Cardiology

Interventional Pharmacology: Antiarrhythmics

General (including evidence of efficacy)

A variety of arrhythmias may be encountered during coronary angiography and intervention. They can range in seriousness from premature complexes to potentially lethal ventricular fibrillation. Life-threatening arrhythmias occur in <1% of all cardiac catheterizations.

If hemodynamically unstable ventricular tachycardia or fibrillation develops, the immediate treatment is electrical defibrillation. This may be supplemented by IV antiarrhythmic agents, such as amiodarone or lidocaine.

Differences between drugs within the class

Amiodarone

Amiodarone, a powerful antiarrhythmic agent, is frequently used in the management of a variety of supraventricular and ventricular tachyarrhythmias in the cardiac catheterization laboratory. It has equivalent or superior efficacy compared to most other antiarrhythmic drugs.

Lidocaine

Lidocaine is an IV antiarrhythmic agent that has moderate efficacy against ventricular arrhythmias. It is particularly useful in the setting of myocardial infarction or ischemia. It may be used as an alternative to amiodarone in the management of recurrent or shock refractory ventricular fibrillation/tachycardia.

Atropine

Atropine is an anticholinergic agent that is used to inhibit the effects of excessive vagal activity on the heart. Vagal reactions usually manifest as bradycardia, atrioventricular (AV) block, and hypotension. In elderly patients, or those who are pacemaker-dependent, the heart rate may not slow and hypotension may be the only manifestation of a vagal episode.

The treatment of choice for patients who experience vagal reactions in the cardiac catheterization laboratory is IV atropine and IV fluids. Vasoconstrictors are reserved for persistent hypotension that is unresponsive to these measures.

Administration

Amiodarone

The loading dose is 150 mg IV over 10 minutes, followed by 1 mg/min over the next 6 hours and then 0.5 mg/min over the next 18 hours. After the first 24 hours, a maintenance infusion of 0.5 mg/min may be continued.

Advanced Cardiovascular Life Support (ACLS) guidelines support a 300 mg rapid IV bolus in the setting of cardiac arrest due to refractory ventricular fibrillation/pulseless ventricular tachycardia (VT).

Lidocaine

Lidocaine is administered as an IV bolus of 75 to 100 mg (1.5 mg/kg). A second bolus of 0.5 mg/kg is usually given 5 to 10 minutes later due to rapid distribution. A continuous infusion at a rate of 1 to 4 mg/min is used to maintain adequate serum levels for 24 to 48 hours. Therapeutic serum levels vary, but <6 mg/L is most accepted.

The maintenance dose should be reduced by 50% in patients with liver disease or impaired hepatic blood flow (heart failure or shock), and in the elderly who have reduced volume of distribution. In rare cases when IV access is not immediately available, lidocaine may be given intramuscularly (4 to 5 mg/kg) resulting in effective serum levels at about 15 minutes.

Atropine

Vagal reactions usually respond promptly to 0.5 to 1 mg IV atropine. If necessary, a repeat dose can be administered in 3 to 5 minutes. In patients with coronary artery disease, the total dose should be restricted to 2 mg to avoid the harmful effects of atropine-induced tachycardia on myocardial oxygen demand.

In cases of cardiac arrest associated with bradyasystole, 1 mg IV atropine can be repeated every 3 to 5 minutes with a cumulative dose not to exceed 3 mg. Doses less than 0.5 mg should not be administered because they may exacerbate the bradycardia by paradoxically enhancing vagal outflow to the heart.

In the rare situation that IV access is not immediately available, atropine can be given intraarterially or endotracheally.

Pharmacologic action

Amiodarone inhibits outward potassium channels, thereby increasing action potential duration (APD) and refractoriness of both atrial and ventricular tissue. In addition to prolonging repolarization, amiodarone also slows sinus node activity and impedes AV node conduction.

When given acutely, IV amiodarone significantly inhibits sodium and calcium currents (class I and class IV effects, respectively). These actions are use-dependent (greater at faster heart rates) and voltage-dependent with preferential activity on tissue that is relatively depolarized (i.e., ischemic myocardium). Therefore, IV amiodarone is effective for ventricular arrhythmias in the setting of acute myocardial infarction/ischemia.

Amiodarone

Amiodarone is classified a class III agent, but displays activity from all four Vaughan Williams classes.

Amiodarone is 95% protein bound and highly lipid soluble with a large volume of distribution. It undergoes extensive hepatic metabolism with excretion into bile. It has a very long half-life (mean of 60 days).

Lidocaine

Lidocaine is approximately 60% to 80% protein bound. It is hepatically metabolized with a half-life of 1 to 2 hours in patients with normal cardiac and liver function. During periods of acute stress, such as acute myocardial infarction, plasma binding increases, which prolongs the half-life to as long as 4 hours.

Lidocaine has a rapid onset of action within 45 to 90 seconds following the IV loading dose.

Atropine

The vagus nerves that innervate the myocardium release acetylcholine, which binds to muscarinic receptors (specifically M2) principally found in the SA and AV nodes. Vagal stimulation produces a Gi-mediated reduction in cAMP, and activation of potassium channels. This hyperpolarizes the cells, and consequently increases the threshold for firing.

Atropine is a competitive antagonist of the muscarinic receptors that prevents acetylcholine from binding and activating these receptors. By blocking the actions of acetylcholine, atropine effectively blocks vagal stimulation of the myocardium. In doing so, it increases sinus node automaticity and enhances AV node conduction.

Atropine may be ineffective in heart transplant recipients due to vagal denervation.

Indications and contraindications

Amiodarone

Indications

IV amiodarone is indicated in the management of refractory or shock-resistant ventricular fibrillation or ventricular tachycardia.

  • IV amiodarone can be useful for rate and/or rhythm control in patients with atrial fibrillation or flutter with rapid ventricular response.

Contraindications

  • In the catheterization laboratory, amiodarone is contraindicated in patients with cardiogenic shock, severe bradycardia, and high degree AV block.

Lidocaine

Indications

  • Lidocaine is indicated for the acute management of ventricular arrhythmias in patients with myocardial infarction/ischemia or during cardiac surgery or catheterization. Amiodarone is generally preferred over lidocaine for recurrent ventricular arrhythmias in other settings.

  • Although routine prophylactic lidocaine reduces the incidence of ventricular fibrillation in acute MI, it is no longer recommended because it increases overall mortality.

  • A single bolus of lidocaine can be administered as an alternative to amiodarone in cases of cardiac arrest due to recurrent or shock refractory ventricular fibrillation/tachycardia.

Contraindications

  • Lidocaine is contraindicated in patients with severe sinus node dysfunction or advanced AV block.

Atropine

Indications

  • Vagal reactions secondary to pain or groin complications

  • Bradycardia, AV block due to increased vagal activity in the setting of inferior MI

  • Cardiac arrest associated with bradyasystole

Contraindications

  • Atropine is contraindicated in patients with acute closed angle glaucoma.

Undesirable effects

Amiodarone

Chronic amiodarone has several adverse effects, but acutely IV amiodarone may cause bradycardia, heart block, hypotension due to systemic vasodilation, heart failure, or arrhythmias.

The predominant side effects of lidocaine are related to the central nervous system. Slurred speech, paresthesia, tremors, ataxia, drowsiness, delirium, seizures, and respiratory arrest can occur and are generally associated with toxic plasma levels. Symptoms resolve with a decrease in dose or discontinuation of the drug.

Cardiovascular side effects are infrequent but may include bradycardia, asystole, and hypotension.

Lidocaine

The predominant side effects of lidocaine are related to the central nervous system. Slurred speech, paresthesia, tremors, ataxia, drowsiness, delirium, seizures, and respiratory arrest can occur and are generally associated with toxic plasma levels. Symptoms resolve with a decrease in dose or discontinuation of the drug.

Atropine

The most common side effects of IV atropine are tachycardia and arrhythmias.

Excessive doses can produce anticholinergic symptoms, such as flushing, delirium, blurry vision, and ataxia. Cardiovascular side effects are infrequent but may include bradycardia, asystole, and hypotension.

What's the Evidence?

Vassallo, P, Trohman, RG. "Prescribing amiodarone: an evidence-based review of clinical indications". JAMA.. vol. 298. 2007. pp. 1312-22.

(Excellent systematic review from the literature (inclusive of 92 studies) examining the efficacy of amiodarone for different arrhythmias and in various clinical conditions as well as its safety profile.)

Fuster, V, Rydén, LE, Cannom, DS. "2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/ American Heart AssociationTask Force on practice guidelines". Circulation. vol. 123. 2011 Mar 15. pp. e269-367.

(Authoritative and updated guideline from the ACCF, AHA, and HRS on the management of atrial fibrillation, inclusive of detailed sections on amiodarone and other antiarrhythmic medications.)

Zipes, DP, Camm, AJ, Borggrefe, M. "ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)". J Am Coll Cardiol. vol. 48. 2006. pp. e247-346.

(Authoritative guideline from the ACCF, AHA, and ESC and other societies on the management of ventricular arrhythmias and prevention of sudden cardiac death, inclusive of detailed sections on amiodarone, lidocaine, and other antiarrhythmic medications.)

Field, JM, Hazinski, MF, Sayre, MR. "Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. vol. 122. 2010. pp. S640-56.

(Authoritative guideline describing the clinical use of amiodarone, lidocaine, atropine and other drugs for the treatment of hemodynamically unstable and symptomatic bradyarrhythmias and tachyarrhythmias.)
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