Guidelines recommend epinephrine as the primary medical intervention for cardiac arrest. However, no randomized trial data are available to support this recommendation. In this observational study from the American Heart Association’s Get With The Guidelines – Resuscitation multi-center registry of in-hospital cardiac arrest, the authors sought to determine if timing of epinephrine administration in the setting of non-shockable (i.e. pulseless electrical activity or asystole) in-hospital cardiac arrest is associated with patient outcomes. Among 25,095 patients with non-shockable in-hospital cardiac arrest, the median time to first epinephrine was 3 minutes (IQR 1-5 minutes). When analyzed at 3 minute intervals, there was a stepwise decrease in survival to discharge with increasing time to epinephrine. As compared to 1-3 minutes, the adjusted odds ratios were 0.91 (95% confidence interval [CI] 0.82 – 1.00; p = 0.055) for 4-6 minutes, 0.74 (95% CI 0.63 – 0.88; p < 0.001) for 7-9 minutes, and 0.63 (95% CI 0.52 – 0.76) for > 9 minutes. The authors also performed sensitivity analyses to ensure the primary analysis was not confounded by overall delays in initiation of resuscitation independent of time to epinephrine, by the selection of 3 minute increments for categorization of epinephrine administration, or by missing covariates. The results of the sensitivity analyses were similar to those of the primary analysis.

Conclusion: In this large observational study, increased time to epinephrine for cardiac arrest with non-shockable rhythm was associated with worse patient outcomes. It is important to consider that duration of resuscitation is an important contributor to patient outcomes, and thus later administration of epinephrine may reflect longer resuscitation events with lower likelihood of survival. However, this study reiterates the need for further investigation of epinephrine for cardiac arrest to define its optimal use to improve patient survival.

Summarized by Steven M. Bradley and Preston M. Schneider

Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014;348.

Figure. Survival to discharge by timing of epinephrine administration among patients with non-shockable in-hospital cardiac arrest.