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Lidocaine is a local anesthetic agent that also has

antiarrhythmic effects. It is a treatment for
ventricular tachycardia or ventricular fibrillation.

For patients who are more hemodynamically stable,

sustained monomorphic ventricular tachycardia due
to myocardial ischemia or infarction may be
successfully treated using lidocaine therapy.

Lidocaine therapy can also be considered for the

treatment of polymorphic ventricular tachycardia
due to myocardial ischemia or infarction.
Lidocaine inhibits transmembrane sodium influx into
the His-Purkinje fiber conduction system thereby
decreasing conduction velocity.

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.

The net effect of these cellular changes is that

lidocaine eradicates ventricular reentrant arrhythmias
by abolishing unidirectional blocks via increased
conduction through diseased fibers.
Therapeutic & Toxic
Lidocaine follows a two compartment model after
administered intravenously. This is especially
apparent when initial loading doses of lidocaine are
given as rapid intravenous injections over 15
minutes (max rate: 2550 mg/min) and a
distribution phase of 3040 minutes is observed
after drug administration.

Lidocaine moves rapidly from the blood into the

heart, and the onset of action is within a few
minutes after completion of the intravenous
injection. Because of these, the heart is considered
to be located in the central compartment of the
two-compartment model for lidocaine.
The generally accepted therapeutic range for
lidocaine is 1.55 g/mL.
In the upper end of the therapeutic range (>3
g/mL), some patients will experience minor side
effects including drowsiness, dizziness,
paresthesias, or euphoria.
Lidocaine serum concentrations above the
therapeutic range can cause muscle twitching,
confusion, agitation, dysarthria, psychosis,
seizures, or coma.
Cardiovascular adverse effects such as
atrioventricular block, hypotension, and circulatory
collapse have been reported at lidocaine
concentrations above 6 g/mL, but are not strongly
correlated with specific serum levels.
Clinical Pharmacokinetic Parameters
Lidocaine is almost completely eliminated by
hepatic metabolism (>95%). Hepatic metabolism is
mainly via the CYP3A enzyme system.
Monoethylglycinexylidide (MEGX) is the primary
metabolite resulting from lidocaine metabolism.
While a portion of MEGX is eliminated renally, most
of the metabolite is further converted hepatically to
glycinexylidide (GX) and other inactive metabolites.
GX is primarily eliminated by the kidney. MEGX and
GX have some antiarrhythmic activity (MEGX 80%
and GX 10%, relative to lidocaine), but have also
been implicated as the cause of some adverse
effects attributed to lidocaine therapy.
Lidocaine is usually given intravenously but may
also intramuscularly. After IM injection, absorption
is rapid and complete with maximum
concentrations occurring 1 hour after
administration and 100% bioavailability as long as
the patients peripheral circulation is not

Oral absorption of lidocaine is nearly 100%.

However, lidocaine is extensively metabolized by
the CYP3A enzymes(intestinal wall and liver)
resulting in a large first-pass effect. Because
roughly 70% of an oral dose is converted to
metabolites, MEGX and GX concentrations are
high after oral administration of lidocaine
resulting in a high incidence of adverse effects.
Plasma protein binding in normal individuals is
70%. Of this value, approximately 30% is
bounded to albumin while 70% is bounded to 1-
acid glycoprotein (AGP).
AGP is secreted in large amounts in response to
certain stresses and disease states such as
trauma, heart failure, and myocardial infarction,
resulting in an unbound fraction as low as 10
The continuous increase in protein binding due to
AGP secretion causes a continuous decrease in
lidocaine clearance in patients with myocardial
infarction, and lidocaine concentrations can
accumulate to unexpectedly high levels.
Disease States and Conditions that
Alter Lidocaine Pharmacokinetics
Patients with liver cirrhosis or acute hepatitis have reduced
lidocaine clearance which results in a prolonged average
lidocaine half life of 5 hours.The mechanism for depressed
clearance in liver disease patients is destruction of liver
parenchyma where hepatic drug metabolizing enzymes are
present and reduction of liver blood flow.
The central volume of distribution and volume of
distribution for the entire body are larger in patients with
liver disease because albumin and AGP concentrations are
lower in these patients and result in reduced lidocaine
plasma protein binding.
An index of liver dysfunction can be gained by applying the
Child-Pugh clinical classification system to the patient
Drug Interactions
Lidocaine has serious drug interactions with -
adrenergic receptor blockers and cimetidine that
decrease lidocaine clearance 30% or more.
Propranolol, metoprolol, and nadolol have been reported
to reduce lidocaine clearance due to the decrease in
cardiac output caused by -blocker agents. Decreased
cardiac output results in reduced liver blood flow which
explains the decline in lidocaine clearance caused by
these drugs.
Cimetidine also decreases lidocaine clearance, cimetidine
decreases lidocaine clearance by inhibiting hepatic
microsomal enzymes.
Lidocaine clearance may be accelerated by
concomitant use of phenobarbital or phenytoin.
Initial Dosage Determination
Pharmacokinetic Dosing Method
- Half-life and elimination rate costant estimate
- Volume of distribution estimate
- Selection of appropriate pharmacokinetic model and
- Steady-state concentration.

Literature-based Recommended Dosing

Doses are based on those that commonly produce
steady-state concentrations in the lower end of the
therapeutic range, although there is a wide variation
in the actual concentrations for a specific patient.
If a patient has a subtherapeutic lidocaine serum concentration and is
experiencing ventricular arrhythmias in an acute situation, it is desirable
to increase the lidocaine concentration as quickly as possible. In this
setting, it would not be acceptable to simply increase the maintenance
dose and wait 35 half-lives for therapeutic serum concentrations to be
established in the patient. A rational way to increase the serum
concentrations rapidly is to administer a booster dose of lidocaine, a
process also known as reloading the patient with lidocaine, computed
using pharmacokinetic techniques. A modified loading dose equation is
used to accomplish computation of the booster dose (BD) which takes into
account the current lidocaine concentration present in the patient:

BD = (C desired C actual )Vc,

C desired is the desired lidocaine concentration,
C is the actual current lidocaine concentration for the patient,
Vc is the central volume of distribution for lidocaine.