Tachycardia: high dose intravenous amiodarone was safe and efficacious.

Clinical bottom line (level 1b)

  1. Patients with ventricular tachycardia or fibrillation who were given high-dose amiodarone, were likely to have a lower median arrhythmia event rate than those given bretylium.
  2. Patients given low dose amiodarone were less likely to suffer from drug-related adverse effects than those given bretylium (NNT = 5 at 48 hours) .
  3. Patients given low-dose amiodarone, were likely to have a higher median arrhythmia event rate than those given bretylium.
Kowey et al: Circulation 1995; 92: 3255-3263
Expires October 2004

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 82 centres, USA

302 patients (aged mean 65 years, 76% male) incessant (recurring immediately after termination) ventricular tachycardia, ventricular fibrillation or at least 2 episodes of haemodynamically destabilising ventricular tachycardia/fibrillation in the 24 hours before enrolment

Excluded if
  • evidence that arrhythmias were drug induced or were secondary to cardiogenic shock
  • use of bretylium or any investigational drug within 5 half-lives of study entry
  • concomitant use of other antiarrhythmics
  • hypotension despite inotropic support
  • severe conduction disease (in the absence of a temporary or permanent pacemaker)
  • prolonged QT interval (>0.50 second)
  • clinically significant renal or hepatic dysfunction


    • Control Group: (n = 103, 103 analysed): bretylium 2500 mg/24 hours- initial rapid infusion 350 mg over 10 mins; loading infusion- 1.5 mg/min for 6 hours; maintenance infusion- 1.5 mg/min for the remainder of the 48 hours
    Experimental Group: (n = 94, 94 analysed): intravenous amiodarone low dose 125 mg/24 hours- initial rapid infusion-18.75 mg over 10 mins; loading infusion- 0.125 mg/min for 6 hours; maintenance infusion- 0.065 mg/min for the remainder of the 48 hours
    Experimental Group: (n = 105, 105 analysed): intravenous amiodarone high dose 1000 mg/24 hours- initial rapid infusion- 150 mg over 10 mins; loading infusion- 1 mg/min for 6 hours; maintenance infusion- 0.52 mg/min for the remainder of 48 hours
    Each patient was treated with study drug for 24 hours and then the investigators could start antiarrhythmic therapy of their choice.
    100% followed for 48 hours
    Outcome notes:
    • drug-related adverse effects: low dose versus control : includes hypotension and heart failure

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    drug-related adverse effects: low dose versus control 48 hours 60
    (58.3%)    		 36
    (38.3%)    		 34%
    (11% to 52%)    		 20.0%
    (6.27% to 33.6%)    		 5
    (3 to 16)
    drug-related adverse effects: high dose versus control 48 hours 60
    (58.3%)    		 44
    (41.9%)    		 28%
    (5% to 46%)    		 16.4%
    (2.94% to 29.8%)    		 6
    (3 to 34)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    median haemodynamically destabilising ventricular tachycardia/fibrillation events per hour (low dose versus control) 0.96
    ()     		1.68
    ()     		-0.72
    ( to )
    median haemodynamically destabilising ventricular tachycardia/fibrillation (high dose versus control) 0.96
    ()     		0.48
    ()     		0.48
    ( to )

    Citation

    1. Kowey PR, Levine JH, Herre JM, et al: Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. Circulation 1995; 92: 3255-3263
    Contributor: Clare Wotton and Bob Phillips, October 1999
    Reviewer:

    Clinical Question.
    Patient ventricular tachycardia or fibrillation
    Intervention or Exposure intravenous amiodarone
    Comparison bretylium
    Outcome safety and efficacy