Increased return of spontaneous circulation at the expense of neurologic outcomes: Is prehospital epinephrine for out-of-hospital cardiac arrest really worth it?

J Crit Care. 2015 Dec;30(6):1376-81. doi: 10.1016/j.jcrc.2015.08.016. Epub 2015 Sep 1.


Introduction: Current guidelines for the management of out-of-hospital cardiac arrest (OHCA) recommend the use of prehospital epinephrine by initial responders. This recommendation was initially based on data from animal models of cardiac arrest and minimal human data, but since its inception, more human data regarding prehospital epinephrine in this setting are now available. Although out-of-hospital return of spontaneous circulation (ROSC) may be higher with the use of epinephrine, worse neurologic outcomes may be associated with its use.

Methods: A systematic review of the literature was conducted by search of databases including PubMed, Embase, and OVID to identify studies comparing patients with OHCA who had received epinephrine before arrival to the hospital with those who had not. Studies were assessed for quality and bias, and data were abstracted from studies deemed appropriate for inclusion. A meta-analysis was conducted using a Mantel-Haenszel model for dichotomous outcomes. Outcomes studied were prehospital ROSC, survival at 1 month, survival to discharge, and positive neurologic outcome.

Results: A total of 14 studies with 655853 patients were included for the meta-analysis. The use of epinephrine for OHCA before arrival to the hospital was associated with a significant increase in ROSC (odds ratio, 2.86; P<.001) and a significant increase in the risk of poor neurologic outcome at the time of discharge (odds ratio 0.51, P=.008). There was no significant difference in survival at 1 month or survival to discharge.

Conclusion: Use of epinephrine before arrival to the hospital for OHCA does not increase survival to discharge but does make it more likely for those who are discharged to have poor neurologic outcome. There is a need for additional randomized controlled trials.

Keywords: CPR; Out of hospital; cardiac arrest; neurologic outcome; resuscitation; return of spontaneous circulation.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenergic beta-Agonists / therapeutic use*
  • Blood Circulation / drug effects*
  • Blood Circulation / physiology
  • Cardiopulmonary Resuscitation / methods
  • Emergency Medical Services / methods
  • Emergency Medical Services / statistics & numerical data
  • Epinephrine / therapeutic use*
  • Humans
  • Nervous System Diseases / etiology*
  • Odds Ratio
  • Out-of-Hospital Cardiac Arrest / drug therapy*
  • Out-of-Hospital Cardiac Arrest / mortality
  • Survival Analysis


  • Adrenergic beta-Agonists
  • Epinephrine