Antiarrhythmic Drugs

Introduction

• Cardiac arrhythmias are a broad class of disorders that are characterized by an abnormal rate or rhythm of the heart.¹
• Clinically, arrhythmias may present with a myriad of symptoms, including syncope, palpitations, and shortness of breath, or they may be asymptomatic.¹ 
• Certain cardiac arrhythmias, such as atrial fibrillation or ventricular tachycardia, can lead to severe complications such as a stroke or sudden cardiac death.
• Antiarrhythmic drugs can suppress or terminate cardiac arrhythmias by blocking ion channels and receptors.
• In the perioperative and acute-care setting, antiarrhythmic drugs are essential for stabilizing the heart rhythm, managing life-threatening arrhythmias, and minimizing hemodynamic compromise, particularly when surgical stress or anesthetic stimulation precipitates dysrhythmias.²

Cardiac Action Potentials

• Cardiac cells depend on an electrochemical potential gradient to produce action potentials.³
• The electrochemical potential gradient is generated by voltage-sensitive ion channels, which allow ions to travel across cellular membranes.³
• Atrial and ventricular myocyte action potentials cause atrial and ventricular contraction and promote perfusion.⁴
• Sinoatrial (SA)/atrioventricular (AV) node action potentials initiate and regulate cardiac rhythm.⁵
• Myocyte action potential
  • Cardiac ventricular muscle cells have an action potential with 5 phases (0-4).
    • Phase 0: Depolarization
      • Voltage-gated fast sodium channels open, and there is a rapid influx of sodium channels.³
    • Phase 1: Initial repolarization
      • Voltage-gated fast sodium channels close and there is a small efflux of potassium from transient potassium channels.³
    • Phase 2: Plateau phase
      • Calcium influx through the voltage-gated calcium channels. Potassium efflux continues, but the calcium influx balances it.³
    • Phase 3: Repolarization
      • Voltage-gated calcium channels close. Several types of potassium channels remain open, so there is a strong potassium efflux.³
    • Phase 4: Resting phase
      • There is no spontaneous depolarization, and the membrane potential is maintained by potassium channels.³

• SA/AV node action potential
  • SA node cells and AV nodal cells have an action potential with three phases (0, 3, and 4).⁵
    • Phase 0: Depolarization
      • Voltage-gated calcium channels open, causing an influx of calcium ions.⁵
    • Phase 3: Repolarization
      • Voltage-gated calcium channels close, and voltage-gated potassium channels open, so there is an efflux of potassium ions.⁵
    • Phase 4: Gradual depolarization
      • Slow influx of sodium ions.⁵ 

Classification of Antiarrhythmic Drugs

• The VW classification system categorizes antiarrhythmic drugs by their mechanisms of action.

• Antiarrhythmic Drugs Not in VW Classification:
  • Magnesium:
    • Magnesium has been shown to prevent and treat arrhythmias, though its mechanism is still not clearly understood.⁸
  • Atropine/Glycopyrrolate:
    • Atropine and glycopyrrolate block muscarinic receptors and increase heart rate.⁹
  • Digoxin:
    • Digoxin blocks sodium-potassium adenosine triphosphatase, which lengthens the cardiac action potential and lowers the heart rate.⁹
  • Adenosine:
    • Adenosine causes an efflux of potassium and inhibits a calcium influx, which slows down the conduction of cardiac cells.⁹

Pharmacokinetic Considerations

Absorption and Routes (intravenous [IV] vs per os)

• The bioavailability of a drug given intravenously is 100% as it is directly administered to the systemic circulation.
• The bioavailability of an orally administered drug can vary depending on several factors, including absorption rate and first-pass metabolism.

Hepatic and Renal Metabolism Considerations

• The metabolic pathways for antiarrhythmic medications play a role in determining appropriate dosing, drug choice, and potential toxicity for patients. This is especially critical in patients with reduced hepatic or renal function.
• Hepatic Metabolism
  • Many antiarrhythmic medications are metabolized by the liver, including amiodarone, lidocaine, propafenone, quinidine, verapamil, and diltiazem.¹⁰
  • Impaired hepatic function can prolong half-life and increase plasma levels, so dosing may have to be adjusted for patients with hepatic disease.¹⁰
• Renally eliminated drugs
  • Antiarrhythmic medications such as sotalol, dofetilide, and procainamide are primarily cleared by the kidneys.⁹
  • Renal impairment can lead to drug accumulation and significantly increase the risk of torsades de pointes.⁹
  • Thus, dosages of renally eliminated agents are routinely adjusted according to creatinine clearance to minimize QT prolongation and proarrhythmic events.⁹

Indications

Supraventricular Arrhythmias

• Atrial fibrillation/atrial flutter
  • The management of atrial fibrillation and atrial flutter in the acute setting depends on the hemodynamic stability of the patient.⁹
    • Hemodynamically unstable:
      • Start immediate synchronized cardioversion with anticoagulant therapy.⁹
    • Hemodynamically stable:
      • If there is evidence of a rapid ventricular response, administer a bolus intravenously of a beta-blocker or nondihydropyridine calcium-channel blocker, and if symptoms do not resolve, then begin an IV drip.⁹
  • For persistent atrial fibrillation or atrial flutter, there are many pharmacological options to prevent recurrence, though specific treatment plans depend on individual comorbidities and clinical needs.⁹
  • Please see the OA summary on atrial fibrillation for more details. Link
• Supraventricular tachycardia (SVT)
  • An SVT is a rapid heart rhythm that, if left untreated, can lead to tachycardia-mediated cardiomyopathy or hemodynamic instability.⁹
    • AV nodal reentrant tachycardia is the most common SVT.⁹
  • The pharmacological interventions of SVT include:
    • First-line for most regular, narrow-complex SVTs
      • Adenosine, an AV node blocker: 6mg IV rapid bolus, if SVT persists, may do 12mg IV bolus.⁹
    • Other options if adenosine fails or is contraindicated:
      • Verapamil, a nondihydropyridine calcium-channel blocker: 2.5-5mg IV over 2 minutes that may be repeated every 15-30 minutes.⁹
      • Metoprolol, a beta-blocker: 2.5-5mg IV bolus every 5 minutes for up to 15mg.⁹
  • Please see the OA summary on supraventricular tachycardia for more details. Link

Ventricular Arrhythmias

• Ventricular tachycardia
  • A ventricular tachycardia is a rapid heart rhythm that can compromise cardiac output and lead to sudden cardiac death, which is why prompt management is necessary to restore normal rhythm and maintain hemodynamic stability.
  • The management of ventricular tachycardia in the acute setting depends on the hemodynamic stability of the patient.⁹
    • Hemodynamically unstable:
      • Start immediate synchronized cardioversion if the patient has a pulse or defibrillation if pulseless.⁹
    • Hemodynamically stable:
      • Amiodarone (class III antiarrhythmic) 150mg IV over 10 minutes, then 1mg/minute for 6 hours, then 0.5mg/min for 18 hours.⁹
  • Please see the OA summary on ventricular tachycardia for more details. Link
• Wolff-Parkinson-White (WPW) Syndrome
  • WPW syndrome is a cardiac conduction disorder that, if untreated, can lead to extreme tachycardia, hemodynamic collapse, ventricular fibrillation, or sudden cardiac death.⁹
  • IV procainamide 20-50mg/min up to 17mg/kg can be administered until the arrhythmia is suppressed.⁹
  • Oral propafenone 150-300mg every 8 hours can also be used to treat certain patients.⁹
  • Please see the OA summary on WPW syndrome for more details. Link
• Torsades de pointes (TdP)
  • Torsades de pointes is a polymorphic ventricular tachycardia that, if untreated, can progress to ventricular fibrillation and sudden cardiac death.⁹
  • IV magnesium sulfate 1-2g over 15 minutes can be administered to treat TdP.⁹
  • Please see the OA summary on prolonged QT intervals for more details. Link

Contraindications

• Certain disease processes are contraindications to the use of specific antiarrhythmic medications.
• Heart block
  • AV-nodal-blocking agents (Beta-blockers, calcium-channel blockers, digoxin, VW Class III drugs) should be avoided in patients with second-degree type II or third-degree AV block unless the patient has a pacemaker.⁹
• Heart failure with reduced ejection fraction (HFrEF)
  • Nondihydropyridine calcium-channel blockers, most VW Class 1 agents, and certain beta-blockers are contraindicated in patients with HFrEF because they may worsen systolic function.⁹
• Prolonged QT
  • VW Class IA and VW Class III agents can prolong the QT-interval, so they should be avoided in patients who already have a prolonged QT-interval, because in these patients, these agents can precipitate torsades de pointes.⁹
• Asthma
  • Nonselective beta-blockers may cause bronchospasm in these patients.⁹

Perioperative Considerations

• Continuation vs holding of chronic anti-arrhythmias
  • Most chronic antiarrhythmics should be continued perioperatively to avoid arrhythmia recurrence.
  • Abrupt discontinuation of antiarrhythmic agents can lead to rebound tachycardia or atrial fibrillation recurrence.
• Drug-anesthetic interactions
  • Volatile anesthetics:
    • Use cautiously with agents that may prolong the QT interval, including sotalol, dofetilide, and VW Class III agents.
  • Propofol:
    • Use cautiously with beta-blockers or digoxin because, in combination, they can exacerbate bradycardia.
  • Sympathomimetics:
    • Use cautiously with patients on VW Class I or III drugs, as in combination, they can precipitate tachyarrhythmias.
• Algorithms for acute management of perioperative arrhythmias

• Intraoperative Drug Use
  • Dosing principles
    • IV administration should be done incrementally to reduce hypotension and bradycardia.
    • Continuous electrocardiographic monitoring should be used for all boluses administered.