A Randomized Controlled Trial of Intravenous Aminophylline for Atropine-resistant Out-of-hospital Asystolic Cardiac Arrest

Abstract

Myocardial ischemia, during cardiopulmonary arrest, can lead to atropine-resistant bradyasystole from interstitial accumulation of endogenous adenosine. Aminophylline is a nonspecific adenosine receptor antagonist capable of reversing ischemia-induced bradyasystole in a variety of settings. The hypothesis of this study was that aminophylline improves the rate of return of spontaneous circulation (ROSC) in atropine-resistant asystolic out-of-hospital cardiac arrest when used early in the resuscitation effort. This was a prospective, randomized, double-blinded, placebo-controlled trial set in an urban emergency medical services system serving a population of 250,000. All non-pregnant, normothermic adults suffering nontraumatic out-of-hospital cardiac arrest (February 1999 to August 2000) with asystole were eligible. Patients remaining in asystole after initial doses of epinephrine and atropine received either aminophylline 250 mg or matching placebo as a bolus injection through a peripheral intravenous line. All other aspects of the attempted resuscitation proceeded in accordance with standard Advanced Cardiac Life Support (ACLS) guidelines. A sample size of 102 patients was calculated to yield a power of 80% to show an absolute improvement of 25% in ROSC. The aminophylline and control groups were compared by calculating 95% confidence intervals (95% CIs) and the data were modeled using logistic regression. The investigators enrolled 112 consecutive patients. One subject was dropped prior to analysis because of missing data. Data for 111 patients were analyzed on an intention-to-treat basis. Baseline characteristics were similar for the two groups. Comparing the control and aminophylline groups, ROSC was achieved in 15.6% (95% CI = 6% to 29%) and 22.7% (95% CI = 13% to 35%), while reversal of asystole occurred in 26.7% (95% CI = 15% to 42%) and 40.9% (95% CI = 29% to 54%), respectively. Group allocation had an odds ratio of 1.8 (95% CI = 0.6 to 5.3) for ROSC. Witnessed arrest was an independent predictor of outcome with an odds ratio of 3.8 (95% CI = 1.3 to 11.2). Addition of aminophylline appears to be a promising new intervention in the ACLS treatment of atropine-resistant asystolic out-of-hospital cardiac arrest.