Is Early Epinephrine Administration in Cardiac Arrest a Bad Idea?

There's still controversy regarding epinephrine's utility in cardiac arrest.

Epinephrine has been used in cardiac arrest since the American Heart Association (AHA) and European Resuscitation Council (ERC) first recommended it in the first Advanced Cardiopulmonary Life Support (ACLS) guidelines in 1974.1,2 Despite these recommendations, there’s still controversy regarding epinephrine’s utility in cardiac arrest.3,4,5

New literature on pharmacotherapy in cardiac arrest has been emerging since the 2015 ACLS guidelines recommended administering epinephrine as soon as possible after the onset of cardiac arrest due to an initial non-shockable rhythm.6

One large observational study in cardiac arrest with an initial non-shockable rhythm compared epinephrine given at 1 to 3 minutes and later time intervals (4 to 6, 7 to 9, and >9 minutes). The study found an association between early administration of epinephrine and increased return of spontaneous circulation (ROSC), survival to hospital discharge, and neurologically intact survival.

There’s a lack of published studies regarding early epinephrine use in hospital patients who experience cardiac arrest with an initial shockable rhythm. AHA guidelines recommend epinephrine after the second defibrillation, while ERC guidelines recommend it after the third defibrillation.

Recently, a study published in the British Medical Journal sought to determine the effects of early administration of epinephrine within 2 minutes after the first defibrillation.7

It had 2 main purposes:

1. Assess compliance with current ACLS guidelines using a large, multicenter cardiac arrest registry.

2. Determine whether early epinephrine administration after the first defibrillation has an association with survival to discharge.

The study analyzed data from the Get With The Guidelines-Resuscitation registry, which is a national prospective quality improvement registry of inpatients in cardiac arrest. It included patients in cardiac arrest with a documented initial shockable rhythm that received a documented first defibrillation within 2 minutes. It also included only patients who had a documented shockable rhythm after the 1st defibrillation.

Patients who received epinephrine before the first defibrillation, had ROSC, or in whom resuscitation was terminated within the same minute as the first defibrillation were excluded.

Contrary to the AHA guidelines, 51% of patients who fit the inclusion criteria for this study received epinephrine within 2 minutes after the first defibrillation. Early administration of epinephrine within the first 2 minutes after the first defibrillation in both the unadjusted analysis and the propensity matched cohort was associated with a decreased likelihood of survival, ROSC, and good functional outcome compared with those who weren’t given epinephrine during this period.

It’s important to note that this was an observational study in hospital patients, so no causality can be drawn from the results or should be extrapolated to non-hospital settings. Although more than 300 hospitals were included in the study, the sample size was inadequate to draw conclusions about epinephrine after the second or third defibrillation.

Nevertheless, the results illuminate deviation from the guidelines regarding the timing of epinephrine in shockable rhythms and the potential detrimental effects of this practice. Clinicians should consider avoiding epinephrine use within the first 2 minutes after the first defibrillation and adhere to the ACLS/ECR guidelines.


1. Monica E. Kleinman, Erin E. Brennan, Zachary D. Goldberger, Robert A. Swor, Mark Terry, Bentley J. Bobrow, Raúl J. Gazmuri, Andrew H. Travers, and Thomas. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:18 suppl 2 S414-S435.

2. Deakin CD, Nolan JP, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. 2010;81:1305-1352.

3. Lin S, Callaway CW, Shah PS, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2014;85:732-740.

4. Perkins GD, Nolan JP. Early adrenaline for cardiac arrest. BMJ. 2014;348:g3245.

5. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest. JAMA. 2012;307:1198-1200.

6. Nakahara S, Tomio J, Takahashi H, et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ. 2013;347:f6829.

7. Andersen LW, Kurth T, Chase M, Berg KM, Cocchi MN, Clifton C, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577.