LIDOCAINE Actions Lidocaine is the prototype of a class IB agent. It is a first-line agent in the treatment of serious ventricular dysrhythmias. It preferentially depresses the automaticity (phase 4) of the distal conduction system of depolarized and ischemic tissue; it does not affect normal myocardium. It has greater activity at faster heart rates. Lidocaine is not effective against atrial dysrhythmias because it preferentially acts on the His-Purkinje and more distal conduction system. Unlike class IA and IC agents, lidocaine only minimally depresses phase 0 (conduction). The refractory period is essentially unchanged, since the shortening of the action potential duration is offset by the relative lengthening of the effective refractory period.
Lidocaine has local anesthetic effects that stabilize membranes, elevate the ventricular fibrillation threshold, and suppress ventricular ectopy in tissues during acute myocardial ischemia. However, lidocaine is no longer routinely recommended for prophylaxis after myocardial infarction (MI). Although it reduces the incidence of ventricular ectopy and fibrillation after MI, it may increase mortality secondary to asystole, which may occur if ventricular escape rhythms are abolished.
The benefits of lidocaine include its rapid onset of action, its short time to recovery from sodium channel blockade, and its relative lack of adverse hemodynamic effects. It is protein-bound and undergoes hepatic metabolism. Given the extensive first-pass effect, it is not available as an oral medication.
Pharmacokinetics The onset of action is 30 to 90 s following intravenous administration and 10 min following an intramuscular dose. Subsequent bolus doses are generally required to attain therapeutic plasma levels early in treatment; maintenance infusions started without an initial bolus dose will not attain therapeutic levels for up to 30 min to several hours (based on disease state). Lidocaine has an approximate Vd of 1.3 L/kg in normal patients and 0.9 L/kg in patients with liver disease or CHF or in those who are hypotensive. The drug is available for intravenous use only because of its lack of gastrointestinal (GI) absorption and its high first-pass metabolism. Less than 10 percent is excreted unchanged in the urine. The major metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), possess antidysrhythmic and neurotoxic actions and are excreted renally.
Lidocaine has a short distribution half-life of 7 to 8 min following an intravenous bolus and 12 to 28 min following intramuscular administration. This short distribution half-life accounts for the short duration of action after a bolus injection. The elimination half-life in healthy patients ranges from 80 to 108 min, but this may increase up to 7 h in patients with CHF or liver disease and is also greatly prolonged in cardiac arrest. Renal dysfunction does not alter kinectics. Therapeutic serum levels range from 1.5 to 6 mg/mL; serum levels greater than 5 mg/mL may cause CNS toxicity. It readily crosses the blood brain barrier, which accounts for its CNS effects. Not all patients require maximum serum levels.
Common ED Indications Lidocaine is the drug of choice for the suppression of ventricular dysrhythmias and ventricular ectopy (frequent multifocal PVCs, couplets, salvos, and especially long runs of VT) in suspected acute myocardial ischemia or unstable angina. 1 Although once popular, the prophylactic routine use of lidocaine during acute MI is generally not recommended. Such therapy has not been shown to reduce mortality following AMI. In addition, lidocaine should not be used to treat chronic PVC that occur in an asymptomatic patient, as it does not prevent VF. The drug is indicated for control of VT and VF refractory to defibrillation and epinephrine. Lidocaine should be given following successful conversion of ventricular tachydysrhythmias to normal sinus rhythm. It is also indicated for ventricular dysrhythmias associated with cardiac arrest, myocardial infarction, and unstable angina. Lidocaine can be an adjunct to procainamide for the treatment of wide-complex supraventricular dysrhythmias of uncertain type (e.g., WPW syndrome).
Dosing and Administration Lidocaine is given as an initial bolus dose of 1.0 to 1.5 mg/kg followed by additional bolus doses of 0.5 to 0.75 mg/kg q5-10 min as needed up to a cumulative dose of 3 mg/kg. An alternative method is to give 1.5 mg/kg initially followed by 50-mg bolus doses every 5 min up to a total dose of 225 mg or 3 mg/kg. When VF is present and defibrillation and epinephrine have failed, an initial bolus of 1.5 mg/kg is recommended for all patients. Conscious patients should receive lidocaine at a rate not exceeding 50 mg/min to minimize adverse CNS effects (< 25 mg/min if infused through a central line). However, in pulseless VT
or VF, lidocaine can be given by rapid intravenous push. When intravenous lines are not available, the drug may be instilled endotracheal^, in which case 2 to 2 2 times the intravenous dose diluted with normal saline solution to a total volume of 10 mL is recommended for optimal drug absorption.
VF and pulseless VT should be managed only with intravenous bolus doses. Maintenance infusions should be started at 2 mg/min and titrated up to 4 mg/min as needed (30 to 50 mg/kg per minute) only upon return of perfusion (poor perfusion will hamper the drug's elimination).
Patients more than 70 years of age as well as those with CHF, liver disease, or impaired hepatic blood flow should have their loading dose and maintenance infusion rate lowered by 50 percent. Drug interactions that can prolong the half-life of lidocaine or increase toxicity include those that potentiate neurologic effects (e.g., procainamide, tubocurarine), drugs that undergo metabolism in the liver and increase lidocaine levels (e.g., cimetidine, propranolol), and drugs that can produce excessive cardiac depression (e.g., phenytoin). Septic shock will also produce increased cardiac depression. Since the half-life of lidocaine can be increased after 24 to 48 h in any of the above, serum levels should be obtained and infusions adjusted if therapy is used for longer than 24 h. Lidocaine toxicity may also develop in patients with renal dysfunction because of accumulation of the metabolites. Patients should be switched over to oral antidysrhythmics within the first 24 h.
Adverse-Effects Profile Adverse effects from lidocaine usually occur when the drug is administered too rapidly in a conscious patient, when excessive doses are administered, or when a drug interaction potentiates toxicity. Symptoms of mild lidocaine toxicity that correlate with levels greater than 5 mg/mL include slurred speech, drowsiness, confusion, nausea, vertigo, ataxia, tinnitus, paresthesias, muscle twitching and tremor. An abrupt change in mental status is classic for lidocaine toxicity and may indicate that an excessive dose was administered or that the rate of administration was excessive. Serious symptoms occurring at plasma levels greater than 9 mg/mL may include psychosis, seizures, and respiratory depression. Lidocaine is contraindicated in patients with known sensitivities to amide-type local anesthetics and those with high degrees of sinoatrial (SA) or AV block. Lidocaine should be used cautiously in sulfite-allergic patients.
PHENYTOIN Phenytoin also a class IB agent, is used to treat ventricular and supraventricular dysrhythmias associated with digitalis intoxication because of its ability to increase aV nodal conduction time. Unlike lidocaine, phenytoin increases AV nodal conduction. Additionally, it has central sympatholytic activity which is responsible for some of its antidysrhythmic effects. The dose for digoxin-induced dysrhythmias is 100 mg IV q5 min to a total of 1000 to 1500 mg. With parental administration, hypotension can occur secondary to the phenol carrier. Toxic serum levels can result in CNS changes. A further general discussion of phenytoin appears in Chap 172.
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