Although the drug epinephrine (adrenaline) is widely used in cardiopulmonary resuscitation for out-of-hospital cardiac arrest, an analysis that included more than 400,000 patients finds that receipt of the drug for this use was associated with a lower likelihood of survival at one month or survival with good functional status, according to a study in the March 21 issue of JAMA.1
Several studies have examined the effectiveness of epinephrine use in cardiopulmonary resuscitation (CPR) for patients with out-of-hospital cardiac arrest (OHCA), but findings have not been consistent, according to background information in the article.
Akihito Hagihara, D.M.Sc., M.P.H., of Kyushu University Hospital, Fukuoka, Japan and colleagues conducted a study to examine the short- and long-term mortality in patients with cardiac arrest who received epinephrine during cardiac resuscitation before hospital arrival. The study consisted of an analysis of data from 417,188 OHCAs occurring in 2005-2008 in Japan in which patients ages 18 years or older had an OHCA before arrival of emergency medical service (EMS) personnel, were treated by EMS personnel, and were transported to the hospital. The primary outcomes for the study were return of spontaneous circulation before hospital arrival, survival at 1 month after cardiac arrest, survival with good or moderate cerebral performance, and survival with no, mild, or moderate neurological disability.
The researchers found associations between epinephrine use and short- and long-term outcomes that were strong and consistent. “Specifically, our data show that intravenous epinephrine use before hospital arrival was associated with decreased 1-month survival on the basis of propensity-matched national data.”
The authors also found that use of prehospital epinephrine was associated with a decreased chance of good functional outcomes 1 month after the event. “… in the total sample, only 1.4 percent of patients in the epinephrine group had good neurological outcomes, despite a 5.4 percent survival rate. Thus, only about 25 percent of survivors had good neurological outcomes.”
“We believe that the present findings are important both theoretically and practically,” the researchers write. They note that epinephrine is reportedly associated with increased myocardial dysfunction, disturbed cerebral microcirculation after cardiac arrest, and ventricular arrhythmias during the period after resuscitation. “The adverse long-term effect might be due to these pharmacological effects of epinephrine.”
In all patients, a positive association was observed between prehospital epinephrine and return of spontaneous circulation before hospital arrival.
“Our findings need to be verified by studies that include in-hospital resuscitation data,” the authors conclude.
In an accompanying editorial2, Clifton W. Callaway, M.D., Ph.D., of the University of Pittsburgh, examines the question of whether clinicians should stop using epinephrine during CPR based on the findings of this study.
“There probably will never be a larger observational study of this topic. The exciting development is that these data create equipoise about the current standard of resuscitation care. The best available observational evidence indicates that epinephrine may be harmful to patients during cardiac arrest, and there are plausible biological reasons to support this observation. However, observational studies cannot establish causal relationships in the way that randomized trials can.”
“Thus, properly evaluating this traditional therapy now seems necessary and timely and should consist of a rigorously conducted and adequately powered clinical trial comparing epinephrine with placebo during cardiac arrest. Such a trial has previously seemed unethical, and investigators who have attempted to perform this comparison have received unwarranted criticism in their communities. While awaiting results of such a definitive trial, physicians and other practitioners involved in cardiac resuscitation must consider carefully whether continued use of epinephrine is justified.”
1. (JAMA. 2012;307:1161-1168.
2. (JAMA. 2012;307:1198-1199.