Early Epinephrine Administration for Cardiac Arrest
Authors: Jasmeet Soar, Katherine M. Berg
Journal: JAMA Network Open (2021)

observed a time-dependent association between epinephrine administration and survival to hospital discharge and a favorable funtional outcome at discharge in adults with out-ofhospital cardiac arrest (OHCA) with an initial shockable (ventricular fibrillation/pulseless ventricular tachycardia) or nonshockable cardiac rhythm (pulseless electrical activity and asystole).Findings of the study suggest that if epinephrine is used during cardiopulmonary resuscitation (CPR) it is more likely to be beneficial if given early in the resuscitation attempt.The authors used a large data set (>40 000 patients from North America) and time-dependent propensity score-matching to limit resuscitation time bias. 2 During CPR, epinephrine treatment is more likely to occur as the duration of CPR increases, but the need for a longer CPR attempt is also associated with a worse outcome and can bias observations toward a harmful treatment effect from epinephrine.This risk of bias can be decreased by comparing patients who received epinephrine after a given number of minutes of resuscitation with similar patients who were at risk of receiving epinephrine in the same minute during their resuscitation (ie, ongoing CPR but not given epinephrine).Most of our recent understanding of the role of epinephrine during CPR comes from the PARAMEDIC-2 randomized clinical trial 3 that compared epinephrine with placebo in 8014 patients with OHCA in the UK and showed that epinephrine increased return of spontaneous circulation (ROSC) (36% vs 12%) and survival to hospital discharge (3.2% vs 2.4%) compared with placebo (unadjusted odds ratio, 1.39 [95% CI, 1.06-1.82];P = .02).The low overall survival was attributed to a median time of 21 minutes between the emergency call and study drug administration.The main concerns raised by the study were regarding secondary end points, such as whether epinephrine increases brain injury in survivors or helps achieve ROSC at a late stage of cardiac arrest when severe brain damage is more likely.Specifically, there was an increase in the proportion of survivors with poor neurological function in the epinephrine group vs the placebo group (39 of 126 patients [31.0%] vs 16 of 90 patients [17.8%] had a poor neurological outcome, 39 of 4015 patients [1.0%] vs 16 of 3999 patients [0.4%] of the patients in each group).Another concern was that epinephrine use increased intensive care admissions in patients who subsequently died.A secondary cost-analysis of PARAMEDIC-2 suggested that epinephrine use was associated with an increase in the number of organs donated by nonsurvivors and the number of organ transplant recipients. 4When organ donation and transplants were taken into account, administration of epinephrine changed from not being a cost-effective option to being a cost-effective intervention.The study by Okuda et al 1 corroborates another secondary finding of the PARAMEDIC-2 study in that any beneficial treatment effect of epinephrine on ROSC, survival to discharge, and favorable functional outcome declined with increasing time to drug administration compared with placebo, and any beneficial treatment effect was greater for initial nonshockable cardiac rhythms. 5There are no randomized clinical trials of epinephrine for in-hospital cardiac arrest (IHCA).For IHCA, the time to drug administration for cardiac arrest is much shorter than for OHCA.The importance of early administration in the IHCA population is supported, however, by an observational study using data from the American Heart Association Get With The Guidelines Resuscitation registry.In that study of patients with initial nonshockable cardiac rhythm, survival decreased in a stepwise fashion for every 3 minutes of delay to administration of the first epinephrine dose. 6For shockable rhythms, however, propensity score-matched data from the same IHCA registry that accounted for resuscitation time bias found that epinephrine given within the first 2 minutes of CPR was associated with decreased ROSC, survival to hospital discharge, and favorable neurological outcome at discharge.