LIDOCAINE

INTRODUCTION
• Lidocaine is a local anesthetic agent that also has
antiarrhythmic effects. It is classified as a type IB
antiarrhythmic agent and is a treatment for
ventricular tachycardia or ventricular fibrillation.
• Lidocaine inhibits transmembrane sodium influx
into the His-Purkinje fiber conduction system
thereby decreasing conduction velocity.2 It also
decreases the duration of the action potential
and as a result decreases the duration of the
absolute refractory period in Purkinje fibers and
bundle of His. Automaticity is decreased during
lidocaine therapy.
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 THERAPEUTIC AND TOXIC CONCENTRATION

• When given intravenously, the serum lidocaine concentration/time

curve follows a two compartment model. This is especially apparent
when initial loading doses of lidocaine are given as rapid
intravenous injections over 1–5 minutes (maximum rate: 25–50
mg/min) and a distribution phase of 30–40 minutes
• The generally accepted therapeutic range for lidocaine is 1.5–5
μg/Ml
• Upper end of the therapeutic range (>3 μg/mL), some patients will
experience minor side effects including drowsiness, dizziness,
paresthesias, or euphoria.
• serum concentrations above the therapeutic range can cause
muscle twitching, confusion, agitation, dysarthria, psychosis,
seizures, or coma.

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Bauer, 2008: 357
• For dose adjustment purposes, lidocaine serum
concentrations are best measured at steady state
after the patient has received a consistent dosage
regimen for 3–5 drug halflives.
• Lidocaine half-life varies from 1–1.5 hours in
normal adults to 5 hours or more in adult
patients with liver failure
• If lidocaine is given as a continuous intravenous
infusion, it can take a considerable amount of
time (3–5 half-lives or 7.5–25 hours) for patients
to achieve effective concentrations
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• the lidocaine volume of distribution for the
central compartment (Vc in L) would have to be
known to compute the loading dose (LD in mg):
LD = Css ⋅ Vc, where Css is the desired lidocaine
concentration in mg/L.
• The volume of distribution for the central
compartment of the two-compartment model is
used to compute the loading dose because
lidocaine distributes rapidly to the myocardium
and the heart is considered to reside in the
central compartment of the model
• it will still take 3–5 half-lives for the patient to
reach steady-state conditions while receiving a
constant intravenous infusion rate

Bauer, 2008: 358

• an additional dose (50% of original loading
dose) can be given 20–30 minutes after the
original loading dose or several additional
doses (33–50% of original loading dose) can
be given every 5–10 minutes to a total
maximum of 3 mg/kg

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Bauer, 2008: 359
 Clinical Monitoring Parameters
• electrocardiogram (ECG or EKG)
• 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
• adverse drug effects: drowsiness, dizziness,
paresthesias, euphoria, muscle twitching, confusion,
agitation, dysarthria, psychosis, seizures, coma,
atrioventricular block, or hypotension.

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Basic Clinical Pharmacokinetic Parameters

• Lidocaine is almost completely eliminated by

hepatic metabolism (>95%).
• Hepatic metabolism is mainly via the CYP3A
enzyme system.
• metabolites are eliminated by the kidney,
patients with renal failure should be monitored
for adverse effects due to metabolite
accumulation even though lidocaine serum
concentrations are within the therapeutic range
Bauer, 2008: 360-361
• Liver blood flow will be the predominate factor
influencing the clearance of lidocaine (Cl ≈ LBF,
where Cl is lidocaine clearance and LBF is liver
blood flow, both in L/min), and many disease
states and conditions that alter lidocaine
clearance do so via changes in liver blood flow
• Lidocaine is usually given intravenously but may
also be given intramuscularly.
• Plasma protein binding in normal individuals is
about 70%.

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 EFFECTS OF DISEASE STATES AND CONDITIONS ON LIDOCAINE
PHARMACOKINETICS AND DOSING

• Normal adults have an average lidocaine half-

life of 1.5 hours (range: 1–2 hours),
• a central volume of distribution of 0.5 L/kg (Vc
= 0.4–0.6 L/kg)
• the volume of distribution for the entire body
of 1.5 L/kg (Varea = 1–2 L/kg)
• The elimination rate constant (k = 0.693/t1/2,
where t1/2 is the half-life) and clearance (Cl =
kVarea)
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• Patients with liver cirrhosis or acute hepatitis
have reduced lidocaine clearance which results in
a prolonged average lidocaine half-life of 5 hours.
• The Child-Pugh score for a patient with normal
liver function is 5 while the score for a patient
with grossly abnormal serum albumin, total
bilirubin, and prothrombin time values in
addition to severe ascites and hepatic
encephalopathy is 15. A Child-Pugh score greater
than 8 is grounds for a decrease in the initial daily
drug dose for lidocaine (t1/2 = 5 hours)

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• Heart failure causes reduced lidocaine clearance
because of decreased hepatic blood flow secondary
to compromised cardiac output

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`

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 Drug Interaction
• Lidocaine has serious drug interactions with β-
adrenergic receptor blockers and cimetidine
that decrease lidocaine clearance 30% or
more
• Lidocaine clearance may be accelerated by
concomitant use of phenobarbital or
phenytoin

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 INITIAL DOSAGE DETERMINATION METHODS

1. Pharmacokinetic dosing method

• HALF-LIFE AND ELIMINATION RATE CONSTANT ESTIMATE
• VOLUME OF DISTRIBUTION ESTIMATE
• SELECTION OF APPROPRIATE PHARMACOKINETIC MODEL
AND EQUATIONS
• Css = k0 / Cl or k0 = Css ⋅ Cl
• STEADY-STATE CONCENTRATION SELECTION
The general accepted therapeutic range for lidocaine is 1.5–
5 μg/mL

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2. Literature-Based Recommended Dosing
• lidocaine steady-state serum concentration
expected from the lower end of the dosage range
was 1.5–3 μg/mL and 3–5 μg/mL for the upper
end of the dosage range. Suggested intravenous
lidocaine continuous infusion maintenance doses
are 1–2 mg/min for patients with liver disease or
heart failure and 3–4 mg/min for all other
patients
• lidocaine is given intravenously at the dose of 1–
1.5 mg/kg (not to exceed 25–50 mg/min) for all
patients except those with heart failure

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• The suggested lidocaine intravenous loading
dose for heart failure patients is 0.5–0.75
mg/kg (not to exceed 25–50 mg/min)
• Intravenous loading doses are 1 mg/kg with
up to two additional doses, if needed (total
dose not to exceed 3–5 mg/kg for first hour).
Continuous intravenous infusions doses are
20–50 μg/kg/min.
• For patients with shock, heart failure, or liver
disease patients, initial doses should not
exceed 20 μg/kg/min

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 USE OF LIDOCAINE SERUM CONCENTRATIONS
TO ALTER DOSES
1. Linear Pharmacokinetics Method
Dnew / Css,new = Dold / Css,old or Dnew = (Css,new / Css,old)Dold

2. Pharmacokinetic Parameter Method

The pharmacokinetic parameter method requires that
steady state has been achieved and uses only a steady-
state lidocaine concentration (Css in mg/L or μg/mL)

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 BAYESIAN PHARMACOKINETIC COMPUTER
PROGRAMS
1. Enter patient’s demographic, drug dosing, and serum
concentration/time data into the computer
program.
2. Compute pharmacokinetic parameters for the
patient using Bayesian pharmacokinetic computer
program
3. Compute dose required to achieve desired lidocaine
serum concentrations.

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