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NewsletterAmiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. Kudenchuk PJ, Cobb LA, Copass MK, Cummins RO, Doherty AM, Fahrenbruch CE, Hallstrom AP, Murray WA, Olsufka M, Walsh T. N Engl J Med 1999; 341:871-8 Reviewer: Albert T. Cheung, MD Background: Limited information exists on the incremental benefit of antiarrhythmic drugs for resuscitation of patients suffering cardiac arrest with ventricular tachycardia or fibrillation. This report described a study designed to determine whether intravenous amiodarone improved the rate of successful resuscitation among patients suffering cardiac arrest. Methods: In a randomized, double-blind, placebo-controlled trial, the rate of survival until admission to the hospital was determined in 504 patients with non-traumatic out-of-hospital cardiac arrest and ventricular fibrillation or pulseless ventricular tachycardia after three or more precordial shocks. Patients were randomly assigned to receive an intravenous bolus of amiodarone 300 mg or its diluent, polysorbate 80 (placebo) after tracheal intubation and 1 mg of intravenous epinephrine during the course of a resuscitation protocol based on American Heart Association guidelines for advanced cardiac life support. The primary end point was admission to the hospital with a stable cardiac rhythm and blood pressure. Patients who died in the emergency department were not considered to have been admitted. Results: Intravenous amiodarone was administered to 246 (49%) of the 504 patients entered into the study. The initial cardiac rhythm was ventricular fibrillation in 84% of patients and asystole or pulseless electrical activity evolving into ventricular fibrillation in the remaining 16% of patients. An average of five shocks was delivered before the administration of amiodarone or placebo. Treatment groups were not different except that more patients in the placebo group had previous treatment for bradycardia or arrhythmias. Thirty-nine percent (197 of 504 patients) survived to be admitted to the hospital. Successful resuscitation and admission to the hospital was more frequent (p=0.03) among patients who received amiodarone (44%) compared to those who received placebo (34%). In amiodarone-treated patients, the adjusted odds ratio for survival to hospital admission was 1.6 (95% confidence interval, 1.1 to 2.4, p=0.02). A survival benefit of amiodarone was detected regardless of the presenting rhythm or the delay in receiving study drug after witnessed arrests (p=0.008). Women tended to have better outcome than men (43% vs. 38% survived to admission) and exhibited a more favorable response to amiodarone with an adjusted odds ratio for admission of 4.3 (95% confidence interval, 1.03 to 17.8). Amiodarone treatment was associated with a lower blood pressure (p=0.02), lower heart rate (p=0.004), more frequent use of vasopressor drugs (p=0.04), and more frequent need to treat bradycardia (p=0.004). Amiodarone treatment did not affect survival to discharge from the hospital which was 13.4% (33 of 246) in the amiodarone group and 13.2% (34 of 258) in the placebo group. Conclusion: The authors concluded that treatment with amiodarone during resuscitation resulted in a greater rate of survival to hospital admission for patients suffering cardiac arrest due to ventricular arrhythmias refractory to initial attempts at defibrillation. Comments: The efficacy of antiarrhythmic drugs for the treatment of cardiac arrest has been controversial. The most current American Heart Association guidelines for advanced cardiac life support (ACLS) acknowledged that, "we do not know the exact incremental value (over continued countershocks) of the these agents [lidocaine, bretylium, magnesium, procainamide, and sodium bicarbonate] in persistent ventricular tachycardia/fibrillation." Considering the difficulties inherent in conducting large prospective trials to address this important question, the investigators should be commended on their accomplishment. Their finding that intravenous amiodarone used as an adjunct to the standard ACLS ventricular fibrillation/pulseless ventricular tachycardia algorithm increased the success rate of resuscitation was not surprising. The finding was consistent with earlier clinical trials that led to the FDA approval of intravenous amiodarone in 1995 for the treatment of unstable patients with ventricular tachycardia or fibrillation (Circulation 1995; 92:3255-63, Circulation 1995;92:3264-72, and J Am Coll Cardiol 1996; 27:67-75). The incremental benefit of amiodarone in comparison to other antiarrhythmic drugs such as lidocaine or bretylium in the setting of cardiac arrest can only be inferred from the study because amiodarone was compared only to placebo. This study also identified potential adverse effects associated with intravenous amiodarone. Patients who received amiodarone had to be treated more often for hypotension and bradycardia. Only a single 300 mg dose of amiodarone was tested. This dose was chosen based on a "best estimate" for efficacy, but it may not necessarily be the "optimal" dose and was not consistent with the recommendations on the drug label. It was tempting to speculate that the increased efficacy of amiodarone observed in women could have been attributed to the receipt of greater dose in relation to body weight as compared to men. Finally, it was not demonstrated that amiodarone treatment improved long-term survival. It can be argued that the study was not powered to detect differences in long-term survival or that it was not possible to control the care administered once patients were admitted into the hospital. Although additional studies will be necessary to determine the long-term benefits of antiarrhythmic drug therapy for resuscitation from cardiac arrest, the demonstrated short-term efficacy of intravenous amiodarone cannot be ignored. Patients must first survive the initial event. Early identification of patients who may benefit from intravenous amiodarone, combined with prompt recognition and treatment of adverse hemodynamic drug effects could potentially increase the success of resuscitation efforts. See also Dr. Balser's response: Evidence-based Pharmacologic Therapy During Cardiac Arrest.
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