Study Examines Optimal Epinephrine Delivery Time in Cardiac Arrest Patients

The role of epinephrine in cardiac arrest resuscitation continues to evolve. Questions include how much to give a patient, how often to give it, how early to give it, and even if it should be administered at all in cardiac arrest.

Background: Ever since Redding and Pearson used epinephrine pre-shock to assist in converting ventricular fibrillation to a perfusing rhythm almost 50 years ago, it has been included in the prehospital and hospital protocols used for v fib and pulseless v tach.1

Currently, the ACLS protocol for v fib and pulseless v tach recommends that epinephrine be given after the second defibrillation. Many hospitals and EMS systems, however, have been giving it earlier.

A recent study published in the British Medical Journal evaluated whether giving epinephrine before the second shock might better optimize survival (“early epi”), or whether defibrillation, followed by two minutes of CPR and a second shock, was more appropriate before administering epinephrine to patients remaining in VF (“late epi”).

Methods: The authors of this study compared two groups of patients: those who received epinephrine before the second shock versus those who received it after the second shock.

They evaluated return of spontaneous circulation (ROSC), survival to discharge and good neurologic survival at discharge. They used the Get With The Guidelines network of hospitals, which is composed of more than 300 U.S. hospitals.

This study included a total of 2,794 patients; 1,510 were in the early epi group and 1,284 were in the late epi group.

Results: Their results showed that those who received epinephrine early (before the second shock) had a decreased rate of ROSC (67% vs. 79%), a decreased rate of survival (31% vs. 48%), and a decrease in good functional outcome (25% vs. 41%).

The p values were < 0.001 in all cases, meaning that each of these differences were statistically significant. These patients were then matched with another group using a propensity score.

When patients who received epinephrine earlier-before the second shock-were carefully matched (for variables like age and underlying diseases) to those who received it post second shock, the results, again, showed that early epinephrine was deleterious: early epinephrine was clearly inferior to waiting for a second shock to administer it and outcomes were worse in the early epi group.

The total number of defibrillations and time to the second defibrillation were equal in both groups. Those in the early epinephrine group received a higher total epinephrine dose (3 mg vs. 1 mg). Time to ROSC and time to termination of resuscitation were equal in both groups.

This study showed that over 50% of the cardiac arrest patients with a shockable rhythm received epinephrine in the first two minutes which is counter to the current AHA recommendations.

Conclusion: The most important finding in this study of 2,794 patients was that those who received epinephrine early had a decreased rate of ROSC, decreased chance of survival, and a decrease in good functional outcomes. Based on the results of this study, emergency care providers should follow the current ACLS guidelines and wait to give epinephrine until after the second shock in a shockable rhythm.


1. Redding JS, Pearson JW. Resuscitation from ventricular fibrillation: Drug therapy. JAMA. 1968;203(4):255-260.

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