TDM OF LIDOCAINE

Clinical Pharmacokinetics &

Pharmacotherapeutic Drug Monitoring

PD514 Shraddha Gupta

PD515 Avanti Jadhav
PD516 Nayana Jayachandran
INTRODUCTION [1]
● Lidocaine, formerly also referred to as lignocaine, is a tertiary amine derived from xylidine,
● Its use became widespread because of its superior safety profile compared to older local anesthetic agents.
● The drug is commonly used for local anesthesia, often combined with epinephrine (which acts as a
vasopressor and extends its duration of action at a site by opposing the local vasodilatory effects of
lidocaine).
● Given intravenously, it can be used during advanced airway management as an adjuvant to tracheal
intubation.
● Lidocaine is a class Ib antiarrhythmic agent on the Vaughan-Williams classification, and its use is
indicated in the management of acute ventricular tachydysrhythmias. It also has roles as an adjuvant
analgesic in managing acute and chronic pain.

1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881/
 INDICATION [2]
1.Local numbing agent-
The efficacy profile of lidocaine as a local anaesthetic is characterized by a rapid onset of action and intermediate
duration of efficacy. Therefore, lidocaine is suitable for infiltration, block, and surface anaesthesia.
2.Heart Arrhythmia
Lidocaine is also the most important class-1b antiarrhythmic drug; it is used intravenously for the treatment of
ventricular arrhythmias.
3. Epilepsy
A 2013 review on treatment for neonatal seizures recommended intravenous lidocaine as a second-line treatment, if
phenobarbital fails to stop seizures.
4. Others
Intravenous lidocaine infusions are also used to treat chronic pain and acute surgical pain as an opiate sparing
technique. Inhaled lidocaine can be used as a cough suppressor acting peripherally to reduce the cough reflex.
2. Lidocaine CV, Lidopen (lidocaine) dosing, indications, interactions, adverse effects, and more [Internet]. reference.medscape.com.
Available from: https://reference.medscape.com/drug/lidocaine-cv-lidopen-342302‌
MECHANISM OF ACTION [1]

● The site of action of lidocaine is at sodium ion channels on the internal surface of nerve cell membranes.
● The uncharged form diffuses through neural sheaths and ionizes by combining with hydrogen ions. The
resulting cation binds reversibly to sodium channels from the inside, locking the open state and preventing
nerve depolarization.
● Efficacy decreases in the presence of inflammation; due to acidosis decreasing the proportion of un-
ionized lidocaine molecules, and potentially also through increased production of inflammatory mediators
like peroxynitrite, which act directly on sodium channels.
● Lidocaine is metabolized by hepatic enzymes to active and inactive metabolites.

1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881 /
 ADMINISTRATION [1]
Various routes of administration utilize different preparations of lidocaine.

● Very dilute concentrations, in the order of 0.05 to 0.1%, is given subcutaneously to provide local anesthesia,
resulting in firmness of the site, which may be beneficial for certain surgical procedures.
● Dilute solutions of 0.25 to 0.5% are used for intravenous regional anesthesia or infiltration into subcutaneous
tissue.
● 1 to 2% solutions are used for regional nerve blocks, including epidural anesthesia, and are also available in
intravenous preparations for antiarrhythmic use.
● 4% solution is used for topical anesthesia of the mucous membranes of the airway, including the mouth,
pharynx, and respiratory tract, either by gargling, spraying, or using an atomizer.
● 5% ointment, typically mixed with hydrocortisone, is employed topically on other mucous membranes such as
the skin or in the rectum.
● 10% solution is also used topically for airway anesthesia, typically by spraying from a metered-dose atomizer.
1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881/
 NEED OF TDM FOR LIDOCAINE [1,3]
● Lidocaine has a narrow therapeutic index, and plasma level monitoring may be necessary for patients with
hepatic impairment who are on prolonged infusions.
● Plasma concentrations should certainly be checked, to minimize toxicity particularly if the infusion is to be
continued beyond 24 h. If inefficacy is an issue, then plasma levels should be checked when clinically
indicated.
● Therapeutic ranges have not been established for treatment of chronic pain
● Old age, and any drug or disease state which influences hepatic blood flow or metabolism will have significant
effects on the pharmacokinetics of lignocaine. Examples: alcoholic liver disease, reduced hepatic blood flow
due to heart failure or β-adrenoceptor blockers, and reduced metabolism due to cimetidine.

1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881 /
3. Campbell TJ, Williams KM. Therapeutic drug monitoring: antiarrhythmic drugs. British Journal of Clinical
Pharmacology [Internet]. 1998 Oct 1;46(4):307–19. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874159/
 CLINICAL PHARMACOKINETIC PROFILE [4,5]
Absorption-

Absorbed rapidly after parenteral administration and from GIT and respiratory tract. Lidocaine is readily
absorbed across mucous membranes and damaged skin but poorly through intact skin.The agent is quickly absorbed
from the upper airway, tracheobronchial tree, and alveoli into the bloodstream. Although lidocaine is also well
absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of
first-pass metabolism.

Volume of distribution-

The volume of distribution determined for lidocaine is 0.7 to 1.5 L/kg. Lidocaine is distributed throughout the
total body water.
Metabolism-

Lidocaine is metabolized predominantly and rapidly by the liver, and metabolites and unchanged drug are
excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the
amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites
monoethylglycinexylidide and glycinexylidide

Excretion-

The excretion of unchanged lidocaine and its metabolites occurs predominantly via the kidney with less than
5% in the unchanged form appearing in the urine. The renal clearance is inversely related to its protein binding
affinity and the pH of the urine.

4. Drugbank. Lidocaine [Internet]. go.drugbank.com. 2022. Available from:https://go.drugbank.com/drugs/DB00281

5. ‌Chapter 7. Lidocaine | Applied Clinical Pharmacokinetics, 2e | AccessPharmacy | McGraw Hill Medical [Internet].
accesspharmacy.mhmedical.com. [cited 2022 Nov 16]. Available from: https://accesspharmacy.mhmedical.com/content.aspx?
bookid=510§ionid=40843081#3519865
‌
ADR/ TOXIC EFFECTS [1]
●Lidocaine is thought to be more neurotoxic than other local anesthetics, especially when high concentrations are applied directly to nervous tissue.
● Use of highly concentrated lidocaine (2.5 to 5%) for spinal anesthesia correlates with a greater incidence of transient radicular irritation syndrome, which is a
self-limiting painful condition affecting the calves, thighs, and buttocks.
●Signs and symptoms of mild toxicity :
1.Slurred speech,
2.Tinnitus,
3.Circumoral paresthesia,
4.Feeling faint
●Above 10 mcg/mL:- seizures or loss of consciousness.
● At 15 mcg/mL: cardiac arrhythmias,
respiratory arrest,
●above 20 mcg/mL: cardiac arrest

1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881/
DRUG INTERACTIONS [5]

1. Cimetidine

2. Propranolol

3. Phenobarbital

4. Phenytoin

5. ‌Chapter 7. Lidocaine | Applied Clinical Pharmacokinetics, 2e | AccessPharmacy | McGraw Hill Medical

[Internet]. accesspharmacy.mhmedical.com. [cited 2022 Nov 16]. Available from:
https://accesspharmacy.mhmedical.com/content.aspx?bookid=510§ionid=40843081#3519865
‌
THERAPEUTIC RANGE [6]

When a therapeutic range for lidocaine is determined, it is important to note that plasma, serum, and whole blood
concentrations are not interchangeable. For conversion from blood (Cb) to serum (Cs) concentrations, a factor of
1.3 should be applied.

Cs= (Cb)(1.3)

The usual therapeutic range in serum is 1.5–6 mg/L of total drug or 0.5–2 mg/L of free or unbound drug.

6. Murphy JE. Clinical Pharmacokinetics. ASHP; 2016.

‌
DOSE ADJUSTMENTS [2]
Dosage of Lidocaine:

Via Infusion-

1.100mg/100ml, 200mg/100ml

Via injectable solution-

1.10mg/100ml, 20mg/100ml

Drug considerations for following conditions-

Ventricular Arrhythmia-

1.Adult-

● 1-1.5 mg/kg slow intravenous (IV) bolus over 2-3 minutes

● May repeat doses of 0.5-0.75 mg/kg in 5-10 minutes up to 3 mg/kg total
● Continuous infusion: 1-4 mg/min intravenously (IV)
2. Paediatric-

● Bolus: 0.5-1 mg/kg IV/IO/ET, not to exceed 100 mg; follow with continuous infusion; if the delay
between bolus and start of infusion is more than 15 minutes, administer a second bolus every
● 5-10 minutes to 5 mg/kg, THEN
● Continuous infusion: 20-50 mcg/kg/min intravenous (IV)
● Monitor ECG

2. Lidocaine CV, Lidopen (lidocaine) dosing, indications, interactions, adverse effects, and more [Internet].
reference.medscape.com. Available from: https://reference.medscape.com/drug/lidocaine-cv-lidopen-342302‌
CONTRAINDICATION [1]
The drug is contraindicated in patients with a known severe adverse reaction. Anaphylactic reactions to lidocaine
are possible but rare.
Methemoglobinemia can occur due to lidocaine metabolism to O-toluidine.This metabolite is more likely to be
present when very high doses are given, but it may also occur with lower doses where the patient is taking other
medications that can precipitate methemoglobinemia or where the patient has a hemoglobinopathy or another
cause of anemia.
Lidocaine should not be used as an antiarrhythmic if the dysrhythmia may be secondary to local anesthetic
toxicity.
Lidocaine preparations containing epinephrine cause demonstrable cardiovascular effects even if only given in
small amounts, and it is prudent for essential hemodynamic monitoring to be carried out before and during use
solutions containing vasopressors, particularly if there is any specific concern over the patient's cardiovascular
status.
1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881/
CLINICAL MONITORING PARAMETERS [5]
● The electrocardiogram (ECG or EKG) should be monitored to determine the response to lidocaine in patients
with ventricular tachycardia or fibrillation.
● lidocaine serum concentrations should be obtained in patients who have a recurrence of ventricular
tachyarrhythmias, are experiencing possible lidocaine side effects, or are receiving lidocaine doses not
consistent with disease states and conditions known to alter lidocaine pharmacokinetics. Serum
concentration monitoring can aid in the decision to increase or decrease the lidocaine dose.
● if the ventricular arrhythmia reappears and the lidocaine serum concentration is <5 μg/mL, increasing the
lidocaine dose is a therapeutic option. However, if the lidocaine serum concentration is over 5 μg/mL, it is
unlikely a dosage increase will be effective in suppressing the arrhythmia and there is an increased likelihood
that drug side effects may occur
● Patients receiving lidocaine infusions for longer than 24 hours are prone to unexpected accumulation of
lidocaine concentrations in the serum and should be closely monitored for lidocaine side effects.
● While receiving lidocaine, patients should be monitored for the following adverse drug effects: drowsiness,
dizziness, paresthesias, euphoria, muscle twitching, confusion, agitation, dysarthria, psychosis, seizures,
coma, atrioventricular block, or hypotension.
● 5. ‌Chapter 7. Lidocaine | Applied Clinical Pharmacokinetics, 2e | AccessPharmacy | McGraw Hill Medical [Internet].
accesspharmacy.mhmedical.com. [cited 2022 Nov 16]. Available from: https://accesspharmacy.mhmedical.com/content.aspx?
bookid=510§ionid=40843081#3519865
FACTORS AFFECTING LIDOCAINE PLASMA
CONCENTRATION [6]
● Site of injection
● Drug used
● Addition of adrenaline
● Concentration of drug
● Speed of injection
● Dosage of drug
● Weight of patient
● Age of Patient
● Speed of elimination

6. https://www.bjanesthesia.org.uk/article/S0007-0912(17)49015-5/pdf
ENHANCING HEALTHCARE TEAM
OUTCOMES [1]
●All interprofessional healthcare team members, including clinicians (MDs, DOs, NPs, PAs), nurses, and pharmacists, who order,
prescribe, administer, or dispense lidocaine, should be familiar with its toxicity and how to manage it.
● Lidocaine may cause significant pain on initial injection due to the agent stimulating nociceptors before it exerts its effects on sodium
channels; this can be counteracted by buffering the lidocaine with small volumes of sodium bicarbonate shortly before use, making the
solution less acidic.
● Pain can also be reduced by warming the solution to body temperature, injecting more slowly, using narrow cannulas, and injecting at
90 degrees to the skin.[13]
●IV infusions of the drug should be treated as high-risk; a 2020 consensus statement suggested that, when used outside of the operating
room or post-anesthesia care unit, patients receiving IV lidocaine infusions should ideally be managed in a high-dependency setting
with continuous monitoring, and the infusion should be delivered through a separate, dedicated cannula using a tamper-proof pump
1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK539881/
References
1. Beecham GB, Amandeep Goyal. Lidocaine [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539881/

2. Lidocaine CV, Lidopen (lidocaine) dosing, indications, interactions, adverse effects, and more [Internet]. reference.medscape.com. Available from:
https://reference.medscape.com/drug/lidocaine-cv-lidopen-342302

3. Campbell TJ, Williams KM. Therapeutic drug monitoring: antiarrhythmic drugs. British Journal of Clinical Pharmacology [Internet]. 1998 Oct
1;46(4):307–19. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874159/

4. Drugbank. Lidocaine [Internet]. go.drugbank.com. 2022. Available from:https://go.drugbank.com/drugs/DB00281

5. Chapter 7. Lidocaine | Applied Clinical Pharmacokinetics, 2e | AccessPharmacy | McGraw Hill Medical [Internet]. accesspharmacy.mhmedical.com.
[cited 2022 Nov 16]. Available from: https://accesspharmacy.mhmedical.com/content.aspx?bookid=510§ionid=40843081#3519865

6. https://www.bjanesthesia.org.uk/article/S0007-0912(17)49015-5/pdf

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THANKYOU