Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms.

Background: Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed.
Research Question: What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?
Study Design and Methods: In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome.
Results: We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85).
Interpretation: Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm.
Trial Registry: Center for Open Science: https://osf.io/arxwq.
Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. S. reports receiving funding from PIPRA AG, outside of the submitted work. B. H. reports receiving research support from Abbott, Edwards Lifesciences, Boston Scientific, and Bayer, outside of the submitted work. L. M. is associate editor of Intensive Care Medicine. E. F. reports receiving personal fees from ALung Technologies, Baxter, Boehringer-Ingelheim, Fresenius Medical Care, MC3 Cardiopulmonary, and Vasomune, outside of the submitted work. D. B. receives research support from ALung Technologies, outside of the submitted work, and has been on the medical advisory boards for Abiomed, Xenios, Medtronic, LivaNova, Inspira, and Cellenkos. S. C. reports receiving research support from Zoll Medical Inc., outside of the submitted work. N. D. F. reports consulting for Baxter and Xenios, outside of the submitted work. C. S. is associate editor of Intensive Care Medicine. G. D. P. receives support from Elsevier for roles as an editor for Resuscitation and editor-in-chief of Resuscitation Plus. J. P. N. receives support from Elsevier for his role as editor-in-chief of Resuscitation. None declared (S. M. F., R. M., B. R., P. D. S., A. T., S. L. M., C. V., D. C. S., S. L., J. S., P. D.).
(Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)