Amiodarone and Cardiac Resuscitation
Amiodarone and Cardiac Resuscitation
Abstract & commentary
Source: Kudenchuk PJ, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999;341:871-878.
Until now, there has been limited evidence to support the use of anti-arrhythmic medications for treatment of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) in patients with out-of-hospital cardiac arrest. These investigators conducted a randomized, double-blind, placebo-controlled study of intravenous amiodarone in patients with VF or pulseless VT that persisted after three or more shocks from an external defibrillator. Patients were treated in accordance with American Heart Association guidelines for advanced cardiac life support (ACLS). After tracheal intubation, eligible patients received 1 mg of epinephrine IV and were randomly assigned to receive either 300 mg of IV amiodarone (246 patients) or its diluent, polysorbate 80, as placebo (258 patients).
The two groups had similar clinical characteristics, and there was no significant difference in the course of their resuscitation before the administration of either amiodarone or placebo. Patients who received amiodarone were more likely to survive to be admitted to the hospital (44% vs 34% of the placebo group; P = 0.03). The adjusted odds ratio for survival to hospital admission in the amiodarone group vs. the placebo group was 1.6 (95% CI, 1.1-2.4; P = 0.02). The benefit of amiodarone was consistent among all subgroups and at all times of drug administration. More patients had hypotension or bradycardia in the amiodarone group than in the placebo group; these are known adverse effects of intravenous amiodarone. Kudenchuck and colleagues note that the trial did not have sufficient statistical power to detect differences in survival to hospital discharge, which "differed only slightly between the two groups."
Comment by Stephanie Abbuhl, MD, FACEP
Recipients of amiodarone were 29% more likely to be resuscitated and admitted to the hospital than were recipients of placebo. As encouraging as these results initially sound, it is critical not to lose sight of the most important outcome in this type of research, which is functional neurologic status at discharge. Anything other than functional neurologic status should be considered an "intermediate outcome" and interpreted with caution. Ultimately, the results of this study may or may not represent a significant advance for patients with out-of-hospital cardiac arrest.
On the other hand, until we have more data, it is clear that amiodarone will find a place in the next version of ACLS guidelines, and possibly as a first- or second-line agent for persistent or recurrent VF or VT. Also of note, as gender is now more commonly evaluated in data analysis, some interesting findings emerge. Women in this study were more likely to be resuscitated than men, particularly when treated with amiodarone. Women treated with amiodarone were more likely than women receiving placebo to survive to be admitted (adjusted odds ratio 4.3; 95% CI, 1.03-17.8). Among men, the comparable adjusted odds ratio was 1.2 (95% CI, 0.3-1.9). As Kudenchuck et al point out, the difference could be due to a greater sensitivity to amiodarone in women or to a higher dose of amiodarone in proportion to body weight in women, because a standard dose of 300 mg was given in the study.
All of the following are true about amiodarone except:
a. amiodarone is often associated with hypotension and bradycardia.
b. amiodarone has been shown to result in a higher rate of survival to hospital admission in out-of-hospital cardiac arrest due to refractory VF when compared to placebo.
c. the benefit of amiodarone was consistent whether the drug was administered early or late in the course of the resuscitation.
d. women treated with amiodarone were more likely than men to survive to be admitted to the hospital.
e. amiodarone has been shown to improve patients’ survival to discharge with functional neurologic status.
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