West Visayas State University – College of Medicine – Batch 2020

Block XX
Module 6 Intravenous Anesthesia
Lecture 7
05/ 15/ 19
Michael Y. Castanos MD, DPBA, FPSA

TOPIC OUTLINE IV DRUG DISTRIBUTION

I. Ideal IV Anesthetic Drug
II. Propofol
III. Barbiturates
IV. Benzodiazepines
V. Ketamine
VI. Etomidate
VII. Dexmedetomedine
Review Questions
References
Appendices

LECTURER BOOK REFERENCE OLD TRANS

IV vs Inhalational anesthesia Figure 1. Drug distribution in different tissues. Source: internet

In IV, drugs are administered directly through
intravenous while inhalational is given through your Upon entering the bloodstream, most of the drug will
trachea and alveoli be present in the plasma & will bind to the plasma
Inhalationaluses gas or volatile anesthetics. proteins. And the remaining unbound drug are free
IV induction drugs drug, which are the active component of the drug.
When given intravenously they will cause rapid Dictum in IV anesthetics: the more lipid loving the
loss of consciousness more potent the drug is, because the brains is mostly
1 arm brain circulation phospholipids.
The time for the drug to travel from the arm to the Three compartments
brain Vessel rich- heart, kidney, lungs & brain. 70% of
The target organ for general anesthesia is the brain the drug will be taken here.
Less- skeletal muscles & skin
I. IDEAL IV ANESTHETIC DRUG Minimal- adipose, bones & connective tissue
It should be without cardiac & respiratory Induction
complications. But there is no single drug that can High concentration of drug in the bloodstream will
attain this so we do multiple drug approach go to the brain which has a lower concentration
• Hypnosis Three characteristics of IV anesthetic drugs
• Amnesia Lipid solubility
• Analgesia Degree of ionization (when the drug is ionized it
Anesthesia vs Analgesia can’t enter the brain)
Anesthesia → no sensation, Analagesia → no pain Arterial concentration
• Muscle relaxation The particular receptor that the IV drugs interact with
Very important especially during abdominal is the GABA which is an inhibitory neuron. The drugs
surgery potentiates the activity of the GABA
Normally, abdominal muscle reacts to an invading
stimuli as part of the protective reflexes of the body II. PROPOFOL
If the anesthetic drugs does not have enough
muscle relaxation property, the surgeon will have a
difficulty in incising the abdomen kay ma tig-a

Figure 2. Propofol chemical structure. Source: internet

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 A. PHYSIOCHEMICAL PROPERTIES C. PHARMACODYNAMICS
• 2, 6 diisopropylphenol • Acts through potentiation of the chloride current
• Alkyl phenol with HYPNOTIC properties through the γ–aminobutyric acid Type A (GABA-A)
• Insoluble in aqueous solutions receptor complex
• Formulated as emulsion
• Usually contains: CENTRAL NERVOUS SYSTEM
10% soybean oil Primarily hypnotic and NOT analgesic
2.25% glycerol Decrease cerebral bloodflow (CBF) and cerebral
1.2% lecithin metabolic rate for oxygen (CMRO) → results in
• The available formulation support bacterial growth → decrease intracranial pressure
GOOD sterile technique is important! Good for neuro procedures
Since lipid emulsions are good for bacterial growth, Monro-Kellie doctrine – any increase in the three
they added bacterial retardants substance of the brain (blood, CSF, brain tissue)
• Bacterial retardants: will cause a decrease of the other two leading to ↑
EDTA 0.05 mg/mL ICP
Metabisulfate 0.25 mg/mL Neuroprotective
Benzyl alcohol 1 mg/mL Anticonvulsant
• Milky-white
• Slightly viscous CARDIOVASCULAR SYSTEM
• pH – 7 Vasodilation
• 1% (10 mg/mL) propofol concentration ─ Occurs in both arterial and venous circulation
When IV propofol is given, it is very painful. Give ─ Reduction in preload and afterload
lidocaine before administering propofol. ↓ systemic blood pressure (SBP) is more
It is a short acting anesthetic. IV drugs should be pronounced
short acting so that there is a rapid onset and rapid ─ Especially with increasing age; patient with
offset. reduced intravascular fluid volume; and with
Onset of action starts 30 sec after drug administration rapid injection
Recovery within 2-4 mins Exacerbates hypotensive effect
Propofol is the ideal drug for IV general anesthetic. Profound bradycardia and asystole, even on
The drug that killed MJ healthy adults despite prophylactic anticholinergic

B. PHARMACOKINETICS RESPIRATORY SYSTEM

• Rapidly metabolized in the liver Potent respiratory depressant → produces apnea
• Excreted through the kidneys post-induction
• High plasma clearance and exceeds hepatic blood flow The brain can only survive 5 mins of apnea due to
Extrahepatic metabolism is important! decreased supply of O2
─ Lungs play the major role Reduction in tidal volume and respiratory rate
─ Accounts for the elimination of up to 30 % of a Reduction in upper airway reflexes → hence, the
bolus dose use of laryngeal mask airway
─ This explains a more complete recovery from Decreases incidence of wheezing and tracheal
propofol with LESS “HANGOVER” than intubation among healthy and asthmatic patients
thiopental
Hangover means the drug eliminated completely OTHERS
within an hour Antiemetic
• Continuous IV infusion Area postrema is the antiemetic area of the brain.
Rapid metabolism – efficient plasma clearance It is modulated by GABA and causes the decrease
Slow redistribution from poorly perfused of serotonin.
compartments back into the central compartments Unexpected tachycardia
Context-sensitive half-time is brief ─ Should prompt laboratory evaluation
The time taken for the blood plasma concentration ─ Possible metabolic acidosis
of the drug to decline by 50% after you stop giving ─ Propofol infusion syndrome
the drug Since propofol is acidic, prolonged infusion of the
drug causes propofol infusion syndrome which
leads to metabolic acidosis, cardiac failure and
kidney failure. It is often critical but rare.

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 MJ chose propofol because it stimulates nucleus C. PHARMACODYNAMICS
accumbens which is the reward system of the brain CENTRAL NERVOUS SYSTEM
that releases dopamine. • Sedation to general anesthesia in induction doses
• No analgesic effect (reduces pain threshold)
D. CLINICAL USES • Potent cerebral vasoconstrictor
• Induction of anesthesia Decrease CBF, CBV, ICP, CMRD
• Maintenance of anesthesia Useful in management of patient with space-
• Sedation occupying intracranial lesions
• Antiemetic • Neuroprotection
For focal cerebral ischemia
III. BARBITURATES
CARDIOVASCULAR SYSTEM
• Decreases SBP
Vasodilation
Barbiturate-induced depression of the medullary
vasomotor center and decreased sympathetic
nervous system from the CNS

RESPIRATORY SYSTEM
• Depresses the respiration → leads to decreased
minute ventilation through reduced tidal volume and
RR
Figure 3. Barbiturate chemical structure. Source: internet • Induction doses induces transient apnea
• Decreases ventilatory response to hypercapnia and
The popular drug used in the hospital is Thiopental, hypoxia
so we will be focusing on it. Chemorecptor area in the brain which senses co2
• Slow breathing rate and decrease tidal volume
A. PHYSIOCHEMICAL PROPERTIES
• Lacks hypnotic effect SIDE EFFECTS
• Both are formulated as sodium salts mixed with • Severe tissue injury involving gangrene – accidental
anhydrous sodium carbonate intra-arterial injection
• After reconstitution with water and NSS, the solution Due to alkaline property
are alkaline with pH > 10 → prevents bacterial growth • Local tissue irritation – accidental subcutaneous
and helps increase the shelf-life injection
• Leads to precipitation when mixed with acidic drug • Life-threatening allergic reaction – RARE
preparation such as NMBD Barbiturates cannot be given to asthmatic patient
Can irreversibly block intravenous delivery lines
Accidental injection into artery will cause extreme D. CLINICAL USES
pain and may lead to severe tissue injury • Induction of anesthesia
NMBDs are often administered shortly after the
B. PHARMACOKINETICS barbiturate to produce skeletal muscle relaxation
• Undergo hepatic metabolism by oxidation, N- Thiopental + Succinylcholine: Classic drug
deakylation, desulfuration, and destruction of barbituric regimen for “rapid sequence induction of
acid ring structure anesthesia”
• Resulting metabolites are inactive and excreted You do rapid sequence induction of anesthesia in
through urine, and after conjugation through bile cases like intestinal obstruction. The patient is
• Should not be administered to patient with acute placed in supine position and he has intestinal
intermittent porphyria obstruction. His abdomen is big and the stomach
Chronic administration enhances barbiturate contents push the diaphragm upwards. During
metabolism giving of anesthetics, the lower esophageal
Production of porphyrin is increased through sphincter will relax and gastric contents will go up
stimulation of aminolevullinic acid synthase and may lead to aspiration. So in rapid sequence
induction, we do the Sellick maneuver(applying
pressure to the cricoid cartilage). We push the

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 cricoid cartilage against the esophagus to seal it to
prevent the gastric content to go up. SPECTRUM OF EFFECTS:
• Neuroprotection • Mediated through the α1-subunitof the GABA
receptors
IV. BENZODIAZEPINES Sedative-hypnotic
Amnestic
Used to treat seizure
• Mediated through the γ-subunit of the GABA receptors
Anxiolysis

CENTRAL NERVOUS SYSTEM

• ↓CMRO, and CBF
• Potent anticonvulsant

CARDIOVASCULAR SYSTEM
• ↓↓SBP
Figure 4. Benzodiazepine chemical structure. Source: internet
RESPIRATORY SYSTEM
The popular drugs are the midazolam (brand name: • Minimal depression of ventilation
Dormicum) and diazepam(brand name: Valium). • Depression increases when co-administered with
We will only tackle midazolam because it has the opioids
highest lipid solubility, it has a rapid action, and it’s
the most common drug used in the hospital. SIDE EFFECTS
• Allergic reaction – rare
A. PHYSIOCHEMICAL PROPERTIES • Pain during injection
• Contains benzene ring fused to a seven-member
diazepine ring, hence the name D. CLINICAL USES
• Highly lipophilic • Preoperative medication
• Midazolam – highest lipid solubility; this speeds its • Intravenous sedation
passage across the blood-brain barrier and its onset of • Intravenous induction of anesthesia
action • Suppression of seizure activity
• Highly protein bound, mainly to serum albumin
V. KETAMINE
B. PHARMACOKINETICS
• Highly lipid soluble
• Rapid onset of action
• Metabolism in the liver through microsomal oxidation,
N-deakylation and aliphatic hydroxylation or
glucuronide conjugation
• Midazolam – has the shortest context-sensitive half-
time, which makes it the only one that is suitable for
continuous infusion

C. PHARMACODYNAMICS Figure 5. Keyamine chemical structure. Source: internet

• Activation of GABA, receptor complex and
enhancement of GABA-mediated chloride currents –
A. PHYSIOCHEMICAL PROPERTIES
leads to hyperpolarization of neurons and reduced • Phencyclidine derivative
excitability • Produces significant analgesia
Benzodiazepine is an anti-anxiety drug. It is given • Known as “dissociative anesthesia”
orally1 night or 1 hour before the procedure to relax It dissociates the thalamus (receives inputs from
the anxious patient. stimuli felt all over the body) from the cortex. When
The drug’s purpose is to make you forget the things it dissociates, the brain can’t interpret sensations.
that hurt you. (anterograde amnesia) When the drug is given before the operation and
• Minimal effects of these drugs outside the CNS → the surgeon starts to incise an area in the patient’s
magnitude of ventilation depression and hypotension body, he cannot feel the pain.
are rare
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 Patient’s eye remain open with a slow nystagmus Causes adrenocortical suppression by producing a
gaze (cataleptic gaze) dose-dependent 11 β-hydroxylase, an enzyme
• Partially water-soluble, but highly lipophilic necessary for the conversion of cholesterol to
cortisol
B. PHARMACOKINETICS Suppression last 4-8 hours
• Lipid soluble Contraindicated to patients with adrenal
• Rapid onset of drug effect insufficiency
• Metabolism occurs primarily in the liver through N-
demethylation by CYP450 system D. CLINICAL USES
• This is the only IV anesthetic that has the low • Alternative to propofol and barbiturate
protein binding
Meaning, it is very potent because less drugs are VII. DEXMEDETOMEDINE
bound to plasma protein and more free drug • Highly selective α2-adrenergic agonist

C. PHARMACODYNAMICS A. PHYSIOCHEMICAL PROPERTIES

• Lacrimation and salivation are increased and • Active S-enantiomer of medetomidine
premedication with an anticholinergic is indicated to • Used in veterinary medicine
limit the effect
A popular anticholinorgic is Atropine B. PHARMACOKINETICS
• Emergence reactions: • Rapid hepatic metabolism
Vividcolorful dreams Conjugation, N-Methylation, and hydroxylation
Hallucinations Bullet 2
Out-of body experience
Increased and distorted visual, tactile, and auditory C. PHARMACODYNAMICS
• Hypnosis results from structure of α2receptor in the
sensation
locus ceruleus and the analgesic effect at the level of
Associated with fear and confusion
spinal cord
D. CLINICAL USES
• Induction and maintenance of anesthesia D. CLINICAL USES
• Short-term sedation
• Analgesia (CS and neuraxial anesthesia)
• Adjunct to general anesthesia to provide sedation
Ketamine vs Propofol vs Barbiturate
REVIEW QUESTIONS
Ketamine has both hypnotic and analgesic effect,
1. Patient scheduled for appendectomy has history
while propofol and barbiturate only has hypnotic
of asthma what will you give. Propofol but not
effect.
thiopental
So you can operate on a patient using ketamine only
a. Propofol or Thiopental
b. Thiopental
VI. ETOMIDATE
c. Propofol
• IV anesthetic with hypnotic but not analgesic properties
d. AOTA
and with minimal hemodynamic effects
2. Patient is scheduled for surgery, shehas
porphyria, can you give thiopental?
A. PHYSIOCHEMICAL PROPERTIES
• Carboxylates imidazole derivative a. Yes
• Has two optical isomers b. No
• Available preparation: c. Maybe
Contain only the active D-(+) isomer, contains d. I don’t know?
hypnotic properties 3. Patient came in with a stab wound on the chest
with BP of 50 palpatory, what is your drug of
B. PHARMACOKINETICS choice during induction of anesthesia.
• Continuous infusion can be safely administered a. Midazolam
Because of its minimal effects on hemodynamics b. Diazepam
and short context-sensitive half-time c. Ketamine
d. Etomidate
C. PHARMACODYNAMICS 4. Patient with adrenal insufficiency is scheduled for
• Effect on endocrine system bilateral knee amputation, what drug will you use
for general anesthesia?
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 a. Etomidate
b. Propofol
c. Barbiturate
d. B or C
5. Hypertensive patient scheduled for general
surgery, what general anesthetic drug will you
use as maintenance to maintain the BP?
a. Dexmetomedine
b. Midazolam
c. Thiopental
d. Ketamine

Answers: CBDDA

REFERENCES
• Doctor’s lecture
• Audio recording
• Internet

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