacts the transverse process, is named), amongst much controversy.
then withdrawn and redirected slightly caudad to pass Catheters may have some of the following features:
the process. A nerve stimulator may be used to identify 70cm long, marked every 10cm.
the optimal injection point (eliciting quadriceps twitch channels/lumina:
with a threshold of 0.30.5mA). Alternatively, a loss-of- - distal (opens at the tip).
resistance technique may be used to identify the psoas - proximal (opens 30cm from the tip).
486 Pulmonary artery pressure

- for inflating the balloon (11.5ml air used). derived data:

- connections to a thermistor, a few cm from the tip. - systemic and pulmonary vascular resistance.
- fibreoptic bundles for continuous oximetry. - cardiac index, stroke volume/index.
- others include those for cardiac pacing and Uses, e.g. perioperatively and in ICU:
Doppler imaging. investigating cardiac shunts.
Insertion: monitoring the above pressures and optimising fluid
all lumina are flushed with saline, and the balloon therapy; particularly useful when right atrial pres-
checked. sures do not reflect left heart function; e.g. left ven-
aseptic technique is used. The catheter is usually tricular failure or infarction, severe bundle branch
passed through a sterile plastic protective sleeve to block, pulmonary hypertension, cardiac tamponade
allow manipulation without contamination after and constrictive pericarditis, valvular heart disease
insertion. (for interpretation, etc., see Pulmonary capillary
insertion is as for central venous cannulation, wedge pressure).
usually employing the Seldinger technique. The measuring cardiac output and derived data.
right internal jugular vein is most commonly used. monitoring mixed venous O2 saturation as a con-
The catheter is threaded down an 8 G introducer tinuous indicator of cardiac output and tissue perfu-
sheath, with continuous visible pressure monitoring sion, e.g. in ICU.
from the distal lumen. The balloon is inflated in the as a route for cardiac pacing.
right atrium and directed by the flow of blood into infusion of drugs into the pulmonary circulation, e.g.
the pulmonary artery via the right ventricle. Pulmo- prostacyclin in pulmonary hypertension.
nary capillary wedge pressure is displayed when the Complications:
balloon occludes a pulmonary vessel; the catheter as for central venous cannulation.
tip is now separated from the left atrium by a con- arrhythmias.
tinuous column of blood. Placement is confirmed infection.
by the changes in the pressure trace obtained catheter knotting.
(Fig. 131). damage to valves, myocardium, etc.
coiling and/or knotting of the catheter within the pulmonary artery damage or rupture.
heart may occur if excessive length of catheter is pulmonary infarction.
inserted without a change in the pressure trace. incorrect positioning, measurement and
once inserted, the balloon is left deflated until interpretation.
wedge pressure measurement is required, to reduce Although previously widely used in critically ill patients,
risk of pulmonary artery damage and infarction. there is no clear evidence that their use reduces morbid-
The distal lumen pressure should always be dis- ity and mortality; indeed there is a suggestion that they
played, to alert to accidental wedging. are associated with increased mortality and their use has
use of a catheter is often limited to 23 days to declined since the widespread introduction of alterna-
reduce risk of complications. tive methods of cardiac output monitoring.
Information gained: [Harold JC Swan (19222005), Irish-born US cardio
mixed venous, right atrial and ventricular gas ten- logist; William Ganz (19192009), Los Angeles
sions and O2 saturations; e.g. for estimation of cardiologist]
cardiac shunt. Continuous monitoring of mixed
venous O2 saturation is possible via fibreoptic
bundles. Pulmonary artery pressure (PAP). Typically one-fifth
measurement of right atrial and ventricular pres- of systemic circulatory pressure; normal ranges are 15
sures, pulmonary artery pressure and pulmonary 30mmHg systolic, 08mmHg diastolic and 1015mmHg
capillary wedge pressure. By convention, measured mean. Usually measured by right-sided cardiac catheter-
at end-systole and end-expiration. isation. Changes may indicate changes in pulmonary
measurement of right ventricular ejection fraction. capillary wedge pressure and pulmonary vascular
cardiac output measurement. resistance.

Pulmonary capillary wedge pressure (PCWP; Pulmo-

nary wedge pressure, PWP; Pulmonary artery occlusion
pressure, PAOP). Pressure measured within the pulmo-
nary arterial system during pulmonary artery catheteri-
sation, with the catheters tip wedged in a tapering
Pressure (mmHg)

20
branch of one of the pulmonary arteries. In most patients,
represents left atrial filling pressure and thus left
ventricular end-diastolic pressure (LVEDP). Thus
10
an indirect indicator of left ventricular end-diastolic
volume and myocardial fibre length (see Starlings law).
Also indicates the likelihood (with measurement of
0
Right Right Pulmonary Wedge
plasma colloid osmotic pressure) of pulmonary oedema
atrium ventricle artery pressure formation, assuming normal pulmonary capillary
permeability.
Time Normal range: 612mmHg; usually 14mmHg less

Fig. 131 Pressure trace obtained during placement of a pulmonary than pulmonary artery diastolic pressure (PADP).
artery catheter Traditionally measured at end-expiration.
 Pulmonary embolism 487

Values should be interpreted with caution in: The vessels are supplied by sympathetic vasoconstrictor
left ventricular failure: LVEDP may exceed PCWP. (-receptors) and vasodilator (2-receptors) fibres, and
mitral valve disease: in stenosis PCWP may exceed by parasympathetic vasodilator fibres. However, resting
LVEDP; in regurgitation large v waves interfere vascular tone is minimal, with vessels almost maximally
with the PCWP waveform. dilated in the resting state. Other factors affecting vessel
raised intrathoracic pressure, e.g. PEEP: LVEDP calibre include vascular responses to local changes, e.g.
may exceed PCWP. hypoxic pulmonary vasoconstriction and other factors
non-compliant left ventricle: LVEDP may exceed affecting pulmonary vascular resistance.
PCWP. The pulmonary circulation contains about 1020% of
aortic regurgitation: LVEDP may greatly exceed the total blood volume (i.e. 0.51.0 l). It changes during
PCWP. respiration (especially IPPV) and may increase by 25
Gradients between PADP, PCWP and LVEDP may be 40% in moving from the erect to the supine position.
increased in tachycardia and increased pulmonary vas- [John B West, Californian physiologist]
cular resistance. The position of the catheter tip is also Fischer LG, van Aken H, Burkle H (2003). Anesth
important; a continuous column of blood between the Analg; 96: 160316
catheter and the left ventricle only occurs if the tip lies See also, Starling resistor; Ventilation/perfusion
in zone 3 of the lung (see Pulmonary circulation). mismatch
Although the catheter usually flows to zone 3, especially
in the supine position, repositioning of the patient may Pulmonary embolism (PE). Mechanical obstruction of
alter the zonal distribution. a pulmonary artery/arteriole; usually refers to blood-
The waveform resembles the venous waveform, with borne thrombus. The most common cause of death
a, c and v waves, and swings with respiration. PCWP within the first 10 postoperative days. Thrombus usually
should not exceed PADP. arises from a DVT in the legs/pelvis, although the venae
As with CVP interpretation, trends are more useful cavae and right side of the heart are sometimes sources.
than single values. Response of PCWP to drug or iv fluid The effects depend on the size and distribution of the
administration may be used to indicate intravascular PE; release of vasoactive mediators (e.g. prostaglandins)
volume status and cardiac function, and guide therapy. may contribute to resultant vasospasm. Massive PEs
Pulmonary oedema is likely at PCWP above 18 cause rapid respiratory and cardiovascular collapse,
20mmHg, with normal colloid osmotic pressure. and death. Smaller PEs may cause few haemodynamic
effects, but may result in infarction of a section of lung
tissue if collateral blood flow is inadequate. Multiple PEs
Pulmonary circulation. Low-pressure/low-resistance may cause widespread pulmonary vascular obstruction
system in series with the systemic circulation, receiving and lead to pulmonary hypertension.
the whole cardiac output. The pulmonary artery divides Risk factors are as for DVT.
into right and left main pulmonary arteries. Pulmonary Features:
arteries are thin-walled and easily distensible, lying close pleuritic chest pain, haemoptysis, dyspnoea and
to the corresponding airways in connective tissue sheaths, mild pyrexia in small PEs.
eventually dividing to form capillaries with a total gas cyanosis, tachypnoea, hypotension, tachycardia,
exchange interface of about 70 m2. Venules run close to raised JVP and bronchospasm. Third and fourth
the septa that separate the lung segments and drain into heart sounds may be present. A pleural rub may
four main pulmonary veins, which deliver oxygenated develop.
blood to the left atrium. arterial blood gas interpretation reveals hypoxae-
The separate bronchial circulation supplies the mia and hypocapnia, with subsequent metabolic
lower airways down to the respiratory bronchioles, acidosis in severe PE. During anaesthesia, end-tidal
local connective tissue and the visceral pleura; it arises CO2 concentration may fall dramatically because of
from the aorta and eventually drains via the azygos increased dead space and reduced cardiac output.
system into the pulmonary veins, i.e. representing an right axis deviation, right bundle branch block and
anatomical shunt. T inversion in leads V14 may occur in the ECG;
The diameter of extra-alveolar vessels (those both a normal ECG and the classic S1Q3T3 pattern
running through lung parenchyma) is affected by lung are rarely seen.
volume, via the pull of lung parenchyma on their walls. CXR may show enlarged proximal pulmonary
That of alveolar pulmonary vessels (predominantly arteries with peripheral oligaemia, but is usually
capillaries) depends on the difference between arterial non-specific. Wedge-shaped infarcts (Hamptons
(Pa), venous (Pv) and alveolar (PA) pressures, and thus hump), elevation of the ipsilateral diaphragm and
on gravity. Four zones have been described by West, pleural effusion may subsequently develop.
from above downwards: Definitive diagnosis is usually made by CT angiography
zone 1: lung apex; PA exceeds both Pa and Pv; thus or ventilationperfusion scan (if the former is unavail-
no flow occurs. Does not occur at normal BP in able). MRI and echocardiography imaging techniques
normal lungs. are also used.
zone 2: Pa > PA > Pv; thus flow depends on the dif- Features of DVT may be present. A normal D-dimer
ference between Pa and PA, and not on Pv. concentration reliably excludes PE.
zone 3: Pa > Pv > PA; i.e. flow depends on the differ- Management:
ence between Pa and Pv, as usually occurs in other immediate CPR if required. A precordial thump
tissues. may break up a large PE and improve circulation.
zone 4: suggested as existing at lung bases; pulmo- O2 therapy, iv fluids, inotropic drugs, analgesia.
nary interstitial pressure exceeds Pa, thus impairing anticoagulation: fondaparinux or heparin (low mw,
blood flow. recommended except in severe renal impairment
488 Pulmonary fibrosis

and/or if the ability to reverse it readily is required), Features:

with subsequent substitution by warfarin as for fatigue, dyspnoea, angina, syncope, haemoptysis.
DVT. Fibrinolytic drugs are indicated in the pres- low cardiac output, cyanosis, features of right ven-
ence of shock or sustained hypotension. tricular enlargement/failure, e.g. sternal heave,
surgical or catheter embolectomy may be required peripheral oedema. On auscultation: reduced split-
for large PEs. Ligation of the inferior vena cava/ ting of the second heart sound, with loud pulmonary
superficial femoral vein, or insertion of a vena caval component.
umbrella, may be required for recurrent PEs. ECG findings: right axis deviation, right bundle
[Aubrey Otis Hampton (19001955), US radiologist] branch block, right atrial and ventricular hyper
Agnelli G, Becattini C (2010). N Engl J Med; 363: trophy. CXR: right atrial and ventricular enlarge-
26674 ment, large pulmonary arteries with peripheral
See also, Air embolism; Amniotic fluid embolism; Fat pruning.
embolism Usually progressive and fatal in primary disease, which
is more common in young women. Treatment may
include calcium channel blocking drugs, warfarin, and
Pulmonary fibrosis. Thickening and infiltration of alve- heartlung transplantation. More recently, prostacyclin
olar walls and perialveolar tissue. analogues (iv or inhaled), endothelin antagonists (e.g.
May result from:
bosentan, nitric oxide and sildenafil) have been investi-
localised loss of lung parenchyma, e.g. following
gated, with some success. Treatment of secondary disease
infection, infarction or aspiration of irritant sub- is directed towards the underlying cause.
stances (e.g. aspiration of gastric contents). May Anaesthetic management is based on avoidance
also follow treatment with cytotoxic drugs, e.g. bleo- of factors that further increase PVR. Monitoring of pul-
mycin. Causes decreased movement and breath monary capillary wedge pressure is more informative
sounds, dullness to percussion and increased vocal than CVP measurement, but risk of pulmonary artery
resonance. Neighbouring structures (e.g. trachea) rupture is increased. Vasodilator drugs have been
may be pulled towards the affected portion. used, e.g. sodium nitroprusside, GTN and phentolamine,
generalised alveolitis: a degree of fibrosis may
but none is specific to the pulmonary circulation;
remain following ARDS. thus systemic hypotension may occur. Use of prostacy-
idiopathic interstitial pneumonitis: progressive, irre-
clin and other newer treatments (see above) have been
versible and usually lethal. reported.
Loss of the pulmonary vascular bed may lead to pulmo- Pritts CD, Pearl RG (2010). Curr Opin Anaesthesiol; 23:
nary hypertension and cor pulmonale. Typically, there is 41116
hypoxaemia with hypocapnia due to hyperventilation. See also, Cor pulmonale
V/Q mismatch is now thought to be responsible for the
hypoxaemia, rather than alveolar membrane thickening,
as previously suspected. Diffusing capacity, compliance Pulmonary irritant receptors. Receptors situated
and lung volumes are reduced, with normal FEV1/FVC between airway epithelial cells, responsible for initiating
ratio. Work of breathing is increased; rapid, shallow bronchospasm and hyperpnoea in response to inhaled
breathing is common. CXR may reveal diffuse nodular/ noxious gases, smoke, dust and cold air. Afferent impulses
reticular shadowing, with local contraction in focal pass via the vagi to the medulla. May be involved in
disease. initiating asthma attacks.
Treatment is of the underlying cause; corticosteroids
are often used.
Anaesthesia: although the pulmonary defect is restric-
Pulmonary oedema. Increased pulmonary ECF (nor-
tive instead of obstructive, principles are as for mally minimal). Small amounts of fluid normally pass
COPD. through the capillary wall into the interstitial space of
the lung. The junctions between alveolar epithelial cells
Pulmonary function tests, see Lung function tests are relatively resistant to fluid, which is removed by the
lymphatic system at about 10ml/h. Lymphatic removal
may increase dramatically if transudation into the inter-
Pulmonary hypertension. Defined as mean pulmonary stitial space increases. Net flux into the interstitial space
artery pressure (PAP) > 25mmHg at rest. May be is governed by Starling forces.
primary, but is usually secondary to: Mechanisms of formation of pulmonary oedema:
pulmonary venous/capillary hypertension, e.g. in alteration of Starling forces:
left ventricular failure, mitral stenosis. - increased hydrostatic pressure, e.g. hypervolae-
increased pulmonary blood flow caused by left-to- mia, left ventricular failure, mitral stenosis.
right cardiac shunts, e.g. ASD, VSD, patent ductus - decreased plasma oncotic pressure, e.g.
arteriosus. hypoproteinaemia.
increased pulmonary vascular resistance (PVR), e.g. - acute severe subatmospheric airway pressure, e.g.
in COPD, recurrent PE, pulmonary fibrosis. upper airway obstruction.
Chronic hypoxaemia, acidosis, polycythaemia and other damage to the alveolarcapillary membrane, e.g.
factors that increase PVR may be involved in develop- ARDS.
ment of pulmonary hypertension. impairment of lymphatic drainage, e.g. lymphangitis
The pulmonary arteries show medial hypertrophy carcinomatosis, silicosis.
and intimal thickening. The right ventricle becomes causes of uncertain aetiology:
hypertrophied and dilates when right ventricular failure - neurogenic: thought to involve sudden catechol-
supervenes. amine release following head injury, with
 Pulmonary vascular resistance 489

vasoconstriction increasing lung capillary pres- Pulmonary valve lesions. Include:

sures and capillary permeability. pulmonary stenosis (PS): may occur at the valve
- following naloxone administration: also thought (90%), infundibulum or within the artery. Almost
to involve catecholamine release. always congenital, accounting for 510% of con-
- in opioid poisoning, possibly related to decreased genital heart disease. Other causes include rheu-
vascular permeability. matic fever and carcinoid syndrome. Usually
- following pulmonary surgery or re-expansion of a asymptomatic; if severe, PS may cause fatigue, dysp
pneumothorax: probably involves local changes in noea and angina secondary to decreased cardiac
capillary pressures and permeability. output. Right ventricular (and later atrial) hyper-
- after exposure to high altitude, possibly via pul- trophy may occur. May be associated with right-to-
monary vasoconstriction. left shunt and cyanosis, e.g. Fallots tetralogy.
As fluid clearance mechanisms are overwhelmed, Features: ejection systolic murmur at the upper
interstitial oedema increases, until alveolar oedema left sternal edge, heard best during inspiration.
occurs. Eventually, frothy oedema fluid fills the airways, Splitting of the second heart sound is increased,
impairing gas exchange. Airways and pulmonary vessels with a quiet pulmonary component in severe PS.
become narrowed by interstitial oedema, and FRC and Right ventricular and atrial enlargement may be
compliance decrease. suggested by the ECG and CXR; a prominent pul-
Features: monary artery and pulmonary oligaemia may
dyspnoea, tachypnoea, cough with pink frothy appear on the latter.
sputum, and tachycardia. Respiratory distress is During anaesthesia, increased right ventricular
worse lying flat (orthopnoea). O2 consumption (e.g. caused by tachycardia and
wheeze and basal crepitations on auscultation. increased contractility) should be avoided.
features of respiratory failure. pulmonary regurgitation (PR): usually a feature of
arterial blood gas interpretation usually reveals pulmonary hypertension, and results from dilata-
hypoxaemia, with hypocapnia secondary to hyper- tion of the valve ring. Other causes include congeni-
ventilation. Metabolic acidosis may be present in tal absence of the valve, endocarditis (usually in iv
severe cases. drug abusers) and surgical valvotomy. Causes right
CXR features include those of the underlying con- ventricular hypertrophy, but usually with little clini-
dition. Lung oedema itself appears as fluffy shadow- cal effect.
ing, typically perihilar (bats wing) in left ventricular Features: high-pitched blowing diastolic murmur at the
failure and patchy (cotton-wool) and peripheral in upper left sternal edge.
ARDS. Bronchial and vascular markings may
appear thickened due to interstitial oedema. Ker- Pulmonary vascular resistance (PVR). Resistance in
leys (B) lines and fluid in the transverse fissure may the pulmonary circulation, analogous to SVR. May be
be present. calculated using the principle of Ohms law:
Differentiation between hydrostatic and other causes
may be aided by measurement of pulmonary capillary mean pulmonary left atrial pressure
80
wedge pressure. Alveolar fluid protein content may also PVR artery pressure (mmHg)
5 =
be measured. Total lung water content has been mea- (dyne s/cm ) cardiac output (l/min)
sured using radioactive or dye dilution techniques.
Treatment of severe acute pulmonary oedema:
where 80 is a correction factor.
of the underlying condition. Normally 20120 dyne s/cm5 (N.B. 1 dyne s/cm5 =
O2 therapy. CPAP may be useful. 100N s/m5).
sitting the patient, with the legs over the edge of Resistance is distributed more evenly than in the
the bed. systemic circulation, with approximately 50% residing
diuretics, e.g. furosemide 20120mg iv (causes in the arteries and arterioles, 30% in the capillaries
vasodilatation and diuresis). and 20% in the veins. The pulmonary arteries are thin-
opioids, e.g. morphine, diamorphine 15mg iv (for walled, large in diameter and easily distensible. The pul-
anxiolysis and vasodilatation). monary circulation is therefore more dependent on
inotropic and vasodilator drugs. gravity, posture and the relationship between alveolar
IPPV may be required. Gas exchange is usually and intravascular pressures than on vascular muscular
improved by PEEP. tone.
venesection may be performed for pulmonary PVR is affected by:
oedema due to volume overload, with removal of passive factors:
200500ml blood. - lung expansion: at lung volumes below FRC,
Ware LS, Matthay MA (2005). N Engl J Med; 353: the radial forces holding the extra-alveolar
278896 vessels open are reduced, thus increasing PVR.
However, at high lung volumes, the increased
airway pressures associated with hyperexpan-
Pulmonary stretch receptors. Mechanoreceptors sion may compress the vessels, also increasing
within the smooth muscle of the lower airways; transmit PVR. PVR is thus lowest at lung volumes
impulses via the vagi to the dorsal medulla. Excitation around FRC.
limits inspiration during pulmonary overinflation - intravascular pressures: PVR falls when either
(HeringBreuer reflex). Sensitivity is increased by pulmonary artery pressure or pulmonary venous
decreased arterial PCO2 and increased pulmonary venous pressure increases, because of recruitment of pre-
pressure. May also be involved in other pulmonary viously closed vessels or distension of individual
reflexes, e.g. gasp and deflation reflexes. capillary segments.
490 Pulse

- cardiac output: as pulmonary blood flow increases, differentiate between the wavelengths, each LED is
vessel diameter increases, thus reducing PVR. alternately switched on and off, the timing of which
- haematocrit and blood viscosity. allows identification of red and infrared pulses. The
active factors via changes in vascular tone: periods when both LEDs are off allow compensa-
- hypoxia (see Hypoxic pulmonary vasoconstric- tion for ambient light conditions.
tion), hypercapnia and acidosis increase PVR, the signal is converted to a DC component repre-
especially in combination, whilst their opposites senting tissue background, venous blood and the
decrease PVR. constant part of arterial blood flow, and an AC com-
- drugs and biological mediators, e.g. vasoconstric- ponent representing pulsatile arterial blood flow.
tor drugs, 5-HT and histamine increase PVR The former is discarded, the latter amplified and
whilst vasodilator drugs, nitric oxide, prostacyclin averaged over a few seconds.
and acetylcholine decrease it. Drugs may also the ratio of pulsatile transmitted red to infrared
affect PVR via changes in cardiac output and lung light is calculated and compared with stored cali-
volumes. bration curves (derived from healthy human volun-
- neural control: sympathetic nervous system sup- teers) to give an estimated SpO2.
plies vasoconstrictor (-adrenergic receptor) and the signal is displayed ideally as a continuous trace,
vasodilator (-adrenergic receptor) fibres to the showing quality of signal and a numerical value of
pulmonary vessels, whilst the parasympathetic SpO2 (suggested as appropriate notation of SaO2
nervous system supplies cholinergic vasodilator measured by a pulse oximeter). Most modern
fibres. machines automatically adjust gain to maintain a
In addition, local vascular resistance may be increased constant size of trace.
by PE, atelectasis, pleural effusions and surgery. Used in routine monitoring, but particularly useful
PVR may be corrected for differences in body size by during one-lung anaesthesia, high-risk cases, paediatric
multiplying by body surface area (PVR index). anaesthesia, or where observation of cyanosis is difficult,
See also, Lung; Pulmonary artery catheterisation; Pulmo- e.g. dark skin, darkened room or poor access to the
nary hypertension patient. Oximetry has also been used to monitor sleep
apnoea, in cardiac and respiratory function testing, CPR
Pulse. Traditionally palpated at the wrist, but commonly and assessment of peripheral circulation. It has been
palpated at the head and neck during anaesthesia (see shown to detect desaturation in patients when clinical
Carotid arteries). assessment reveals no abnormality, e.g. during anaesthe-
May be assessed for: sia, recovery and transport of patients.
heart rate: speed, rhythm, regularity. Inaccuracy may result from excessive ambient light,
volume and character, i.e. reflecting pulse pressure movement artefact, poor peripheral perfusion, elec-
and arterial waveform. Pulsus alternans and pulsus trical interference, venous congestion, and when SaO2
paradoxus are two specific abnormalities. is less than 80% (as calibration data below this level
simultaneous pulsation at upper and lower limb are extrapolated). Response time to detecting desatu-
arteries; femoral delay occurs in coarctation of the ration varies with probe location (e.g. up to 3060 s
aorta. with a finger probe). Coloured nail polish may
produce inaccuracies (tend to increase readings).
Pulse deficit. Difference between the auscultated heart Effects of other pigments:
rate and palpated pulse rate. Occurs when one heart beat carboxyhaemoglobin: most is counted as HbO, thus
follows another so quickly that ventricular filling is insuf- SpO2 is falsely high.
ficient for a palpable pulsation, e.g. in ventricular ectopic methaemoglobin and bilirubin: counted as Hb, thus
beats and AF. SpO2 is falsely low (but may be falsely high if true
saturation is very low, i.e. < 70%).
Pulse detector. Several devices have been used to methylthioninium chloride (methylene blue), indo-
detect the pulse, e.g. to monitor heart rate or to aid in cyanine green, etc.: may temporarily decrease SpO2
arterial BP measurement. Each utilises a small trans- for a few minutes after iv injection.
ducer positioned over a peripheral artery or attached to fetal haemoglobin, polycythaemia: no effect.
a digit: Machines are calibrated during manufacture. Some are
microphone or Doppler probe. preset for low values of carboxyhaemoglobin and met
finger probe containing a light source and photocell haemoglobin. More recent designs use multiple wave-
that detects changes in reflected or transmitted light lengths of light to allow estimation of carboxy- and
due to arterial pulsation. methaemoglobin levels, as well as Hb concentration.
Simple devices emit a noise or flashing light in time with Burns and pressure sores have been reported follow-
the pulse, or register the pulse rate on a meter. These ing prolonged use, especially with finger probes on
have been largely replaced by more sophisticated devices children.
displaying a waveform, e.g. pulse oximeter.
Pulse pressure. Difference between systolic and dia-
Pulse oximeter. Device used to determine arterial O2 stolic blood pressures, normally about 3545mmHg.
saturation using oximetry. Consists of the following Depends on:
components: stroke volume.
two light-emitting diodes (LEDs) within the probe compliance of the arterial tree; e.g. arterial calcifica-
emit monochromatic light at red (660nm) and tion in the elderly results in reduced compliance
infrared (940nm) wavelengths. and increased pulse pressure.
a photodiode on the opposite side of the probe duration and speed of ventricular ejection.
detects the transmitted light; since it is unable to aortic valve function.
 Pupillary reflex 491

site of measurement; increased as the arterial wave- ipsilateral fixed dilatation in head injury, followed
form moves peripherally. by bilateral dilatation due to herniation of the brain
See also, Pulse through the tentorium, causing compression of the
third cranial nerve.
Pulseless electrical activity (PEA). Cardiac state in Horners syndrome.
which there is electrical activity adequate to produce Argyll Robertson pupil: small and irregular, fixed to
myocardial contraction but contractions either do light but responsive to accommodation. Classically
not occur or they do not produce a detectable cardiac occurs in tertiary syphilis but may occur in diabetes
output. Distinguished from electromechanical dissocia- mellitus and brainstem encephalitis.
tion (EMD), in which there are no contractions despite HolmesAdie pupil: large and regular, with sluggish
apparently adequate electrical activity. The term pseudo- light reflex. Often associated with loss of knee
EMD has been proposed for PEA in which flow is so reflexes but no other pathology.
low it cannot be detected by non-invasive means. [Douglas Argyll Robertson (18371909), Scottish
See also, Cardiac arrest surgeon; Gordon M Holmes (18761965), Irish-born
English neurologist; William J Adie (18861935),
Pulsus alternans. Alternating weak and strong pulses Australian-born English neurologist]
reflecting similar alterations in left ventricular filling and
output. Common in left ventricular failure. Pupillary reflex. Easily tested reflex arcs involving the
See also, Arterial waveform pupils:
light reflex (Fig. 132): pupillary constriction nor-
Pulsus paradoxus. Defined as an abnormally large mally follows direct or contralateral (consensual)
inspiratory decrease in arterial BP (e.g. greater than illumination. Occasionally, phasic contraction and
10mmHg). The paradox lies in the observation that the dilatation occur (hippus). Pathway: from retina via
radial pulse may disappear during inspiration despite the optic nerve to the optic chiasma, thence to both
continued presence of the cardiac impulse at the precor- lateral geniculate bodies via the optic tracts. Fibres
dium. Cardiac output and BP fall due to reduced left then pass to the EdingerWestphal nuclei of the
ventricular filling. Proposed mechanisms for this include: third cranial nerve. Efferent parasympathetic fibres
pooling of blood in the pulmonary circulation due to pass to the ciliary ganglia, then via oculomotor and
increased negative intrathoracic pressure (e.g. in COPD short ciliary nerves to the iris sphincter muscles
or upper airway obstruction); and impaired LV filling of both sides. The cerebral cortex is not involved in
due to inspiratory RV filling within a restricted pericar- the reflex.
dium (e.g. cardiac tamponade, constrictive pericarditis). accommodation reflex: constriction normally occurs
Bilchick KC, Wise RA (2002). Lancet; 359: 19402 when the eyes converge. Fibres from the lateral
See also, Pulse geniculate bodies pass to the visual areas of the
cerebral cortex; impulses then pass via superior lon-
Pumping effect. Increased vaporiser output when pres- gitudinal fasciculus and internal capsule to the ocu-
sure within the breathing system/back bar increases lomotor nuclear mass next to the EdingerWestphal
intermittently, e.g. during IPPV or use of the O2 flush.
During the pressure increase, gas within the back bar
(i.e. containing the set concentration of volatile agent) is To ciliary
compressed back into the vaporiser chamber, where it muscle
becomes saturated with the volatile agent. When the
downstream pressure falls, this gas re-expands into the
back bar, thus increasing the concentration of volatile
agent within the back bar. In addition, saturated vapour
in the vaporiser chamber may be forced retrogradely
into the vaporiser bypass, increasing the delivered con-
centration of volatile agent further.
The effect is greatest at low vaporiser settings and low Ciliary
gas flows, and may be minimised by: ganglion
increasing resistance to flow through the vaporiser Optic nerve
and bypass.
lengthening the path through which the retrograde Lateral 3rd cranial nerve
flow must pass before reaching the bypass. geniculate
minimising the volume of the vaporiser chamber. body
placing a non-return valve downstream of the
Optic tract
vaporiser.

Pupil. Central orifice of the iris; normally 18mm in

size. Contraction (miosis) is caused by parasympathetic
stimulation, drugs including opioid analgesic drugs EdingerWestphal nucleus
and anaesthesic agents, and pontine lesions. Dilatation
(mydriasis) is caused by sympathetic stimulation and
Pretectal nucleus
anticholinergic drugs. Dilated pupils may occur during
awareness or hypercapnia during anaesthesia. Fig. 132 Pupillary light reflex, showing pathways from one side of the
Abnormal pupils and pupillary reflex may occur in visual field. The right lateral geniculate body and pretectal nucleus have
particular lesions, e.g.: been omitted
492 PVS

nucleus. When both medial recti are adducted, the months. Useful in tuberculous meningitis because of
pupils constrict. good penetration into CSF.
Impaired reflexes are caused by lesions anywhere along Dosage: 1.52.0g daily for 2 months.
their paths. Side effects: hepatotoxicity, anaemia, vomiting.
[Ludwig Edinger (18551918) and Karl FO Westphal
(18331890), German neurologists] Pyrexia. Increased core body temperature, usually taken
as 38C (100.4F), although definitions vary. The term
PVS, Persistent vegetative state, see Vegetative state implies intact homeostatic mechanisms, whereas hyper-
thermia refers to thermoregulatory failure. Common in
Pyloric stenosis. Stenosis of the gastric outflow. May be: ICU patients, it is a feature of the general inflammatory
congenital: response and brought about by cytokines (especially
- hypertrophy of the circular pyloric muscle; cause interleukin-6) and other mediators.
is unknown. Occurs in 1:500 births, 80% in males Caused by:
(usually first-born). infection, including chest infection, urinary tract
- usually presents within 312 weeks of age, with infection, catheter-related sepsis and sinusitis.
persistent projectile vomiting, failure to gain others: primary inflammatory diseases (e.g. connec-
weight and hunger. A tumour may be palpable tive tissue disease), drugs (e.g. antibacterial drugs),
in the right hypochondrium. The diagnosis is con- MI, PE, endocrine disorders (e.g. hyperthyroidism),
firmed by ultrasonography. acute adrenocortical insufficiency, MH and many
- marked dehydration and metabolic alkalosis others. May occur postoperatively, especially in chil-
may be present. Resultant aldosterone secretion dren (in whom it has been reported in up to 40%
causes exchange of potassium and hydrogen ions of cases).
for sodium in the urine, resulting in hypokalaemia Management includes careful examination and
and hypochloraemia with paradoxical acid urine. investigation (including blood culture and culture
- treated initially by nasogastric drainage and res- of sputum, urine, wound; X-rays, etc.), removal/
toration of electrolyte/fluid balance, e.g. using replacement of catheters, and review of drug therapy.
0.9% saline followed by dextrosesaline with Symptomatic treatment includes surface or core
potassium supplementation according to plasma cooling and simple antipyretics. However, some
electrolyte analysis. suggest that antipyretics should not be administered,
- corrective surgery (pyloromyotomy; Ramstedts as they may have deleterious effects (they deny the
procedure) should only be performed following patient an important host defence mechanism and
adequate resuscitation, as indicated by clinical eliminate an important diagnostic aid). Empirical use
examination, good urine output, and normal acid of antibiotics to treat isolated pyrexia is rarely
base and electrolyte (especially chloride) status. advocated.
Anaesthetic management is as for paediatric Marik PE (2000). Chest; 117: 85569
anaesthesia, taking measures to avoid aspiration
of gastric contents. Rapid sequence induction is Pyridostigmine bromide. Acetylcholinesterase inhibi-
usual, but awake intubation and inhalational tor. Pyridine analogue of neostigmine, with slower onset
induction have been used. and longer duration of action. Also has weaker nicotinic
acquired: usually results from gastric carcinoma or action on voluntary muscle and less muscarinic action
ulcer. Metabolic features are similar to those above. on viscera. Used in myasthenia gravis but less useful than
Residual gastric contents may be voluminous. neostigmine for reversing non-depolarising neuromus-
[Wilhelm C Ramstedt (18671963), German surgeon] cular blockade. Half-life is 34h.
Dosage: 30120mg orally 412-hourly, up to
Pyrazinamide. Bactericidal antituberculous drug used 1.2g/day.
in combination with other drugs. Effectiveness lasts 23 Side effects: as for neostigmine.
 Q
Q wave. Initial downward deflection of the QRS complex Quality assurance. Systematic process by which the
of the ECG (see Fig. 59b; Electrocardiography). Small quality of care is examined and deficiencies analysed in
(q) waves are normal in leads aVL and I when left axis order to develop strategies for improvement.
deviation is present, and in leads II, III and aVF with Classically applies to three areas:
right axis deviation. They may be large in aVR. Patho- structure, i.e. the system in place, e.g. assessment of
logical (Q) waves are wide (e.g. > 3040ms) and deep staffing levels, equipment, type of patients.
(e.g. > 24mm, or more than a quarter of the height of process, i.e. how the care is delivered, e.g. anaes-
the R wave in the same lead). In the absence of left thetic techniques, monitoring.
bundle branch block they suggest MI, which may be old outcome, i.e. use of quality indicators, e.g. death
or of new onset; in acute S-T elevation MI, Q waves are rates, pain scores, patient satisfaction.
associated with poorer outcomes. Various methods of investigating each of these areas
Wong CK, Herbison P (2011). Int J Cardiol; 148: 3058 have been described, often translated from use in indus-
try or commercial business. Audit and risk management
QRS complex. Represents ventricular depolarisation; are commonly used in medicine. The drive for quality
normally follows the P wave of the ECG (see Fig. 59b; assurance programmes has come from clinical, adminis-
Electrocardiography). Upper-case letters are used if a trational and political quarters.
particular wave is considered large, lower-case if small. See also, Clinical governance; Healthcare Commission;
The initial deflection is termed the q (Q) wave if down- National Institute for Health and Clinical Excellence
ward, and R wave if upward. The downward S wave
follows an R wave. The QRS complex may be used to
Quantal theory. Widely accepted theory proposed in
calculate the electrical axis. Normally has rS pattern in
the 1960s to explain miniature end-plate potentials
V1, qR pattern in V6. The initial small deflection repre-
recorded from the neuromuscular junction postsynaptic
sents left-to-right septal depolarisation; the larger subse-
membrane, at approximately 2Hz. Postulates that small
quent deflection represents (mainly left) ventricular
quanta (packets) of acetylcholine are released ran-
depolarisation. Normal duration: < 0.12s. Abnormalities
domly from the nerve cell membrane, even in the
may represent arrhythmias, heart block, bundle branch
absence of motor nerve activity. Each quantum is thought
block or MI.
to be one vesicles content, about 400010000 acetylcho-
line molecules. During single motor nerve activation
QT interval. Represents the duration of ventricular
about 200 quanta are released into the synaptic cleft.
systole; varies with age, sex and heart rate. Measured
from the beginning of the QRS complex to the end of
the T wave of the ECG (see Fig. 59b; Electrocardiogra- Quantiflex apparatus. Continuous-flow anaesthetic
phy). Corrected for heart rate by dividing by the square machines that can deliver preset mixtures of O2 and N2O,
root of the preceding RR interval in seconds (Bazetts adjusted by a percentage control (minimum of 30% O2).
formula). Normal range is 0.350.43. A single dial adjusts total gas flow delivered. Individual
Shortened in hypercalcaemia, hyperkalaemia and flowmeters indicate flow of O2 and N2O; the O2 flowme-
digoxin therapy. Prolonged QT syndromes may be ter is usually on the right, and N2O flowmeter on the left.
caused by hypocalcaemia, hypothyroidism and hypo- They are sometimes used in dental surgery.
thermia, and are associated with recurrent syncope or
sudden death due to ventricular arrhythmias, including
Quincke, Heinrich Irenaeus (18421922). German phy-
VT and torsade de pointes.
sician; described and standardised lumbar puncture in
[H Cuthbert Bazett (18851950), English-born US
1891, originally as a treatment for hydrocephalus. Used
physiologist]
the paramedian approach and suggested 24 hours bed
rest afterwards. His bevelled needle design is still used
QTc dispersion. Difference between the longest and
for lumbar puncture and spinal anaesthesia. Quinckes
shortest measurable corrected QT interval on the
sign is pulsation in the nail capillary bed and is seen in
12-lead ECG. Originally described using manual calcula-
aortic regurgitation.
tion, although automatic measuring methods have been
Minagar A, Lowis GW (2001). J Med Biogr; 9: 1215
described. Has been shown to be a powerful predictor
of arrhythmias and sudden cardiac death in several
cardiac conditions. Quinidine. Class Ia antiarrhythmic drug. An isomer of
Suggested explanations for QTc dispersion include quinine. Used to treat SVT and VT, but rarely used now
patchy myocardial fibrosis and left ventricular dilatation, because of side effects. Peak plasma levels occur 12h
although the exact mechanism is unclear. following oral administration; half-life is 59h. Highly
Sahu P, Lim PO, Rana BS, Struthers AD (2000). Q J Med; protein-bound, it may displace digoxin if the two drugs
93: 42531 are given concurrently.

493
494 Quinine sulphate/dihydrochloride

Dosage: 200400mg orally tds/qds. 4-Quinolones. Class of broad-spectrum antibacterial

Side effects are common due to a low therapeutic drugs, which include ciprofloxacin, levofloxacin, moxi-
ratio and include ventricular arrhythmias (e.g. torsade floxacin and ofloxacin. More effective against Gram-
de pointes). Anticholinergic effects may result in GIT negative than Gram-positive bacteria, they have limited
disturbances; CNS effects (cinchonism) include tin- activity against anaerobes. Side effects include pro-
nitus and visual changes. Hypersensitivity reactions longed QT syndromes, spontaneous tendon rupture
include rash, haemolysis and thrombocytopenia. and muscle weakness. May also induce convulsions in
Severe overdose results in confusion and psychosis. susceptible individuals, especially if NSAIDs are taken
concurrently. They should be used with caution in hepatic
Quinine sulphate/dihydrochloride. Antimalarial drug, or renal impairment.
reserved for treatment (but not prophylaxis) of falci-
parum malaria. Also used to treat nocturnal leg cramps. Quinupristin/dalfopristin. Antibacterial drugs com-
Dosage bined in a 3:7 ratio, presented as a mixture of mesilates.
malaria: Active against Gram-positive bacteria (including staph-
- 600mg orally tds for 7 days. ylococci but excluding Enterococcus faecalis) resistant to
- 20mg/kg over 4h iv as initial dose (unless a other antibacterials. Inactive against Gram-negative
related drug has been given within 24h), then organisms.
10mg/kg over 4h tds until able to complete the Dosage: 7.5mg/kg iv via central vein bd for 710 days
7-day course with oral therapy. (inflammation, pain and other reactions are common
leg cramps: 200300mg orally at night. after peripheral administration).
Side effects: tinnitus, headache, visual disturbances Side effects: GIT disturbance, myalgia, rash, confu-
(cinchonism), GIT disturbances, hypersensitivity sion, hypotension, hepatic impairment; rarely, renal
(including thrombocytopenia and DIC), arrhythmias, impairment and blood dyscrasias.
renal failure, hypoglycaemia, convulsions.
 R
R on T phenomenon. Arises when the R wave of a and runs distally on the tendons and muscles attached
ventricular ectopic beat falls on the T wave of the pre- to the radius (biceps tendon, supinator, pronator teres,
ceding beat. At the middle of the T wave, the myocar- flexor digitorum superficialis, flexor pollicis longus, pro-
dium is partly depolarised and partly repolarised, and nator quadratus). Lies deep to brachioradialis muscle in
thus vulnerable to establishment of re-entrant and cir- the upper forearm, but subcutaneous in the lower
culatory conduction, leading to VF or VT. forearm and easily palpable, especially over the distal
quarter of the radius. Runs deep to abductor pollicis
R wave. First upward deflection of the QRS complex of longus and extensor pollicis brevis tendons at the radial
the ECG (see Fig. 59b; Electrocardiography). Tends to styloid, entering the anatomical snuffbox. Then enters
increase in size from V1 to V6, with an accompanying the palm between the first and second metacarpals,
reduction in size of S wave across these leads. Loss of forming the deep palmar arch. Branches include a super-
this R wave progression, with a sudden increase in R ficial palmar branch (enters the palm superficial to the
wave size in V5 or V6, may indicate old anterior MI. In flexor retinaculum), which supplies the muscles of the
V16, at least one normally exceeds 8mm, but none thenar eminence before anastomosing with the superfi-
exceeds 27mm. cial palmar arch. At the wrist, it is a common site for
palpation of the pulse and for arterial cannulation.
Rabeprazole sodium. Proton pump inhibitor; actions See also, Ulnar artery
and effects are similar to those of omeprazole.
Dosage: 20mg orally od.
Side effects: as for omeprazole.
Radial nerve (C5T1). Terminal branch of the posterior
cord of the brachial plexus. Descends in the posterior
upper arm, passing laterally behind the middle of the
Rabies. Infection caused by a lyssavirus of the rhabdo-
humerus in the radial groove. Crosses the antecubital
virus family, eradicated from Britain in 1902; however,
fossa anterior to the elbow joint, between brachialis and
occasional cases thought to have originated outside the
brachioradialis. Descends under brachioradialis lateral
UK have occurred in animals, e.g. dogs and bats. Fewer
to the radial artery in the forearm, passing posteriorly
than 5 cases occur annually in Europe and the USA.
proximal to the wrist to end on the dorsum of the hand
Spread mainly via domestic dogs and cats, but also by
as digital branches.
foxes, bats and other wildlife. Transmitted via infected Branches:
saliva penetrating broken skin or intact mucosa; the
axillary: to deltoid, teres minor and skin of the pos-
virus replicates in local muscle then migrates proximally
teromedial upper arm.
along peripheral nerves to dorsal root ganglia and the
upper arm:
CNS, eventually causing lethal encephalitis. Incubation
- to triceps, brachioradialis and extensor carpi radi-
period is usually 2090 days in humans, but may be 4
alis longus.
days to several years.
- skin of the lower posterolateral arm.
Malaise, fever, depression and psychosis may be fol-
forearm:
lowed by laryngeal spasm, and extreme anxiety on drink-
- to the elbow joint.
ing fluids. Respiratory and autonomic failure occurs
- posterior interosseous nerve arising at the elbow
early and cardiac involvement, including myocarditis, is
joint: passes posteriorly round the radial neck to
common.
supply the elbow, wrist and intercarpal joints, and
Treatment of established rabies includes injection of
all extensor muscles of the forearm apart from
human anti-rabies immunoglobulin, early IPPV, seda-
extensor carpi radialis longus.
tion and paralysis, with careful maintenance of acidbase
- via digital branches to the lateral side of the
and fluid balance. Almost inevitably fatal once estab-
dorsum of the hand and posterior aspects of the
lished (death typically occurs 210 days after symptoms
lateral 2.5 digits up to the distal phalanx.
appear), it may be prevented by wound cleaning and
May be blocked at the elbow, wrist, and at mid-humerus
active and passive immunisation.
with the elbow flexed (the nerve is palpable in the radial
Warell MJ (2008). Curr Opin Infect Dis; 21: 2517
groove).
See also, Brachial plexus block; Elbow, nerve blocks;
Radford nomogram. Diagram showing the relationship
Wrist, nerve blocks
between tidal volume, patients weight and respiratory
frequency. Used to aid appropriate selection of ventila-
tor settings for children and adults. Now rarely used. Radiation. Emission of energy in the form of waves or
[Edward P Radford (19222001), US physiologist] particles. Includes emission of electromagnetic waves
(e.g. light), most of which is non-ionising (does not
Radial artery. Terminal branch of the brachial artery. have sufficient energy to overcome electron binding
Arises in the antecubital fossa, level with the radial neck, energy). Ionising radiation may result in displacement of

495
496 Radiography in intensive care

electrons in organic material with the potential for tissue iodine-123 accumulates in a clot and may be used to
damage, and includes: detect DVT. Therapeutic use includes radiotherapy.
particles: helium nuclei consisting of two protons See also, Radioisotope scanning
and two neutrons. Have high energy but penetrate
matter poorly. Radiological contrast media. Contain large molecules
particles: electrons or positrons with variable that absorb X-rays (e.g. barium [enteral] or iodine
energy and velocity. Those with high energies are [enteral or iv]) or have paramagnetic properties (e.g.
more penetrating than particles but much less gadolinium) for MRI scanning. Adverse reactions may
than -rays and X-rays. follow iv injection:
-rays and X-rays: electromagnetic waves emitted related to high osmolality (up to 7 that of plasma):
from (-rays) or outside (X-rays) the nuclei of - initial hypervolaemia followed by osmotic diure-
excited atoms. Have extremely high penetration of sis and hypovolaemia.
matter and thus pose a health hazard requiring - damage to red blood cells and vascular
radiation safety precautions. -Rays are used in endothelium.
radiotherapy and imaging, and X-rays in imaging. immunological:
Exposure to ionising radiation is kept to a minimum with - reactions range from mild symptoms to cardiovas-
appropriate storage and handling of radioisotopes, cular collapse and death.
minimal use of X-rays and appropriate use of shielding. - adverse reactions are most likely to be due to
Formal training is required for those performing or direct histamine release or complement activa-
directing radiology procedures. tion. True anaphylaxis is not thought to occur.
See also, Environmental safety of anaesthetists direct toxicity: myocardial depression and systemic
vasodilatation.
Radiography in intensive care. Increasingly used as the Thus initial hypertension may be followed by prolonged
range and quality of techniques and equipment available hypotension. Renal failure may result from cardiovascu-
increase. Consultation with radiologists aids the proper lar changes plus direct toxicity.
selection and interpretation of many imaging techniques. Incidence of reactions and renal failure is decreased
In most cases, the use of mobile equipment results in less by using low osmolar, non-ionic media. Other measures
than optimal results but may be acceptable given the to prevent renal injury include adequate hydration and
difficulty of transporting critically ill patients from the administration of N-acetylcysteine. Resuscitation equip-
ICU; subtle changes between sequential films may be ment and drugs must always be available.
misleading if this is not taken into account. Investiga- Dickinson MC, Kam PCA (2008). Anaesthesia; 63:
tions include CXR, ultrasound and CT and MRI scan- 62634
ning; bedside CT scanners are now available but MRI See also, Adverse drug reactions
requires transport to the imaging department. Radioiso-
tope scanning usually requires transfer from the ICU. Radiology, anaesthesia for. Most radiological proce-
Practical considerations include the requirement for dures require neither general anaesthesia nor sedation.
sedation and adequate monitoring during transport or Anaesthesia may be required for the very young, con-
the procedure itself, the interference of the procedure fused or agitated patients and those with movement
with background therapy including the requirement disorders. Procedures include CT scanning, MRI, angi-
for moving the patient (e.g. to place films underneath), ography and invasive procedures, e.g. embolisation of
and the potentially adverse effects of radiological con- vascular lesions in neuroradiology.
trast media. Main anaesthetic considerations:
See also, Imaging in intensive care underlying disease process.
remote location, often cramped conditions, with
Radioisotope scanning. Use of radioisotopes to label poor lighting.
certain parts of the body in order to investigate organ old or incomplete anaesthetic/monitoring equip-
function, either directly or attached to circulating cells. ment.
Includes the following: poor access to the patient.
assessment of blood flow: cerebral blood flow, renal adverse effects of radiological contrast media.
blood flow, lung perfusion scans (e.g. combined with specific problems of MRI.
ventilation scans in suspected PE). Preoperative assessment and preparation should be as
nuclear cardiology. for any anaesthetic procedure.
localisation of lesions: PE, bone metastases/
infection/fracture, intra-abdominal sepsis. Radiotherapy. Use of ionising radiation to treat neo-
The radiation contained within the body after scanning plasms. May involve:
is negligible, posing no risk to staff. external radiation.
implantation of internal sources (brachytherapy),
Radioisotopes. Isotopes of elements that undergo dis- e.g. in gynaecological or CNS tumours.
integration; i.e. the nucleus emits , or radiation administration of radioactive radioisotopes, e.g.
either spontaneously or following a collision. Used clini- iodine-131 in hyperthyroidism, phosphorus-32 in
cally as labels to determine fluid compartments, blood polycythaemia.
flow, pulmonary V /Q distribution and sites of infection. General anaesthesia is rarely required, except when
Technetium-99m and xenon-133 are often suitable patients are uncooperative, i.e. mainly children and
because they are easy to use and their half-lives are patients with movement disorders. Anaesthetic
short. Also used to label metabolically active substances considerations:
which are taken up by certain tissues, allowing imaging general condition of the patient: features of
of the tissue concerned, e.g. fibrinogen labelled with malignancy, site and nature of the neoplasm and
 RBBB 497

drug therapy. Haematological abnormalities are lasts about 8h. Half-life is about 2h. Undergoes hepatic
common. metabolism and is excreted via urine, hence the dose is
repeated anaesthetics: multiple treatments are reduced in renal failure.
required, e.g. daily for several weeks. Consider- Dosage:
ations include fear of injections and repeated 50mg iv/im tds. Effective if given 4560min preop-
periods of starvation (especially important in chil- eratively. If administered iv, 50mg should be diluted
dren). IV cannulation may be difficult, although into 20ml and injected over at least 2min, since
long-term catheters are often sited. severe bradycardia may occur. May also be given by
immobilisation of the head may be required, e.g. for continuous infusion: 125250g/kg/h.
CNS tumours; clear plastic casts that cover the 150300mg orally bd. For prophylaxis against aspi-
whole face are often used, with risks of airway ration pneumonitis, 150mg orally qds (e.g. in
obstruction. Head-down positioning may be labour), or 2h preoperatively (preferably preceded
required. by 150mg the night before).
treatments usually consist of short periods of radia- Side effects: blood dyscrasias, impaired liver function
tion (e.g. a few minutes), during which the anaes- and confusion; all are rare.
thetist cannot be present. Monitoring is usually
visible via remote-control cameras, but may be Ranking, see Statistical tests
restricted.
Techniques used include sedation or general anaesthesia Raoults law. The addition of a solute to an ideal solu-
using TIVA with propofol, or intermittent boluses of tion reduces the vapour pressure of the solvent in pro-
ketamine (especially in children). portion to the molar concentration of the solute.
Patients formerly treated by radiotherapy may have [Franois M Raoult (18301901), French scientist]
inflammatory or fibrotic changes in the irradiated area. See also, Colligative properties of solutions
Pulmonary, cardiac, neuroendocrine, renal and hepatic
involvement may be present. Tissue fibrosis around the RAP, Right atrial pressure, see Cardiac catheterisation;
airway may make tracheal intubation difficult. Central venous pressure
McFadyen JG, Pelly N, Orr RJ (2011). Curr Opin Anaes-
thesiol; 24: 4338 Rapacuronium bromide. Non-depolarising neuromus-
cular blocking drug, introduced in the USA in 1999
Randomisation. Technique for allocating subjects (e.g. and withdrawn in 2001 just before its introduction in the
patients to treatment groups in clinical trials) that UK, because of reports of fatal bronchospasm. Chemi-
reduces allocation bias when samples are compared. cally related to vecuronium, it causes rapid onset of
Ensures that factors such as age, sex and weight are neuromuscular blockade (tracheal intubation possible
randomly distributed amongst the groups; i.e. any differ- within 60s) with fast recovery (630min depending on
ence in these factors is due to chance alone. dosage) and was thus suggested as an alternative to
Randomisation may be: suxamethonium.
simple: no restriction on allocation. Groups may be
unequally sized. Rapid opioid detoxification. Technique for treating
block: allocation is performed in blocks, so that opioid addiction by precipitating withdrawal using
groups are equally sized within each block. opioid receptor antagonists, e.g. naloxone or naltrexone,
stratified: factors such as age and sex are randomised supposedly reducing relapse rates compared with con-
separately, so that they are equally distributed ventional management. Ultra-rapid opioid detoxifica-
amongst the groups. A more sophisticated method, tion refers to administration of general anaesthesia or
minimisation, involves the distribution of successive heavy sedation for prolonged periods to reduce aware-
subjects to the groups by taking into account the ness or recall of unpleasant withdrawal symptoms whilst
number of subjects already allocated who have the opioid antagonists are given. The technique is con-
these various factors, using a scoring system. For troversial (especially the ultra-rapid form) since deaths
example, if age, weight and female sex are felt to be have occurred and supportive evidence for its efficacy
important prognostic factors in a particular study, is poor.
an obese subject may still be allocated to a group Singh J, Basu D (2004). J Postgrad Med; 50: 22732
that already has several obese subjects in it, if there
are fewer older subjects and females than in the Rapid sequence induction, see Induction, rapid
other groups. sequence
Computer-generated random numbers are usually
employed. Use of coins or dice is tedious and presents Ratepressure product (RPP). Product of heart rate
the temptation to repeat an allocation if the result is not and systolic BP, used as an indicator of myocardial work-
liked. Other methods have also been used, e.g. allocation load and O2 consumption. It has been suggested that
of alternate patients, or according to patients birthdays RPP should be maintained below 15 000 in patients with
or record numbers. However, these methods cannot ischaemic heart disease during anaesthesia. Its useful-
always be guaranteed free of hidden bias. ness has been questioned, since a proportional increase
in rate may increase myocardial O2 demand more than
Ranitidine hydrochloride. H2 receptor antagonist; the same increase in BP. A pressurerate quotient (MAP/
better absorbed and more potent than cimetidine, with rate) of < 1 has been suggested as being a better predic-
fewer side effects. Does not inhibit hepatic enzymes or tor of myocardial ischaemia.
interfere with metabolism of other drugs. Oral bioavail-
ability is about 50%. Plasma levels peak within 15min RBBB, Right bundle branch block, see Bundle branch
of im injection and 23h after oral administration; effect block
498 RDS

RDS, see Respiratory distress syndrome ASA system) or nominal (e.g. presence of different
features on the ECG to diagnose MI) scales. They may
Reactance. Portion of impedance to flow of an alternat- also be drawn for different tests in the same plot, allow-
ing current not due to resistance; e.g. due to capacitance ing comparison between the tests. They also allow selec-
or inductance. Given the symbol X, and measured in tion of the best cut-off to use clinically, usually the
ohms. uppermost and most left-hand part of the curve, being
[Georg S Ohm (17871854), German physicist] the best compromise between sensitivity and specificity.
They are increasingly used to analyse the usefulness of
Rebreathing techniques, see Carbon dioxide tests or scoring systems in anaesthesia and intensive
measurement care, including difficult tracheal intubation and other
outcomes.
Receiver operating characteristic (ROC) curves. Galley HF (2004). Br J Anaesth; 93: 6236
Curves drawn to indicate the usefulness of a predictive
test, originally derived from analysis of radar signals
Receptor theory. States that receptors are specific pro-
between the World Wars (i.e. did a deflection represent
teins or lipoproteins located on cell membranes or
a real signal or just random noise; and if the former, with
within cells that interact selectively with extracellular
what degree of certainty?). For the test to be analysed
compounds (agonists) to initiate biochemical events
(e.g. the usefulness of ASA physical status to predict
within cells. The structures of the agonist and receptor
mortality after anaesthesia), each cut-off level is exam-
determine the selectivity and quantitative response.
ined in turn, and sensitivity and specificity calculated for
Drugs that interact with the receptor and inhibit the
it. Thus, for example, an ASA grade of 1 has high sensi-
effect of an agonist are antagonists. Degree of binding
tivity (all deaths have an ASA grade of 1 or above) but
to receptors is affinity; ability to produce a response is
low specificity (most patients with a grade of 1 or above
intrinsic activity.
do not die). For an ASA grade of 2, sensitivity is a little
Initial assumptions that the degree of response is pro-
lower (some patients who die have a grade of 1, and will
portional to the number of receptors occupied are not
not be predicted by a grade of 2) whilst specificity is
universally accepted. Other suggestions include:
higher, although still poor (a grade of 2 is better at pre-
reduced occupancy is required for a potent agonist
dicting death than a grade of 1, although most patients
compared with a less potent agonist, to produce the
achieving 2 or above still do not die). The process con-
same response.
tinues until grade 5, which has low sensitivity (few of the
degree of response is proportional to the rate of
deaths have a grade of 5) but high specificity (most
receptoragonist interaction and dissociation.
patients who are graded 5 do, by definition, die). Sensi-
Interaction of drug and receptor may resemble
tivity is plotted against (1 specificity) and a curve
MichaelisMenten kinetics. Covalent, ionic and hydro-
obtained (Fig. 133); the area under the curve (AUC)
gen bonding, and van der Waals forces may be involved.
represents the usefulness of the test: a perfect test Different types of receptor:
includes 100% of the available area and one where pre-
ligand-gated ion channels: direct opening of mem-
diction is no better than chance, 50%.
brane pores allowing passage of ions (e.g. Na+, K+,
ROC curves may be drawn using continuous (e.g.
Ca2+, Cl) across the membrane, e.g. nicotinic acetyl-
C-reactive protein to predict infection), ordinal (e.g.
choline receptor. Typically fast responses (< 1ms).
G protein-coupled receptors: binding to the recep-
tor causes a change in the guanine binding proper-
ties of the neighbouring G protein, which then leads
1 to the intracellular response, e.g. adrenergic recep-
100 tors. Typically of the order of many milliseconds to
2 A
seconds.
3 ligand-activated tyrosine kinases: binding at the cell

B surface causes activation of tyrosine kinase at the

Sensitivity (%)

inner surface of the cell, which catalyses phosphory-

lation of target proteins via ATP, e.g. insulin recep-
C tors. Typically minutes to hours.
4
nuclear receptors: the lipid-soluble agonist passes
through the cell membrane to interact with the
D
receptor, leading to alteration of DNA transcrip-
tion, e.g. corticosteroid and thyroid hormones.
5
0 Typically up to several hours.
E Expression of receptors varies. Chronic stimulation (e.g.
0 100
1 specificity (%) asthmatics taking 2-adrenergic receptor agonists)
results in a decreased number of receptors (downregula-
tion) whereas understimulation (e.g. following spinal
AUC = 78% cord injury) leads to an increased number of receptors
AUC = 56% (upregulation).
See also, Doseresponse curves; Pharmacodynamics
Fig. 133 Examples of two receiver operating characteristic curves for
the usefulness of two different five-point scales (15 and AE) for
predicting an outcome. The 15 scale performs better than the AE Recommended International Non-proprietary
scale. The dotted line denotes the curve for a test where prediction is Names (rINNs), see Explanatory Notes at the beginning
no better than chance of this book
 Recovery position 499

Record-keeping. The first anaesthetic chart was devised communicate. The anaesthetist is responsible for
by Codman and Cushing in 1894 at the Massachusetts removal of tracheal tubes.
General Hospital, for recording of respiration and pulse O2 should be administered at least until awake.
rate. BP charting was included in 1901 at Cushings insis- level of consciousness, arterial O2 saturation, BP,
tence. FIO2 was included by McKesson in 1911. heart rate, respiratory rate, pain intensity, iv infu-
Careful record-keeping is now recognised as sions and drugs administered (including O2) should
essential to chart preoperative risk factors, the periop- be recorded, along with other variables as appropri-
erative course of anaesthesia and postoperative events/ ate (e.g. temperature, urine output).
instructions. It is particularly useful when taking over there should be criteria for discharge, including full
another anaesthetists anaesthetic, and for providing consciousness, clear airway, respiratory and cardio-
information to those administering anaesthesia subse- vascular stability, adequate postoperative analgesia
quently. Similarly, ICU records should chart physiologi- and control of PONV, stable temperature and pre-
cal data, therapy and instructions relating to the stay of scription of postoperative drugs, including O2 and
any patient in an ICU. Record-keeping is also important iv fluids as appropriate. There should be adequate
for teaching, research and audit, and is extremely impor- handover during discharge from the recovery area.
tant in medicolegal aspects of anaesthesia. Although children should be recovered in a designated area.
tending to include similar information, anaesthetic and Patients are often placed on their side, e.g. the recovery
intensive care charts are not standardised nationally, position. In the tonsillar position, the pillow is placed
although this has been suggested. under the loin and the trolley tipped head-down.
Automated anaesthetic record systems are increas- Problems during recovery:
ingly used, sometimes incorporated into anaesthetic respiratory, e.g. hypoventilation, hypercapnia,
machines or ICU monitoring systems. They provide hypoxaemia, airway obstruction, bronchospasm,
accurate, legible and complete documents for data aspiration of gastric contents.
acquisition and subsequent scrutiny. Data from monitor- cardiovascular, e.g. hypotension, hypertension,
ing devices are incorporated with information provided arrhythmias, myocardial ischaemia.
by the anaesthetist/intensive care staff (e.g. drug or other confusion and agitation. Pain and bladder disten-
interventions), although lack of familiarity with key- sion are common causes of restlessness and hyper-
boards or computers may be a hindrance. tension postoperatively. The above causes must also
Postoperative recovery and progress may be recorded be excluded.
on separate charts, or on the anaesthetic chart. related to anaesthetic drugs, e.g. inadequate rever-
[Ernest A Codman (18691940), US surgeon] sal of non-depolarising neuromuscular blockade,
adverse drugs reactions, MH, dystonic reactions,
Recovery from anaesthesia. Period from the end of emergence phenomena, central anticholinergic
surgery to when the patient is alert and physiologically syndrome.
stable. Definition is difficult because some drowsiness hypothermia, nausea and vomiting, shivering.
may persist for many hours. Recovery testing is used for related to surgery, e.g. bleeding.
more precise investigation. Time to recovery depends on The speed and quality of recovery from anaesthesia have
the patients condition, drugs given, their doses, and the been proposed as a possible measure of quality of
patients ability to eliminate them. For inhalational anaesthesia.
anaesthetic agents, similar considerations as for uptake See also, Anaesthetic morbidity and mortality
are involved, plus length of operation and degree of
redistribution to fat. Thus blood gas solubility is the most Recovery position. Position recommended for uncon-
important factor initially, but more potent agents (e.g. scious but spontaneously breathing subjects, assuming
isoflurane) are more extensively bound to fat after pro- no contraindication, e.g. cervical spine injury. Encour-
longed anaesthesia than less potent ones, e.g. desflurane. ages a clear airway and drainage of vomitus, secretions
For iv anaesthetic agents, initial recovery is due to drug and blood away from the airway. Often used during
redistribution from vessel-rich to vessel-intermediate recovery from anaesthesia.
tissues; subsequent course is related to the rate of clear- Any recovery position is a compromise between the
ance from the body. Thus propofol characteristically full prone position (better airway and drainage but more
results in rapid clear-headed emergence, whereas thio- diaphragmatic splinting) and the full lateral position (less
pental is more likely to produce drowsiness lasting diaphragmatic splinting but less effective for the airway
several hours, especially after repeated dosage. Recom- and less stable; also may be harmful in neck injury). Clas-
mendations for provision of recovery care (Association sically includes flexion of both arms with the upper hand
of Anaesthetists): placed under the jaw to support the airway (Fig. 134).
designated recovery rooms or areas should be used.
during transfer to the recovery area O2 should
be administered, and appropriate monitoring
performed.
the anaesthetist should formally hand over the
patients care to properly trained staff, giving
details of the operation, anaesthetic technique,
preoperative morbidity, perioperative problems,
including blood loss, and antiemetic and analgesic
drugs given.
all patients should be observed by at least one
member of staff until there is a clear airway
and cardiovascular stability, and they are able to Fig. 134 Recovery position
500 Recovery room

The actual position adopted should reflect the particular - perception of auditory stimuli in a similar
circumstances of the case and the need to protect the fashion, including discrimination between left
airway, stabilise the neck and allow unhindered ventila- and right ears.
tion. It should be possible to observe the patient at memory:
all times and to turn him/her supine easily when - recall or recognition of objects, pictures, words or
required. word associations shown a short time before.
- orientation in time and space.
cognitive function, e.g. adding/subtracting numbers,
Recovery room. An area reserved for postoperative
or adding values of different coins.
care was described by Florence Nightingale in 1863, but
physiological function, e.g. divergence of eyes
the first dedicated recovery room was opened in the
caused by reductions in extraocular muscle tone.
USA in 1923. Many more were introduced there after
Problems of detailed recovery testing are related to the
experiences in World War II and the Korean War. First
time taken, cumbersome equipment required, fatigue,
introduced in the UK in 1955.
Features:
boredom and learning if tests are repeated. Critical
flickerfusion, reaction testing, letter deletion and
staffed by fully trained personnel.
memory tests are most widely used and thought to be
placed near the operating suite, if possible near
reasonably efficient, the first two especially so. General
ICU.
advice to patients is usually to avoid potentially danger-
open ward, allowing good patient observation.
ous activities (e.g. driving, cooking, using machinery) for
at least two bays per operating theatre are
24h following day-case anaesthesia, although subtle
recommended.
changes may persist beyond this period; 48h has been
each bay is equipped for monitoring (ECG, BP, O2
suggested.
saturation) and patient care (suction, O2).
a supply of iv equipment and fluids, blankets and
Rectal administration of anaesthetic agents. Results
airways should be available.
in effective absorption of drugs because of a rich blood
resuscitation equipment, ventilator and drugs
supply provided by communicating plexuses formed by
should be readily available, with an emergency call
the superior, middle and inferior rectal arteries and
system.
veins. Drugs undergo minimal first-pass metabolism,
adequate ventilation is required to remove exhaled
because the plexuses are anastomoses between portal
anaesthetic gases.
Drugs available should include:
and systemic circulations. The technique is usually
restricted to children. Traditionally used more in conti-
analgesics, antiemetics, sedatives, anticonvulsants,
nental Europe, e.g. France. Drugs used have included
naloxone, flumazenil.
diazepam 0.40.5mg/kg (widely used for treatment of
doxapram, bronchodilators, corticosteroids,
convulsions in children), methohexital 1525mg/kg and
antihistamines.
thiopental 4050mg/kg as 510% solutions. Opioids and
anticholinergics, antiarrhythmics, antihypertensives,
ketamine have also been given in this way. Diethyl ether
diuretics, heparin.
was administered rectally by Pirogoff. Bromethol and
antibiotics, anticholinesterases, neuromuscular
paraldehyde were used in the 1920s to produce uncon-
blocking drugs, insulin, dextrose, dantrolene.
sciousness (basal narcosis).
local anaesthetics, lipid emulsion.
[Florence Nightingale (18201910), English nurse]
Rectus sheath block. Performed as part of abdominal
See also, Recovery
field block or alone to reduce pain from abdominal inci-
sions. Abdominal contents are not anaesthetised.
Recovery testing. Ranges from simple clinical assess- With the patient supine, a blunted needle is intro-
ment to more sophisticated methods, e.g. used for experi- duced 36cm above and lateral to the umbilicus. A
mental comparison between anaesthetic techniques and gentle scratching motion may aid identification of the
drugs. Routine testing is usually limited to assessment of tough anterior layer of the sheath, puncture of which is
general alertness and orientation, and ability to respond, accompanied by a click. The needle is advanced up to
drink, dress and walk where appropriate (e.g. day-case the resistance offered by the posterior layer of the
surgery). sheath, and 1520ml local anaesthetic agent injected
Sophisticated techniques used include tests of: after negative aspiration. Deposition of solution between
psychomotor function: rectus muscle and posterior layer allows spread up and
- assessing speed and number of errors made whilst down, blocking the lower 56 intercostal nerves within
performing set tasks: the sheath. Spread between the muscle and anterior
- moving pegs from one set of holes in a board to layer is limited by the tendinous intersections along its
another set. length. Multiple injections have been suggested between
- deleting every letter p from a page of text. intersections, to improve spread, but the posterior layer
- connecting dots on a page. is deficient below a point halfway between the umbilicus
- reaction testing: and pubis, and peritoneal puncture is more likely below
- being faced with four light sources, and pressing this level.
the correct switch (out of four choices) when
one of them flashes. Recurarisation. Recurrence of non-depolarising neuro-
- tracking moving targets with a pen or light. muscular blockade after apparent reversal with acetyl-
perception: cholinesterase inhibitors. Originally described with
- noting the frequency at which a flashing light tubocurarine in patients with impaired renal function,
appears to be continuous (critical flickerfusion where the duration of action of the neuromuscular
threshold). blocking drug exceeds that of the acetylcholinesterase
 Regional anaesthesia 501

inhibitor. Has been described with other neuromuscular sense organ, afferent neurone, one or more synapses,
blocking drugs. efferent neurone and effector. The afferent neurones
enter the spinal cord via dorsal roots or brain via cranial
Red cell concentrates, see Blood products nerves; the efferent neurones leave via ventral nerve
roots or corresponding motor cranial nerves. Also
Reducing valve, see Pressure regulators involved in autonomic functions. The simplest reflex arc
is monosynaptic, e.g. knee jerk and other stretch reflexes
Refeeding syndrome. Clinical syndrome seen after involving muscle spindles. Polysynaptic reflex arcs (two
reintroduction of nutrition to previously starved patients, or more synapses) include the withdrawal reflex. Wide-
often seen on ICU. First noted after World War II, when spread effects may result from activation of a single
malnourished prisoners of war inexplicably died of reflex arc because of ascending, descending, excitatory
cardiac failure after receiving a normal diet. Associated and inhibitory interneurones.
with any condition leading to malnutrition (e.g. anorexia
nervosa, alcoholism, intra-abdominal sepsis). Reflex sympathetic dystrophy, see Complex regional
Pathophysiology: pain syndrome
restoration of carbohydrates as a dietary substrate
leads to increased insulin secretion and activation Reflux, see Gastro-oesophageal reflux
of anabolic pathways. Hypophosphataemia, hypo-
magnesaemia, hypokalaemia and vitamin deficiency Refractometer, see Interferometer
(particularly thiamine) may follow due to increased
intracellular uptake on a background of whole body Refractory period. Period during and following the
depletion. action potential during which the neurone is insensitive
depletion of ATP and 2,3-DPG leads to tissue to further stimulation. Subdivided thus:
hypoxia and mitochondrial dysfunction. absolute: excited by no stimulus, however strong.
Clinical features: relative: excitation may follow stronger stimuli than
hyperglycaemia and electrolyte disturbances as normal.
above.
sodium and fluid retention. Refrigeration anaesthesia. Use of cold to reduce pain
cardiac failure, arrhythmias. sensation. Used by Larrey in 1807, although the effect
muscle weakness, contributing to respiratory failure of cold on pain has been recognised for centuries. Up to
and difficulty weaning from ventilators. 3h packing in ice was recommended for operations
Wernickes encephalopathy due to thiamine through the thigh. The principle is still used today, e.g.
deficiency. ethyl chloride spray.
Prevention and treatment:
correction of electrolyte deficiencies before reintro- Regional anaesthesia. Term originally coined by
ducing feeding. Cushing to describe techniques of abolishing pain using
gradual introduction and escalation of caloric local anaesthetic agents as opposed to general anaesthe-
intake, with close monitoring of electrolytes and sia. Pioneers included Halstead, Corning and Labat in
replacement as required. the USA and Bier, Braun and Lawen in Europe.
vitamin supplementation. Techniques include:
close attention to fluid balance to prevent fluid topical anaesthesia.
overload. infiltration anaesthesia, Vishnevisky technique and
Byrnes MC, Stangenes J (2011). Curr Opin Clin Nutr tumescent anaesthesia.
Metab Care; 14:18692 peripheral nerve blocks: plexus and single nerve
blocks.
Referred pain. Pain felt in a somatic site remote to the central neuraxial blockade: epidural and spinal
source of pain, usually visceral; e.g. diaphragmatic pain anaesthesia.
is felt in the shoulder tip. The aetiology is obscure, but is IVRA and intra-arterial regional anaesthesia.
thought to be related to the embryological segment from sympathetic nerve blocks.
which the organ arose, e.g. diaphragm from the neck others, e.g. interpleural analgesia.
region, and heart from the same region as the arm. Advantages of regional anaesthesia:
Theories include: conscious patient, able to assist in positioning,
convergence: somatic and visceral afferents con- and warn of adverse effects (e.g. in carotid endar-
verge on the same spinothalamic tracts. The brain terectomy and TURP). There is less interruption
assumes that neural activity in a particular pathway of oral intake, especially beneficial in diabetes
arises from somatic input, rather than visceral, since mellitus.
the former is far more common than the latter. good postoperative analgesia.
facilitation: input from visceral afferents increases reduction of certain postoperative complications,
sensitivity of neurones receiving somatic afferents, e.g. atelectasis and DVT, possibly myocardial
thus promoting somatic sensation. ischaemia.
Effects of local anaesthetic injected at referred areas are Contraindications:
inconsistent, supporting both theories (should ease the absolute: patient refusal, anaesthetists inexperi-
pain if facilitation is responsible, but not if convergence ence and localised infection.
is responsible). relative: abnormal anatomy or deformity, coagula-
tion disorders, previous failure of the technique,
Reflex arc. Involves predictable, repetitive stereotypic and neurological disease or other medicolegal
responses to a particular sensory stimulus. Consists of considerations.
502 Regional tissue oxygenation

Specific contraindications may exist for specific excessive spread, e.g. total spinal block during epi-
techniques. dural anaesthesia, or phrenic nerve block during
Management: brachial plexus block.
preoperatively: failure of the technique.
- preoperative assessment and preparation as for those of specific techniques, e.g. hypotension follow-
general anaesthesia. ing spinal anaesthesia.
- full explanation of the procedure, and consent. others, e.g. injection of the wrong solution through
- preparation of drugs and equipment for catheters.
general anaesthesia and resuscitation, in addition See also, specific blocks; Nerve injury during anaesthesia
to those required for the regional technique
chosen. Regional tissue oxygenation. Important because shock
perioperatively: and hypoxaemia cause redistribution of blood flow and
- monitoring should be applied as for general alter the metabolic properties of cells; global measure-
anaesthesia, i.e. before starting the procedure and ments thus fail to detect areas of local ischaemia. Mea-
continued throughout it. surement of regional tissue oxygenation may be useful
- aseptic technique should be observed. in critically ill patients because deficiencies may be
- for nerve or plexus blocks, short-bevelled needles involved in the development and continuation of MODS.
are traditionally used to minimise nerve contact, Lack of evidence of benefit and technical difficulties have
although nerve damage may be greater should the hindered the more intricate techniques from becoming
nerve be impaled. Nerve stimulators (using 0.3 routine practice. Methods of assessment include:
1.0mA current lasting 12ms and delivered at blood lactate levels (> 2mmol/l suggests insufficient
13Hz) increase the success of many blocks and oxygen delivery): a late marker.
may reduce damage further. A distant ground mixed venous O2 saturation (Sv O 2), measured using
electrode is required. The needle (preferably repeated blood sampling or continuous oximetry
sheathed) is placed near the target nerve and via a pulmonary artery catheter. Regional Sv O 2 (e.g.
stimulated until paraesthesia or twitches are elic- hepatic = Shv O 2; jugular = Sjv O 2) can be determined
ited; the output is reduced, the needle reposi- using indwelling catheters.
tioned and the process repeated. intestinal regional capnography (i.e. gastric tonom-
Ultrasound imaging is increasingly used to etry). Measures PCO2 in an air- or saline-filled tono-
guide needle placement. The appearance of metric balloon, placed in the GIT.
nerves is variable but usually distinct from that of surface or tissue O2 electrodes: based upon the
other tissues. Addition of colour Doppler imaging Clark electrode (see Oxygen measurement), they are
identifies blood vessels. Claimed advantages formed of a noble metal (e.g. gold, silver, platinum).
include more accurate placement of the needle, Change in voltage between the anode and cathode
especially if anatomy is abnormal, reduced volume is proportional to the amount of O2 reduced at the
of injectate required, greater success rate and cathode.
reduced complication rate. optode sensors: use the change in the optical prop-
- a single injection of local anaesthetic, repeated erties (e.g. absorbance or fluorescence) of indicator
boluses (using repeated injections or a catheter) substances generated by photochemical reactions to
or continuous infusions may be used. measure the concentration of a substance (e.g. O2)
- the extent of the block should be assessed (e.g. by in tissues. Can be mounted in intravascular cathe-
response to pinprick or cold) before allowing ters (e.g. Paratrend monitor).
surgery to start. near infrared spectroscopy.
- if sedation is used, care should be taken to ensure reflectance spectrophotometry. Measures the
that respiratory and cardiovascular depression absorption of reflected visible light on a tissue
does not occur. Analgesic drugs (e.g. N2O or surface, e.g. gut wall, fetal scalp.
opioid analgesic drugs) may be used to supple- nicotinamide adenine dinucleotide (NADH) fluo-
ment incomplete blockade. General anaesthesia rescence: during tissue hypoxia, NADH accumu-
may be used as a planned part of the technique, lates in tissues. The absorption properties of NADH,
or if the technique is unsuccessful. and its reduced state, NAD+, are different. Tissue
postoperatively: catheters have been used in both animal and human
- close monitoring and supervision should continue models.
as for general anaesthesia. imaging using online microscopic observation of the
- patients should be advised to protect insensate microcirculation.
limbs e.g. using a sling for upper limb blocks. Dyson A, Singer M (2011). Curr Opin Crit Care; 17:
- patients should be warned of potentially unpleas- 2819
ant paraesthesia as the block recedes.
- neurological complications may only become Regression, see Statistical tests
apparent once the block has worn off.
Complications: Regurgitation. Term usually describing passive passage
technical: direct trauma to nerves, blood vessels and of gastric contents into the pharynx. Silent, thus aspira-
pleura, breakage of needles or catheters. tion of gastric contents may occur unnoticed. Normally
associated with positioning of the patient, e.g. com- prevented by the lower oesophageal sphincter; however,
pression of an anaesthetised limb. swallowed dyes have been found to stain areas of
local anaesthetic toxicity: intravascular injection or the pharynx and larynx during/after anaesthesia in
systemic absorption. normal patients.
 Renal blood flow 503

Relative analgesia. Technique used in dental surgery infusions may be due to upregulation of NMDA recep-
involving nasal administration of subanaesthetic concen- tors. Has been used via patient-controlled analgesia
trations of N2O, e.g. 10% in O2, slowly increased to 30 during labour (see Obstetric analgesia and anaesthesia).
50%. Verbal contact is maintained at all times, and the Not recommended for epidural or spinal use since the
concentration of N2O reduced if excessive drowsiness formulation contains glycine. Postoperative respiratory
occurs. Performed by the dentist, it depends partly on depression may occur if any drug is left in the dead space
suggestion. of iv lines and subsequently flushed with other drugs or
fluids.
Relative risk reduction. Indicator of treatment effect in Dosage:
clinical trials. For a reduction in incidence of events from to supplement induction of anaesthesia: 0.51.0g/
a% to b%, it equals ([a b] a)%. Gives an overesti- kg/min, initial bolus of 1.0g/kg over at least 30s.
mated impression of treatment effect if events are rare, during anaesthesia: 0.052.0g/kg/min during
and an underestimate if events are common. IPPV; 0.0250.1g/kg/min during spontaneous ven-
See also, Absolute risk reduction; Meta-analysis; Number tilation. For target-controlled infusions, a plasma
needed to treat; Odds ratio concentration of 38ng/ml will generally achieve
adequate intraoperative analgesia (very stimulating
Relatives of critically ill patients. Present particular procedures may require up to 15ng/ml).
challenges to ICU staff because of the serious nature of
the patients condition, unfamiliarity with the ICU envi- Remote ischaemic preconditioning, see Ischaemic
ronment and the natural behavioural responses to preconditioning
extreme stress, including fear, anger and guilt. The sud-
denness of many severe conditions may exacerbate rela- Renal blood flow (RBF). Normally 1200ml/min
tives distress. Relatives must be kept informed about (400ml/100g/min); i.e. 22% of cardiac output.
the patients progress, preferably by a consistent single Measurement:
senior doctor accompanied by a member of the nursing direct: circumferential electromagnetic flow mea-
staff; they should also feel included in discussions about surement, Doppler or thermodilution techniques.
treatment (including its withdrawal). indirect:
Honest and clear explanations, using lay language, - clearance methods: a substance neither metabo-
may need repeating several times and the potential frus- lised nor taken up by the kidney, and completely
tration felt by the medical team must not be transmitted cleared, is required, e.g. para-amino hippuric acid
to the relatives. Most ICUs have a separate room for (PAH). Clearance then equals renal plasma flow.
interviews with patients families and friends, which is RBF = plasma flow divided by (1 haematocrit).
preferable to the open ward or corridor. In general, few Continuous iv infusion of PAH is required; inac-
restrictions are placed on visiting times, and most rela- curacies may occur since clearance of PAH is only
tives appreciate and respect the need for staff to perform 90% in humans. Radioactive markers have been
basic care and procedures during which they may be used; almost 100% cleared, they require only a
asked to leave the unit. However, some may choose to single injection.
stay and participate in some aspects of their relatives - digital subtraction angiography and radioactive
care, e.g. washing or shaving. Counselling and religious inert gas washout techniques have also been used,
support may be required and is often best arranged via the latter indicating regional blood flow.
the ICU staff. Affected by:
Whether relatives should witness attempts at resusci- arterial BP: maintained by autoregulation at MAP
tation (e.g. in casualty departments) has attracted recent between 70 and 170mmHg in normal subjects.
debate, with some welcoming the opportunity for rela- sympathetic nervous system: stimulation causes
tives to see that appropriate attempts to save the patient vasoconstriction and reduction of RBF, and also
are being made, whilst others argue that their presence increases release of renin and prostaglandins.
may be stressful for medical and nursing staff. Dopamine may increase RBF by vasodilatation via
Curtis JR, White DB (2008). Chest; 134: 83543 dopamine receptors.
renin/angiotensin system: angiotensin II decreases
Remifentanil. Ultra-short-acting synthetic opioid anal- RBF via vasoconstriction, and increases aldoste-
gesic drug, 2000 times more potent than morphine, intro- rone secretion. The latter increases fluid retention,
duced in the UK in 1997. Available as a white powder which inhibits further renin release.
for reconstitution to a 0.1% solution which is stable for vasopressin: causes renal vasoconstriction, espe-
24h at room temperature. Further diluted for adminis- cially cortical.
tration; in adults a 50g/ml solution is recommended by intravascular volume: in haemorrhage, autoregula-
the manufacturer. Approximately 70% protein-bound. tion is overridden, with vasoconstriction and intra-
Rapidly metabolised by non-specific plasma and tissue renal redistribution of blood away from the cortex.
esterases to remifentanil acid (very low potency) and prostaglandins: increase cortical blood flow, and
excreted renally. Its context-sensitive half-life is about reduce medullary blood flow.
3min regardless of the duration of infusion; thus pro- atrial natriuretic peptide: causes vasodilatation,
vides a rapid recovery when stopped. although effects on RBF are unclear. May alter
Because it is cleared so rapidly and completely, blood flow distribution.
patients very soon experience pain postoperatively RBF and GFR are reduced by most anaesthetic agents,
unless longer-acting analgesics are given before discon- mainly via reduced cardiac output and BP. Volatile
tinuation. In addition, it has been suggested that the agents are also thought to interfere with autoregulation,
hyperalgesia that can occur following remifentanil although some benefit may arise from the vasodilatation
504 Renal failure

they cause, maintaining blood flow. Urine output there- - pre-existing arteriovenous fistulae or shunts
fore often falls perioperatively. should be noted.
Other factors include pre-existing renal disease or - premedication as required.
conditions predisposing to renal failure or impairment, perioperatively:
e.g. vascular surgery, toxic drugs, trauma, jaundice, - iv cannulae should not be sited near arteriove-
hypovolaemia. nous fistulae, which should be loosely padded for
protection.
Renal failure. Loss of renal function causing abnormali- - potassium-containing iv fluids should be avoided.
ties in electrolyte, fluid and acidbase balance with - drugs whose actions are not terminated by renal
increases in plasma urea and creatinine. Divided into excretion are preferred. Thus a common tech-
acute and chronic renal failure. nique consists of propofol followed by atracurium
Acute renal failure (see Acute kidney injury for defini- and isoflurane, sevoflurane or desflurane.
tions, diagnosis and management). - drugs that accumulate in renal failure (e.g. mor-
Chronic renal failure (CRF): phine) should be used with caution. Patients are
irreversible, and often follows acute kidney injury. more sensitive to many iv agents, including
glomerulonephritis is the most common cause, with opioids, because of smaller volumes of distribu-
others, including pyelonephritis, diabetes, polycystic tion and reduced plasma protein levels.
disease, vascular disease and hypertension, drugs - suxamethonium is not contraindicated unless
and familial causes. there is pre-existing peripheral neuropathy or
features (may not be present until GFR falls below hyperkalaemia.
15ml/min): - nephrotoxic drugs (e.g. NSAIDs) should be
- malaise, anorexia, confusion leading to con avoided. Enflurane has been avoided because of
vulsions and coma. Peripheral and autonomic fluoride ion formation, although the need for this
neuropathy may occur. is controversial. Previous concerns regarding
- oedema, pericarditis, hypertension (in 80%; sevoflurane and compound A formation are not
thought to result from increased renin/angiotensin thought to be relevant in humans.
system activity, sodium and water retention and - regional techniques are often suitable, e.g. bra-
secondary hyperaldosteronism), peripheral vas- chial plexus block for fistula formation.
cular disease, cardiac failure. Ischaemic heart postoperatively: close attention to fluid balance is
disease is 20 times more common in CRF patients. required.
- nausea, vomiting, diarrhoea. Dennen P, Douglas IS, Anderson R (2010). Crit Care
- osteomalacia, muscle weakness, bone pain, hyper- Med; 38: 26175
parathyroidism, hyperphosphataemia.
- amenorrhoea, impotence. Renal failure index, see Renal failure
- pruritus, skin pigmentation, poor healing,
increased susceptibility to infection. Renal transplantation. First performed in 1950, and
- normocytic normochromic anaemia: caused by now widespread but limited mainly by the supply of
reduced erythropoietin production, shortened kidneys. Cadaveric graft survival is up to 8090% at 2
red cell survival and bone marrow depression. years. Previously considered an emergency and per-
Impaired platelet function may cause bruising formed on unprepared patients, but the importance of
and bleeding. proper preoperative assessment and preparation is now
- hypernatraemia or hyponatraemia may occur. generally accepted. Dialysis is usually performed within
Hyperkalaemia is usual, but hypokalaemia may 24h before surgery.
follow diuretic therapy. Acidosis is common. Anaesthetic problems and techniques are as for
management: chronic renal failure and transplantation. Additional
- reduction of dietary protein. points:
- control of hypertension and cardiac failure. general anaesthesia is preferred, although epidural
- erythropoietin is increasingly used for anaemia. and spinal anaesthesia have been successfully used.
- dialysis. direct arterial blood pressure measurement is not
- renal transplantation. necessarily required (although ischaemic heart
Anaesthesia in renal failure: disease and cardiac failure are common in these
preoperatively: patients); CVP monitoring is routinely used to
- features of the underlying disease must be guide perioperative fluid therapy. Optimal hydra-
assessed, e.g. diabetes, hypertension. tion is vital to support graft function.
- assessment for the above features of renal failure, mannitol, furosemide, calcium channel blocking
in particular cardiovascular complications, fluid drugs and dopamine are sometimes given before
and electrolyte and acidbase derangements. the vessels to the new kidney are unclamped, in
Dialysis may be required; if it has been recently order to stimulate urine production and improve
performed, patients are often hypovolaemic, and renal function.
therefore vulnerable to perioperative hypoten- transient hypertension may follow unclamping of
sion. Anaemia rarely requires transfusion because the renal vessels.
of its chronicity with compensatory mechanisms. there is an increased incidence of kidney rejection
Patients may be at risk from aspiration of gastric in patients who have received blood transfusion
contents if autonomic neuropathy is present. during transplantation; preoperative correction of
- drugs taken commonly include antianginal anaemia with erythropoietin should be considered.
and antihypertensive drugs, insulin and Both live and cadaveric donors should be well
corticosteroids. hydrated to maintain urine output before harvesting.
 Respiratory distress syndrome 505

Sarinkapoor H, Kaur R, Kaur H (2007). Acta Anaesthe- oedema and free radicals. Although any tissue may be
siol Scand; 51: 135467 affected, most work has focused on cardiac function fol-
See also, Organ donation lowing hypoxic insult or hypoperfusion. Arrhythmias
and myocardial stunning (reversible impairment of
Renal tubular acidosis. Group of conditions character- cardiac function) may also follow reperfusion.
ised by decreased ability of each nephron to excrete See also, Isoprostanes, No reflow phenomenon
hydrogen ions (cf. renal failure, where the overall number
of functioning nephrons is reduced, but those that Reptilase time, see Coagulation studies
remain excrete more hydrogen ions than normal). Char-
acterised by normal GFR, metabolic acidosis, hyper- Reserpine. Antihypertensive drug, rarely used now
chloraemia and a normal anion gap. May be associated because of its unfavourable side-effect profile. Depletes
with distal tubule dysfunction (type 1), proximal tubule postganglionic adrenergic neurones of noradrenaline by
dysfunction (type 2; usually associated with other abnor- irreversibly preventing its reuptake from axoplasm into
malities of proximal tubule function, e.g. Fanconis syn- storage vesicles. Crosses the bloodbrain barrier and
drome), or aldosterone deficiency or resistance (type 4). depletes central amine stores. Effects may last 12 weeks.
Type 3 is now considered a combination of types 1 and Side effects include bradycardia and postural hypo-
2 and not a separate entity. Acidosis may be severe, and tension, depression, sedation and extrapyramidal signs.
accompanied by marked hypokalaemia (hyperkalaemia No longer available in the UK.
in type 4). Treatment includes alkali (e.g. oral sodium
bicarbonate) in types 1 and 2, thiazides in type 2 and Reservoir bag. Usually 2 litre capacity in most adult
mineralocorticoid therapy in type 4. anaesthetic breathing systems and 0.51.0 litre for pae-
[Guido Fanconi (18921979), Swiss paediatrician] diatric use; its volume must exceed tidal volume. Move-
Reddy P (2011). Int J Clin Pract; 65: 35060 ment indicates ventilation, but estimation of tidal volume
from the degree of movement is inaccurate. Made of
Renin/angiotensin system. Renin, a proteolytic enzyme rubber (increasingly, latex-free), distending when under
(mw 37kDa), is synthesised and secreted by the juxta- pressure; maximal pressure is thus prevented from rising
capillary apparatus of the renal tubule. Formed from two above about 60cmH2O (Laplaces law).
precursors, prorenin and preprorenin, its half-life is
about 80min. Secretion is increased in hypovolaemia, Residual volume (RV). Volume of gas remaining in the
cardiac failure, cirrhosis and renal artery stenosis. Secre- lungs after maximal expiration. About 1.5 litres in the
tion is decreased by angiotensin II and vasopressin. average 70kg male; measured as for FRC. Increased RV
Renin cleaves the circulating glycoprotein angiotensino- accounts for most cases of increased FRC.
gen with subsequent production of the peptides angio-
tensin I, II and III, involved in arterial BP control and Resistance. In electrical terms, the ratio of the potential
fluid balance (Table 38). Angiotensin I is a precursor for difference across a conductor to the current flowing
angiotensin II, a powerful vasoconstrictor with a half-life through it (Ohms law). Measured in ohms (). Resis-
of a few minutes. It causes aldosterone release from the tance to flow of a fluid through a circular tube is analo-
adrenal cortex, and noradrenaline release from sympa- gous to this; it equals the ratio of the pressure gradient
thetic nerve endings. It also stimulates thirst and release along the tube to the flow through it.
of vasopressin, and acts directly on renal tubules, result-
ing in sodium and water retention. Some may also be Resistance vessels. Term given to those blood vessels
produced in the tissues. Angiotensin III also causes involved in regulation of SVR. 50% of resistance to
aldosterone release and some vasoconstriction. blood flow is due to arterioles, which are thus the main
Angiotensin converting enzyme inhibitors and angio- regulators of SVR and therefore distribution of cardiac
tensin II receptor antagonists are used to treat hyperten- output.
sion. Aliskiren, a direct renin inhibitor, has recently been
introduced. Resonance. Situation in which an oscillating system
Angiotensin II or its analogues have been used as responds with maximal amplitude to an alternating
vasopressor drugs when -agonists are unable to correct external driving force. Occurs when the driving force
severe hypotension, e.g. during surgery for hepatic frequency coincides with the natural oscillatory fre-
tumours secreting vasodilator substances. quency (resonant frequency) of the system. May occur
in pressure transducer systems if long, compliant tubing
Reperfusion injury. Tissue injury resulting from restora- is used. May give rise to artefacts in the arterial wave-
tion of blood flow after a period of ischaemia. Mecha- form during direct arterial BP measurement.
nisms include intracellular calcium excess, cellular
Resonium, see Polystyrene sulphonate resins

Table 38 Peptides of the renin/angiotensin system

Respiration, see Breathing ; Lung ; Metabolism

Substance Converted to By the action of Site Respirators, see Ventilators

Angiotensinogen Angiotensin I Renin Plasma Respiratory centres, see Breathing, control of

Angiotensin I Angiotensin II Angiotensin Mainly in
converting lungs Respiratory depression, see Hypoventilation
enzyme
Angiotensin II Angiotensin III Aminopeptidase Many tissues Respiratory distress syndrome (RDS; Hyaline mem-
brane disease). Occurs in approximately 1% of all live
506 Respiratory exchange ratio

births, almost exclusively in premature babies. Caused Respiratory muscle fatigue. Inability of the respiratory
by deficiency of surfactant. Surfactant is normally detect- muscles to sustain tension with repeated activity. May be
able in the fetal lung at 24 weeks gestation, although caused by:
reversal of amniotic fluid lecithin/sphingomyelin ratio decreased central drive, e.g. caused by CNS depres-
(related to fetal lung maturity) only occurs at 30 weeks. sant drugs (e.g. opioid analgesic drugs).
Decreased lung compliance, increased work of breathing increased ventilatory load caused by increased
and alveolar collapse may lead to respiratory failure, airway resistance and reduced compliance (e.g.
with characteristic granular appearance of the CXR. asthma, COPD) or increased demand (e.g. exercise,
Treatment is directed towards preventing hypoxae- fever, hypoxaemia).
mia with CPAP initially, although IPPV is usually neces- respiratory muscle weakness (e.g. following pro-
sary, whilst trying to avoid O2 toxicity, barotrauma and longed IPPV, malnutrition, electrolyte imbalance,
retinopathy of prematurity. Exogenous surfactant given thyroid disorders, neurological disease, hypoxae-
immediately after birth decreases mortality. Extracorpo- mia, sepsis).
real membrane oxygenation has been used. Causes hypercapnic respiratory failure and difficulty in
weaning from ventilators. Treatment is directed at the
Respiratory exchange ratio. Estimation of respiratory underlying cause.
quotient derived from expired CO2/inspired O2 mea- Tobin MJ, Laghi F, Brochard L (2009). J Appl Physiol;
surements, thus dependent on ventilation. 107: 96270

Respiratory failure. Defined as an arterial PO2 < 8kPa Respiratory muscles. Muscle actions during:
(60mmHg) breathing air at sea level, and at rest, without quiet inspiration:
intracardiac shunting. - diaphragm (the most important muscle of respira-
Divided into: tion) flattens and moves 12cm caudally.
type I failure: hypoxaemia with normal or low arte- - external intercostal muscles (fibres pass down-
rial PCO2. Usually due to V/Q mismatch, with intra- wards and forwards) lift the upper ribs and
pulmonary right-to-left shunt if severe. Causes sternum up and forwards, and the lower ribs
include chest infection, asthma, pulmonary embolus, mainly up and outwards. The first rib remains
pulmonary oedema, PE, ARDS, aspiration pneu- fixed.
monitis. O2 therapy improves hypoxaemia due to forced inspiration: as above, with the diaphragm
V /Q
 mismatch but not shunt; the response to breath- descending up to 10cm, plus accessory muscles:
ing 100% O2 may indicate the degree of shunt. PCO2 - scalene muscles.
is often low because of hyperventilation in response - sternomastoid.
to hypoxaemia. - serratus anterior.
type II failure (ventilatory failure): hypoxaemia - pectoralis major.
accompanied by arterial PCO2 > 6.5kPa (49mmHg). - ala nasi.
Causes are as for hypoventilation. Acute exacerba- quiet expiration: passive recoil of chest and
tion of COPD is a common cause. abdomen.
Diagnosis is made by arterial blood gas interpretation, forced expiration:
but may be suspected clinically by signs of hypoxaemia - mainly abdominal muscles (internal and external
and hypercapnia, with tachypnoea and use of accessory oblique, rectus abdominis).
respiratory muscles. - internal intercostal muscles (pass downwards and
Treatment: backwards); opposite action to the external inter-
of underlying cause. costals, and prevent intercostal bulging.
sitting the patient up increases FRC and often
improves oxygenation. Respiratory quotient (RQ). Ratio of the volume of
oxygen therapy: should be used cautiously in type CO2 produced by tissues to the volume of O2 consumed
II failure if chronic hypercapnia is suspected. per unit time. At rest, it depends on the type of substrate
aminophylline may have an inotropic action on the being utilised: RQ of carbohydrate is 1, RQ of fat 0.7
diaphragm and may reduce respiratory muscle and that of protein about 0.82. Also depends on the ratio
fatigue; it is often used in neonates. of aerobic to anaerobic respiration that is occurring;
carbonic anhydrase inhibitors may increase respira- after strenuous exercise RQ may rise transiently to up
tory drive in COPD associated with hypercapnia. to 2 (due to excess lactic acid reacting with available
respiratory stimulant drugs (e.g. doxapram) have bicarbonate).
been used to avoid IPPV, e.g. in COPD. Whole body RQ calculated by measurement of
CPAP or non-invasive positive pressure ventilation expired CO2 and inspired O2 only approximates to true
may improve oxygenation and ventilation, avoiding RQ, since these volumes are affected by respiration. The
the need for tracheal intubation. term respiratory exchange ratio (R) is therefore becom-
IPPV may be required if PCO2 is rising or the patient ing more commonly used for this measurement.
is exhausted. Criteria similar to those used in
weaning from ventilators have been suggested for Respiratory sounds. Traditionally assessed with a
institution of IPPV. Tracheostomy may be necessary stethoscope, more recently analysed by digital process-
to aid weaning from mechanical ventilation. ing using microphones or accelerometers placed on the
intravenous oxygenator, extracorporeal oxygen- chest wall. Sounds arise from vibration of airways and
ation and extracorporeal CO2 removal have movement of fluid films within them. The nature of the
been used. sounds depends on the tissue through which they pass,
e.g. quiet or absent in pleural effusion and pneumotho-
Respiratory function tests, see Lung function tests rax, increased transmission in consolidation. The pitch is
 Retrobulbar block 507

related to the size of the airway involved and the density rotation of a double-vaned turbine within the
of the gas. chamber. Rotation is measured and displayed as the
Classification: volume of gas passing through the device, using an
basic sounds: arise from: indicator needle attached to the vane, and a dial.
- central airways of the lung. Normally audible Electrical versions are also available; rotations of a
throughout inspiration and the beginning of expi- disc attached to the vane interrupt passage of light
ration, with a gap between the two. between an emitter and photosensitive cell mounted
- large airways and trachea. Typically audible astride the disc. Less prone to inertia inaccuracies
throughout both inspiratory and expiratory than the Wrights respirometer.
phases, with no gap. Usually audible only over the Wrights respirometer: measures gas volume passing
trachea, this bronchial breathing sound may be in one direction only; thus it may be placed in the
heard over the chest if transmitted to the stetho- two-way portion of a breathing system. It tends to
scope via abnormally solid tissue (e.g. consoli- underestimate at low volumes and overestimate at
dated lung). high volumes, due to inertia/momentum of the vane.
Range from under 100Hz to over 10003000Hz. others: include flowmeters, whose signals may be
adventitious sounds: integrated to indicate volume.
- wheezing: arises from the central/lower airways [B Martin Wright (19122001), London engineer]
with a sinusoidal frequency (polyphonic), ranging See also, Spirometer
from 100Hz to over 1000Hz.
- rhonchi: snore-like, arise from the larger airways. Resuscitation, see Cardiopulmonary resuscitation
Typically under 300Hz and rapidly damped, but
lasting over 100ms. Occur in small airway col- Resuscitation Council (UK). Multiprofessional group
lapse and secretions. formed in 1981 to facilitate education of lay and profes-
- crackles: fine; arise from the lower airways. sional members of the population in the most effective
Rapidly damped, typically lasting under 20ms. methods of resuscitation. Aims of the Council include:
Occur in secretions, oedema and fibrosis. encouraging research and study of resuscitation tech-
Other sounds may occur (e.g. stridor), although not from niques; the promotion of training and education in resus-
the lung itself. citation; and the establishment and maintenance of
Gurung A, Scrafford CG, Tielsch JM, Levine OS, standards. The Council has published guidelines for CPR
Checkley W (2011). Respir Med; 105: 1396403 and has set up a series of advanced courses in adult and
paediatric resuscitation (i.e. ALS, ILS).
Respiratory stimulant drugs, see Analeptic drugs; See also, European Resuscitation Council
Opioid receptor antagonists
Resuscitators, see Self-inflating bags
Respiratory symbols. By convention, standardised thus:
general variables: Reteplase. Recombinant plasminogen activator, used as
V = gas volume } with a dot above = a fibrinolytic drug in management of acute coronary
Q = volume of blood } volume per unit time syndromes. Has a longer half-life (1316min) than
P = pressure or tension alteplase.
F = fractional concentration in dry gas mixture Dosage: 10U iv in under 2min, repeated after 30min.
f = respiratory frequency Side effects: as for fibrinolytic drugs. May precipitate
C = content of a gas in blood with heparin solutions.
D = diffusing capacity
R = respiratory exchange ratio Reticular formation/activating system, see Ascending
S = saturation of haemoglobin with O2 or CO2 reticular activating system
A dash above a symbol indicates mean value.
localisation (in subscript): Retinopathy of prematurity (Retrolental fibroplasia).
I = inspired gas Abnormal proliferation of retinal vessels in response to
E = expired gas high arterial PO2 for long periods. Very premature infants
A = alveolar gas of low birth weight are the most susceptible, remaining
T = tidal gas so until 44 weeks postconceptual age. O2 therapy should
D = dead space gas therefore be monitored closely. Precise mechanisms
B = barometric are unclear, as it may occur in infants who have not
a = arterial blood received additional O2. Genetic factors appear to be
c = pulmonary capillary blood important. The role of O2 administered during anaesthe-
v = venous blood sia is controversial, but FIO2 is generally thought to
e.g. FIO2 = inspired fractional concentration of O2; be best restricted to 0.3 unless higher concentrations
PaO2 = arterial O2 tension. are required to maintain arterial PO2 of 8.511kPa
SpO2 has been suggested as representing haemoglobin (6080mmHg).
saturation as measured by pulse oximetry. Saugstad OD (2006). J Perinatol 26 (Suppl 1): S4650

Respirometer. Device for measuring expiratory gas Retrobulbar block. Performed to allow surgery to the
volumes. Examples: globe of the eye, e.g. cataract extraction. Cranial nerves
Wrights anemometer (axial turbine flowmeter): a III and VI, and long and short ciliary nerves (branches
design commonly integrated into ventilators. of V1) are blocked within the cone formed by the extra-
Expired gas is passed into its chamber through ocular muscles. Now rarely used due to its relatively
oblique slits, creating circular gas flow that causes high frequency of complications, including retrobulbar
508 Retrolental fibroplasia

haemorrhage, intravascular and subarachnoid injection (Rh)-positive and -negative usually refer to the D
and globe perforation. Peribulbar block and sub-Tenons antigen, as it is the most immunogenic. Rh-negative indi-
block are safer and equally effective alternatives. viduals have no D antigen, and form anti-D antibodies
With the patient supine and looking straight ahead, a when injected with Rh-positive blood. 85% of Cauca-
3.0cm needle is inserted through the conjunctiva at the sians are Rh-positive, 99% of Orientals.
lower lateral orbital rim. It is passed backward and 10 Clinical importance:
upward until its tip has passed the mid-globe, then blood transfusion reactions: administration of
angled medially and upward to reach a point behind the Rh-positive blood to Rh-negative individuals who
globe at the level of the iris. After aspiration, 24ml have anti-D antibodies following previous exposure
lidocaine with hyaluronidase 5U/ml is injected. to Rh-positive blood.
See also, Orbital cavity haemolytic disease of the newborn: occurs in
Rh-positive fetuses of Rh-negative mothers. Passage
Retrolental fibroplasia, see Retinopathy of prematurity of fetal blood cells into the maternal circulation
during pregnancy or labour causes formation of
Retzius cave block. Used to supplement anaesthesia for maternal anti-D antibodies. These may pass into
prostatectomy and bladder surgery. The cave of Retzius subsequent Rh-positive fetuses, causing haemolysis,
is the space between the bladder and pubic symphysis, which may be fatal. Incidence of primary immunisa-
containing nerves of the sacral plexus and a venous tion in primigravidae is about 15%. Uncommon
plexus. After subcutaneous infiltration 23cm above the now with widespread availability of anti-Rh immu-
pubis, an 8cm needle is directed to the back of the sym- noglobulin, which is administered to Rh-negative
physis. After negative aspiration for blood, 10ml local mothers at delivery, and after abortion or amnio-
anaesthetic agent with adrenaline is injected in the centesis. Routine administration of anti-Rh to all
midline, with a further injection on each side. Rh-negative pregnant women has been suggested
[Anders Retzius (17961860), Swedish anatomist] as a way of reducing the problem further.

Reuben valve, see Non-rebreathing valves Rheumatic fever. Acute systemic autoimmune disease
occurring after infection by certain serotypes of group
Revised trauma score (RTS). Trauma scale derived A streptococci. Most common between 5 and 15 years
from the trauma score but simplified and with greater of age; now rare in the West but still common in develop-
emphasis on the presence of head injury. Uses the ing countries. Typically occurring 26 weeks after a
Glasgow coma scale, systolic BP and respiratory rate, sore throat, features include fever, flitting arthritis, car-
each assigned a value of 04 according to deviation from ditis, chorea and erythema marginatum (erythema
normal, with 0 representing the most severe. The values spreading out from a central macule whilst the centre
are added to give a total RTS, with a normal of 12. Supe- returns to normal). Subcutaneous nodules (Aschoff
rior to the trauma score at predicting outcome; a RTS bodies) may occur over the extensor surfaces of the
of < 4 suggests the need for transfer to a specialist wrists, elbows and knees. Epistaxis and abdominal pain
trauma unit. are common.
Gilpin DA, Nelson PG (1991). Injury; 22: 357 Diagnosed clinically and by evidence of recent strep-
tococcal infection. Traditionally treated with rest, peni-
Reyes syndrome. Rare condition of unknown aetiology, cillin, aspirin and corticosteroids, but the effect of drugs
characterised by vomiting, depression of consciousness on valve disease is controversial. 50% of patients with
and hepatic failure. Jaundice is typically absent or carditis progress to valvular heart disease, which may not
minimal. Usually occurs in children, typically following present until later in life. Mitral and aortic valves are
a viral illness; aspirin has been implicated in epidemio- most commonly affected.
logical studies and is thus contraindicated under 16 years Anaesthetic management of patients previously
of age. Thought to be due to an acquired mitochondrial affected is directed towards any existing valve disease
abnormality. Treatment is mainly supportive, with cor- and associated complications (e.g. cardiac failure, pul-
rection of metabolic disturbances, cerebral oedema and monary hypertension).
raised ICP. Thought to be improved by administering up [Karl Albert Ludwig Aschoff (18661942), German
to a third of the fluid intake as 10% dextrose. pathologist]
[R Douglas Reye (19121977), Australian pathologist] Carapetis JR, McDonald M, Wilson NJ (2005). Lancet;
366: 15568
Reynolds number (Re). Dimensionless number pre- See also, individual valve lesions
dicting when flow of a fluid becomes turbulent:
density velocity diameter of tube Rheumatoid arthritis (Rheumatoid disease). Systemic
Re = inflammatory disease with many features of connective
viscosity tissue diseases. Characterised by symmetrical polyar-
Turbulent flow occurs at Re > 2000, laminar flow at < thropathy, but affects other organs too. Three times more
2000. common in females; peak incidence is at ages 3050 years.
[Osborne Reynolds (18421912), Irish-born English Up to 5% of females over 60 years are affected in the
engineer] UK. Aetiology is unclear but may involve an immuno-
logical process triggered by infectious agents coupled
Rhabdomyolysis, see Myoglobinuria with a genetic predisposition. Recent advances in treat-
ment, including early therapy with disease-modifying
Rhesus blood groups. System of blood group antirheumatic drugs (DMARDS), including biological
antigens first described in 1939 following work on rhesus agents which block tumour necrosis factor, appear to
monkeys. Includes many antigens but the terms Rhesus improve the course and severity of the condition.
 Ribs 509

Anaesthetic considerations: Side effects are rare but include anaemia and worsen-
systemic effects: ing respiration.
- skeletal: temporomandibular joint involvement,
atlantoaxial subluxation, reduced mobility of the Rib fractures. Middle ribs are most commonly affected.
lumbar/cervical spine. Fracture usually occurs at the posterior axillary line, the
- neuromuscular: nerve entrapment, sensory/motor point of maximal stress. If the first three ribs are affected,
neuropathy, myopathy. injury to the aorta and tracheobronchial tree should be
- respiratory: restrictive defect due to pulmo- considered. If the lower ribs are involved, damage to
nary fibrosis and costochondral disease, pulmo- liver, spleen and kidneys may occur. Pneumothorax and
nary nodules, pleural effusions, cricoarytenoid haemothorax may be present.
arthritis. Rib fractures cause pain on breathing, with splinting
- cardiovascular: ischaemic heart disease (often of the chest wall, inability to cough and atelectasis. Mul-
with silent MI), pericarditis, heart block, coro- tiple fractures may cause flail chest. The mainstay of
nary arteritis, peripheral vasculitis. treatment is good analgesia; this may involve systemic
- haematological: anaemia (usually normochromic analgesics, epidural anaesthesia or intercostal nerve
normocytic), leucopenia. Feltys syndrome con- block.
sists of rheumatoid arthritis, splenomegaly and General management is as for chest trauma and
leucopenia; thrombocytopenia, malaise and fever abdominal trauma.
may occur.
- renal: amyloidosis, pyelonephritis, drug-related Ribs. Exist in 12 (thoracic) pairs, with occasional addi-
impairment. tional cervical or lumbar ribs. Attached to thoracic ver-
- others: ophthalmic complications, including tebrae posteriorly and costal cartilage anteriorly. Ribs
Sjgrens syndrome, and atrophic skin and subcu- 28 are typical (Fig. 135a), consisting of:
taneous tissues.
drug therapy: may include NSAIDs, corticosteroids
(a)
and immunosuppressive drugs. Gold may cause
blood dyscrasias, peripheral neuritis, pulmonary
fibrosis, hepatic and renal impairment. Penicilla-
mine may cause blood dyscrasias, renal impair-
ment, neuropathy and a myasthenia gravis-like
syndrome.
Shaft
practical considerations:
- airway maintenance difficulties: caused by
involvement of the temporomandibular joint, cer-
vical spine and larynx. Clinical evidence of laryn-
geal involvement should prompt a preoperative
nasendoscopy to assess degree of laryngeal steno- Subcostal groove
sis. The value of preoperative cervical spine
Lower articular
X-rays is uncertain; flexion/extension radiographs
facet
may worsen atlantoaxial subluxation, are often
diagnostically adequate, and may not alter anaes- Head
thetic technique (although proven cervical insta-
bility mandates minimal neck manipulation). Neck
- venous cannulation may be difficult; skin and
veins are fragile, and joints may have reduced
mobility. Tubercle Angle
- discomfort lying flat; skeletal involvement may
make regional techniques unsuitable. Careful
positioning and padding are required. Skin is (b)
easily damaged.
- wrist and hand arthritis may preclude the use of
patient-controlled analgesia.
[Augustus R Felty (18951963), US physician; Henrik SC
Sjgren (18991986), Swedish ophthalmologist] Scalenus medius
Samanta R, Shoukrey K, Griffiths R (2011). Anaesthesia;
66: 114659
See also, Intubation, difficult
Scalenus anterior Groove for subclavian
Ribavirin (Tribavirin). Antiviral drug; a nucleoside, it a and brachial plexus
inhibits DNA synthesis and is active against many RNA Groove for subclavian v
and DNA viruses, although usually reserved for treat-
ment of respiratory syncytial viral infection and Lassa
fever. Also used in combination with interferon alfa for
the treatment of chronic hepatitis C.
Dosage: nebulisation or aerosol inhalation of 20mg/
ml solution for 1218h for 37 days. For hepatitis C, Fig. 135 Anatomy of (a) a typical rib, seen from undersurface; (b) the
400600mg orally bd. first rib, seen from above
510 Rifabutin

head: bears two facets for articulation with adjacent A modified version, the AKIN (Acute Kidney Injury
vertebrae. Network) classification, includes the following changes:
neck. stages 13 corresponding to RIF categories; removal
tubercle: articulates posteriorly with the transverse of Loss and End-stage categories.
process of the corresponding vertebra. addition of an absolute increase in Cr of 26.5 mol/l
shaft: flattened in the vertical plane. Curves for- to stage 1.
wards and inwards from the angle, lying lateral to 48h timeframe specified for period of
the tubercle. The intercostal neurovascular bundle deterioration.
runs in the subcostal groove at the inferior border. patients receiving renal replacement therapy auto-
The first rib is of particular anaesthetic importance matically classed as stage 3.
because of its relationship to the brachial plexus and diagnostic criteria to be applied only after fluid
other structures (Fig. 135b). Features: optimisation.
short, wide and flattened in the horizontal plane. Borthwick E, Ferguson A (2010). Br Med J; 340: 8591
lower surface is smooth and lies on pleura.
upper surface is grooved for the subclavian vessels Right atrial pressure, see Cardiac catheterisation;
and brachial plexus. Central venous pressure
sympathetic chain, superior intercostal artery and
upper branch of the first intercostal nerve lie ante- Right ventricular function. The right ventricle (RV)
rior to its neck, between it and the pleura. receives blood from systemic and coronary veins, and
scalenus anterior and medius attach to the scalene pumps it into the left ventricle (LV) across the pulmo-
tubercle and body of the rib respectively. nary vascular bed. The pulmonary bed is of low resis-
See also, Intercostal nerve block; Intercostal space tance, therefore RV pressures (1525/812mmHg) are
lower than systemic. The low intraventricular pressure
Rifabutin. Antituberculous drug used for prophylaxis permits right coronary blood flow to be continuous
against Mycobacterium avium in immunocompromised throughout the cardiac cycle. The output of the right
patients. heart is influenced by its preload, contractility and
Dosage: prophylaxis: 300mg orally od; treatment: afterload.
150450mg od. The RV is very compliant and, when afterload
Side effects: blood dyscrasias, nausea, vomiting, increases (e.g. because of pulmonary vascular resistance
hepatic impairment, orange discoloration of body secondary to lung injury), the RV dilates. The end-
secretions. diastolic volume may increase to a greater extent than
the preload; consequently, the RV ejection fraction will
decrease markedly with increasing afterload. Changes in
Rifampicin. Antibacterial drug, used primarily as an the geometry of the RV affect the function of the LV,
antituberculous drug but also in brucellosis, Legion- and vice versa (ventricular interdependence), e.g.
naires disease, severe staphylococcal infection, leprosy impaired RV function (whether acute or chronic) may
and as prophylaxis against meningococcal disease (thus hinder LV function via RV distension and deviation of
may be given to ICU staff after caring for an infected the interventricular septum.
patient or to household contacts). Causes hepatic enzyme Although the RV is analogous to the LV in terms of
induction and thus decreases the efficacy of oral contra- control mechanisms, it is more difficult to assess; e.g. the
ceptives, anticoagulants and phenytoin. relationship between RV preload, RV volume and RV
Dosage: 300mg orally (iv in severe infections)
filling pressures is not always constant. In addition,
bdqds. attempts to study RV function are hindered by the
Side effects: GIT upset, haemolytic anaemia, dysp
greater effect of respiratory excursions on the RV
noea, renal and hepatic impairment, rashes, myopa- because the pressures involved are less than those on the
thy. Colours body secretions orange. left side of the heart.
RV function may be altered in acute respiratory
RIFLE criteria Consensus staging classification of acute failure, sepsis, chest trauma, ischaemic heart disease, and
kidney injury described in 2004, consisting of five stages after cardiac surgery. The possibility of RV ischaemia or
of increasingly severe impairment graded according infarction in critically ill patients as a cause of RV dys-
to plasma creatinine (Cr) level, GFR and/or urine function is increasingly recognised. During IPPV,
output (UO): decreased venous return subsequent to the increased
Risk: Cr > 1.5 baseline/GFR > 25% decrease; UO intrathoracic pressure results in decreased RV end-
< 0.5ml/kg/h for 6h. diastolic volume and thus cardiac output. RV impair-
Injury: Cr > 2.0 baseline/GFR > 50% decrease; ment may result in the classic features of right-sided
UO < 0.5ml/kg/h for 12h. cardiac failure, but may present as a general poor perfu-
Failure: Cr > 3.0 baseline/> 355mol/l (with a rise sion state.
of > 44)/GFR > 75% decrease/or UO < 0.3ml/kg/h
for 24h or anuria for 12h. Ringers solution. Developed as an in vitro medium for
Loss: complete loss of renal function for > 4 weeks. tissues and organisms, emphasising the importance of
End-stage renal disease: complete loss of function inorganic ions in maintaining cellular integrity. Exact
for > 3 months. constitution varies between laboratories, but approxi-
Limitations of the classification include: frequent dispar- mates to sodium 137mmol/l, potassium 4mmol/l,
ity between Cr and UO criteria; requirement for knowl- calcium 3mmol/l and chloride 142mmol/l. Modifica-
edge of baseline Cr/GFR; poor sensitivity of the Risk tions include Ringer lactate (Hartmanns solution) and
criteria, i.e. less severe renal impairment is also associ- Ringers acetate (similar to Hartmanns solution but
ated with worse outcome. with acetate instead of lactate).
 Rotameter 511

[Sydney Ringer (18341910), English physician] enoxaparin at preventing DVT and PE, with comparable
Lee JA (1981). Anaesthesia; 36: 111521 risks of haemorrhagic side effects.
Rapidly absorbed via the oral route (peak plasma
concentration within 24h) with 80100% oral bioavail-
rINNs, Recommended International Non-proprietary
ability. 70% undergoes hepatic metabolism (by the cyto-
Names, see Explanatory notes
chrome P450 system) to inactive products; 30% is excreted
unchanged in urine. Thus, caution is required in patients
Risk management. Process for reducing the frequency with renal failure, and those taking drugs that cause
and overall cost of adverse events, e.g. complications of hepatic enzyme induction/inhibition.
anaesthesia. Consists of: Dosage:
analysis of risks (e.g. morbidity/mortality meetings, 10mg orally od, starting 610h after surgery. For 2
critical incident reporting schemes). Risks are often or 5 weeks, after knee or hip replacement surgery
categorised into: respectively.
- individual-based (e.g. arising from human error), Side effects: nausea, haemorrhage.
e.g. wrong drug given.
- environment-based (e.g. arising from the interac- Rivastigmine, see Acetylcholinesterase inhibitors
tion between anaesthetists and the operating
theatre), e.g. disconnection of breathing system. ROC curves, see Receiver operating characteristic
- system-based (human actions superimposed on curves
inherent flaws in a system or process), e.g. because
of alterations to the operating list caused by can- Rocuronium bromide. Non-depolarising neuromuscu-
cellations due to lack of beds, a patient arrives in lar blocking drug, introduced in 1994. Chemically related
the anaesthetic room without the diseased limb to vecuronium, with similar lack of cardiovascular
marked and has the wrong leg amputated. effects, although tachycardia may accompany very large
prevention of risks associated with routine activities doses. Has been suggested as the drug of choice when
(e.g. proper training and supervision, provision of suxamethonium is contraindicated. Good intubating
trained anaesthetic assistants). conditions occur 60s after an initial dose of 0.6mg/kg;
avoidance of particularly high-risk activities (e.g. relaxation lasts for about 3040min (about 20min after
wider use of regional anaesthesia for caesarean 0.45mg/kg). During a rapid sequence induction, an intu-
section). bating dose of 11.2mg/kg is advocated by some; it pro-
minimising the severity of adverse events should duces better intubating conditions in a shorter time.
they occur (e.g. training in defibrillation, mainte- Supplementary dose: 0.15mg/kg; effects last for about
nance of emergency drugs and equipment). 15min. May be infused iv at 0.30.6mg/kg/h after a
risk financing (e.g. indemnity). loading dose. Primarily excreted by the liver. Cumula-
having a system for dealing with disasters and com- tion is unlikely at recommended doses. Reversed by
plaints, to reduce both psychological and legal sugammadex.
sequelae.
Audit is an integral part of a risk management pro- Ropivacaine hydrochloride. Amide local anaesthetic
gramme, the costs of which may be considerable, agent, introduced in 1997. Chemically related to bupiva-
although the avoidance of litigation is a strong incentive. caine (a propyl group replacing a butyl group) but less
Protocols may contribute to risk management by stan- lipid-soluble and less toxic, being associated with less
dardising care, although they are not universally viewed severe CNS and CVS adverse effects. pKa is 8.1. Pre-
with approval. sented as the (S)-enantiomer (see Isomerism). Used in
Postgraduate issue (2010). Br J Anaesth; 105: 1101 0.21.0% concentrations; initially reported to be approx-
See also, Clinical governance; Quality assurance imately equipotent to bupivacaine in terms of analgesia
whilst producing less motor block, e.g. for epidural
anaesthesia. However, this is disputed, the reduced
Ritodrine hydrochloride. -Adrenergic receptor
motor block seen with ropivacaine being related to its
agonist, used as a tocolytic drug in premature labour.
Dosage:
lower potency and thus selection of non-comparable
solutions in comparative studies. In addition, compara-
50350g/min iv (or 10mg 38-hourly, im), contin-
ble concentrations contain slightly less ropivacaine than
ued for 1248h after contractions have ceased.
bupivacaine.
10mg orally, 30min before stopping iv infusion,
Has vasoconstrictor properties; thus relatively unaf-
repeated 2-hourly for 24h then 1020mg
fected by addition of vasoconstrictor drugs. About 94%
46-hourly.
Side effects: nausea, vomiting, sweating, tremor,
protein-bound; undergoes hepatic metabolism with 1%
excreted unchanged in the urine. Has about 40% greater
hypokalaemia, tachycardia, hypotension, pulmonary
clearance than bupivacaine. Maximal safe dose is esti-
oedema, arrhythmias, increased uterine bleeding
mated at 3.5mg/kg.
after caesarean section, blood dyscrasias and hepatic
impairment on prolonged therapy. Administration of
Rotameter. The trade name of a type of flowmeter
excessive volumes of iv fluids may increase the risk of
commonly used on anaesthetic machines; first used in
pulmonary oedema.
the 1930s.
Features include:
Rivaroxaban. Orally active direct factor Xa inhibitor, constant pressure, variable orifice.
licensed in adults for DVT prophylaxis after elective hip consists of a needle valve, below a bobbin within a
or knee replacement surgery and, in the USA, CVA tapered tube. Gas flow rates are marked along the
prophylaxis in non-valvular AF. More effective than tubes length. Readings are taken from the top of
512 Rotational therapy

the bobbin. Tubes are arranged in banks at the back face/limbs, stimulation of coughing and cardiovascular
of the anaesthetic machine, traditionally for O2, CO2 instability. Accessibility to the patient remains good.
and cyclopropane (the last two on older machines Goldhill DR, Imhoff M, McLean B, Waldmann C (2007).
only), N2O, and air, from left to right in the UK (see Am J Crit Care; 16: 5061
below).
accurate to within 2%. Rowbotham, Edgar Stanley (18901979). English
bobbins are made of light metal alloy; each is indi- pioneer of anaesthesia. With Magill, developed tracheal
vidually matched to its particular tube, and specific intubation, including blind nasal intubation, and endo-
for a certain gas. tracheal anaesthesia. Also pioneered basal narcosis with
the tubes taper is narrower at the bottom to allow rectal paraldehyde, and local and intravenous tech-
accurate measurement of low flow rates, and wider niques. The first anaesthetist in the UK to use cyclopro-
above to measure higher flows. pane. Designed several pieces of apparatus, including a
the space between the bobbin and walls of tube is vaporiser, airway, local anaesthetic needles and other
narrow at the bottom of the tube; gas flow behaves equipment. Latterly worked at Charing Cross, London.
as through a tube, i.e. is largely laminar. Thus gas Particularly interested in anaesthesia for thyroid surgery.
viscosity is important at low flow rates. Higher up Condon HA, Gilchrist E (1986). Anaesthesia; 41: 4652
the tube, the space between the bobbin and tube is
wide compared with the length of the bobbin, Royal College of Anaesthetists. Arose from the grant-
because of the tubes taper. Gas flow behaves as ing of a Charter to the College of Anaesthetists by
through an orifice, i.e. is turbulent. Thus gas density Queen Elizabeth II in March 1992. Regulates and pro-
is important at high flow rates. motes research, training, education and maintenance of
inaccuracies may result from sticking of the bobbin standards in anaesthesia. Administers the FRCA exami-
against the sides of the tube. This is reduced by: nation. Has around 6500 Fellows (including overseas);
- keeping the tube vertical to reduce friction together with Members (non-trainees without the Final
between bobbin and tube. FRCA, a membership category introduced in 2001) and
- angular notches in the bobbin, causing it to rotate registered trainees, this amounts to ~12 000 Members in
when gas flows. total. Created the Faculty of Pain Medicine in 2007 and
- regular cleaning to prevent dirt accumulating the Faculty of Intensive Care Medicine in 2010. The
within the tube. British Journal of Anaesthesia has been its official
- reduction of static charge building up within the journal since 1990; it also publishes guidelines, a regular
tube. Many are internally coated with a thin layer Bulletin and CEPD Reviews.
of gold. Alternatively, regular spraying with anti- Spence AA (1992). Br J Anaesth; 68: 4578
static solution may be performed.
the O2 control knob is larger than the others and RR interval. Time between successive R waves on the
differently shaped to aid recognition. All are colour- ECG. Thus heart rate =
coded as for cylinders. 60
on some older machines, the CO2 bobbin could be
hidden at the top of the tube if the CO2 valve was R R interval(s)
accidentally left fully open. Normally varies by less than 0.16s at rest (sinus arrhyth-
with the traditional arrangement of rotameters, i.e. mia). Useful in the diagnosis of autonomic neuropathy.
O2 upstream, O2 may be lost if there is a leak from
a tube downstream. This may be prevented by RT, Reptilase time, see Coagulation studies
placing the O2 inlet downstream from the others,
e.g. by fitting a baffle across the top of the rotameter RTS, see Revised trauma score
tubes so that N2O enters first, and O2 last.
in modern machines, N2O and O2 rotameters are Rule of nines. Guide to the percentage of body surface
mechanically linked such that less than 25% O2 area represented by various parts of the body; used in
cannot be delivered. assessment and treatment of burns:
head: 9%.
Rotational therapy (Kinetic therapy). Technique in arms: 9% each.
which critically ill patients are turned laterally from the trunk: 18% front; 18% back.
horizontal to an angle of about 40, often several times legs: 18% each.
per hour on a programmable bed. Thought to reduce the perineum: 1%.
incidence of nosocomial pneumonia, decubitus ulcers, For small areas, the patients palmar surface of the hand
DVT and PE. Also reported to shorten duration of both and fingers represents about 1% of surface area. For
IPPV and ICU stay. May share mechanisms of action children, proportions of body parts vary with age, with
with prone ventilation techniques. Compared with the the head comprising up to 18% in infants (and the lower
prone position, it has less chance of accidental displace- limbs contributing proportionally less); for accurate
ment of tubes and catheters/cannulae, damage to eyes/ assessment specialised charts should be used.
 S
S-100 protein. Calcium-binding protein present in
Articular process
glial cells, studied as an early marker of damage to the
bloodbrain barrier, e.g. after CVA, head injury, cardiac
surgery and neurosurgery. A normal level reliably
excludes significant CNS injury. Metabolised in the
kidney with a half-life of ~25min, the serum concentra-
tion is usually negligible but increases after brain injury, Sacral foramen
although it is thought that S-100 may also be produced
from other tissues and its relationship with functional
impairment is uncertain.
Cata JP, Abdelmalak B, Farag E (2012). Br J Anaesth;
107: 84458 Sacral hiatus Cornu

S wave. Downward deflection following the R wave of

the ECG (see Fig. 59b; Electrocardiography). Its size
usually decreases from V2 to V6; the deepest wave is
normally less than 30mm. Prominence in standard leads Fig. 136 Anatomy of the sacrum (posterior view)
I, II and III (S1S2S3 pattern) may be normal in young
people but may be associated with right ventricular
hypertrophy. May also be seen in MI along with other
changes. L4
See also, QRS complex
L5
SA node, Sinoatrial node, see Heart, conducting system
S1
Sacral canal. Cavity, 1015cm long and triangular in
Superior gluteal n
section, running the length of the sacrum, itself formed S2
from five fused sacral vertebrae (Fig. 136). Continuous
Inferior gluteal n
cranially with the lumbar vertebral canal. The anterior
S3
wall is formed by the fused bodies of the sacral verte-
brae, and the posterior walls by the fused sacral laminae.
Due to failure of fusion of the fifth laminar arch, the S4 Posterior cutaneous
posterior wall is deficient between the cornua, forming n of thigh Sciatic n
the sacral hiatus, which is covered by the sacrococcygeal
membrane (punctured during caudal analgesia). Con- Perforating cutaneous n
genital variants of fusion are common, e.g. deficient
Pudendal n
fusion of several laminae; this is thought to be a contrib-
uting cause of unreliability of caudal analgesia. The canal Fig. 137 Plan of the sacral plexus
contains the termination of the dural sac at S2, the sacral
nerves and coccygeal nerve, the internal vertebral venous
plexus and fat. Its average volume in adults is 32ml in Safe transport and retrieval (STaR). Course conceived
females and 34ml in males. by the Advanced Life Support Group and first run in
Crighton IM, Barry BP, Hobbs GJ (1997). Br J Anaesth; 1998. Teaches a systematic approach to the safe transfer
78: 3915 and retrieval of critically ill and injured patients. Aimed
at doctors, nurses and paramedics.
Sacral nerve block, see Caudal analgesia See also, Transportation of critically ill patients

Sacral plexus. Supplies the pelvic and hip muscles, and Salbutamol. -Adrenergic receptor agonist, used mainly
the skin of the buttock and posterior thigh. Lies on piri- as a bronchodilator drug. Relatively selective for 2-
formis muscle on the posterior wall of the pelvis, deep receptors, although it does cause 1-receptor stimulation.
to the pelvic fascia, and is formed from the anterior Undergoes extensive first-pass metabolism if given
primary rami of L4S4 (Fig. 137). Its major branches are orally, thus usually administered by inhalation or iv.
the sciatic, pudendal and gluteal nerves. Produces bronchodilatation within 15min; effects last
See also, Sciatic nerve block 34h. May also reduce the release of histamine and
inflammatory mediators from mast cells sensitised with
Saddle block, see Spinal anaesthesia IgE, hence its particular use in asthma.

513
514 Salicylate poisoning

Also used as a tocolytic drug in premature labour and endothelial cyclo-oxygenase; at low dosage, they selec-
to improve cardiac output in low perfusion states, via tively inhibit platelet cyclo-oxygenase. They are thus
2-receptor-mediated smooth muscle relaxation in the used as antiplatelet drugs. Effects on platelets are
uterus and blood vessels respectively. irreversible, lasting until new platelets are synthesised
Dosage: (710 days).
24mg orally tds/qds. Used for mild-to-moderate pain, pyrexia, rheumatic
500g im/sc, 4-hourly as required. fever, rheumatoid arthritis, and peripheral and coronary
250g iv slowly, repeated as required. 320g/min artery disease. Contraindicated in gout as they may
infusion may be used. IV injection may be more impair excretion of uric acid.
effective than inhalation in severe asthma, but this Absorbed rapidly from the upper GIT after thera-
is controversial. Up to 45g/min may be required peutic dosage, with peak plasma levels within 2hof
in premature labour. ingestion. Absorption is determined by the composition
12 puffs by aerosol (100200g) tds/qds. 200 of tablets, intestinal pH and gastric emptying. About
400g is recommended for dry powder inhalation, 90% protein-bound, they compete with other substances
since bioavailability for the latter is lower. for protein binding sites, e.g. thyroxine, penicillin, phe-
2.55mg by nebulised solution, 46-hourly. nytoin. Metabolised in the liver and excreted mainly in
Side effects: tachycardia, tremor, headache. Hypoka- the urine, especially if the latter is alkaline. Half-life is
laemia may occur with prolonged use. Pulmonary about 15min, but is very dependent on the dose taken.
oedema may occur after use for tocolysis. Side effects: as for NSAIDs and salicylate poisoning.
Implicated in causing Reyes syndrome in children.
Contraindicated in children < 16 years and patients with
Salicylate poisoning. Usually acute but may be chronic,
peptic ulcer disease; used with caution in those with
especially in children.
Features:
coagulation disorders or taking anticoagulant drugs.
nausea, vomiting, haematemesis, sweating, tinnitus,
Saline solutions. IV fluids containing sodium chloride,
deafness, confusion, hallucinations. Loss of con-
used extensively to replace sodium and ECF losses, e.g.
sciousness is uncommon unless poisoning is
in dehydration, and perioperatively. A 0.9% solution is
severe.
most commonly used (physiological saline, often erro-
hyperventilation results from direct respiratory
neously called normal saline); other saline-containing
centre stimulation, possibly via central uncoupling
solutions include Hartmanns solution, Ringers solution
of oxidative phosphorylation. Respiratory alkalosis
and dextrose/saline mixtures. Twice normal saline
results. Compensatory renal excretion of bicarbon-
(1.8%) is used in hyponatraemia, and up to 7.5% solu-
ate results in urinary water and potassium loss with
tions have been used (largely experimentally) in hypo-
dehydration and hypokalaemia.
volaemic shock.
metabolic acidosis is caused by the salicylic acid,
Administration of large volumes of saline may result
and its metabolic effects (increased production of
in hyperchloraemic acidosis, the clinical significance of
ketone bodies, lactic acid and pyruvic acid, hyper-
which is unclear.
glycaemia or hypoglycaemia). Thus the urine, ini-
See also, Hypertonic intravenous solutions; Normal
tially alkaline, becomes acid.
solution
arrhythmias, hypotension.
convulsions, pulmonary oedema, hyperthermia and
Samples, statistical. Parts of populations, selected for
acute kidney injury may occur.
statistical tests or analysis. In order to represent the true
impaired coagulation is rarely significant.
Treatment:
population, samples should be as large as possible to
ensure appropriate power, and free of bias; i.e. should be
general measures as for poisoning and overdose, e.g.
random. Matched samples refer to groups matched for
O2 therapy, iv fluid administration. Activated char-
possible confounding variables, allowing better compari-
coal (1mg/kg) should be given to all patients who
son of the desired measurements. Optimum matching
have ingested > 150mg/kg or those who are acutely
occurs when subjects act as their own controls (i.e. mea-
symptomatic. Additional doses may be given if
surements are paired).
serum salicylate levels continue to rise.
See also, Clinical trials; Randomisation; Statistics
increased elimination may be indicated if plasma
levels exceed 500mg/l (3.6mmol/l) in adults
Sanders oxygen injector, see Injector techniques
or 300g/l (2.2mmol/l) in children. Techniques
include forced alkaline diuresis, dialysis and
Saphenous nerve block, see Ankle, nerve blocks; Knee,
haemoperfusion.
nerve blocks
Mortality of acute overdose is approximately 2%; mor-
tality of chronic overdose about 25%.
SAPS, see Simplified acute physiology score
Pearlman BL, Gambhir R (2009). Postgrad Med; 121:
1628
Sarcoidosis. Systemic disease, possibly caused by an
See also, Forced diuresis
infective agent or immunological derangement, charac-
terised by non-necrotising granuloma formation. The
Salicylates. Group of NSAIDs derived from salicylic lungs or hilar lymph nodes are affected in over 80% of
acid. Aspirin (acetylsalicylic acid) is the most commonly patients, but the disease may involve the eyes, skin, mus-
used; others are available but are less potent, e.g. culoskeletal system, abdominal organs, heart or nervous
sodium salicylate. Have anti-inflammatory and anti- system. Often acute in onset and self-limiting.
pyretic effects; they inhibit both central and peripheral Diagnosed on clinical grounds, supported by tissue
synthesis of prostaglandins. Inhibit platelet and vascular biopsy, CXR, hypercalcaemia (due to derangement of
 Sciatic nerve block 515

vitamin D metabolism), raised angiotensin converting disposal system: may be:

enzyme levels and positive Kveim test (granuloma for- - passive: no external energy supply; the gases pass
mation following intradermal injection of sarcoid tissue through wide-bore tubing to the roof of the build-
suspension). ing, terminating in a ventile. Maximal resistance
Anaesthetic and ICU considerations include the pos- should be 0.5 cmH2O at 30 l/min. The least effi-
sibility of pulmonary fibrosis, cardiac failure, heart cient system, since it depends on wind direction.
block, laryngeal fibrosis, renal failure and hypercalcae- Requires a water trap to remove condensed water
mia. Corticosteroids are often prescribed. vapour.
[Morten A Kveim (18921967), Norwegian pathologist] - assisted passive: employs the air-conditioning sys-
Dempsey OJ, Paterson EW, Kerr KM, Denison AR tems extractor ducts.
(2009). Br Med J; 339: 6205 - active: uses a dedicated fan system or ejector flow-
meter. Requires a low-pressure high-volume
SARS, see Severe acute respiratory syndrome system (able to remove 75 l/min with a peak flow
of 130 l/min); thus hospital suction equipment is
Saturated vapour pressure (SVP). Pressure exerted by unsuitable.
the vapour phase of a substance, when in equilibrium Workplace exposure limits set out in COSHH regula-
with the liquid phase. Indicates the degree of volatility; tions for Great Britain and Northern Ireland are 100ppm
e.g. for inhalational anaesthetic agents, diethyl ether N2O, 50ppm enflurane/isoflurane and 10ppm halothane
(SVP 59kPa [425mmHg]) is more volatile and easier to (each over an 8-h period). Maximum permitted levels
vaporise than halothane (SVP 32kPa [243mmHg]). vary between countries; e.g. in the USA, the National
SVP increases with temperature, therefore SVPs of vola- Institute for Occupational Safety and Health has recom-
tile agents are quoted at standard temperature (usually mended an 8-h time-weighted average limit of 2ppm for
20C). At boiling point, SVP equals atmospheric halogenated anaesthetic agents in general (0.5ppm
pressure. together with exposure to N2O).
See also, Vapour pressure See also, Environmental safety of anaesthetists;
Pollution
Scalp, nerve blocks. Local anaesthetic infiltration is
usually performed with added adrenaline, because of the SCCM, see Society of Critical Care Medicine
rich vascular supply of the scalp. Injection is performed
first in the subcutaneous tissue above the aponeurosis Schimmelbusch mask, see Open-drop techniques
(where nerves and vessels lie), then below. Infiltration in
a band around the head, above the ears and eyebrows, Sciatic nerve block. Used for surgery to the lower leg,
provides anaesthesia of the scalp. Individual branches of often combined with femoral nerve block, obturator
the maxillary nerve may also be blocked. The occipital nerve block and lateral cutaneous nerve of the thigh
nerves supplying the posterior scalp may be blocked by block (see Fig. 66; Femoral nerve block). May also be
infiltrating between the mastoid process and occipital performed to provide analgesia after fractures, or sym-
protuberance on each side. pathetic nerve block of the foot.
The sciatic nerve (L4S3) arises from the sacral
Scavenging. Removal of waste gases from the expira- plexus, leaving the pelvis through the greater sciatic
tory port of anaesthetic breathing systems; desirable foramen beneath the piriformis muscle, and between the
because of the possible adverse effects of exposure to ischial tuberosity and the greater trochanter of the
inhalational anaesthetic agents. Adsorption of volatile femur. It becomes superficial at the lower border of
agents using activated charcoal (Aldasorber device) has gluteus maximus, and runs down the posterior aspect of
been used but does not remove N2O. the thigh to the popliteal fossa, where it divides into
Scavenging systems consist of: tibial and common peroneal nerves. It supplies the hip
collecting system: usually a shroud enclosing the and knee joints, posterior muscles of the leg and skin of
adjustable pressure limiting valve. For paediatric the leg and foot below the knee, except for the medial
breathing systems, several attachments have been calf. The posterior cutaneous nerve of the thigh runs
described, including various connectors and funnels. close to it and is usually blocked by it.
tubing: standard plastic tubing is usual; all connec- Four different approaches are commonly used:
tions should be 30mm to avoid improper connec- posterior: with the patient lying with the side to be
tion to the breathing system. blocked uppermost, and the uppermost hip and
receiving system: incorporates a reservoir to enable knee flexed, a line is drawn between the greater
adequate removal of gases, even if the volume trochanter and posterior superior iliac spine. At the
cleared per minute is less than peak expiratory flow lines midpoint, a perpendicular is dropped 3cm,
rate. May use rubber bags or rigid bottles. If the and a 12cm needle introduced at this point, at right
system is closed, a dumping valve and pressure- angles to the skin. The nerve lies on the ischial spine
relief valve are required to prevent excess negative and is identified using a nerve stimulator (seeking
or positive pressure, respectively, being applied to contraction of the hamstrings and muscles of the
the patients airway. Vents are often present in rigid back of the lower leg and foot). 1530ml local
reservoirs. Requirements: anaesthetic agent is injected. Onset of blockade
- negative pressure: maximum 0.5 cmH2O at 30 l/ may take 30min.
min gas flow. anterior: with the patient lying supine, a line is
- positive pressure: maximum 5 cmH2O at 30 l/min drawn between the pubic tubercle and anterior
gas flow, and 10 cmH2O at 90 l/min. Ideally, the superior iliac spine, and divided into thirds. A per-
relief valve should be as near to the expiratory pendicular line is dropped from the junction of
valve as possible. the medial and middle thirds. Another line, parallel
516 Scleroderma

with the original line, is drawn from the greater patient and the procedure performed. Patient-controlled
trochanter; its intersection with the perpendicular sedation has been used during procedures performed
marks the site of needle insertion. A 12cm needle under local or regional anaesthesia; the patient uses
is directed slightly laterally to encounter the femur, a patient-controlled analgesia device containing e.g.
then withdrawn and directed medial to the femur propofol as required.
to a depth of 5cm from the femurs anterior edge. On ICU, sedative and analgesic drugs are given to
1530ml solution is injected. This approach is par- reduce pain, distress and anxiety, and to aid tolerance
ticularly useful if movement is painful, e.g. fractured of tracheal tubes, IPPV, tracheal suction and physiother-
femur. apy. Cardiovascular depression is undesirable, although
lithotomy: with the hip and knee on the side to be respiratory depression may be an advantage if IPPV is
blocked flexed to 90, a needle is inserted perpen- required. Long-term administration is often required;
dicular to the skin at the midpoint of a line between thus side effects not seen after brief administration may
the greater trochanter and the ischial tuberosity. occur, and drugs with long half-lives may accumulate.
1520ml solution is injected at a depth of 48cm. The desired end-point is usually a calm, cooperative
The posterior cutaneous branch (supplying the pos- patient who can respond to commands, with deeper
terior thigh) may be missed. levels of sedation provided for stimulating procedures.
lateral: with the patient lying supine, a needle is Sedation scoring systems have been devised to assist
inserted horizontally at a point 23cm below and titration of drugs.
45cm distal to the greater trochanter. When the The following drugs have been used for sedation in
femur is encountered it is withdrawn and redirected ICU or for short procedures:
posteriorly ~30 and cranially ~3045 to reach the opioid analgesic drugs: commonly used on ICU.
nerve at 810cm. 2030ml solution is injected. Provide analgesia and euphoria, and aid toleration
See also, Regional anaesthesia of IPPV. All produce respiratory depression. Hypo-
tension is particularly likely if hypovolaemia is
Scleroderma, see Systemic sclerosis present and following rapid iv injection. GIT motil-
ity is reduced. Drugs used include:
Scoliosis, see Kyphoscoliosis - morphine 2.55mg boluses (2060g/kg/h infu-
sion). Accumulation of metabolites may occur
Scopolamine, see Hyoscine after prolonged infusion, especially in renal
failure. Increased susceptibility to infection has
Scribner shunt, see Shunt procedures been shown in experimental animals receiving
very large doses.
SCUF, Slow continuous ultrafiltration, see - fentanyl 15g/kg/h; accumulation readily occurs
Ultrafiltration after prolonged infusion, since its short duration
of action initially is due to redistribution, and
SDD, see Selective decontamination of the digestive tract clearance is slower than that of morphine.
- alfentanil 3060g/kg/h; accumulation is less
Second. SI unit of time; defined according to the fre- likely than with fentanyl.
quency of radiation emitted by caesium-133 in its lowest - remifentanil 0.0250.1mg/kg/min (with or
energy (ground) state. without an initial dose of e.g. 0.5mg/kg/min) is
also used, either alone or in combination with
Second gas effect. Increased alveolar concentration of propofol/midazolam.
one inhalational anaesthetic agent caused by uptake benzodiazepines: often used in conjunction with
of a second inhalational agent. Most marked when opioids. Widely used for short procedures. May
the second gas occupies a large volume, e.g. N2O. Analo- produce cardiorespiratory depression, and may
gous but opposite to the Fink effect at the end of accumulate in impaired hepatic/renal function and
anaesthesia. after prolonged administration. Tachyphylaxis may
also occur. Verbal contact with the patient may be
Second messenger. Intracellular substance (e.g. cAMP, impaired. Flumazenil may be used to reverse over-
calcium ions) linking extracellular chemical messengers sedation. Commonly used drugs:
(first messengers) with the physiological response. G - diazepam 2.510mg boluses. It and its metabo-
protein-coupled receptors are often involved in second lites have long duration of action.
messenger systems. - midazolam 25mg boluses (50200g/kg/h
infusion).
Sedation. State of reduced consciousness in which iv anaesthetic agents, e.g.:
verbal contact with the patient may be maintained. Used - ketamine 510mg boluses (12mg/kg/h infu-
to reduce discomfort during unpleasant procedures, e.g. sion). Used during regional anaesthesia, but rarely
regional anaesthesia, dental surgery, endoscopy, cardiac used in ICU except in asthma.
catheterisation, and on ICU. For short procedures, drugs - thiopental 13mg/kg/h; mainly used in neurologi-
of short duration of action causing minimal cardiorespi- cal disease (e.g. status epilepticus). Recovery may
ratory depression are preferable. Best control is usually be prolonged.
achieved with iv administration, although other routes - propofol 0.34.0mg/kg/h; allows rapid recovery.
may be used, e.g. oral premedication. Routine monitor- For patient-controlled sedation: boluses of 10
ing should be employed during procedures as for general 20mg with no background infusion and a lockout
anaesthesia. Drugs may be given by intermittent bolus, of 25min. Target-controlled infusion (TCI) is
or by continuous infusion; the latter is easier to titrate. also used: 0.53.0g/ml target with or without
The level of sedation required depends on the individual patient-controlled increases as required. Propofol
 Selective serotonin reuptake inhibitors 517

is licensed for 3 days sedation of adults (but Seebeck effect, see Temperature measurement
should be avoided in children). It is licensed for
longer use in neurosurgical patients. May cause Seldinger technique. Method for percutaneous cannu-
propofol infusion syndrome. lation of a blood vessel, described in 1953. A needle is
- etomidate: no longer used in ICU because of inserted into the vessel, and a guide-wire passed through
adrenal suppression. it. After removal of the needle, the cannula is introduced
inhalational anaesthetic agents:
into the vessel over the wire, which is then removed.
- N2O up to 70% is commonly used during regional Refinements include the use of a dilator passed over the
anaesthesia, but haematological side effects pre- wire to enlarge the hole made by the needle, before the
clude prolonged or frequent use. cannula is inserted. Widely used for central venous can-
- isoflurane has been used on ICU with good nulation; favoured by many as being safer and more
results, although high plasma levels of fluoride reliable than using cannula-over-needle techniques,
ions have been reported after prolonged use. May although more costly.
be administered using highly efficient delivery Also used to cannulate other body cavities, e.g. the
devices without the need for anaesthetic machines. trachea in percutaneous tracheostomy formation, the
others:
chest for insertion of a chest drain or the abdominal
- clonidine and dexmedetomidine have been used cavity in paracentesis.
successfully for the sedation of patients on ICU. [Sven-Ivar Seldinger (19211998), Swedish radiologist]
- clomethiazole, droperidol, chlorpromazine; rarely
used. Chloral hydrate, 3050mg orally/rectally
repeated as required, may be useful in children. Selective decontamination of the digestive tract
Neuromuscular blocking drugs are sometimes used in (SDD; Selective parenteral and enteral antisepsis
ICU to facilitate IPPV, especially if chest compliance is regimen, SPEAR). Technique for preventing infections
reduced or ICP is raised. Their use has declined in recent in patients requiring ventilatory support on ICU. SDD
years because of the risk of paralysis with concurrent aims to prevent colonisation of the GIT by potentially
inadequate sedation, increased risk from accidental pathogenic organisms, based on the premise that most
disconnection, possible increased incidence of DVT, infections on ICU are endogenous.
PE, critical illness polyneuropathy and impaired com- Non-absorbable antibacterial drugs (e.g. tobramycin,
munication. Atracurium and vecuronium are most colistin, amphotericin, neomycin) are administered
commonly used. to the pharynx/mouth/upper GIT, whilst another (e.g.
NSAIDs and regional techniques may also be used to cefotaxime) is administered iv. Sparing of the normal
provide analgesia in ICU. anaerobic GIT organisms prevents overgrowth by
Patel SB, Kress JP (2012). Am J Respir Crit Care Med; pathogens. SDD significantly reduces nosocomial pneu-
185: 48697 monia, with some evidence of mortality benefit; however,
concerns over inducing antibiotic resistance have not
Sedation scoring systems. Used in intensive care to been fully addressed. Its place in ICU continues to be
assess the level of sedation of patients in order to balance debated.
its beneficial (reduced stress, cardiovascular stability, Schulz MJ, Haas LE (2011). Crit Care; 15: R18
ventilator synchrony) and adverse (increased risk of
ventilator-associated pneumonia, deep vein thrombosis) Selective serotonin reuptake inhibitors (SSRIs).
effects. Provide an opportunity to titrate the level of Antidepressant drugs, introduced in 1987 and increas-
sedation against predefined end-points (e.g. assessments ingly replacing tricyclic antidepressant drugs as the main
of consciousness, agitation and/or ventilator synchrony). group of drugs used in depression and other disorders.
Other parameters assessed include pain, anxiety, muscle Inhibit the presynaptic reuptake of 5-HT in the CNS,
tone and reaction to tracheal suction. Most systems use leading to an increase in 5-HT activity. Include citalo-
single numerical scores: pram, escitalopram, fluoxetine, fluvoxamine, paroxetine
Ramsay scale: described in 1974. Score ranges from and sertraline; they have similar actions and are metabo-
1 (awake) to 6 (no response). lised in the liver with half-lives of about a day (46 days
comfort scale: described in 1992. Comprises eight for fluoxetine).
items with responses ranging from 1 to 5. Measures Have fewer side effects than tricyclic antidepressants
level of consciousness, facial grimacing, muscle tone, since muscarinic, dopamine, histamine and noradrener-
level of agitation and physiological parameters (e.g. gic receptors are unaffected. However, GIT upset,
heart rate, BP). insomnia and agitation may occur; the syndrome of inap-
sedationagitation scale: described in 1999. Score propriate antidiuretic hormone and impaired platelet
ranges from 1 (minimal or no response to noxious function have been reported. In overdose, severe adverse
stimuli) to 7 (pulling at tracheal tube, trying to effects are uncommon, although the serotonin syndrome
remove catheters). may occur if tricyclics or monoamine oxidase inhibitors
Motor Activity Assessment Scale (MAAS): devel- are also taken.
oped in surgical patients in 1999. Score ranges from May cause hepatic enzyme inhibition (by competing
0 (unresponsive) to 6 (dangerously agitated and with other drugs for the same metabolic pathways), thus
uncooperative). increasing the action of certain tricyclics, type Ic antiar-
Richmond Agitation Sedation Score (RASS): rhythmic drugs (especially lipid-soluble -adrenergic
developed in 2002. Score ranges from 5 (unrous- receptor antagonists), phenytoin and benzodiazepines.
able) to +4 (combative, danger to staff). Increased bleeding may occur in warfarin therapy. Con-
[Michael AE Ramsay, US anaesthetist] current administration of drugs which have 5-HT reup-
De Jonghe B, Cook D, Appere-De-Vecchi C, etal (2000). take blocking effects (e.g. pethidine) may provoke the
Intensive Care Med; 26: 27585 serotonin syndrome.
518 Selenium

Selenium. Trace element found in meat, chicken and Usually kept inflated for 1224h; the oesophageal
fish; normal intake ~6075g/day. Selenoproteins are balloon is deflated first. Careful placement is essential to
antioxidants and are involved in certain biological reac- avoid airway obstruction, pulmonary aspiration, isch-
tions, e.g. conversion of thyroxine to triiodothyronine. aemic necrosis of gastric mucosa or oesophageal rupture.
Low blood selenium levels have been recorded in ICU The tubes are very uncomfortable.
patients, especially those with septic shock. Low sele- [Robert W Sengstaken and Arthur H Blakemore (1879
nium levels are associated with a high ICU mortality; the 1970), US surgeons]
replenishment of plasma selenium is associated with a
decrease in nosocomial infections and a decreased mor- Sensitivity. In statistics, the ability of a test to exclude
tality in patients with sepsis. false negatives. Equals:
Berger MM, Shenkin A (2007). Crit Care Med; 35: the number correctly identified as positive
3067
total with the condition
Self-inflating bags. Rubber or silicone bags used for See also, Errors; Predictive value; Specificity
IPPV, which reinflate when released after compression.
Thus may be used for IPPV without requiring an exter- Sensory evoked potentials, see Evoked potentials
nal gas supply, e.g. during draw-over anaesthesia, trans-
fer of ventilated patients or CPR. May be thick-walled Sensory pathways. The sensory system includes the
or lined with foam rubber. Usually assembled with a special senses, visceral sensation and general somatic
non-rebreathing valve at the outlet and a one-way valve sensation. The latter is divided into:
at the inlet; thus fresh air is drawn in during refilling. O2 exteroreceptive sensation: provides information
may be added through a port at the inlet; a reservoir bag about the external environment and includes
may also be added to the inlet to increase FIO2. Available modalities such as touch, pressure, temperature
in adult and paediatric sizes. Bellows may be used in a and pain.
similar way, but are less convenient to use. proprioceptive sensation: provides information
about body position and movement.
Sellicks manoeuvre, see Cricoid pressure Free nerve endings may be associated with nociception.
Some nerve endings are specialised, e.g. Meissners cor-
Semons law, see Laryngeal nerves puscles (touch), Pacinian corpuscles (vibration and joint
position) and Ruffini corpuscles (joint position). The last
SengstakenBlakemore tube. Double-cuffed gastric two may be involved with muscle spindles.
tube designed to compress gastro-oesophageal varices, The sensory fibres enter the spinal cord through the
thereby controlling bleeding. Passed via the mouth into dorsal root, their cell bodies lying in the dorsal root
the stomach; the distal balloon is then inflated with 150 ganglia. Subsequent pathways (Fig. 139):
250ml air, preventing accidental removal. The proximal dorsal columns: carry impulses concerned with pro-
balloon is then inflated to 3040mmHg (45kPa), com- prioception (movement and joint position sense),
pressing the varices. Traction has been advocated but is vibration and discriminative touch:
rarely used. Newer versions include channels for aspira- - first-order neurones turn medially and ascend in
tion of gastric and oesophageal contents (Fig. 138); the the ipsilateral posterior columns (the fasciculus
latter may be aspirated continuously to reduce pulmo- gracilis and cuneatus) to the lower medulla, where
nary soiling. Thus four lumina may be present: they synapse with cells in the cuneate or gracile
for aspiration above the oesophageal balloon. nuclei.
for aspiration from the stomach. - second-order neurones cross (decussate) to the
for inflation of each balloon. contralateral side of the medulla and ascend in
the medial lemniscus to the ventral posterior
nucleus of the thalamus.
- third-order neurones project to the somatosen-
sory cortex.
spinothalamic tract: carries impulses concerned
with pain, temperature, non-discriminative touch
For aspiration and pressure:
- first-order neurones synapse in the dorsal horn of
the spinal cord (most nociceptive A- and C-fibres
terminate in laminae III whereas A fibres ter-
minate in laminae IIIIV).
- second-order neurones carrying pain and tem-
Oesophageal cuff perature cross within one segment of their origin,
whereas those carrying touch and pressure may
ascend for several segments before crossing. They
ascend in the spinothalamic tract; in the medulla,
this forms the spinal lemniscus, which ascends to
Gastric cuff the ventral posterior nucleus of the thalamus.
- third-order neurones project to the somatosen-
sory cortex.
For aspiration The primary somatosensory area of the cerebral cortex
is in the postcentral gyrus, although there is a large dis-
Fig. 138 Distal end of SengstakenBlakemore tube tribution of sensory fibres in other areas. Regions of
 Sepsis 519

Leg

Face

Head of caudate nucleus Internal capsule

Putamen Ventral posterolateral

nucleus of thalamus
Globus pallidus

Cerebrum

Medial lemniscus

Spinal lemniscus

Medulla Spinothalamic tract

Dorsal columns:
vibration, proprioception,
discriminative touch

Spinal cord

Spinothalamic tract:
pain, temperature,
non-discriminative touch,
pressure

Fig. 139 Anatomy of sensory pathways

greatest importance (e.g. face, mouth, hands) have a dis- and pain sensation. Pure thalamic lesions may
proportionately greater representation than other areas. result in central pain.
Signs of sensory pathway loss: sensory cortex lesions: paraesthesia may be felt,
peripheral nerve lesion: complete loss of sensation with or without impaired sensation, e.g. inability to
in the nerves distribution (although the zone of loss distinguish between heat and pain, or inability to
may be limited because of overlap between nerves). identify objects by touch.
posterior root lesion: pain and paraesthesia are [Georg Meissner (18291905), German anatomist;
experienced in the dermatomal distribution. If the Filippo Pacini (18121883), Italian anatomist; Angelo
root involves a reflex arc, the reflex will be dimin- Ruffini (18641929), Italian histologist]
ished or lost. See also, Dermatomes; Spinal cord injury
posterior column lesion: ipsilateral loss of position
and vibration sense with preservation of pain, touch Sepsis. SIRS as a result of proven or suspected infection
and temperature sensation. (i.e. invasion of normally sterile host tissue by micro-
spinothalamic tract lesion: contralateral loss of pain organisms and the inflammatory response to their pres-
and temperature sensation. ence). Severe sepsis is defined as sepsis plus organ
brainstem and thalamus lesions: upper brainstem or dysfunction, hypoperfusion or hypotension, and replaces
thalamic lesions may cause complete hemisensory the now obsolete term septicaemia (bacteraemia is the
disturbance with loss of postural sense, light touch presence of viable circulating bacteria). A major cause
520 Sepsis-related organ failure assessment

of organ failure in ICU, severe sepsis is directly or indi- See also, Catheter-related sepsis; Fungal infection in the
rectly responsible for 75% of all ICU deaths. ICU; Nosocomial infection; Sepsis-related organ failure
Most ICU infections are endogenous, caused by assessment; Sepsis score; Sepsis severity score
colonisation of the patients GIT by pathogenic organ-
isms. Gram-negative bacteria (e.g. Escherichia coli, Sepsis-related organ failure assessment (SOFA).
klebsiella, pseudomonas and proteus species) have tra- Scoring system devised in 1994 to describe quantitatively
ditionally been most commonly responsible, because of and objectively the degree of organ dysfunction in sepsis
their widespread presence, their tendency to acquire over time. Intended to improve the understanding of
resistance to antibacterial drugs and their resistance organ dysfunction/failure and to assess the effect of par-
to drying and disinfecting agents. Gram-positive ticular therapies on its progression. The function of six
bacteria (e.g. streptococci, staphylococci) are increas- different organ systems (respiratory, cardiovascular,
ingly common, especially associated with invasive can- central nervous, coagulation, hepatic and renal systems)
nulation; other organisms (e.g. fungi) may also be is weighted (each scored 14) according to the degree of
responsible. The inflammatory response involves cyto- physiological derangement observed. Minimum SOFA
kines, nitric oxide, thromboxanes, leukotrienes, platelet score is 6; maximum 24.
activating factor, prostaglandins and complement. Vincent JL, Moreno R, Takala J, etal (1996). Intensive
Endothelial and neutrophil adhesion molecule expres- Care Med; 22: 70710
sion increases, resulting in cellular infiltration into
the tissues. Sepsis score. Index of severity of sepsis, devised in 1983;
Critically ill patients are susceptible to sepsis
assigns scores according to local infection, pyrexia, sys-
because of: temic response and laboratory results. Now rarely used.
impaired local defences, e.g. anatomical barriers,
Elebute EA, Stoner HB (1983). Br J Surg; 70: 2931
ciliary activity, coughing, gastric pH. Tracheal tubes,
indwelling catheters and cannulae provide routes
for infection. Sepsis severity score. Index of severity of sepsis,
impaired immunity. Contributory factors include
devised in 1983 by assigning scores of 15 according to
drugs, malnutrition, diabetes mellitus, old age, the degree of impairment of each of the following organ
malignancy, organ failure and infection itself. Infec- systems: lung, kidney, coagulation, CVS, liver, GIT and
tion control is important in reducing sepsis in neurological. The three highest (worst) scores are then
the ICU. squared to produce the final score.
Management: Stevens LE (1983). Arch Surg; 118: 11902
supportive, e.g. iv fluids, O2 therapy, inotropic drugs.
Current recommendations in severe sepsis are for Sepsis syndrome. Obsolete term for the systemic
haemodynamic resuscitation to be guided by spe- response to infection.
cific goals, including: See also, Sepsis; Septic shock; Septicaemia; Systemic
- CVP 812mmHg; MAP 6590mmHg. inflammatory response syndrome
- central venous oxygen saturation > 70%.
- haematocrit > 30%. Septic shock. Hypotension (or the requirement for ino-
- urine output > 0.5ml/kg/h. tropic or vasopressor drugs) despite adequate fluid
early use of antibacterial and/or antifungal drugs. resuscitation, with evidence of perfusion abnormalities
Initial choice is based on the most likely infective (e.g. lactic acidosis, oliguria), associated with sepsis.
organisms. Samples of urine, sputum, blood and Initial features include hyperthermia, tachycardia, tach
CSF should be taken before starting therapy. ypnoea, hypotension and vasodilatation with a hyperdy-
source control: e.g. surgical drainage, debridement, namic circulation and increased cardiac output. In later
removal of infected lines and catheters. stages, or if hypovolaemia or poor myocardial function
use of corticosteroids is controversial (see Septic is present, hypotension with vasoconstriction super-
shock). venes. Mortality is about 50%, although it varies with
activated protein C is no longer recommended in patients characteristics and the nature of the sepsis.
severe sepsis. Most cases are caused by bacteria (approximately
new immunomodulatory treatments (e.g. anti- equally split between Gram-positive and -negative,
endotoxin antibodies, anti-cytokine products) have although traditionally associated with Gram-negative
been investigated, with disappointing clinical results. organisms); other organisms may also be responsible.
This may represent the heterogeneous patient Risk factors include: age (< 10 years and > 70 years);
population and/or the complex pathophysiology diabetes mellitus; alcoholic liver disease; ischaemic heart
of sepsis. disease; malignancy; immunosuppression; prolonged
nutrition is important as hypercatabolism is hospital stay; invasive monitoring; tracheal intubation;
common. and prior use of antibacterial agents. The underlying
evidence-based care bundles have been developed pathophysiology is as for sepsis; microvascular abnor-
to support timely and effective management. malities supervene, including impaired autoregulation,
Complications include septic shock and multiple organ altered blood cell morphology, increased endothelial
failure, including acute lung injury, acute kidney injury, permeability and opening of arteriovenous shunts.
hepatic failure, pancreatitis and diabetes mellitus, DIC, Cardiovascular features include:
cardiac failure and coma. GIT haemorrhage is common; reduced SVR with relative hypovolaemia.
prophylaxis includes proton pump inhibitors and H2 increased pulmonary vascular resistance.
receptor antagonists. increased capillary permeability.
Eissa D, Carton EG, Buggy DJ (2010). Br J Anaesth; 105: reduced myocardial contractility caused by circulat-
73443 ing depressant factors, acidaemia and hypoxaemia.
 Sevoflurane 521

O2 consumption may be normal but O2 extraction F CF3

and utilisation are reduced.
Management:
H C O C H
as for sepsis.
high-dose corticosteroids are associated with H CF3
increased mortality; however recent evidence
suggests that at lower doses (e.g. hydrocortisone Fig. 140 Structure of sevoflurane
200mg/day) they may reduce vasopressor require-
ments and speed resolution of shock (by increasing
the sensitivity of -adrenergic receptors on vascular patients < 24 years to > 50% in those > 65 years. CXR,
smooth muscle). A corticotropin (Synacthen) stim- initially normal, may show focal interstitial infiltrates
ulation test was previously advocated to identify which may become generalised. Thrombocytopenia and
patients with impaired pituitaryadrenal axis func- leucopenia are common; raised liver function tests
tion; this is no longer considered necessary for may occur but renal function usually remains normal.
identifying patients who may benefit from steroid Treatment is largely supportive, although the following
therapy. Survival benefits are unclear and steroid have been used empirically:
use remains controversial; however, in extremely ribavirin 8mg/kg iv tds (N.B. not licensed for this
sick patients with high vasopressor requirements, use in UK) or 1.2g orally bd after a loading dose
many advocate administering a therapeutic trial of 4g orally, for 714 days (caution in impaired
with cessation if there is no clinical improvement. renal function).
Complications: as for sepsis. hydrocortisone 24mg/kg iv tds/qds, for ~7 days.
Eissa D, Carton EG, Buggy DJ (2010). Br J Anaesth; 105: Methylprednisolone 10mg/kg/day iv has been used
73443 for 2 days before hydrocortisone.
antibacterial prophylaxis.
Septicaemia, see Sepsis Staff require protection from infection since several
cases of transmission to healthcare workers have
Sequential analysis, see Statistical tests occurred.
Lai TS, Yu WC (2010). Clin Med; 10: 503
Serotonin, see 5-Hydroxytryptamine
Severinghaus electrode, see Carbon dioxide
Serotonin reuptake inhibitors, see Selective serotonin measurement
reuptake inhibitors
Sevoflurane. 1,1,1,3,3,3-hexafluoroisopropyl fluoro-
Serotonin syndrome. Impaired mental state, increased methyl ether (Fig. 140). Inhalational anaesthetic agent,
muscle activity and autonomic instability arising from first synthesised in 1968 but not introduced in the UK
excessive 5-HT activity in the brainstem and spinal cord. until 1995 because of the development of isoflurane in
Seen in selective serotonin reuptake inhibitor (SSRI) preference.
overdose, especially in combination with other antide- Properties:
pressant drugs (especially monoamine oxidase inhibi- colourless liquid with pleasant smelling vapour, 7.5
tors). Has also been reported after intraoperative use of times heavier than air.
methylene blue (a potent inhibitor of monoamine mw 200.
oxidase) in a patient taking SSRIs. Also associated with boiling point 58C.
the use of tramadol, pethidine and cocaine. Features SVP at 20C 21kPa (160mmHg).
include confusion, agitation, convulsions, myoclonus, partition coefficients:
rigidity, hyperreflexia, fever, diarrhoea, hyper- or hypo- - blood/gas 0.69.
tension and tachycardia. DIC, renal and cardiac failure - oil/gas 53.
may also occur. Treatment is supportive; 5-HT antago- MAC 1.4% (80 years) 2.5% (children/young
nists, e.g. methysergide, cyproheptadine, have been used. adults); up to 3.3% in neonates.
Usually lasts for < 24hbut deaths have been reported. non-flammable, non-corrosive.
A washout period of several weeks has been sug- supplied in liquid form with no additive.
gested between monoamine oxidase inhibitor and SSRI interacts with soda lime at temperature of 65C to
therapy. produce Compounds A, B, C, D and E, the first two
Boyer EW, Shannon M (2005). N Engl J Med; 352: the only ones produced in clinical practice. Produc-
111220 tion is more likely at high temperatures, high con-
centrations of sevoflurane, use of baralyme and low
Severe acute respiratory syndrome (SARS). Infec- gas flows. Compound A (pentafluoroisopropenyl
tious respiratory condition caused by a new coronavirus, fluoromethyl ether) is no longer thought to be sig-
first reported in East Asia in early 2003 and thought to nificant, despite its toxicity in rats at high dosage;
have spread via air travellers to Europe and North clinical experience has never implicated it in causing
America. Has mostly affected previously healthy adults, harm in humans, even with sevoflurane at low fresh
with an incubation period of 211 days. Spread mainly gas flows (maximal concentrations of Compound A
via airborne droplets, with most cases of transmission around 30ppm; minimal levels for human toxicity
thought to involve close exposure to an infectious indi- thought to be around 150200ppm).
vidual. Features include high fever initially with malaise, Effects:
myalgia and headache; after 37 days dry cough and CNS:
dyspnoea may occur, leading to acute respiratory failure - smooth, extremely rapid induction and recovery.
in 1020% of cases and a mortality ranging from 1% in Concentrations of 48% produce anaesthesia
522 Shivering, postoperative

within a few vital capacity breaths. Early postop- that anaesthetic agents suppress descending pathways
erative analgesia may be required as emergence which normally inhibit spinal reflexes; this may be more
is so rapid. likely than a response to intraoperative hypothermia,
- increases the risk of emergence agitation, com- although the latter may be of importance if severe.
pared with isoflurane, in children < 5 years. Suggested treatment:
- anticonvulsant properties as for isoflurane. O2 administration.
- at concentration of < 1 MAC has minimal effect fentanyl 25g iv or pethidine 1025mg iv may be
on ICP in patients with normal ICP. Studies effective. Pentazocine 30mg or doxapram 1mg/kg
suggest that autoregulation is preserved in or pre-induction ondansetron has also been used.
patients with cerebrovascular disease, in contrast Shivering after epidural anaesthesia is common, and is
to other inhalational agents. thought to be caused by differential nerve blockade,
- reduces CMRO2 as for isoflurane, with about a either suppressing descending inhibition of spinal
50% reduction at 2 MAC. reflexes or allowing selective transmission of cold sensa-
- decreases intraocular pressure. tion. Shivering is rare in spinal anaesthesia, where block-
- has poor analgesic properties. ade is more dense. Warming of epidural injectate has
RS: produced conflicting results. Epidural administration of
- well-tolerated vapour with minimal airway opioid analgesic drugs, e.g. sufentanil 50g, fentanyl
irritation. 25g, pethidine 25mg, may be an effective remedy.
- respiratory depressant, with increased rate and De Witte J, Sessler DI (2002). Anesthesiology; 96:
decreased tidal volume. 46784
- causes bronchodilatation.
CVS: Shock. Syndrome, originally described by Crile, in which
- vasodilatation and hypotension may occur, but tissue perfusion is inadequate for the tissues metabolic
less than with isoflurane and with little myocar- requirements. Sympathetic compensatory mechanisms
dial depression. Little compensatory tachycardia, may preserve organ perfusion initially, but subsequent
unlike isoflurane. organ dysfunction may lead to irreversible organ damage
- myocardial O2 demand decreases. and death.
- arrhythmias uncommon, as for isoflurane. Little Classically divided into:
myocardial sensitisation to catecholamines. hypovolaemic shock, e.g. following haemorrhage,
- renal and hepatic blood flow generally burns, dehydration.
preserved. cardiogenic shock, e.g. following MI.
other: septic shock.
- dose-dependent uterine relaxation. others, e.g. anaphylaxis, adrenocortical insufficiency,
- nausea/vomiting occurs in up to 25% of cases. neurogenic shock (e.g. in high spinal cord injury).
- skeletal muscle relaxation; non-depolarising neu- Division into hypovolaemia, myocardial failure and
romuscular blockade may be potentiated. peripheral vascular failure has been suggested as being
- may precipitate MH. more indicative of underlying mechanisms. Thus shock
Under 5% metabolised in the liver to hexafluoroisopro- may arise from inadequate cardiac output or maldistri-
panol and inorganic fluoride ions, the rest being excreted bution of blood flow; the latter has been increasingly
by the lungs. High levels of fluoride have never been implicated by studies of O2 delivery ( D  O2 ) and total
reported, even after prolonged surgery, but avoidance in body O2 consumption (V O2 ). A decrease in V O2 is
renal impairment has been suggested. Inducers of the thought to represent maldistribution rather than an
particular cytochrome P450 enzyme involved (e.g. isonia- absolute decrease in blood flow. In cardiogenic shock
zid, alcohol) increase metabolism of sevoflurane, but both V O2 and cardiac output are reduced; in septic shock
barbiturates do not. they may both increase initially. Features depend on the
0.53.0% is usually adequate for maintenance of aetiology but include hypotension, tachycardia, oliguria
anaesthesia, with higher concentrations for induction. and metabolic acidosis. MODS may follow, with acute
Tracheal intubation may be performed easily with spon- kidney injury and ARDS. Hepatic, gastrointestinal and
taneous respiration. Considered the agent of choice for pancreatic impairment, and DIC may occur.
inhalational induction in paediatrics because of its rapid Management:
and smooth induction characteristics. Has also been used directed at the primary cause.
for the difficult airway, including airway obstruction. cardiovascular support: achieved with iv fluids,
See also, Vaporisers blood products, inotropic drugs and vasodilator
drugs. Haemodynamic monitoring consists of
Shivering, postoperative. Tremors were first described measurement of BP, pulse rate, CVP, urine output,
after barbiturate administration, but they may occur fol- pulmonary capillary wedge pressure and cardiac
lowing all types of general anaesthesia. Traditionally said output. Lactate and central venous oxygen satura-
to be more common following halothane (halothane tions are also measured. D  O2 , V O2 and gastric
shakes). Rarer in elderly patients due to decreased ther- tonometry have previously been used to guide
moregulatory control. May increase metabolic rate by therapy.
up to six times and triple O2 consumption. Can also support of other organs: as for renal failure and
aggravate postoperative pain, damage surgical wounds ARDS.
and increase intraocular and intracranial pressures. Mortality exceeds 50% for cardiogenic and septic shock.
Damage to teeth may occur, especially in the presence
of an oral airway. Shock index (SI). Ratio of heart rate to systolic blood
EMG studies suggest that postoperative shivering pressure; has been used to identify and monitor haemor-
differs from shivering due to cold. It has been suggested rhage in trauma patients. An elevated shock index
 Shunt procedures 523

(> 0.9) has been suggested as an indication for admission where CaO2 = arterial O2 content
to ICU. CcO2 = end-capillary O2 content
C v O2 = mixed venous O2 content
Shock lung, see Acute respiratory distress syndrome  T Ca O2 = (Q T Cc O2 ) (Q
 S Cc O2 ) + (Q
 S C v O2 )
Thus Q
  
or (QS Cc O2 ) (QS C v O2 ) = (QT Cc O2 ) (Q  T Ca O 2 )
Shunt. One extreme form of V/Q mismatch, causing
hypoxaemia. Refers to the actual amount of venous  
or QS (Cc O2 C v O2 ) = QT (Cc O2 Ca O2 )
blood bypassing ventilated alveoli and mixing with pul- Therefore
monary end-capillary blood (cf. venous admixture, the  S (Cc O2 Ca O2 )
calculated amount of shunt required to produce the Q
 = = shunt fraction.
observed arterial PO2). QT (Cc O2 C v O2 )
May be:
Arterial and venous O2 contents may be estimated thus:
intrapulmonary, e.g. atelectasis, chest infection.
extrapulmonary, e.g. congenital heart disease.
Ca O2 = ( Pa O2 S) + (Hb 1.34 Sa O2 ),
Physiological shunt (venous admixture) = shunt-like C v O2 = ( Pv O2 S) + (Hb 1.34 Sv O2 ),
effect of V /Q
 mismatch + anatomical shunt (actual
where PaO2 and SaO2 = arterial PO2 and haemoglobin
shunt). The latter includes pathological shunt and normal saturation respectively,
mixing of bronchial and Thebesian venous blood with Pv O2 and Sv O2 = mixed venous PO2 and haemo-
oxygenated pulmonary venous blood. globin saturation respectively,
Hypoxaemia due to shunt responds poorly to S = volume of O2 dissolved in 100ml blood per
increased FIO2, since the O2 content of pulmonary end- kPa applied O2 tension (0.0225) or mmHg (0.003),
capillary blood is already near maximum, because of the Hb = haemoglobin content in g/100ml,
shape of the oxyhaemoglobin dissociation curve. Some 1.34 = Hfners constant.
benefit is derived from increased dissolved O2. Thus the
amount of shunt may be estimated from the response to End-capillary O2 content cannot be measured directly,
breathing high concentrations of O2, assuming a haemo- but is estimated from calculation of the alveolar air
globin concentration of 1014g/100ml, arterial PCO2 of equation:
3.35.3kPa (2540mmHg) and arteriovenous O2 differ- Cc O2 = ( PA O2 S) + (Hb 1.34),
ence of 5ml/100ml (Fig. 141). Amount of shunt may
where PAO2 = ideal alveolar PO2, and saturation is
also be estimated from the shunt equation.
assumed to be 100%.
[Adam Thebesius (16861732), German physician]
Shunt procedures. Performed to provide access to the
Shunt equation
circulation for haemodialysis and related procedures,
 S (Cc O2 Ca O2 )
Q thus requiring the capacity for high flow rates of blood
 =
QT (Cc O2 C v O2 ) both out of and back into the circulation. May involve:
temporary cannulation of vessel(s), e.g. central
Allows calculation of shunt. Derived as follows. Total
 T , made up of blood flow venous cannulation with a double-lumen catheter
pulmonary blood flow equals Q
 S) and blood flow to ventilated (or two single ones). Choice of vessel and technique
to unventilated alveoli (Q
T Q  S; Fig. 142). is as for placement of any central line, although
alveoli (Q
the catheter is usually required for a longer time.
In unit time, the volume of O2 leaving the lungs equals
Venous stenosis or thrombosis may be more
the volume of O2 in blood draining ventilated alveoli
common if the subclavian vein is used. Most double-
plus the volume of O2 in shunted blood. Or,
lumen dialysis catheters are designed with one
Q T Ca O2 = [(Q T Q S ) Cc O2 ] + [Q
 S C v O2 ],
channel for withdrawal and one for return of blood;
the latter opens proximal to the former to reduce
the withdrawal of freshly dialysed blood from the
return channel via the withdrawal channel, and thus
(kPa) (mmHg) inefficiency.
surgical creation of a permanent arteriovenous
0% 10%
60 shunt between adjacent vessels, e.g. radial artery/
400
50

40 300
Pao2

Pao2

30 20%
200
20 . .
30% (QT QS)
100
10 50%
. .
QT QT
0
20 30 40 50 60 70 80 90 100
.
FIo2 (%) QS

Fig. 141 Pao2 at varying FIo2 for different percentages of shunt Fig. 142 Calculation of shunt equation
524 ShyDrager syndrome

cephalic vein, using either direct anastomosis of the precipitated by anaesthesia and result in refractory bra-
vessels (fistula) or insertion of a Silastic catheter dycardia or even asystole. Requires cardiac pacing if
(Scribner shunt). Venous wall thickening allows diagnosed preoperatively or if it occurs perioperatively.
repeated cannulation, although thrombosis and Staikou C, Chondrogiannis K, Mani A (2012). Br J
venous stenosis may occur. Other complications Anaesth; 108: 73044
include infection, pseudoaneurysm and arm isch- See also, Heart, conducting system
aemia. Surgical shunts may be performed under
local infiltration anaesthesia, regional anaesthesia Sickle cell anaemia. Haemoglobinopathy, first described
(e.g. brachial plexus block) or general anaesthesia. in 1910 in Chicago. Caused by substitution of glutamic
Anaesthetic considerations are as for renal failure. acid by valine in the sixth amino acid from the N-terminal
[Belding H Scribner (19212003), Seattle nephrologist] of haemoglobin chains. Inherited as an autosomal gene;
heterozygotes (genotype HbAS; sickle cell trait) possess
ShyDrager syndrome, see Autonomic neuropathy both normal (HbA) and abnormal (HbS) haemoglobins
(though they may also possess other abnormal haemo-
SI units, Units of the Systme International dUnits, see globin combinations [e.g. HbSC]) or thalassaemia (S);
Units, SI homozygotes (HbSS) possess only abnormal haemoglo-
bin. Thought to have originated from spontaneous
SIADH, see Syndrome of inappropriate antidiuretic genetic mutation, with subsequent selection owing to the
hormone secretion relative resistance against falciparum malaria conferred
Siamese twins, see Conjoined twins by sickle cell trait. Most common in West Central Africa,
North-East Saudi Arabia and East Central India, but has
Sick Doctor Scheme. Scheme set up in 1981 in the UK been described in Southern Mediterranean populations.
by the Association of Anaesthetists and Royal College Incidence of HbSS in US Blacks is < 1%; incidence of
of Psychiatrists, to encourage voluntary reporting of sick HbAS is 810%.
doctors practising anaesthesia. The anonymous reporter, Deoxygenated HbS polymerises and precipitates
having contacted the Association, is given the name and within red blood cells, with distortion and increased
telephone number of a referee. The latter contacts an rigidity. Sickle-shaped red cells are characteristic. The
appointed psychiatrist from another region, who in turn distorted cells increase blood viscosity, impair blood
contacts the sick doctor. A similar scheme (National flow and cause capillary and venous thrombosis and
Counselling Service for Sick Doctors) is now available organ infarction. They have shortened survival time. O2
to doctors from all specialties. Intended as an alternative affinity of dissolved HbS is normal, but overall affinity is
to the more formal scheme available via the Department reduced if some of the HbS is polymerised. HbS poly-
of Health (previously involving appropriate action taken merises at PO2 of 56kPa (4050mmHg); thus HbSS
via a subcommittee [three wise men procedure]; more patients are continuously sickling. HbAS patients red
recently replaced by a framework involving the National cells contain both HbS and HbA and sickle at 2.5
Clinical Assessment Service) and General Medical 4.0kPa (2030mmHg).
Features:
Council (assesses doctors on health and performance as
well as conduct). HbSS:

A scheme of the same name exists in Ireland, to help - haemolysis causing anaemia and hyperbilirubin
doctors affected by substance abuse. aemia. Gallstones may occur. Enlargement of the
skull and long bones is common, due to compen-
Sick euthyroid syndrome (Non-thyroidal illness syn- satory bone marrow hyperplasia. Acute aplastic
drome). Abnormal thyroid function tests occurring in crises may occur, and sequestration crises in
critically ill patients. The most common pattern is low children.
triiodothyronine (T3) with normal or raised thyroxine - impaired tissue blood flow may result in CVA,
(T4) and thyroid stimulating hormone (TSH). Low T3 papillary necrosis of the kidney, ulcers, pulmonary
and T4 are generally associated with more severe critical infarcts, priapism and avascular necrosis of bone.
illness and worse prognosis. Most patients are clinically Crises are caused by acute vascular occlusion, and
euthyroid. Thought to result from impaired pulsatile may feature neurological lesions and severe pain,
secretion of TSH, reduced peripheral conversion of T4 e.g. abdominal, back, chest (the sickle chest syn-
to T3 and reduced plasma protein binding. drome is a common cause of death and includes
It is not clear if the changes seen are an appropriate cough, fever and severe hypoxaemia). They may
response to severe illness or a maladaptive response that be precipitated by hypothermia, dehydration,
should be treated; correction of deficits with thyroid infection, exertion and hypoxaemia. Treatment is
hormone replacement has not shown consistent survival with analgesia (often requiring opioids, e.g. by
benefit. PCA), O2 and rehydration. Exchange blood trans-
Bello G, Ceaichisciuc I, Silva S, Antonelli M (2010). fusion may be required.
Minerva Anestesiol; 76: 91928 - increased susceptibility to infection (especially
pneumococcal infections) due to splenic infarc-
Sick sinus syndrome. Syndrome caused by impaired tion. Osteomyelitis is typically caused by unusual
sinoatrial node activity or conduction; may lead to periods organisms, e.g. salmonella.
of severe bradycardia with intermittent loss of P waves HbAS: usually asymptomatic, since arterial PO2 is
or sinus arrest, and may alternate with periods of SVT unlikely to reach the level required to induce
or AF (bradycardiatachycardia syndrome; bradytachy sickling.
syndrome). Although it usually occurs in elderly patients combinations of HbS with other haemoglobins
with ischaemic heart disease, it is also a major cause usually produce mild disease. In heterozygotes for
of sudden death in children and young adults. May be HbS and haemoglobin C (HbC), red cells may sickle
 Siggaard-Andersen nomogram 525

at around 4kPa (30mmHg) because HbC is less - hypoxaemia, dehydration, hypothermia and
soluble than HbA, and makes red cells more rigid. acidosis should be prevented at all times periop-
Diagnosis is by detection of HbS in the blood. The eratively. Prophylactic antibiotics are often
Sickledex test involves addition of reagent to blood, with administered.
observation for turbidity. It detects HbS but provides intraoperatively:
no information about other haemoglobins. A sodium - standard techniques may be used, apart from
metabisulphite test induces sickling in susceptible cells, tourniquets which cause tissue ischaemia (IVRA
which are then counted. Haemoglobin electrophoresis is is contraindicated). Heat loss should be prevented
the definitive method of determining the nature of the and cardiovascular stability maintained. Preoxy-
haemoglobinopathy. genation and FIO2 of 50% reduces the risk of
Sickle cells are usually present in peripheral blood hypoxaemia by increasing arterial PO2 and pul-
in HbSS. monary O2 reserve. IV hydration should be main-
Anaesthetic considerations: tained. Frequent analysis of acidbase status is
preoperatively: required in HbSS patients. Prophylactic bicarbon-
- all races at risk should be screened for HbS, ideally ate administration has been suggested, but admin-
by electrophoresis. In the UK, Sickledex testing is istration according to acidbase analysis is usually
usual initially, with progression to electrophoresis preferred.
if positive. In emergencies, if the Sickledex test is - intraoperative crises may present with changes in
positive, diagnosis may be aided by blood counts breathing pattern or BP, acidosis and hypoxaemia.
and peripheral film. If the history does not suggest Detection may be difficult.
HbSS, and haemoglobin/reticulocyte count and postoperatively: the precautions already instituted
peripheral film are normal with no red cell frag- should continue, since complications may occur
ments, HbAS is likely, although HbSC and other postoperatively. Patients are generally considered
heterozygous variants may still be present. Man- unsuitable for most day-case surgery. O2 adminis-
agement ultimately depends on the nature of the tration for at least 24his usually advocated.
surgery and availability of blood. de Montalembert M (2008). Br Med J; 337: 62630
- preoperative assessment is directed towards the
above complications, especially impairment of SID, see Strong ion difference
pulmonary and renal function. Preoperative folic
acid has been suggested. Exchange transfusion is Siggaard-Andersen nomogram. Diagram derived
often used in HbSS patients before major surgery, from analysis of many blood samples, showing the plot
aiming to reduce HbS concentrations to < 30%. A of log arterial PCO2 against plasma pH, with base excess,
less aggressive transfusion strategy is to aim for a standard bicarbonate and buffer base illustrated as addi-
haematocrit of > 30%; both approaches have tional lines (Fig. 143). Allows determination of arterial
similar efficacy. PCO2 by equilibrating a blood sample with two known

48

10 20
0
80
9 (68)
Haemoglobin Buffer base (mmol/l)
(g/dl)
Arterial Pco2 (kPa (mmHg))

10 20 30 40
5.3 (40)
0 Standard bicarbonate (mmol/l)
20

+ 20 Base excess (mmol/l)

Titration line of normal blood
3 (23)

- 20

7.2 7.4 7.6

plasma pH

Fig. 143 Siggaard-Andersen nomogram

526 Sigh

concentrations of CO2, and measuring the sample pH at combined within the setting of an entire operating suite
each concentration. The points are plotted on the with monitoring equipment and controlled with comput-
diagram and joined by a line, and the PCO2 read from ers (high-fidelity simulation), often interacting through
the vertical scale according to the pH of the original a mathematical model.
sample. Alternatively, if arterial PCO2 can be measured Are now widely used in areas other than anaesthesia,
directly, a single measurement of pH and PCO2, together e.g. obstetrics, emergency medicine and surgery.
with haemoglobin concentration (since haemoglobin is Despite best efforts, simulators may not always reflect
a major blood buffer), allows determination of the real conditions accurately. For instance, some activities
derived data. Modern blood-gas machines automatically may be easier to perform on simulators than in the oper-
perform the required calculations, making such plotting ating room; conversely, some may be more difficult.
unnecessary. Reality is further impeded by the need to model average
[Ole Siggaard-Andersen, Danish biochemist] patients who may not respond in the extreme ways of
some real patients; equally, subjects responses may be
Sigh, see Intermittent positive pressure ventilation different when they are aware that they are working with
a simulator. The cost of sophisticated simulators and the
labour-intensive staffing requirements are further disin-
Significance, see Statistical significance centives. Nevertheless, simulation has become an estab-
lished part of training programmes in many countries,
Sildenafil (Viagra). Orally active phosphodiesterase and has also been studied as a means of assessing
inhibitor, selective for cyclic guanine monophosphate practitioners.
(cGMP)-specific phosphodiesterases. Licensed for use in Castanelli DJ (2009) Anaesth Intensive Care; 37:
pulmonary hypertension and male erectile dysfunction. 90310
Catastrophic interactions with nitrates (e.g. GTN) have See also, Crisis resource management
been reported, resulting in severe hypotension and
death; thus a history must be obtained in suspected SIMV, Synchronised intermittent mandatory ventilation,
ischaemic heart disease before administering nitrates. see Intermittent mandatory ventilation
Tadalafil and vardenafil are related drugs.
Simvastatin, see Statins
Simplified acute physiology score (SAPS). Scoring
system used to assess severity of illness by determining Single-pass albumin dialysis, see Liver dialysis
the degree of deviation of physiological variables from
normal values. Originally incorporating 14 variables and Sinoatrial node, see Heart, conducting system
excluding pre-existing disease, a modified version (SAPS
II) has been developed in which 12 variables are weighted Sinus arrhythmia. Normal phenomenon (especially in
according to age and underlying disease. SAPS III uses young people) characterised by alternating periods of
a new, improved model for risk adjustment. Used in a slow and rapid heart rates. The ECG shows sinus rhythm
similar way to APACHE. with irregular spacing of normal complexes. Most com-
Capuzzo M, Moreno RP, Le Gall JR (2010). Curr Opin monly related to respiration, with a rapid rate at end-
Crit Care; 16: 47781 inspiration and a slower rate at end-expiration. A
See also, Mortality/survival prediction on intensive care number of mechanisms have been proposed, including:
unit activation of pulmonary stretch receptors during inspira-
tion, causing inhibition of the cardioinhibitory centre via
vagal afferents; changes in intrathoracic pressure causing
Simpson, James Young (18111870). Scottish obstetri- stretching of the sinoatrial node, producing cardiac
cian; Professor of Midwifery at Edinburgh. The first to accelerations during inspiration; and lower intrathoracic
administer an anaesthetic for obstetrics in 1847, using pressure during inspiration, causing reduced cardiac
diethyl ether. Following a suggestion by Waldie later that output, leading to an increase in heart rate mediated by
year, he used chloroform for the same purpose. Encoun- the baroreceptor reflex. May also involve direct impulse
tered stiff opposition from the clergy and others, who conduction between medullary respiratory and cardiac
maintained that painful childbirth was either Gods will, neurones. Also seen in patients treated with digoxin.
beneficial to the patient, or both; this continued until Abolished by atropine.
Snows administration of chloroform to Queen Victoria
in 1853 (chloroform la reine). Helped popularise chlo- Sinus bradycardia. Usually defined as sinus rhythm at
roform as the replacement for ether. Was made baronet less than 60 beats/min. The ECG shows normal P waves
in 1866. and QRS complexes occurring at a slow rate.
[David Waldie (18131889), Scottish-born Liverpool Caused by:
doctor and chemist] physiological slowing, e.g. in athletes, or during
McKenzie AG (2011). Anaesthesia; 66: 43840 sleep.
disease states, e.g. hypothyroidism, raised ICP, acute
Simulators. Training devices that allow the duplication MI, sick sinus syndrome, jaundice.
of specific clinical scenarios. Useful in the development activation of vagal reflexes, e.g. carotid sinus
of diagnostic and therapeutic skills, decision-making, massage, Valsalva manoeuvre. During anaesthesia,
team training, analysing tasks and errors and assessing it may follow skin incision, stretching or dilatation
risks. Allow prospective and repeated observation of the anus, cervix, mesentery and bladder (Brewer
and analysis of actions rather than retrospective assess- Luckhardt reflex), pulling on the ocular muscles
ment. Individual components, e.g. mannikins, may be (oculocardiac reflex). May occur in critically ill
used to teach specific skills (part-task trainers), or patients during tracheobronchial suctioning.
 Skull X-ray 527

hypoxaemia, especially in children. Thought to be SIRS, see Systemic inflammatory response syndrome
caused by central depression of the vasomotor
centre. Skin diseases. Anaesthetic considerations may be
blockade of the cardiac sympathetic innervation related to:
during high spinal or epidural anaesthesia. diseases with cutaneous and systemic manifesta-
drugs, e.g. propofol, neostigmine, digoxin, opioid tions, e.g. connective tissue diseases, porphyria,
analgesic drugs, -adrenergic receptor antagonists. polymyositis, neurofibromatosis, severe skin disease
If it occurs, the stimulus should be stopped. It may with anaemia and malnutrition.
be treated with anticholinergic drugs (e.g. atropine), scarring or fibrosis of tissues around the face, mouth
-adrenergic receptor agonists or cardiac pacing, but or neck causing difficulty with tracheal intubation,
treatment is only required if accompanied by symptoms, e.g. systemic sclerosis, epidermolysis bullosa dystro-
hypotension or escape beats. phica. In the latter, bullous lesion formation may
follow instrumentation (e.g. laryngoscopy), and may
Sinus rhythm. Normal heart rhythm in which each P be followed by scarring.
wave is followed by a QRS complex on the ECG; i.e. involvement of the immune system causing airway
each impulse originates in the sinoatrial node, which has obstruction (e.g. hereditary angioedema) or severe
the fastest inherent rhythmicity of all cardiac pacemaker manifestations of histamine release (e.g. urticaria
cells. Normal heart rate is usually defined as 60100 pigmentosa). Histamine-releasing drugs should be
beats/min. avoided.
See also, Cardiac cycle; Heart, conducting system; Sinus increased heat loss during anaesthesia if large areas
arrhythmia; Sinus bradycardia; Sinus tachycardia of erythema are present.
susceptibility to skin trauma following handling,
Sinus tachycardia. Usually defined as sinus rhythm at laryngoscopy, and use of sticking plaster or ECG
over 100 beats/min. The ECG shows regular normal P electrodes.
waves and QRS complexes at a rapid rate. effect of drug therapy, e.g. corticosteroids, immuno-
Caused by: suppressive drugs.
increased sympathetic activity, e.g. fear, anxiety; In addition, anaesthetic agents may precipitate cutane-
during anaesthesia, it may represent hypoxaemia, ous lesions (e.g. in adverse drug reactions, bullous erup-
hypercapnia, and inadequate anaesthesia or neuro- tion following barbiturate poisoning, porphyria).
muscular blockade. It may also occur as a compen-
satory mechanism, e.g. in anaemia, hypovolaemia, Skull. The upper part contains the brain, whilst the lower
air embolism/PE. anterior portion forms the facial skeleton:
increased metabolic rate, e.g. hyperthyroidism, superior aspect: divided from left to right by
fever, pregnancy, MH. the coronal suture, separating the frontal bone
drugs, e.g. sevoflurane, isoflurane, pancuronium, anteriorly and the parietal bones posteriorly. The
sympathomimetic drugs, cocaine, anticholinergic sagittal suture separates the two parietal bones
drugs. in the midline, and the lambdoid suture separates
Reduces the time available for ventricular filling and the parietal bones and occipital bone posteriorly.
coronary blood flow; it may precipitate myocardial isch- The anterior fontanelle closes at about 18 months
aemia if severe. Treatment is usually directed at the of age.
cause; -adrenergic receptor antagonists may be required lateral aspect: consists of parietal and occipital
if the patient is at risk of myocardial ischaemia. bones posteriorly, temporal and sphenoid bones
inferiorly, and frontal bone, with the zygomatic and
Sinusitis. Infection of the nasal sinuses of the skull. May maxillary bones below, anteriorly. The mandible
occur as a consequence of upper respiratory tract infec- articulates with the temporal bone at the temporo-
tion, trauma or, especially relevant to ICU, prolonged mandibular joint.
tracheal intubation; has been reported in 240% of anterior aspect: consists of frontal bone superiorly,
patients requiring IPPV. Up to 10 times more common zygomatic bones at the inferolateral edges of the
if nasotracheal or nasogastric tubes are in place; thought orbits, and maxilla centrally, with the mandible infe-
to be related to obstruction of drainage through the riorly. Nerves and vessels pass through the anterior
sinus ostia (although in a third of cases the contralateral foramina and the inferior and superior orbital fis-
side is affected). Also more common in immunosup- sures (Fig. 144a). In addition, the foramen rotun-
pressed and diabetic patients. Usually affects the maxil- dum (below and medial to the superior orbital
lary or sphenoid sinuses, although ethmoid and frontal fissures medial end) transmits the maxillary divi-
sinusitis may also occur (and may result in cerebral sion of the fifth cranial nerve.
venous thrombosis). inferior aspect: especially important because of the
May present with non-specific features of sepsis; structures transmitted by its foramina (Fig. 144b).
diagnosed by CT scanning (although plain X-rays In addition, branches of the first cranial nerve pass
may be helpful), antral puncture and aspiration. Ultra- through the cribriform plates perforations.
sound examination may be useful, but requires spe- See also, Mandibular nerve blocks; Maxillary nerve
cialised equipment. Organisms involved are usually blocks; Ophthalmic nerve blocks; Orbital cavity
Gram-negative bacteria, staphylococci or anaerobes.
Management includes extubation, antibacterial drugs Skull X-ray. Useful investigation for the detection
surgical drainage. Antihistamines and decongestants of linear and depressed skull fractures following
have also been used. Usually resolves within a week of head injury, for classifying facial trauma and planning
extubation. of maxillofacial surgery. Although the presence of a
See also, Intubation, complications of fracture increases the likelihood of intracranial
528 Skull X-ray

(a)
Supraorbital foramen:
Optic canal:
supraorbital nerve (from
2nd cranial nerve (with dural
ophthalmic division, 5th cranial
cuff) + ophthalmic artery
nerve)

Superior orbital fissure:

3rd, 4th, 5th (nasociliary, frontal
+ lacrimal branches of the
ophthalmic division) + 6th
cranial nerve, ophthalmic Inferior orbital fissure:
veins, orbital branch of middle maxillary + zygomatic nerves
meningeal artery + branch of (from maxillary division, 5th
lacrimal artery, sympathetic fibres cranial nerve), infraorbital
vessels

Zygomaticofacial foramen:
Infraorbital foramen:
zygomaticofacial nerve
infraorbital nerve
(from maxillary division,
(from maxillary division,
5th cranial nerve) + artery
5th cranial nerve)

Mental foramen:
mental nerve (from
mandibular division, 5th
cranial nerve)
(b)

Incisive canal:
nasopalatine nerve + greater
palatine artery

Greater palatine foramen:

greater palatine nerve +
Lesser palatine foramen: vessels
lesser palatine nerve + vessels
Foramen ovale:
mandibular division of 5th
cranial nerve
Foramen lacerum: Foramen spinosum:
filled with cartilage during life middle meningeal artery
Carotid canal:
Jugular foramen: internal carotid artery +
internal jugular vein, 9th, 10th + sympathetic fibres
11th cranial nerves
External auditory meatus

Hypoglossal canal: Stylomastoid foramen:

12th cranial nerve 7th cranial nerve

Foramen magnum: Condylar canal:

spinal cord/medulla junction, ascending vein from sigmoid sinus to
spinal portion of 11th cranial nerve, spinal + vertebral veins of neck
vertebral arteries, branches of C13 spinal nerves

Fig. 144 Skull: (a) anterior aspect; (b) base, showing foramina
 Smoke inhalation 529

damage, significant injury may be present with a normal Risk factors:

X-ray. Investigation of choice for demonstrating basal obesity: neck circumference of > 40cm (17 inches)
skull fractures, which are poorly visualised by CT scan- is a good predictor of OSA.
ning. Pneumocephalus is easily evident on a plain pharyngeal abnormalities (e.g. retrognathia, tonsil-
skull X-ray. lar hypertrophy, acromegaly) and other conditions
(e.g. hypothyroidism, neuromuscular disorders).
sedative drugs (including alcohol) can precipitate or
Sleep. Naturally occurring state of unconsciousness; exacerbate the condition.
the response to external stimuli is decreased, but the Features:
subject may usually be readily roused. Two patterns are loud snoring, restlessness, morning headaches and
described: daytime somnolence.
non-rapid eye movement (NREM) sleep, divided medical consequences of OSA include increased
into four stages according to EEG activity: incidence of cognitive disorders, hypertension,
- stage 1: occurs as the subject falls asleep; charac- CVA, arrhythmias, MI and diabetes mellitus.
terised by low-amplitude, high-frequency theta severe OSA may result in cor pulmonale (obesity
waves (312Hz). hypoventilation syndrome).
- stage 2: sleep spindles occur (1214Hz) and high- Screening questionnaires are used to identify those at
amplitude K complexes. high risk; formal diagnosis requires sleep studies, with
- stages 3 and 4: known as slow-wave sleep with polysomnography (monitoring of respiratory airflow,
high-amplitude, low-frequency delta waves (0.5 chest and abdominal movements, EEG and oximetry).
2Hz, 75V). OSA severity is classified according to the apnoea
rapid eye movement (REM) sleep (paradoxical hypopnoea index (number of apnoeas/hypopnoeas
sleep): rapid, irregular, low-amplitude waves occur, divided by the number of hours of sleep): 515 = mild;
similar to those seen in awake subjects. Dreaming 1530 = moderate; > 30 = severe.
occurs. The eyes make rapid movements, accompa- Treatment includes weight loss, nasal CPAP and
nied by tachycardia, tachypnoea, skeletal muscle removal of tonsils if enlarged. Uvulopharyngopalato-
relaxation and penile erection. plasty (UVPP) is of dubious benefit. Tracheostomy may
In a typical nights sleep, a young adult rapidly passes be indicated in severe cases.
through stages 1 and 2, spending about 6090min in Anaesthetic implications:
stages 3 and 4. A period of REM sleep follows, lasting of any predisposing cause.
6090min. This cycle repeats, thus providing about five sedative premedication may precipitate complete
episodes of REM sleep per night (25% of total sleep airway obstruction and should be avoided. If feasi-
time). Sleep disruption is common in the ICU and may ble, regional anaesthesia should be considered; if
be related to: not, rapidly cleared anaesthetic agents should be
pre-existing disease: e.g. patients with COPD show used (e.g. propofol, desflurane).
decreased total sleep time and REM sleep with fre- maintenance of the airway during induction of
quent arousals caused by hypoxaemia, hypercapnia anaesthesia and tracheal intubation may be
and coughing. difficult.
drugs: e.g. benzodiazepines abolish stages 3 and 4 patients are particularly sensitive to the depressant
NREM sleep; opioid analgesic drugs increase effects of sedatives and opioid analgesic drugs;
arousal frequency; tricyclic antidepressant drugs, airway obstruction, hypoventilation, hypoxia and
barbiturates and amfetamines inhibit REM sleep. carbon dioxide narcosis may readily occur
Catecholamines increase wakefulness. postoperatively.
anaesthesia and surgery: the stress response to patients are often nursed in ICU/HDU with
surgery, fever, pain, opioids, starvation and age nocturnal CPAP and maintenance of a 30 head-
decrease stages 3 and 4 NREM sleep and abolish up tilt.
REM sleep on subsequent nights. Adesanya AO, Lee W, Greilich NB, Joshi GP (2010).
environmental factors: noise (e.g. telephones, Chest; 138: 148998
conversations, alarms), bright lighting, extremes of
temperature. Slow-reacting substance-A, see Leukotrienes
Sleep deprivation may result in ICU delirium, increased
catabolism (due to increased corticosteroid secretion
and insulin resistance), fatigue and difficulty in weaning Smallpox, see Biological weapons
from ventilators.
Hardin KA (2009). Chest; 136: 28494 Smoke inhalation. Resultant pulmonary insufficiency is
the commonest cause of death in patients admitted to
hospital with burns.
Sleep apnoea/hypopnoea. Cessation (apnoea) or Problems are related to:
reduction of > 30% (hypopnoea) of breathing for > 10s low FIO2 of inspired gas, and inhalation of carbon
during sleep. Resultant hypoxaemia and hypercapnia monoxide, cyanide, nitrogen oxides and other sub-
causes arousal, thus disrupting normal sleep architec- stances. All may result in hypoxaemia.
ture. Affects 510% of the adult population. May have inhaled carbon particles coated with irritant sub-
a central mechanism (caused by lack of respiratory drive, stances (e.g. aldehydes) which may cause laryngo-
e.g. Ondines curse) or may be obstructive (obstructive spasm, bronchospasm and inhibition of ciliary
sleep apnoea; OSA). OSA is caused by decreased tone activity.
of the pharyngeal muscles during deep sleep, resulting V/Q mismatch, shunt and pulmonary oedema may
in intermittent upper airway obstruction. occur.
530 Smoking

thermal injury to the airway may be followed by Society of Critical Care Medicine (SCCM). Founded
upper airway obstruction, bronchospasm, tracheal in 1970 to support the specialty of critical care as a sepa-
and bronchial oedema and sloughing. rate but interdisciplinary entity, with Critical Care Med-
Further respiratory impairment may occur if infection icine as its official journal. Supports research, education
and acute lung injury supervene. and provision of resources.
Management: as for burns, carbon monoxide poison-
Soda lime. Mixture used for CO2 absorption in
ing, cyanide poisoning, respiratory failure. Early
anaesthetic breathing systems, composed of calcium
fibreoptic bronchoscopy for assessment and pulmo-
hydroxide (~90%), sodium hydroxide (45%), potas-
nary toilet is advocated by some.
sium hydroxide (traditionally 1%; in the UK modern
See also, Nitrogen, higher oxides of
preparations do not contain potassium hydroxide), sili-
cates (for binding; less than 1%) and indicators. Used
Smoking. Common cause of cardiovascular and respira-
with 1419% water content. CO2 in solution reacts with
tory pathology in surgical and non-surgical patients.
Effects:
sodium ( potassium) hydroxides to form the respective
carbonates, which then react with calcium hydroxide to
cardiovascular:
produce calcium carbonate, replenishing sodium and
- nicotine is an agonist at nicotinic acetylcholine
potassium hydroxides. Heat and water are also produced
receptors in sympathetic ganglia; it increases
during the reaction. Exhaustion of its activity is indicated
heart rate, SVR and thus BP. It also increases
by dyes; several have been used, but the most common
myocardial O2 demand, and possibly decreases
one changes from pink to white.
coronary blood flow.
Provided in granules of size 48 mesh (will pass
- carbon monoxide combines with up to 15% of
through a mesh of 48 strands per inch in each axis; i.e.
haemoglobin to form carboxyhaemoglobin, re-
pore size of 1/161/64 in2). Canisters should be tightly
ducing the O2-carrying ability of blood. Causes
packed to reduce channelling of gases through large
shift of the oxyhaemoglobin dissociation curve to
gaps. The total volume of space between granules should
the right, further impeding release of O2. Thus
equal the volume of the granules themselves. Dust may
haemoglobin concentration and packed cell
be inhaled using older systems, especially the to-and-
volume are often increased, increasing blood vis-
fro system. Large canisters containing up to 2kg soda
cosity and hindering oxygen delivery further.
lime are commonly employed.
- increased risk of ischaemic heart disease and fre-
Known to react with trichloroethylene, with the risk
quency of ventricular arrhythmias.
of neurological damage. The modern inhalational anaes-
- increased risk of DVT.
thetic agents, especially sevoflurane, may react with soda
pulmonary:
lime if the latter is warm and very dry. Compound A,
- impaired ciliary activity.
carbon monoxide, formic acid and formaldehyde may be
- impaired leucocyte activity.
produced. Compound A is a particular product of sevo-
- increased risk of bronchial carcinoma.
flurane, leading to fears over its use in circle systems,
- increased bronchial reactivity and COPD.
although evidence of toxic levels of compound A within
Smokers are more likely to have increased sputum pro-
such systems has not been found. Significant levels of
duction and retention, bronchospasm, coughing, atelec-
carbon monoxide have been reported. Furthermore, the
tasis and chest infection perioperatively. Poor wound
temperature in the absorber may increase to dangerous
and bone healing is also more common.
levels and there may be some absorption of the volatile
Stopping smoking is thought to be beneficial preop-
agent itself. The minimal level of moisture that will
eratively, in order to minimise its acute adverse effects.
prevent such reactions is 2% for sodium hydroxide and
Effects of carbon monoxide and nicotine are signifi-
4.7% for potassium hydroxide, leading to the latters
cantly reduced after 1224habstinence; up to 68 weeks
removal from modern preparations in the UK. Normal
is thought to be necessary for restoration of ciliary and
use of circle systems is not thought to result in such low
immunological activity.
levels of moisture, but they have been found after pro-
Sweeney BP, Grayling M (2009). Anaesthesia; 64:
longed passage of dry gas through the absorber, e.g. at
17986
the start of a Monday morning operating session if gases
See also, Carbon monoxide poisoning
are left running over the weekend.
Attempts to prevent the soda lime drying out include
Snake bites, see Bites and stings
shutting off anaesthetic machines after use, changing the
soda lime regularly and not relying on colour changes to
Snow, John (18131858). Pioneer of English anaesthesia,
indicate dehydration, checking for unusually hot absorp-
born in York. Moved to London in 1836. Developed the
tion canisters or unexpectedly low concentrations of
science and art of anaesthesia, describing five stages of
volatile agent, and addition of zeolites that can physi-
anaesthesia in 1847. Designed inhalers for diethyl ether
cally trap water, or inorganic chlorides that crystallise
and chloroform, and wrote two famous textbooks on the
water within the soda lime. A new mixture (calcium
use of these agents (his book on chloroform was pub-
hydroxide lime) consisting of calcium hydroxide with
lished posthumously). Widely regarded as the expert in
calcium chloride (plus calcium sulphate and polyvinyl-
his field, he administered chloroform to Queen Victoria
pyrrolidone to improve hardness and porosity) has been
during childbirth in 1853 and 1857. Also famous for dem-
developed which does not contain sodium or potassium
onstrating that cholera was spread by contaminated
hydroxide and does not react with any of the currently
drinking water, not by foul air, as previously believed.
used volatile agents.
Removal of the Broad Street water pump handle on his
See also, Baralyme
suggestion is said to have stopped the London epidemic
of 1854. One of the heraldic supporters of the Royal Sodium (Na+). Principal cation in the ECF, accounting
College of Anaesthetists (with Clover). for 90% of the osmotically active solute in plasma and
 Sodium/potassium pump 531

interstitial fluid. Thus the prime determinant of ECF Sodium dichloroacetate. Activator of pyruvate dehy-
volume. Total body content is about 4000mmol, of which drogenase, resulting in increased oxidation of lactate to
50% is in bone, 40% in ECF, and 10% intracellular. acetylcoenzyme A and CO2. Has been used to treat lactic
About 70% is available for exchange. Normal plasma acidosis, although randomised trials have not found an
levels: 135145mmol/l. Of central importance in the increase in survival.
function of excitable cells, e.g. concerning membrane
potentials and action potentials. Sodium nitrite, see Cyanide poisoning
Actively absorbed from the small intestine and colon,
facilitated by aldosterone and the presence of glucose Sodium nitroprusside (SNP). Vasodilator drug, used as
in the gut lumen. The kidney filters approximately an antihypertensive drug, e.g. in hypotensive anaesthe-
26000mmol Na+/day, of which 99.5% is reabsorbed by sia. Also used in cardiac failure. Presented as a powder
passage through the nephron (mostly at the proximal for reconstitution in 5% dextrose. Unstable in solution,
convoluted tubule). Reabsorption is influenced by renal with decomposition to highly coloured products. Solu-
tubular hydrostatic and oncotic gradients, aldosterone, tions require protection from light and should be used
adrenocortical hormones, atrial natriuretic hormone and within 24hof preparation.
the rate of secretion of hydrogen and potassium ions. Reacts with thiol groups in vascular smooth muscle
Daily losses: about 150mmol in the urine, with and converted to nitrite, which reacts with hydrogen ions
10mmol via each of faeces, sweat and skin. Saliva to produce nitric oxide. Acts mainly on arteries, although
contains 10mmol/l, sweat 50mmol/l, gastric secre- veins are also affected. Thus reduces SVR, maintaining
tions 60mmol/l and the rest of the GIT about cardiac output and tissue perfusion. Also reduces myo-
130mmol/l. cardial O2 consumption whilst increasing coronary blood
Daily requirement: about 1mmol/kg/day; a normal flow, although coronary steal has been reported. Com-
diet usually far exceeds this. pensatory tachycardia is common. Hepatic blood flow
Regulated via changes in: remains constant, whilst renal blood flow and cerebral
ECF sodium concentration and osmolality via blood flow increase. Active within 30s of administration.
osmoreceptors, affecting the renin/angiotensin Broken down non-enzymatically within red blood cells
system and aldosterone secretion. (catalysed by haemoglobin) to produce five cyanide ions
ECF volume changes: via baroreceptors, affecting from each molecule, some of which combine with hae-
atrial natriuretic peptide secretion in addition to the moglobin to form methaemoglobin; the remainder are
above hormones. converted to thiocyanate in the liver by rhodonase and
See also, Hypernatraemia; Hyponatraemia then excreted in the urine. Plasma half-life of SNP is
about 2min.
Sodium bicarbonate, see Bicarbonate Dosage: initially 0.51.5g/kg/min iv, increased to a
maximum of 8g/kg/min (maximal total dose of
Sodium calcium edetate. Chelating agent, used in the 1mg/kg over 23h). Tachyphylaxis may occur.
Side effects:
treatment of acute and chronic lead poisoning. Has also
may cause rapid and profound hypotension.
been used successfully in poisoning with copper and
rebound hypertension following its abrupt with-
radioactive materials.
Dosage: 40mg/kg iv bd for 5 days; repeated if neces-
drawal. Caused by activation of the renin/angiotensin
sary after a 7-day break. system and increased plasma catecholamine levels.
raised ICP may occur.
Side effects: nephrotoxicity, nausea and vomiting,
platelet aggregation may be inhibited.
myalgia, hypotension, T wave abnormalities on the
pulmonary shunt may be increased in normal
ECG.
lungs via impairment of pulmonary hypoxic
vasoconstriction.
Sodium citrate. Non-particulate antacid, widely used cyanide toxicity (hence limitation of dose). More
preoperatively to increase gastric pH in patients at likely in vitamin B12 deficiency. May present
risk of aspiration of gastric contents, e.g. before with metabolic acidosis, and reduced arteriovenous
general anaesthesia in obstetrics. Thought to be less O2 difference. Treated as for cyanide poisoning.
harmful than magnesium trisilicate if inhaled. Effective Combination of SNP with trimetaphan and prophy-
for 3050min following oral intake of 30ml 0.3 molar lactic administration of thiosulphate have been sug-
solution. gested as methods for reducing risk of cyanide
Also used to relieve discomfort from urinary tract toxicity.
infection by raising urinary pH. thiocyanate may cumulate after more than 3 days
infusion, with possible interference with thyroid
Sodium clodronate, see Bisphosphonates function.

Sodium cromoglicate (Cromoglycate). Drug used in Sodium/potassium pump. Protein pump present in
the prophylaxis of asthma; of no value in acute attacks. every cell membrane, responsible for active transport of
Thought to stabilise mast cells by preventing calcium ion sodium out of cells and potassium into cells. The protein
entry, thus preventing IgE-triggered release of inflam- is an enzyme which catalyses hydrolysis of ATP to ADP,
matory mediators. Particularly useful in allergic and providing the energy required for the transport. Consists
exercise-induced asthma in children. Should be taken of two subunits (mw 95000) that extend through the
regularly as a powder, aerosol or nebulised solution, membrane and provide the binding site for ATP, and two
usually 1020mg 48 times daily. Generally less effective subunits (mw 40000). Three sodium ions are trans-
than corticosteroids. ported for every two potassium ions, creating a net nega-
See also, Bronchodilator drugs tive charge within the cell. Required for maintenance of
532 Sodium thiosulphate

cellular membrane potential and electrolyte composi- toluene, petroleum products and carbon tetrachloride.
tion. Inhibited by cardiac glycosides. Acute problems may include depressed consciousness
and arrhythmias, the latter probably related to myo
Sodium thiosulphate, see Cyanide poisoning cardial sensitisation to endogenous catecholamines.
Sudden death has occurred. Specific organ damage
Sodium valproate. Anticonvulsant drug used for all (renal, hepatic) may occur with specific substances, e.g.
forms of epilepsy. Acts mainly by blocking neuronal toluene after prolonged usage. Management is largely
sodium channels but also by inhibiting calcium channels supportive.
in thalamic neurones and enhancing GABA activity.
Rapidly absorbed by mouth and largely protein-bound Somatostatin (Growth hormone inhibiting hormone).
(90%), its half-life is approximately 12h. Hormone secreted by the pancreas, GIT mucosa and
Dosage:
hypothalamus. Exists in two forms, with either 14 or 28
2030mg/kg/day orally, up to 2.5g daily.
amino acid residues. Also a neurotransmitter in the brain
400800mg (up to 10mg/kg) iv over 35min fol-
and spinal cord (especially substantia gelatinosa, where
lowed by iv infusion up to 2.5g/day. Plasma levels it may be involved in pain transmission somatostatin
are poor indicators of efficacy but are useful in has been shown to produce analgesia when injected epi-
monitoring toxicity at high doses. durally). Other actions include:
Side effects: GIT disturbances, transient hair loss,
inhibition of release of growth hormone and thyroid
rarely thrombocytopenia and impaired platelet func- stimulating hormone.
tion, pancreatitis and severe hepatitis. An increase in suppression of release of GIT hormones e.g. gastrin,
plasma ammonia level occurs in 20% of patients but cholecystokinin, vasoactive intestinal peptide.
is usually transient. inhibition of release of insulin and glucagon.
Analogues (lanreotide and octreotide) have been used:
SOFA, see Sepsis-related organ failure assessment
to control diarrhoea and flushing in the carcinoid syn-
Solubility. Extent to which a substance dissolves in drome, possibly via inhibition of 5-HT release; in the
another substance. management of bleeding oesophageal varices; and in the
Examples of clinical relevance: management of acromegaly.
inhalational anaesthetic agents: speed of onset of
anaesthesia depends on their solubility in blood, Sonoclot, see Coagulation studies
and potency depends on their solubility in lipids
(MeyerOverton rule). The ability of N2O to expand Sore throat, postoperative. Reported in up to 90% of
gas-containing cavities depends on its greater blood cases in some studies, and in up to 25% of patients fol-
solubility than nitrogen. For a gas dissolving in a lowing spontaneous breathing via a facemask.
May be related to:
liquid, solubility depends on the temperature (solu-
tracheal intubation:
bility decreases as temperature increases), and the
properties of the gas and liquid (expressed by the - use of suxamethonium.
solubility coefficient). Some volatile agents, (e.g. - shape and type of tracheal tube and cuff; larger
halothane) may also dissolve in rubber anaesthetic tubes are associated with a greater incidence of
tubing, producing significant concentrations even sore throat and hoarse voice than smaller ones.
when the vaporiser is turned off. - trauma on laryngoscopy, intubation and
non-gaseous drugs: solubility in water determines
extubation.
requirement for other solvents, e.g. Cremophor EL - use of stylets or bougies.
or propylene glycol for parenteral injection. Solu- - pharyngeal suction.
bility in lipid membranes affects the extent to which - use of throat packs.
a drug crosses membranes, e.g. GIT wall, blood - use of lubricating/local anaesthetic gel or spray.
use of nasogastric tubes.
brain barrier.
anticholinergic premedication.
See also, Partition coefficient
use of an LMA or oro-/nasopharyngeal airways.
Solubility coefficients. Expression of solubility. Two use of unhumidified gases.
coefficients are commonly used: Also common after tracheal intubation in the ICU, espe-
Bunsen solubility coefficient: volume of gas mea- cially after prolonged IPPV.
sured at STP that dissolves in unit volume of liquid McHardy FE, Chung F (1999). Anaesthesia; 54: 44453
at the stated temperature and pressure.
Ostwald solubility coefficient: volume of gas dis- Sotalol hydrochloride. Water-soluble non-selective
solved in unit volume of liquid at the stated tempera- -adrenergic receptor antagonist and class III antiar-
ture and pressure, i.e. equals the partition coefficient rhythmic drug, available for oral and iv administration.
between liquid and gas phases. If measured at 0C, it Used for prophylaxis and treatment of SVT and VT.
equals the Bunsen solubility coefficient. Dosage:

For solubility of inhalational anaesthetic agents, the 80mg orally daily in 12 doses (with ECG monitor-
Ostwald solubility coefficient (at 37C) is usually used ing), increased up to 160320mg/day. Dosage is
as it is independent of pressure. reduced in renal failure.
[Robert WE Bunsen (18111899) and Wilhelm Ostwald 20120mg iv over 10min, repeated qds as required.
(18531932), German chemists] Side effects: as for -adrenergic receptor antagonists.
Prolonged QT interval and torsades de pointes may
Solvent abuse. Form of substance abuse involving the occur, especially in the presence of hypokalaemia
intake (usually by inhalation) of a variety of solvents (electrolyte deficiencies should be corrected before
used in glues, paints and similar products; include starting treatment).
 Spinal anaesthesia 533

SPAD, Single-pass albumin dialysis, see Liver dialysis devices employ a single chamber instead of two,
and some use a rotating perforated wheel to
SPEAR, Selective parenteral and enteral antisepsis divide the beam(s) of light into pulses. The wheel
regimen, see Selective decontamination of the digestive may incorporate different filters to measure dif-
tract ferent substances. The technique may be used for
multiple simultaneous gas analysis.
Specific dynamic action. Energy required to assimilate Sources of error include overlap of absorption
food into the body, manifested as an increase in meta- spectra by several gases (e.g. CO, CO2 and N2O
bolic rate following intake. Thus the net total amount all share some absorption range) and collision
of energy obtained from food is reduced (by 30% for broadening, whereby the presence of one gas
protein, 6% for carbohydrates and 4% for fats). broadens the absorption spectrum of another.
See also, Nutrition These may be compensated for with electronic
correction factors and the use of a different (or
Specific gravity (Relative density). The density of a more than one) wavelength for each gas.
substance divided by that of water. Still used to indicate - main stream: analysis takes place at the breathing
urinary concentration because measurement is easy system itself, by incorporating a special connector
(using a hydrometer), although not as useful clinically as near the patient end of the tubing. An emitter/
osmolality. Varies with temperature. Depends on the detector is attached to the connector and light is
mass and number of solute particles, whereas osmolality passed through small sapphire windows in the
depends only on number of particles. Thus heavy mole- connector. Although more rapid and not requiring
cules (e.g. radiographic contrast media) greatly increase sample tubing, the device may be bulky and heavy.
specific gravity with only small increases in osmolality. photoacoustic spectroscopy: relies on absorption of
Normal values: for urine (at 20C), 1.0021.035; for infrared light of different wavelengths by different
plasma (at 20C), 1.010; for CSF (at 37C), 1.0041.008. molecules, with subsequent emission of sound at the
Glucose 2.7g/l and protein 4g/l each increase specific wavelengths concerned for each molecule. Detec-
gravity by 0.001. tion is with a microphone. Multiple simultaneous
For a gas, the ratio of substance to that of air is often gas analysis may be performed.
used. Most anaesthetic-related gases and vapours are Raman spectroscopy: relies on Raman scattering,
heavier than air, e.g. isoflurane, enflurane, sevoflurane the absorption and immediate emission of light
and desflurane ( 7.5), halothane ( 6.8), N2O ( 1.53), by gases in a pattern specific to the individual mol-
CO2 ( 1.5), O2 ( 1.1). ecules. All gaseous molecules may be analysed in
this way (but not single atoms). Powerful light
Specific heat capacity, see Heat capacity sources (e.g. lasers) are required to give an ade-
quate signal. Multiple simultaneous gas analysis
Specific latent heat, see Latent heat may be performed.
ultraviolet spectroscopy: has been used to measure
Specificity. In statistics, the ability of a test to exclude halothane concentrations. Requires lengthy warm-
false positives. Equals: ing up and frequent calibration; now rarely used
the number correctly identified as negative routinely.
gas discharge meter: used to measure nitrogen con-
he condition
total without th centration. 1500 V potential is passed across the gas
See also, Errors; Predictive value; Sensitivity sample in a tube. Intensity of purple light at a spe-
cific wavelength is measured.
SPECT, Single photon emission computed tomography, mass spectroscopy: now usually referred to as mass
see Positron emission tomography spectrometry (see Mass spectrometer).
[Chandrasekhara V Raman (18881970), Indian
Spectroscopy. In anaesthesia, used for gas analysis, physicist]
especially for estimation of CO2, N2O and volatile agent See also, Carbon dioxide, end-tidal; Carbon dioxide mea-
concentrations. Different types: surement; Near infrared spectroscopy
infrared spectroscopy: depends on the ability of
gases containing different atoms to absorb infrared Spider bites, see Bites and stings
light (thus O2 and nitrogen cannot be analysed):
- side stream: sample gas is drawn into a chamber Spinal anaesthesia (Subarachnoid/intrathecal anaes-
through which half of a split infrared beam is thesia). Probably first performed by Corning in 1885, but
passed, the other half passing through a reference first performed for surgery by Bier in 1898. Initial use of
chamber containing air. The amount of infrared cocaine was associated with tremor, headache and
light absorbed by the sample gas depends on the muscle spasms. The less toxic procaine was first used by
amount of gas present, and is determined by com- Braun in 1905 and was soon used widely. Hyperbaric
paring the emergent beams from the sample and solutions were introduced by Barker in 1907. Further
reference chambers. This is done with photoelec- refinements were related to new local anaesthetic agents.
tric cells behind each chamber, or by passing the Continuous spinal techniques were described in the
beams through two further chambers containing 1940s, initially via rubber tubing connected to the needle
e.g. CO2, separated by a diaphragm. The heating left in situ.
effect of the infrared light causes pressure to rise Popularity waned in the late 1940s following reports
within these chambers; the difference in pressure of neurological damage and the introduction of neuro-
between them depends on the amount of infrared muscular blocking drugs for general anaesthesia (GA).
light absorbed by the original gas sample. Some In the classic Woolley and Roe case in the UK in 1947,
534 Spinal anaesthesia

two cases of paraplegia during the same operating list are easier to use but increase the risk of headache.
followed spinal anaesthesia. Phenol contamination via Thinner needles are often inserted through a 19
cracks in the cinchocaine ampoules was blamed at the G iv needle or introducer, e.g. Sise introducer. The
time, although contamination of the syringes and needles bevel (if present) is faced laterally to reduce the
with acidic descaler solution from the steriliser has been risk of headache.
suggested as being more likely. - resistance increases as the ligamentum flavum is
Increasing popularity over the last 4050 years has entered and when dura is encountered, with a
followed better understanding of the technique, and sudden give as the dura is pierced. Correct loca-
acceptance that the incidence of side effects is low when tion is confirmed by CSF at the needle hub; aspi-
spinal anaesthesia is correctly performed. ration may be required with very fine needles.
Indications: surgical procedures to the lower body, Rotation of the needle in 90 steps may produce
especially perineum and legs. Considered the method CSF if none is obtained initially.
of choice (with epidural anaesthesia) by many anaes- Hanging drop and other techniques have been
thetists for TURP, caesarean section and orthopaedic used to identify the epidural space before dural
surgery, e.g. of the hip. Has also been used for upper puncture.
abdominal surgery. Deliberate high or total spinal - with the other hand securing the needle against
anaesthesia was formerly used for hypotensive anaes- the patients back to avoid dislodgement, the solu-
thesia, and to provide abdominal muscle relaxation. tion is injected, with aspiration before, during and
Anatomy: after injection to confirm correct placement.
the spinal cord ends at L12 in adults, lower levels Injection should cease if pain is experienced.
in children. The dura ends at S2; therefore lumbar - non-Luer connector systems are now available to
puncture is usually performed at the L34, L45 or reduce the risk of wrong-route drug administra-
L5S1 interspaces (n.b. the actual interspace used is tion errors (i.e. intrathecal administration of an iv
commonly higher than that intended). drug).
the L4 or L45 interspace is usually crossed by a paramedian approach: requires less back flexion,
line drawn between the iliac crests, although this is and is easier if the vertebral ligaments are
not very reliable. The spinous process of T12 has a calcified:
notched lower edge. - infiltration is performed 1.5cm lateral to the
the course taken by the needle is as for reaching the cranial border of the spinous process at the
epidural space, plus the dura (see also, Meninges; selected interspace.
Vertebrae; Vertebral canal; Vertebral ligaments). - the needle is inserted, aiming medially and crani-
Technique: ally until the resistance of the ligamentum flavum
preoperative assessment, preparation and premedi- is felt. If the lamina is encountered, the needle is
cation are as for GA. Facilities for resuscitation and walked off its cranial edge.
progression to GA must be available. - dural puncture and injection as before.
monitoring is as for GA. An iv cannula must be a continuous catheter technique may be used as for
placed. Preloading with fluid is controversial (see epidural anaesthesia; it has been unpopular because
below). of fears over infection and CSF leak, difficulty of
the patient is placed in the lateral position, with chin handling the very fine catheters (2832 G), and the
on the chest and knees drawn up, or sitting on the occurrence of cauda equina syndrome following use
edge of the trolley. Back flexion opens the interver- of lidocaine, but allows incremental injection of solu-
tebral spaces. An assistant is required to steady the tion and therefore greater cardiovascular stability
patient. during onset of block. Both catheter-through-needle
sterile gloves are considered mandatory. The back and catheter-over-needle systems are available.
is cleaned, avoiding contamination of gloves and Solutions used (Table 39):
needles with cleaning solution (implicated in only hyperbaric bupivacaine 0.5%, hyperbaric pri-
causing arachnoiditis and meningitis). Masks reduce locaine 0.5% and plain levobupivacaine 0.5% are
both forward and downward dispersal of the anaes- available specifically for spinal anaesthesia in the
thetists oral bacteria during talking and are usually
recommended. Use of gown and drapes is contro-
versial; they are usually employed in the UK, but
less so in the USA. (a) (b) (c) (d)
median approach:
- the chosen interspace is infiltrated with local
anaesthetic.
- the spinal needle is inserted in the midline, aiming
slightly cranially. Non-cutting needles, e.g. Sprotte
(smooth-sided pointed tip, with wide lateral hole
proximal to the tip), Whitacre (pencil tip-shaped,
with the hole just proximal to the tip) or Greene
(oblique bevel, with bevel edges rounded) are
associated with a lower incidence of post-dural
puncture headache and are often used (Fig. 145).
The Quincke needle point, with its short-bevelled
cutting tip, is less often used nowadays, except in
patients at low risk of headache, e.g. the elderly. Fig. 145 Different types of spinal needles: (a) Sprotte; (b) Whitacre;
2229 G needles are commonly used; the larger (c) Greene: (d) Quincke
 Spinal anaesthesia 535

lateral position with immediate turning into the

Table 39 Doses (mg) of local anaesthetics required for spinal
supine position usually produces blockade
blockade of different heights
to T46.
Agent L4 T10 T46 Duration (h) - patient factors, e.g. weight, height, sex, age, are not
thought to be as critical as previously suspected,
Bupivacaine 0.5% (heavy) 510 1015 1520 1.52.5 but they have a small influence. Large variability
Cinchocaine 0.5% (heavy) 46 68 1012 23 of blockade between patients is normally found.
Levobupivacaine 0.5% 2.57.5 7.512.5 12.515 1.52 Recently, volume of CSF has been implicated at
(plain) least partly in this variability. Reduced volumes of
Lidocaine 5% (heavy) 2550 5075 75100 11.5 agent are required in obstetric analgesia and
Prilocaine 2% (heavy) 2040 4060 6080 1.52 anaesthesia.
Tetracaine 1% (heavy; 46 812 1416 1.52.5
- technical factors, e.g. speed of injection, barbotage
mixed with equal
volumes of CSF)
(repeated aspiration of CSF into syringe, mixing
it with local anaesthetic before re-injection) and
direction of the needle, tend to affect variability
of blocks; thus slow injection without barbotage
produces the most reliable results.
UK. In the USA, hyperbaric 0.75% bupivacaine, spinal opioids improve the quality and duration of
hyperbaric tetracaine (amethocaine) 1% and lido- analgesia but at the risk of specific side effects.
caine 5% are available (the latter for dilution to other drugs have been studied, e.g. ketamine, mid-
2.5% before administration because of risks of tran- azolam and clonidine, but these are not licensed.
sient radicular irritation syndrome or damage). Effects:
larger volumes are required for plain solutions than results in rapid onset of block (usually within
for heavy ones. Duration of block may be extended 35min), although maximal effect may take up to
by addition of vasopressors; adrenaline 0.20.5ml 30min. Vasodilatation in the feet is usually seen
1:1000 and phenylephrine 0.55mg have been first, with flushing and increased warmth.
used, although rarely in the UK. Fears have been thought to act mainly at spinal nerve roots, although
expressed concerning possible cord ischaemia pro- some effect is possible at the spinal cord itself. Dif-
voked by their use. L5S2 segments remain blocked ferential blockade of different motor and sensory
for the longest. modalities is thought to be related to the size and
low-dose techniques are increasingly used, e.g. therefore sensitivity of different neurones to local
in obstetrics; a common combination for labour anaesthetics. Thus the smaller sympathetic pregan-
consists of 1ml bupivacaine 0.25% with fentanyl glionic fibres are more easily blocked than larger
1025g. sensory and motor fibres, with the sympathetic
spread of solution and extent of blockade are level higher than the sensory level. Assessment of
affected by many factors, including: the sympathetic level is difficult; the galvanic skin
- dose: thought to be the most important; increased response has been used. The level of blockade for
variability may occur with altered concentration touch sensation is usually 12 segments below that
and volume. for pinprick, whilst that for motor innervation is 12
- site of injection. segments lower than that for sensory innervation.
- baricity of solution and position: thus hyperbaric CVS:
solutions affect dependent parts, hypobaric solu- - sympathetic blockade causes vasodilatation below
tions, e.g. tetracaine 0.1%, affect upper parts. Plain the level of block. Reductions in cardiac output
bupivacaine 0.5% is slightly hypobaric; tetracaine and BP are thought to be caused mainly by reduced
1% is isobaric. venous return consequent to venous dilatation,
Use of hyper- or hypobaric solutions relies on although the fall in SVR contributes. Increased or
lateral/supine positioning and head-up/down tilt, unaltered cardiac output has also been reported.
combined with the normal curvature of the spine: Reflex vasoconstriction occurs above the level of
- thoracic curve is concave anteriorly; T4 is tradi- block. Hypotension is particularly likely in hypo-
tionally held to be the most posterior part (most volaemia, since cardiac output in this case is depen-
dependent in the supine position) but recent dent on resting vasoconstriction.
imaging studies suggest T8 instead. Hypotension is also more likely in obstetrics,
- lumbar curve is convex anteriorly; L34 is the when aortocaval compression may occur. Hypo-
most anterior part (uppermost in the supine posi- tension may be exacerbated by bradycardia and
tion). This curve may be abolished by flexing the sedative drugs (depressant effects of local anaes-
hips in the supine position. thetic are minimal). The drop in BP may be
In addition, the greater width of females hips greater with higher levels of blockade, but this is
compared with their shoulders tends to tip their not always so.
spinal canal head-down, in the lateral position; in - bradycardia may be due to block of sympathetic
males, the opposite occurs. cardiac innervation (T14), vagal stimulation
Thus slow injection of 1ml hyperbaric solution during surgery or a reflex response to decreased
at L5S1 with the patient sitting produces saddle venous return. Cardiac arrest has been reported,
block suitable for perineal surgery, with minimal possibly involving the BezoldJarisch reflex.
hypotension. Blocks may be restricted to one side - cardiac work and O2 demand are reduced.
by injection in the lateral position, although - renal, hepatic, cerebral and coronary blood flows
fixing of local anaesthetic may require up to are maintained if marked hypotension does
40min. Injection of hyperbaric solution in the not occur.
536 Spinal anaesthesia

- reduction in perioperative bleeding is thought to nausea: may be related to vagal stimulation, e.g.
be due to reduced BP, lack of venous hyperten- during handling of the bowel. Hypotension is an
sion due to venodilatation and pooling of blood important cause.
in dependent vessels. sedation is used to reduce awareness and improve
- reduction of postoperative DVT is thought to be patient comfort. Benzodiazepines and propofol are
due to vasodilatation, haemodilution and reduced commonly used; ketamine provides some analgesia,
viscosity secondary to iv fluid administration, e.g. whilst positioning for injection in trauma cases.
increased fibrinolysis. Disadvantages include respiratory and cardiovascu-
- absorbed adrenaline may have systemic effects, lar depression and confusion, especially if sedation
if used. is excessive. General and spinal anaesthesia may be
RS: intercostal and abdominal weakness may impair combined, not necessarily with increased risk of
active exhalation and coughing, although tidal hypotension.
volume and inspiratory pressure are maintained by Complications:
intact diaphragmatic innervation (C35). FRC is hypotension and high blockade as above.
reduced when supine, and hypoventilation may post-dural puncture headache.
follow sedation; thus O2 is usually administered via neurological injury:
a facemask as a precaution, and to allow concurrent - transient radicular irritation: more common with
N2O administration if required. lidocaine.
GIT: bowel contraction results from dominant para- - direct trauma is extremely rare. Injection should
sympathetic tone following sympathetic blockade. stop immediately if pain is felt.
Sphincters relax and peristalsis increases. - haematoma formation with spinal cord compres-
urinary retention may occur. sion is extremely rare with normal coagulation. It
stress response to surgery is attenuated. Injected may be masked by regional blockade. Permanent
drug is eliminated via absorption by subarachnoid neurological damage may occur if surgical decom-
and epidural vessels. pression is delayed > 812h.
Management: - cord ischaemia, e.g. anterior spinal artery syn-
assessment: level of sensory blockade is usually drome, thought usually to occur with severe hypo-
determined by testing for temperature (e.g. using tension. Vasopressor drugs have been implicated
ice or ethyl chloride spray) or pinprick sensation, but their role is unclear.
though touch may be more reliable. Knowledge - infection/aseptic meningitis.
of appropriate dermatomes is required. Motor - cauda equina syndrome.
block is assessed by testing muscle groups of appro- - arachnoiditis.
priate myotomes; commonly expressed using the backache (the contribution of spinal anaesthesia
Bromage scale. itself is doubtful but muscular relaxation with pos-
positioning of the patient may be used to extend or sible stretching of ligaments has been suggested
reduce spread of the block as required, until fixed. rather than direct trauma).
a high level of block may produce feelings of Contraindications:
impaired breathing and nasal stuffiness, plus non-acceptance by the patient.
impaired sensation or power in the arms. Total infection, both generalised and local.
spinal blockade results in apnoea and loss of con- hypovolaemia/shock.
sciousness, with fixed dilated pupils. Treatment is as neurological disease: raised ICP is an absolute con-
for hypotension, plus tracheal intubation and IPPV. traindication because of the risk of coning. Other
Recovery is complete if BP and oxygenation are disease is controversial; medicolegal implications
maintained. are usually quoted (e.g. fear of being blamed if a
preloading with iv fluid before performing spinal naturally progressive lesion becomes worse).
anaesthesia is controversial, with some authorities abnormal coagulation: full anticoagulation and sig-
favouring the use of vasoconstrictors as being nificant coagulopathy are considered absolute con-
equally efficacious and more logical. In addition, traindications due to the risk of vertebral canal
fears have been expressed concerning fluid over- haematoma. Low-dose heparin therapy is contro-
load, especially in the elderly. versial; the decision usually depends on con
A drop in systolic BP by one-third normal value sideration of individual risks and benefits, and
is usually considered acceptable in healthy patients. coagulation studies. Widely accepted guidelines
Management of larger decreases: state that a spinal or epidural needle or catheter
- positioning the patient head-down: increases should not be inserted (or a catheter manipulated
venous return but risks higher level of block or removed) within 6hof unfractionated prophy-
unless the head is raised. lactic heparin or 12hafter low-molecular-weight
- iv fluid administration. Crystalloids are usually heparin. Heparin should not be given until
acceptable initially. 24hafter an epidural or spinal. Although these
- use of vasopressor drugs. May increase myocar- guidelines are not based on strong evidence, they
dial work and O2 demand secondary to increases are widely followed (but may be overridden if the
in SVR. Ephedrine (36mg iv repeated as clinical circumstances suggest the benefit outweighs
required) is commonly used; effects on venous the risk).
tone may be greater than with other drugs, e.g. A platelet count of 80100 109/l is usually taken
phenylephrine (1050g increments iv), meta- as the lower safe limit, but the true safe value is
raminol (0.51mg increments iv). unknown. Platelet dysfunction is clearly important,
- atropine 0.30.6mg or glycopyrronium 0.20.3mg but the actual risks of antiplatelet drugs are unclear.
if bradycardia occurs. Current guidance recommends against central
 Spinal cord 537

Ascending Descending
Fasciculus gracilis
Fasciculus cuneatus

Posterior spinocerebellar tract

Lateral corticospinal tract

Anterior spinocerebellar tract Rubrospinal tract

Lateral spinothalamic tract Tectospinal tract
Spinotectal tract
Anterior spinothalamic tract

Vestibulospinal tract
Anterior corticospinal tract

Fig. 146 Anatomy of spinal cord showing ascending and descending tracts

neuraxial blockade in patients taking aspirin in and posterior horns, with lateral horns (sympathetic
combination with any other antiplatelet agent; columns) in the thoracic region. The two halves are
aspirin in isolation is not a contraindication. For joined across the midline by the grey commissure, which
patients taking clopidogrel, a period of 7 days contains the central canal (Fig. 146).
between discontinuation of therapy and neuraxial Main ascending tracts:
blockade is recommended by international consen- posterior (dorsal) columns: convey ipsilateral touch
sus and the drug manufacturer. and vibration/proprioception sensation, from the
Spinal anaesthesia has been claimed to be safer lower body via the fasciculus gracilis and upper
than epidural anaesthesia, since the needles are body via the fasciculus cuneatus.
finer. posterior and anterior spinocerebellar tracts:
emergency abdominal surgery, especially intestinal convey proprioception sensation to the cerebellum
obstruction: hypovolaemia may be present, and via inferior and superior cerebellar peduncles
increased GIT activity following spinal anaesthesia respectively.
may increase the risk of perforation. lateral and anterior spinothalamic tracts: the former
[Albert Woolley (1891?) and Cecil Roe (1902?), conveys contralateral pain and temperature sensa-
English labourers; Nicholas Greene (19222005) and tion; the latter conveys contralateral touch and
Lincoln F Sise (18741942), US anaesthetists; G Sprotte, pressure sensation.
German anaesthetist; Rolland J Whitacre (19091956), spinotectal tract: conveys information to the brain-
US anaesthetist] stem involved in spinovisual reflexes.
Liu SS, McDonald SB (2001). Anesthesiology; 94: Main descending tracts:
888906 lateral and anterior corticospinal tracts: convey
motor innervation from the cerebral cortex; the
Spinal cord. Cylindrical structure lying within the ver- former via crossed (pyramidal) fibres and the latter
tebral canal, beginning at the foramen magnum and ter- via uncrossed (extrapyramidal) fibres.
minating inferiorly level with L12 (L3 at birth, rising to rubrospinal, tectospinal and vestibulospinal tracts:
the adult level by 20 years). May rarely end at T12 or L3. contain extrapyramidal fibres passing from brain-
Continuous superiorly with the medulla oblongata, it stem nuclei to lower motor neurones.
tapers inferiorly to form the conus medullaris. The filum Blood supply:
terminale, an extension of the pia mater, attaches the anterior spinal artery: formed from two branches of
lower end to the back of the coccyx. Has cervical and the vertebral arteries, and descends in the anterior
lumbar enlargements corresponding to innervation of median fissure from the brainstem to the conus
the upper and lower limbs respectively. Surrounded by medullaris. Supplies the anterior two-thirds of
the meninges and bathed in CSF. The anterior median the cord.
fissure is a deep longitudinal fissure and the posterior posterior spinal arteries: arise from the vertebral
median sulcus is a shallow furrow. Gives off 31 pairs of arteries, each dividing into two branches which
spinal nerves throughout its length. On cross-section, descend along the side of the cord, one anterior and
consists of central H-shaped grey matter surrounded by one posterior to the dorsal nerve roots. Supply the
white matter. The grey matter is composed of anterior posterior one-third of the cord.
538 Spinal cord injury

radicular branches: arise from local arteries (e.g. Anaesthetic management is related to:
intercostal, lumbar) and feed the spinal arteries. The other injuries and cardiorespiratory impairment.
most important are at T1 and the lower thoracic/ potential difficult intubation and risk of aspiration.
upper lumbar level (artery of Adamkiewicz). The hyperkalaemic response to suxamethonium within
cord at T35 and T12L1 is thought to be most at 10 days6 months of injury.
risk from ischaemia. positioning of the patient.
[Albert Adamkiewicz (18501921), Polish pathologist] impaired temperature regulation.
See also, Anterior spinal artery syndrome; Motor path- requirement for postoperative IPPV.
ways; Sensory pathways; Spinal cord injury impaired cardiovascular responses and autonomic
hyperreflexia.
Spinal cord injury. Most common in males aged 1535, [Charles E Brown-Squard (18181894), Mauritius-born
mostly caused by motor vehicle accidents. C56 and US, English and French physician]
T12L1 levels of the spinal cord are affected most often. Miko I, Gould R, Wolf S, Afifi S (2009). Int Anesthesiol
Associated injuries (especially head injury) occur in Clin; 47: 3754
2565% of cases. See also, Anterior spinal artery syndrome
Features of acute injury:
initial hypertension and peripheral vasoconstric- Spinal headache, see Post-dural puncture headache
tion. Arrhythmias are common. Hypotension and
bradycardia may occur in lesions above T6 and T1 Spinal nerves. Consist of pairs of nerves (8 cervical, 12
respectively, caused by sympathetic disruption thoracic, 5 lumbar, 5 sacral and 1 coccygeal). Formed
(spinal shock). Autonomic hyperreflexia may occur within the vertebral canal from anterior (ventral) and
after 46 weeks if the lesion is above T56. posterior (dorsal) roots, themselves formed from root-
neurogenic pulmonary oedema is common with cer- lets that emerge from the antero- and posterolateral
vical lesions. aspects of the spinal cord. The anterior roots convey
initial flaccid paralysis is followed after 23 weeks efferent motor fibres from the cord, and the posterior
by spastic paralysis. Paralytic ileus is common for roots convey afferent sensory fibres to the cord; thus
23 weeks. they are mixed nerves. Each spinal nerve leaves the ver-
Certain clinical syndromes may occur: tebral canal through an intervertebral foramen. The pos-
complete injury, with loss of motor or sensory func- terior (dorsal) root ganglia lie within the foramina,
tion below a certain level. except for C1 and C2 (lie on the posterior vertebral
incomplete injury syndromes: arches) and the sacral and coccygeal ganglia (lie within
- central cord: arms paralysed more than legs, the canal). The first cervical nerve emerges between the
with bladder dysfunction and variable sensory occiput and the arch of the atlas; C27 emerge above
loss. their respective vertebrae and C8 emerges between C7
- anterior cord: paralysis below the level of lesion, and T1. Below this, each spinal nerve emerges below its
with proprioception, touch and vibration sense corresponding vertebra. After giving off a small menin-
preserved. geal branch, each divides into a large anterior and
- posterior cord: only touch and temperature sensa- smaller posterior primary ramus (Fig. 147).
tion impaired. Anterior primary rami:

- hemisection of cord (Brown-Squard): ipsilateral supply cutaneous and motor innervation of the
paralysis and loss of proprioception, touch and limbs, and front and sides of the neck, thorax and
vibration sensation, with loss of contralateral pain abdomen.
and temperature sensation. cervical: C14 form the cervical plexus, C58 the
Primary damage is from the initial injury; the following brachial plexus.
have been suggested as causing secondary damage: isch- thoracic: the intercostal nerves; T1 contributes to
aemia, compression, oedema, release of free radicals, the brachial plexus.
arachidonic acid metabolites and excitatory amino acids, lumbar: L14 form the lumbar plexus.
and leakage of calcium into cells and potassium out of sacral and coccygeal: contribute to the sacral plexus.
cells. Thus initial treatment is aimed at reducing isch-
aemia, inflammation and oedema formation.
Management:
as for any trauma, with particular emphasis on the Posterior (dorsal) ramus
airway, maintenance of cardiac output and oxygen-
Posterior (dorsal) Posterior (dorsal) root
ation, and stabilisation of the spine.
root ganglion
high-dose methylprednisolone (30mg/kg iv, fol-
lowed by 5.4mg/kg/h for 2448h) within 8hof
injury has been shown to reduce the incidence and
severity of long-term sequelae.
IPPV is required in lesions above C35.
prevention of DVT, stress ulcers and bedsores.
Mortality is highest in patients under 1 year and over 70
years. Pulmonary complications (e.g. hypoventilation,
aspiration pneumonitis, chest infection, PE) are the
commonest causes of death within the first 3 months of Anterior (ventral) ramus
injury. Other complications are related to nutrition, Anterior (ventral) root
urinary function and sepsis, osteoporosis, psychological
problems and pain syndromes. Fig. 147Typical spinal nerve
 Spinal shock 539

Posterior primary rami:

Table 40 Epidural and spinal doses of commonly used opioids
supply motor and sensory innervation to the muscles
and skin of the back. Drug Epidural dose Spinal dose Duration (h)
do not contribute to limb innervation or plexus
formation. Buprenorphine 60300g 2550g 810
divide into medial and lateral branches (except for Diamorphine 15mg 100300g 68
C1, S4, S5 and coccygeal rami). Cutaneous innerva- Fentanyl 50150g 1025g 24
tion of T6 and above is contained in the medial Methadone 48mg 0.52.0mg 46
branch, below this in the lateral branch. Morphine 18mg 100400g 1218
cervical: Pethidine 25100mg 10100mg 68
- C1: entirely motor, supplying the muscles of the Sufentanil 1075g 520g 26
upper neck.
- C2: supplies the skin of the back of the head via
the greater occipital nerve; motor supply to the
neck muscles.
- C38: sensory supply to the lower occiput and diamorphine 0.252.0mg/h; morphine 0.5mg/h.
neck; motor fibres to the neck muscles. fentanyl 40100g/h; sufentanil 2050g/h.
thoracic, lumbar, sacral and coccygeal: methadone 0.5mg/h.
unremarkable. pethidine 1015mg/h.
Embryonic segmental distribution of nerves to the skin Pethidine is unique in that it has local anaesthetic prop-
and muscles is represented by the segmental distribution erties and has thus been used as the sole agent e.g. for
of cutaneous and motor innervation (dermatomes and spinal anaesthesia and epidural infusion.
myotomes respectively). An extended-release preparation of morphine is
available for epidural administration, consisting of
morphine sulphate pentahydrate encapsulated within
Spinal opioids. Spinal or epidural administration of ~20m diameter liposomes, suspended in 0.9% saline.
opioid analgesic drugs has become widespread since the Onset of analgesia takes ~3h, with duration of action up
first report of epidural morphine administration in to 48hafter a single lumbar epidural injection of
humans in 1979. Thought to bind to opioid receptors in 1015mg.
the substantia gelatinosa of the spinal cord, modulating Side effects of spinal opioids:
pain pathways. Although systemic absorption may con- respiratory depression:
tribute to analgesia, a spinal site of action is suggested - early (within an hour of administration): due to
by a high CSF:plasma drug ratio and the low doses systemic absorption; thus more common if highly
required compared with iv administration. lipid-soluble drugs are used and if sedative drugs
The main advantage of spinal opioids over systemic are also given.
opioids is profound, long-lasting analgesia. Advantages - late (424hafter administration, depending on
over spinal or epidural local anaesthetic agents are the the drug): caused by rostral spread of the drug
lack of sympathetic, motor or sensory blockade, and within the CSF to the medullary respiratory
the ability to provide analgesia distant to the level of centre. Although uncommon (0.53.0%), more
injection. likely with poorly lipid-soluble drugs (e.g. mor-
A segmental effect has been reported, i.e. maximal phine), after intrathecal administration, in the
analgesia corresponding to the level of injection, elderly, and if systemic opioids are also given.
although lumbar administration has been used for anal- Respiratory rate alone is a poor indicator of the
gesia after thoracic surgery. This may be related to the degree of depression; arterial oxygen saturation
lipid solubility of the opioid used; thus morphine diffuses and level of sedation may be more useful. Nalox-
further in the CSF than more lipid-soluble drugs. Onset one may reverse respiratory depression without
and duration of action are also determined by lipid solu- affecting analgesia.
bility. Highly lipid-soluble drugs (e.g. fentanyl and meth- urinary retention: occurs in 3040% of cases,
adone) cross the CSF and bind to the spinal cord rapidly. although its occurrence in up to 90% of males has
Only a small amount is thus available to diffuse through- been reported. Presence of vesical opioid receptors
out the CSF. However, their duration of action is short has been suggested.
since they are more rapidly absorbed into the blood- pruritus: affects up to 70% of patients after mor-
stream. They are more likely to act (at least partially) via phine, 10% after fentanyl. More common after
systemic absorption. Poorly lipid-soluble drugs (e.g. mor- intrathecal administration. May be relieved by anti-
phine) have slower onset time (up to 1h) and their histamine drugs, naloxone and ondansetron. The
actions last for up to 24h(Table 40). cause is unknown.
Opioids are often mixed with local anaesthetics since nausea and vomiting: similar incidence to that after
combination has been shown to be synergistic. Such mix- parenteral administration, although more common
tures may be given by bolus or by infusion; commonly after intrathecal opioids.
used mixtures for the latter include 0.10.2% bupiva- herpes simplex virus reactivation has been described
caine plus fentanyl 24g/ml or diamorphine 50100g/ in obstetric patients.
ml, infused at 515ml/h for e.g. postoperative analgesia
and chronic pain management. In obstetric analgesia Spinal shock. Syndrome following sudden spinal cord
and anaesthesia, fentanyl is widely used in the UK for injury, characterised by hypotension (level of injury
bolus and infusion in labour; in the USA sufentanil is above T6) and bradycardia (level above T1), with flaccid
commonly used. Epidural infusion of opioids alone is paralysis. Hypotension arises from interrupted sympa-
less commonly used: thetic vasoconstrictor tone, and is greatest in the upright
540 Spinal surgery

position. Usually replaced by autonomic hyperreflexia Dry spirometers (e.g. the Vitalograph) are more con-
after 46 weeks. Hypotension may be dramatic on induc- venient for clinical use. It contains bellows attached to a
tion of anaesthesia and institution of IPPV. pen, with a sheet of recording paper automatically
See also, Valsalva manoeuvre moved by a motor during expiration. The best results
from three attempts are usually recorded.
Spinal surgery. May be required for kyphoscoliosis,
trauma, laminectomy, tumours or abscess. Spironolactone. Diuretic, acting via competitive
Anaesthetic management is as for kyphoscoliosis and antagonism of aldosterone. Inhibits sodium/potassium
neurosurgery; main points: exchange in the distal renal tubule, with retention of
preoperative assessment for co-morbidity, ventila- potassium and hydrogen ions. Used to treat oedema
tory impairment or neurological deficits. due to secondary hyperaldosteronism, e.g. associated
traction and impaired movement may hinder access with hepatic failure and cardiac failure, and in primary
and tracheal intubation, especially for cervical spine hyperaldosteronism. Diuresis occurs 23hafter oral
surgery. administration.
severe hyperkalaemia may follow suxamethonium Dosage: 100400mg orally od (2550mg daily for
if spinal cord injury is present. Period of risk: 10 cardiac failure).
days6 months. Side effects: GIT disturbances, gynaecomastia,
surgery may be prolonged with major blood loss or hyperkalaemia.
hypothermia. Damage to inferior vena cava, aorta
and iliac arteries may lead to rapid exsanguination Splitting ratio. Ratio of gas flow bypassing an anaes-
without obvious bleeding from the operation site. thetic vaporiser to the gas flow entering it. At a splitting
hypotensive anaesthesia reduces blood loss but may ratio of zero, the total gas flow passes through the vapo-
risk spinal cord ischaemia. Infiltration with vaso- riser; at a ratio of infinity, none passes through (i.e. the
pressors has been used. vaporiser is switched off).
epidural anaesthesia has been used with good
results, e.g. for laminectomy. Sprays. In anaesthesia, usually employed to deliver local
cord function may be assessed by the wake-up test anaesthetic agent (usually 4% lidocaine) to the larynx
or by monitoring evoked potentials. and trachea, e.g. for awake tracheal intubation, and to
airway obstruction may follow anterior cervical reduce stimulation during positioning and tracheal extu-
spine surgery if extensive. Ondines curse may also bation. Spraying the cords at laryngoscopy does not
occur. attenuate the hypertensive response to laryngoscopy
Admission to ICU/HDU may be required if there is a itself. Most commonly used sprays are now either single-
risk of airway obstruction, respiratory impairment or use (e.g. prefilled syringes with long perforated nozzles)
excessive bleeding and for pain management. or with disposable, single-use nozzles for attachment to
metered-dose aerosols (e.g. delivering 10mg of 10%
Spirometer. Device for measuring lung volumes. The lidocaine per spray). Previously, reusable sprays con-
wet spirometer consists of a lightweight cylinder sus- sisted of metal nozzles with red rubber bulbs.
pended over a breathing chamber with a water seal (Fig. Sprays may also be used to apply cocaine to the nose,
148). Vertical movement of the cylinder corresponding to produce anaesthesia and vasoconstriction. Other
to respiratory movements is recorded on a rotating drum sprays used in anaesthesia include the ethyl chloride
via a pen attached to the cylinder. spray for refrigeration anaesthesia and testing regional
May be used to measure volumes directly, or using anaesthesia, and disinfectant sprays and dressings.
dilution techniques. Also used to calculate flow rates and
basal metabolic rate. Inaccuracies may arise from inertia SRS-A, Slow reacting substance-A, see Leukotrienes
of the system at high respiratory rates, and the dissolu-
tion of small amounts of gas into the water of the seal. SSRIs, see Selective serotonin reuptake inhibitors

ST segment. Portion of the ECG between the end of

the QRS complex and the beginning of the T wave (see
Fig. 59b; Electrocardiography). Represents the depolar-
Cylinder Rotating drum
ised plateau phase of the ventricular action potential. As
there is no net current flow during this period, the ST
segment is normally within 1mm of the isoelectric line
Pen (between the T wave and following P wave). Myocardial
Breathing damage results in injury currents that cause ST eleva-
chamber tion (e.g. MI and pericarditis) or depression (e.g. myo-
cardial ischaemia). ST depression may also be caused
by hypokalaemia and digoxin therapy, the latter typically
Water
producing a reverse tick pattern. May also be depressed
in reciprocal leads following ST elevation MI.
See also, Acute coronary syndromes

Gas out Stages of anaesthesia, see Anaesthesia, stages of

Gas in Standard bicarbonate. Plasma concentration of

bicarbonate when arterial PCO2 has been corrected to
Fig. 148Wet spirometer 5.3kPa (40mmHg), with haemoglobin fully saturated
 Starlings law 541

and at a temperature of 37C. Thus eliminates the respi- Lin MY, Hayden MK (2010). Crit Care Med; 38 (Suppl):
ratory component of acidosis or alkalosis. Normally 33544
2433mmol/l.
See also, Acidbase balance STaR, see Safe transport and retrieval

Starch solutions, see Hydroxyethyl starch

Standard deviation (SD). Expression of the variability
of a population or sample. Equals the square root of Starling forces. Factors determining the movement of
variance, i.e. fluid across the capillary wall endothelium. Movement
 ( x x )2 into the interstitial space is normally encouraged by the
hydrostatic pressure gradient (capillary hydrostatic pres-
SD =
n1 sure [Pc] interstitial fluid hydrostatic pressure [Pi]).
Squaring (x x ) eliminates any minus signs, i.e. for those This is opposed by the normal colloid osmotic gradient
values of x less than x. (capillary colloid osmotic pressure [c] interstitial fluid
In a sample of normal distribution, a range of 1 SD on colloid osmotic pressure [i]):
either side of the mean includes about 68% of all obser- Q = K[( Pc Pi ) ( c i )]
vations, 2 SDs on either side include about 95%, and 3  = net flow of fluid for a given surface area
where Q
SDs on either side include about 99.7%.
K = permeability or filtration coefficient (flow
See also, Statistical frequency distributions; Statistics
rate per unit pressure gradient across the
endothelium)
Standard error of the mean (SE). Indication of how = reflection coefficient (represents permeability
well the mean of a sample represents the true population of the endothelium to plasma proteins).
mean. The equation does not account for active transport of
standard deviation (SD) solutes and effects of surface tension in the lung.
SE =
n In a standard systemic capillary: c ~ 25mmHg; i ~
5mmHg; Pi ~ 0mmHg. Pc falls from about 30mmHg at
where n = number of values. the arteriolar end (favouring net flow of fluid out of the
SE is large when n is small, i.e. the sample mean capillary) to 15mmHg at the venous end (favouring net
is less likely to represent the population mean. flow in). In health, the volume of fluid leaving the capil-
Often presented with the mean in statistical data, lary exceeds that being reabsorbed by about 10%, the
because the data appear tidier, and mean SE has a excess being absorbed by the lymphatic system. Greater
smaller spread than mean SD. Apart from this, SE has imbalance may result in oedema.
no advantage over SD. [Ernest H Starling (18661927), London physiologist]
See also, Statistical tests; Statistics
Starling resistor. Model consisting of a length of col-
lapsible tubing passing through a rigid box (Fig. 149).
Staphylococcal infections. Caused by members of the The effects of different upstream pressures (P1), pres-
staphylococcus genus of Gram-positive bacteria. S. sures in the chamber (P2) and downstream pressures
aureus is the major pathogen, causing a spectrum of (P3) on flow through the tubing can be studied. Used to
infections, including boils, abscesses, cellulitis, wound illustrate the effect of gravity on regional pulmonary
infection, osteomyelitis, chest infection and septic shock. circulation, P1, P2 and P3 representing arterial, alveolar
Infection is especially problematic in immunodeficiency, and venous pressures respectively. Also used to model
e.g. in critically ill patients. Other conditions arise from the interaction between MAP, ICP and CVP.
exotoxin production, e.g. toxic shock syndrome, scalded See also, Ventilation/perfusion mismatch; Cerebral perfu-
skin syndrome and food poisoning. sion pressure
S. aureus produces an enzyme (coagulase) which con-
verts fibrinogen to fibrin and thus clots blood. Strains Starlings law (FrankStarling law). Intrinsic regulatory
may be typed by viral bacteriophages; up to 65% of mechanism of the heart stating that force of myocardial
strains produce exotoxins. Nasal carriage of S. aureus contraction is proportional to initial fibre length, up to a
occurs in about a third of normal subjects; the organism point (Fig. 150). Neither variable is easily measured;
may also be present on the skin, especially perineum. hence myocardial contraction is often represented by
Over 30 coagulase-negative staphylococcus species exist, cardiac output, stroke volume, stroke index or stroke
mostly as skin commensals, although they may cause work (y-axis) and initial fibre length is represented by
clinical infection, especially S. epidermidis (typically
associated with prosthesis- and catheter-related sepsis)
and S. saprophyticus (typically causing urinary tract
P2
infection).
Bacterial resistance is an increasing problem, with P1 P3
90% of hospital staphylococci resistant to benzylpenicil-
lin and related drugs via production of -lactamase. Rigid box
Meticillin-resistant S. aureus (MRSA) is a particular
Upstream Downstream
problem in hospitals and increasingly in the community
too. Glycopeptides are usually reserved for its treatment, Collapsible
although resistance has been reported. Strict infection tubing
control is required to reduce cross-contamination and
spread of infection. Fig. 149 Starling resistor (see text)
542 Starvation

Frequency of occurrence
B
Force of contraction

C
D
A

Mean
Initial myocardial fibre length
Measurement values
Fig. 150 Starlings law Fig. 151 Normal frequency distribution curve

left ventricular end-diastolic volume, left ventricular Examples: atorvastatin (1080mg orally od); simvas-
end-diastolic pressure or pulmonary capillary wedge tatin (1080mg orally od); pravastatin (1040mg
pressure (x-axis). Increasing stretch is thought to facili- orally od); and rosuvastatin (540mg orally od).
tate greater actinmyosin cross-link formation; the Dosages vary according to target LDL levels and
optimum sarcomere length is 2.2m. indication (e.g. lower doses for primary prevention;
The law explains how right and left ventricular higher doses after acute coronary syndromes).
outputs remain matched, i.e. if right ventricular output Side effects (more likely with higher doses): myopa-
increases, the increase in pulmonary venous pressure in thy, myalgia, rhabdomyolysis, abnormal liver function
turn increases left ventricular filling; the resultant (severe hepatitis rarely), depression, fatigue, skin
increased stretch increases left ventricular output in line reactions.
with that of the right ventricle. Brookes ZLS, McGowan CC, Reilly CS (2009). Br J
Changes in myocardial contractility shift the curves Anaesth; 103: 99107
position; e.g. in cardiac failure and MI it is moved down-
wards and to the right (e.g. in Fig. 150, from the upper Statistical frequency distributions. In statistics, rela-
curve to the lower curve). Cardiac dilatation compen- tionships between measured variables and the frequency
sates initially, by moving along the curve to the right. with which each value occurs. For continuous data, the
The (Starling) curves may be plotted for individual resultant curve may often be described by a mathemati-
patients, and have been used to guide management of cal equation, allowing statistical tests and other analyses
reduced output states. Therapeutic measures alter the to be performed. Many types of biological data have a
hearts position on the curve (Fig. 150), e.g. use of ino- normal (Gaussian) distribution (Fig. 151). Such data
tropic drugs moves heart function from A to B, venodila- are described by the mean and standard deviation (SD).
tors move it from C to D, and a fluid bolus challenge The standard normal deviate (z) describes any individ-
moves it from D to C. ual value by relating it to the mean and SD, and can be
[Otto Frank (18651944), German physiologist] used to calculate the probability that such a value lies
ORourke MF (1984). Aust N Z J Med; 14: 87987 within the normal range. Parametric statistical tests
may be used to test the hypothesis that different samples
Starvation, see Malnutrition of normally distributed data are in fact taken from the
same population (null hypothesis). They compare within-
Static electricity, see Antistatic precautions; Explosions group variability with between-group differences; e.g.
and fires two samples are likely to represent different populations
if the scatter (SD) of each is small and their means are
Statins. Group of competitive inhibitors of 3-hydroxy- very different.
3-methylglutaryl coenzyme A (HMG CoA) reductase, Data that are not normally distributed (e.g. skewed)
an enzyme required for hepatic cholesterol synthesis. may often be normalised (e.g. by logarithmic transfor-
Since most cholesterol is endogenously synthesised, they mation), allowing application of parametric tests, which
significantly reduce plasma levels of total and low- are more sensitive than non-parametric tests.
density lipoprotein (LDL) cholesterol. Licensed for both Other types of distribution include the binomial (in
treatment of primary/familial hypercholesterolaemia which there are two possibilities for each measurement,
and prevention of cardiovascular events (e.g. acute coro- e.g. yes or no, dead or alive), multinomial and Poisson
nary syndromes, ischaemic CVA). Reduce mortality and distribution (which describes random events where non-
morbidity in all patients with symptomatic CVS disease events cannot be counted, e.g. radioactive decay).
(i.e. secondary prevention), regardless of baseline cho- [Karl F Gauss (17771855), German mathematician;
lesterol level. Their use for primary prevention is advo- Simeon D Poisson (17811840), French mathematician]
cated in those at high risk (e.g. 20% 10-year risk) of See also, Samples, statistical
developing CVS disease; all patients over 40 years with
diabetes mellitus should be considered for primary pre- Statistical significance. Term denoting a probability of
vention. Also have anti-inflammatory properties that less than an arbitrary cut-off for a statistical test or a
may be helpful in sepsis and preventing vasospasm fol- result of inferential statistics. By convention, usually
lowing subarachnoid haemorrhage and head injury. taken as a value for P < 0.05, though more stringent
 Statistical tests 543

levels of probability are sometimes used (e.g. P < 0.01), - ordinal data: KruskalWallis test. Similar
e.g. to account for the increased likelihood of a signifi- basis to the MannWhitney test.
cant result due to chance alone when large numbers of - same subjects before and after a treatment:
comparisons are made. The terms very or highly sig- - two groups:
nificant to describe very small P values should not be - parametric: paired t test. More powerful than
used when presenting data, but the P value itself should the unpaired test because intersubject vari-
be provided. ability is reduced, since each subject acts as his
See also, Errors or her own control.
- non-parametric:
Statistical tests. Methods of comparing or extrapolat- - nominal data: McNemars test.
ing data in inferential statistics, e.g. in clinical trials. - ordinal data: Wilcoxon signed-rank sum
Involve mathematical calculations depending on the test. Ranks the differences between the
descriptive statistics of each sample group. Results are paired results.
traditionally expressed as the probability that any - serial measurements following a treatment:
observed differences between groups are due to chance - parametric: repeated-measure ANOVA.
alone, i.e. the likelihood that the samples are taken from - non-parametric:
the same population (null hypothesis). Increasingly, con- - nominal data: Cochranes test.
fidence intervals are used to indicate the range within - ordinal data: Friedman statistic.
which a real difference is likely to lie. comparing two variables for association:
Many different tests have been described, applicable - parametric: linear regression analysis and correla-
to specific types of data and situations, e.g.: tion. Regression analysis determines the magni-
comparing groups consisting of: tude of change of one variable produced by the
- different subjects with different treatments: other variable. Expressed as the slope of the line
- two groups: of best fit, the equation relating the two variables,
- parametric (for normally distributed continu- indicators of scatter or statistical differences from
ous data): unpaired (Students) t test. Com- the line of no association. Correlation indicates
pares the mean and standard deviation for the degree of association only and is expressed as
each group. Two-tailed tests allow for either the Pearson correlation coefficient (r). An r of +1
an increase or a decrease in the variable or 1 indicates complete positive or negative
measured. association respectively, whilst an r of 0 indicates
- non-parametric: no association. For comparison of two methods of
- nominal data: chi-squared test (contingency measurement (e.g. invasive and non-invasive arte-
table) with Yatess correction for continuity. rial BP measurement), the difference between the
Compares the observed frequency of events two values obtained at each measurement is cal-
with the expected frequency. Fishers exact culated. Bias and precision (mean and standard
test is used if any expected frequency is less deviation respectively of the differences) indicate
than 5. the degree of agreement between the two methods
- ordinal data: MannWhitney rank sum test. (Bland and Altman plot).
Ranks all the results in ascending order and - non-parametric:
compares the groups distributions within - nominal data: contingency coefficient.
the ranking. - ordinal data: Spearman rank correlation.
- all types of data: sequential analysis. Relies Non-normally distributed interval data may be trans-
on the relationship between the size of dif- formed and normalised before application of parametric
ference between groups, and the number of tests; otherwise weaker non-parametric tests must be
subjects required to achieve statistical sig- applied.
nificance for that difference (as the size of Inappropriate study design or tests may result in
difference increases, fewer subjects are errors and incorrect conclusions. Common examples
required). A graph is drawn with precalcu- include:
lated significance boundaries, with an indi- multiple testing without correction. With a proba-
cator of sample size on the x-axis and an bility (P) of 0.05 taken as representing statistical
indicator of size of difference on the y-axis. significance, one test in 20 would be expected to
Results are analysed at intervals as the study produce a significant result by chance. The Bonfer-
progresses, and points plotted on the graph; roni correction is commonly used to account for
the study is stopped when a boundary is multiple comparisons between groups.
crossed, thus minimising the number of sub- insufficient power.
jects required to achieve a significant result. application of the incorrect test, e.g. use of the t test
- more than two groups: to compare ordinal data.
- parametric: analysis of variance (ANOVA). The tests and modifications are usually named after the
Similar basis to the t test. Only indicates that mathematicians who described or developed them
a significant difference exists, not between (apart from Students t test).
which groups it exists. StudentNeuman [Student: pseudonym used by William S Gosset
Keuls, Tukeys and other tests are used to indi- (18761937), English chemist, in order to publish his
cate which of the comparisons achieve work (publication of papers on any subject was banned
statistical significance. by his employers, Guinness, after trade secrets had been
- non-parametric: included in a paper published by another employee);
- nominal data: chi-squared test as above Arthur Guinness (17251803), Irish brewer]
(Yatess correction is not required). See also, Statistical frequency distributions
544 Statistics

Statistics. Collection, analysis and interpretation of up to 60% of patients. Intranasal midazolam is

numerical data, used to describe and compare samples increasingly used.
and populations. May be: - in the emergency department: lorazepam 2mg, in
descriptive; i.e. describes sample data without increments up to a total dose of 0.1mg/kg iv, is
extrapolation to the whole population. Descriptive the drug of choice because of its long clinical half-
terms vary according to the type and distribution of life. If seizures persist, phenytoin (15mg/kg iv) or
data but include measures of: fosphenytoin should be given.
- central tendency, e.g. mean, mode, median. - if seizures continue, the stage of refractory status
- scatter, e.g. standard deviation, percentiles. epilepticus has been reached; this requires tra-
Thus normally distributed data are described by cheal intubation and transfer to a specialised unit
their mean and standard deviation, ordinal data with continuous EEG monitoring and anaesthesia
by the median and percentiles (usually 25th75th with thiopental or propofol whilst longer-term
[i.e. interquartile range]) and range, and nominal by antiepileptic agents (e.g. levetiracetam, sodium
the mode and a list of possible categories. valproate, lacosamide) are given.
inferential (analytical); i.e. used to relate sample Perks A, Cheema S, Mohanraj R (2012). Br J Anaesth;
data to the whole population. Applications include 108: 56271
the use of clinical or laboratory measurements to
define disease, and determining whether different Status lymphaticus. Obsolete term used to describe a
samples are from the same population (null hypoth- syndrome causing unexpected intraoperative death in
esis). The latter is commonly performed in clinical children. Now thought not to exist, and merely an excuse
trials, using statistical tests. for poor management.
See also, Confidence intervals; Predictive value; Sensitiv- Macintosh RR, Pratt FB (1995). Paediatr Anaesth; 5:
ity; Specificity; Standard error of the mean; Statistical 354, 388
frequency distributions; Statistical significance
Stellate ganglion block. Performed for painful arm
Status asthmaticus. Obsolete term describing refrac-
conditions (e.g. complex regional pain syndrome type 1,
tory, acute, severe asthma. Acute severe asthma is now
herpes zoster, phantom limb, shoulder/hand syndrome)
the preferred term.
and to improve circulation, e.g. in Raynauds syndrome,
postembolectomy. Has formerly been performed in
Status epilepticus. Continuous or rapidly repeating
quinine poisoning, angina and asthma.
convulsions persisting for > 30min without regaining
The ganglion represents the fused inferior cervical
consciousness, although it has been suggested that sei-
and first thoracic sympathetic ganglia, and is present in
zures lasting > 5min are unlikely to stop spontaneously.
80% of subjects. It usually lies on or above the neck of
Generalised convulsive status epilepticus (GCSE) is the
the first rib. Some sympathetic fibres may leave the sym-
most common form; in one-third of cases it is the first
pathetic chain below the ganglion of T1, and run directly
presentation of epilepsy. After 30min seizures, increased
to the brachial plexus, bypassing the ganglion. The
ICP, hypotension and failure of cerebral autoregulation
precise site of action of the block is controversial, since
result in decreased cerebral perfusion pressure. Failure
studies using dye have shown that the ganglion itself may
of central control of breathing causes hypoxaemia, pul-
not be affected by injected solution.
monary hypertension and cardiac failure. At this stage,
Usually performed under fluoroscopic guidance. With
visible seizures may be absent despite continuing cere-
the patient supine and the neck extended, Chassaignacs
bral seizure activity (non-convulsive status).
Aetiology:
tubercle (transverse process of C6) is palpated level with
the cricoid cartilage. The carotid sheath is retracted lat-
acute processes, e.g. electrolyte imbalance, renal
erally with the fingers, and a skin wheal raised over the
failure, sepsis, head injury, CVA, drug abuse (e.g.
tubercle. A 5cm needle is inserted directly posteriorly
alcohol, cocaine), CNS infection (e.g. encephalitis,
to contact the tubercle, passing medial to the retracted
meningitis), hypoxic brain injury.
carotid sheath. It is withdrawn 12mm and correct posi-
chronic disease, e.g. pre-existing epilepsy low anti-
tioning is confirmed by appropriate spread of injected
convulsant drug levels, chronic alcoholism, cerebral
radiological contrast media; 510ml local anaesthetic
lesions.
Management:
agent is then injected after careful aspiration. A 2ml test
dose has been suggested before injection of the main
general:
dose. Successful block results in ipsilateral Horners
- initial rapid assessment and CPR. O2 and iv
syndrome.
cannulation are mandatory and tracheal intuba-
Complications include intravascular injection (includ-
tion often necessary. Monitoring of BP, ECG and
ing into the vertebral artery), recurrent laryngeal nerve
temperature should be instituted.
and brachial plexus blocks, pneumothorax, subarachnoid
- 50ml of 50% glucose should be given iv with thia-
and epidural injection, and haematoma formation.
mine 100mg if hypoglycaemia is suspected or if
[Maurice Raynaud (18341881), French physician]
alcoholism/malnutrition is present.
See also, Sympathetic nerve blocks; Sympathetic nervous
- acidosis may require bicarbonate therapy,
system
although it usually corrects itself with
resuscitation.
- hyperthermia may require active cooling. STEMI, ST segment elevation myocardial infarction,
common UK and US regimen for anticonvulsant see Acute coronary syndromes
therapy:
- out-of-hospital treatment: lorazepam or diazepam Stents, coronary, see Percutaneous coronary
is most commonly used and terminates GCSE in intervention
 Streptococcal infections 545

Sterilisation of breathing equipment, see Contamina- Stoichiometric mixture. Mixture of reactants in such
tion of anaesthetic equipment proportions that none remains at the end of the reaction.
Stoichiometric mixtures often react violently, and are
Steroid therapy, see Corticosteroids thus more likely to be involved in explosions and fires.

StokesAdams attack. Syncope secondary to cardiac

Stethoscope. Invented in its monaural form (as a arrhythmias. Occurs without warning, and may progress
wooden trumpet-shaped tube) by Laennec in 1819; to convulsions. Recovery is typically rapid. Originally
Cammanns binaural model appeared in 1852. During described in complete heart block, but is also used in
anaesthesia, allows continuous auscultation of breath reference to syncope due to other arrhythmias (e.g.
sounds and heart sounds. May indicate air embolism. tachybrady syndrome, paroxysmal VT/VF). The term is
Two forms are commonly used in anaesthesia: now less frequently used in favour of more precise diag-
precordial stethoscope: often connected to a mono-
nostic classifications. Differential diagnosis includes
aural earpiece to allow the anaesthetist greater postural hypotension, vasovagal syncope, transient isch-
freedom. aemic attack, micturition and cough syncope. Treatment
oesophageal stethoscope: a modified nasogastric
may involve antiarrhythmic drugs, electrophysiological
tube. Widely used in the USA; less so in the UK, ablation, cardiac pacing or insertion of an implantable
apart from paediatric anaesthesia. Addition of tem- defibrillator as appropriate.
perature probe, ECG electrodes and pacing wires [William Stokes (18041878), Irish physician; Robert
has been described. Adams (17911875), Irish surgeon]
[Ren TH Laennec (17811826), French physician; Harbison J, Newton JL, Seifer C, Kenny RA (2002).
George Cammann (18041863), US physician] Lancet; 359: 15860

StevensJohnson syndrome. Immune complex- Stovaine. Local anaesthetic drug, introduced in 1904, as
mediated hypersensitivity skin disorder resulting in the a less toxic alternative to cocaine. Slightly irritant, and
separation of the epidermis from the dermis. Erythema replaced in turn by procaine.
multiforme major and toxic epidermal necrolysis are [Ernest Forneau (18721949), French chemist; fourneau
respectively considered lesser and more severe forms of is French for stove]
the same condition. Caused by drugs (especially anticon-
vulsant and antibacterial agents), viral infections (includ- STP/STPD. Standard temperature and pressure (0C;
ing HIV) and malignancy, although in 50% of cases the 101.3kPa [760mmHg]) and STP dry. Used for standard-
cause is unknown. ising gas volume measurements.
In its severe forms, may present with fever and wide-
spread epidermal erythema, blistering and necrosis, Streptococcal infections. Caused by members of the
including membranes (e.g. pharyngitis, conjunctivitis, streptococcus genus of Gram-positive bacteria. Several
and rarely involving the oesophagus, rest of the GIT, species exist, usually as normal commensals in the upper
tracheobronchial tree and kidney). May result in signifi- respiratory tract, but they may cause a wide range of
cant fluid loss, altered temperature regulation and clinical infections. Classified according to the type of
increased susceptibility to infection. haemolysis they cause on blood agar (none, and ), the
Treatment is mainly supportive but includes careful latter also subclassified according to cell wall antigens
fluid and electrolyte replacement; skin lesions are treated into groups AH and KV.
as burns. Specific treatment with cyclophosphamide, Important pathogenic streptococci:
plasmapheresis and intravenous immunoglobulins has S. pyogenes (Group A -haemolytic): the major
been used. Mortality is up to 50% depending on the pathogen, causing pharyngitis, cellulitis, necrotising
body surface area involved. fasciitis, erysipelas, scarlet fever and septic shock.
[Albert M Stevens (18841945), Frank C Johnson (1894 The organism is further subdivided into strains and
1934), New York paediatricians] types according to surface antigens. The M antigen
Mockenhaupt M (2011). Expert Rev Clin Immunol; 7: confers particular virulence. Several exotoxins may
80313 contribute to the clinical features of infection, e.g.
scarlet fever, toxic shock syndrome. In addition,
StewartHamilton equation. Formula used in cardiac cross-reactivity between anti-streptococcal anti
output measurement when using thermodilution bodies and host tissue may result in disease, e.g.
techniques: rheumatic fever and glomerulonephritis.
Group B -haemolytic: especially important in
 = V (TB T1 )K1K 2
Q neonates/infants (arthritis, meningitis, peritonitis)
TB (t )dt and obstetrics/gynaecology (septic abortion, chorio-

where Q = cardiac output amnionitis). May also cause adult meningitis, endo-
V = volume of injectate carditis or osteomyelitis.
TB = blood temperature Group C and G -haemolytic: similar to Group A

T1 = injectate temperature organisms; Group D are different and have been

K1 and K2 = computer constants renamed enterococci (e.g. Enterococcus faecalis;
TB(t)dt = change in blood temperature over time. may cause nosocomial infection).
S. viridans: a group of partial - or non-haemolytic
[GN Stewart (18601930), Canadian-born US scientist; streptococci; may cause endocarditis and abscesses,
WF Hamilton (18931964), US physiologist] especially in immunodeficiency, e.g. on the ICU and
in the elderly. Includes S. mitis, S. sanguis, S. mutans
Stings, see Bites and stings and S. milleri.
546 Streptokinase

S. pneumoniae (pneumococcus): -haemolytic Effects of anaesthesia:

organism present in up to 70% of the populations inhalational anaesthetic agents have little effect.
oropharynx. May cause pneumonia (the most opioid analgesic drugs in high dosage (e.g. 50
common cause in the community; in hospital it is 100g/kg fentanyl, 24mg/kg morphine) attenuate
especially common in impaired protective reflexes, the response to abdominal and pelvic surgery, but
e.g. the elderly and frail, CNS depression), otitis do not abolish the response to initiation of cardio-
media, meningitis and septic shock. Prophylactic pulmonary bypass.
pneumococcal vaccine is recommended for those at etomidate infusion prevents the cortisol response,
risk, e.g. those with immunodeficiency or diabetes, but with little other effect.
following splenectomy and in the elderly. spinal and epidural anaesthesia with local anaes-
Usually sensitive to penicillins amongst other antibacte- thetic agents abolish the response to surgery on the
rial drugs. lower part of the body. The effect on upper abdomi-
nal and thoracic surgery is less clear, with suppres-
Streptokinase. Enzyme obtained from group C sion of the glucose response but not of the cortisol
-haemolytic streptococci; used as a fibrinolytic drug in response. Block of autonomic and somatic afferent
life-threatening arterial or venous thromboembolism, pathways is thought to be required for complete
e.g. acute PE and MI. Binds to plasminogen to form an prevention. Spinal opioids do not prevent the
activator complex, resulting in breakdown of plasmino- response despite good analgesia, although slight
gen to form plasmin, which causes fibrinolysis. Since modification may occur.
most individuals have antibodies to streptokinase, a To be effective, the above require administration
loading dose is required to overcome this natural resis- before the surgical stimulus; their effects last for
tance. Resultant immune complexes are rapidly cleared several hours after single dosage.
from the bloodstream; subsequent streptokinase is split The benefit of attenuating the stress response is contro-
into fragments during its action and cleared. versial, although improved outcome has been claimed in
Dosage: MI: 1 500000 units iv over 60min; otherwise critically ill patients.
250000 iv over 30min, then 100000/h for up to Kohl BA, Deutschman CS (2006). Curr Opin Crit Care;
2472h. 12: 32532
Side effects: nausea, vomiting, bleeding (including
CVA), embolic complications from break-up of Stress ulcers. Acute gastric ulceration secondary to any
thrombi, allergic reactions (including anaphylaxis). severe medical or surgical illness, e.g. classically burns
Contraindicated in conditions where bleeding is (Curlings ulcers) and head injury (Cushings ulcers).
likely. Usually involve the fundus and may be multiple. Associ-
ated with hypovolaemia, reduced cardiac output and
Streptomycin. Aminoglycoside and antibacterial splanchnic hypoperfusion. Gastric mucosal ischaemia
drug; now used as an antituberculous drug in drug- and acid production are thought to be involved, although
resistant TB or in brucellosis. Half-life is about 2.5hwith the aetiology is unclear. Routine prophylaxis with proton
normal renal function. pump inhibitors or H2 receptor antagonists is no longer
Dosage: 15mg/kg daily (up to 1g) by deep im advocated for ICU patients as they increase the inci-
injection. dence of nosocomial infection. Early enteral feeding
Side effects: as for aminoglycosides. Hypersensitivity reduces the incidence of GIT ulceration.
may occur. Plasma concentrations should be moni- Marik PE, Vasu T, Hirani A, Pachinburavan M (2010).
tored, especially in renal impairment; peak and trough Crit Care Med; 38: 22228
levels should not exceed 40g/ml and 5g/ml See also, Peptic ulcer disease
respectively.
Stridor. Harsh high-pitched sound occurring in upper
Stress response to surgery. Term used to encompass airway obstruction. Inspiratory stridor suggests obstruc-
the metabolic and hormonal changes following surgery, tion at or above the upper trachea (e.g. epiglottitis), since
although the same may occur after trauma, burns or extrathoracic obstruction is exacerbated by the negative
haemorrhage. The response has been suggested as being intrathoracic pressures generated during inspiration.
necessary for survival and recovery after trauma. Expiratory stridor suggests obstruction of the lower
Tissue trauma, hypovolaemia and pain initiate a neu- trachea or bronchi with exacerbation as the airways are
roendocrine reflex involving secretion of ACTH, end compressed during forced expiration. Typically present
orphins, growth hormone, vasopressin and prolactin. on exertion initially, progressing to stridor at rest as
Stimulation of the sympathetic nervous system increases obstruction worsens.
plasma catecholamines. Plasma cortisol and aldosterone More common in children because of the smaller
increase, with increased renin/angiotensin system activ- diameter of their airways. Slight narrowing thus has a
ity. These changes induce a state of catabolism, the mag- proportionately greater effect.
nitude and duration of which are proportional to the Treatment is as for airway obstruction. Helium/O2
extent of injury. Fatty acids are mobilised and utilised, mixtures (which are less dense than air/O2 mixtures)
amino acids are converted to carbohydrate and negative may decrease work of breathing and improve
nitrogen balance occurs. Plasma glucose is raised, with oxygenation.
reduced insulin secretion. Metabolic rate, body tempera-
ture, O2 consumption and CO2 production increase. Stroke, see Cerebrovascular accident
Water and sodium retention occurs, with increased
urinary potassium loss. Immunological and haematologi- Stroke index. Stroke volume divided by body surface
cal changes include increased cytokine production, area, thus accounting for the effect of body size. Nor-
acute-phase reactions, leucocytosis and lymphocytosis. mally 3050ml/m2.
 Subarachnoid haemorrhage 547

Stroke volume (SV). Volume of blood ejected by the initial rupture: sudden, severe headache (ipsi-
ventricle per contraction; i.e.: lateral in 30%), vomiting, syncope, loss of
cardiac output consciousness.
SV = focal neurological deficit, especially cranial
heart rate nerve III. Ocular haemorrhage may accompany
Also equals end-diastolic volume end-systolic volume. diplopia.
Normally 7080ml for a 70kg man at rest. meningism within 624h.
Affected by ventricular filling and preload, myocar- cerebral vasospasm within 312 days (peaks at 68
dial contractility, and outflow resistance and SVR. days); may cause reversible or irreversible neuro-
See also, Starlings law logical damage. Degree depends on the volume of
blood in the subarachnoid space. A major cause of
Stroke work. The ventricular work done per cardiac morbidity and mortality in those surviving the
cycle, usually with reference to the left ventricle. Cor- initial bleed, causing symptoms in 2030% of
relates with stroke volume multiplied by the change in cases, especially those with grades 35 haemorrhage
ventricular pressure. Described using several units of (see below).
measurement (e.g. g, g/m, g m). Strictly correct expres- hydrocephalus (20%): caused by obstruction of
sion is in terms of work (e.g. joule, N m, mmHg ml): CSF circulation by blood.
Patients are graded thus (Hunt and Hess scale):
Stroke work ( J)
grade 0: unruptured aneurysm.
= stroke volume (ml) (MAP PCWP [mmHg])
grade 1: asymptomatic or mild headache and neck
where PCWP = pulmonary capillary wedge pressure stiffness. Mortality 05%.
Stroke work index = stroke work divided by body surface grade 2: severe headache, neck stiffness, cranial

area. nerve palsy. Mortality 210%.

grade 3: mild focal deficit, lethargy, confusion. Mor-
Increased in hypertension and hypervolaemia, and tality 815%.
decreased in shock, cardiac failure and aortic stenosis. grade 4: stupor, hemiparesis, early decerebrate
Schramm W (2010). J Clin Monit Comput; 24: 21317 rigidity. Mortality 6070%.
grade 5: deep coma, decerebrate posture. Mortality
Strong ion difference (SID). Difference between the 70100%.
concentrations of the strong cations (those that dissoci- CT scanning detects SAH in 95% of cases; it may indi-
ate almost totally at the pH of interest e.g. in blood, cate the volume of blood present, allow rough localisa-
Na+, K+, Ca2+, Mg2+) and strong anions (e.g. Cl, lactate, tion of the aneurysm and demonstrate hydrocephalus.
SO42) in a solution. Based on the concept of electroneu- Lumbar puncture (revealing xanthochromic CSF) is
trality, proposed in the 1980s by Stewart as part of his only necessary in questionable circumstances. Cerebral
alternative approach to acidbase balance, in which the angiography demonstrates an aneurysm in 80% of cases;
number of positive ions in a solution equals the number the anterior (30%) and posterior (25%) communicating
of negative ones. An SID > 0 represents the presence of arteries, middle cerebral (20%) and basilar (10%) arter-
unmeasured anions; the normal value is 4044mmol/l in ies are most commonly affected (see Cerebral circula-
plasma, this value representing the contribution made by tion). It may also demonstrate vasospasm.
weak acids (mostly albumin) and carbon dioxide. As SID Management:
falls it results in increased dissociation of water to main- admission with careful monitoring. ECG changes
tain electroneutrality, leading to increased H+ and occur in 50% of cases (typically T wave inversion,
therefore reduced pH, i.e. metabolic acidosis. As SID ST segment changes or arrhythmias; caused by
increases, plasma pH rises. increased catecholamine secretion).
The strong ion gap (SIG) accounts for the effect of unconscious patients are managed as for coma.
other anions not included in the SID equation; i.e. SIG maintenance of good hydration and control of
= SID [HCO3] [albumin]. severe hypertension.
[Peter A Stewart (19211993), Canadian-born US drainage of hydrocephalus with an intraventricular
physiologist] catheter, which also allows measurement of ICP
Morris CJ, Low J (2008). Anaesthesia; 63: 294301 and cerebral perfusion pressure.
nimodipine to prevent/relieve vasospasm: 60mg
Stump pressure, see Carotid endarterectomy orally, 4-hourly, for 21 days. Established vasospasm
is treated by ensuring adequate flow through the
Subarachnoid block, see Spinal anaesthesia narrowed vessel using triple H therapy haemo-
dilution, hypervolaemia and hypertension.
Subarachnoid haemorrhage (SAH). Bleeding into the analgesia and anticonvulsant drugs as necessary.
subarachnoid space. Commonest cause is trauma, early surgical clipping or coil embolisation of the
although non-traumatic SAH usually results from aneurysm is now advocated to reduce the risk of
rupture of an intracranial (Berry) aneurysm (7580%) rebleeding and to allow safe maintainance of cere-
or arteriovenous malformation (5%). Incidence of aneu- bral perfusion pressure.
rysmal SAH is 1030 per 100000 population/year. Most Complications:
frequent at 4060 years of age. Risk factors include death (1015% of patients before reaching hospi-
hypertension, smoking, oral contraceptive pill and tal). Overall hospital mortality is ~40%.
cocaine abuse. rebleeding: most common on the first day (4% of
Features: cases), with 1520% occurring within 2 weeks and
50% of patients have headaches for 23 weeks 50% within 6 months.
beforehand (sentinel headache). neurological deficit resulting from vasospasm.
548 Subclavian venous cannulation

hyponatraemia may result from the syndrome of Treated by surgical evacuation.

inappropriate antidiuretic hormone secretion or See also, Neurosurgery
cerebral salt-wasting syndrome.
Anaesthetic considerations:
Substance abuse. Difficult to define, since society toler-
as for neurosurgery and neuroradiology.
ates intake of certain substances (e.g. alcohol, tobacco)
hypotensive anaesthesia has previously been
but not others (illicit drugs); in addition, excessive intake
employed but normotension is now recommended
of otherwise acceptable substances (e.g. alcohol) is gen-
to maintain cerebral perfusion pressure.
erally considered abuse. Addiction is a state of compul-
[Sir James Berry (18601946), Canadian surgeon;
sive use associated with physical, psychological or social
Robert M Hess and William Hunt (19211999), US
harm and despite evidence of that harm; dependence is
neurosurgeons]
a physiological adaptation associated with withdrawal
Diringer MN, Bleck TP, Hemphill C, etal (2011). Neuro-
symptoms when ingestion ceases.
crit Care; 15: 21140 Potential problems for anaesthesia or intensive care:
See also, Transcranial Doppler ultrasound
alcohol poisoning and alcoholism commonly accom-
pany abuse of other substances. Solvent abuse is
Subclavian venous cannulation. The subclavian vein is
more common in young patients.
the continuation of the axillary vein and arises at the
malnutrition may accompany chronic substance
lateral border of the first rib (see Fig. 86; Internal jugular
abuse.
venous cannulation). It passes over the first rib anterior
effects of iv administration, often with non-sterile
to the subclavian artery, separated from it by scalenus
needles (e.g. opioid analgesic drugs, barbiturates):
anterior, to join with the internal jugular vein at the
- high risk of sepsis, thrombophlebitis, cellulitis,
medial end of the clavicle. It receives the external jugular
bacterial endocarditis and septic systemic and
vein at the clavicles midpoint. The right phrenic nerve
pulmonary embolism.
lies between the vein and scalenus anterior, the left
- veins are often difficult to find and cannulate.
phrenic nerve between the vein and artery.
Technique:
- high-risk group for hepatitis and HIV infection.
chronic effects of the substance, e.g. hepatic
head-down position distends the vein and reduces
impairment/enzyme induction (e.g. opioids, barbitu-
risk of air embolism. The head is turned to the con-
rates); cardiomyopathy (cocaine). Thrombocytope-
tralateral side. Aseptic technique is used.
nia may occur in cocaine and opioid abuse.
a finger is run medially in the subclavian groove
acute effects:
until an obstruction is felt (subclavius muscle), also
- depressant, e.g. opioids, barbiturates: respiratory
marked by a notch on the undersurface of the clav-
depression, hypotension.
icle. This point lies between the midpoint of the
- excitatory, e.g. amfetamines, cocaine, lysergic acid
clavicle and a point dividing its middle and medial
diethylamide (LSD): tachycardia, hypertension,
thirds.
arrhythmias, pyrexia. Hallucinations may occur
after local anaesthetic infiltration, a needle is intro-
postoperatively. Anticholinergic drugs, drugs
duced under the clavicle and directed towards the
which sensitise the myocardium to catechol-
sternal notch, aspirating during advancement. When
amines and indirectly acting sympathomimetic
the vein has been entered, the cannula is advanced
drugs should be avoided. LSD may impair plasma
or a wire inserted (Seldinger technique).
cholinesterase.
The approach is contraindicated in patients with coagu-
effects of withdrawal:
lopathy, since direct pressure cannot be applied to the
- opioids: tachycardia, tremor, acute anxiety,
bleeding vessel.
GIT symptoms, piloerection and sweating (cold
See also, Central venous cannulation, for complications
turkey). Unpleasant but rarely life-threatening.
and comparison with other techniques
- barbiturates: anxiety, tremor, hallucinations and
convulsions. May be life-threatening.
Subdural haemorrhage. Haemorrhage between the pia Conduct of anaesthesia:
and arachnoid layers of the meninges. May be:
patients may be resistant to iv anaesthetic agents,
cranial:
with rapid recovery.
- acute: usually caused by accelerationdeceleration
surgical cut-down, central venous cannulation or
head injury resulting in tearing of surface or
inhalational induction may be required if peripheral
bridging vessels. Patients usually present with
venous cannulation is impossible.
confusion or loss of consciousness following a
estimation of appropriate doses of opioids may be
lucid interval. CT scanning shows a hyperdense
difficult, especially in opioid addicts. Inhalational
mass, often with surrounding oedema. Mortality
and regional techniques are often preferred. Opioid
ranges from 60 to 90% depending on the underly-
antagonists may provoke acute withdrawal and
ing brain injury, Glasgow coma scale on admis-
should be avoided.
sion, patients age and concurrent anticoagulant
withdrawal states may occur postoperatively.
therapy.
See also, Abuse of anaesthetic agents; Barbiturate poison-
- chronic: usually occurs in elderly patients, with
ing; Misuse of Drugs Act; Opioid poisoning; Rapid
head injury identified in < 50%. Presents with a
opioid detoxification; Solvent abuse
variety of symptoms, including headaches, confu-
sion, dementia, language difficulties, convulsions
and transient ischaemic attacks. CT scanning Substance P. 11-amino-acid tachykinin neuropeptide,
shows an isodense lesion; bilateral haematomata involved in pain pathways (see Gate control theory
occur in 25% of cases. of pain). High levels are found in axons and cell bodies
spinal (very rare), e.g. following lumbar puncture. of primary afferent fibres in the dorsal root ganglia,
 Sugammadex sodium 549

also in the superficial levels of the dorsal horn of the and compressed gases using the Venturi principle.
spinal cord. Piped suction systems use a high displacement
Evidence for its involvement in pain transmission pump connected to a large central reservoir, with
includes: traps to prevent contamination.
distribution in the regions of pain pathways. reservoir: must be large enough to enable aspiration
depletion by capsaicin, a red pepper extract, reduces of large volumes, but not so large that the desired
sensitivity to noxious thermal and chemical stimuli, vacuum takes too long to achieve. A filter and float
without affecting other sensory modalities. valve prevent contamination of the pump with aspi-
Also involved in the regulation of the respiratory rhythm, rated liquid.
nausea and vomiting, and mood. delivery tubing; usually disposable, attached to rigid
(Yankauer) or flexible catheters. Smooth-tipped
Substantia gelatinosa, see Pain pathways; Sensory path- catheters may reduce mucosal damage following
ways; Spinal cord endotracheal suctioning. Prolonged tracheobron-
chial suctioning may cause lung collapse and hypox-
Sub-Tenons block. Used in ophthalmic surgery as an aemia; bradycardia is common in critically ill
alternative to retrobulbar block and peribulbar block. patients. Preoxygenation should thus precede tra-
Tenons capsule is a connective tissue layer surrounding cheal suction. Enclosed suction catheters that do
the eye and extraocular muscles. The posterior part sepa- not require detachment of the patient from the
rates the globe from the retrobulbar space; injection of breathing system are available; the catheter is
local anaesthetic between the capsule and sclera poste- handled through a plastic sleeve, maintaining steril-
riorly results in spread along the extraocular muscles ity. Hypoxaemia and dispersal of infectious droplets
and diffusion into the retrobulbar space. are thus reduced.
Topical anaesthesia is applied first. With the patient Minimal flow rate of 35 l/min air, and generation of at
looking up, the conjunctiva and anterior Tenons capsule least 80kPa (600mmHg) negative pressure, have been
are picked up with toothed forceps, 56mm inferome- suggested for apparatus for anaesthetic use.
dial to the limbus (the junction of the cornea and sclera). [Sidney Yankauer (18721932), US surgeon]
A small incision is made with scissors, which are then
passed backwards around the globe underneath Tenons Sudecks atrophy, see Complex regional pain
capsule to reach the posterior part. A curved, blunt syndrome
cannula is then passed into this space and 34ml solu-
tion slowly injected. Gentle external pressure is applied Sufentanil citrate. Synthetic opioid analgesic drug,
to the eye and further injections made if required. Suit- introduced in 1984. Available in the USA but not the
able solutions include a mixture of lidocaine 2% and UK, for marketing reasons. An analogue of fentanyl,
bupivacaine 0.50.75% in equal volumes with or without with 57 times the latters potency. Of shorter elimina-
adrenaline 1:400000 and hyaluronidase 5U/ml. tion half-life (about 23h) than fentanyl, with similar
Provides rapid anaesthesia and akinesia with less risk clearance and slightly smaller volume of distribution.
of globe perforation or retrobulbar haemorrhage than Has similar clinical effects to fentanyl, including cardio-
retrobulbar block; the block is also usually more com- vascular stability and lack of histamine release. Usual
fortable than alternatives. dose is 0.10.5g/kg for minor surgery, up to 8g/kg for
Complications include: pain on injection; subconjunc- longer procedures and up to 30g/kg as the sole agent
tival oedema (chemosis); subconjunctival or retrobulbar for, e.g. cardiac surgery. May be given epidurally (10
haemorrhage; globe perforation (rarely). 75g) and spinally (520g), effects lasting 26h.
[Jacques R Tenon (17241816), French ophthal
mologist] Sugammadex sodium. Modified -cyclodextrin licensed
Jeganathan VS, Jeganathan VP (2009). Curr Opin for reversal of non-depolarising neuromuscular block-
Ophthalmol; 20: 2059 ade caused by rocuronium or vecuronium. It has a ring-
shaped structure that forms a water-soluble complex
Succinylcholine, see Suxamethonium with rocuronium/vecuronium, thus favouring removal
from the neuromuscular junction into the plasma.
Sucralfate. Complex of aluminium hydroxide and sul- Dosage:
phated sucrose. Provides mucosal protection from gastric routine reversal: 2mg/kg if spontaneous recovery of
acid and promotes ulcer healing. Has no antacid effect. > 1 twitch has occurred on train-of-four nerve stim-
Used in peptic ulcer disease, and has been used on ICU ulation; 4mg/kg if > 12 post-tetanic counts are
as prophylaxis against peptic ulceration; thought to be present. Recovery of T4:T1 ratio to 0.9 occurs
associated with fewer nosocomial infections than the H2 within 23min. Recovery is slightly slower with
receptor antagonists. vecuronium than rocuronium.
Dosage: 1g orally/nasogastrically 46-hourly. immediate reversal of rocuronium-induced block-
Side effects are rare; include constipation, nausea, ade (e.g. after failed intubation during rapid
vomiting, rash. sequence induction): 16mg/kg; if administered
3min after a bolus dose of 1.2mg/kg rocuronium,
Suction equipment. Consists of: produces recovery of T4:T1 ratio to 0.9 after 1.5min.
pump to generate a vacuum. Effectiveness of the recurrence of neuromuscular blockade: additional
system is related to the degree of subatmospheric dose of 4mg/kg.
pressure generated, and the volume of air that can in obese patients, dosing should be based on actual
be moved in unit time (displacement). Pumps may body weight.
employ pistons (usually low displacement), rotating Side effects: bronchospasm, anaphylaxis (rarely),
fans (high displacement), foot-operated bellows taste disturbance.
550 Sulfadiazine

Due to high cost, its use is largely confined to the emer- Superior vena caval obstruction (Superior vena
gency setting. caval syndrome). 8090% of cases are caused by malig-
See also, Neuromuscular blockade monitoring nancy, especially bronchial carcinoma and lymphoma.
Other causes include mediastinal fibrosis and thrombo-
Sulfadiazine (Sulphadiazine). Sulphonamide and anti- sis. Results in distended veins, oedema and cyanosis in
bacterial drug, used as prophylaxis against rheumatic the arm, head and neck, with prominent collateral vessels
fever and in toxoplasmosis. in the chest wall. Visual disturbances and headache may
Dosage: 500mg1.0g orally/iv od. occur. Most patients have dyspnoea and orthopnoea.
Side effects: as for sulphonamides. Emergency radiotherapy may be required if malignancy
is the cause. Steroids have also been used to reduce
Sulphaemoglobinaemia. Presence of an abnormal hae- oedema.
moglobin of uncertain chemical structure, but which may Anaesthetic considerations:
be produced by adding hydrogen sulphide in vitro. Often patients should be nursed sitting up preoperatively,
coexists with methaemoglobinaemia. Reduces O2- to minimise facial and neck swelling.
carrying capacity of blood and shifts the oxyhaemoglo- induction of anaesthesia with iv agents may be pro-
bin dissociation curve to the left, decreasing O2 delivery longed if an arm vein is used.
to the tissues. Usually due to ingestion of phenacetin, tracheal intubation may be difficult. Laryngeal
sulphonamides, primaquine or metoclopramide. Treat- oedema may be present.
ment includes O2 therapy; normal haemoglobin cannot bleeding may be torrential, especially during median
be regenerated from sulphaemoglobin. sternotomy.

Sulphonamides. Group of broad-spectrum antibacterial Supine hypotension syndrome, see Aortocaval

drugs, less commonly used now because of bacterial compression
resistance and side effects. Also active against certain
protozoa, e.g. toxoplasma and pneumocystis. Act by Supraorbital nerve block, see Ophthalmic nerve blocks
inhibiting bacterial dihydrofolate synthesis; their action
is enhanced by trimethoprim which inhibits tetrahydro- Suprascapular nerve block. Performed for analgesia in
folate production from dihydrofolate. Toxic effects painful shoulders. A needle is inserted 12cm cranial to
include renal impairment, blood dyscrasias and allergic the scapular spine, on a line bisecting the inferior scapu-
reactions. lar angle. 5ml local anaesthetic agent is injected when
the scapular notch is identified.
Sulphonylureas. Group of oral hypoglycaemic drugs,
used in non-insulin-dependent diabetes mellitus. Act by Supraventricular tachycardia (SVT). Paroxysmal
stimulating secretion of insulin by surviving pancreatic tachycardia with a rate of 140250 beats/min, caused by
cells, and possibly by increasing peripheral uptake of a rapidly firing ectopic focus in the atria or atrioventricu-
glucose. Several are available, e.g.: lar node. Circular conduction of impulses via abnormal
chlorpropamide: half-life 3545h. anatomical pathways or within the node itself results in
glibenclamide, gliclazide and glibornuride: half-life re-entry and perpetuation of the arrhythmia. Occurs
812h. in otherwise healthy individuals, although it may be
tolbutamide, tolazamide, glimepiride: half-life 58h. associated with heart disease, WolffParkinsonWhite
glipizide: half-life 24h. and LownGanongLevine syndromes, hyperthyroid-
gliquidone: half-life 12h. ism, and excessive consumption of caffeine, nicotine or
All of the above are excreted by the liver except chlor- alcohol. Typically sudden in onset. May cause palpita-
propamide, which is excreted renally. tions, dyspnoea, dizziness and polyuria if prolonged.
The shorter-acting drugs may be stopped on the Features: regular narrow QRS complexes on the
day of surgery; perioperative hypoglycaemia is most ECG (Fig. 152), unless bundle branch block is also
likely in the elderly and with long-acting drugs, e.g. present (causing widened QRS complexes). A degree
chlorpropamide. of atrioventricular block may be present, especially
when associated with digoxin toxicity. It may be dif-
Sumatriptan. 5-HT1D receptor agonist, used to treat ficult to distinguish SVT from VT.
acute migraine and cluster headache. Should not be used
for prophylaxis. Has also been used in post-dural punc-
ture headache, although evidence is anecdotal only.
Almotriptan, eletriptan, frovatriptan, naratriptan, rizat-
riptan and zolmitriptan are newer, related drugs.
Dosage: 50100mg orally, 6mg sc or 20mg intrana-
sally as soon as possible after onset; the dose may be
repeated (not during the same attack) if migraine
recurs, up to 300mg orally, 12mg sc or 40mg intra-
nasally in 24h.
Side effects: tingling, heaviness or tightness of any
part of the body, chest pain, flushing, dizziness, nausea,
drowsiness, hypotension, brady- or tachycardia, con-
vulsions, hepatic dysfunction. Contraindicated in
ischaemic heart disease and concurrent therapy with
related drugs or ergotamine. Coronary vasospasm
may follow iv injection. Fig. 152 SVT
 Suxamethonium chloride 551

Treatment: European Resuscitation Council normally reduced by pulmonary surfactant. Measured

guidelines: in N/m.
O2 therapy, iv cannulation. See also, Laplaces law
if there are adverse signs (e.g. shock, myocardial
ischaemia, cardiac failure or syncope): synchronised Surfactant. Complex material composed of dipalmitoyl
electrical cardioversion (up to three attempts) with phosphatidyl choline (DPPC), protein and carbohydrate,
sedation if required, followed by amiodarone which prevents alveolar collapse at lower lung volumes
300mg over 15min and 900mg over 24 h. by reducing alveolar surface tension. Thought to do
if there are no adverse signs, then options include:
this by alignment of the hydrophilic parts of the DPPC
vagal stimulation manoeuvres (e.g. carotid sinus molecules on the surface of the alveolar fluid lining,
massage, Valsalva manoeuvre) and: with repulsion between adjacent molecules. Repulsion
antiarrhythmic drugs:
increases as the molecules are pressed together at low
- adenosine 6mg iv initially; if unsuccessful, two volumes. Compliance is increased, alveoli are held open
further doses of 12mg may be given at 12-min and alveolar fluid is reduced.
intervals. Produced by type II pneumocytes, partly under
- if heart rate is still above 200 beats/min, one or control of the hypothalamicpituitaryadrenal axis.
more of the following may be used: Appears at about 24 weeks gestation. Deficiency due to
- amiodarone 300mg iv over 1015min. immaturity causes the respiratory distress syndrome
- digoxin up to two iv doses of 0.5mg over 30min (RDS). It may also be deficient in areas of lung affected
(not in WolffParkinsonWhite syndrome). by PE, bronchial obstruction, and in heavy smokers.
- verapamil 510mg iv. Bovine/porcine surfactant is licensed for prophylaxis
- esmolol 40mg iv over a minute followed by and treatment of neonatal RDS; it has no proven benefit
4mg/min, repeated and increased up to 12mg/ in adult acute lung injury.
min respectively. Surviving sepsis campaign. Global initiative of the
overdrive cardiac pacing (not in atrial fibrillation).
European Society of Intensive Care Medicine, Society
hypokalaemia and hypomagnesaemia should be
of Critical Care Medicine and International Sepsis
corrected if present. Forum (the latter no longer involved), with the aim of
Other drugs, e.g. -adrenergic receptor antagonists, improving the management, diagnosis and treatment of
disopyramide, diltiazem, have also been used. Ablation sepsis through increasing awareness, educating health-
therapy or surgery may be required. care professionals, developing guidelines/care bundles
Nolan JP, Soar J, Zideman DA, etal (2010). Resuscita- and facilitating data collection.
tion; 81: 121976
See also, Atrial flutter Suxamethonium chloride (Succinylcholine). Depola-
rising neuromuscular blocking drug, introduced in 1951.
Sural nerve block, see Ankle, nerve blocks Structurally composed of two acetylcholine molecules
joined together (Fig. 153). Stored at 4C to prevent
Surface area, body. Used to estimate drug doses, and in hydrolysis. Incompatible with thiopental (causes
physiological calculations (e.g. cardiac index, basal meta- crystallisation).
bolic rate), since it reflects body requirements and activ- Dosage:
ity more accurately than weight and height; however, 0.51.5mg/kg iv depending on the relaxation
use of basal metabolic rate has been suggested as being required. Usual initial dose is 1mg/kg iv, producing
more logical. paralysis within 3090s which lasts 25min. Subse-
The rule of nines is used to estimate surface area of quent doses: 0.20.5mg/kg. Low doses (510mg)
parts of the body. Nomograms for total surface area are are used for treatment of laryngospasm.
based on the formula: may be given by infusion of 0.1% solution with 5%

surface area (m 2 ) = weight 0.425 (kg) dextrose or 0.9% saline at 25mg/min.

may also be given im (24mg/kg) or sc.
height0.725 (cm) 0.007184
Rapidly hydrolysed by plasma cholinesterase to succinyl
monocholine and choline, then to succinic acid and
Surface tension. Tangential force in the surface of a choline. Succinyl monocholine has weak blocking
liquid, defined in terms of the force acting perpendicu- properties.
larly across a line of unit length. Caused by attraction Hexafluorenium and tetrahydroaminocrine have
between the liquid molecules; whereas molecules in the been used to prolong suxamethoniums action.
main body of the liquid are attracted in all directions, Side effects:
those at the surface are only attracted inwards and along prolonged paralysis. May be caused by:
the surface. Thus the surface tends to contract to the - reduced cholinesterase activity (see Cholinester-
smallest possible area, e.g. a free drop tends to be spheri- ase, plasma) due to:
cal. Has important implications in lung mechanics; - inherited atypical cholinesterase.

CH3 O O CH3
+ +
CH3 N CH2 CH2 O C CH2 CH2 C O CH2 CH2 N CH3
CH3 CH3

Fig. 153 Structure of suxamethonium

552 Suxethonium bromide/iodide

- reduced amount of cholinesterase. - calcium 10mmol iv. Arrhythmias may occur.

- inhibition of cholinesterase by drugs. - magnesium sulphate 12g iv.
- excessive dosage, cumulation of succinylcholine - chlorpromazine 0.1mg/kg.
and production of dual block. The latter may - hexafluorenium.
occur after 200500mg in adults. hyperkalaemia. Plasma potassium increases usually
Dual block may also develop with reduced by 0.5mmol/l in normal patients, and lasts for
enzyme activity. Management of prolonged 35min. This follows normal movement of potas-
paralysis: sium out of myocytes during depolarisation at the
- maintenance of anaesthesia and oxygenation. neuromuscular junction, with some leakage due
- diagnosis of the nature of block using to trauma following fasciculations, as above. The
neuromuscular blockade monitoring. Edropho- increase may be dangerous in patients whose
nium has been suggested to distinguish non- plasma potassium levels are already high (typically
depolarising from depolarising blockade, but is renal failure, although the response is of normal
less commonly used. magnitude unless neuropathy is present). Increases
- neostigmine may be used to reverse dual block. of several mmol/l may occur if the acetylcholine
- in prolonged depolarising blockade (suxame- receptors are not confined to the neuromuscular
thonium or Scoline apnoea), recovery usually junction, but have spread along the whole length of
occurs within 4h. It may be speeded by admin- the muscle fibres, as occurs in denervation hyper-
istering fresh frozen plasma, but spontaneous sensitivity. This process is also thought to occur in
recovery is usually preferable. other conditions in which massive hyperkalaemia
- blood may be analysed for cholinesterase activ- may follow administration of suxamethonium for
ity, and screening of relatives performed. certain periods after the lesion:
muscle fasciculations, coinciding with initial depo- - burns: 9 days2 months.
larisation of muscle fibres. They are painful if the - spinal cord injury, intracranial lesions (e.g. CVA,
patient is awake. Thought to contribute to: subarachnoid haemorrhage, head injury) and
- postoperative muscle pains, typically around the muscle trauma: 10 days67 months.
neck, back and upper arms, lasting 23 days. Most - peripheral nerve injury: 4 days67 months.
common in young fit women and after early - peripheral neuropathy, tetanus and severe infec-
ambulation. tion: uncertain period of risk.
- increased intraocular pressure. Suxamethonium Maximal risk occurs at 1428 days. Severe arrhyth-
causes contraction of the extraocular muscles, but mias and cardiac arrest may occur, usually respond-
may also cause choroidal vasodilatation; the ing well to iv calcium and CPR. The same drugs
response may still occur if the extrinsic muscles used to attenuate the fasciculations have been used
are cut. The increase usually lasts for under to reduce the hyperkalaemic response, with varying
10min. Suxamethonium is usually avoided in success. Salbutamol has also been used.
penetrating eye injuries but this is controversial The risk of hyperkalaemia in disseminated scle-
(see Eye, penetrating injury). rosis and Parkinsons disease is unclear. It has been
- increased intragastric pressure. Formerly thought described in muscular dystrophies (related to
to increase risk of aspiration of gastric contents, massive rhabdomyolysis and possibly MH), but not
but an accompanying increase in lower oesopha- in motor neurone disease.
geal sphincter tone maintains barrier pressure. bradycardia: common after the second dose, but
- increased plasma potassium. Although this arises may occur after the first dose, especially in children.
mainly from depolarisation (see below), leakage Other muscarinic effects may occur, e.g. increased
of potassium from damaged muscle fibres may GIT motility and secretion.
contribute. Plasma myoglobin and creatine phos- adverse drug reactions. Although rare, they may be
phokinase (normally intracellular) are increased severe, e.g. anaphylaxis.
after injection of suxamethonium. MH.
Fasciculations and the resulting complications may masseter spasm.
be reduced by pretreatment with other drugs, abnormal sustained contraction in dystrophia
although not consistently. Adverse effects may also myotonica.
still occur despite lack of fasciculations. Drugs that Resistance occurs in myasthenia gravis due to reduced
have been described include: receptor density, and increased sensitivity is seen in the
- non-depolarising neuromuscular blocking drugs myasthenic syndrome.
(usually 1/10 usual intubating dose), given Its use has declined because of its many disadvan-
23min before suxamethonium, which may be tages and the introduction of alternative drugs, e.g.
required in increased dosage. Tubocurarine is atracurium, vecuronium, rocuronium and mivacurium.
the best studied, although others have been However, the conditions suxamethonium provides for
used. The possibility of aspiration pneumonitis tracheal intubation are generally considered superior
precludes this technique in rapid sequence and occur faster than those attained by other drugs. Its
induction. short duration of action allows tracheal intubation with
- lidocaine 12mg/kg iv, given 23min before subsequent spontaneous ventilation, and is especially
suxamethonium. advantageous if intubation is difficult.
- diazepam 10mg iv. See also, Depolarising neuromuscular blockade
- dantrolene 100200mg orally, 2h preopera-
tively. Suxethonium bromide/iodide. Depolarising neuro-
- suxamethonium 0.1mg/kg iv 12min before muscular blocking drug, introduced with suxametho-
the main dose. nium in 1951. Similar to suxamethonium, but the
 Sympathetic nervous system 553

quaternary ammonium group at each end of the mole- emerge from spinal segments T1L2 into the corre-
cule contains two methyl and one ethyl group instead of sponding primary ramus at each level, and pass via
three methyl groups. a white ramus communicans into the sympathetic
trunk (see Fig. 21; Autonomic nervous system). They
SVP, see Saturated vapour pressure may then:
synapse in the corresponding ganglion and pass via

SVR, see Systemic vascular resistance a grey ramus communicans to the corresponding
spinal nerve for distribution.
ascend or descend in the sympathetic chain, and
SVT, see Supraventricular tachycardia
synapse at a distant ganglion.
pass without synapsing to a peripheral ganglion, to
Swallowing (Deglutition). Active passage of liquid or synapse there.
food bolus from mouth to stomach. Initiated voluntarily The sympathetic trunk is a ganglionated nerve chain
by the tongue pressing against the palate from the tip extending from the base of the skull to the coccyx, and
back, pushing food into the oropharynx. Continues by lying about 23cm lateral to the vertebral column. The
reflex activity, with afferent fibres in the 9th and 10th portion above T1 does not receive any rami communi-
cranial nerves; impulses pass to the tractus solitarius cantes; i.e. the cervical sympathetic outflow must descend
and nucleus ambiguus of the medulla, with efferent to T1, then into the sympathetic trunk and ascend to the
fibres to pharyngeal and tongue muscles via 9th, 10th cervical ganglia. The trunk descends in the neck behind
and 12th nerves. The nasopharynx is sealed by soft palate the carotid sheath and enters the thorax anterior to the
elevation and superior constrictor contraction, and the neck of the first rib. It passes over the heads of the upper
larynx by elevation and glottic closure. The epiglottis ribs and overlies the sides of the lower four thoracic
moves posteriorly but does not seal the glottic opening, vertebrae. It enters the abdomen behind the medial
as formerly suspected. Respiration ceases. Food is pro- arcuate ligament (see Diaphragm) and lies between the
pelled by the inferior constrictor into the upper oesoph- lumbar vertebral bodies and psoas major, passing into
agus, where it initiates peristalsis (see Oesophageal the pelvis anterior to the sacral ala. The two chains meet
contractility). and terminate on the anterior surface of the coccyx.
Suppressed in plane 1 of surgical anaesthesia; its reap- Ganglia:
pearance may herald the onset of vomiting. cervical:
Difficulty with swallowing (dysphagia) may be caused - superior:
by anatomical (e.g. local tumours, inflammation, achala- - lies opposite C23.
sia) or neurological (e.g. myasthenia gravis, bulbar - branches: superior cardiac nerve, and branches
palsies) factors; pulmonary aspiration of food and saliva to the upper four cervical nerves, internal
may lead to repeated chest infection. carotid plexus and cranial nerves VII, IX, X and
XII.
SwanGanz catheter, see Pulmonary artery - middle:
catheterisation - lies opposite C6.
- branches: middle cardiac nerve, and branches to
Sympathetic nerve blocks. Although blockade of sym- C5 and C6.
pathetic nerves commonly accompanies various regional - inferior:
techniques (e.g. epidural or spinal anaesthesia, brachial - lies opposite C7; often fused with the first tho-
plexus block), selective blockade of sympathetic fibres is racic ganglion to form the stellate ganglion on
used for: the neck of the first rib.
pain management: certain pain syndromes are - branches: inferior cardiac nerve, and branches
thought to involve abnormal sympathetic activity, to C7 and C8.
e.g. complex regional pain syndrome, phantom limb thoracic:
pain. The underlying mechanism is unknown but - usually 12, although variable.
may involve abnormal linkage between mechanore- - branches: to splanchnic and intercostal nerves.
ceptors and sympathetic neurones. Recent evidence lumbar: usually four ganglia.
suggests that sympathetic blocks may not actually sacral: usually four ganglia.
improve outcome, as traditionally believed. Sympathetic innervation of viscera is via the cardiac,
improvement of blood flow, e.g. in peripheral isch- coeliac and hypogastric plexuses. The sympathetic
aemia, Raynauds disease, accidental intra-arterial nervous system is concerned with the flight or fight
injection of thiopental. response to stress. Stimulation causes:
treatment of excessive sweating. pupillary dilatation and ciliary muscle relaxation.
Sympathetic ganglia may be blocked at three levels: tachycardia and increased myocardial contractility.
the cervicothoracic ganglia (stellate ganglion block), -adrenergic receptor-mediated vasoconstriction
coeliac plexus (coeliac plexus block) and lumbar ganglia (2-receptor-mediated vasodilatation in skeletal
(lumbar sympathetic block). Blockade may be short- muscle, abdominal viscera, and coronary, pulmo-
term (using local anaesthetic agents) or permanent nary and renal circulations).
(chemical sympathectomy), when neurolytic agents such bronchodilatation and reduced bronchial
as phenol or alcohol are used. IVRA using guanethidine secretion.
is also used. decreased GIT motility, contraction of sphincters
[Maurice Raynaud (18341881), French physician] and reduction of secretions (thick viscous secretion
from salivary glands). Mixed effects on insulin and
Sympathetic nervous system. Part of the autonomic glucagon secretion (decreased by -receptor stimu-
nervous system. Myelinated preganglionic efferent fibres lation, increased by 2-receptor stimulation).
554 Sympathomimetic drugs

the synaptic cleft and binds to specific receptors in the

Table 41 Actions of sympathomimetic drugs
postsynaptic membrane. This elicits a response in the
Direct stimulation Indirect activity
postsynaptic cell (e.g. change in membrane potential,
activation of a second messenger); the neurotransmitter
Drug is then broken down by a specific enzyme (e.g. acetyl-
cholinesterase), diffuses into surrounding tissues or
Adrenaline + ++ is taken up by the presynaptic nerve ending (e.g.
Noradrenaline ++ + noradrenaline).
Isoprenaline ++ Initiation of an action potential in the postsynaptic
Phenylephrine ++ cell depends on the number and frequency of impulses
Methoxamine ++ arriving from different presynaptic cells; impulses
Salbutamol ++ may be excitatory or inhibitory, depending on the
Ephedrine ++ neurotransmitter/receptor complex. In addition, presyn-
Metaraminol ++ + ++
aptic inhibition and facilitation may occur, via neurones
Amfetamine + + ++
forming synapses at the presynaptic nerve ending.
Some synapses are electrical, with transmission across
gap junctions; some are both electrical and chemical. A
bladder relaxation and sphincteric contraction. synaptic delay of at least 0.5 ms occurs at chemical syn-
Increased renin secretion. apses, but not at electrical ones.
variable effect on the uterus. See also, Neuromuscular transmission
ejaculation of semen.
piloerection and sweating of palms. Synchronised intermittent mandatory ventilation,
hepatic glycogenolysis and adipose lipolysis. see Intermittent mandatory ventilation
Acetylcholine is the neurotransmitter at ganglia and the
adrenal medulla; noradrenaline is the neurotransmitter Syndrome of inappropriate antidiuretic hormone
at postganglionic nerve endings (except for sweat glands, secretion (SIADH). Increased plasma vasopressin
where acetylcholine is the transmitter). The adrenal levels and water retention despite plasma hypo-
medulla is effectively a sympathetic ganglion that osmolality and expanded or normal ECF.
secretes directly into the bloodstream. Caused by:
Central control of sympathetic activity is from the ectopic production of vasopressin, e.g. by carcinoma
medulla, pons and ventromedial hypothalamus. of bronchus, pancreas, prostate, colon and other
Neukirchen M, Kienbaum P (2008). Anesthesiology 109: tissue, or lymphoma.
111331 pulmonary disease, e.g. chest infection, TB, abscess.
See also, Acetylcholine receptors; Sympathetic nerve CNS disorders, e.g. brain tumour, CVA, head injury,
blocks encephalitis, meningitis, surgery.
stress, e.g. pain, severe illness, trauma.
Sympathomimetic drugs. Drugs that stimulate acute intermittent porphyria.
adrenergic receptors. Actions of individual drugs vary drugs, e.g. vasopressin overtreatment, oxytocin,
depending on whether they affect predominantly - or indometacin, antidepressants, chlorpropamide,
-receptors, or both. Some stimulate receptors directly; carbamazepine.
others act indirectly via release of endogenous catechol- Features: those of hyponatraemia. Urinary sodium
amines (Table 41). exceeds 20mmol/l (often 50150mmol/l), plasma
Used clinically as vasopressor, inotropic and bron- osmolality is low (< 280 mosmol/kg), and urinary/
chodilator drugs. Amfetamine is used in narcolepsy for plasma osmolality ratio exceeds 1.
its CNS stimulant action. Treatment:
See also, individual drugs of primary cause.
water restriction (e.g.11.5 l/day); hypertonic saline
Synapse. Specialised junction between a neurone (pre- has been used in severe cases.
synaptic cell) and another (postsynaptic) cell, usually demeclocycline 600mg daily in divided doses if per-
another neurone but also muscle or glandular cells. sistent (thought to block the renal effects of vaso-
Allows unidirectional transmission of action potentials pressin). Furosemide and phenytoin have been
between cells (synaptic transmission), via neurotransmit- used.
ter release (although electrical transmission across gap vasopressin receptor antagonists.
junctions may also occur). One presynaptic neurone may as for hyponatraemia if severe.
contribute to over 1000 synapses. Most presynaptic nerve Peri A, Pirozzi N, Parenti G, Festuccia F, Mer P (2010).
endings bear terminal buttons (synaptic knobs), with up J Endocrinol Invest; 33: 67182
to several thousand from different cells contacting each See also, Cerebral salt wasting syndrome
postsynaptic neurone. The terminal buttons contain many
mitochondria and vesicles containing neurotransmitter, Syphilis. Sexually transmitted infection caused by the
and are separated from the postsynaptic membrane by spirochaete Treponema pallidum.
the synaptic cleft (3050nm wide). Neurotransmitter Divided clinically into:
receptors are present in high concentrations in the post- primary stage: appearance of chancre at site of
synaptic membrane opposite the terminal buttons. infection, 10 days10 weeks after inoculation.
See also, Neuromuscular junction secondary stage: faint macular rash, condylomata
and lymphadenopathy.
Synaptic transmission. Usually involves release from tertiary stage: lesions in skin, subcutaneous
presynaptic cells of a neurotransmitter that passes across tissue, bone, tongue, testes, liver and CNS
 Systemic sclerosis 555

(meningovascular syphilis, tabes dorsalis, general common in Afro-Caribbeans. Its aetiology is unknown;
paralysis of the insane). both genetic and environmental factors have been impli-
Carditis and aortitis may occur, leading to ascending or cated. May also be drug-induced; classic causes include
arch aortic aneurysm and aortic regurgitation. Angina methyldopa, procainamide and hydralazine. Involves
may occur in 50% of patients with aortitis. many abnormalities of the immune system, with autoan-
Serological tests are strongly positive after 3 months tibodies a central feature; they may affect tissues directly
in untreated cases. Treatment is usually with penicillin. or via immune complex deposition. General features
Anaesthetic considerations are mainly related to the and anaesthetic considerations are as for connective
CVS effects. Blood donors are screened for syphilis tissue diseases; the most common features of SLE are
before donation. fatigue, fever, arthralgia and myalgia, skin rashes, psy-
chological involvement and haematological abnormali-
Syringe labels. The system of colour-coded labels widely ties (thrombocytopenia and anaemia in about 50% and
used in the UK differed from that in use in the USA, lupus anticoagulant in about 10%; the latter may prolong
Canada, Australia and New Zealand, until in 2003 the coagulation, especially the intrinsic pathway. Risk of
Royal College of Anaesthetists, Association of Anaes- bleeding is not increased if other factors and platelets
thetists, Faculty of Accident and Emergency Medicine, are normal, but risk of thrombosis is increased, possibly
and Intensive Care Society agreed to recommend the via inhibition of prostacyclin production and platelet
international system, updated in 2004: aggregation).
sedatives/tranquillisers: orange. Renal, cardiac and pulmonary complications (e.g.
induction agents: yellow. nephritis, peri- or myocarditis, pneumonitis) each occur
neuromuscular blocking drugs: red. in about 50% of cases. Patients may present with acute
opioids: blue. organ failure requiring admission to the ICU. Laryngeal
vasopressors: violet. oedema, epiglottitis and cricoarytenoiditis requiring
local anaesthetics: grey. emergency intubation have been reported.
anticholinergics: green. Diagnosed by clinical features and results of investi-
antiemetics: salmon. gations, especially autoantibody titres (e.g. antinuclear
others: white. Antagonists are marked by appropri- and anti-double-stranded DNA antibodies), although
ately coloured oblique stripes on the labels upper these may be elevated in other connective tissue diseases
and side edges. and other conditions.
Because of the importance of recognising suxametho- Treatment includes corticosteroids, NSAIDs, immu-
nium and adrenaline rapidly, these two drugs are high- nosuppressive drugs and antimalarial drugs. Prognosis is
lighted by their labels bearing a black upper half with generally good, although long-term treatment is usually
the drugs name in reverse colour. Combinations of required; prognosis is worse with CNS involvement,
drugs bear both relevant colours. hypertension and early onset.
Ben-Menachem E (2010). Anesth Analg; 111: 66576
Syringes. First use is attributed to both Wood and Pravaz
in 1855, although parenteral administration of drugs had Systemic sclerosis (SS; Scleroderma). Rare connective
been described earlier (e.g. by Wren in 1656). Disposable tissue disease most commonly affecting women in their
polystyrene or polypropylene syringes are now widely 40s. Its aetiology is unknown. Involves increased deposi-
used. Glass syringes are used for injecting drugs that are tion of connective tissue components and fibrosis affect-
incompatible with plastic (e.g. paraldehyde) and for ing small vessels, skin and other tissues. General features
location of the epidural space. Plastic loss of resistance and anaesthetic considerations are as for connective
devices resemble syringes but do not meet the required tissue diseases; the disease may be limited to the skin or
standards to be termed as such. be truly systemic, involving:
[Alexander Wood (18171884), Scottish physician; peripheral vasculature and skin: calluses, ulceration
Charles Gabriel Pravaz (17911853), French surgeon; Sir or ischaemia of the extremities may occur. The tight
Christopher Wren (16321723), English architect, math- skin may make iv cannulation or mouth opening
ematician and physicist] difficult.
Ball C, Westhorpe R (2000). Anaesth Intensive Care; oesophagus: impaired motility occurs in about 90%
28: 125 of cases, with potential risk of aspiration of gastric
contents.
Systemic inflammatory response syndrome (SIRS). lungs: pleurisy, effusions, fibrosis and pulmonary
Clinical state resulting from many different disease pro- hypertension are common.
cesses (e.g. trauma, pancreatitis, burns, infection) but kidneys: affected to some degree in most patients
which are all thought to involve activation of the cyto- with diffuse SS. Hypertension may signal acceler-
kine cascade. Defined as two or more of: ated renal impairment and the need for angiotensin
hypothermia (< 36C) or hyperthermia (> 38C). converting enzyme inhibitor therapy. Function may
heart rate > 90 beats/min. recover after many years dysfunction.
tachypnoea (> 20 breaths/min.) heart: involved in over 90% of cases, usually peri-
3
leucopenia (< 4000/mm ), leucocytosis (> 12000/ cardial effusion.
mm3), or the presence of greater than 10% imma- others: joints, muscle peripheral nerves.
ture neutrophils. The CREST syndrome comprises calcinosis, Raynauds
Sepsis is defined as SIRS due to infection. phenomenon, (o)esophagitis, sclerodactyly and
telangiectasia.
Systemic lupus erythematosus (SLE). Connective Treatment includes penicillamine, colchicine and
tissue disease most commonly affecting women aged immunosuppressive drugs, including corticosteroids.
1555, with a prevalence of up to 250 per 100000. More [Maurice Raynaud (18341881), French physician]
556 Systemic vascular resistance

Systemic vascular resistance (SVR; Peripheral vascu- - other neurotransmitters may be involved, e.g.
lar resistance, PVR; Total peripheral resistance, TPR). substance P, vasoactive intestinal peptide.
Resistance against which the heart pumps. May be cal- circulating substances, e.g. noradrenaline, angioten-
culated using the principle of Ohms law: sin II, vasopressin, vasopressor drugs (causing vaso-
SVR (dyne s/cm 5 ) constriction); vasodilator drugs, atrial natriuretic
peptide (causing vasodilatation). Adrenaline causes
MAP CVP (mmHg) vasodilatation in skeletal muscle and the liver.
= 80 (correction factor)
cardiac output (1/min) Toxins released in septic shock may cause vasodila-
Normally 10001500 dyne s/cm5 (N.B. 1 dyne s/cm5 = tation. The locally produced substances above may
100 N s/m5). also cause systemic effects.
The above equation ignores the effects of blood SVR increases progressively with age. Chronically
viscosity, pulsatile flow and the different results of pres- increased SVR is the hallmark of essential hypertension.
sure changes on different vascular beds. SVR body surface area (SVR index; SVRI) adjusts
SVR is mainly determined by the diameter of the
for differences in body size between individuals.
arterioles, small changes in their calibre producing See also, Arterial blood pressure; Renin/angiotensin
large changes in resistance. Arteriolar calibre may be system
affected by:
intrinsic contractile response of vascular smooth Systole, see Cardiac cycle
muscle to increased intravascular pressure (myo-
genic theory of autoregulation).
locally produced substances causing vasodilatation Systolic time intervals. Measurements derived from
(e.g. CO2, potassium and hydrogen ions, lactic acid, the systolic phase of the cardiac cycle, obtained from
histamine, nitric oxide, adenosine, prostaglandins simultaneous phonocardiography and recording of
and kinins; metabolic theory of autoregulation), or ECG and carotid artery tracing. Allow evaluation of left
vasoconstriction, e.g. 5-HT. Hypoxia causes vasodi- ventricular function.
latation peripherally and vasoconstriction in the Include:
lungs. Increased temperature causes vasodilatation, QS2 (qA2): interval between the ECG QRS complex
whilst cold causes vasoconstriction. and the aortic component of the second heart
neural innervation: sound.
- -adrenergic receptors: the most important left ventricular ejection time (LVET): period from
type, affecting most vessels. Stimulation causes the beginning of the carotid upstroke to the dicrotic
vasoconstriction. notch.
- 2-adrenergic receptors: stimulation causes vaso- pre-ejection period (PEP): QS2 LVET. Represents
dilatation of arterioles to muscle and viscera. the rate of ventricular isometric pressure change,
- dopamine receptors: stimulation causes vasodila- i.e. dp/dt.
tation of renal and splanchnic vessels. others, e.g. duration of mechanical systole, are less
- sympathetic cholinergic receptors: stimulation commonly measured. Ratios of the intervals have
causes vasodilatation in skeletal muscle. been calculated, e.g. PEP LVET.
 T
t1/2, see Half-life Tapentadol hydrochloride. Opioid analgesic drug,
similar in structure to tramadol, used to treat moderate-
T-piece breathing systems, see Anaesthetic breathing to-severe pain. Acts via agonism at mu opioid receptors
systems and inhibition of reuptake of noradrenaline. Rapidly
absorbed via the oral route; undergoes extensive first-
t tests, see Statistical tests pass metabolism. Cleared by hepatic metabolism to inac-
tive metabolites, followed by renal excretion; used with
T wave. Wave on the ECG representing ventricular caution in patients with hepatic failure.
repolarisation (see Fig. 59b; Electrocardiography). Nor- Dosage: 50mg orally 46-hourly, adjusted to response,
mally upright in leads I, II and V36; the upper height maximum 600mg daily.
limit is 5mm in the standard leads and 10mm in the Side effects: nausea, vomiting, dizziness, dry mouth,
chest leads. sweating, confusion, hallucinations, seizures, respira-
Abnormalities: tory depression, sedation (the latter two less com-
may be inverted in myocardial ischaemia, ventricu- monly than with morphine). Drug dependence and
lar hypertrophy, mitral valve prolapse, bundle withdrawal have been reported, especially following
branch block and digoxin toxicity. prolonged treatment.
may be notched in pericarditis.
tall peaked waves may occur in hyperkalaemia. Target-controlled infusion (TCI). Technique utilising a
computer-controlled intravenous infusion device to
Tachycardias, see Sinus tachycardia; Supraventricular achieve and maintain a desired target drug concentra-
tachycardia; Ventricular tachycardia tion (in plasma, or at the effect site). May be used for
sedation or total intravenous anaesthesia. Requires:
Tachykinins. Group of neuropeptides involved in car- an accurate infusion pump.
diovascular, respiratory, endocrine and behavioural a computer programmed with an algorithm based
responses. Include substance P, neurokinin A and neu- on a model of the drugs pharmacokinetics. Famil-
rokinin B, which are natural agonists at NK1, NK2 and iarity with the specific model incorporated into the
NK3 receptors, respectively. Particular interest has TCI system being used is important; the clinical
focused on NK1 and NK2 receptor activation, which effect associated with a given target concentration
results in bronchoconstriction, and on development of for one model may be different for another.
neurokinin-1 receptor antagonists as antiemetic drugs. an interface for the anaesthetist to select the appro-
priate drug, target concentration and patient-
Tachyphylaxis. Term usually referring to acute drug tol- specific variables (e.g. weight, sex, age).
erance, usually due to depletion of receptors (or for a second microprocessor that calculates the
indirectly acting drugs, depletion of neurotransmitter/ expected plasma concentration from the amount of
signalling molecule) following repeated exposure. drug actually administered, and shuts down the
pump if there is a discrepancy with that predicted
Tacrine, see Tetrahydroaminocrine by the first.
The first licensed TCI system was for propofol, using a
Tacrolimus. Immunosuppressive drug; acts by inhibiting proprietary microprocessor that could only be used with
cytotoxic lymphocyte proliferation and cytokine expres- electronically tagged pre-filled syringes. Since the expiry
sion. Used to prevent graft rejection after liver and renal of the patent on propofol, several open-label pharma-
transplantation. A topical preparation is available for cokinetic protocols have been developed and incorpo-
treatment of dermatitis. Extensively bound to red blood rated into a range of TCI devices. TCI systems for other
cells and plasma proteins. Achieves steady-state concen- drugs (e.g. remifentanil and sufentanil) are also available
trations after about 3 days administration; half-life and widely used.
varies from 3 to 40hwith mainly hepatic metabolism Absalom AR, Mani V, De Smet T, Struys MM (2009). Br
and biliary excretion. J Anaesth; 103: 2637
Dosage: 100300g/kg orally in two doses or iv over
24h. TB, see Tuberculosis
Side effects: renal impairment, various central and
peripheral neurological disturbances, cardiomyopa- TCD, see Transcranial Doppler ultrasound
thy, diabetes.
TCI, Target-controlled infusion, see Propofol
Tamponade, see Cardiac tamponade
TEE, Transesophageal echocardiography, see Trans
TAP block, see Transversus abdominis plane block oesophageal echocardiography

557
558 Teeth

Teeth. Composed of the crown (consisting of enamel,

Table 42 Corresponding points on different temperature scales
dentine and pulp from outside inwards) and root. All
parts may be damaged during anaesthesia; the deeper Kelvin (K) Celsius (C) Fahrenheit (F)
the damage, the more extensive is the treatment required.
Traumatic damage is involved in about 30% of malprac- Absolute zero 0 273 459
tice claims against anaesthetists, with a rough incidence Melting point of ice 273 0 32
of 1:1000 general anaesthetics and, because of its fre- Boiling point of water 373 100 212
quency, claims are rarely contested. Damage most com-
monly occurs during intubation or postoperatively when
the patient bites on an oral airway. Preoperative assess-
ment of the teeth is essential, noting any loose, chipped
or false teeth. Patients with caries, prostheses and peri- Temperature measurement. Performed routinely as
odontal disease, and those in whom tracheal intubation part of basic monitoring in ICUs. Used perioperatively
is difficult, are at particular risk. Appropriate warnings to monitor heat loss during anaesthesia and detect
should be given and noted on the anaesthetic chart hyperthermia.
preoperatively. Methods used:
Dentures and removable bridges are traditionally electrical:
removed before anaesthesia, in case they become dis- - thermocouple: relies on the Seebeck effect; i.e.
lodged and obstruct or pass into the airway. However, the production of voltage at the junction of two
the need for routine preoperative removal of dentures different conductors joined in a loop; the magni-
has been questioned since this may cause distress to tude of the voltage generated is proportional
patients. If damage to teeth does occur, avulsed or to the temperature difference between the
broken teeth should be retrieved and stored in saline for two junctions. The circuit thus consists of a mea-
possible reimplantation (up to 90% success rate if per- suring junction and a reference junction, with
formed within 30min); the extent of damage should be measurement of the voltage difference between
documented and the patient referred as soon as possible the two. Because voltage is also produced at the
to a dentist (ideally in the same hospital) who can carry reference junction, electrical manipulation is
out necessary emergency treatment. required to compensate for changes in tempera-
Yasny JS (2009). Anesth Analg; 108: 156473 ture at the latter.
See also, Dental surgery; Mandibular nerve blocks; Max- - thermistor: semiconductor whose resistance
illary nerve blocks changes predictably with temperature; a com-
monly used type consists of a metal oxide bead
with resistance that falls exponentially as tem-
Teicoplanin. Glycopeptide and antibacterial drug, perature rises. Small enough to be placed within
related to vancomycin but longer acting, allowing once- body cavities. Calibration may be difficult.
daily dosing. Active against most Gram-positive organ- - platinum resistance wire: resistance increases
isms, as for vancomycin. 90% protein-bound, with a proportionately with temperature. Very accurate
half-life of 7 days. Excreted unchanged in urine. but fragile.
Dosage: 400mg bd for three doses, od thereafter.
non-electrical:
400mg may also be given for prophylaxis before - liquid thermometers: the liquid (usually mercury)
surgery. expands as temperature increases, and moves out
Side effects: GIT disturbance, allergic reactions, blood
of its glass bulb and up the barrel of the instru-
dyscrasias, hepatic and renal impairment, erythema. ment. Temperature is read from a scale along its
length. A constriction just above the bulb pre-
Temazepam. Benzodiazepine used in insomnia, and vents the mercury from withdrawing back into the
commonly used for premedication. Shorter acting than bulb. Alcohol is used for very low temperatures.
diazepam, with faster onset of action. Half-life is 8h. - gas expansion thermometers, e.g. an anaeroid
1030mg orally, 4560min preoperatively, is usually gauge used for pressure measurement is cali-
an effective anxiolytic. For children, 0.5mg/kg may brated in units of temperature. Accuracy is poor
be given. Gel-filled capsules were withdrawn from and calibration may be difficult.
NHS use in 1995 because of abuse by iv drug users, the - bimetallic strip, arranged in a coil. A pointer is
liquefied gel causing marked vascular damage on injec- moved by coiling or uncoiling of the strip as tem-
tion. Temazepam became a Schedule 3 Controlled perature changes.
Drug in 1996, although without special prescription - infrared thermometry: relies on the principle that
requirements. the maximal amount of radiation (black box radi-
See also, Misuse of Drugs Act ation) emitted by a body depends only on that
bodys temperature. The radiation emitted by a
surface is less than that emitted by a black body
Temperature. Property of a system that determines at the same temperature; the ratio is defined as
whether heat is transferred to or from other systems. emissivity of the surface. Measurement of radia-
Related to the mean kinetic energy of its constituent tion emitted by a surface plus knowledge of its
particles. Three temperature scales are recognised: emissivity allows calculation of the surfaces tem-
Kelvin (formerly Absolute) scale, Celsius (formerly Cen- perature. Infrared thermometers detect infrared
tigrade) scale and Fahrenheit scale (Table 42). The SI radiation emitted by the tympanic membrane
unit of temperature is the kelvin. and calculate its temperature in under a second,
[Anders Celsius (17011744), Swedish scientist; Gabriel allowing for heat loss in the ear canal. They
D Fahrenheit (16861736), German scientist] may also be used to measure surface temperature
 Terbutaline sulphate 559

at other sites (e.g. skin) or to estimate tempera- blood vessels, sweat glands and piloerector muscles.
ture at these sites from tympanic membrane Local reflexes are also involved. Efferents also pass to
temperature. somatic motor centres in the lower brainstem to cause
- chemical thermometers: consist of a plastic strip shivering, and to higher centres.
containing a number of cells, each holding liquid Regulatory mechanisms:
crystals which melt and change colour according behavioural, e.g. curling up in the cold, wearing
to temperature. Accurate to 0.5C. appropriate clothing.
Sites of measurement: skin blood flow: may be altered by vasodilatation or
tympanic membrane: correlates most closely with vasoconstriction of skin vessels, and by opening
hypothalamic temperature, and has rapid response or closing of arteriovenous anastomoses in the
time. Carries risk of tympanic perforation if direct skin. Affects all routes of heat loss. Alteration alone
contact techniques are used. is sufficient to maintain constant body temperature
oesophageal: accurate if the lower third is used, in environments of 2028C in adults and 3537C
otherwise measured temperature is influenced by in neonates (thermoneutral range).
the temperature of inspired gases. shivering and piloerection (reduced or absent in
nasopharyngeal and bladder: similar to babies, brown fat metabolism occurring instead).
oesophageal. Reflex shivering can hinder induced hypothermia;
rectal: usually 0.51.0C higher than core tempera- measures to inhibit shivering include use of neuro-
ture, because of bacterial fermentation. Response muscular blocking drugs, 2-adrenergic receptor
time is slow because of insulation by faeces. agonists and skin surface warming (with core
blood: thermistors incorporated into pulmonary cooling).
artery catheters allow continuous measurement. sweating.
skin: does not reflect core temperature. The differ- Pitoni S, Sinclair HL, Andrews PJD (2011). Curr Opin
ence between core and skin temperatures gives Crit Care; 17: 11521
some indication of peripheral perfusion, and may See also, Heat loss during anaesthesia
be used in the ICU.
[Thomas J Seebeck (17701831), Russian-born German Temporomandibular joint (TMJ). Synovial joint
physicist] between the mandibular condyle and the articular
surface of the squamous temporal bone. Protrusion,
Temperature regulation. Humans are homeothermic, retraction and grinding movements of the lower jaw
maintaining body core temperature at 37 1C. The core occur by a gliding mechanism whereas mouth opening
usually includes cranial, thoracic, abdominal and pelvic and closing involve gliding and hinging movements.
contents, and variable amounts of the deep portions of Joint stability is least when the mouth is fully open (e.g.
the limbs. Temperature is lowest at night and highest in during laryngoscopy) and forward dislocation may
mid-afternoon, also varying with the menstrual cycle. occur. Affected by rheumatoid arthritis, degenerative
Constant temperature is required for optimal enzyme disease, ankylosing spondylitis and systemic sclerosis.
activity. Denaturation of proteins occurs at 42C. Loss of Mouth opening may be severely limited, hindering
consciousness occurs at hypothermia below 30C. laryngoscopy.
Mechanisms of heat loss/gain: See also, Intubation, difficult; Trismus
heat gain:
- from the environment. Tenecteplase. Fibrinolytic drug, used in acute manage-
- from metabolism (mainly in the brain, liver and ment of acute coronary syndromes. Binds to fibrin, the
kidneys): approximately 80 W is produced in an resultant complex converting plasminogen to plasmin,
average man under resting conditions. This would which dissolves the fibrin.
raise body temperature by about 1C/h if totally Dosage: 0.50.6mg/kg (to a maximum of 50mg) iv
insulated. Vigorous muscular activity may increase over 10s.
heat production by up to 20 times. In babies, Side effects: as for fibrinolytic drugs.
brown fat produces much heat.
heat loss: TENS, see Transcutaneous electrical nerve stimulation
- radiation from the skin. May account for 40% of
total loss. Tensilon test, see Edrophonium
- convection: related to airflow (e.g. wind chill).
Accounts for up to 40% of total loss. Tension. In physics, another word for force, implying
- evaporation from the respiratory tract and skin: stretching (cf. compression). Also refers to the partial
the latter is increased by sweating, which normally pressure of a gas in solution.
accounts for 20% of total loss, but this figure may
increase markedly. Tension time index. Area between tracings of left ven-
- conduction: of little importance in air, but signifi- tricular pressure and aortic root pressure during systole,
cant in water. multiplied by heart rate (see Fig. 61; Endocardial viabil-
Temperature-sensitive cells are present in the anterior ity ratio). Represents myocardial workload and hence O2
hypothalamus (thought to be the most important demand; when taken in conjunction with diastolic pres-
site), brainstem, spinal cord, skin, skeletal muscle and sure time index, it may indicate the myocardial O2
abdominal viscera. Peripheral temperature receptors are supply/demand ratio and the likelihood of myocardial
primary afferent nerve endings and respond to cold and ischaemia.
hot stimuli via A and C fibres respectively. Central
control of thermoregulation is by the hypothalamus. Terbutaline sulphate. -Adrenergic receptor agonist,
Efferents pass via the sympathetic nervous system to used as a bronchodilator drug and tocolytic drug. Has
560 Terlipressin

similar effects to salbutamol, but possibly has less spasm around the site of injury; generalised tetanus is
cardiac effect. characterised by trismus, irritability, rigidity and opis-
Dosage: thotonos. Cardiac arrhythmias/arrest and hypertension
2.55mg orally bd/tds. may occur due to sympathetic hyperactivity. As binding
250500g im/sc qds as required. of tetanospasmin is irreversible, recovery depends on
250500g iv slowly, repeated as required. 15g/ formation of new nerve terminals. The diagnosis is based
min infusion may be used (containing 35g/ml). on clinical findings but the spatula test (touching the
Up to 25g/min may be required in premature oropharynx with a wooden spatula; in tetanus this results
labour (see Ritodrine). in spasm of the masseter muscles causing biting of the
12 puffs by aerosol (250500g) tds/qds. spatula) is highly sensitive and specific for tetanus.
510mg by nebulised solution qds as required. Treatment:
Side effects: as for salbutamol. human antitetanus immunoglobulin (500010000
units): neutralises circulating toxin.
Terlipressin, see Vasopressin surgical excision and debridement of the wound.
metronidazole to eradicate existing organisms.
Terminal care, see Palliative care; Withdrawal of treat- sedation, neuromuscular blocking drugs and IPPV
ment in ICU may be required. Dantrolene and magnesium sul-
phate have been used. The latter reduces sympa-
Test dose, epidural. In epidural anaesthesia, injection thetic overactivity and reduces spasm by decreasing
of a small amount of local anaesthetic agent through the presynaptic activity.
catheter before injection of the main dose, in order to of cardiovascular complications.
identify accidental subarachnoid or iv placement of the Mortality is 15% in those treated in modern ICUs
catheter. Less commonly performed before through the (greater in previously unvaccinated individuals, if age
needle epidural block, since leakage of CSF or blood exceeds 50, and if generalised spasms rapidly follow
should be more easily noticeable. initial symptoms).
Controversial, since it is not always reliable. The Active immunisation with tetanus vaccine should
volume and strength of the test solution are also contro- always be performed in trauma and burns unless within
versial. 3ml 2% lidocaine with adrenaline 1:200000 has 510 years of previous administration. Antitetanus
been suggested as the ideal solution; subarachnoid injec- immunoglobulin is given to non-immune patients with
tion produces spinal anaesthesia within 23min, and iv heavily contaminated or old wounds.
injection produces tachycardia within 90s. Injection of Gibson K, Bonaventure Uwineza J, Kiviri W, Parlow J
fentanyl 50100g or 1ml air (with Doppler monitor- (2009). Can J Anaesth; 56: 30715
ing) has also been used. In modern low-dose techniques See also, Clostridial infections
(e.g. epidural analgesia for labour), each dose acts as its
own test since a standard dose of e.g. 10ml bupivacaine Tetany. Increased sensitivity of excitable cells, mani-
0.1% with 20g fentanyl would be expected to produce fested as peripheral muscle spasm. Usually facial and
noticeable effects were it to be injected subarachnoid or carpopedal, the shape of the hand in the latter termed
iv without causing a dangerously high block or severe main daccoucheur (French: obstetricians hand). Usually
systemic toxicity. caused by hypocalcaemia; it also occurs in hypomagne-
Camorcia M (2009). Curr Opin Anesthesiol; 22: 33640 saemia and may be hereditary.

Tetanic contraction. Sustained muscle contraction Tetracaine hydrochloride (Amethocaine). Ester local
caused by repetitive electrical stimulation of a motor anaesthetic agent, introduced in 1931. Widely used in the
nerve. About 25Hz stimulation is required for frequent USA for spinal anaesthesia; in the UK, used only for
enough action potentials to produce it, although the nec- topical anaesthesia, e.g. in ophthalmology. More potent
essary rate varies according to the muscle studied. The and longer lasting than lidocaine, but more toxic. Toxic-
force produced exceeds that of single muscle twitches. ity resembles that of cocaine. Weak base with a pK
During tetanic contraction, acetylcholine is mobilised of 8.5. Rapidly absorbed from mucous membranes.
from reserve stores to the readily available pool. Hydrolysed completely by plasma cholinesterase to
Produced during neuromuscular blockade form butylaminobenzoic acid and dimethylaminoetha-
monitoring. nol. Administration: 0.51% solution for spinal anaes-
See also, Neuromuscular junction; Neuromuscular trans- thesia; 0.40.5% for epidural anaesthesia; 0.10.2%
mission; Post-tetanic potentiation solution for infiltration, usually with adrenaline; 0.51%
solutions for surface analgesia.
Tetanus. Disease caused by infection with Clostridium Available in a 4% gel (available over the counter
tetani, a prevalent spore-forming Gram-positive bacillus without prescription) for topical anaesthesia of the skin,
found in soil, dust and faeces. Inoculation may be via e.g. before venepuncture. The melting point of the drug
minor injury. Rare in developed countries following is lowered by the formation of specific hydrates within
immunisation programmes, but accounts for up to 1 the gel. The resultant oil globules penetrate the skin
million deaths annually worldwide. Recently reported in readily with onset of action about 3045min; effects last
drug abusers skin-popping contaminated heroin. 46h. Skin blistering may occur. Has been combined
Clinical features are caused by a potent exotoxin, with lidocaine and a heating compound in a plaster, for
tetanospasmin, which moves along peripheral nerves to topical anaesthesia before venepuncture.
the spinal cord, where it blocks release of neurotransmit- Maximal safe dose: 1.5mg/kg.
ters at inhibitory neurons, causing muscle spasm and
autonomic disturbance. Incubation period is 321 days Tetracycline. Broad-spectrum antibacterial drug, used
(average 7 days). Local infection may cause muscle mainly for chlamydia, rickettsia, spirochaete and
 Thiazolidinediones 561

brucella infections, certain mycoplasma infections, acne, Therapeutic intervention scoring system (TISS).
acute exacerbations of COPD and leptospirosis. Several Scoring system for assessing the severity of critical illness
tetracyclines exist, with tetracycline itself the only one according to the number of interventions a patient
administered iv. Has also been instilled into the pleural receives. Originally comprising over 70 interventions
cavity to treat recurrent pleural effusions. that were scored 14 according to complexity and inva-
Dosage: 250500mg orally tds/qds or 500mg iv bd. siveness; more recent modifications have reduced this
Side effects: stained teeth (if given to children), renal number to < 30. Although of value in an individual clini-
impairment, GIT upset, benign intracranial hyperten- cians practice, the score for a particular patient may
sion, hepatic impairment. vary between clinicians and units according to differ-
ences in treatment strategies. Has been used as a means
Tetrahydroaminocrine hydrochloride (Tacrine). Ace- of assessing the need for ICU resources.
tylcholinesterase inhibitor formerly used to prolong the Miranda DR (1997). Intensive Care Med; 23: 61517
action of suxamethonium. Also used prophylactically to
Therapeutic ratio/index. Relationship between the
reduce muscle pains following suxamethonium, and as a
doses of a drug required to produce toxic and therapeu-
central stimulant. Used as a treatment for Alzheimers
tic effects. A drug with a high therapeutic ratio has a
disease.
greater margin of safety than one with low therapeutic
[Alois Alzheimer (18641915), German neurologist and
ratio. Defined experimentally as the ratio of median
pathologist]
lethal dose to median effective dose:
LD50
Tetrodotoxin. Toxin obtained from puffer fish, that
selectively blocks neuronal voltage-gated fast sodium ED50
channels. Used experimentally, e.g. for investigating neu-
romuscular transmission. Thermal conductivity detector, see Katharometer

Thermistor, see Temperature measurement

Thalassaemia. Group of autosomally inherited disor-
ders involving decreased production of the or chains Thermocouple, see Temperature measurement
of haemoglobin (Hb). More common in Mediterranean,
African and Asian areas. Severity is related to the Thermodilution cardiac output measurement, see
pattern of inheritance of the Hb genes (normally, one Cardiac output measurement
gene and two genes are inherited from each parent).
Divided into: Thermoneutral range. Temperature range in which
thalassaemia: temperature regulation may be maintained by changes
- not apparent immediately as fetal haemoglobin in skin blood flow alone. Corresponds to the tempera-
does not contain chains. ture that feels comfortable. About 2028C in adults
- heterozygous thalassaemia (thalassaemia and 3537C in neonates. Neonatal metabolic rate and
minor) produces mild (often asymptomatic) mortality are reduced if body temperature is kept within
anaemia, but may be associated with other types the thermoneutral range.
of Hb (e.g. HbC, HbE, HbS); resultant anaemia
may vary from mild to severe. Thiamylal sodium. IV anaesthetic agent, with similar
- homozygous thalassaemia (Cooleys anaemia; properties to thiopental. Unavailable in the UK.
thalassaemia major) results in severe anaemia in
infancy, with no production of HbA. Features Thiazide diuretics. Group of diuretics used to treat mild
include craniofacial bone hyperplasia, hepato- hypertension, oedema caused by cardiac failure and
splenomegaly and cardiac failure. Haemosidero- nephrogenic diabetes insipidus. Chlorothiazide was the
sis may occur due to repeated blood transfusion. first to be studied but many now exist, e.g. bendroflume-
Usually fatal before adulthood, although bone thiazide (bendrofluazide). Act mainly at the proximal
marrow transplantation may offer a cure. Some part of the distal convoluted tubule of the nephron,
genetic subtypes are associated with a milder where they inhibit sodium reabsorption. They also act at
clinical course (thalassaemia intermedia). the proximal tubule, causing weak inhibition of carbonic
thalassaemia: severity varies, depending on anhydrase and increasing bicarbonate and potassium
the number of gene deletions. Usually causes mild excretion, and have a direct vasodilator action. Their
anaemia; deletion of all four genes is incompatible antihypertensive action increases only slightly as dosage
with life. is increased. Rapidly absorbed from the GIT with
Peters M, Heijboer H, Smiers F, Giordano PC (2012). Br onset of action within 12h, lasting 1224h. Some non-
Med J; 344: e228 thiazide drugs have thiazide-like properties (e.g. chlor-
[Thomas B Cooley (18711945), US paediatrician] talidone, metolazone).
Side effects include hypokalaemia, hyponatraemia,
hyperuricaemia, hypomagnesaemia, hypochloraemic
THAM, tris-(hydroxymethyl)-aminomethane, see 2-
alkalosis, hyperglycaemia, hypercholesterolaemia, exac-
Amino-2-hydroxymethyl-1,3-propanediol
erbation of renal and hepatic impairment, impotence,
and, rarely, rashes and thrombocytopenia.
Theophylline. Bronchodilator drug, used alone or in
combination with ethylenediamine as aminophylline. Thiazolidinediones. Oral hypoglycaemic drugs used in
Actions and effects: as for aminophylline. management of type II diabetes mellitus. Bind to a
Dosage: 125250mg orally tds/qds; slow-release nuclear receptor, PPAR, in adipose cells, liver and
preparations, 250500mg bd. skeletal muscle, increasing sensitivity to insulin. Not
562 Thigh, lateral cutaneous nerve block

indicated for monotherapy; usually used in combination compensatory tachycardia with increased myo-
with a biguanide or sulphonylurea. Agents include pio- cardial O2 demand. Cardiovascular depression is
glitazone (restricted in some countries because of the related to speed of injection and is exacerbated
risk of bladder cancer), rosiglitazone (restricted in the by hypovolaemia.
USA and unavailable in Europe because of the risk of - has little effect on SVR but may decrease venous
cardiovascular events) and troglitazone (withdrawn vascular tone, reducing venous return.
because of the risk of hepatitis). RS:
- causes dose-related depression of the respiratory
centre, decreasing the responsiveness to CO2 and
Thigh, lateral cutaneous nerve block. Provides anal-
hypoxia. Apnoea is common after induction.
gesia of the anterolateral thigh/knee, e.g. for leg surgery
- laryngospasm readily occurs following laryngeal
(especially skin graft harvesting) and diagnosis of meral-
stimulation.
gia paraesthetica (numbness and paraesthesia caused by
- has been implicated in causing bronchospasm, but
lateral cutaneous nerve compression by the inguinal
this is disputed.
ligament, under which it passes).
CNS:
With the patient supine, a needle is introduced per-
- anticonvulsant.
pendicular to the skin, 2cm medial and caudal to the
- decreases pain threshold (antanalgesia).
anterior superior iliac spine. A click is felt as the fascia
- reduces cerebral perfusion pressure, ICP and
lata is pierced. 1015ml local anaesthetic agent is
cerebral metabolism.
injected in a fan shape laterally.
other:
- causes brief skeletal muscle relaxation at peak
Thiopental sodium (Thiopentone; 5-ethyl-5-(1- CNS effect.
methylbutyl)-2-thiobarbiturate). IV anaesthetic agent, - reduces renal and hepatic blood flow secondary
synthesised in 1932 and first used in 1934 by Lundy and to reduced cardiac output. Causes hepatic enzyme
Waters. Also used in refractory status epilepticus. The induction.
sulphur analogue of pentobarbitone (Fig. 154). Stored as - reduces intraocular pressure.
the sodium salt, a yellow powder with a faint garlic smell, - has no effect on uterine tone.
with 6% anhydrous sodium carbonate added to prevent Metabolised by oxidation in the liver (1015% per
formation of (insoluble) free acid when exposed to hour), with < 1% appearing unchanged in the urine.
atmospheric CO2 and presented in an atmosphere of Desulphuration to pentobarbitone may also occur fol-
nitrogen. Most commonly used as a 2.5% solution, with lowing prolonged administration. Elimination half-life is
pH of 10.5. pKa is 7.6; at a pH of 7.4 about 60% is non- 510h. Up to 30% may remain in the body after 24h.
ionised. The solution is stable for 2436hafter mixing, Accumulation may occur on repeated dosage.
although the manufacturers recommend discarding Complications:
after 7h. extravenous injection causes pain and erythema.
About 85% bound to plasma proteins after injection. intra-arterial injection causes intense pain, and may
Follows a multicompartmental pharmacokinetic model cause distal blistering, oedema and gangrene, attrib-
after a single iv injection, with redistribution from vessel- uted to crystallisation of thiopental within arterioles
rich tissues (e.g. brain) to lean body tissues (e.g. muscle), and capillaries, with local noradrenaline release and
with return of consciousness. Slower redistribution then vasospasm. Endothelial damage and subsequent
occurs to vessel-poor tissues (e.g. fat: see Fig. 88; Intrave- inflammatory reaction have been suggested as
nous anaesthetic agents). being more likely. Particularly hazardous with the
Effects: 5% solution, now rarely used. Treatment: leaving
induction: the needle/cannula in the artery, the following may
- smooth, occurring within one armbrain circula- be injected:
tion time. Involuntary movements and painful - saline, to dilute the drug.
injection are rare. - vasodilators, traditionally papaverine 40mg,
- recovery within 510min after a single dose. tolazoline 40mg, phentolamine 25mg, to reduce
CVS: arterial spasm.
- causes dose-related direct myocardial depres- - local anaesthetic, traditionally procaine 50
sion, decreasing cardiac output and causing 100mg (also a vasodilator), to reduce pain.
- heparin, to reduce subsequent thrombosis.
Brachial plexus block and stellate ganglion block
have been used to encourage vasodilatation (before
heparinisation). Postponement of surgery has been
suggested.
O H respiratory/cardiovascular depression as above.
CH3
adverse drug reactions. Severe anaphylaxis is rare
C N
CH3 CH2 CH2 CH (1:1400035000), typically occurring after several
previous exposures.
C C S Contraindicated in porphyria.
Dosage:
CH2 36mg/kg iv. Requirements are reduced in hypo-
C N proteinaemia, hypovolaemia, the elderly and criti-
CH3
O H cally ill patients. Injection should be over 1015s,
with a pause after the expected adequate dose
Fig. 154 Structure of thiopental before further administration.
 Thoracic surgery 563

has also been given rectally: 4050mg/kg as 510% noted as this may hinder endobronchial intuba-
solution. tion. Rarely, bronchography is performed, e.g. in
by infusion for convulsions: 23mg/kg/h. bronchiectasis. Arterial blood gas interpretation
and lung function tests are routinely performed,
Thiosulphate, see Cyanide poisoning e.g. spirometry, flowvolume loops. A poor post-
operative course following pneumonectomy is
Third gas effect, see Fink effect suggested if any of FVC, FEV1, maximal volun-
tary ventilation, residual volume:total lung capac-
Third space. Non-functional interstitial fluid compart- ity ratio or diffusing capacity is < 50% of predicted.
ment, to which fluid is transferred following trauma, Pulmonary hypertension is also associated with
burns, surgery and other conditions, including infection, poor outcome.
pancreatitis. Most of the fluid originates from the ECF, - cardiopulmonary exercise testing may be
but some movement from intracellular fluid also occurs. employed; a maximum O2 uptake of < 15ml/kg/
Includes fluid lost to the transcellular fluid compartment, min is cited as predictive of poorer outcomes.
e.g. ascites, bowel contents. Although not lost from the - preparation includes antibiotic therapy, physio-
body, fluid shifts to the third space are equivalent to therapy and use of bronchodilator drugs as
functional ECF losses and must be accounted for when appropriate.
estimating fluid balance. Losses may exceed 10ml/kg/h - premedication commonly includes anticholiner-
during abdominal surgery, and should be replaced ini- gic drugs to reduce secretions.
tially with 0.9% saline or Hartmanns solution, although perioperatively:
colloids may also be used. - specific diagnostic procedures include bron-
See also, Stress response to surgery choscopy, mediastinoscopy, bronchography and
oesophagoscopy.
Thoracic inlet. Kidney-shaped superior (cranial) - preoxygenation is usually employed. IV induction
opening of the thorax, bounded by the superior border of anaesthesia is usually suitable; difficulties
of the manubrium sternum anteriorly, first thoracic ver- may include cardiovascular instability, airway
tebra posteriorly, and the first ribs laterally. Anteropos- obstruction, difficult tracheal intubation, risk of
terior diameter is about 5cm; transverse diameter about aspiration of gastric contents in oesophageal
10cm. Its plane slopes downward (60 to the horizontal) disease and problems of lesions affecting the
and forward. mediastinum.
Contents (see Fig. 26; Brachial plexus and Fig. 104; - endobronchial tubes are often used, although
Mediastinum): standard tracheal tubes are usually acceptable
median plane (from anterior to posterior): unless isolation of lung segments is required.
sternohyoid and sternothyroid muscles; remains of Endobronchial blockers may also be used.
thymus; inferior thyroid braciocephalic veins; - large-bore iv cannulae are vital, since blood loss
trachea; oesophagus; recurrent laryngeal nerve; tho- may be severe.
racic duct. - standard monitoring is used; arterial and central
laterally: venous cannulation is often employed.
- both sides: upper pleura/apex of lung; sympathetic - maintenance of anaesthesia is usually with stan-
trunk, superior intercostal artery and ventral dard agents and techniques. Pendelluft, V/Q mis-
ramus of T1 (from medial to lateral) between the match and decreased venous return secondary to
pleura and neck of the first rib; internal thoracic mediastinal shift may also occur. Hypoxaemia is
artery anteriorly. common during one-lung anaesthesia. Injector
- right side: brachiocephalic vessels; vagus; phrenic techniques and high-frequency ventilation have
nerve. been used for tracheal resection.
- left side: common carotid/subclavian arteries; - positioning of the patient: the lateral position
vagus; brachiocephalic vein; phrenic nerve. with the operative lung uppermost is usual.
Thoracic inlet X-ray views may be useful if tracheal com- The arm is placed over the head, displacing the
pression or displacement is suspected. scapula upwards. Drainage of secretions from
the affected lung without soiling the unaffected
Thoracic surgery. The first pneumonectomy was per- lung may be achieved using the Parry Brown posi-
formed in 1895 by Macewan. Surgical and anaesthetic tion (prone, with a pillow under the pelvis and
techniques improved with experience of treating a 10cm rest under the chest; the arm on the
chest injuries during World War II. The commonest operated side overhangs the tables edge with the
indication for thoracic surgery was formerly TB and head turned to the opposite side, and the table is
empyema but is now malignancy, especially bronchial tipped head-down so that the trachea slopes
carcinoma. downwards).
Main anaesthetic principles: - at closure of the chest, the lung is re-expanded
preoperatively: after endobronchial suction. Up to 40 cmH2O
- preoperative assessment of exercise tolerance, airway pressure may be requested by the surgeon
cough and haemoptysis. Ischaemic heart disease to test bronchial sutures. Tubes are placed for
secondary to smoking is common. Cyanosis, tra- chest drainage. After pneumonectomy, chest
cheal deviation, stridor, abnormal chest wall drains are often not used; air is introduced or
movement, pleural effusion and systemic features removed to equalise the intrapleural pressures on
of malignancy may be present. both sides and centralise the mediastinum. The
- investigations include CXR, CT scanning and pleural space slowly fills with fluid postopera-
MRI. Distortion of the trachea/bronchi should be tively, with eventual fibrosis.
564 Thoracocardiography

postoperatively: mucocutaneous, gastrointestinal, cerebral. Diagnosis of

- IPPV is usually avoided if possible, as it risks the underlying condition requires examination of the
leakage from the bronchial stump with possible blood film and bone marrow and coagulation studies.
fistula formation. Treatment: according to the underlying cause. Platelet
- postoperative analgesia is vital to ensure adequate transfusion is required for counts below 2030
ventilation. Standard techniques are used, includ- 109/l or if bleeding occurs; transfusion may be ineffec-
ing patient-controlled analgesia, thoracic epidural tive if antibody-mediated platelet destruction is
anaesthesia and use of spinal opioids. Cryoanal- responsible.
gesia and intercostal nerve block may be per- Regional anaesthesia in the presence of thrombocytope-
formed by the surgeon whilst the chest is open. nia (e.g. in obstetric analgesia and anaesthesia) is con-
- physiotherapy is important postoperatively. troversial, with any benefits weighed against the potential
Specific procedures and conditions include removal of risk of spinal haematoma. Many anaesthetists would
inhaled foreign body, repair of bronchopleural fistula, consider a platelet count above 7080 109/l acceptable
chest trauma and bronchopulmonary lavage. if there is no clinical evidence of impaired function (e.g.
Similar considerations apply to oesophageal surgery. bruising or noticeably prolonged bleeding), coagulation
Ivor Lewis oesophagectomy (performed for carcinoma studies are normal, the count has been stable for at least
of the middle third of the oesophagus) involves lapa- several days and regional anaesthesia would be particu-
rotomy to mobilise the stomach and duodenum, fol- larly advantageous.
lowed by turning of the patient and right thoracotomy. Arnold DM, Lim W (2011). Semin Hematol; 48: 2518
Patients are often malnourished.
[Arthur I Parry Brown (19082007), London anaesthe-
tist; Ivor Lewis (18951982), London surgeon] Thromboelastography (TEG). Point-of-care coagula-
See also, Pneumothorax tion monitoring technique that assesses the speed and
quality of clot formation (and resolution). A pin is sus-
Thoracocardiography, see Inductance cardiography pended via a torsion wire in a sample of whole fresh
blood held in a rotating cuvette (usually combined with
Three-in-one block, see Femoral nerve block; Lumbar a coagulation activator); as the clot forms, the rotation
plexus of the cuvette is transmitted to the pin, the movement
of which thus reflects the viscoelastic properties of the
clot as it forms and resolves. This movement is trans-
Thrombin inhibitors. Group of compounds that bind to duced to an electrical signal and displayed, giving the
various sites on the thrombin molecule, investigated as characteristic TEG trace (Fig. 155). A related technique
alternatives to heparin. Includes hirudin and related uses an optical detector system to measure the move-
substances. Ximelagatran, a prodrug for melagatran, was ment of the pin (termed ROTEM or rotational throm-
extensively investigated as an oral anticoagulant but boelastometry). Initially used mainly during liver
withdrawn in 2006 following reports of hepatic impair- transplantation and cardiac surgery, it is increasingly
ment. Rivaroxaban and dabigatran are licensed for the being used to guide administration of blood products
prevention of DVT in adults undergoing elective hip or in other situations involving major haemorrhage, e.g.
knee replacement; the latter is also used for prevention obstetrics and trauma.
of CVA in high-risk patients with atrial fibrillation. TEG parameters and normal ranges:
Lee CJ, Ansell JE (2011). Br J Clin Pharmacol; 72: reaction/R time (time until initial fibrin forma-
58192 tion): 48min. Prolonged by anticoagulants and low
levels of clotting factors/fibrinogen.
Thrombin time, see Coagulation studies clot formation/K time (time for clot firmness to
reach 20mm): 14min. Prolonged by thrombocyto
Thrombocytopenia. Defined as a platelet count below penia, hypofibrinogenaemia and anticoagulants.
100 109/l. Common in critically ill patients. -angle (a tangent to the TEG trace drawn at
Caused by: the end of the K interval): 4774. Reduced
decreased production: e.g. bone marrow depression by thrombocytopenia, hypofibrinogenaemia and
(by drugs, infection, etc.), vitamin B12/folate defi- anticoagulants.
ciency, hereditary defects, paroxysmal nocturnal maximum amplitude (MA; maximum clot strength):
haemoglobinuria, thiazide diuretics, alcoholism. 5573mm. Parameter most influenced by platelet
shortened survival: number and function; reduced by thrombocytope-
- immune: autoantibodies (e.g. idiopathic throm nia and antiplatelet drugs.
bocytopaenic purpura, SLE, rheumatoid arthritis, LY30 (per cent clot lysis at 30s): < 7.5%. Increased
malignancy, drugs (e.g. quinine, heparin, - in early DIC.
methyldopa), infection (e.g. HIV), alloantibodies Advantages over standard laboratory studies:
(e.g. post-transfusion). faster acquisition of results.
- non-immune: DIC, thrombotic thrombocytopenic incorporates assessment of platelet function.
purpura, cardiopulmonary bypass, haemolytic analysis can be performed at the patients body
uraemic syndrome. temperature (thus taking into account the effect of
abnormal distribution, e.g. hypersplenism, hypothermia if present).
hypothermia. ability to add activators/inhibitors to analyse spe-
Patients with platelet counts above 50 109/l are usually cific aspects of coagulation (e.g. heparinase to assess
asymptomatic. Bleeding time increases progressively as the effect of administered heparin)
the count falls below 100 109/l. Counts below 2030 Ganter MT, Hofer CK (2008). Anesth Analg; 106:
109/l may be associated with spontaneous bleeding, e.g. 136675
 Thyroid gland 565

MA

-angle
mm

LY30

R time K 30 min
Time

Fig. 155Thromboelastography (TEG) trace. (See text for explanation of symbols.)

Thromboembolism, see Coagulation; Deep vein throm- Thyroid crisis (Thyroid storm). Rare manifestation of
bosis severe hyperthyroidism. May be triggered by stress,
including surgery and infection. Features include tachy-
Thrombolytic drugs, see Fibrinolytic drugs cardia, arrhythmias (including VT, VF and AF), cardiac
failure, fever, diarrhoea, sweating, hyperventilation, con-
Thrombophlebitis, see Intravenous fluid administra- fusion and coma.
Treatment:
tion
supportive, e.g. cooling, sedation, rehydration, treat-
ment of arrhythmias (-adrenergic receptor antago-
Thromboplastin time, see Coagulation studies
nists are usually employed). IPPV may be required
in respiratory failure.
Thrombotic thrombocytopenic purpura (TTP). Rare hydrocortisone 100mg iv qds.
disorder characterised by intravascular thrombosis, con- antithyroid drugs:
sumptive thrombocytopenia and haemolytic anaemia - 200mg potassium iodide orally/iv qds.
(due to mechanical damage to red cells). May be difficult - 60120mg carbimazole or 6001200mg propyl-
to distinguish from haemolyticuraemic syndrome (with thiouracil orally/day.
which it is thought to overlap) and DIC. Often associ- plasmapheresis and exchange transfusion have
ated with increased plasma levels of large von Wille- been used in severe cases.
brand factor multimers and a congenital deficiency of a
specific metalloprotease that cleaves it, ADAMTS13. Thyroid gland. Largest endocrine gland, extending from
Clinical episodes are often preceded by triggering the attachment of sternothyroid muscle to the thyroid
events (e.g. surgery, infection, pregnancy) in susceptible cartilage superiorly, to the sixth tracheal ring inferiorly.
individuals. The two lateral lobes lie lateral to the oesophagus and
Typically presents with abdominal pain, nausea/ pharynx, with the isthmus overlying the second to fourth
vomiting and weakness. Neurological symptoms (e.g. tracheal rings anteriorly. Arterial supply is via the supe-
CVA, convulsions) may also occur. Diagnosed largely rior and inferior thyroid arteries (branches of the exter-
clinically. nal carotid arteries and thyrocervical trunk of the
Treated by plasmapheresis, for which there is good subclavian artery respectively). The external and recur-
evidence of efficacy. Immunosuppressive drugs have rent laryngeal nerves are closely related to the superior
also been used, e.g. corticosteroids. Refractory disease and inferior thyroid arteries respectively.
has been treated with intravenous immunoglobulins. Produces thyroxine (T4) and triiodothyronine (T3),
Untreated, may rapidly progress to death in ~80% of which increase tissue metabolism and growth. They also
cases; mortality with treatment is ~20%. increase the effects of catecholamines by increasing the
Kiss JE (2010). Int J Hematol; 91: 3645 number and sensitivity of -adrenergic receptors. Iodine
is absorbed from the GIT as iodide and actively trans-
Thromboxanes. Substances related to prostaglandins, ported into the thyroid gland, where it is oxidised by a
synthesised by the action of cyclo-oxygenase on arachi- peroxidase and bound to thyroglobulin. Iodination of
donic acid. Thromboxane A2 is released by platelets at tyrosine residues of thyroglobulin produces T3 and T4,
sites of injury, causing vasoconstriction and platelet which are cleaved from the parent molecule. Both hor-
aggregation, and is opposed by prostacyclin. It is metab- mones are more than 99% bound to plasma proteins,
olised to thromboxane B2, which has little activity. including thyroxine binding globulin (TBG) and
albumin. T3 is secreted in smaller amounts than T4, is 35
Thymol. Aromatic hydrocarbon used as an antioxidant times as potent, is faster acting, and has a shorter half-
in halothane and trichloroethylene. May build up inside life. T4 is converted to T3 peripherally.
vaporisers unless cleaned regularly. Also used as a disin- Control of T3 and T4 production is by thyroid stimu-
fectant and deodorant, e.g. in mouthwashes. lating hormone (TSH), secreted by the pituitary gland.
566 Thyroidectomy

Secretion is inhibited by T3, T4 and stress, and stimulated leading to respiratory and bulbar involvement within
by thyrotrophin releasing hormone (TRH), secreted a few days unless the tick is removed. The causative
by the hypothalamus. TRH secretion is also inhibited by agent is unknown. Treatment is supportive, with
T3 and T4. appropriate antibacterial drugs (e.g. tetracyclines or
Tests of thyroid function: aminoglycosides).
radioactive iodine uptake. Graham J, Stockley K, Goldman RD (2011). Pediatr
total plasma T3 and T4 (normally 13nmol/l and Emerg Care; 27: 1417
60150nmol/l respectively). Increased in hyperthy-
roidism, and when TBG levels are raised, e.g. in Tidal volume. Volume of gas inspired and expired with
pregnancy, hepatitis. Decreased in hypothyroidism each breath. Normally 7ml/kg. Measured using spirom-
and when TBG levels are reduced, e.g. corticoste- eters or respirometers. Effective tidal volume equals
roid therapy, or when binding of T3 and T4 is inhib- tidal volume minus dead space volume.
ited, e.g. by phenytoin and salicylates. See also, Lung volumes
free T3 or T4 index: obtained by adding radioactive
T3/T4 to plasma, then adding a hormone-binding Tigecycline. Antibacterial drug related to tetracycline;
resin. Any radioactive T3/T4 not bound to TBG is active against Gram-positive and -negative organisms
taken up by the resin. Free T3/T4 index is the product and some anaerobic bacteria. Reserved for complicated
of the resin uptake and plasma T3/T4 levels. soft tissue and abdominal infections.
plasma TSH: indicates the level of hypersecretion Dosage: 100mg iv initially, then 50mg bd.
in hyperthyroidism (usually depressed, due to nega- Side effects: as for tetracyclines.
tive feedback by T3 and T4). High in primary hypo-
thyroidism. May be measured after injection Time constant (). Expression used to describe an
of TRH. exponential process. Equals the time in which the
The gland also secretes calcitonin, important in calcium process would be completed if the rate of change were
homeostasis, from parafollicular (C) cells. maintained at its initial value. May also be described as
Anaesthetic considerations of thyroid surgery: as for the ratio of quantity present to the rate of change of
hyper-/hypothyroidism. quantity at that moment. At 1 the process is 63% com-
See also, Neck, cross-sectional anatomy; Sick euthyroid plete (i.e. 37% of the initial quantity remains), at 2 it is
syndrome 86.5% complete, and at 3 it is 95% complete. After 6
the process is 99.75% complete.
Thyroidectomy, see Hyperthyroidism; Thyroid gland When used to refer to passive expiration of air from
the lungs, equals compliance resistance; thus stiff
Thyrotoxicosis, see Hyperthyroidism; Thyroid crisis alveoli served by narrow airways empty at similar rates
to compliant alveoli served by wide airways. May also be
Tibial nerve block, see Ankle, nerve blocks; Knee, nerve applied to the washout of nitrogen from the lungs during
blocks preoxygenation; equals FRC divided by alveolar
ventilation.
Ticagrelor. Nucleoside analogue antiplatelet drug, used See also, Half-life
in combination with aspirin in patients with acute coro-
nary syndromes. More effective than clopidogrel at
Time to sustained respiration. Time for adequate
reducing ischaemic events and all-cause mortality, but
regular respiration to occur in the neonate after delivery,
with a higher risk of minor bleeding.
without stimulation. Related to fetal wellbeing and
Antagonises platelet P2Y12 ADP receptors, thereby
respiratory depression caused by drugs administered to
inhibiting ADP-mediated platelet aggregation by block-
the mother before delivery.
ing the glycoprotein IIb/IIIa pathway. Oral bioavailabil-
See also, Fetus, effects of anaesthetic drugs on; Obstetric
ity is 35%, with peak clinical effect occurring within
analgesia and anaesthesia
24h. Eliminated via hepatic metabolism, with a half-
life of 78h. As with clopidogrel, cessation 7 days before
surgery is recommended. Tinzaparin sodium, see Heparin
Dosage: 180mg orally initially, followed by 90mg bd.
Side effects: bleeding, GI upset, dyspnoea, rash. Tirofiban. Antiplatelet drug, used in acute coronary syn-
dromes, within 12hof the last episode of chest pain.
Ticarcillin. Carboxypenicillin antibacterial drug, used Acts by reversibly inhibiting activation of the glycopro-
primarily for pseudomonas infections, although also tein IIb/IIIa complex on the surface of platelets.
Dosage: 400ng/kg/min iv for 30min, followed by
active against other Gram-negative organisms. Available
in the UK only in combination with clavulanic acid. 100ng/kg/min for at least 48h(and during and 12
Dosage: 3.2g 48-hourly (depending on severity), iv 24hafter percutaneous coronary intervention if per-
3.2g contains 3g ticarcillin and 200mg clavulanic formed). If angiography < 4hafter diagnosis, 2500ng/
acid. kg iv bolus at start of procedure, followed by infusion
Side effects: as for benzylpenicillin. of 150ng/kg/min for 1824h.
Side effects are related to increased bleeding. Platelet

Tick-borne diseases. Common worldwide, although function takes up to 24hto return to normal after
uncommon in the UK; soft ticks cause a variety of skin discontinuation of therapy.
lesions and transmit spirochaetal relapsing fevers whilst
hard ticks are the vectors for arboviral haemorrhagic TISS, see Therapeutic intervention scoring system
fevers, encephalitis, typhus and Lyme disease. Rarely,
tick bites may result in ascending flaccid paralysis, Tissue oxygen tension, see Oxygen, tissue tension
 Tonsil, bleeding 567

TIVA, see Total intravenous anaesthesia Tongue. Muscular organ attached to the hyoid bone and
mandible. Covered by mucous membrane and divided
TMJ, see Temporomandibular joint into anterior two-thirds and posterior one-third by a
V-shaped groove, the sulcus terminalis. At the latters
TNS, Transcutaneous nerve stimulation, see Transcuta- apex is a small depression, the foramen caecum. The
neous electrical nerve stimulation lower surface is attached to the floor of the mouth by
the frenulum.
Muscles of the tongue:
Tobramycin. Aminoglycoside and antibacterial drug
genioglossus: fibres fan back from the superior
with similar activity to gentamicin but more active
against pseudomonas, although less active against other genial spine of the mandible to the tip and whole
Gram-negative organisms. length of the dorsum of the tongue. The lowest
Dosage: 1mg/kg im/slowly iv tds; increased to up to fibres attach to the hyoid bone.
hyoglossus: attached to the body and greater horns
5mg/kg/day in severe infections (decreased again as
soon as possible). Blood concentrations: 1hpost- of the hyoid bone, passing upwards and forwards
dose < 10mg/l; pre-dose < 2mg/l. into the sides of the tongue.
Side effects: as for aminoglycosides. palatoglossus and styloglossus: pass from the palate
and styloid process respectively.
intrinsic muscles: include vertical, longitudinal and
Tocainide hydrochloride. Class Ib antiarrhythmic drug
transverse fibres.
previously used for life-threatening ventricular arrhyth- Nerve supply:
mias. Withdrawn from use in the UK and USA due to
sensory: glossopharyngeal nerve to the posterior
severely toxic side effects, including life-threatening
one-third and lingual branch of mandibular division
agranulocytosis, thrombocytopenia, hepatitis, pneumoni-
of the trigeminal nerve (V3) to the anterior two-
tis and an SLE-like syndrome.
thirds. Gustatory fibres pass from the anterior two-
thirds of the tongue via the chorda tympani to the
Tocolytic drugs. Used to inhibit uterine contractions facial nerve.
when premature delivery of the fetus is threatened, to motor: hypoglossal nerve.
prevent uterine activity during/after incidental maternal The tone of genioglossus is important in preventing
surgery or fetal surgery, and to relax the uterus acutely, approximation of the tongue and posterior pharyngeal
e.g. in fetal distress, obstructed delivery or uterine inver- wall, which results in airway obstruction. Genioglossus
sion. Drugs traditionally used are 2-adrenergic receptor tone varies with respiration and is maximal in inspira-
agonists and include ritodrine, salbutamol and terbuta- tion. It also decreases during sleep; this may contribute
line. Side effects may persist after discontinuation of the to the development of sleep apnoea. Anaesthetic and
infusion; these include tachycardia, arrhythmias, hypo- sedative agents decrease this tone and thus predispose
tension and occasionally pulmonary oedema (unclear to obstruction, which may be relieved by elevating the
mechanism, but thought to involve increased pulmonary jaw, placing the patient in the lateral position, and use of
hydrostatic pressure; fluid administration and concomi- pharyngeal airways.
tant corticosteroids may also contribute). Arrhythmias Macroglossia predisposes to respiratory obstruction
may occur if halothane is subsequently used. and may hinder tracheal intubation, e.g. in acromegaly,
Other tocolytic drugs include atosiban (an oxytocin Downs syndrome and light chain amyloidosis. It may
antagonist), which is more expensive but has fewer side also occur after posterior fossa neurosurgery. Tongue
effects than 2-agonists in preterm labour (although it piercing studs should be removed preoperatively.
may cause nausea, vomiting, tachycardia and hypoten-
sion). Nifedipine, magnesium sulphate and inhibitors of Tongue forceps, see Forceps
prostaglandin synthesis (e.g. indometacin) also cause
tocolysis but are not widely used in the UK. GTN Tonicity. Refers to the effective osmotic pressure of
patches have also been used. Acutely, GTN 100400g solutions in relation to that of plasma. Thus a urea solu-
iv or sublingually is also used. tion may be isosmotic with plasma but its effective
See also, Obstetric analgesia and anaesthesia osmotic pressure (and thus tonicity) falls after infusion
because urea distributes evenly across cell membranes.
TOE, see Transoesophageal echocardiography Similarly, 5% dextrose solution is isosmotic with plasma
but hypotonic when infused since the dextrose is metab-
Tolazoline hydrochloride. -Adrenergic receptor olised by red blood cells leaving water.
antagonist, structurally related to phentolamine. Tradi- See also, Intravenous fluids
tionally used by iv infusion to relieve arterial spasm
following accidental intra-arterial injection of thiopen- Tonometry, gastric, see Gastric tonometry
tal. Also used to reduce pulmonary vascular resistance,
e.g. in congenital diaphragmatic hernia. Tonsil, bleeding. Haemorrhage usually occurs within a
Dosage: 1mg/kg. few hours postoperatively, but may be delayed.
Problems include:
Tolerance. Progressively decreasing response to hidden blood loss if the patient (usually a child)
repeated administration of a drug. May result from swallows it; hypovolaemia may thus be severe
altered number of receptors, altered response to recep- before diagnosis is made.
tor activation, altered pharmacokinetics (e.g. enzyme risk of aspiration of gastric contents (mostly altered
induction) or development of physiological compensa- blood).
tory mechanisms. Classically occurs with morphine. airway management and tracheal intubation may be
See also, Tachyphylaxis difficult if bleeding is torrential.
568 Topical anaesthesia

significant amounts of the anaesthetic agents used Treatment:

previously may still be present. of predisposing condition.
possibility of an undiagnosed coagulation cardioversion.
disorder. magnesium sulphate.
Management: increasing the heart rate, e.g. isoprenaline, cardiac
preoperative assessment of coagulation and cardio- pacing.
vascular status, with iv resuscitation. Nasogastric Class I antiarrhythmic drugs should be avoided.
aspiration is controversial, since it may exacerbate
bleeding. Total intravenous anaesthesia (TIVA). Anaesthetic
experienced assistance is required. Each of the fol- technique employing iv agents alone, and avoiding the
lowing techniques has its advocates: use of inhalational agents. The patient breathes O2, air,
- inhalational induction in the left lateral position or a mixture of the two. Drugs are given usually by infu-
(with suction available), traditionally using halo- sion to achieve anaesthesia and appropriate analgesia.
thane (superseded by sevoflurane) in O2, and The drugs chosen are usually of short action and half-life
tracheal intubation during spontaneous ventila- to prevent accumulation and prolonged recovery. Exam-
tion. The main advantage is the maintenance ples include propofol, together with alfentanil, fentanyl
of spontaneous ventilation if intubation is diffi- or remifentanil. Ketamine has been used for its analgesic
cult. However, induction may be prolonged properties, e.g. together with midazolam. Neuroleptan-
and hindered by bleeding and gagging and aesthesia has also been used.
the high concentrations of volatile agent Advantages:
required plus hypovolaemia may cause significant avoids unwanted effects of inhalational anaesthetic
hypotension. agents.
- rapid sequence induction using a small dose of iv avoids pollution by gases and vapours.
agent, e.g. thiopental followed by suxamethonium may be used without complex apparatus such as
and intubation. Advantages of this technique anaesthetic machines, cylinders and vaporisers, e.g.
include rapidity of intubation and the greater in war zones.
familiarity of most anaesthetists with it. However, Disadvantages:
it should only be attempted if intubation was easy requires repeated injections or infusion devices.
at the initial operation. Hypotension may follow accurate prediction of plasma levels of anaesthetic
induction, and laryngoscopy may be difficult in agents is more difficult than with inhalational
torrential haemorrhage. agents, because of the more complicated pharmaco-
nasogastric aspiration is performed before extuba- kinetics and the absence of actual measurements of
tion, which should be performed when the patient drug concentration. Thus awareness or excessive
is awake and laryngeal reflexes have returned. dosage may occur unless one is familiar with the
See also, Ear, nose and throat surgery; Induction, rapid technique. Computer-assisted infusion has been
sequence employed to provide steady plasma levels according
to pharmacokinetic data collected from hundreds of
Topical anaesthesia. Application of local anaesthetic patients. Target-controlled infusion (TCI) devices
agent (e.g. cocaine, lidocaine, tetracaine) to skin or employ similar data to run a special syringe driver
mucous membranes to produce anaesthesia. Used on the according to the patients age, weight and desired
skin, conjunctiva, nasal passages, larynx and pharynx, plasma drug concentration, which are entered by
tracheobronchial tree, rectum and urethra. Local anaes- the anaesthetist.
thetic has also been instilled into the bladder, pleural once a drug has been infused, it cannot be removed
cavity, peritoneal cavity and synovial fluid of joints. from the body other than by metabolism and excre-
May be applied via direct instillation, soaked swabs, tion. Thus there is less control than with inhalational
pastes/ointments or sprays. Systemic absorption may be agents, which may be removed by ventilation.
rapid and the maximal safe doses should not be exceeded.
See also, EMLA cream; Iontophoresis Total lung capacity. Volume of gas in the lungs after
maximal inspiration. Normally approximately 6 litres.
Torr. Non-SI unit of pressure; 1 torr = 1/760 atmosphere Determined by helium dilution (does not measure gas
= 1mmHg. in poorly ventilated regions) or with the body
[Evangelista Torricelli (16081647), Italian physicist] plethysmograph.
See also, Lung volumes
Torsade de pointes. Atypical VT characterised by poly-
morphic QRS complexes with repeated fluctuations of
QRS axis, the complexes appearing to twist about the
baseline (Fig. 156). Often associated with a prolonged
QT interval. Initiated by a ventricular ectopic beat
occurring during a prolonged pause after a previous
ectopic.
Causes include:
electrolyte abnormalities, e.g. hypokalaemia, hypo-
magnesaemia, hypocalcaemia.
drugs, e.g. class I antiarrhythmic drugs, tricyclic anti-
depressant drugs, phenothiazines.
ischaemic heart disease.
congenital prolonged QT syndromes. Fig. 156Torsade de pointes
 Tracheal tubes 569

Total parenteral nutrition, see Nutrition, total in this way. Many respiratory drugs are administered
parenteral using inhalers and nebulisers.

Tourniquets. Used to reduce bleeding during limb Tracheal extubation, see Extubation, tracheal
surgery, and to allow IVRA. Inflated following exsangui-
nation of the limb, e.g. by raising it for 23min with the Tracheal intubation, see Intubation, tracheal
artery compressed, or by using a rubber Esmarch
bandage. The latter increases CVP and may provoke Tracheal tubes. Developed along with techniques for
cardiac failure in susceptible patients. It may also dis- tracheal intubation. ODwyer described his intubating
lodge emboli from DVTs. Complications from tourni- tube in 1885, although various tubes had been used pre-
quets include: direct skin, muscle, nerve or vascular viously, e.g. for CPR. The modern wide-bore tracheal
injury; reperfusion hyperaemia and limb oedema; and tube was developed by Magill and Rowbotham after
hypertension and tachycardia due to pain. World War I, following the use of thin gum-elastic tubes
Measures suggested to reduce compression and for insufflation techniques. Separate tubes were placed
ischaemic injury: into the trachea for delivery and removal of gases; these
inflation pressures: were eventually replaced by a single rubber (Magill)
- arm: systolic BP + 75100mmHg (+ 100mmHg tube. Cuffs were introduced by Guedel in 1928. Red
for IVRA). rubber tracheal tubes have largely been replaced by
- leg: systolic BP 2. sterile disposable polyvinyl chloride tubes, since the
Suggested values vary, and depend partly on age, former deteriorate on repeated sterilisation, are more
weight, etc. costly to use, and are irritant to the respiratory mucosa.
inflation time: 2hmaximum is the most common Plastic tubes soften as they warm, e.g. in the trachea, and
recommendation, although 60min for the arm and may be vulnerable to kinking.
90min for the leg are often quoted. Periodic defla- Size 9mm and 8mm internal diameter orotracheal
tion and reinflation may allow longer use. tubes are often employed for men and women respec-
Equipment should be checked before use. Tourniquets tively; smaller tubes (e.g. 7mm and 6mm) are often
should not be used in sickle cell anaemia (avoidance in used in the elective surgical setting since they are associ-
sickle trait has also been suggested). Protective padding ated with a lower incidence of sore throat and hoarse
is required under the tourniquet. Skin preparation solu- voice. However, for emergency intubation and ICU
tions may cause chemical burns if allowed to soak into admission, larger-bore tubes are preferred to facilitate
the padding. tracheobronchial suctioning and fibreoptic bronchos-
[Johann FA von Esmarch (18231908), German copy. Average suitable length is 2225cm for oral tubes,
surgeon] and 2528cm for nasal tubes (for sizes of tubes for
Estebe JP, Davies JM, Richebe P (2011). Eur J Anaes- children, see Paediatric anaesthesia).
thesiol; 28: 40411 Features of typical modern tracheal tubes
See also, Compartment syndromes (Fig. 157a):
marked with the following information:
Toxic epidermal necrolysis, see StevensJohnson - size (internal diameter in mm; the external diam-
syndrome eter may be marked in smaller lettering).
- the letters IT or Z79-IT (for plastic tubes) denote
Toxic shock syndrome. Systemic illness associated with that the material has been implantation tested in
certain Staphylococcus aureus strains, thought to be rabbit muscle for tissue compatibility, according
caused by exotoxins (possibly with concurrent Gram- to the American National Standards Committee
negative endotoxin production). Streptococci have also which met in committee room no. Z79 in 1956.
been implicated. - the distance from the tip of the tube is marked at
First described in 1978; the reported incidence intervals along the tubes length. Most plastic
increased around 1980, especially associated with men- tubes are longer than is usually required, and may
struation and use of tampons. Features typically occur be cut to size.
rapidly and include fever, hypotension, GIT upset, head- - other markings may refer to the manufacturer,
ache and myalgia. Generalised rash and/or oedema lead the trade name of the type of tube, and whether
to desquamation 1020 days later. MODS may occur. it is intended for oral or nasal use.
Treatment is supportive, with antibacterial drug therapy. A radio-opaque line is incorporated in most modern
tubes, to aid detection on CXR.
TPN, Total parenteral nutrition, see Nutrition, total curved with a left-facing bevel at the distal end.
parenteral There may be a hole in the wall opposite the bevel
(Murphy eye) to allow ventilation should the end
TPR, Total peripheral resistance, see Systemic vascular become obstructed by the tracheal wall or mucus.
resistance attached to a tracheal tube connector at the proxi-
mal end.
Trachea, see Tracheobronchial tree may bear a cuff near the distal end, with a pilot
balloon running towards the proximal end.
Tracheal administration of drugs. Previously used Other shapes and types of tubes (Fig. 157be):
when iv administration was not possible, e.g. cardiac Oxford tube: conforms more closely with the shape
arrest. Superseded by the intraosseous route in the of the mouth and pharynx, thus less liable to kink.
emergency setting. Previously advocated at 23 times the The bevel faces posteriorly; insertion of the tube is
iv dose, diluted in 10ml saline; atropine, adrenaline and aided by a gum-elastic bougie protruding a short
lidocaine were the drugs most commonly administered distance from the distal end. Traditionally made of
570 Tracheobronchial suctioning

(a) (b)
Connector

(c)

Pilot balloon

(d) (e)

Cuff

Murphy eye

Fig. 157Tracheal tubes: (a) typical; (b) Oxford; (c) oral and nasal RAE; (d) Cole; (e) reinforced (not to scale)

red rubber, they are thicker-walled than traditional Tubes may bear an extra channel for sampling of distal
red rubber tubes. Available with or without cuffs. gases or for jet ventilation. A directional tube has also
RAE tube: plastic; designed to be even more ana- been described, in which traction on a ring at the proxi-
tomically shaped than the Oxford tube. Nasal RAE mal end flexes the distal end, aiding placement during
tubes are also available, as are other manufacturers tracheal intubation. Laser-protected tubes include tubes
versions. Available with or without cuffs. made totally out of metal and those coated with laser-
Cole tube: used in neonates. Shouldered, with thick- proof substances.
ened walls to prevent kinking. Designed to mini- [Francis J Murphy (19001972), Detroit anaesthetist;
mise resistance to flow of gas by virtue of their wide Frank Cole (19181977), US anaesthetist; RAE: Wallace
proximal portion; however, they increase resistance H Ring, John C Adair, Richard A Elwyn, Salt Lake City
by causing turbulence at the junction with the anaesthetists]
narrow portion. They also may cause damage to the See also, Endobronchial tubes; Intubation, tracheal;
larynx and trachea if the shoulder is forced too far Tracheostomy
distally. Their avoidance has therefore been repeat-
edly suggested. Tracheobronchial suctioning. Required in patients
reinforced tubes: resemble standard tubes but who have a tracheal tube in place because of inability to
contain a spiral of metal or nylon in the tube wall. mobilise secretions effectively. Also useful for diagnostic
Used where kinking of the tube may otherwise purposes, e.g. for obtaining sputum samples. The catheter
occur, e.g. neurosurgery, maxillofacial surgery. should be inserted gently until resistance is felt, with-
Originally made of latex rubber, they are now drawn slightly and suction applied whilst withdrawing.
commonly made of plastic. They cannot be cut to Closed suction systems are used in the ICU setting to
size. Available with or without cuffs. The silicone reduce the risk of bacterial contamination of the airway.
tube supplied with the intubating LMA is rein- Complications:
forced and has a tapered tip, making it easier to pass hypoxaemia: may be related to rapid removal of
through the device without catching on the vocal airway gases, causing atelectasis, bronchospasm/
cords or arytenoids. This tube is also easier to coughing or disconnection from the ventilator. Par-
railroad over a fibreoptic scope than standard ticularly likely if the patient is PEEP-dependent.
tracheal tubes. Reduced by preoxygenation before and after
 Tracheo-oesophageal fistula 571

suctioning, limitation of catheter size and use of crossed anteriorly by the isthmus of the thyroid
self-contained suction catheters within the breath- gland. Laterally lie the lateral lobes of the thyroid,
ing system that avoid the need for disconnection. the inferior thyroid artery and carotid sheath
atelectasis: reduced by avoiding excessive negative (containing the internal jugular vein, common
pressures and prolonged suction, and limiting the carotid artery and vagus nerve). In the thorax (see
catheter size, e.g. appropriate size (FG) = 3 (tra- Fig. 104b; Mediastinum) it is crossed anteriorly by
cheal tube internal diameter 2). the brachiocephalic artery and left brachioce-
trauma, haemorrhage and oedema: reduced by phalic vein. On the left lie the common carotid
careful technique, avoidance of excessive negative and subclavian arteries above, and the aorta
pressure, use of rounded-tipped catheters and below. On the right lie the mediastinal pleura,
intermittent rather than continuous, suction. right vagus nerve and azygous vein.
Special care should be taken in the presence of - right and left main bronchi (generation 1): arise
coagulopathy. at T45:
cross-infection/dispersal of infected material: - right: 3cm long, and wider and more vertical than
reduced by sterile technique and self-contained the left, and therefore likelier to receive inhaled
suction equipment incorporating a catheter within foreign bodies. The right upper main bronchus
the breathing tubing. arises about 2.5cm from its origin.
arrhythmias: may be related to hypoxaemia. Relations: separated from the pericardium and
Sinus bradycardia is especially common, via vagal superior vena cava by the right pulmonary artery.
stimulation. The azygous vein lies above.
increased ICP: especially detrimental in patients - left: about 5cm long.
with pre-existing raised ICP. May be reduced by Relations: separated from the left atrium by
increased sedation. the left pulmonary artery. The aortic arch lies
See also, Ciliary activity above, and the bronchial vessels posteriorly (sep-
arating it from the oesophagus and descending
Tracheobronchial tree. Branching system consisting thoracic aorta).
of 23 generations of passages from trachea to alveoli, - lobar and segmental bronchi (generations 24)
comprising: (Fig. 158).
conducting airways: make up anatomical dead space: - small bronchi to terminal bronchioles (genera-
- trachea (generation 0): 10cm long and 2cm wide tions 516).
in the adult. Descends from the larynx level with respiratory airways:
C6, passing through the neck and thorax to its - respiratory bronchioles (generations 1719): bear
bifurcation level with T45 (at the level of the occasional alveoli.
angle of Louis). Its walls are formed of fibrous - alveolar ducts (generations 2022): lined with
tissue reinforced by 1520U-shaped cartilaginous alveoli.
rings (deficient posteriorly), united behind by - alveoli (generation 23).
fibrous tissue and smooth muscle. Lined with cili- [Pierre CA Louis (17871872), French physician]
ated epithelium. See also, Alveolus; Ciliary activity; Lung
Relations: lies anterior to the oesophagus, with
the left and right recurrent laryngeal nerves in Tracheo-oesophageal fistula (TOF). Oesophageal
the grooves between them. In the neck (see atresia occurs in 1:3000 births, with TOF in 25% of
Fig. 113; Neck, cross-sectional anatomy) it is cases. Different forms exist (Fig. 159). Babies may be

Lobar bronchi Segmental bronchi Right Left Segmental bronchi Lobar bronchi

Upper Apical Apical Upper

Posterior Posterior
Anterior Anterior

Middle Lateral Superior lingular

Medial Inferior lingular

Lower Superior Superior Lower

Anterior basal Anterior basal
Medial basal Medial basal

Lateral basal Lateral basal

Posterior basal Posterior basal

Fig. 158 Lobar and segmental bronchi

572 Tracheostomy

85% 810% 24% 1% 1%

Oesophagus
Trachea

Fig. 159 Different forms of tracheo-oesophageal fistulae and their incidence

premature and have other congenital abnormalities. laryngeal reflexes are obtunded, e.g. neurological
TOF may present with choking during feeds, production disease.
of copious frothy mucus from the mouth or repeated to allow suction and removal of secretions.
chest infections following pulmonary aspiration. It is prolonged IPPV in ICU. Advantages over conven-
diagnosed by passing a radio-opaque nasogastric tube tional tracheal intubation include easier nursing
into the blind pouch; contrast medium is avoided because management, improved patient comfort (and there-
of risk of aspiration. Treated by surgery, performed fore reduced sedation requirements), potential for
thorascopically or via right thoracotomy. Primary anas- eating and speaking, decreased incidence of sinus-
tomosis of the oesophagus is performed if possible. itis, and possibly assistance of weaning by a 3050%
Anaesthesia is as for paediatric anaesthesia. In reduction in dead space.
particular: The traditional open procedure may be performed
preoperatively: under general or local anaesthesia. The patient lies
- the baby is nursed head-up, with continuous supine with the neck hyperextended, and a horizontal
suction to the blind pouch to prevent pulmonary incision is made 1.5cm below the level of the cricoid
aspiration. cartilage. After location of the trachea, a vertical incision
- correction of electrolyte abnormalities. is made through the second, third and fourth tracheal
perioperatively: rings. A slit or circular opening is made in the trachea
- traditionally, tracheal intubation is performed (creation of a tracheal flap has been implicated in causing
awake, avoiding IPPV by facemask to prevent tracheal stenosis). During general anaesthesia, ventila-
gastric inflation. Intubation of the fistula may tion with 100% O2 should precede withdrawal of the
occur; if this happens the tracheal tube may be tracheal tube (which is withdrawn into the larynx only,
withdrawn and reinserted with the bevel direction in case readvancement is required). The tracheostomy
altered. Positioning of the tip of the tube distal to tube is then inserted. Stay sutures may be brought out
the fistula prevents gastric inflation; this may be on to the skin from the trachea, to aid subsequent tube
achieved by deliberate endobronchial intubation, reinsertion.
followed by careful withdrawal of the tracheal Increasingly, surgical tracheostomy is being
tube until breath sounds are heard on both sides replaced by the percutaneous procedure, especially in
of the chest. critically ill patients receiving IPPV (see Tracheostomy,
- classically, neuromuscular blockade and IPPV are percutaneous).
avoided until the chest is open, to prevent gastric Tracheostomy tubes:
distension. Many paediatric anaesthetists use uncuffed: plastic or metal (usually silver). They
gentle manual IPPV, since gastric distension may allow speech if a one-way valve is used; air
is rare. is drawn into the lungs through the tracheostomy
- surgical manipulation may cause sudden increases and exhaled through the larynx and mouth. A fen-
in airway pressures or reductions in cardiac estration in the tube improves the strength of
output. the voice.
postoperatively: IPPV may be required. cuffed: plastic, with low-pressure, high-volume cuffs
After repair, a blind passage may remain at the site to minimise tracheal mucosal damage. The cuff may
of the fistula, making subsequent tracheal intubation be deflated and the tube occluded with a finger
difficult. Tracheomalacia may also occur. during expiration, to allow speech. Cuffed tubes
Broemling N, Campbell F (2011). Pediatr Anesth; 21: may also be fenestrated. Some incorporate a sepa-
10929 rate catheter opening just above the cuff, through
which O2 may be diverted using a manual control
Tracheostomy. First performed in the 1700s for upper to allow speech. The catheter may also be used for
airway obstruction. Modern indications: suction.
prophylactic or therapeutic relief of airway Complications may be early or late:
obstruction. early:
to protect the tracheobronchial tree against aspira- - haemorrhage, especially from branches of the
tion of food, saliva, etc., when pharyngeal and anterior jugular veins or thyroid isthmus.
 Train-of-four nerve stimulation 573

- displacement of the tube: extrusion or endobron- tube is withdrawn into the larynx under direct
chial intubation. vision to avoid damage). Fibreoptic endoscopy is
- blockage, e.g. by secretions, compression by the usually used to confirm correct needle placement
cuff or occlusion against the carina. but may result in damage to the scope.
- subcutaneous emphysema. the cannula is left in the trachea, a wire advanced
- pneumothorax. through it and the cannula withdrawn.
late: blunt dissection of the superficial tissues is per-
- infection, including superficial wound infection, formed using artery forceps. Some operators would
tracheitis and chest infection. regard blunt dissection down to the trachea, before
- tracheal erosion and ulceration, e.g. into blood location of the tracheal lumen with the needle and
vessels, oesophagus. subsequent cannulation, as being a safer technique.
- tracheal stenosis; usually occurs level with the Once the wire is in place in the trachea, different
stoma or the tubes cuff, although subglottic ste- methods of passing the tracheostomy tube have
nosis may also occur. Surgical resection may be been described:
required. - serial dilatation method (original Ciaglia tech-
- tracheal dilatation may occur. nique): special dilators are slid over the wire,
Tracheostomy care includes: starting with 12 FG and proceeding up to 36 FG,
humidification: vital to reduce risk of obstruction by depending on the size of tracheostomy tube,
viscous secretions. which is finally passed into the trachea mounted
tracheobronchial suctioning: sterile technique is on the appropriate dilator.
mandatory. The suction catheters diameter should - single dilatation method: a specially tapered
not exceed half that of the tracheostomy tube. smooth dilator (Ciaglia Blue Rhino), with a pro-
Suction is applied on withdrawal, not insertion, of gressively larger diameter along its length, is slid
the catheter. over the wire. After a single-pass dilatation, the
daily cleaning and dressing to reduce risk of tracheostomy tube is passed into the trachea
infection. mounted on the same dilator. A related method
secure fixation, e.g. with double tapes. involves a conical threaded dilator that is screwed
presence of tracheal dilators, spare tracheostomy into place over a guide-wire akin to a self-tapping
tubes, and equipment for manual ventilation and screw.
tracheal intubation, in case of displacement. - balloon dilatation (Blue Dolphin): a balloon dila-
provision of a means of communication, e.g. pen tation catheter is introduced over the guide-wire;
and paper. inflation of the balloon dilates the tracheal wall
The initial tube is usually left in situ for at least a week, and soft tissues. Removes the need for application
to allow formation of a tract. The tube may be changed of downwards force with a rigid dilator, theoreti-
over a thin catheter or guide-wire. Once decannulated, cally reducing the risk of injury to the posterior
the stoma usually closes spontaneously within a few tracheal wall.
days, but surgical closure may be required. - dilating forceps (Griggs) method: a special pair of
Mallick A, Bodenham AR (2010). Eur J Anaesthesiol; curved forceps, incorporating a groove in the
27: 67682 opposing surfaces of its jaws, is slid over the wire
See also, Minitracheotomy with the jaws closed. The forceps are then opened
outside the trachea to dilate the soft tissues before
Tracheostomy, percutaneous. Increasingly used in being closed and passed into the trachea. They are
critically ill patients requiring tracheostomy instead of then opened forcibly within the trachea and
the traditional open procedure because of the following removed whilst still open; the tracheostomy tube
advantages: is then passed over the wire into the trachea.
may be performed in the ICU or other clinical area, - translaryngeal tracheostomy method: a guide-
thus avoiding transfer of critically ill patients to the wire is passed retrogradely into the mouth via a
operating suite. percutaneous needle in the trachea, under bron-
does not require a surgeon. choscopic control. A reinforced flexible tube with
may be quicker in skilled hands. a cuff at its proximal end and a cone-shaped
may be associated with fewer complications, e.g. dilator fixed to its distal end are then passed over
wound infection. the guide-wire from the mouth and pulled out
provides an opportunity for teaching emergency through the front of the neck; the cone portion is
access to the airway (i.e. percutaneous location of then removed and the tube manipulated so that
the trachea). the intratracheal portion (bearing the cuff) passes
Avoided in children and in the presence of coagulopathy, caudally to lie in the standard tracheostomy tube
localised infection and difficult anatomy. position.
Methods: Complications are as for open surgery; initial studies
neck ultrasound may be performed before the pro- suggest their incidence is low. Tracheal tears and oesoph-
cedure to exclude thyroid enlargement over the ageal perforation may occur with all the above methods.
planned entry site. [Pasquale Ciaglia (19122000), US thoracic surgeon; Bill
initial preparation and positioning as for the open Griggs, Australian intensivist]
procedure. Cabrini L, Monti G, Landoni G, etal (2012). Acta Anaes-
following infiltration with local anaesthetic, a small thesiol Scand; 56: 27081
horizontal incision is made over the space between
the first/second tracheal rings and the trachea Train-of-four nerve stimulation, see Neuromuscular
located with a syringe and cannula (the tracheal blockade monitoring
574 TRALI

TRALI, Transfusion-related acute lung injury, see Blood of pain transmission; i.e. stimulation of A fibres (by
transfusion high-frequency TENS) and A fibres (by low-frequency
TENS) inhibits pain transmission by C fibres. Current is
Tramadol hydrochloride. Opioid analgesic drug, intro- provided by a battery-powered pulse generator, which
duced in the UK in 1994. A pure agonist at mu opioid typically delivers a range of currents (050mA), fre-
receptors, it is also a delta and kappa receptor agonist; quencies (0200Hz) and pulse widths (0.10.5 ms).
it also inhibits noradrenaline uptake and enhances 5-HT Rectangular pulses are usually employed. Surface elec-
release. Undergoes hepatic and renal elimination; con- trodes are usually carbon-impregnated silicone rubber.
traindicated in patients with end-stage renal failure. The electrodes are placed either side of the painful
Half-life is about 6h. Administration with morphine was area or its supplying nerves, and the current increased
previously suggested to reduce the efficacy of both (i.e. until tingling is felt. Experimentation with timing and
an infra-additive effect); however, this is disputed, and duration is usually required to achieve maximal effects.
several studies demonstrate that tramadol improves Has been used successfully in acute pain (e.g. for
analgesia and reduces morphine requirements after fractured ribs, labour, postoperatively), but is usually
major surgery. employed for chronic pain management (peripheral
Dosage: nerve disorders, spinal cord and root disorders, muscle
50100mg orally 46-hourly up to 400mg/day for pain and joint pain). Efficacy is difficult to assess as there
short courses. A slow-release formulation is avail- is significant placebo effect, but TENS may reduce anal-
able: 100200mg od/bd. A combined preparation gesic requirements.
with paracetamol is also available (37.5mg trama- Allergic dermatitis at electrode sites may occur. Con-
dol with 325mg paracetamol): 12 tablets qds. traindicated in patients with pacemakers.
50100mg im/slowly iv 46-hourly (up to 250mg in
divided doses as initial dose for postoperative pain, Transducers. Devices that convert one form of energy
up to 600mg/day). Dosage interval should be to another, usually to electricity in monitoring systems.
increased in the elderly and those with liver and/or May be:
renal impairment. passive: involving changes in:
Side effects: nausea, vomiting, dizziness, dry mouth, - resistance, e.g. strain gauge, thermistor,
sweating, confusion and hallucinations, respiratory photoresistor.
depression, sedation (the latter two less commonly - inductance, e.g. pressure transducers.
than with morphine). Drug dependence and with- - capacitance, e.g. condenser microphone.
drawal have been reported, especially following pro- active, i.e. involving generation of potentials:
longed treatment. Convulsions have been reported, - piezoelectric effect: generation of voltage across
especially in combination with other drugs known to the faces of a quartz crystal when deformed.
reduce seizure threshold, e.g. tricyclic antidepressants - photoelectric cell.
and selective serotonin reuptake inhibitors. Contrain- - thermocouple.
dicated in patients receiving monoamine oxidase - radiation counters.
inhibitors. Analgesic efficacy is reduced by concur- - electrode potentials, e.g. pH electrode.
rent administration of 5-HT3 receptor antagonists - electromagnetic induction.
(e.g. ondansetron). See also, Arterial blood pressure measurement; Damping;
pH measurement; Pressure measurement; Temperature
Tranexamic acid. Antifibrinolytic drug, used to reduce measurement
bleeding, e.g. in trauma, cardiac surgery, prostatectomy,
menorrhagia or dental extraction in haemophiliacs; it Transfer factor, see Diffusing capacity
has also been used in streptokinase overdose and heredi-
tary angioneurotic oedema. Transfusion, see Blood transfusion
Dosage: 1.01.5g orally tds/qds; 0.51.0g iv tds.
Side effects: GIT disturbances, dizziness. Contraindi- Transfusion-related acute lung injury, see Blood
cated in thromboembolic disease. transfusion

Transcranial Doppler ultrasound (TCD). Application Transient radicular irritation syndrome (Transient
of ultrasound to demonstrate cerebral vessels. A low- neurologic syndrome). Pain and dysaesthesia in the
frequency (2MHz) pulse range-gated ultrasound beam buttock, thighs or calves following spinal anaesthesia;
is directed through the thin-boned transtemporal usually occurs within 24hof the block and typically
window; this allows assessment of the middle and ante- resolves within 72h. Particularly associated with the
rior cerebral arteries of the cerebral circulation. Using use of lidocaine in hyperbaric solutions of higher con-
the Doppler effect, flow velocities within these vessels centrations (2.55%), and very narrow-gauge needles or
can be determined. Uses include the detection of microcatheters, which result in pooling of the drug
cerebral vasospasm following subarachnoid haemor- around nerve roots. The lithotomy position has also been
rhage, assessment of cerebral blood flow (e.g. in head implicated, via stretching of the lumbosacral nerve roots
injury, carotid endarterectomy) and the detection of air and increasing their vulnerability. The syndrome may
embolism. Has also been used to assess cerebral reflect a transient form of cauda equina syndrome
autoregulation. following continuous spinal anaesthesia.
Kincaid MS (2008). Curr Opin Anaesthesiol; 21: 5529 Zaric D, Pace NL (2009). Cochrane Database Syst Rev;
2: CD003006
Transcutaneous electrical nerve stimulation (TENS).
Stimulation of peripheral nerves via cutaneous elec- Transoesophageal echocardiography (TOE). Form of
trodes, to relieve pain. Based on the gate control theory echocardiography allowing imaging of the heart in a
 Transposition of the great arteries 575

variety of different planes without requiring access to Ideally, transfer and retrieval systems should be planned
the chest. Increasingly used to assess cardiac function in and coordinated at local, regional and national levels,
awake, anaesthetised and critically ill patients. Basic with adequate funding, clear guidelines and communica-
principles are as for echocardiography and ultrasound, tion channels, and a transport coordinator (consultant)
combined with the ability to manipulate the probes tip identified in each hospital. Considerable stabilisation
and place it under the heart within the stomach, behind may be required before transfer, avoiding transfer of
the heart in the oesophagus or anywhere in between. unstable patients. All relevant notes and radiographs
Views may be obtained of the left and right atria and should accompany the patient.
ventricles (both transversely and longitudinally), all Requirements:
valves and outflow tracts, and proximal aorta and pul- vehicle: standard ambulance or a specifically
monary vessels. designed mobile ICU. Dedicated aircraft have been
Can be used to detect structural abnormalities, used.
myocardial ischaemia or MI (manifest by changes in team: should be experienced in transporting criti-
segmental wall motion), presence of valve vegetations, cally ill patients. Includes a suitably senior doctor,
pericarditis and aortic abnormalities. Doppler analysis assistant (ICU nurse, ODP, nurse) and driver/pilot
allows estimation of blood flows and cardiac output. other staff for ongoing training.
Commonly used perioperatively during cardiac surgery, equipment: should be robust, lightweight and por-
especially for: table, including a ventilator (allowing synchronised
assessment of the mitral valve pre- and post-repair. intermittent mandatory ventilation and PEEP),
detecting perivalvular leaks after valve replacement. monitors (as for any anaesthetic/ICU), O2, defibril-
determining the position/extent of aortic atheroma- lator, infusion pumps/syringe drivers, anaesthetic/
tous plaques or dissection. resuscitation drugs and all necessary disposables.
removal of intracardiac air before coming off car- All equipment should be battery-operated with suf-
diopulmonary bypass. ficient charge. Other equipment includes a mobile
guiding fluid therapy and assessing myocardial telephone. A mobile ICU stretcher makes transfer
contractility. easier.
guiding the position of an intra-arterial balloon Other aspects include audit of transfers (there should be
pump distal to the left subclavian artery. documentation of patient observations, transfer events
Also used in high-risk patients undergoing non-cardiac and any critical incidents) and team insurance. Although,
surgery, and in ICU and emergency departments. in general, patients relatives should not travel with the
Complications include dental, pharyngeal and patient, arrangements should be made for them to travel
oesophageal trauma and cardiovascular disturbances. and be received at the receiving hospital. Patients may
Contraindicated in oesophageal disease and upper GIT also require transfer between departments in a single
bleeding. hospital, e.g. from ICU to the radiology department.
Greenhalgh DL, Patrick MR (2012). Anaesthesia; 67: Similar considerations apply to those above.
3436 See also, Safe transport and retrieval
Handy JM (2011). Anaesthesia; 66: 33740
Transplantation. Use of cadaveric or live donor tissues
has increased with improved techniques and introduc- Transposition of the great arteries. Accounts for 5%
tion of immunosuppressive drugs such as ciclosporin. of congenital heart disease. Caused by failure of the
Main points: truncus arteriosus to rotate during embryological devel-
identification of donors and matching with recipi- opment. The aorta arises from the right ventricle and the
ents. There may be underutilisation of potential pulmonary artery from the left ventricle. Thus the pul-
donor organs following brainstem death in some monary and systemic circulations work independently,
ICUs. resulting in severe hypoxaemia. Survival is only possible
organ donation. if a connection exists between the two circulations, e.g.
preoperative state of the recipient, surgical proce- ASD, VSD or patent ductus arteriosus. Other malposi-
dure and postoperative course. tions of the great arteries may occur.
chronic physical and psychological effects of Features include cyanosis, early cardiac failure and
transplantation, drug therapy and possible organ right ventricular hypertrophy, with normal pulmonary
rejection. and systemic pressures. 8590% of infants die within a
See also, Heartlung transplantation; Heart transplanta- year without treatment.
tion; Liver transplantation; Lung transplantation; Renal Treatment:
transplantation palliation: shunt procedures, e.g. creation of an ASD
by balloon septostomy or surgery.
Transportation of critically ill patients. May be correction: use of baffles, e.g. Mustard procedure (or
primary (from site of injury or illness to hospital, e.g. by atrial switch): redirection of vena caval flow into
ambulance) or secondary (from one ICU to another). the left atrium, and pulmonary venous blood into
Up to 10000 interhospital transfers of critically ill the right atrium, using a pericardial patch. The right
patients occur per year in the UK. ventricle thus supplies the systemic circulation. Sys-
Reasons include: temic venous obstruction and poor long-term right
upgrade in the level of care required (e.g. for spe- ventricular function have led to increased use of
cialist surgery, dialysis). procedures which switch the pulmonary and sys-
to obtain a specialised investigation unavailable in temic circulations, at ventricular or arterial levels.
the base hospital. [William T Mustard (19141987), Toronto surgeon]
local lack of ICU resources (no bed available). Sommer RJ, Hijazi ZM, Rhodes JF (2008). Circulation;
repatriation to a unit closer to the patients home. 117: 114050
576 Transpulmonary thermodilution cardiac output measurement

Transpulmonary thermodilution cardiac output pierced and a second give as the needle passes through
measurement, see Cardiac output measurement the internal oblique aponeurosis. After aspiration, 20ml
solution (e.g. 0.250.5% bupivacaine) is injected.
An in-plane ultrasound-guided technique may also
Transurethral resection of the prostate (TURP). Cys-
be used, allowing visual confirmation of accurate place-
toscopic procedure for the removal of hypertrophied
ment of local anaesthetic; the ultrasound probe is placed
prostatic tissue.
Anaesthetic considerations:
in the mid-axillary line midway between the iliac crest
and the costal margin.
preoperative assessment: most patients are elderly,
Petersen PL, Mathieson O, Torup H, Dahl JB (2010).
with coexisting disease. Some may have prostatic
Acta Anaesthesiol Scand; 54: 52935
malignancy with systemic manifestations; oestrogen
See also, Abdominal field block, Rectus sheath block
therapy may cause fluid retention. Renal impair-
ment may be present.
Trauma. Most common cause of death in young adults
use of irrigating solution (usually glycine) may
in the UK and USA, and the third commonest cause
result in the TURP syndrome. Absorption rates of
overall.
irrigating solution of up to 240ml/min have been
Management has been consistently shown to be inad-
reported. Suggested monitoring includes measure-
equate in many cases, exacerbated by poor coordination
ment of the volume of irrigation in and out of the
of resources. Care in some countries (e.g. USA, Germany
patient, the patients weight, or plasma sodium,
and Australia) is better organised than in the UK (e.g.
osmolality, isotopes (for research only) or ethanol
20% of deaths were considered preventable in recent
added to the irrigation bag (10%), the latter usually
Royal College of Surgeons of England reports).
measured via a breath analyser, which gives an esti- Measures to improve outcomes include:
mation of plasma ethanol concentration. A drop in
improved prehospital care and transport, e.g. via
plasma sodium concentration of > 10mmol/l or a
helicopter; possibly doctors should accompany
plasma ethanol concentration of > 0.6mg/ml sug-
emergency vehicles. The debate concerning stabili-
gests absorption of more than 2 l fluid, and surgery
sation at the scene of the accident versus scoop and
should be stopped.
run continues.
Use of saline is possible with bipolar diathermy
centralised trauma centres, with facilities for CPR,
and reduces the risk of dilutional hyponatraemia,
imaging and surgery, to handle severe injuries.
though fluid (saline) overload may still occur.
Patients present directly from accidents or via refer-
positioning of the patient in lithotomy position, with
ring hospitals, which would deal with less severe
restricted ventilation and increased venous return.
trauma cases. Emergency, anaesthetic, ICU, ortho-
Hypotension due to venous pooling in the legs may
paedic, neurosurgical, cardiothoracic and general
occur when the legs are brought down at the end of
surgical staff should be available at all times.
the procedure.
use of trauma scales and triage to facilitate
blood loss may be major but is difficult to assess
appropriate management, especially in major
clinically. Devices for bedside measurement of cap-
incidents.
illary blood haemoglobin concentration may be Management of individual cases:
useful. Portable photometric devices may be used
initial rapid assessment and management (primary
to estimate haemoglobin concentration in the irri-
survey): O2 administration via a patent airway, with
gating fluid.
ventilatory support as required. Cervical spine
hypothermia may contribute to the features of the
injury should be assumed until proven otherwise,
TURP syndrome. Irrigating fluid should be warmed
and the neck immobilised with a collar, head
since this may be a major route of heat loss.
restraints and a long spinal board. Full stomach and
postoperative complications are common and
alcohol intake should be anticipated. Antigravity
include urinary and chest sepsis, and haemorrhage.
suits may be useful in severe blood loss, especially
mortality is up to 6%, usually due to perioperative
before transfer to hospital. Appropriate fluid resus-
acute coronary syndromes.
citation via large iv cannulae; until definitive hae-
General or regional techniques may be used. Post
mostasis is achieved, damage control resuscitation
operative course is generally considered to be better
is now advocated, consisting of restricted fluid
with the latter (spinal or epidural anaesthesia), which
resuscitation (aiming for BP compatible with cere-
also allows monitoring of CNS function during the
bration, except in those with head injury), early use
procedure.
of blood products and aggressive management of
hypothermia. Tranexamic acid has been shown to
Transversus abdominis plane block (TAP block). reduce mortality in patients at risk of major haem-
Block of the nerves supplying the anterior abdominal orrhage, if given within 3h of injury.
wall by deposition of local anaesthetic agent in the Life-threatening conditions requiring immediate
fascial plane between the internal oblique and trans detection and treatment include:
versus abdominis muscles. Useful as part of a multi- - airway obstruction.
modal postoperative analgesia strategy, reducing - tension or open pneumothorax, haemothorax.
requirements for opioid analgesic drugs after major - flail chest.
abdominal surgery. - hypovolaemia.
With the patient supine, a blunt needle is inserted - cardiac tamponade.
perpendicular to the skin just cranial to the iliac crest further assessment (secondary survey):
and just anterior to the edge of the latissimus dorsi - exposure and examination of the patients
muscle. A resistance is felt as the external oblique apo- face and head, spine, chest, back, abdomen and
neurosis is encountered, followed by a give as it is limbs.
 Triage 577

- type of injury is important, e.g.: Trauma scales. Scoring systems developed to aid assess-
- penetrating injury: internal damage is likely, ment and triage of trauma cases, prediction of outcome,
especially with high-velocity missiles. comparison between centres/countries. Several have
- blunt injury: crushing, shearing damage and been described:
fractures may result. Speed of collision and primarily used for triage: simple and quick to
height of fall are important. perform; examples include:
- burns/blast injury, etc. - Glasgow coma scale.
- trauma scales/triage. - trauma score and revised trauma score.
specific management as for haemorrhage, head - circulation, respiration, abdomen, motor and
injury, chest trauma, spinal cord injury, abdominal speech scale.
trauma, pelvic trauma; coexistent conditions, e.g. - prehospital index.
smoke inhalation, aspiration of gastric contents, - AVPU.
hypothermia, eye injury may be present. Intra- - paediatric trauma score.
abdominal bleeding may be revealed by peritoneal primarily used for outcome prediction: more
lavage. detailed; examples include:
monitoring of oxygen saturation, pulse, BP, urine - injury severity score.
output, neurological signs and CVP. - trauma revised injury severity score.
imaging, e.g. X-ray, CT scanning, as appropriate. - abbreviated injury scale.
analgesia, e.g. Entonox, local blocks, iv opioids. - a severity characterisation of trauma.
late problems: - international classification injury severity score.
- fat embolism: classically occurs on the second day; See also, Audit; Mortality/survival prediction on intensive
its incidence may be reduced if fractures are fixed care unit
early.
- DVT. Trauma score. Scoring system based on the Glasgow
- wound infection: tetanus prophylaxis and antibi- coma score, systolic BP, respiratory rate and effort, and
otics are given as appropriate; staphylococcal, capillary refill. Each is awarded points between 01 and
streptococcal and anaerobic infections are most 15, giving a total of 116, with 16 the best possible.
common. Originally presented as a means of triage, with transfer
- chest infection/acute lung injury. of patients scoring under 12 to a trauma centre. Since
- those associated with massive blood transfusion. capillary refill and respiratory effort may be difficult to
- acute kidney injury, e.g. associated with hypoten- assess in the field, they have been removed in the revised
sion, crush syndrome. trauma score.
- catabolism may be marked after multiple trauma.
Anaesthesia may be required for fixation of fractures,
Traumatic neurotic syndrome. Obsolete psychological
removal of foreign bodies, cleaning/debridement/ diagnosis applied to patients whose claims of awareness
suturing of wounds, evacuation of clot, control of during anaesthesia were met with professional denial,
internal haemorrhage and skin grafting. Problems: before the possibility of awareness was fully appreciated
nature of injury.
by anaesthetists. Sharing features with a general post-
alcohol or other drugs.
traumatic stress syndrome, it was characterised by recur-
gastric emptying is reduced by trauma; the time
rent nightmares, anxiety, irritability, preoccupation with
between last oral intake and injury is more impor- death and fear of insanity. An excellent prognosis was
tant than the time between intake and surgery. possible once the patients experience was accepted by
hypovolaemia.
health workers.
risk of massive hyperkalaemia following suxame-
thonium administration; time of onset is related to
the nature of injury. Treacher Collins syndrome, see Facial deformities,
Adequate resuscitation is required first unless surgery is congenital
life-saving. For surgery, regional techniques may be
useful if no contraindications exist. Sedation should be TREM-1 (Triggering receptor expressed on myeloid
avoided in head injury. Postoperative care should be on cells-1). Immunoglobulin molecule thought to be
ICU/HDU unless injury is minor. involved in, and to amplify, the inflammatory pathway
Recommendations now exist for the uniform report- that is activated in sepsis.
ing of data following major trauma using an Utstein style Klesney Tait J, Turnbull IR, Colonna M (2006). Nat
system. Immunol; 7: 126673
See also, Emergency surgery; Transportation of critically
ill patients Triage. Sorting of patients according to severity of injury
in order to maximise total number of survivors. Usually
Trauma revised injury severity score (TRISS). Trauma refers to trauma cases in battles or major incidents,
scale combining the revised trauma score (RTS), injury although similar approaches have been used in other
severity score (ISS), age and type of injury in an attempt fields of acute medicine, e.g. chest pain. First used during
to improve the individual scoring systems usefulness. Napoleons Russian campaign by Larrey, who scored
Used primarily in audit since it provides a probability of soldiers according to their need for medical treatment,
survival and thus comparison against actual survival treating the most severely injured first. Modern triage
rates. Revised trauma and injury severity scores are each systems give first priority to those patients who might
weighted by a coefficient depending on whether injury survive only if treated, leaving until later those expected
was blunt or penetrating, and the result adjusted again to die even if treated, and those expected to survive even
by a factor accounting for the patients age. without treatment.
578 Trials, clinical

Many systems exist, but most divide survivors into: to the cranial nerves, especially V and VII. Very soluble
first priority: immediate treatment/transfer required. in blood (blood/gas partition coefficient of 9); induction
second priority: treatment urgent, but with stabilisa- and recovery are thus slow. Extremely potent (MAC
tion first. 0.17) and a powerful analgesic. Previously popular in
third priority: minor injury, e.g. walking wounded. obstetrics as an analgesic agent, and for providing anal-
fourth priority: expected to die, therefore low gesia during IPPV; traditionally used instead of N2O by
priority. the Armed Forces (e.g. in the triservice apparatus).
Assisted by trauma scales, with attention also paid to the
mechanism of injury. Some systems include colour-coded Triclofos. Related drug to chloral hydrate. Metabolised
labels with details of injuries, treatments, to be attached to trichloroethanol, as is chloral hydrate. Discontinued
to patients. Triage may be repeated at different stages of in the UK in 2010.
retrieval and treatment, e.g. at the scene of accident, at Dosage: 12g orally in adults; 2530mg/kg in
the receiving hospital, on wards; thus patients may children < 1 year; 250mg1.0g in children aged
change in priority as circumstances change. 112 years.
Side effects: as for chloral hydrate but causes fewer
Trials, clinical, see Clinical trials GIT side effects.

Tribavirin, see Ribavirin Tricuspid valve lesions. Tricuspid stenosis is usually

associated with mitral stenosis and aortic valve disease
Tricarboxylic acid cycle (Citric acid cycle; Krebs cycle). resulting from rheumatic fever; may also coexist with
Final common pathway for oxidation of carbohydrate, pulmonary stenosis in the carcinoid syndrome. Isolated
fat and some amino acids to CO2 and water. Consists of tricuspid stenosis is very rare.
a sequence of reactions that occur within mitochondria Features:
and require O2. Acetyl coenzyme A (containing two increased right atrial pressure with peripheral
carbon atoms) enters the cycle, having been formed from oedema and hepatomegaly.
fat metabolism or glycolysis via pyruvate (Fig. 160). At prominent a wave in the jugular venous
each step where a carbon atom is lost, CO2 is produced. waveform.
For each turn of the cycle, 15 ATP molecules are formed mid and late diastolic heart murmur, heard best in
via transfer of hydrogen atoms to the cytochrome inspiration at the left lower sternal edge.
oxidase system or formation of guanosine triphosphate right atrial enlargement may be shown on CXR
(including the two ATP molecules generated by conver- and ECG.
sion of pyruvate to acetyl coenzyme A). Tricuspid regurgitation usually results from right ven-
[Hans A Krebs (19001981), German-born English tricular enlargement, e.g. in right-sided cardiac failure.
biochemist] Usually causes little functional impairment.
Features:
Trichloroethylene. CCl2CHCl. Inhalational anaesthetic large systolic wave in the jugular venous
agent, synthesised in 1864 and used clinically in 1935; waveform.
withdrawn from use in the UK in 1988. Similar smell and pansystolic murmur at the left lower sternal edge.
properties to chloroform (hence coloured with waxoline Anaesthetic considerations are related more to the
blue to distinguish them). Decomposed by light, and accompanying mitral and aortic lesions than to the tri-
stabilised by thymol 0.01%. Interacts with soda lime at cuspid lesion itself.
60C to form dichloroacetylene (C2Cl2), a potent neuro- See also, Ebsteins anomaly
toxin that may cause temporary or permanent damage
Tricyclic antidepressant drug poisoning. Accounts for
about 10% of cases of poisoning. Newer drugs (e.g. selec-
tive serotonin reuptake inhibitors) have better safety
profiles.
Acetyl CoA 2C Features:
tachycardia, hypotension; impaired myocardial con-

Oxaloacetate
tractility and conduction may cause AF, widening
of the QRS complex, heart block, VT and VF.
4C severe metabolic acidosis may occur.
agitation, hyperreflexia, hallucinations, convulsions,
Malate 4C 6C Citrate
coma, blurred vision, urinary retention, pyrexia.
Management:
ICU admission has been suggested at plasma levels
> 1mg/ml or when QRS complex duration exceeds
Fumarate 4C 6C Isocitrate
100 ms.
as for general poisoning and overdoses, including
CO2 measures to prevent gastric absorption.
ECG monitoring is usually recommended for at
5C Ketoglutarate least 1224h. Lipid emulsion has been used suc-
Succinate 4C
4C cessfully in refractory cardiovascular collapse.
induction of alkalaemia (pH > 7.5) is used to reduce
Succinyl CoA CO2 the amount of free drug, e.g. with bicarbonate
or hyperventilation. -Adrenergic receptor
Fig. 160Tricarboxylic acid cycle antagonists have been used in ventricular
 Trismus 579

tachyarrhythmias; cardiac pacing may be required myofascial pain syndromes. Examination may reveal
for bradyarrhythmias. Physostigmine has been used tender nodules within taut bands of muscle, felt espe-
to restore consciousness and slow the heart rate, cially if the fingertips are moved perpendicular to the
although this is controversial and convulsions have direction of muscle fibres. May be numerous, and may
occurred following its use. correspond to traditional acupuncture points. Local
See also, Tricyclic antidepressant drugs anaesthetic injection and acupuncture may relieve
symptoms.
Tricyclic antidepressant drugs. Group of antidepres-
sant drugs; the term includes several newer one-, two- Trimeprazine, see Alimemazine
and four-ring structured drugs with similar actions.
Competitively block neuronal reuptake of noradrena- Trimetaphan camsylate. Ganglion blocking drug, no
line and 5-HT. Also have CNS anticholinergic proper- longer generally available in the UK, used to lower BP
ties. Used in depression and pain management; analgesic during hypotensive anaesthesia. Its hypotensive effect is
properties are thought to be associated with impairment enhanced by a direct relaxant action on vascular smooth
of 5-HT reuptake (e.g. especially by amitriptyline and muscle and by histamine release from mast cells. Rapid
clomipramine). Many cause sedation, e.g. amitriptyline, onset and offset, thus usually given by iv infusion. Com-
dosulepin (dothiepin), mianserin, trazodone and trimip- pensatory tachycardia is common. Tachyphylaxis may
ramine. Sedation is less likely with clomipramine, nor- occur. Partially broken down by plasma cholinesterase
triptyline, imipramine and desipramine. and may have prolonged action in patients with
24 weeks therapy is required before their effect is decreased activity of this enzyme.
apparent. Half-lives may be up to 48h. Metabolised in
the liver and excreted renally. Trimethoprim. Antibacterial drug used especially in
Anaesthetic considerations: increased sensitivity to urinary tract infections, exacerbations of COPD and in
catecholamines may result in hypertension and combination with the sulphonamide sulfamethoxazole
arrhythmias following administration of sympathomi- (co-trimoxazole). Reversibly inhibits bacterial dihydro-
metic drugs. Ventricular arrhythmias may occur with folate dehydrogenase.
high concentrations of volatile anaesthetic agents, Dosage: 200mg orally bd or 150250mg iv bd.
especially halothane. Side effects: GIT upset, pruritus.
See also, Tricyclic antidepressant drug poisoning
Triple point. Temperature and pressure at which the
Trigeminal nerve blocks, see Gasserian ganglion block; solid, liquid and gas phases of a substance exist in equi-
Mandibular nerve blocks; Maxillary nerve blocks; librium. The kelvin is defined according to the triple
Nose; Ophthalmic nerve blocks point of water (273.16K at 611.2Pa).

Trigeminal neuralgia (Tic douloureux). Chronic pain Triservice apparatus. Anaesthetic apparatus adopted
state characterised by brief, severe lancinating pain by the Armed Forces for battle use. Consists of (in order,
involving the trigeminal nerve distribution. Usually starting at the patient):
involves the mandibular division; may also involve the facemask with non-rebreathing valve fitted.
glossopharyngeal nerve. Pain tends to be unilateral short length of ordinary tubing connected to a self-
during the acute attack, which may be triggered by non- inflating bag.
noxious stimulation of the ipsilateral nasal or perioral another length of tubing.
region (sometimes restricted to one specific zone). two Oxford miniature vaporisers in series.
There is minimal or no sensory loss in the trigeminal an O2 cylinder may be attached, between the vapo-
distribution. Pain-free intervals typically separate risers and a further length of tubing which acts as a
attacks, which may be so severe as to cause suicide. Aeti- reservoir.
ology is uncertain, although it may be associated with an For spontaneous ventilation, a draw-over technique is
aberrant blood vessel loop abutting the trigeminal root employed. Controlled ventilation may be performed by
in the pons. squeezing the bag, or replacing it with a suitable ventila-
Treatment includes: tor. A variety of volatile agents may be used in the vapo-
drugs, including carbamazepine (beneficial in 70% risers, the calibration scales of which may be changed
of cases), phenytoin, clonazepam, tricyclic antide- accordingly. They are specially adapted to contain more
pressant drugs, gabapentin and simple analgesics. liquid (50ml), and are fitted with extendable feet. Halo-
trigeminal nerve blocks. thane, enflurane or isoflurane is traditionally used in the
surgical decompression of the trigeminal nerve. upstream vaporiser, and trichloroethylene (to compen-
destructive lesions, e.g. with alcohol injection, radio- sate for the absence of N2O) in the downstream one.
frequency coagulation or surgical destruction.
Anaesthesia dolorosa may ensue. Trismus. Spasm of the masseter muscles, resulting in
acupuncture. impaired mouth opening (lockjaw).
Zakrzewska JM, McMillan R (2011). Postgrad Med J; 87: Causes may be:
41016 local:
See also, Gasserian ganglion block - abscess/infection around jaw, teeth, etc.
- mandibular fractures.
Trigger points. Areas in muscle or fascia in which - parotitis.
mechanical stimulation may cause muscle pain, weak- - temporomandibular joint disease.
ness and/or local twitching. May be latent (tender when systemic:
palpated) or active (painful at rest or on exertion or - tetanus.
stretching). Pain is often referred, giving rise to - strychnine poisoning.
580 Trisodium edetate

- phenothiazines. TS, see Trauma score

- CVA.
- hysteria. TSR, see Time to sustained respiration
May occur after administration of suxamethonium (e.g.
masseter spasm or in dystrophia myotonica). TT, Thrombin time, see Coagulation studies
Anaesthesia in the presence of trismus is as for airway
obstruction and difficult intubation. Injection of local TTP, see Thrombotic thrombocytopenic purpura
anaesthetic into the masseter muscle may relieve the
spasm. Tuberculosis (TB). Infection with the acid- and alcohol-
See also, Intubation, difficult fast bacillus Mycobacterium tuberculosis that most com-
monly affects the lungs and lymph nodes, although any
Trisodium edetate. Chelating agent used in severe tissues may be affected. Declined in incidence through
hypercalcaemia. Rarely used because of the risk of renal much of the twentieth century until an increase in the
damage. 1980s/90s, thought to be related to increases in world
Dosage: up to 70mg/kg iv over 23h, daily.
population, population movement, resistance to antitu-
Side effects: hypocalcaemia, nausea, diarrhoea, pain
berculous drugs (itself related to poor compliance with
on injection, renal impairment. treatment) and HIV infection, with which it is often
associated. It has been estimated that one-third of the
TRISS, see Trauma revised injury severity score worlds population is infected with TB. In the UK, it is
Tropical diseases. Many diseases are restricted to tropi- still largely restricted to migrants from developing coun-
cal and subtropical regions. Several are considered trop- tries, immunosuppressed patients and the homeless.
Classified into:
ical because they have been largely eradicated in
primary TB: occurs in patients not previously
developed countries, but may be imported by travellers.
Anaemia and malnutrition are common features. Anaes- infected (i.e. tuberculin-negative). Following a mild
thetic involvement may be related to ICU management inflammatory reaction at the site of infection (e.g.
or perioperative care. lung or GIT), infection spreads to the regional
Examples include: lymph nodes. The lesions usually heal and calcify
malaria.
without further sequelae, but occasionally active
diarrhoeal illness (e.g. typhoid, giardiasis, amoebic
organisms enter the bloodstream. This may cause
dysentery, cholera): cause electrolyte imbalance and haematogenous lesions, especially involving the
dehydration. lungs, bones, joints and kidneys. Rarely, a tubercu-
amoebiasis: may cause systemic illness, diarrhoea,
lous focus ruptures into a vein, causing acute dis-
bowel perforation and hepatic abscesses. Treatment semination (acute miliary TB).
may include surgery. Patients may be asymptomatic, with evidence of
hydatid disease: parasites may form cysts, usually in
infection provided by routine CXR or conversion of
the liver but occasionally in the lungs, heart, kidneys the tuberculin test from negative to positive. Primary
or brain. Spillage of hydatic fluid intraoperatively infection may be accompanied by a febrile illness.
may cause anaphylaxis. Occasionally primary TB is progressive and may
leprosy: chronic infective granulomatous disease
cause pleurisy, pleural effusions and meningitis.
postprimary pulmonary TB: occurs in patients
affecting peripheral nerves, skin and upper respira-
tory tract mucosa. Patients may be taking cortico- previously infected (i.e. tuberculin-positive).
steroids. Areas of skin may be anaesthetic. Usually affects the upper lobes. Reactivation (or
trypanosomiasis:
reinfection) causes a brisk inflammatory response;
- African (sleeping sickness): parasitic CNS inva- resultant fibrosis tends to limit the spread of infec-
sion with confusion, coma and death. Myocarditis tion. Regional lymph node involvement is therefore
and hepatitis may occur. unusual. Again the lesion usually heals, but it may
- American (Chagas disease): meningoencephali- rupture into a bronchus, causing cavitation. It may
tis, hepatic failure, cardiomyopathy and achalasia then spread throughout the lung, or rarely via the
of the cardia may occur. bloodstream, causing miliary TB.
Other diseases much more common in developing Usually insidious in onset, features include pro-
countries include: ductive cough, haemoptysis (early) and dyspnoea
syphilis.
(late). Pleuritic pain may be caused by pleurisy or
tetanus.
pneumothorax.
hepatitis.
Diagnosis includes history and examination, CXR,
HIV infection.
examination and culture of sputum for acid-fast bacilli
TB.
(poor sensitivity), tuberculin test (poor specificity), and
poliomyelitis.
interferon-gamma release assays (e.g. T-SPOT).
Management includes isolation, testing of contacts
rabies.
[Carlos Chagas (18791934), Brazilian physician] and antituberculous drug therapy (isoniazid, rifampi-
cin, pyrazinamide, ethambutol, streptomycin, capreo-
Tropisetron hydrochloride. 5-HT3 receptor antagonist, mycin, cycloserine, azithromycin, clarithromycin
licensed as an antiemetic drug in chemotherapy-induced and 4-quinolones). Programmes of supervised drug
nausea and vomiting. Similar to ondansetron but with administration have been instituted in many coun-
longer duration of action. tries to improve compliance. Multidrug resistance
Dosage: 25mg orally or iv. occurs in about 25% of cases in China, India and
Russia. Extensively resistant and completely drug-
Trypanosomiasis, see Tropical diseases resistant strains of TB are now emerging.
 Twilight sleep 581

Ideally, single-use anaesthetic and respiratory equip- TURP, see Transurethral resection of the prostate
ment should be used for patients with active TB. Cases
of spread to other patients have been reported in the TURP syndrome. Syndrome following TURP, thought
ICUs of UK hospitals. to occur in a mild form in up to 8% of cases but severe
Lawn SD, Zumla AI (2011). Lancet; 378: 5772 in only 12%. Caused by absorption of irrigating fluid
See also, Contamination of anaesthetic equipment (usually hypotonic glycine 1.5%) through open prostatic
vessels or from the extraprostatic tissues. Has also been
Tubocurarine chloride (D-tubocurarine chloride). Non- reported following other procedures involving irrigation
depolarising neuromuscular blocking drug, isolated with electrolyte-free solutions, e.g. percutaneous litho-
from curare in 1935. Its name is derived from the early tripsy and hysteroscopic endometrial resection.
classification of curare according to the means of storage Symptoms are caused by intravascular volume over-
(tubes refers to tubular bamboo canes). Commonly load, dilutional hyponatraemia and intracellular oedema.
caused histamine release and ganglion blockade, with Additional effects are caused by glycine and its metabo-
vasodilatation and hypotension. Severe anaphylaxis is lites, e.g. ammonia.
rare. Excreted mainly in the urine, but 30% via the liver. Features include bradycardia, hypotension (often
Discontinued in the UK since 1996. preceded by hypertension), angina, dyspnoea, visual and
mental changes, convulsions and coma. Severity depends
Tumescent anaesthesia. Method of infiltrating large on the volume of irrigant absorbed (e.g. lethargy and
volumes of dilute local anaesthetic agent into tissues nausea after 12 litres glycine; severe symptoms after >
until they become swollen, used mainly for plastic 2 litres) and the rate of absorption (faster onset if
surgery, e.g. liposuction. Typical solutions contain 0.05 absorbed via prostatic veins; slower if absorbed from
0.1% lidocaine 1:10000001:2000000 adrenaline; the extravascular tissues). Features may occur during
bicarbonate, steroids and antibiotics have also been surgery, or postoperatively.
added. The volumes may exceed several litres, leading to Preventive measures:
the risk of local anaesthetic toxicity and fluid overload. limiting the height of the reservoir bag of irrigant
PE and surgical complications have also been reported. to 60cm, and using low-pressure irrigation systems.
May be used alone or in combination with sedation or limiting the volume of irrigant infused.
general anaesthesia. restriction of resection time to 60min.
resection by experienced surgeons.
Tumour lysis syndrome. Condition in which medical avoidance of hypotonic iv fluids.
treatment of an aggressive malignancy (typically haema- Measures to aid its detection:
tological) causes sudden release of intracellular contents, use of spinal or epidural anaesthesia, allowing
resulting in severe and potentially life-threatening respiratory monitoring and detection of mental
hyperkalaemia, hypocalcaemia, hyperphosphataemia, changes.
lactic acidosis and hyperuricaemia. May occasionally CVP measurement for patients at risk.
occur spontaneously. Individual electrolyte abnormali- monitoring of plasma sodium concentration (more
ties are managed along standard lines. Good hydration than a 10mmol/l drop indicates > 2 litres irrigating
and prevention of renal uric acid precipitation by alka- fluid absorbed) or osmolality gap.
lisation of the urine (e.g. with bicarbonate or acetazol- monitoring of tracer substances, e.g. ethanol 10%
amide) and allopurinol administration may prevent added to the irrigating fluid and measured in the
acute kidney injury from developing. blood or breath (over 0.6mg/ml indicating > 2 litres
Howard SC, Jones DP, Pui CH (2011). N Engl J Med; fluid absorbed).
364: 184454 Management: as for hyponatraemia, convulsions,
raised ICP, acidosis. Diuretics (e.g. furosemide) are
Tumour necrosis factor, see Cytokines used if pulmonary oedema is present. Hypertonic
saline solutions have been used to expand circulating
Turbulence, see Flow volume. Vasopressor drugs may be required.
Hahn RG (2006). Br J Anaesth; 96: 820
Turners syndrome (Gonadal dysgenesis). Congenital
absence of the second X chromosome. Sufferers are Twilight sleep. Obsolete technique formerly popular in
female in appearance, but with primary amenorrhoea obstetrics as a means of easing labour pain and reducing
and immature genitalia. Other features include short subsequent recall. Injection of morphine and hyoscine
stature, short webbed neck and high palate; thus tracheal was followed by hyoscine alone. Apart from causing
intubation may be difficult. Renal abnormalities, hyper- maternal restlessness, it often caused neonatal respira-
tension and coarctation of the aorta may occur. tory depression.
[Henry H Turner (18921970), US physician] See also, Obstetric analgesia and anaesthesia
 U
U wave. Low-amplitude positive deflection following and the ulnar side of the hand. Paralysis of the small
the T wave of the ECG, possibly representing slow repo- muscles of the hand results in clawing.
larisation of papillary muscle. Seen best in the right chest May be blocked at various sites.
leads and at slow heart rates but not always present. See Brachial plexus block; Elbow, nerve blocks; Wrist,
Made more prominent by hypokalaemia. Reversed nerve blocks
polarity may indicate myocardial ischaemia.
Ultrafiltration. Process by which water is removed from
UD interval. During caesarean section, the time the blood during various forms of dialysis. Water passes
between incision of the uterus and delivery of the baby. across the semipermeable membrane as a result of posi-
As the interval increases, so fetal wellbeing is compro- tive pressure on the blood side of the membrane (e.g.
mised, probably due to disruption of placental blood the patients BP or use of a pump), negative pressure
flow. Fetal acidosis is thought to be unlikely at UD on the other side, or an osmotic gradient from use of
intervals of 1.53min. dialysate fluid. Rates of up to 1.5l/h may be removed
See also, ID interval by intermittent isolated ultrafiltration (IIUF) in which
a haemodialysis circuit is used but without dialysate,
UEMS, European Union of Medical Specialties (Union but more controlled removal of fluid (100150ml/h)
Europenne des Mdecins Spcialistes; UEMS), see may be achieved in slow continuous ultrafiltration
European Board of Anaesthesiology (SCUF), with greater haemodynamic stability and
without the need for fluid replacement. Effective for
treatment of decompensated heart failure. Combination
Ulcerative colitis, see Inflammatory bowel disease with dialysis may also be employed (SCUF-D) but
removal of larger molecules is less efficient than with
Ulnar artery. A terminal branch of the brachial artery, continuous haemofiltration.
arising at the apex of the antecubital fossa. Lies superfi-
cial to flexor digitorum profundus and deep to the super- Ultra-rapid opioid detoxification, see Rapid opioid
ficial flexors in the forearm. Then passes deep to flexor detoxification
carpi ulnaris, lateral to the ulnar nerve. At the wrist, it
lies between flexor carpi ulnaris and flexor digitorum Ultrasound (u/s). Sound waves of frequency above the
profundus tendons. Passes anterior to the flexor reti- normal upper limit of human hearing (> 20kHz). Origi-
naculum to end lateral to the pisiform bone. Branches nally developed for use in industry, now has a wide range
supply the deep extensor and ulnar muscles of the of medical applications including: soft tissue imaging;
forearm, the wrist and elbow joints and the deep and assessment of blood flow; tumour ablation; and fragmen-
superficial palmar arches. May be cannulated for arterial tation of renal and biliary calculi (lithotripsy).
BP measurement but the radial artery is preferred Principles of u/s imaging:
because the latter is thought to be associated with a a transducer uses a piezoelectric material to convert
lower risk of digital ischaemia. electrical energy into intermittent pulses of high
See also, Allens test frequency (315MHz) sound waves.
as the pulses travel through the tissues they are
Ulnar nerve (C7T1). A terminal branch of the medial partially reflected at tissue interfaces; these echoes
cord of the brachial plexus. Descends on the medial side are detected by the transducer (which alternates
of the upper arm, first in the anterior, and later in the between emitting and receiving modes). The degree
posterior compartment. Passes behind the medial epi- of reflection depends on the difference in acoustic
condyle to enter the forearm; descends on the medial impedance between tissues; acoustic gel must there-
side deep to flexor carpi ulnaris, medial to the ulnar fore be applied to the transducer to ensure that
artery. Divides into cutaneous branches 5cm above the there is no air (which has high acoustic impedance)
wrist. Dorsal and palmar cutaneous sensory branches between the transducer and the skin.
supply the skin of the ulnar half of the hand and palm, the intensity and time delay of reflected signals are
and the medial 1 1 2 fingers. Also supplies the elbow joint, interpreted and displayed. The simplest system uses
flexor carpi ulnaris and the ulnar side of flexor digitorum a single beam and displays the amplitude of
profundus. In the hand, it supplies the hypothenar reflected echoes as a function of depth, either as a
muscles, interossei, medial two lumbricals and adductor series of lines or shaded spots (amplitude or A
pollicis. mode). If pulses are emitted in rapid succession,
The nerve may be damaged by trauma to the elbow, detailed assessment of movement at tissue inter-
or if the elbows rest on unpadded surfaces during pro- faces (e.g. a heart valve) can be made (movement
longed anaesthesia in the supine position. Injury results or M mode). If an array of piezoelectric elements is
in loss of cutaneous sensation on the ulnar 1 1 2 fingers used to produce a series of pulses along a plane, a

583
584 Unconsciousness

two-dimensional real-time image may be produced temperature of a perfect gas. Equals 8.3144J/K/mol
(brightness or B mode); this is the mode utilised (1.987cal/K/mol).
most commonly for soft-tissue imaging.
transducer probes may have linear, curvilinear or Uraemia. Strictly, a plasma urea exceeding 7.0mmol/l;
phased arrays. Linear arrays tend to emit at a higher the term was formerly used to describe the clinical
frequency than curvilinear arrays (e.g. 10 vs. 3MHz), picture in renal failure.
delivering greater resolution, but poorer tissue pen-
etration; they are therefore suitable for imaging Urapidil. 1-Adrenergic receptor antagonist with central
superficial structures, e.g. for internal jugular venous 5-HT1A receptor agonist activity. Causes reduction in
cannulation. Curvilinear arrays produce a signal preload and afterload by causing arterial and vasodilata-
that spreads out within the body, allowing imaging tion with little reflex tachycardia. Has little effect on the
of deeper and larger structures (e.g. fetus). Phased coronary vessels. Although studied experimentally with
arrays deliver electronically angulated beams that promising results, it is not available commercially.
can be swept through the body, providing rela-
tively large sector images from a small probe foot- Urea (NH2CONH2). A product of hepatic amino acid
print (e.g. allowing passage of the beam between breakdown to ammonia. Produced in the urea cycle from
ribs for echocardiography). hydrolysis of arginine; ornithine is also produced and
Clinical applications: reacts with carbamoyl phosphate and then aspartate to
diagnostic and fetal imaging. reform arginine. Ammonia and CO2 are introduced into
echocardiography. the cycle by carrier molecules. Freely filtered at the
assessment of blood flow (using the Doppler effect): glomerulus of the nephron; about 50% is reabsorbed in
e.g. in cardiac output measurement; transcranial the proximal tubule. Excretion in the urine accounts
Doppler ultrasound; assessing patency of peripheral for 85% of daily nitrogen excretion. Normal plasma
vessels. levels: 2.57.0mmol/l. Increased production (e.g. from
regional anaesthesia: increased protein intake or catabolism) or dehydration
- real-time guided needle placement for blockade may increase plasma urea slightly, but levels above
of peripheral nerves and nerve plexuses. 13mmol/l usually represent impaired renal function.
- identification of vertebral anatomy and estima- Creatinine measurement or clearance studies may aid
tion of the depth of the epidural space during diagnosis.
central neuraxial blockade. See also, Nitrogen balance
confirmation of normal anatomy and/or real-time
guided needle placement during central venous Urinalysis, see Urine
cannulation (recommended by NICE).
When used to guide needle placement, the needle may Urinary retention. Inability to pass urine. May be either
either be viewed in-plane (needle shaft parallel to the acute or chronic (the latter often leading to retention
long axis of the transducer) or out-of-plane (needle with overflow). May occur with prostatic enlargement,
perpendicular to the long axis of the transducer); the urethral stricture, spinal or epidural anaesthesia (includ-
former allows continuous viewing of the entire needle ing use of spinal opioids), after abdominal or pelvic
shaft and tip, while the latter allows only the portion of surgery and following administration of drugs with anti-
the shaft crossing the beam to be seen. The preferred cholinergic effects. Neurological causes are rarer but
approach depends on the structures being imaged and include spinal cord injury, cauda equina syndrome,
related anatomy. GuillainBarr syndrome and autonomic neuropathies,
Marhofer P, Harrop-Griffiths W, Willschke H, Kirchmair e.g. diabetic. Signs include a full bladder, tender to palpa-
L (2010). Br J Anaesth; 104: 67383 tion and dull to percussion. Can be confirmed with
See also, Doppler effect; Imaging in intensive care; bladder ultrasound. May cause agitation and confusion
Transoesophageal echocardiography postoperatively; can cause hypertension, tachycardia
and raised ICP in unconscious patients. May cause acute
Unconsciousness, see Coma pyelonephritis.
Urinary catheterisation (either urethral or, occasion-
Units, SI. System of units (Systme Internationale ally, suprapubic) may be required if encouragement is
dUnits) introduced in 1960 by the General Conference unsuccessful.
of Weights and Measures (Confrence Gnrale des See also, Oliguria
Poids et Mesures) and based on the metric system. There
are seven base (or fundamental) units: metre, second, Urinary tract infection (UTI). Most common nosoco-
kilogram, ampere, kelvin, candela and mole. Derived mial infection seen in critically ill patients and a common
units include the newton, pascal, joule, watt and hertz. cause of generalised sepsis. In hospitals, almost always
Standard terms denote multiples and divisions of units, associated with urinary catheterisation, with the risk
e.g. kilo- (103), mega- (106), giga- (109), tera- (1012) increasing the longer the catheter is in place. Gram-
and peta- (1015); and milli- (103), micro- (106), negative organisms (e.g. Escherichia coli, pseudomonas)
nano- (109), pico- (1012) and femto- (1015) are commonly involved, gaining entry to the bladder
respectively. either through the catheters lumen or along its surface.
Manohin A, Manohin M (2003). Eur J Anaesth; 20: Diagnosis is confirmed by the presence of white blood
25981 cells and > 100000 organisms/mm3 on urine microscopy.
Urinary catheterisation should only be performed
Universal gas constant. Constant (symbol R) in the when necessary, aseptic technique used (often accompa-
ideal gas law equation PV = nRT, where P = pressure, nied by a single prophylactic dose of gentamicin) and
V = volume, n = number of moles of gas and T = the catheter removed as soon as possible. Treatment of
 Utstein style 585

established UTI is with antibacterial drugs according to cardiovascular regulation and a potential role for uro-
the results of urine culture. tensin II antagonists have been suggested.
Hooton TM, Bradley SF, Cardenas DD, etal (2010). Clin McDonald J, Batuwangala M, Lambert DG (2007).
Infect Dis; 50: 62563 J Anesth; 21: 37889

Urine. Liquid containing urea and other waste products, Uterus. Pear-shaped pelvic organ, 7.5cm long, 5cm
excreted by the kidneys. Normal output in temperate wide and 2.5cm thick when non-gravid. Divided into the
climates is 8002500ml/day. Coloured yellowish by the upper body and lower cervix, separated by the isthmus.
pigments urochrome and uroerythrin, it darkens on Separated from the bladder anteriorly by the uterovesi-
standing by oxidation of urobilinogen to urobilin (colour cal pouch, and from the rectum posteriorly by the utero-
does not necessarily reflect urines concentration). rectal pouch. The broad ligaments lie laterally.
Coloured red by haemoglobin or myoglobin and purple Blood supply is from the uterine artery, a branch of
in porphyria. Specific gravity is normally 1.0021.035. the internal iliac artery. The uterine vein drains into the
Osmolality may range between 30 and 1400mosmol/kg, internal iliac vein.
depending on fluid and hormonal status. pH is usually Nerve supply:
below 5.3. Normally contains under 150mg protein/ sympathetic motor preganglionic fibres from T1L2
24h. Abnormal constituents include glucose, ketones, and parasympathetic motor preganglionic fibres
bilirubin, erythrocytes, large numbers of leucocytes from S24 via the paracervical plexus. Actions are
and casts. variable, depending on the stage of the menstrual
Urinalysis is usually performed using reagent sticks; cycle and pregnancy.
the reagents change colour according to the presence sensory fibres via sympathetic pathways, emerging
and amount of various normal and abnormal constitu- in the paracervical tissues and passing through the
ents in the sample. Specific gravity, electrolyte and solute hypogastric plexus to T1112, sometimes also to
content and pH can also be quantified. T10 and L1.
Despite the kidneys ability to concentrate the urine, Actions of drugs on the pregnant uterus:
a minimum of 500ml/day is required to eliminate urea -adrenergic receptor agonists, e.g. noradrenaline:
and other electrolytes. Oliguria is usually defined as less increase uterine tone and strength of contraction.
than 0.5ml/kg/h and may indicate hypovolaemia or -adrenergic receptor agonists, e.g. adrenaline, sal-
renal failure; anuria is complete cessation of urine flow butamol: decrease uterine tone and strength of con-
and may indicate obstruction or urinary retention in traction. Agonists specific for 2-receptors are used
addition. Polyuria occurs in diabetes insipidus, renal as tocolytic drugs to delay premature labour.
failure, diuretic therapy, diabetes mellitus (because of oxytocin and ergometrine: produce powerful con-
the osmotically active glucose load) and excessive water traction. Atosiban (oxytocin antagonist) causes
intake (water diuresis). uterine relaxation.
Urine output is routinely measured during critical prostaglandins PGE2 and PGF2: stimulate uterine
illness and major surgery, since it reflects tissue perfusion contraction.
and volume status of the circulation (assuming normal volatile inhalational anaesthetic agents: cause dose-
renal and cardiac function). Although renal blood flow related reduction of uterine tone.
is often reduced and circulating levels of vasopressin are iv anaesthetic agents, sedative and analgesic drugs,
high during surgery, urine output is usually maintained. neuromuscular blocking drugs, acetylcholinesterase
An hourly urine output of > 0.5ml/kg/h is regarded as inhibitors: no effect on uterine tone.
the minimum acceptable during critical illness or surgery others: acetylcholine, bradykinin, histamine and 5-
by most anaesthetists. HT increase contraction. Smooth muscle relaxants
See also, Nephron (e.g. amyl nitrite, GTN and papaverine) cause relax-
ation. Alcohol has a direct relaxant action and sup-
Urokinase. Enzyme extracted from male human urine, presses oxytocin secretion from the pituitary gland.
used as a fibrinolytic drug mainly for thrombolysis in the See also, Obstetric analgesia and anaesthesia
eye and arteriovenous shunts, although also indicated in
PE or DVT. Acts via activation of plasminogen. UTI, see Urinary tract infection
Dosage:
500025500 iu instilled into the shunt. Utstein style. Uniform system of reporting data for out-
PE/DVT: 4400iu/kg iv over 10min, then 4400iu/ of-hospital cardiac arrests, arising from a meeting of
kg/h for 1224h. representatives of international Resuscitation Councils
Side effects: nausea, vomiting, back pain. Allergic in Utstein Abbey on the Island of Mosteroy off Norway
reactions are rare. in June 1990. A second meeting (the Utstein II confer-
ence) in London the same year resulted in the publica-
Urotensin II. Peptide hormone found in fish and discov- tion of recommended guidelines for uniform reporting
ered in human tissues in 1999, with specific receptors in of such data, the Utstein style. This style has been
the heart and arterial vessels and CNS. Has extremely recommended for in-hospital CPR attempts, paediatric
potent vasoconstrictive properties that vary according to CPR, laboratory CPR research and trauma.
vessel type. Its role as a major mediator in metabolic and Dick WF, Baskett PJF (1999). Resuscitation; 42: 81100
 V
Vacuum insulated evaporator (VIE). Container for
storage of liquid O2 and maintenance of piped gas Pressure
Safety valve regulator
supply. An outer carbon steel shell is separated by a Outlet
vacuum from an inner stainless steel shell, which con-
tains O2. The inner temperature varies between 160 and Superheater
180C, at a pressure of 710 bar. Gaseous O2 is with-
drawn and heated to ambient temperature (and thus
expanded) as required (Fig. 161); a pressure regulator
Gas
distal to the superheater prevents pipeline pressure from
exceeding 4.1 bar. If pressure within the container falls Control valve
due to high demand, liquid O2 may be withdrawn, vapo-
rised in an evaporator and returned to the system,
restoring working pressure. If passage of heat across the
insulation causes vaporisation of liquid O2 and a rise in
Liquid Evaporator
pressure, gas is allowed to escape through a safety valve.
The contents are indicated by a weighing device incor-
porated into the chambers supports.
Howells RS (1980). Anaesthesia; 35: 67698

Vagus nerve. Tenth cranial nerve. Arises in the medulla

from the:
dorsal nucleus of the vagus (parasympathetic).
nucleus ambiguus (motor fibres to laryngeal, pha- Fig. 161Vacuum insulated evaporator
ryngeal and palatal muscles).
nucleus of the tractus solitarius (sensory fibres from
the larynx, pharynx, GIT, heart and lungs, including biliary tract, uterus, bladder, urethra, testes, larynx,
taste fibres from the valleculae). glottis, bronchial tree and carotid sinus. Also involved in
Leaves the medulla between the olive and inferior cer- the diving reflex.
ebellar peduncle, and passes through the jugular foramen Anticholinergic drugs antagonise vagal reflexes
of the skull. Descends in the neck within the carotid during surgery. Should they occur, surgical activity
sheath between the internal jugular vein and internal/ should cease, and atropine or glycopyrronium be admin-
common carotid arteries (see Fig. 113; Neck, cross- istered if necessary.
sectional anatomy, and Fig. 104a; Mediastinum). Passes
behind the root of the lung to form the pulmonary Valence. Capacity of an atom to combine with others in
plexus, then on to the oesophagus to form the oesopha- definite proportions; compared with that of hydrogen
geal plexus with the vagus from the other side. Both pass (value of 1). Dependent on the number of electrons in
through the oesophageal opening of the diaphragm to the outer shell of the atom; covalent bonds are formed
supply the abdominal contents and GIT as far as the when electrons are shared between different atoms, e.g.
splenic flexure (see Fig. 21; Autonomic nervous system). water: HOH.
Branches:
VALI, see Ventilator-associated lung injury
to the external auditory meatus and tympanic
membrane. Valproate/valproic acid, see Sodium valproate
to muscles of the pharynx and soft palate.
laryngeal nerves. Valsalva manoeuvre. Forced expiration against a closed
to cardiac, pulmonary and oesophageal plexuses. glottis after a full inspiration, originally described as a
to intra-abdominal organs. technique for expelling pus from the middle ear. In its
The vagi form a major part of the parasympathetic standardised form, 40mmHg pressure is held for 10s.
nervous system. Vagal reflexes causing bradycardia, Direct arterial BP tracings in normal subjects show
laryngospasm and bronchospasm may occur during four phases (Fig. 162):
anaesthesia. Intense stimulation may result in partial or phase I: increase in intrathoracic pressure expels
complete heart block or even asystole. Anal and cervical blood from thoracic vessels.
stretching (e.g. BrewerLuckhardt reflex) and traction phase II: decrease in BP due to reduction of
on the extraocular muscles (oculocardiac reflex) are par- venous return; activation of the baroreceptor reflex
ticularly intense stimuli, but it may also follow skin inci- causes tachycardia and vasoconstriction, raising
sion and stimulation (e.g. surgical) of the mesentery, BP towards normal.

587
588 ValtisKennedy effect

[Heyman H Samson, South African anaesthetist; Hafnia:

Latin name for Copenhagen]

Valves, see Adjustable pressure-limiting valves; Demand

Pulse rate

valves; Non-rebreathing valves

Valvular heart disease. Causes, features and anaes-

thetic management: as for congenital heart disease and
individual lesions. Valve replacement: as for cardiac
surgery. Many prosthetic valves are available in different
sizes, e.g. Silastic ball-and-cage, metal flaps and porcine
valves. Thrombosis may form on prostheses, hence the
I II III IV requirement for long-term anticoagulation. Patients
with prosthetic valves may also require prophylactic
antibiotics as for congenital heart disease.

Van der Waals equation of state. Modification of the

BP

ideal gas law, accounting for the forces of attraction

between gas molecules, and also the volume of the
Increased molecules:
intrathoracic RT = ( P + a /V 2 )(V b)
pressure
where R = universal gas constant
Time T = temperature
P = pressure exerted by the gas
Fig. 162 Normal Valsalva response (see text) V = molar volume of gas
a and b = correction terms.
[Johannes van der Waals (18371923), Dutch physicist]
phase III: second drop in BP as intrathoracic pres-
sure suddenly drops, with pooling of blood in the Van der Waals forces. Weak attractive forces between
pulmonary vessels. neutral molecules and atoms, caused by electric polarisa-
phase IV: overshoot, as compensatory mechanisms tion of the particles induced by the presence of other
continue to operate with venous return restored. particles.
Increased BP causes bradycardia. See also, Van der Waals equation of state
Abnormal responses:
square wave response, seen in cardiac failure, con- Van Slyke apparatus. Device used to measure blood gas
strictive pericarditis, cardiac tamponade and valvu- partial pressures. O2 and CO2 are released into a burette
lar heart disease, when CVP is markedly raised. BP from the blood by addition of a liberating solution. Each
rises, remains high throughout the manoeuvre and gas in turn is converted to a non-gaseous substance by
returns to its previous level at the end. chemical reaction, and the pressure drop in the burette
autonomic dysfunction, e.g. autonomic neuropathy, measured for each. The same reagents may be used as
drugs. BP falls and stays low until intrathoracic in the Haldane apparatus.
pressure is released. Pulse rate changes and over- [Donald D van Slyke (18831971), US chemist]
shoot are absent. See also, Carbon dioxide measurement; Gas analysis;
an exaggerated reduction in BP may be seen in Oxygen measurement
hypovolaemia, e.g. during IPPV.
Useful as a bedside test of autonomic function. Concur- Vancomycin. Glycopeptide and antibacterial drug
rent ECG tracing allows accurate measurement of with bactericidal activity against aerobic and anaero-
changes in heart rate. The manoeuvre may be useful bic Gram-positive bacteria (including multi-resistant
in evaluating heart murmurs, and may be successful in staphylococci). Usually reserved for severe infections,
terminating SVT (because of increased vagal tone in resistant organisms or penicillin allergy. Despite this
phase IV). restriction in use, resistant species of vancomycin-
[Antonio Valsalva (16661723), Italian anatomist] resistant Staphylococcus aureus and entercocci are
increasingly seen. Not absorbed orally.
ValtisKennedy effect. Shift to the left of the oxyhae- Dosage:
moglobin dissociation curve during blood storage, origi- usual starting dose of 1g iv bd, subsequently
nally described in 1954 for acidcitratedextrose storage. adjusted according to plasma levels; the pre-dose
The shift reflects progressive depletion of 2,3-DPG. (trough) level should be 1015mg/l and the peak
[DJ Valtis, Greek physician; Arthur C Kennedy (1922 (if measured) should be <30mg/l 2h post-dose.
2009), Glasgow physician] May also be given by continuous 24-h infusion,
delivering more consistent plasma levels; dosing is
Valveless anaesthetic breathing systems. Anaesthetic then guided by a random plasma level.
breathing systems designed to eliminate resistance due 125250mg orally qds, in pseudomembranous
to adjustable pressure-limiting valves. In the Samson colitis (for 710 days).
system, the valve is replaced by an adjustable orifice; in Side effects: renal impairment, ototoxicity, blood dys-
the Hafnia systems, expired gases pass through a port, crasias, nausea, fever, allergic reactions, phlebitis.
assisted by an ejector flowmeter. Rapid infusion may cause hypotension, urticaria,
 Vaporisers 589

pruritus, flushing (red man syndrome), dyspnoea included a large mass of copper as a heat sink,
and cardiac arrest. hence its name.
See also, Infection control - have high resistance, so unsuitable for positioning
in a circle system.
Vancomycin-resistant enterococci, see Infection - performance is not affected by whether ventila-
control; Vancomycin tion is spontaneous or controlled.
- include the Tec series of vaporisers. Features of
VAP, see Ventilator-associated pneumonia the Mark 4 over the Mark 3 (Fig. 163b):
- flow of liquid agent into the delivery line is pre-
Vaporisers. Devices for delivering accurate and safe vented if the vaporiser is inverted.
concentrations of volatile inhalational anaesthetic agents - interlock system prevents use of more than one
to the patient. vaporiser at a time, if mounted side by side.
Classified into: - fitted with the key filling system (not fitted to all
plenum vaporisers (plenum = chamber): widely Mark 3 models).
used in modern anaesthesia despite their cost and Features of the Mark 5 over the Mark 4:
complexity, because of their reliability, safety fea- - increased capacity.
tures and accuracy: - improved filling system.
- gas passes through the vaporiser under pressure Features of the Mark 6 (desflurane vaporiser):
at the back bar of the anaesthetic machine. - cannot use the above mechanism because des-
- in most modern types (e.g. Tec [temperature- fluranes BP is very close to room temperature
compensated] vaporisers) fresh gas is divided by and therefore small variations in the latter
the control dial into two streams, one of which result in large changes in SVP.
enters the vaporisation chamber, becomes fully - requires an electrical power supply for the
saturated with agent and rejoins the other stream heating elements and control mechanisms.
at the outlet (Fig. 163a). The ratio of the two - the fresh gas does not enter the vaporising
streams (splitting ratio) determines the final chamber, but passes along a separate path to
delivered concentration (N.B. a different mecha- mix with pure desflurane vapour, leaving the
nism exists for the Tec 6 desflurane vaporiser: see chamber at the outlet (produced by heating the
below). In older vaporisers the delivered concen- vaporising chamber to 39C, thus ensuring com-
tration was also affected by other factors (see plete vaporisation).
below). In the obsolete copper kettle type, a - fresh gas encounters a flow restriction within
separate supply of O2 was passed through the the vaporiser, causing back pressure which
vaporiser, becoming fully saturated. It was then varies according to fresh gas flow.
added to the main fresh gas flow, at a rate calcu- - a system of pressure transducers and internal
lated according to desired final concentration circuitry is used to monitor and adjust the per-
and vaporiser temperature. The original design formance to produce a consistent output even
if fresh gas flow alters (detected by a change in
back pressure). Internal switches cut out the
system if temperature increases above 57C or
if the vaporiser is tilted or becomes empty.
Features of the Mark 7 over the Mark 5 (all
(a) Adjustable dial/valve modern agents but desflurane):
- more accurate and easily controllable output
throughout different flow ranges.
- improved filling options and protection against
spillage and contamination.
draw-over vaporisers: despite their variable output,
Inlet Outlet
often preferred in the battlefield (e.g. triservice
apparatus) and developing countries because they
are cheap, simple and portable:
Bimetallic strip
- gas is drawn into the vaporising chamber by the
patients inspiratory effort.
- resistance must be low.
- performance is affected by minute ventilation, the
output falling as ventilation increases.
Wick - may be suitable for use within circle systems, e.g.
Goldman vaporiser (Fig. 163b), a small, light,
uncompensated device with a glass container
(originally adapted from a motor vehicle fuel
pump). Similar vaporisers were designed by
Reservoir of volatile agent
McKesson and Rowbotham, the latters contain-
ing a wire gauze wick.
Fig. 163 (a) Principles of modern Tec vaporiser (considerably
simplified). When the dial/valve is adjusted, it alters the splitting ratio
- also used for draw-over techniques, e.g.
of the gas that passes through the two paths shown. When it is in the (Fig. 163b):
off position, all the gas passes via an additional route through the top - EMO (Epstein and Macintosh of Oxford)
(not shown) that bypasses these two paths completely. Pale arrows: diethyl ether inhaler: large vaporiser, incorpo-
no volatile agent vapour; dark arrows: containing vapour. rating a large vaporisation chamber, a water
590 Vaporisers

(b)

Fig. 163 (Continued) (b) Classic types of vaporiser: (i) Tec Mark 2; (ii) Tec Mark 3; (iii) Tec Mark 4; (iv) Goldman; (v) EMO; (vi) OMV (see text). (N.B.
the external appearance of the Tec Mark 5 and onwards did not change significantly from that of the Mark 4)
 Vasculitides 591

jacket for a heat sink and a temperature- consistently. Draw-over vaporisers are more effi-
compensating fluid-filled bellows at the outlet. cient at lower gas flows.
- OMV (Oxford miniature vaporiser): small pumping effect.
uncompensated device, containing a water-filled For vaporisers in series: contamination of the second
heat sink (with antifreeze). Contains wire wicks; with vapour from the first may occur if both are turned
may thus be emptied of one agent, flushed and on simultaneously. Although this cannot occur with
refilled with another. Different calibration modern vaporisers, for other types the one containing
scales may be fixed to the control valve for the the less volatile agent (i.e. with lower SVP) should be
various agents. A modified form is used in the placed upstream, because:
triservice apparatus. it requires proportionally more of the fresh gas flow
- obsolete types, used formerly for obstetric than the vaporiser containing the more volatile
analgesia: agent, and would thus receive more contaminant if
- Emotril (Epstein and Macintosh of Oxford/ placed downstream.
Trilene) trichloroethylene apparatus: incorpo- the more volatile agent, being easier to vaporise,
rated within a metal box. would attain higher (and thus potentially danger-
- Cardiff methoxyflurane inhaler: free-standing ous) concentrations than those set if it contami-
on a base. nated the vaporiser designed for a less volatile
systems involving addition of liquid volatile agent agent.
directly to the fresh gas stream: Vaporisers have been associated with many hazards, and
- require delivery of liquid agent at a rate calcu- require regular servicing.
lated automatically to produce the desired [Heinrich Drger (18471917), German engineer; Victor
concentration. Goldman (19031993), London anaesthetist; Hans G
- incorporated into computerised anaesthetic Epstein (19092002), Berlin-born Oxford physicist]
machines. See also, Altitude, high
- combined with a carbon filter/evaporator system
that fits into the patients breathing system, con- Vapour. Matter in the gaseous state below its critical
serving and recycling ~90% of the administered temperature; i.e. its constituent particles may enter the
agent. Have been used for sedation on ICU liquid state. As liquid vaporises, heat is required (latent
without the need for anaesthetic machines. heat of vaporisation); as vapour condenses, an equal
Factors affecting the delivered concentration: amount of heat is produced. These processes occur con-
splitting ratio (plenum vaporisers). tinuously above the surface of a liquid at equilibrium.
SVP of the volatile agent: equals the partial pres- See also, Vapour pressure
sure of the agent within the vaporiser. Agents with
high SVP (e.g. diethyl ether) vaporise more readily Vapour pressure. Pressure exerted by molecules escap-
than those with low SVPs, e.g. methoxyflurane. ing from the surface of a liquid to enter the gaseous
temperature of the liquid: affects the SVP. As liquid phase. When equilibrium is reached at any temperature,
vaporises, latent heat of vaporisation is lost, and the number of molecules leaving the liquid phase equals
temperature and thus SVP fall. Delivered concen- the number entering it; the vapour pressure now equals
tration of agent would therefore fall if not for SVP. Raising the temperature of the liquid increases the
temperature compensation devices, e.g.: molecules kinetic energy, allowing more of them to
- bimetallic strip at the outlet (Tec Mark 2) or escape and raising the vapour pressure. When SVP
inlet (subsequent Tec models) of the vaporisation equals atmospheric pressure, the liquid boils.
chamber.
- fluid-filled bellows at the gas outlet, e.g. EMO Vaptans, see Vasopressin receptor antagonists
inhaler (see below); expands as temperature rises.
- longitudinally expanding metal rod at the gas Variance. Standard deviation squared. Thus an indicator
outlet, e.g. Drger models. of spread of values within a sample. Although standard
Temperature loss is reduced by providing heat sinks deviation is commonly used when describing data, many
of metal (e.g. Tec) or water (EMO). Older vaporis- statistical calculations employ its square, hence the use
ers incorporated heating devices or thermometers of variance as a meaningful term (e.g. analysis of vari-
to allow adjustment as temperature changed. ance, ANOVA).
surface area of the gas/liquid interface: increased See also, Statistics
with:
- wicks and baffles, e.g. most plenum vaporisers VAS, Visual analogue scale, see Linear analogue scale
(see below). Wicks maintain surface area
despite gradual emptying of the vaporiser (level Vascular access, see Central venous cannulation; Intra-
compensation). venous fluid administration
- a cowl to direct gas flow on to or into the liquid
(e.g. the original Boyles bottle). Vascular resistance, see Pulmonary vascular resistance;
- production of many tiny bubbles with a sintered Systemic vascular resistance
brass or glass diffuser, e.g. copper kettle-type
vaporisers. Vasculitides. Group of conditions characterised by
fresh gas flow: the output of older devices varied inflammation of blood vessels. All except giant cell
considerably with gas flow (e.g. the Tec Mark 2 arteritis are uncommon and associated with connective
was supplied with charts showing the delivered tissue diseases or drug hypersensitivity. Diagnosis
versus the set concentrations at various flow requires biopsy, which often shows granuloma formation
rates); modern plenum vaporisers perform more associated with vessel inflammation.
592 Vasoactive intestinal peptide

Classification: Used to reduce SVR and thus:

group 1: systemic necrotising arteritis of small/ systemic BP, e.g. in hypotensive anaesthesia, hyper-
medium arteries: tensive crisis, pre-eclampsia. Their effect is some-
- polyarteritis nodosa. times offset by reflex tachycardia.
- Kawasakis disease. afterload and ventricular work, e.g. in cardiac
- Wegeners granulomatosis. failure, shock. Increase stroke volume and reduce
- connective tissue disease-associated arteritis. myocardial O2 demand.
group 2: small vessel vasculitis: Also reduce preload via venous dilatation. Also used to
- HenochSchnlein purpura: usually occurs in reduce pulmonary vascular resistance in pulmonary
childhood following an upper respiratory tract hypertension, although the systemic circulation is usually
infection. Features include fever, headache, affected too.
macular/urticarial rash becoming purpuric, over See also, Antihypertensive drugs; Inotropic drugs
the buttocks and limbs. Inflammatory synovitis is
common. Focal glomerulonephritis may lead to Vasomotor centre. Group of neurones in the ventro-
nephrotic syndrome and, rarely, renal failure. lateral medulla, involved in the control of arterial BP.
- mixed cryoglobulinaemic vasculitis. Projects to sympathetic preganglionic neurones in the
- connective tissue disease-associated vasculitis. spinal cord. Normal continuous discharge causes partial
group 3: giant cell arteritis/large artery vasculitis: contraction of vascular smooth muscle (vasomotor tone)
- temporal arteritis: usually affects the elderly and and resting sympathetic stimulation of the heart.
often associated with polymyalgia rheumatica. Discharge is increased by:
Headache, often localised, is the predominant chemoreceptor discharge.
symptom. Blindness may result if corticosteroids pain, emotion.
are not given promptly. hypoxia (causes direct stimulation initially, but
- Takayasus arteritis: rare large vessel arteritis depression follows).
affecting young women. Affects the aorta and its Discharge is decreased by:
branches, causing inflammation and then stenosis baroreceptor discharge.
of affected vessels. Features include cerebro lung inflation.
vascular insufficiency (fainting, dizziness) and prolonged pain, emotion.
reduced peripheral pulses. Treatment depends on Thus responds to hypotension (reduced baroreceptor
the underlying condition but usually includes discharge) by increasing sympathetic activity.
immunosuppressive drugs. Dorsal and medial neurones functionally constitute
[Eduard H Henoch (18201910), German physician; the cardioinhibitory centre, stimulation of which inhibits
Johann L Schnlein (17931864), German paediatri- the vasomotor centre and increases vagal activity.
cian; Michishige Takayasu (18601938), Japanese
ophthalmologist] Vasopressin (Arginine vasopressin, AVP; Antidiuretic
hormone, ADH). Neuropeptide synthesised in the cell
Vasoactive intestinal peptide (VIP). GIT hormone, bodies of the supraoptic and paraventricular nuclei of
also found in the hypothalamus, cortex, primary afferent the hypothalamus. Transported down their axons to the
neurones, spinal cord, retina and bloodstream. Causes posterior lobe of the pituitary gland, from where it is
oesophageal relaxation preceding a peristaltic wave, secreted. Metabolised in the kidney and liver, it has a
relaxation of sphincters, stimulation of intestinal electro- circulatory half-life of 1030min. There are at least three
lyte and water secretion and inhibition of gastric secre- types of vasopressin receptor, all of which are G protein-
tion. Dilates peripheral blood vessels and causes coupled receptors: V1 receptors are Gq-coupled and
bronchodilatation. Has positive inotropic and chrono- located primarily on vascular smooth muscle and plate-
tropic action on the heart and causes coronary vasodila- lets; V2 receptors (Gs-coupled) mediate vasopressins
tation. Has an important role in the regulation of antidiuretic actions on the kidney; and V3 receptors
circadian rhythms. Tumours secreting VIP (VIPomas) (coupled to multiple G proteins) are located centrally
may cause severe diarrhoea and hypotension. and involved in vasopressins neurotransmitter actions.
Main effects:
water retention by the kidney, acting via V2 vaso-
Vasoconstrictor drugs, see Vasopressor drugs pressin receptors. These increase adenylate cyclase
activity and cAMP levels, triggering insertion of
Vasodilator drugs. Drugs causing vasodilatation as water channels (aquaporins) into the luminal mem-
their primary effect (cf. isoflurane, morphine). The term branes of cells in the renal collecting ducts. This
is sometimes reserved for drugs acting directly at vascu- results in water reabsorption from the renal tubules.
lar smooth muscle. Nitric oxide is thought to be a Urine volume decreases; its concentration increases.
common end pathway for most drugs. Conversely, plasma volume increases; its concentra-
May be divided according to their main site of action, tion decreases.
although considerable overlap occurs: vasoconstriction, acting via V1 vasopressin recep-
venous system: GTN, isosorbide. tors on vascular smooth muscle. Thought to have a
arterial system: hydralazine, calcium channel minor role in normal BP regulation.
blocking drugs, salbutamol, diazoxide, minoxidil, has a role in temperature regulation, control of cir-
adenosine. cadian rhythm and memory function.
venous and arterial systems: sodium nitroprusside, increased plasma levels of coagulation factor VIII.
-adrenergic receptor antagonists, angiotensin con- Release is increased by:
verting enzyme inhibitors, ganglion blocking drugs, increased plasma osmolality; detected by osmore-
potassium channel activators. ceptors in the anterior hypothalamus.
 Vegetative state 593

decreased ECF volume and hypotension (e.g. in BP, they are now reserved for situations where vaso
haemorrhage); detected by baroreceptors. dilatation is a specific problem, e.g. anaphylaxis, spinal
pain, nausea, hypoxaemia, emotional and physical anaesthesia.
stress. Mostly sympathomimetic drugs:
drugs, e.g. morphine, barbiturates. catecholamines, e.g. adrenaline, noradrenaline,
angiotensin II. dopamine.
Release is inhibited by: non-catecholamines, e.g. ephedrine, metaraminol,
decreased plasma osmolality. phenylephrine.
increased ECF volume. Directly acting vasopressor hormones and their ana-
drugs, e.g. alcohol, butorphanol. logues have also been used, e.g. in hypotension refrac-
Used therapeutically in various forms: tory to other potent vasopressors:
argipressin: synthetic vasopressin; used in pituitary vasopressin and its synthetic analogues.
diabetes insipidus (DI; 520U sc/im, 4-hourly) and angiotensin (see Renin/angiotensin system).
for control of bleeding oesophageal varices (20U See also, Inotropic drugs
iv over 15min). Side effects include pallor, nausea,
abdominal cramps and myocardial ischaemia. GTN Vasovagal syncope. Fainting, often caused by emotion
(patch or iv) has been used to reduce the incidence or pain. May occur in patients undergoing venous
and severity of side effects. cannulation or regional anaesthesia. Vasodilatation in
terlipressin: a prodrug, it is enzymatically cleaved to muscle (sympathetic discharge) and bradycardia (vagal
release vasopressin. Dosage: 2mg iv followed by discharge) cause hypotension and loss of consciousness,
12mg 46-hourly for up to 72h. Side effects are usually short-lived.
milder than after argipressin. Kapoor WN (2002). Circulation; 106: 16069
lypressin: used as a nasal spray in pituitary DI:
510U 68-hourly. Side effects are milder than vCJD, see CreutzfeldtJakob disease
after argipressin.
desmopressin: may be given nasally, orally or by im/ Vecuronium bromide. Non-depolarising neuromuscu-
sc/iv injection. Minimal vasoconstrictor activity; lar blocking drug, introduced in the UK in 1983. A
used in pituitary DI and to boost factor VIII levels monoquaternary aminosteroid, similar in structure to
in haemophilia and von Willebrands disease. pancuronium. Initial dose is 80100g/kg; good intubat-
felypressin: used as a vasoconstrictor in local ing conditions occur within 90120s. Relaxation lasts for
anaesthesia. 2030min; duration is increased to 50min if 150g/kg
Vasopressin has been used as an alternative to adrena- is used, and 80min if 250g/kg is used. Supplementary
line in the treatment of cardiac arrest and septic dose: 2030g/kg (3050g/kg initial dose after admin-
shock, and as a means of preserving organ function in istration of suxamethonium for intubation). May also be
brainstem-dead donors. Vasopressin receptor antago- given by infusion, at 5080g/kg/h.
nists have been studied for use in cardiac failure and Causes minimal histamine release, ganglion or
hyponatraemia. vagal blockade, even at several times the usual doses.
Treschan TA, Peters J (2006). Anesthesiology; 105: Thus has minimal effects on BP and pulse, but may
599612 allow unopposed vagal stimulation to cause brady-
See also, Syndrome of inappropriate antidiuretic hormone cardia. Metabolised in the liver to the active
secretion 3-desacetylvecuronium. Excreted mainly in bile, but also
in urine. Reversal of action is fast, and acetylcholinester-
Vasopressin receptor antagonists (Vaptans). Com ase inhibitors may not always be required. Cumulation
petitive antagonists at V2 vasopressin receptors, used for is unlikely.
the treatment of hyper- and euvolaemic hyponatraemia,
e.g. in cardiac failure/hepatic failure and syndrome of Vegetative state. Disorder of consciousness in which
inappropriate antidiuretic hormone secretion (SIADH) the patient appears to be awake but is unaware of him-/
respectively. Cause increased free water excretion, herself or the surrounding environment; differs from
leading to an increase in plasma sodium concentration coma (patient is neither awake nor aware) or the mini-
and reduced total body water. mally conscious state (patient is awake and appears to
Increased water intake due to increased thirst may be intermittently aware). Due to injury to cortical, sub-
reduce their efficacy. Other side effects include dehydra- cortical and thalamic structures.
tion, nausea, skin rashes and orthostatic hypotension. May be:
Contraindicated in hypovolaemic hyponatraemia. All acute: head injury, hypoxic/anoxic brain injury,
vaptans are substrates and inhibitors of the CYP3A4 infection (meningitis, encephalitis), CVA.
isoenzyme of the cytochrome oxidase system; caution is subacute: in the course of a neurodegenerative
therefore required when co-administered with drugs process e.g. Alzheimers disease.
causing enzyme induction/inhibition. Tolvaptan is the Clinical features include complete non-responsiveness
only agent available in the UK and is licensed for the with preservation of hypothalamic/brainstem function
treatment of SIADH. and cycles of eye opening/closing suggestive of sleep
Robertson GL (2011). Nat Rev Endocrinol; 7: 15161 wake cycles. Diagnosis is based on the lack of reproduc-
ible response to visual, olfactory, auditory, tactile or
Vasopressor drugs. Drugs causing vasoconstriction; noxious stimuli. Recent functional MRI and EEG
used to increase arterial BP, e.g. during anaesthesia, studies suggest that some patients formerly diagnosed as
intensive care or CPR, or to prolong the action of local being in a vegetative state are, in fact, in a minimally
anaesthetic agents by preventing their systemic absorp- conscious state but are unable to respond to stimuli due
tion. Formerly used rather indiscriminately to increase to their disability.
594 Venous admixture

The vegetative state is considered to be persistent

when it lasts >1 month and permanent after >6 months.
Prognosis depends on:
time spent in vegetative state (only 3% of patients
regain independence after 6 months).
age (best prognosis is in those <20 years old).
type of brain injury (traumatic injuries have better Axillary vein
outcomes than non-traumatic).
Cephalic vein
[Alois Alzheimer (18641915), German neurologist and
pathologist]
Monti MM, Laureys S, Owen AM (2010). Br Med J; 341:
2926

Venous admixture. Refers to lowering of arterial PO2

from the ideal level which would occur if there were no
shunt or V/Q mismatch, either of which may lower PO2.
Defined as the amount of true shunt that would give Median cubital vein
the observed PO2. May be calculated from the shunt
equation. Basilic vein

Venous cannulation, see Central venous cannulation; Cephalic vein

Intravenous fluid administration

Venous drainage of arm. Deep veins accompany the

arteries (deep venae comitantes). Superficial veins on
the back of the hand form the dorsal venous arch, from Median vein of forearm
which the basilic and cephalic veins arise. Smaller veins
arise from the anterior aspect of the arm (Fig. 164). The
anatomy of the veins may vary considerably, especially
that of the cephalic vein.
Main veins of the forearm:
basilic vein: ascends on the posteromedial side of
the forearm, passing to the anterior side below the
elbow. Passes along the medial side of the biceps
muscle and pierces the deep fascia. At the axilla it
joins the deep venae comitantes of the brachial
artery to form the axillary vein.
cephalic vein: ascends on the lateral side of the
forearm, passing anterior to the elbow. Runs on the
lateral aspect of biceps, along the groove between
deltoid and biceps, and pierces the clavipectoral Fig. 164 Superficial venous drainage of the arm
fascia at the lower border of pectoralis major, to
join the axillary vein. The angle at which the vessels
meet, and the presence of valves at the junction,
may cause difficulty in passing an iv catheter past
this point. membrane, joining the posterior tibial veins to
See also, Antecubital fossa form the popliteal vein. This ascends through the
popliteal fossa to form the femoral vein, which
Venous drainage of head and neck, see Cerebral circu- becomes the external iliac vein deep to the inguinal
lation; Jugular veins ligament.

Venous drainage of leg. Comprises superficial and deep Venous pressure, see Central venous pressure; Jugular
veins (Fig. 165): venous pressure; Venous waveform
the important superficial veins arise at the ankle:
- long (great) saphenous vein: passes anterior to the Venous return. Refers to the volume of blood entering
medial malleolus behind the saphenous nerve. the right atrium per minute. A major determinant of
Ascends behind the medial condyles of the tibia cardiac output, as described by Starlings law.
and femur, passing into the thigh and through the Depends on:
saphenous opening in the deep fascia to end in venous tone.
the femoral vein. intrathoracic pressure.
- short (small) saphenous vein: passes behind the intra-abdominal pressure.
lateral malleolus, piercing the deep fascia to join blood volume.
the popliteal vein. right and left ventricular function.
deep veins start as digital and metatarsal veins in skeletal muscle activity (muscle pump).
the sole, forming the lateral and medial plantar posture.
veins. These form the posterior tibial veins. The vasodilator/vasopressor drug therapy.
anterior tibial veins pass through the interosseus See also, Preload
 Ventilation/perfusion mismatch (V/Q mismatch) 595

(a) (b)

Ventilation/perfusion ratio (V/Q

V or perfusion (Q )

V/Q 3

Common iliac
vein Q
2
External iliac vein

Ventilation (V)
V
1

V/Q
ratio)
Femoral vein

Bottom of lung Top of lung

Long (great)
saphenous vein Fig. 167 V /Q mismatch graph

enlarged a wave:
- tricuspid stenosis.
- stiff right ventricle, e.g. pulmonary stenosis, pul-
Popliteal vein monary hypertension.
enlarged v wave: tricuspid regurgitation, e.g. due
to cardiac failure.
cannon waves (large waves, not corresponding to

Short (small) a, v or c waves):

saphenous vein - complete heart block (irregular).
- junctional arrhythmias (regular).
A similar waveform is seen in the left atrial pressure
tracing.
See also, Cardiac cycle

Ventilation, controlled, see Airway pressure release ven-

tilation; Assisted ventilation; High-frequency ventilation;
Inspiratory pressure support; Inspiratory volume support;
Intermittent mandatory ventilation; Intermittent negative
pressure ventilation; Intermittent positive pressure venti-
lation; Inverse ratio ventilation; Mandatory minute venti-
lation; Pressure-regulated volume control ventilation;
Fig. 165Venous drainage of the leg: (a) anterior; (b) posterior
Proportional assist ventilation; Synchronised intermittent
mandatory ventilation

Ventilation, liquid, see Liquid ventilation

a v
Ventilation, spontaneous, see Breathing, control of;
c Breathing, work of; Respiratory muscles

Ventilation/perfusion mismatch (V /Q  mismatch).

x y Imbalance between alveolar ventilation (V)  and pul
monary capillary blood flow (Q).  In the ideal lung model,
Fig. 166Venous waveform (see text) ventilation would be distributed uniformly to all parts of
the lung and would be matched by uniform distribution
of blood flow (i.e. V /Q
 = 1). However, even in a healthy
Venous waveform. Obtained from the tracing of CVP. 70kg male, alveolar ventilation and blood flow are
Can be seen but not felt in the neck as the JVP. Consists unequal (4l/min and 5l/min respectively), giving a V /Q 
of named waves and descents (Fig. 166): ratio of 0.8.
a wave is due to atrial contraction. In addition, gravitational forces result in a gradient of
c wave is thought to be due to transmitted pulsa- V /Q
 ratios in the lung as one travels from the base to the
tion from the carotid arteries, or to bulging of the apex in the upright position (Fig. 167). Both ventilation
tricuspid valve into the right atrium. and perfusion decrease from base to apex, but perfusion
v wave is due to atrial filling. to a greater extent than ventilation. Thus the V /Q  ratio
x descent is due to atrial relaxation. is higher at the apex (V /Q  = 3.3) than at the base (V /Q

y descent is due to atrial emptying as the tricuspid = 0.63). Similar but smaller changes occur across the lung
valve opens and blood drains into the ventricle. in the supine position.
Abnormalities seen in the JVP wave may assist diag- V /Q
 mismatch may result in V /Q  ratios ranging from
nosis of certain valve and rhythm disorders: zero (perfusion but no ventilation) to infinity (ventila-
no a wave: AF. tion but no perfusion). Its effects on gas exchange are
596 Ventilator-associated lung injury

those of shunt and dead space respectively, and can be Divided into:
assessed by determining venous admixture and physio- negative pressure devices used for intermittent
logical dead space. V /Q mismatch is a common cause of negative pressure ventilation: the negative pressure
hypoxaemia in pulmonary disease, e.g. COPD, asthma, around the thorax causes chest expansion and
chest infection and pulmonary oedema and circulatory draws in air:
disorders, e.g. PE. - tank ventilators (iron lungs):
Mismatch may be measured using radioisotope scan- - enclose the whole body (apart from the head
ning of ventilation and perfusion separately, e.g. with and neck) within an airtight casing.
xenon and technetium. - efficient, but access to the patient is very
See also, Pulmonary circulation restricted.
- cuirass ventilators:
Ventilator-associated lung injury (VALI). Acute lung - enclose the thorax and upper abdomen. Inflat-
injury associated with mechanical IPPV. Attributed to: able jacket versions have been described.
the use of high inspiratory plateau pressures; high tidal - less restrictive but less efficient.
volumes; and repeated collapse and expansion of Do not protect against aspiration of gastric con-
airways and associated lung units. These result in baro- tents. Their effectiveness may be reduced by indraw-
trauma, volutrauma and atelectrauma, respectively ing of the soft tissues of the upper airway during
which, in turn, lead to biotrauma (local and systemic inspiration. Tracheostomy may be required if this
inflammation with activation of neutrophils and release occurs.
of cytokines). Lung protection strategies aim to miti- positive pressure devices used for IPPV: deliver
gate these effects. positive pressure to the lungs either invasively via
Gattinoni L, Protti A, Caironi P, Carlesso P (2010). Crit a tracheal tube, tracheostomy, or injector device,
Care Med; 38(Suppl): S53948 or non-invasively via facemask or nasal mask
See also, Barotrauma; Intermittent positive pressure (non-invasive positive pressure ventilation).
ventilation Positive pressure ventilators are widely used dur-
ing anaesthesia and in ICU. They may be powered:
Ventilator-associated pneumonia (VAP). Nosocomial - electrically, e.g. employing a crankshaft (e.g. Cape
pneumonia developing more than 48h after tracheal ventilator) or solenoid (e.g. Siemens or Engstrm
intubation and IPPV. Accounts for ~30% of ICU infec- ventilators).
tions and is an important cause of ICU mortality. Early - by a separate supply of compressed air or O2,
infections are most often due to common respiratory employing fluidics or pneumatics (e.g. Penlon
flora, late infections often due to pseudomonas species, Nuffield ventilator).
resistant staphylococci and acinetobacter species. - by anaesthetic gases (e.g. Manley ventilator).
Viruses and fungi may also be causal agents. These types are minute volume dividers (see
Risk factors: below).
patient-related: age, cardiorespiratory disease, Classification of positive pressure ventilators: many
immunodeficiency, ARDS, coma, MODS. different classifications have been suggested, e.g.
ventilator-related: duration of IPPV >7 days, according to the mechanism of action:
tracheal cuff pressure <20cmH2O, reintubation, mechanical thumbs: intermittent occlusion of the
tracheostomy. open limb of a T-piece, e.g. by a solenoid, e.g. the
general ICU care: supine position, invasive devices, Sheffield infant ventilator. Intermittent blowers
aspiration, H2 receptor antagonists, recent antibi- may be used to achieve a similar effect by moving
otic therapy. a column of driving gas forwards and backwards
Diagnostic criteria include: CXR infiltrates; fever; leuco- along a length of tubing connecting the ventilator
cytosis; purulent sputum; and positive microbiological with the T-piece, e.g. the Penlon Nuffield ventilator
cultures of tracheobronchial aspirates or brush speci- attached to the Bain coaxial anaesthetic breathing
mens. Differential diagnosis includes pulmonary oedema, system. Anaesthetic gases are delivered separately
atelectasis, PE, ARDS and pulmonary haemorrhage. through the other limb of the T-piece. A similar
Treatment includes chest physiotherapy and appro- technique may be used with a circle system.
priate antibiotic therapy, guided either by positive cul- minute volume dividers: supply only the minute
tures and sensitivities, or empirical selection based on volume of anaesthetic gas delivered to them, by
the most likely organisms. dividing the preset minute volume into equally
Preventive measures, often delivered as a care bundle, sized breaths, e.g. Manley ventilators and (obsolete)
include: good oral care; elevation of the bed-head to vents (e.g. Minivent, EastFreeman automatic
3045; prevention of over-sedation; protocol-driven vent: small devices, placed at the patient end of an
weaning from ventilators; and monitoring of tracheal anaesthetic breathing system, that intermittently
cuff pressures. allow gas flow when upstream pressure is sufficient
Hunter JD (2012). Br Med J; 344: e3325 to overcome the resistance offered by a magnetised
See also Chest infection; Intubation, tracheal; Nosocomial bobbin within them). Delivered minute volume
infections; Sepsis may be read directly from the anaesthetic machine
flowmeters.
Ventilators. Mechanical devices for ventilating the bag-squeezers: employ mechanical or pneumatic
lungs. First described in the early 1900s as an alterna- force to compress the bag or bellows intermittently,
tive to resuscitation equipment incorporating bellows. e.g. Air-shields ventilator, Oxford ventilator (pneu-
The polio epidemic in Denmark in 1952 was a major matic), Cape ventilator (mechanical). Widely used
impetus to the development of reliable positive pressure with modern circle systems. Bellows that ascend
ventilators. during filling are preferable to those that descend
 Ventricular ectopic beats 597

during filling, since the former will not fill if there is I-to-E cycling:
a disconnection or leak, whereas the latter will still - time-cycled: the duration of inspiration is preset,
descend. e.g. Manley MP2, Penlon Nuffield, Siemens Servo
intermittent blowers: produce intermittent flow 900 series.
from a high-pressure source, e.g. cylinders. Include - pressure-cycled: expiration begins when a preset
the Bird ventilators used on ICU, and small devices airway pressure is reached, e.g. Bird ventilator.
used for transportation of ventilated patients, e.g. - volume-cycled: expiration begins when a preset
Pneupac ventilator. The Penlon Nuffield ventilator tidal volume has been delivered, e.g. Manley Pul-
is suitable for use with the Bain and circle systems; movent ventilator.
it may also be used for children (with a paediatric - flow-cycled (pressure generators only): expiration
pressure release valve) using the T-piece. begins when a preset inspiratory flow is reached,
jet ventilators: include those used for injector tech- e.g. Bennett PR-2 ventilator. Rarely used as a
niques and high-frequency ventilation. method of cycling.
Another widely used classification is that suggested Most of the above have been superseded by modern
by Mapleson in 1969, according to the characteristics ventilators, which may be employed as either flow gen-
during the inspiratory phase and inspiratory to expi- erators or pressure generators, with a choice of cycling
ratory (I-to-E) cycling: methods. Thus they may be used both for anaesthesia
inspiratory characteristics: and (with more complex features) for different clinical
- flow generators: produce a high generating pres- situations, e.g. on ICU.
sure (e.g. 400kPa) and are thus able to deliver During expiration, airway pressure may be allowed
flow which is unaffected by patient characteristics. to fall to atmospheric pressure; most ventilators also
The flow produced may be constant or non- allow application of PEEP. Negative end-expiratory
constant (usually the former). Non-constant flow pressure is no longer used. The switch from expiratory
generators include the Cape ventilator, in which to inspiratory phases is usually time-cycled, although it
flow is sinusoidal because of the crank mechanism may be triggered by the patient in some modes.
employed. Most ICU ventilators are flow genera- The ideal ventilator for use on ICU should: be flexible
tors (Fig. 168a), as they are able to produce the in flow or pressure generation and cycling as above;
high inflation pressures required to achieve the allow PEEP and special modes (e.g. for weaning); allow
preset flow in non-compliant lungs, e.g. in bron- humidification and administration of nebulised drugs; be
chospasm. Barotrauma may occur if high airway easy to sterilise; and incorporate monitors and alarms.
pressures are reached. Specific advanced ventilator modes used in ICU include
- pressure generators: produce low generating pres- airway pressure release ventilation, inspiratory pressure
sure (e.g. 1.5kPa); thus the flow delivered is support, inspiratory volume support, intermittent man-
affected by patient characteristics (Fig. 168b). datory ventilation, inverse ratio ventilation, mandatory
Since the airway pressure attainable is preset, the minute ventilation, pressure-regulated volume control
risk of barotrauma is reduced. However, the tidal ventilation, proportional assist ventilation and synchro-
volume delivered depends on the resistance of the nised intermittent mandatory ventilation. Many permit
tubing and the patients respiratory mechanics, alteration of the I:E ratio, inspiratory waveform and
e.g. compliance, airway resistance. Pressure gen- PEEP.
erators are usually employed in paediatric anaes- [Ernst W von Siemens (18161892), German engineer;
thesia, to reduce the risk of barotrauma. Examples Carl-Gunnar Engstrm (19121987), Swedish physician;
of constant pressure generators are the Manley Roger EW Manley (19301991), UK anaesthetist and
and East Radcliffe ventilators. engineer; William W Mapleson, Cardiff physicist; Forrest
M Bird, US aviator and engineer]
Smallwood RW (1988). Anaesth Intensive Care; 14:
(a) (b) 2517
See also, Monitoring

Ventile, see Scavenging

Flow

Flow

Ventricular ectopic beats (VEs, VEBs; Premature ven-

tricular contractions/beats, PVCs/PCBs). Contraction of
ventricular muscle caused by an ectopic focus instead of
normal impulse conduction. The ventricles discharge
Time Time early; the next sinus impulse finds the ventricular muscle
refractory, causing a pause before the next beat. VEs
typically appear as wide bizarre complexes on the ECG
Alveolar pressure

Alveolar pressure

(Fig. 169); VEs arising from different sites (i.e. multifo-

cal) may have different configurations.
They may occur in normal hearts, but may also indi-
cate organic heart disease. Other causes include drugs
(e.g. halothane, digoxin, antiarrhythmic drugs), electro-
lyte and acidbase disturbances, hypoxaemia, hypercap-
Time Time nia and pain. Common during anaesthesia, especially
with spontaneous ventilation with halothane. May occur
Fig. 168 Inspiratory characteristics of (a) constant flow and at regular intervals, e.g. every second or third beat.
(b) constant pressure generators Usually do not require treatment, apart from correction
598 Ventricular fibrillation

Capture beat Fusion beat

Fig. 169Ventricular ectopic beat (arrowed)
Fig. 171Ventricular tachycardia, showing capture and fusion beats

succession). The pulse rate usually lies between 130 and

250beats/min. Normal atrial activity may continue inde-
Fig. 170Ventricular fibrillation
pendently, or the ventricular impulses may pass retro-
gradely to the atria.
of the cause. Antiarrhythmic drugs (usually lidocaine) Distinguished from SVT by the following features
are usually recommended for VEs more common than (Fig. 171):
5 per minute, or if multifocal or close to the preceding QRS complexes are usually wide and bizarre.
T wave with risk of the R on T phenomenon. retrograde conduction to the atria may result in
See also, Arrhythmias inverted P waves (which may be hidden by the QRS
complexes).
Ventricular fibrillation (VF). Uncoordinated and inef- independent atrial activity may be suggested by:
fective ventricular contraction caused by completely - occasional P waves.
irregular ventricular depolarisation. May follow the R - capture beats (normal QRS complexes following
on T phenomenon. Causes include myocardial isch- occasional normal atrioventricular conduction).
aemia, MI, hypoxaemia, electrocution, electrolyte imbal- - fusion beats (with combined features of normal
ance, hypothermia and drug toxicity (e.g. adrenaline, and ectopic QRS complexes, representing simul-
digoxin). There is no cardiac output; asystole therefore taneous atrially conducted and ectopic ventricular
follows unless treated. VF is the most common cause of activity).
cardiac arrest. The ECG shows continuous random elec- marked left axis deviation, with all of the chest leads
trical activity without QRS complexes (Fig. 170). either negative or positive.
Treated by defibrillation, although a single precordial Both VT and SVT may be regular, and associated
thump is advocated for monitored arrests. with normotension or hypotension. Differentiation
between broad-complex VT and SVT may be particu-
Ventricular septal defect (VSD). Accounts for 2030%
larly difficult. The response to adenosine may aid
of congenital heart disease; may also follow MI or
diagnosis. Causes are as for ventricular ectopic beats.
trauma. The commonest congenital form involves the Treatment (following CPR if necessary):
membranous septum immediately below the tricuspid
antiarrhythmic drugs, e.g. amiodarone.
valve; bulbar or muscular septal involvement is rarer.
cardioversion if there are adverse signs (e.g. hypo-
Blood flows across the defect from left to right during
tension) or drugs are contraindicated/ineffective.
systole. As right ventricular pressures decrease after
cardiac pacing has also been used.
birth, shunt increases. May cause cardiac failure in
management of recurrent VT includes antiarrhyth-
infancy. Small defects with normal pulmonary artery
mic drugs, catheter ablation of the ectopic focus and
pressures are often asymptomatic (maladie de Roger)
implantable defibrillators.
and may close spontaneously. Large defects may lead to
European Resuscitation Council (2010). Resuscitation;
pulmonary hypertension and Eisenmengers syndrome.
Features:
81: 121976
See also, Torsade de pointes
harsh pansystolic murmur, heard best in the left
fourth intercostal space (louder with small defects).
Venturi principle. Entrainment of a fluid into an area
Splitting of the second heart sound.
of low pressure caused by a constriction in a tube
of Eisenmengers syndrome if present.
(Bernoulli effect). Entrainment depends on appropriate
of left and right ventricular hypertrophy on ECG
positioning of the side-arm or entrainment port, a suit-
and CXR.
ably shaped constriction and the gradual increase in
Up to 25% of patients may be affected by bacterial
diameter of the limb distal to the constriction.
endocarditis at some time.
Treated by surgery or placement of a septal occluder
The principle is employed in gas-mixing devices
(including fixed performance oxygen therapy devices),
using a percutaneous technique. Anaesthesia is as for
suction equipment, ejector flowmeters, scavenging
congenital heart disease and cardiac surgery.
equipment and devices used to circulate gases round
[Henri L Roger (18091891), French physician]
breathing systems.
Ventricular stretch receptors, see Baroreceptors [Giovanni Venturi (17461822), Italian physicist]

Ventricular tachycardia (VT). Rapid series of ventricu- Verapamil hydrochloride. Calcium channel blocking
lar ectopic beats (usually defined as more than three in drug, mainly used as an antiarrhythmic drug to treat
 Verapamil hydrochloride 599

SVT. Acts by prolonging conduction through the atrio- Side effects: hypotension, bradycardia, complete
ventricular node. Also used in angina and hypertension. heart block and asystole, especially if the patient
Undergoes extensive first-pass metabolism when given has received -adrenergic receptor antagonists. Con-
orally. Excreted renally. traindicated in WolffParkinsonWhite syndrome,
Dosage: since atrioventricular block may promote conduction
SVT: 510mg by slow iv injection, repeated up to through accessory pathways with resultant arrhyth-
1520mg at 5-min intervals, or 40120mg orally tds. mia. Its action may be potentiated by inhalational
hypertension: up to 480mg orally tds. anaesthetic agents, especially halothane.

(a) Body
Anterior tubercle
Posterior tubercle
Foramen transversarium

Superior articular facet

Vertebral canal
Inferior articular process
Lamina

Bifid spinous process

(b)
Body

Superior articular facet Superior costal facet

Superior costal facet
Pedicle Facet for rib
Vertebral canal
Superior articular facet

Inferior costal facet

Spinous process Lamina Transverse process

(c)

Body Superior articular facet

Pedicle
Transverse process
Vertebral canal

Inferior articular process Superior articular facet Inferior articular facet

Spinous process

Fig. 172Typical vertebrae: (a) cervical, superior view; (b) thoracic, superior and lateral views; (c) lumbar, superior and lateral views
600 Vertebrae

Vertebrae. Bony components of the vertebral column, - L5: short but massive transverse processes, arising
which is about 70cm long in the adult male and is flexed from the sides of the body and pedicles. The body
throughout its length in the fetus; after birth two second- is deeper anteriorly than posteriorly.
ary curves appear so that the cervical and lumbar regions sacral: fused to form the sacrum, enclosing the
are convex forwards and the thoracic and sacral regions sacral canal.
are concave. There are 7 cervical vertebrae, 12 thoracic, coccygeal: fused to form the triangular coccyx, the
5 lumbar, 5 fused sacral and 35 fused coccygeal. Verte- base of which articulates with the sacrum.
bral bodies of C2 to L5 are separated by fibrocartilagi-
nous vertebral discs, accounting for about 25% of the Vertebral arteries. Arise from the subclavian arteries,
spines total length. Each has an outer fibrous annulus passing upwards through the foramina transversaria of
fibrosus, and the more fluid inner nucleus pulposus. The the upper six cervical vertebrae and passing medially
latter may prolapse through the former, impinging upon behind the lateral mass of the atlas. They enter the skull
the spinal cord or spinal nerves. Discs thin with age, through the foramen magnum, uniting to form the
resulting in reduced height. Vertebrae and discs are basilar artery after piercing the dura. Vertebrobasilar
united by the vertebral ligaments. insufficiency typically results in dizziness, vertigo, diplo-
Structure of a typical vertebra: pia and hemiparesis.
body: short and cylindrical and lies anteriorly. May be punctured during central venous cannulation
arch: encloses the vertebral canal and lies posteri- and brachial plexus block.
orly. Composed of the rounded pedicles anteriorly See also, Cerebral circulation
and the flattened laminae posteriorly. The laminae
Vertebral canal. Triangular canal within the vertebrae,
are united in the midline by the spinous process.
with its base posteriorly. Contains:
They also bear transverse processes and superior
epidural space and contents.
and inferior articular processes which bear facets
spinal cord and spinal nerves/roots.
for articulation with adjacent vertebrae.
Regional differences:
Vertebral ligaments. Individual vertebrae are linked by
cervical (Fig. 172a): a number of ligaments (Fig. 173):
- each has the foramen transversarium passing
through its transverse processes, through which
pass the vertebral arteries. (a)
- C1 (atlas): Anterior longitudinal Dural sac
- has neither body nor spine. ligament Ligamentum flavum
- articular facets articulate superiorly with the
base of the skull.
- facet on the anterior edge of the vertebral canal
Vertebral body
articulates with the odontoid peg.
Spinous
- C2 (axis): odontoid peg projects from the superior process
surface of the body, held against the body of the
atlas by the transverse ligament. The gap between Intervertebral disc
Interspinous
the peg and atlas is normally less than 3mm on ligament
neck flexion (5mm in children).
- C26: bifid spinous processes.
- C7 (vertebra prominens): non-bifid spine (the first
easily palpable spine encountered, feeling from
the skull downwards; T1 below it has a more A B
prominent spine).
thoracic (Fig. 172b):
- body: heart-shaped, articulating with the ribs via
superior and inferior costal facets at the rear of
Posterior
the body.
longitudinal Epidural space
- transverse processes: large, passing backwards ligament
and laterally, and bearing facets that articulate Supraspinous ligament
with the ribs tubercles (except the last two tho- (b)
racic vertebrae).
- spinous processes: long, inclined at about 60 to Anterior longitudinal Dural sac
ligament Ligamentum flavum
the horizontal.
- anatomical variations: Supraspinous
- T1: has a longer upper facet for the first rib and ligament
a smaller lower facet for the second rib. Vertebral body
- T1012: usually bear single costal facets on their
bodies. Interspinous
- T12: spinous process has notched lower edge. ligament
lumbar (Fig. 172c):
- body: kidney-shaped. Posterior longitudinal
- transverse processes: thick, passing laterally. ligament Epidural space
Bear the accessory processes posteriorly at their
bases. Fig. 173Vertebral ligaments: (a) longitudinal section of vertebral
- spines: project horizontally backwards. column; (b) transverse section through AB
 Vitamin deficiency 601

anterior longitudinal ligament: runs from C2 to the layers. Dependent on intermolecular attractive forces
sacrum, attached to the anterior aspects of the ver- (e.g. van der Waals forces) and entanglement of bulky
tebral bodies. Continues superiorly to form the molecules. Decreased at high temperatures; particles
anterior atlanto-occipital membrane. have more kinetic energy and may escape from their
posterior longitudinal ligament: as for the anterior, neighbours more easily. Laminar flow is inversely pro-
but attached to the posterior vertebral aspects. Con- portional to viscosity.
tinues superiorly to form the membrana tectoria Blood viscosity depends largely on haematocrit
between the axis and occiput. (increasing exponentially as haematocrit increases), red
ligamenta flava (yellow ligaments): run between the cell characteristics and blood protein concentration. It
laminae of adjacent vertebrae. More developed in rises with age and smoking. It is increased slightly by
the lumbar than thoracic regions. Continue superi- volatile anaesthetic agents. Blood viscosity alters with
orly as the posterior atlanto-occipital membrane. different flow rates; i.e. blood is a non-Newtonian fluid.
interspinous ligaments: run between the spines of At vessel diameters of less than 0.3mm, it drops mark-
adjacent vertebrae. edly, resulting in greater flow than with a Newtonian
supraspinous ligament: runs from C7 to the sacrum, fluid. The reason is unclear, but may involve plasma
attached to the tips of the spines. skimming (the tendency of cellular components of
Additional ligaments at the atlanto-occipito-axial blood to remain in the middle of vessels whilst plasma
complex: passes into branches arising from the vessel wall). Blood
transverse ligament of the atlas: runs between cell deformability may also be important. At very low
medial aspects of the atlas lateral masses, securing blood flow, viscosity increases as the cells clump together.
the odontoid peg. Relative viscosity (compared with water) of normal
alar ligaments: pass from the sides of the odontoid plasma is 1.5; that of normal whole blood is 3.5.
peg to the occipital condyles. Viscosity may be derived by measuring the time
apical ligament: thin band, connecting the odon- taken for a liquid to drain through a narrow tube. Alter-
toids tip to the anterior aspect of the foramen natively, the torque on an inner drum may be measured
magnum. when an outer drum is rotated, the specimen liquid
Sacrococcygeal ligaments: filling the space between the drums.
posterior: overlies the sacral hiatus. [Sir Isaac Newton (16421727), English scientist]
anterior: passes over the anterior aspect of the
sacrum and coccyx. Vishnevskiy technique (Transverse injection anaesthe-
lateral: joins the lateral angle of the sacrum to the sia). Injection of local anaesthetic agent into a transverse
transverse processes of the coccyx. slice of a limb; originally described using procaine. Infil-
tration is performed from skin to bone, using large
VF, see Ventricular fibrillation volumes of agent. Has been called the squirt and cut
technique.
Viagra, see Sildenafil [Aleksandr V Vishnevskiy (18741948), Russian
surgeon]
Victoria, Queen (18191901). British monarch, given
chloroform by Snow during the births of her eighth and Vital capacity. The maximum volume of gas that can be
ninth children: Prince Leopold in 1853, and Princess expired slowly after maximal inspiration; measured by a
Beatrice in 1857 (on the latter occasion, Prince Albert spirometer. Reduced in the supine position. Also reduced
administered chloroform himself before Snows arrival). in the elderly, and in patients with restrictive lung disease,
This gave respectability to pain relief during labour, muscle weakness, abdominal swelling and pain.
which had been criticised as being against Gods will. See also, Forced vital capacity; Lung function tests; Lung
[Leopold (18531884), Beatrice (18571944), Albert volumes
(18191861)]
See also, Obstetric analgesia and anaesthesia Vitamin B12 (Cobalamin). Water-soluble vitamin
present in many animal tissues, especially eggs and liver.
VIE, see Vacuum insulated evaporator Exists as various related compounds, e.g. hydroxo- or
cyanocobalamin. Combines with gastric intrinsic factor,
Vigabatrin. Anticonvulsant drug used as an adjuvant enabling its absorption from the terminal ileum.
treatment for partial and secondary generalised seizures. Required for red blood cell maturation and as a cofac-
Its efficacy in tonicclonic seizures is less well docu- tor for methionine synthase. Deficiency may be caused
mented. Irreversibly inhibits -aminobutyric acid trans- by failure of intrinsic factor production due to atrophic
aminase (GABA-T), the enzyme responsible for gastritis (pernicious anaemia) or gastric resection, or by
breakdown of GABA. Duration of action approximately disease/resection of the ileum. Dietary deficiency is rare.
24h with elimination half-life of 7h. Excreted unchanged Inhibited by N2O. Deficiency results in macrocytic meg-
in the urine. aloblastic anaemia and subacute combined degenera-
Dosage: 1g orally initially, increased up to 23g/day. tion of the spinal cord.
Side effects: sedation, dizziness, headache, agitation, Administered im 3-monthly as hydroxocobalamin;
psychosis, visual disturbances. cyanocobalamin requires more frequent administration.
Also used in the treatment of cyanide poisoning.
VIP, see Vasoactive intestinal peptide
Vitamin deficiency. May occur in:
Viscosity (). Tendency of fluids to resist flow. Measured inadequate intake relative to requirements, e.g.
in poise. Equal to shear force (force per unit surface malnutrition (including inadequate provision
area) divided by velocity gradient between adjacent fluid during TPN).
602 Vitamin K

Table 43 Functions, sources and adult daily requirements of vitamins

Vitamin Function Sources Daily requirements

A Retinal pigmentation, fetal development Yellow vegetables and fruit 1520g/kg

B1 (Thiamine) Cofactor in decarboxylation Liver, cereals 20g/kg
B2 (Riboflavin) Flavoproteins Liver, milk 20g/kg
Niacin Constituent of NAD and NADP Yeast and lean meat 0.4mg/kg
B6 (Pyridoxine) Decarboxylases and transaminases Yeast, wheat and liver 20g/kg
Pantothenic acid Constituent of coenzyme A Eggs, liver 0.30.8mg/kg
Biotin Fatty acid synthesis Egg yolk, liver 23g/kg
Folic acid Methylating reactions Green vegetables 23g/kg
Vitamin B12 Amino acid metabolism, erythropoiesis Liver, meat, eggs 0.040.1g/kg
Vitamin C (ascorbic acid) Collagen synthesis Citrus fruits 1.0mg/kg
Vitamin D Intestinal absorption of calcium and phosphate Fish, liver 0.10.2g/kg
Vitamin E Antioxidants Milk, eggs, meat 0.10.2g/kg
Vitamin K Blood coagulation Green vegetables 1.0g/kg

malabsorption, e.g. due to gastric disease (vitamin May be given orally, iv or im to help correct deficiency
B12), pancreatic disease (fat-soluble vitamins: A, D, or as an antidote to excessive anticoagulation with war-
E and K). farin; takes up to 12h to work. May cause several weeks
impaired metabolism of precursors, e.g. osteomala- upset to coagulation control in patients on long-term
cia in renal failure. warfarin therapy. Available as a synthetic analogue
antagonism by drugs, e.g. warfarin (vitamin K), N2O (menadiol sodium phosphate) or as phytomenadione
(folate and vitamin B12). (vitamin K1).
Specific deficiency states of possible anaesthetic Dosage: 220mg, repeated as necessary (iv injections
importance: should be given slowly). Prothrombin time should be
vitamin A: night blindness, dry skin. monitored.
vitamin B1 (thiamine): peripheral neuropathy, Anaphylaxis has been reported.
Wernickes syndrome (ataxia, nystagmus, ophthal- See also, Coagulation studies
moplegia and encephalopathy), cardiomyopathy
(beriberi). May accompany chronic alcoholism. Vitamins. Term derived from vital amines. Group of
Vitamin B1 is used in ethylene glycol poisoning. dietary compounds necessary for health and growth but
vitamin B2 (riboflavin): anaemia, mouth lesions. which do not supply energy (Table 43). Lack of one or
vitamin B6 (pyridoxine): convulsions, anaemia. more produces vitamin deficiency states. Vitamins A, D,
May accompany chronic alcoholism. Vitamin B6 is E and K are fat-soluble; the rest are water-soluble.
used in ethylene glycol poisoning and isoniazid
therapy. Vocal cords, see Larynx
niacin: dermatitis, diarrhoea, dementia (pellagra).
vitamin B12: anaemia, subacute combined degenera-
tion of the cord. Volatile anaesthetic agents, see Inhalational anaes-
vitamin C: generalised bleeding (especially thetic agents
gums), anaemia, weakness, poor wound healing
(scurvy). Volt. Unit of electrical potential. One volt is the poten-
vitamin D: hypocalcaemia, hyperphosphataemia, tial difference between two points when 1 joule of work
muscle weakness, rickets (in children), osteomalacia is done per coulomb of electricity passing from one point
(in adults). to the other.
vitamin E: haemolysis, oedema. [Alessandro Volta (17451827), Italian physicist]
vitamin K: bleeding tendency.
[Karl Wernicke (18481904), German neurologist] Volume of distribution (Vd). Theoretical term indicat-
ing the degree to which a drug redistributes and/or accu-
Vitamin K. Fat-soluble group of vitamins that catalyse mulates in body tissues. Equals the ratio of the amount
the carboxylation of glutamic acid residues to activate of drug present in the body at a given time, to the con-
coagulation factors II, VII, IX and X. Deficiency results centration of the drug in plasma at that time. Alterna-
in increased tendency to bleed and may result from: tively described as the volume of plasma throughout
inadequate intake: rare in adults, common in the which an injected dose would have to be distributed in
newborn. order to give the measured plasma concentration. May
inadequate absorption, e.g. malabsorption syn- be used to estimate the loading dose required to achieve
dromes, biliary obstruction. a desired plasma concentration, e.g. in a target-controlled
inadequate utilisation, e.g. liver disease. infusion.
drug therapy: especially warfarin and similar drugs, Initial volume of distribution (VdI or Vc) refers to
which act as vitamin K antagonists. the Vd immediately after injection, when the drug is
 Voriconazole 603

distributed throughout the central compartment, but usually considered together since the neurological
before any elimination or redistribution to the tissues pathways are similar. The incidence of PONV has been
has occurred. However, commonly cited values for dif- found to vary from 15 to 90%. Usually distressing, it is
ferent drugs usually refer to Vd at equilibrium or steady particularly undesirable in ear and ophthalmic surgery,
state (VdSS): and neurosurgery.
for a drug confined to the intravascular compart- Effects of prolonged vomiting:
ment (e.g. large, highly plasma protein-bound mol- loss of water and hydrogen, chloride, potassium and
ecules), VdSS equals blood volume. sodium ions, causing metabolic alkalosis.
for a drug that can leave the intravascular space renal bicarbonate loss to restore pH, causing alka-
but cannot freely enter cells (e.g. highly ionised line urine.
molecules), VdSS equals the ECF volume. fall in sodium and ECF causing aldosterone release,
for a drug that can easily penetrate cell membranes which causes renal sodium and fluid retention,
(and distributes equally throughout the body), it in exchange for potassium and hydrogen ions. If
equals total body water volume. hypokalaemia is severe, hydrogen ion loss predomi-
for a drug that concentrates preferentially in nates, with paradoxical acid urine.
the tissues (e.g. lipophilic drugs accumulating in thus dehydration, metabolic alkalosis and total
adipose), VdSS may greatly exceed total body water body potassium depletion may occur.
volume.
Examples (approximate values for a 70kg man): Von Recklinghausens disease, see Neurofibromatosis
propofol: 7001200 litres.
morphine: 210280 litres.
insulin: 50 litres.
Von Willebrands disease. Commonest inherited coag-
atracurium: Vd = 12 litres.
ulation disorder (affects ~1:1001000 people but may be
warfarin: Vd = 9 litres.
very mild); first described in 1926, with mostly autosomal
Drugs or poisons with a small Vd are more readily dominant transmission, depending on the subtype.
cleared from the plasma by haemodialysis or haemo- Abnormality of von Willebrand factor (VWF), a protein
perfusion; those with large Vd may be cleared from the involved in platelet adhesion and carriage of coagulation
plasma but levels tend to rise again (with possible factor VIII, leads to factor VIII deficiency, abnormal
recurrence of toxic effects) following cessation of platelet adhesiveness and abnormal vascular endothe-
dialysis. lium. Epistaxis and bruising are more common than hae-
See also, Pharmacokinetics marthrosis and haematoma, although there is marked
variation in clinical severity.
Classified into three main types:
Volume support, see Inspiratory volume support type 1: quantitative reduction in VWF; accounts for
~90% of cases.
Volutrauma, see Ventilator-associated lung injury type 2: qualitative abnormality of VWF, resulting in
decreased (2A) or increased (2B) activity; accounts
Vomiting. Reflex involving retrograde passage of gastric for ~10% of cases.
type 3: similar to type 1 but a severe autosomal
contents through the mouth. The vomiting centre in the
lateral medullary reticular formation receives afferent recessive form; accounts for <1% of cases.
impulses from the: Definitive diagnosis is made via VWF activity assay,
GIT, abdominal organs and peritoneum via the
VWF antigen testing and factor VIII assay; in combina-
vagus and sympathetic nerves. tion these have high sensitivity and specificity but may
heart mainly via the vagus nerve.
not be readily available, e.g. for emergency surgery.
vestibular apparatus.
Routine coagulation studies are more accessible, but less
chemoreceptor trigger zone (CTZ).
useful for diagnosis:
platelet count: low or normal.
higher centres.
prothrombin time: normal.
Chemical irritants stimulate the vomiting centre via
bleeding and activated partial thromboplastin
receptors in the GIT. Drugs (e.g. apomorphine) and neu-
rotransmitters (e.g. dopamine, noradrenaline, acetylcho- times: prolonged.
line, 5-HT) stimulate the CTZ. Raised ICP is thought to Desmopressin boosts levels of factor VIII and VWF, and
cause vomiting via increased pressure on the floor of the may be used preoperatively (0.3g/kg iv, effects lasting
fourth ventricle. 68h) for treatment of mild type 1 and 2A disease.
Motor impulses travel through cranial nerves V, VII, Severe disease is treated with fresh frozen plasma, cryo-
IX, X and XII to the facial muscles and upper GIT and precipitate or specific factor concentrates before surgery.
through spinal nerves to the diaphragm and abdominal Tranexamic acid 1g orally may be useful. Antiplatelet
muscles. drugs must be avoided.
Sequence of events: During pregnancy, levels of factor VIII and VWF
salivation increases.
increase, but they may fall rapidly after delivery.
breathing deepens.
[Erik von Willebrand (18701949), Swedish physician]
glottis closes.
Mazzeffi MA, Stone ME (2011). J Clin Anesth; 23:
breath is held in mid-inspiration.
41826
abdominal muscles contract.
See also, Blood products
oesophageal sphincters relax.
gastric contents are expelled. Voriconazole. Broad-spectrum triazole antifungal
Nausea is a sensation that may or may not be associated drug, related to fluconazole and used for severe fungal
with the act of vomiting itself, although the two are infections.
604 V/Q mismatch

Dosage: 400mg orally bd for 2 doses, then 200300mg VRE, Vancomycin-resistant enterococci, see Infection
bd. Alternatively 6mg/kg iv bd for 2 doses, then control; Vancomycin
4mg/kg bd.
Side effects: as for fluconazole, though most organ VSD, see Ventricular septal defect
systems can be affected.
VT, see Ventricular tachycardia
V/Q mismatch, see Ventilation/perfusion mismatch
 W
Wakefulness, see Awareness other valves: aspirin 75mg or dipyridamole 300mg/
day is started when warfarin is stopped. Heparin is
Wake-up test. Intraoperative awakening to allow restarted 612h postoperatively until able to take
assessment of spinal cord function during spinal surgery. warfarin. Increasingly, low-mw heparin is being
Has also been used to assess cerebral function during used to bridge coagulation perioperatively instead
basilar artery clipping. of unfractionated heparin.
other conditions: stop warfarin for 4872h before
Warfarin sodium. Oral anticoagulant drug, first synthe- surgery. The INR should be less than 1.5. Heparin
sised in 1944. Rapidly absorbed by mouth and almost may be given perioperatively sc to reduce thrombo-
totally protein-bound. Competes with vitamin K in the embolism until warfarin is restarted, or iv infusion
synthesis of coagulation factors II, VII, IX and X in the used postoperatively in high-risk cases, e.g. recur-
liver; therefore requires 12 days for its effect to develop. rent PE.
Also inhibits protein C and S. Metabolised in the liver emergency surgery: give vitamin K, and wait for
and excreted in urine and faeces. Half-life is about 30h. synthesis of new clotting factors (about 612h); this
Dosage is adjusted according to results of coagulation may interfere with subsequent anticoagulation for
studies: the International Normalised Ratio (INR) is weeks afterwards. Alternatively, fresh frozen plasma
maintained at about 23 for prophylaxis and treatment or prothrombin complex concentrate may be given.
of DVT, PE, transient ischaemic attacks and in patients The INR is monitored throughout.
with atrial fibrillation at high risk of embolisation; 34.5 [Wisconsin Alumni Research Foundation, where warfa-
for recurrent DVT/PE, cardiac and arterial prostheses. rin was developed]
The usual maintenance dose is 39mg/day. The INR is
usually checked daily or on alternate days initially, but Warren, John C (17781856). Professor of Surgery and
thereafter up to every 2 months, depending on the Anatomy at Harvard Medical School. It was at Warrens
response. invitation that Wells gave his demonstration of N2O
Drugs causing hepatic enzyme induction (e.g. rifam- anaesthesia, which ended in failure. Later, at Mortons
picin, phenytoin) reduce its effect. If the second drug is first public demonstration of diethyl ether, Warren per-
withdrawn without reducing the dose of warfarin, haem- formed the surgery.
orrhage may occur. Effects may be enhanced by drugs Cooper DKC (2012). Br Med J; 345: 423
that displace it from protein-binding sites, e.g. sulphon-
amides, NSAIDs. Emergency treatment of haemorrhage Washout curves. Graphs displaying the exponential
due to excessive warfarin effect involves use of vitamin decline in concentration of a substance that is con
K injection (up to 5mg iv) and the administration of tinuously being removed from a system. The substance
factors II, VII, IX and X (prothrombin complex concen- may be washed out by blood flow, in the case of dye
trate, or fresh frozen plasma). dilution cardiac output measurement, or by ventilation
Teratogenic; thus avoided in the first trimester of of the lungs, in the case of nitrogen washout. The term
pregnancy, although there is evidence it may be more is sometimes used to describe any negative exponential
effective than heparin at preventing valve thrombosis process.
and thus safer for pregnant women with prosthetic heart
valves. Warfarin crosses the placenta, risking placental or Water, see Fluid balance; Fluids, body
fetal haemorrhage if given in the third trimester.
Patients taking warfarin who present for surgery may Water balance, see Fluid balance
pose problems with perioperative coagulation. Sug-
gested guidelines: Water diuresis. Diuresis occurring about 15min after
heart valves: maintain warfarin therapy for short the intake of a large volume of hypotonic fluid. Absorp-
(under 30min) surgery, with fresh frozen plasma tion of the fluid is followed by inhibition of vasopressin
available. Otherwise, stop warfarin 3 days preopera- secretion and by increased urinary water loss.
tively, and start heparin infusion 24h later (about
15000 units/12h), maintaining activated partial Water intoxication, see Hyponatraemia
thromboplastin time (APTT) at 23 times normal.
Stop heparin 6h preoperatively, and check INR and WaterhouseFriderichsen syndrome, see Adrenocor-
APTT 1h preoperatively. Surgery may be delayed, tical insufficiency
or plasma administered, if INR exceeds 1.5. Restart
warfarin as soon as possible postoperatively, or Waters bag, see Anaesthetic breathing systems
heparin if nil by mouth for over 48h. Extra precau-
tions have been suggested for prosthetic mitral Waters canister, see Carbon dioxide absorption in
valves, since the risk of emboli is greater than for anaesthetic breathing systems

605
606 Waters, Ralph Milton

Waters, Ralph Milton (18831979). US anaesthetist; airway occlusion pressure greater than 6 cmH2O
became Assistant Professor of Surgery in charge of below atmospheric.
anaesthetics at University of Wisconsin, leading to his tidal volume > 5ml/kg.
appointment as the first university Professor of Anaes- minute ventilation < 10 litres.
thesia in the USA (1933). Was the first to establish a vital capacity > 1015ml/kg.
resident training programme in anaesthesia and the first FRC > 50% of predicted value.
to use cyclopropane clinically (1930). Re-examined chlo- ratio of breaths/min to tidal volume in litres < 100.
roform toxicity, advocated the use of inflatable cuffs on After long-term ventilation, scoring systems have been
tracheal tubes, and was involved in many aspects of proposed to predict difficult weaning, reflecting FIO2
anaesthesia, including the use of thiopental and endo- and level of PEEP required, lung compliance, work of
bronchial intubation. Designed his to-and-fro cannister breathing, temperature, pulse rate and arterial BP. Other
for CO2 absorption in anaesthetic breathing systems, and risk factors for difficult weaning include: increased
the Waters airway, a metal oropharyngeal airway with a airway resistance (e.g. COPD, tracheal stenosis); respira-
side-arm for attachment to a gas supply. tory muscle fatigue; hypoxia and acidosis; cardiac failure;
confusion; sleep deprivation; prolonged illness; and criti-
Waterton, Charles (17831865). Squire of Walton Hall, cal illness polyneuropathy/myopathy.
Yorkshire; made his first voyage to South America in Techniques of weaning:
1812. Described the preparation of curare and the blow- humidification of inspired air.
pipes, darts, bows and arrows used by the Indians of the sitting the patient up increases FRC and diaphrag-
Amazon and Orinoco basins. Experimented with the matic efficiency.
drug on his return to England, and maintained life in a the lowest FIO2 necessary to maintain adequate
paralysed donkey by employing IPPV. Published details oxygenation should be used, to decrease the risk
of his work and travels in Wanderings in South America of absorption atelectasis, and possibly promote
(1825). hypoxic pulmonary vasoconstriction. Inappropri-
ately high FIO2 should be avoided in CO2-retaining
Watt. Unit of power. One watt (W) = 1 joule per second patients with COPD.
(J/s). a simple T-piece is often used when IPPV has been
[James Watt (17361819), Scottish engineer] for a short duration. A 30cm expiratory limb and
fresh gas flow of twice minute volume will prevent
Waveforms. Repetitive patterns plotted against time indrawing of room air with lowering of FIO2, and
produce waveforms that may be complex (e.g. ECG) or rebreathing. Use should be limited in duration as
simple, as in the sine wave. All complex waveforms may the loss of physiological PEEP may increase the risk
be mathematically deconstructed into component sine of atelectasis.
waves (Fourier analysis). For any sine wave, there is CPAP is often preferred, especially following
oscillation about a mean value, the maximal displace- high PEEP, in ARDS and in left ventricular
ment from which is the amplitude. The number of com- dysfunction.
plete oscillations per second is the frequency, and the specific ventilatory modes:
distance between successive points at the same stage of IMV and variants: the set mandatory ventilator
the cycle is the wavelength. Waveform monitoring is very rate is decreased as patient spontaneous rate
common in anaesthesia and intensive care, e.g. cardio- increases. Spontaneous breaths are usually aug-
vascular (ECG, intravascular pressures, plethysmogra- mented with inspiratory pressure support (see
phy), respiratory (rate, depth, pattern), ventilatory (gas below). Allows closer monitoring of recovery and
flow, pressure), neurological (intracranial pressure, EEG, reduces complications of IPPV.
nerve conduction studies). airway pressure release ventilation, inspiratory
pressure support, pressure-regulated volume
Weaning from ventilators. Process of gradual with- control ventilation, mandatory minute ventila-
drawal of ventilatory support. Usually presents no prob- tion, inspiratory volume support, high-frequency
lems after less than a few days ventilation; following ventilation and variants and negative pressure
longer periods or poor baseline respiratory function, ventilation have also been used.
rapid weaning is less likely. non-invasive positive pressure ventilation.
Criteria for beginning weaning vary considerably; the overall time for completion of weaning may not be
following have been suggested: reduced by the above methods, but sedation and
absence of major organ or system failure, particu- complications of IPPV may be reduced, and patient
larly CVS. morale may benefit from coming off the ventilator
precipitating illness is successfully treated. sooner. Assessment is also made easier.
absence of severe infection or fever. short periods of spontaneous or assisted ventila-
adequate nutrition. tion may be introduced and gradually increased,
low intra-abdominal pressure. with clinical monitoring, assessment of SpO2 and fre-
absence of severe fluid, acidbase, endocrine or quent arterial blood gas measurements. Inspiratory
electrolyte disturbance, e.g. of potassium, magne- muscle resistance training may be incorporated.
sium, calcium or phosphate. Recommencement of IPPV should be considered if
minimal sedation with absence of severe pain. tachypnoea (> 30 breaths/min), tachycardia (> 110
respiratory function: beats/min), fatigue, restlessness, distress or falling
arterial blood gases are near premorbid values. SpO2 occur.
respiratory rate < 35 breaths/min. extubation may be performed when the patient is
maximal negative inspiratory airway pressure stable and able to protect the airway. Excessive
attainable exceeds 25 cmH2O. secretions may be removed via minitracheotomy.
 Wind-up 607

Elective formation of a tracheostomy may assist in WFSA, see World Federation of Societies of
weaning by reducing dead space, allowing easy Anesthesiologists
access for tracheobronchial toilet and permitting a
reduction in sedation. Wheezing. Sustained, polyphonic whistling respiratory
Work of breathing is increased by demand and expira- sound produced usually during expiration, indicating
tory valves and tubing, especially using CPAP and IMV narrowing of the natural or artificial airway. Distin-
circuits through certain ventilators. Modern ventilators guished from stridor by being lower-pitched and com-
provide circuits of low resistance, with minimal exertion posed of a wider range of frequencies, and usually
required to open demand valves. represents smaller airways obstruction. May be gener-
McConville JF, Kress JP (2012). N Engl J Med; 367: alised or localised.
22339 Caused by:
narrowed bronchi: bronchospasm, bronchiolitis,
Wedge pressure, see Pulmonary capillary wedge pulmonary oedema, aspiration of gastric contents,
pressure inhaled foreign body, airway tumour, pneumotho-
rax, coughing or straining (causing airway collapse
Wegeners granulomatosis. Necrotising small vessel via increased intrathoracic pressure).
granulomatous vasculitis, particularly involving pulmo- narrowed artificial airway: kinked tracheal tube,
nary and renal vessels. Features include non-specific over-inflated tracheal/tracheostomy tube cuff,
symptoms (malaise, weight loss, fever, night sweats), placement of the tracheal tubes bevel against the
nasal discharge and ulceration, pleurisy, haemoptysis, posterior wall of the trachea, endobronchial intu
myalgia, arthralgia and renal failure. Subglottic stenosis bation, kinked/obstructed respiratory tubing, mal-
may result in difficult airway management. Progression function of breathing system or ventilator valves.
is variable but some cases rapidly develop MODS Bronchospasm should be diagnosed only when other
requiring ICU admission for IPPV and haemofiltration/ causes have been excluded.
dialysis. The diagnosis may be suspected clinically if
both lungs and kidneys are involved, supported by Whistle discriminator. Obsolete device used to confirm
detecting antineutrophil cytoplasmic antibodies correct attachment of N2O and O2 supplies to an anaes-
(ANCA) in plasma. Tissue biopsies are frequently thetic machine by virtue of the differently pitched sounds
unhelpful as granulomatous deposits are difficult to produced when the gases flow through it, because of
locate in life, even in the kidney. their different densities.
Treatment of organ failure is supportive; Wegeners
itself is treated with cyclophosphamide and corticoste- WHO Surgical Safety Checklist, see World Health
roids. Eventual remission is complete in approximately Organization Surgical Safety Checklist
75% of cases.
[Friedrich Wegener (19071990); German pathologist]
See also, Vasculitides Whole bowel irrigation. Technique of GIT decontami-
nation used in the treatment of poisoning and overdoses,
Weight. The force exerted upon a body due to gravity. especially with metals and delayed-release drug prepa-
Equals the product of the mass of the body and local rations, although convincing evidence for its efficacy is
acceleration due to gravity. The weight of a body of mass lacking. Employs large volumes (up to 2 l/h in adults) of
1 kilogram is 1 kilogram weight (kilogram force). polyethylene glycol administered via mouth or nasogas-
tric tube until the rectal effluent is clear. Should not be
Weils disease, see Leptospirosis used in obtunded patients or in the presence of gastro-
intestinal ileus, intestinal obstruction, perforation or
Wells, Horace (18151848). US dentist, present at haemorrhage. Electrolyte disturbances have not been
Coltons demonstration of N2O in Hartford, Connecticut reported with polyethylene glycol, unlike preoperative
on 10 December 1844. Noticing that a member of the bowel preparations, which were studied initially.
audience (Samuel Cooley) had knocked his shin under
the influence and felt no pain, he suggested its use for Wilcoxon signed rank test, see Statistical tests
dental extraction. Wells had one of his own teeth pulled
out by John Riggs the following day, whilst breathing Willis, circle of, see Cerebral circulation
N2O prepared by Colton. Performed successful painless
extractions in several patients over subsequent days, Wind-up. Phenomenon in which the electrophysiologi-
before his ill-fated demonstration of N2O before Warren cal response of central pain-carrying neurones (e.g. those
at Harvard Medical School, Boston, at which the patient in the dorsal horn of the spinal cord) increases with
complained of pain and Wells was denounced as a fraud. repetitive stimulation of peripheral nociceptors; in addi-
Continued to practise dentistry, but became increasingly tion the receptive fields of the individual neurones
disillusioned as acceptance of N2O was overshadowed expand. Partly explains the hyperalgesia and allodynia
by Mortons discovery of diethyl ether. Later a chloro- that may occur in acute and chronic pain states, and the
form addict, he committed suicide by cutting his femoral concept of plasticity within the CNS by which painful
artery whilst in prison. input may alter the connections and activity of central
[Samuel Cooley (1809?), druggists assistant; John neurones. Excitatory amino acids (e.g. glutamate) are
Riggs (18101885), US dentist] thought to be involved, acting especially via NMDA
receptors, although other receptor types are also thought
Wenckebach phenomenon, see Heart block to be involved, as are other modulating substances such
as dynorphin, substance P and calcitonin gene-related
Wernickes encephalopathy, see Vitamin deficiency peptide. Intracellular accumulation of these and other
608 Withdrawal of treatment in ICU

substances via gene induction is also thought to be

important. Prevention of wind-up is a central tenet of
preventive and pre-emptive analgesia. wave

Withdrawal of treatment in ICU. Cessation of all or

individual components of treatment is a frequent mode
of death in the ICU. In general, treatment is withdrawn Fig. 174 ECG showing waves
when it has ceased or failed to achieve the benefits for
which it was employed. It usually takes place when there
is confirmed brainstem death or the patients prognosis
is poor with no prospect of returning to a reasonable Where the condition that precipitated the patients
quality of life. Occasionally, even a treatment that admission to ICU involves suspicious circumstances (e.g.
might produce benefit may be withheld or withdrawn poisoning, assault), contact with the coroner is advised
if the patient is suffering from a terminal illness. before treatment withdrawal. Whatever the circum-
Withdrawal of each medical treatment should be consid- stances, good clinical records should be kept.
ered from the patients perspective in the context of See also, Ethics; Euthanasia; Mental Capacity Act; Pallia-
benefit. Withdrawal of treatment should be regarded as tive care
permitting the dying process to continue, rather than
causing death. WolffParkinsonWhite syndrome. Condition in
Factors taken into account in the decision to with- which a congenital accessory connection between the
draw treatment include the patients physiological atria and ventricles conducts more rapidly than the
reserve, diagnosis, severity of disease, co-morbidity, atrioventricular (AV) node, but has a longer refractory
prognosis, response to treatment, anticipated quality of period. An atrial extrasystole finds the accessory bundle
life and wishes, if known. still refractory, but when the impulse passes via the
Ethical issues include: AV node to the ventricles, the accessory bundle
the wishes (often unknown) of an unconscious has recovered, and can conduct the impulse back to the
patient. atria. Circular conduction can continue with resultant
the validity and legality of decisions made by a SVT. AF and atrial flutter may also occur, but less
surrogate. commonly.
the diversion of limited resources from patients The ECG classically shows a short PR interval and
with a good chance of survival to those who are wide QRS complexes with waves (Fig. 174). A positive
unlikely to benefit. QRS complex in lead V1 denotes type A (accessory
the definition of futility. bundle on the left side of the heart); if negative, type B
the definition of a good quality of life. (right side of heart).
the nature of medical treatment, i.e. feeding, Anaesthetic management of known cases should
hydration. be directed at avoiding increased sympathetic activity,
consideration of religious beliefs. including that due to anxiety. Antiarrhythmic drugs
Before withdrawal of treatment, the following should should be continued perioperatively. Drugs causing
be undertaken/sought: tachycardia (e.g. atropine, ketamine, pancuronium)
full discussion between all medical, nursing and should be avoided. Isoflurane is probably the volatile
paramedical staff treating the patient during which anaesthetic agent of choice as it suppresses accessory
consensus should be obtained that the patient is pathway conduction.
dying. Treatment of arrhythmias (including perioperatively)
the views of the family, the legal status of any follows standard measures. Digoxin and verapamil may
appointed representative and advance decision of increase impulse conduction through accessory path-
the patient. ways by blocking conduction through the AV node, and
consensus on the mode, extent and timing of should be avoided. Management of established cases
treatment withdrawal by clinical staff and includes electrophysiological assessment (accessory
patients family. pathway mapping), long-term prophylactic therapy (e.g.
If brainstem death is diagnosed and organ donation is with flecainide, sotalol) and radiofrequency ablation of
intended, withdrawal of support takes place after organ the accessory pathway.
removal (beating heart donation). Otherwise, observa- [Sir John Parkinson (18851976), London cardiologist;
tions, monitoring, drugs, procedures and routine care Louis Wolff (18981972) and Paul White (18861973),
(apart from symptom palliation) can be withdrawn once US cardiologists]
clinical staff and the patients family have reached a
consensus. IPPV may continue unchanged during this Work. Product of force and the distance through which
period or the technique of terminal weaning of ventila- it acts. Work is done whenever the point of application
tion may be employed, in which inspired oxygen concen- of a force moves in the direction of that force. Also
tration is reduced to an FIO2 of 0.21. Feeding/antibiotics expressed as the product of the change in volume of a
are stopped and inotropic support terminated. Sedation system and the pressure against which this change occurs
and analgesia are maintained, or increased if the patient (e.g. stroke work). SI unit is the joule.
becomes distressed, to ensure a peaceful, humane,
comfortable and dignified death for the patient and to Work of breathing, see Breathing, work of
diminish distress for the family. Privacy is important for
the patient and family during the dying process. Organ World Federation of Societies of Anaesthesiologists
donation after death is known as non-beating heart (WFSA). Founded in 1955 at the first World Congress of
donation. Anaesthesiologists in The Hague, Holland, in order to
 Wrist, nerve blocks 609

promote anaesthetic education, research, training and Wrist, nerve blocks. Used for minor surgery to the hand.
safety standards throughout the world. World Con- The following nerves are blocked (Fig. 175):
gresses are held every 4 years (since 1960). Membership median nerve (C6T1): at the level of the proximal
is via 40 anaesthetic societies in different countries. skin crease, it lies between flexor carpi radialis
Has three regional sections: Latin American, Asia/ tendon laterally and palmaris longus tendon medi-
Australian and European. The last of these was founded ally. With the wrist dorsiflexed, 25ml local anaes-
in 1966 and renamed the Confederation of European thetic agent is injected just lateral to the palmaris
National Societies of Anaesthesiology in 1998. longus tendon, at a depth of 0.51cm.
Baird WLM (1995). Acta Anaesthesiol Scand; 39: ulnar nerve (C7T1): lies under flexor carpi ulnaris
4367 tendon proximal to the pisiform bone, medial and
deep to the ulnar artery. At the level of the ulnar
World Health Organization Surgical Safety Check- styloid process, a needle is inserted between flexor
list. Tool introduced by the World Health Organization carpi ulnaris tendon and the ulnar artery, and 25ml
(WHO) in 2008 to improve patient safety during surgery, solution injected. The two cutaneous branches of
and implemented within the NHS in 2010. Consists of a the nerve may be blocked by subcutaneous infiltra-
series of questions confirming the main issues that may tion around the ulnar side of the wrist from the
hinder safe operating or result in adverse outcomes, flexor carpi ulnaris tendon.
arranged in three phases: radial nerve (C5T1): its branches pass along the
Before anaesthesia (sign in): patients identity, radial and dorsal aspects of the wrist. At the level
site and type of procedure and consent; presence of the proximal skin crease, a needle is inserted
of allergies; expected blood loss; anaesthetic lateral to the radial artery, and 3ml solution
equipment/drugs checked; risk of aspiration or diffi- injected. Infiltration around the radial border of the
cult airway. wrist blocks superficial branches.
Before the surgical procedure (time out): introduc-
tion of all team members; patients identity, site and
type of procedure; ASA physical status, expected
blood loss; any anticipated critical events; need for
antibiotics or imaging/specialised equipment (includ- Median nerve
ing monitoring); sterility of instruments.
Before the patient leaves the operating theatre (sign
out): correct record of procedure and labelling of
specimens; correct instrument, sponge and needle Ulnar nerve
counts; any equipment issues addressed; any key con-
cerns for recovery.
Supported by evidence in many hospital settings, with
the biggest reductions in morbidity and mortality seen Radial nerve
in (but not restricted to) developing countries. Has been
modified according to local needs, e.g. in obstetric and
other specialised units.
Sparkes D, Rylah B (2010). Br J Hosp Med (Lond); 71:
27680 Fig. 175 Cutaneous innervation of the hand
 X
Xanthines (Methylxanthines). Derivatives of dioxypu- environmental properties (unlike N2O), have led to
rine; they include caffeine and theophylline. Phosphodi- investigations into its use as an anaesthetic agent, despite
esterase inhibitors, with wide spectra of activity, including its high cost.
CNS stimulation, diuresis, increased myocardial contrac- Its radioactive isotope 133Xe is used in estimations of
tility and smooth muscle relaxation. May also inhibit organ blood flow (e.g. Xe CT for assessment of cerebral
adenosine and reduce noradrenaline release. blood flow) and in analysis of distribution of ventilation
in lung perfusion/ventilation scans.
Xenon. Inert gas, making up less than 0.00001% of air. Dickinson R, Franks NP (2010). Crit Care; 14: 229.
Shown to have analgesic and anaesthetic properties with
a blood/gas partition coefficient of 0.14, resulting in Xylometazoline. Vasoconstrictor sympathomimetic
extremely rapid uptake and excretion regardless of drug, acting via -adrenergic receptor agonism. Used as
duration of use. Oil/gas partition coefficient is 1.9, with a nasal decongestant and to reduce bleeding during
an MAC of 71%. Has respiratory depressant effects nasal intubation, including awake intubation. Instilled
but little effect on cardiovascular stability. Increases into each nostril as either drops or a spray of a 0.1%
cerebral blood flow and intracranial pressure but may solution. Hypertension may rarely occur in susceptible
have neuroprotective properties through its inhibition of patients, e.g. those taking monoamine oxidase inhibitors.
NMDA receptors. These features, plus its lack of adverse Should be avoided in closed-angle glaucoma.

611
 Y
Yatess correction, see Statistical tests Yohimbine, see -Adrenergic receptor antagonists

613
 Z
Zeolite. Hydrous silicate, used for ion or molecule Dosage:
trapping. An artificial zeolite is used in O2 concentrators, 250300mg orally bd.
to retain nitrogen from compressed air. Has also 0.81mg/kg iv over an hour, 4-hourly.
been added to soda lime to retain water and prevent Side effects include bone marrow depression, nausea
drying out. and vomiting, anorexia, GIT disturbance, neuropathy,
convulsions, myopathy, hepatic impairment.
Zero, absolute. The lowest possible temperature that
can be attained: 0 kelvin (corresponds to 273.15C). Zinc deficiency. May occur in patients with inadequate
diets, malabsorption, catabolism and during TPN. Causes
Zero-order kinetics, see Pharmacokinetics angular stomatitis, eczematous eruptions and impaired
wound healing. Normal plasma zinc level (assuming
Ziconotide acetate. Synthetic form of a peptide derived normal serum albumin) is 1220mol/l; daily require-
from the venomous sea snail Conus magus, introduced ment is 2.56.4mg/day.
in 2006 for the treatment of chronic pain. Acts as a Replacement therapy dosage: 125mg zinc sulphate
neurone-specific N-type calcium channel blocking drug monohydrate odtds. Side effects of therapy include
and thought to interrupt ascending pain pathways in the abdominal pain and dyspepsia.
spinal cord.
Dosage: 2.4g/day by continuous intrathecal infu- Zoledronic acid, see Bisphosphonates
sion, increased up to 19.2g/day.
Side effects: confusion, dizziness, headache, visual dis- Zone of risk, see Explosions and fires
turbances, nausea/vomiting, agitation and psychiatric
symptoms. Zopiclone Non-benzodiazepine hypnotic agent used
for the short-term (< 4 weeks) treatment of insomnia.
Zidovudine (Azidothymidine; AZT). Nucleoside Acts at GABAA receptors, potentiating the action of
reverse transcriptase inhibitor; a thymidine derivative, endogenous GABA. Rapidly absorbed, with minimal
it inhibits DNA synthesis via incorporation into DNA. hangover. Undergoes hepatic metabolism with minimal
The first anti-HIV drug used; other similar drugs are renal excretion of the unchanged drug; dosage should
now available but zidovudine is still used for prevention therefore be reduced in hepatic failure.
and treatment of HIV infection and AIDS. Tradition- Dosage: 3.757.5mg at night.
ally used in cases of needlestick injury to medical/ Side effects: taste disturbance, nausea, dry mouth,
nursing staff. headache, rebound insomnia upon cessation.

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Examination revision
checklist
This checklist has been compiled from entries of particu- Heart rate.
lar relevance to examination candidates, classified and Hfner constant.
listed alphabetically in order to support systematic study Hypotension.
of examination topics. This list is not exhaustive, and, for Insensible water loss.
clarity, entries that summarise a topic and incorporate Left atrial pressure.
multiple crossreferences (e.g. Opioid analgesic drugs) Left ventricular end-diastolic pressure.
have been included in preference to listing every rele- Mixed venous blood.
vant entry, e.g. Alfentanil, Fentanyl, Remifentanil, etc. Myocardial contractility.
The latter should still be referred to where appropriate, Myocardial metabolism.
to gain relevant detail. Myoglobin.
Oedema.
Index checklist: Oncotic pressure
Osmolality and osmolarity.
Physiology p. 617 Osmolar gap.
Clinical Anatomy p. 619 Osmoreceptors.
Pharmacology p. 620 Osmosis.
Physics and Measurement p. 621 Osmotic pressure.
Statistics p. 622 Pacemaker cells.
Clinical Anaesthesia p. 623
Perfusion pressure.
Critical Care p. 624
Equipment p. 625 Preload.
Medicine p. 626 Pulmonary artery pressure.
Organisational p. 628 Pulmonary circulation.
Radiology p. 628 Pulmonary vascular resistance.
Pulse pressure.
Right ventricular function.
Sinus arrhythmia.
PHYSIOLOGY Sinus bradycardia.
CARDIOVASCULAR
Sinus rhythm.
Afterload. Sinus tachycardia.
Albumin. Starling forces.
Anaerobic threshold. Starlings law (FrankStarling law).
Arterial blood pressure. Stroke volume.
Atrial natriuretic peptide. Stroke work.
Autoregulation. Systemic vascular resistance.
Baroreceptor reflex. Valsalva manoeuvre.
Baroreceptors. Vasomotor centre.
Blood. Venous return.
Blood flow. Venous waveform.
Blood groups. Vitamin K.
Blood volume.
Capacitance vessels.
Capillary refill time. CELLULAR/MOLECULAR/METABOLISM
Cardiac cycle. Action potential.
Cardiac output. Active transport.
Cardioinhibitory centre. Acute-phase response.
Central venous pressure (CVP). Adenosine triphosphate and diphosphate.
Coagulation. Adrenergic receptors.
Coronary blood flow. Basal metabolic rate.
2,3-Diphosphoglycerate (2,3-DPG). Calcium.
Ejection fraction. Carbohydrates.
Exercise. Carbonic anhydrase.
Fetal haemoglobin. Catabolism.
Fibrinolysis. Catechol-O-methyl transferase (COMT).
Fluids, body. Complement.
Haemoglobin (Hb). Cyclo-oxygenase (COX).
Haemorrhage. Cytochrome oxidase system.

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 Examination revision checklist

Cytokines. NERVOUS SYSTEM

Donnan effect (GibbsDonnan effect). Acetylcholine.
Energy balance. Acetylcholine receptors.
Fats. Acetylcholinesterase.
G protein-coupled receptors. -Aminobutyric acid (GABA) receptors.
Glycolysis. Autonomic nervous system.
Goldman constant-field equation. Bloodbrain barrier.
Histamine and histamine receptors. Catecholamines.
Homeostasis. Cerebral blood flow.
5-Hydroxytryptamine (5-HT, Serotonin). Cerebral metabolism.
Immunoglobulins. Cerebral perfusion pressure.
Ketone bodies. Cerebrospinal fluid (CSF).
Lactate. Chemoreceptor trigger zone.
Magnesium. Chemoreceptors.
Membrane potential. Dermatomes.
Membranes. Dopamine receptors.
Metabolism. End-plate potentials.
Methionine and methionine synthase. Evoked potentials.
Monoamine oxidase (MAO). Gag reflex.
Muscle. Gate control theory of pain.
Muscle contraction. Glutamate.
Nernst equation. Intracranial pressure (ICP).
Nitrogen balance. Memory.
Phosphate. MonroKellie doctrine.
Potassium. Motor pathways.
Prostaglandins. Motor unit.
Second messenger. Muscle spindles.
Sodium. Myelin.
Sodium/potassium pump. N-Methyl-D-aspartate (NMDA) receptors.
Tricarboxylic acid cycle. Nerve conduction.
Vitamins. Neuromuscular junction.
Neurone.
Neurotransmitters.
ENDOCRINE/REPRODUCTIVE Nociception.
Adrenal gland. Pain pathways.
Calcitonin. Parasympathetic nervous system.
Corticosteroids. Pupil.
Glucagon. Referred pain.
Growth hormone. Reflex arc.
Insulin. Refractory period.
Pituitary gland. Sensory pathways.
Placenta. Sleep.
Pregnancy. Sympathetic nervous system.
Thyroid gland. Synaptic transmission.
Uterus. Wind-up.
Vasopressin.

GASTROINTESTINAL RENAL
Ammonia. Clearance.
Amylase. Clearance, free water.
Biliary tract. Creatinine clearance.
Gastric contents. Filtration fraction.
Gastric emptying. Glomerular filtration rate (GFR).
Liver. Juxtaglomerular apparatus.
Lower oesophageal sphincter. Kidney.
Nutrition. Nephron.
Swallowing. Renal blood flow.
Urea. Renin/angiotensin system.
Vomiting. Urine.

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 Examination revision checklist

RESPIRATORY AND ACID/BASE Oxygen flux.

Acidbase balance. Oxygen saturation.
Acidosis, metabolic. Oxygen transport.
Acidosis, respiratory. Oxyhaemoglobin dissociation curve.
Airway pressure. Peak expiratory flow rate.
Airway resistance. pH.
Alkalosis, metabolic. Pulmonary irritant receptors.
Alkalosis, respiratory. Pulmonary stretch receptors.
Alveolar air equation. Respiratory muscles.
Alveolararterial oxygen difference. Respiratory quotient.
Alveolar gas transfer. Respiratory symbols.
Alveolar gases. Shunt.
Alveolar ventilation. Shunt equation.
Alveolus. Siggaard-Andersen nomogram.
Anion gap. Standard bicarbonate.
Aortic bodies. Strong ion difference.
Apnoea. Surfactant.
Arteriovenous oxygen difference. Venous admixture.
Base. Ventilation/perfusion mismatch.
Base excess/deficit.
Bicarbonate.
Blood gas analyser.
Blood gas interpretation.
CLINICAL ANATOMY
Bohr effect.
CARDIOVASCULAR SYSTEM
Bohr equation.
Breathing, control of. Brachial artery.
Breathing, work of. Carotid arteries.
Buffers. Coronary circulation.
Carbon dioxide (CO2). Femoral artery.
Carbon dioxide dissociation curve. Fetal circulation.
Carbon dioxide, end-tidal. Heart.
Carbon dioxide response curve. Heart, conducting system.
Carbon dioxide transport. Jugular veins.
Carbon monoxide (CO). Mediastinum.
Carotid body. Pericardium.
Chloride shift (Hamburger shift). Venous drainage of arm.
Closing capacity. Venous drainage of leg.
Compliance. Vertebral arteries.
Cough.
Cyanosis.
Davenport diagram. MUSCULOSKELETAL SYSTEM
Dead space. Cervical spine.
Diffusing capacity (Transfer factor). Ribs.
Elastance. Skull.
Fink effect. Temporomandibular joint.
FIO2. Vertebrae.
Haldane effect.
HendersonHasselbalch equation.
HeringBreuer reflex (Inflation reflex).
Hydrogen ions (H+). NERVOUS SYSTEM
Hypoxia. Brachial plexus.
Hypoxic pulmonary vasoconstriction. Brain.
Intrapleural pressure. Cerebral circulation.
Laryngeal reflex. Cranial nerves.
Lung. Hypothalamus.
Lung volumes. Lumbar plexus.
Minute ventilation. Meninges.
Nitrogen washout. Myotomes.
Oxygen cascade. Sacral plexus.
Oxygen delivery. Spinal cord.
Oxygen extraction ratio. Spinal nerves.

619
 Examination revision checklist

RESPIRATORY SYSTEM Drug interactions.

Airway. Efficacy.
Diaphragm. Enzyme induction/inhibition.
Intercostal spaces. Exponential process.
Laryngeal nerves. Extraction ratio.
Larynx. First-pass metabolism.
Nose. Half-life (t1/2).
Pharynx. Ionisation of drugs.
Phrenic nerves. Isomerism.
Pleura. MichaelisMenten kinetics.
Tongue. Pharmacodynamics.
Tracheobronchial tree. Pharmacogenetics.
Pharmacokinetics.
pK.
SPECIAL ZONES Potency.
Antecubital fossa. Prodrug.
Epidural space. Protein-binding.
Femoral triangle. Receptor theory.
Neck, cross-sectional anatomy. Tachyphylaxis.
Orbital cavity. Target-controlled infusion (TCI).
Popliteal fossa. Therapeutic ratio/index.
Sacral canal. Time constant ().
Thoracic inlet. Volume of distribution (Vd).
Washout curves.

PHARMACOLOGY CARDIOVASCULAR
ANAESTHETIC AGENTS/SEDATIVES
-Adrenergic receptor agonists.
Anaesthesia, mechanism of. -Adrenergic receptor antagonists.
Concentration effect. -Adrenergic receptor agonists.
Fluoride ions. -Adrenergic receptor antagonists.
Inhalational anaesthetic agents. Antiarrhythmic drugs.
Intravenous anaesthetic agents. Anticholinergic drugs.
MeyerOverton rule. Antihypertensive drugs.
Minimal alveolar concentration (MAC). Calcium channel blocking drugs.
Second gas effect. Calcium sensitisers.
Cardiac glycosides.
ANALGESICS Diuretics.
Analgesic drugs. Inotropic drugs.
Capsaicin. Phosphodiesterase inhibitors.
Ethyl chloride. Statins.
Non-steroidal anti-inflammatory drugs. Sympathomimetic drugs.
Opioid analgesic drugs. Vasodilator drugs.
Opioid receptor antagonists. Vasopressor drugs.
Opioid receptors.
ENDOCRINE/REPRODUCTIVE
ANTI-INFECTIVES Carboprost.
Antibacterial drugs. Contraceptives, oral.
Antifungal drugs. Corticosteroids.
Antimalarial drugs. Desmopressin (DDAVP).
Antituberculous drugs. Ergometrine maleate.
Antiviral drugs. Hormone replacement therapy.
Hypoglycaemic drugs.
Misoprostol.
BASIC PRINCIPLES
Oxytocin.
Adverse drug reactions. Tocolytic drugs.
Affinity.
Agonist.
Antagonist. GASTROINTESTINAL
Bioavailability. Antacids.
Doseresponse curves. Antispasmodic drugs.
Drug development. Emetic drugs.

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 Examination revision checklist

H2 receptor antagonists. RESPIRATORY

Laxatives. Bronchodilator drugs.
Octreotide. Doxapram hydrochloride.
Prokinetic drugs. Mucolytic drugs.
Proton pump inhibitors.
OTHER
HAEMATOLOGICAL
N-Acetylcysteine.
Anticoagulant drugs. Alcohols.
Antifibrinolytic drugs. Chemical weapons.
Antiplatelet drugs. Dantrolene sodium.
Cytotoxic drugs. Herbal medicines.
Eptacog alfa. Hyaluronidase.
Fibrinolytic drugs. Lipid emulsion
Granulocyte colony-stimulating factor. Magnesium sulphate.
Immunoglobulins, intravenous (IVIG). Propylene glycol.
Immunosuppressive drugs.
Protamine sulphate.
PHYSICS AND MEASUREMENT
Thrombin inhibitors.
APPLIED PHYSICS AND CHEMISTRY
Activation energy.
INTRAVENOUS FLUIDS
Adiabatic change.
Colloid. Atmosphere.
Colloid/crystalloid controversy. Avogadros hypothesis.
Crystalloid. Bar.
Electrolyte. BeerLambert law.
Intravenous fluid administration. Bernoulli effect.
Intravenous fluids. Boiling point.
Tonicity. Boyles law.
Calorie.
LOCAL ANAESTHETICS Charge, electric.
EMLA cream. Charles law.
Local anaesthetic agents. Coanda effect.
Minimal blocking concentration (Cm). Colligative properties of solutions.
Minimal local anaesthetic concentration/dose/ Critical pressure.
volume. Critical temperature.
Critical velocity.
NEUROLOGICAL/PSYCHIATRIC Daltons law.
Density.
Anticonvulsant drugs.
Dew point.
Antidepressant drugs.
Diffusion.
Antiemetic drugs.
Doppler effect.
Antihistamine drugs.
Energy.
Antiparkinsonian drugs.
Ficks law of diffusion.
Antipsychotic drugs.
Flammability.
Central anticholinergic syndrome.
Flow.
Dystonic reaction.
Fluid.
Flumazenil.
Force.
Nicotine.
Gas.
Gas flow.
NEUROMUSCULAR TRANSMISSION Grahams law.
Acetylcholinesterase inhibitors. HagenPoiseuille equation.
Cholinesterase, plasma. Harmonics.
Denervation hypersensitivity. Heat.
Depolarising neuromuscular blockade. Heat capacity.
Dibucaine number. Henrys law.
Dual block (Phase II block). Humidity.
Hofmann degradation. Ideal gas law.
Neuromuscular blocking drugs. Isotherms.
Non-depolarising neuromuscular blockade. Laplaces law.
Priming principle. Laser surgery.
Recurarisation. Latent heat.
Sugammadex sodium. Molarity.

621
 Examination revision checklist

Normal solution. LiMON.

Ohms law. Mass spectrometer.
Partial pressure. Monitoring.
Partition coefficient. Neuromuscular blockade monitoring.
Pascal. Oscillotonometer.
Power (in Physics). Oximetry.
Poynting effect. Oxygen measurement.
Pressure. Peak flowmeters.
Pseudocritical temperature. pH measurement.
Radiation. Phase shift.
Radioisotopes. Plethysmography.
Raoults law. Pneumotachograph.
Resonance. Pressure measurement.
Reynolds number. Pulse oximeter.
Saturated vapour pressure (SVP). Respirometer.
Solubility. Rotameter.
Solubility coefficients. Spectroscopy.
Specific gravity (Relative density). Spirometer.
Starling resistor. Thromboelastography (TEG).
Stoichiometric mixture. Transducers.
STP/STPD.
Surface tension. ELECTRICITY
Temperature measurement. Antistatic precautions.
Tension. Capacitance.
Units, SI. Conductance.
Vapour. Coulomb.
Venturi principle. Current.
Viscosity (). Current density.
Work. Defibrillation.
Electrical symbols.
Electrocution and electrical burns.
CLINICAL MEASUREMENT Impedance, electrical.
Amplifiers. Inductance.
Arterial blood pressure measurement. Resistance.
Arterial cannulation. Volt.
Arterial waveform.
Becquerel.
Bispectral index monitor. STATISTICS
Body mass index (BMI). Absolute risk reduction.
Calibration. Confidence intervals.
Capnography. Data.
Carbon dioxide measurement. Degrees of freedom.
Cardiac output measurement. Errors, statistical.
Cerebral function monitor. Likelihood ratio.
cgs system of units. Mean.
Damping. Median.
Dilution techniques. Meta-analysis (Systematic review).
End-tidal gas sampling. Mode.
Fade. Null hypothesis.
Fick principle. Number needed to treat (NNT).
Flame ionisation detector. Odds ratio.
Flowmeters. Percentile.
Flowvolume loops. Populations.
Gain, electrical. Power (in Statistics).
Gas analysis. Predictive value.
Gas chromatography. Probability (P).
Haldane apparatus. Randomisation.
Hygrometer. Receiver operating characteristic curves.
Hysteresis. Relative risk reduction.
Impedance plethysmography. Samples, statistical.
Isobestic point. Sensitivity.
Korotkoff sounds. Specificity.

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 Examination revision checklist

Standard deviation. Laparoscopy.

Standard error of the mean. Laryngoscopy.
Statistical frequency distributions. Laryngospasm.
Statistical significance. Liver transplantation.
Statistical tests. Malignant hyperthermia.
Variance. Medicolegal aspects of anaesthesia.
Nerve injury during anaesthesia.
Obesity.
Plastic surgery.
CLINICAL ANAESTHESIA Positioning of the patient.
GENERAL TOPICS Postoperative analgesia.
Air embolism. Postoperative cognitive dysfunction.
Altitude, high. Postoperative nausea and vomiting.
Altitude, low. Premedication.
Anaesthesia, depth of. Preoperative assessment.
Anaesthesia, stages of. Preoperative optimisation.
Anaesthetic morbidity and mortality. Preoxygenation.
Anaesthetists non-technical skills. Radiology, anaesthesia for.
Anaphylaxis. Recovery from anaesthesia.
ASA physical status. Regurgitation.
Aspiration of gastric contents. Sedation.
Awareness. Seldinger technique.
Bariatric surgery. Shivering, postoperative.
Blood loss, perioperative. Smoking.
Bronchospasm. Sore throat, postoperative.
Carbon dioxide narcosis. Stress response to surgery.
Cardiac risk indices. Substance abuse.
Cardiopulmonary exercise testing. Teeth.
Cell salvage. Temperature regulation.
Central venous cannulation. Total intravenous anaesthesia (TIVA).
Confusion, postoperative. Tourniquets.
Consent for anaesthesia.
Cricoid pressure (Sellicks manoeuvre).
CARDIOTHORACIC
Cricothyrotomy.
Day-case surgery. Cardiac surgery.
Elderly, anaesthesia for. Cardiopulmonary bypass.
Electroconvulsive therapy. Heart transplantation.
Emergence phenomena. Lung transplantation.
Emergency surgery. One-lung anaesthesia.
Environmental impact of anaesthesia. Thoracic surgery.
Environmental safety of anaesthetists.
Explosions and fires. ENT/MAXILLOFACIAL
Extubation, tracheal.
Airway obstruction.
Eye care.
Bronchoscopy.
Fluid balance.
Dental surgery.
Heat loss, during anaesthesia.
Ear, nose and throat surgery.
Hypotensive anaesthesia.
Epistaxis.
Hypothermia.
Facial trauma.
Hypoventilation.
Foreign body, inhaled.
Hypovolaemia.
Injector techniques.
Induction of anaesthesia.
Insufflation techniques.
Induction, rapid sequence.
Ludwigs angina.
Intubation, awake.
Maxillofacial surgery.
Intubation, blind nasal.
Stridor.
Intubation, complications of.
Tonsil, bleeding.
Intubation, difficult.
Trismus.
Intubation, failed.
Intubation, fibreoptic.
Intubation, oesophageal. NEUROANAESTHESIA
Intubation, tracheal. Head injury.
Investigations, preoperative. Neurosurgery.
Jehovahs Witnesses. Spinal surgery.

623
 Examination revision checklist

OBSTETRICS REGIONAL
Amniotic fluid embolism. Ankle, nerve blocks.
Antepartum haemorrhage. Blood patch, epidural.
Aortocaval compression. Brachial plexus block.
Caesarean section. Caudal analgesia.
Confidential Enquiries into Maternal Deaths. Cervical plexus block.
Fetal monitoring. Combined spinalepidural anaesthesia.
Fetus, effects of anaesthetic drugs on. Dural tap.
HELLP syndrome. Epidural anaesthesia.
Obstetric analgesia and anaesthesia. Fascia iliaca compartment block.
Placenta praevia. Femoral nerve block.
Placental abruption. Inguinal hernia field block.
Postpartum haemorrhage. Intercostal nerve block.
Pre-eclampsia. Interpleural analgesia.
Intravenous regional anaesthesia.
OPHTHALMIC Knee, nerve blocks.
Paravertebral block.
Eye, penetrating injury.
Penile block.
Intraocular pressure.
Peribulbar block.
Oculocardiac reflex.
Post-dural puncture headache.
Ophthalmic surgery.
Psoas compartment block.
Rectus sheath block.
ORTHOPAEDICS Regional anaesthesia.
Bone marrow harvest. Retrobulbar block.
Fat embolism. Sciatic nerve block.
Kyphoscoliosis. Spinal anaesthesia.
Methylmethacrylate. Sub-Tenons block.
Orthopaedic surgery. Transversus abdominis plane block.
Wrist, nerve blocks.
PAEDIATRICS
UROLOGY
Apgar scoring system.
Choanal atresia. Extracorporeal shock wave lithotripsy.
Croup. Renal transplantation.
Diaphragmatic herniae. Transurethral resection of the prostate.
Epiglottitis. TURP syndrome.
Facial deformities, congenital. Urinary retention.
Gastroschisis and exomphalos.
Necrotising enterocolitis. VASCULAR
Neonate. Aortic aneurysm, abdominal.
Paediatric anaesthesia. Aortic aneurysm, thoracic.
Pyloric stenosis. Aortic dissection.
Tracheo-oesophageal fistula. Carotid endarterectomy.
Transposition of the great arteries.

CRITICAL CARE
PAIN
GENERAL TOPICS
Acupuncture.
Critical care.
Central pain.
Imaging in intensive care.
Coeliac plexus block.
Lactic acidosis.
Complex regional pain syndrome.
Multiple organ dysfunction syndrome (MODS).
Dorsal column stimulation.
Paediatric intensive care.
Gasserian ganglion block.
Transportation of critically ill patients.
Pain.
Withdrawal of treatment in ICU.
Pain evaluation.
Pain management.
Patient-controlled analgesia. CARDIOVASCULAR
Phantom limb. Cardiogenic shock.
Stellate ganglion block. Pulmonary artery catheterisation.
Sympathetic nerve blocks. Pulmonary capillary wedge pressure.
Transcutaneous electrical nerve stimulation. Septic shock.
Trigger points. Shock.

624
 Examination revision checklist

GASTROINTESTINAL Cardiopulmonary resuscitation (CPR).

Abdominal compartment syndrome. Cardiopulmonary resuscitation, neonatal.
Nutrition, enteral. Cardiopulmonary resuscitation, paediatric.
Nutrition, total parenteral (TPN). Choking.
Pancreatitis. Intraosseous fluid administration.
Refeeding syndrome. Near-drowning.
Selective decontamination of the digestive tract.
Stress ulcers. TRAUMA
Abdominal trauma.
NEUROLOGICAL Burns.
Brainstem death. Chest trauma.
Cerebral protection/resuscitation. Compartment syndromes.
Coma. Golden hour.
Confusion in the intensive care unit. Pelvic trauma.
Coning. Peritoneal lavage.
Critical illness polyneuropathy. Rib fractures.
GuillainBarr syndrome. Trauma.
ICU delirium.
Intracranial pressure monitoring. EQUIPMENT
Sedation scoring systems. AIRWAY
Spinal cord injury.
Airway exchange catheter.
Status epilepticus.
Airways.
Vegetative state.
Cuffs, of tracheal tubes.
Endobronchial tubes.
ORGANISATIONAL Facemasks.
APACHE scoring system. Fibreoptic instruments.
Care bundles. Intubation aids.
Intensive care follow-up. Laryngeal mask airway (LMA).
Intensive care unit. Laryngoscope.
Mortality/survival prediction on intensive care unit. Laryngoscope blades.
Minitracheotomy.
RESPIRATORY Oesophageal obturators and airways.
Tracheal tubes.
Acute lung injury.
Alveolar recruitment manoeuvre.
Assisted ventilation. BREATHING SYSTEMS
Barotrauma. Adjustable pressure-limiting valves.
Continuous positive airway pressure. Anaesthetic breathing systems.
Dynamic hyperinflation. Carbon dioxide absorption, in anaesthetic
Extracorporeal membrane oxygenation. breathing systems.
High-frequency ventilation. Circle systems.
Hypercapnia. Coaxial anaesthetic breathing systems.
Hypoxaemia. Demand valves.
Inspiratory: expiratory ratio (I:E ratio). Filters, breathing system.
Intermittent positive pressure ventilation. Heatmoisture exchanger (HME).
Lung protection strategies. Humidification.
Non-invasive positive pressure ventilation. Nebulisers.
Pleural effusion. Non-rebreathing valves.
Pneumothorax. Reservoir bag.
Respiratory failure. Scavenging.
Respiratory muscle fatigue. Self-inflating bags.
Tracheostomy. Soda lime.
Ventilator-associated lung injury. Triservice apparatus.
Ventilator-associated pneumonia.
Ventilators. GAS SUPPLY
Weaning from ventilators.
Air.
Bodok seal.
RESUSCITATION Cylinders.
Advanced life support, adult. Filling ratio.
Basic life support, adult. Oxygen.
Cardiac arrest. Oxygen concentrator.

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 Examination revision checklist

Oxygen failure warning device. Marfans syndrome.

Pin index system. Muscular dystrophies.
Piped gas supply. Myotonic syndromes.
Pressure regulators. Rheumatoid arthritis.
Vacuum insulated evaporator (VIE). Sarcoidosis.
StevensJohnson syndrome.
OTHER
Systemic lupus erythematosus.
Vasculitides.
Anaesthetic machines.
Blood filters.
Checking of anaesthetic equipment. ENDOCRINOLOGY
Contamination of anaesthetic equipment. Acromegaly.
Diathermy. Adrenocortical insufficiency.
Gauge. Cushings syndrome.
Luer connectors. Diabetes mellitus.
Needles. Diabetic coma.
Suction equipment. Hyperaldosteronism.
Syringes. Hyperthyroidism
Vaporisers. Hypopituitarism.
Hypothyroidism.
MEDICINE Phaeochromocytoma.
CARDIOLOGY Sick euthyroid syndrome.
Acute coronary syndromes. Thyroid crisis.
Aortic regurgitation.
Aortic stenosis. GASTROENTEROLOGY
Arrhythmias.
Bundle branch block. Ascites.
Cardiac catheterisation. Carcinoid syndrome.
Cardiac enzymes. Diarrhoea.
Cardiac failure. Gastrointestinal haemorrhage.
Cardiac pacing. Gastro-oesophageal reflux.
Cardiac tamponade. Hepatic failure.
Cardiomyopathy. Hepatitis.
Cardioversion, electrical. Hiatus hernia.
Congenital heart disease. Liver function tests.
Cor pulmonale.
Defibrillators, implantable cardioverter.
GENERAL
Echocardiography.
Electrocardiography (ECG). Alcoholism.
Endocarditis, infective. Anaemia.
Heart block. Decompression sickness.
Hypertension. Deep vein thrombosis (DVT).
Ischaemic heart disease. Dehydration.
Mitral regurgitation. Downs syndrome.
Mitral stenosis. Hypercalcaemia.
Myocardial ischaemia. Hyperglycaemia.
Myocarditis. Hyperkalaemia.
Percutaneous coronary intervention (PCI). Hypernatraemia.
Pericarditis. Hyperthermia.
Prolonged QT syndromes. Hypocalcaemia.
Pulmonary hypertension. Hypoglycaemia.
Pulmonary oedema. Hypokalaemia.
Pulmonary valve lesions. Hypomagnesaemia.
StokesAdams attack. Hyponatraemia.
Torsades de pointes. Hypophosphataemia.
Transoesophageal echocardiography. Inborn errors of metabolism.
Tricuspid valve lesions. Malignancy.
Malnutrition.
Porphyria.
DERMATOLOGY/MUSCULOSKELETAL/RHEUMATOLOGY Pyrexia.
Ankylosing spondylitis. Syndrome of inappropriate antidiuretic hormone
Connective tissue diseases. secretion (SIADH).

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Systemic inflammatory response syndrome. Coma scales.

Vasovagal syncope. Convulsions.
Demyelinating diseases.
Electroencephalography (EEG).
HAEMATOLOGY/IMMUNOLOGY Electromyography (EMG).
Autoimmune disease. Encephalopathy.
Blood compatibility testing. Epilepsy.
Blood products. Extradural (epidural) haemorrhage.
Blood storage. Horners syndrome.
Blood transfusion. Hydrocephalus.
Bone marrow transplantation. Lumbar puncture.
Coagulation disorders. Meningitis.
Coagulation studies. Migraine.
Disseminated intravascular coagulation. Motor neurone disease.
Glucose 6-phosphate dehydrogenase deficiency. Motor neurone, lower.
Haemoglobinopathies. Motor neurone, upper.
Haemolysis. Myasthenia gravis.
Haemophilia. Neurofibromatosis.
Immunodeficiency. Neuroleptic malignant syndrome.
Latex allergy. Paralysis, acute.
Methaemoglobinaemia. Parkinsons disease.
Rhesus blood groups. Peripheral neuropathy.
Thrombocytopenia. Post-traumatic stress disorder.
Thrombotic thrombocytopenic purpura. Subdural haemorrhage.
Tumour lysis syndrome. Trigeminal neuralgia.
Von Willebrands disease.

MICROBIOLOGY AND INFECTIOUS DISEASES POISONING

Bacteria. -Adrenergic receptor antagonist poisoning.
Blood cultures. Alcohol poisoning.
Catheter-related sepsis. Barbiturate poisoning.
Cellulitis. Benzodiazepine poisoning.
Clostridial infections. Carbon monoxide poisoning.
Human immunodeficiency viral (HIV) infection. Charcoal, activated.
Infection control. Chelating agents.
Influenza. Cocaine poisoning.
Meningococcal disease. Cyanide poisoning.
Necrotising fasciitis. Heavy metal poisoning.
Nosocomial infection. Iron poisoning.
Notifiable diseases. Opioid poisoning.
Pseudomonas infections. Organophosphorus poisoning.
Sepsis. Paracetamol poisoning.
Staphylococcal infections. Paraquat poisoning.
Streptococcal infections. Poisoning and overdoses.
Tropical diseases. Salicylate poisoning.
Tuberculosis (TB). Serotonin syndrome.
Tricyclic antidepressant drug poisoning.

NEUROLOGY/PSYCHIATRY
Amnesia.
Anorexia nervosa. RENAL
Anterior spinal artery syndrome. Acute kidney injury (AKI).
Autonomic hyperreflexia. Crush syndrome.
Autonomic neuropathy. Diabetes insipidus.
Cauda equina syndrome. Dialysis.
Central pontine myelinolysis. Glomerulonephritis.
Cerebral abscess. Hepatorenal syndrome.
Cerebral ischaemia. Myoglobinuria.
Cerebral oedema. Oliguria.
Cerebrovascular accident (CVA; Stroke). Renal failure.
Cholinergic crisis. RIFLE criteria.

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 Examination revision checklist

RESPIRATORY Clinical trials.

Aspiration pneumonitis. Coroner.
Asthma. COSHH regulations (Control of Substances
Atelectasis. Hazardous to Health).
Bronchial carcinoma. Critical incidents.
Bronchiectasis. Do not attempt resuscitation orders.
Bronchoalveolar lavage. Ethics.
Chest drainage. Incident, major.
Chest infection. Mental Capacity Act 2005.
Chronic obstructive pulmonary disease. Organ donation.
Cystic fibrosis. Pollution.
Dyspnoea. Recovery room.
Forced expiration.
Fowlers method. RADIOLOGY
Helium. Chest X-ray.
Hypocapnia. Computed (axial) tomography (CT).
Lung function tests. Magnetic resonance imaging (MRI).
Oxygen, hyperbaric. Positron emission tomography (PET).
Oxygen therapy. Radioisotope scanning.
Oxygen toxicity. Radiological contrast media.
Pulmonary embolism (PE). Ultrasound.
Pulmonary fibrosis.
Sleep apnoea/hypopnoea.

ORGANISATIONAL
Advance decision.
Clinical governance.

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