Epinephrine for Out-of-Hospital Cardiac Arrest: An Updated Systematic Review and Meta-Analysis*

Objectives: To perform an updated systematic review and meta-analysis of clinical trials evaluating epinephrine for adult out-of-hospital cardiac arrest resuscitation. Data Sources: The search included MEDLINE, EMBASE, and Ovid Evidence-Based Medicine, clinical trial registries, and bibliographies. Study Selection: Randomized and quasi-randomized controlled trials that compared the current standard dose of epinephrine to placebo, high or low dose epinephrine, any other vasopressor alone or in combination were screened by three independent reviewers. Data Extraction: Randomized and quasi-randomized controlled trials that compared the current standard dose of epinephrine to placebo, high or low dose epinephrine, any other vasopressor alone or in combination were screened by three independent reviewers. Data Synthesis: A total of 17 trials (21,510 patients) were included; seven were judged to be at high risk of bias. Compared to placebo, pooled results from two trials showed that standard dose of epinephrine increased return of spontaneous circulation (risk ratio, 3.09; 95% CI, 2.82-3.89), survival to hospital admission (risk ratio, 2.50; 95% CI, 1.68-3.72), and survival to discharge (risk ratio, 1.44; 95% CI, 1.11-1.86). The largest placebo-controlled trial showed that standard dose of epinephrine also improved survival at 30 days and 3 months but not neurologic outcomes, standard dose of epinephrine decreased return of spontaneous circulation (risk ratio, 0.87; 95% CI, 0.77-0.98) and survival to admission (risk ratio, 0.88; 95% CI, 0.78-0.99) when compared with high dose epinephrine. There were no differences in outcomes between standard dose of epinephrine and vasopressin alone or in combination with epinephrine. Conclusions: Largely based on one randomized controlled trial, standard dose of epinephrine improved overall survival but not neurologic outcomes in out-of-hospital cardiac arrest patients compared with placebo. There is a paucity of trials with meaningful patient outcomes; future epinephrine trials should evaluate dose and method of delivery on long-term survival, neurologic function, and quality of life after cardiac arrest.