Lidocaine (SubGroup 1B)

LIDOCAINE (SUBGROUP 1B)

Lidocaine has a low incidence of toxicity and a high degree of effectiveness in arrhythmias associated with acute myocardial infarction. It is used only by the intravenous route.

Cardiac Effects

Lidocaine blocks activated and inactivated sodium channels with rapid kinetics (Figure 14–10); the inactivated state block ensures

greater effects on cells with long action potentials such as Purkinje and ventricular cells, compared with atrial cells. The rapid kinetics at normal resting potentials result in recovery from block between action potentials and no effect on conduction. The increased inac-tivation and slower unbinding kinetics result in the selective depression of conduction in depolarized cells. Little effect is seen on the ECG in normal sinus rhythm.

Toxicity

Lidocaine is one of the least cardiotoxic of the currently used sodium channel blockers. Proarrhythmic effects, including SA node arrest, worsening of impaired conduction, and ventricular arrhyth-mias, are uncommon with lidocaine use. In large doses, especially in patients with preexisting heart failure, lidocaine may cause hypoten-sion—partly by depressing myocardial contractility.

Lidocaine’s most common adverse effects—like those of other local anesthetics—are neurologic: paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, and convulsions. These occur most commonly in elderly or other-wise vulnerable patients or when a bolus of the drug is given too rapidly. The effects are dose-related and usually short-lived; seizures respond to intravenous diazepam. In general, if plasma levels above 9 mcg/mL are avoided, lidocaine is well tolerated.

Pharmacokinetics & Dosage

Because of its extensive first-pass hepatic metabolism, only 3% of orally administered lidocaine appears in the plasma. Thus, lido-caine must be given parenterally. Lidocaine has a half-life of 1–2 hours. In adults, a loading dose of 150–200 mg administered over about 15 minutes (as a single infusion or as a series of slow boluses) should be followed by a maintenance infusion of 2–4 mg/min to achieve a therapeutic plasma level of 2–6 mcg/mL. Determination of lidocaine plasma levels is of great value in adjusting the infusion rate. Occasional patients with myocardial infarction or other acute illness require (and tolerate) higher con-centrations. This may be due to increased plasma α₁-acid glyco-protein, an acute-phase reactant protein that binds lidocaine, making less free drug available to exert its pharmacologic effects.

In patients with heart failure, lidocaine’s volume of distribu-tion and total body clearance may both be decreased. Therefore, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased; the elimina-tion half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life deter-mines the time to steady state. Although steady-state concentra-tions may be achieved in 8–10 hours in normal patients and patients with heart failure, 24–36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition.

Therapeutic Use

Lidocaine is the agent of choice for termination of ventricular tachycardia and prevention of ventricular fibrillation after cardio-version in the setting of acute ischemia. However, routine prophy-lactic use of lidocaine in this setting may actually increase totalmortality, possibly by increasing the incidence of asystole, and is not the standard of care. Most physicians administer IV lidocaine only to patients with arrhythmias.