Study Examines the Role of Epinephrine for Out-of-Hospital Cardiac Arrest

Research article: Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. July 18, 2018. [Epub ahead of print.] Full text available here.

Background: The role of epinephrine in cardiac arrest has been debated since Redding and Pearson studied the efficacy of multiple different medications including epinephrine in the early 1960s.

Methods: This month, an article titled “A randomized trial of epinephrine in out-of-hospital cardiac arrest” was published in The New England Journal of Medicine. The article studied the role of EMS-administered epinephrine in out of hospital cardiac arrest (OOHCA) in a large, double-blind, placebo-controlled trial, using 8,014 patients over the age of 16 in the United Kingdom.

A total of 4,015 patients in asystole, PEA or v fib/v tach were randomized to receive epinephrine 1 mg every 3—5 minutes, and 3,999 patients were randomized to receive placebo. This study evaluated survival at 30-days and functional neurologic outcome.

Results: The median time from emergency call to EMS arrival was 6.6 minutes. The median time from emergency call to epinephrine or placebo administration was about 21 minutes. The average dose of epinephrine was 4.9 mg (+/- 2.5 mg) and the placebo used was saline.

Return of spontaneous circulation was achieved in 36.3% of the epinephrine group compared to 11.7% of the placebo group. This study also found that there was a statistically significant higher rate of 30-day survival using epinephrine when compared to placebo. There were 3.2% (130) in the epinephrine group, compared to 2.4% (94) in the placebo group. Multiple calculations were performed that showed there was still a greater 30-day survival with epinephrine when analysis was adjusted to control for whether the cardiac arrest was paramedic-witnessed vs. bystander-witnessed or unwitnessed; when shockable vs. non-shockable rhythms were analyzed; or when arrests were medical vs. non-medical (including traumatic).

Further analysis was done to assess the neurologic outcome in survivors after cardiac arrest when given epinephrine compared to placebo. Severity of neurologic outcome was defined by the Modified Rankin Scale (mRS). On this scale, a score of 0 represents no disability, a score of 3 represents disability requiring daily assistance, and a score of 6 represents death.

Importantly, this study found that there was no statistically significant difference in favorable neurologic outcome of survivors (mRS of 0—3) when using epinephrine compared to placebo. Favorable neurologic outcome was 2.2% in the epinephrine group vs 1.9% in the placebo group and that the number of survivors who could care for themselves (mRS of 0—2) was equal at 1.3% whether epinephrine was used or not.

Furthermore, it found that patients who had received epinephrine where more likely to have severe neurologic impairment at the time of discharge (Modified Rankin score 4-5).  Severe neurologic disability was almost double at 31% in the epinephrine survivors versus 17.8% in the placebo survivors.

Discussion/Conclusion: There will be much debate over this article and at least three different conclusions can be drawn:

  1. Epinephrine in OOHCA arrest improves ROSC and likelihood for hospital discharge or;
  2. Epinephrine does not improve neurologically intact survival in OOHCA, or finally;
  3. Epinephrine in OOHCA just increases the likelihood of being neurologically devastated without significantly increasing the number of neurologically intact survivors.

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