What is the efficacy of bretylium in managing ventricular storm?

Efficacy of Bretylium in Ventricular Storm

Bretylium has potent antifibrillatory effects but is not recommended as first-line therapy for ventricular storm; it should only be used for resistant ventricular fibrillation or hemodynamically unstable ventricular tachycardia after other agents have failed. 1

Mechanism of Action and Pharmacology

Bretylium is a quaternary ammonium compound with both direct (Class III) and indirect (sympathetic neuronal) actions:

• Initial phase: Causes norepinephrine release from adrenergic nerve endings leading to:

  • Transient hypertension
  • Tachycardia
  • Shortening of AV nodal refractory periods

• Subsequent phase: Produces neuronal blockade resulting in:

  • Hypotension (most significant side effect)
  • Class III effect (refractory period lengthening)

The antiarrhythmic effect may take up to 20 minutes to manifest, necessitating continued resuscitation efforts during this period 1.

Position in Treatment Algorithm

Bretylium is positioned as a later-line agent in ventricular storm management:

1. First-line therapies:

   • Beta-blockers (IV metoprolol 5 mg over 1-2 minutes, maximum 15 mg)
   • Amiodarone (300 mg IV bolus, followed by infusion)
   • Lidocaine (for ischemia-related VT)

2. For refractory VF/pulseless VT:

   • Bretylium is recommended after defibrillation, epinephrine, and lidocaine have failed
   • It may be used for VT in patients with a pulse, but only after lidocaine and procainamide have failed 1

3. For electrical storm:

   • Modern guidelines prioritize amiodarone, beta-blockers, and deep sedation
   • Bretylium is rarely mentioned in current protocols 2

Dosing and Administration

For ventricular fibrillation:

• Initial dose: 5 mg/kg IV bolus
• If VF persists: Supplemental doses of 10 mg/kg every 5 minutes
• Maximum total dose: 30-35 mg/kg
• Maintenance: 1-2 mg/min infusion if successful

For stable ventricular tachycardia:

• Loading dose: 5 mg/kg diluted in 50 mL dextrose given over 8-10 minutes
• If unsuccessful: Additional 10 mg/kg dose
• Maintenance: 1-2 mg/min infusion 1

Efficacy Evidence

Clinical studies show variable efficacy:

• In prehospital ventricular fibrillation, approximately 35% of patients with refractory VF responded following bretylium administration, but only 5% survived to hospital discharge 3

• Comparative studies with amiodarone showed comparable efficacy between bretylium and high-dose amiodarone (1000 mg/24h) for treating malignant ventricular arrhythmias, but bretylium caused significantly more hypotension 4

• Bretylium demonstrates substantial activity in several clinical circumstances of ventricular fibrillation, particularly in cases where standard antiarrhythmic therapy is ineffective 5

Side Effects and Precautions

Major side effects include:

• Orthostatic and supine hypotension (most significant)
• Nausea and vomiting (with rapid administration)
• Initial sympathomimetic effects (hypertension, tachycardia)

Hypotension may require management with:

• Fluid administration
• Pressor agents
• Position changes
• Dose adjustment 6

Clinical Pearls and Pitfalls

• Bretylium's antifibrillatory effect is more pronounced than its antiarrhythmic effect, making it more suitable for VF than for suppression of simple ventricular ectopy 5

• The delayed onset of action (up to 20 minutes) necessitates continued resuscitation efforts during this period 1

• Modern protocols have largely replaced bretylium with amiodarone, which has a more favorable side effect profile while maintaining similar efficacy 4

• For incessant VT/electrical storm, current guidelines recommend a combination of amiodarone and beta-blocker, along with deep sedation to reduce sympathetic tone, with consideration of urgent catheter ablation if medication fails 2