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

Shannon M. Fernando, Rebecca Mathew, Behnam Sadeghirad, Bram Rochwerg, Benjamin Hibbert, Laveena Munshi, Eddy Fan, Daniel Brodie, Pietro Di Santo, Alexandre Tran, Shelley L. McLeod, Christian Vaillancourt, Sheldon Cheskes, Niall D. Ferguson, Damon C. Scales, Steve Lin, Claudio Sandroni, Jasmeet Soar, Paul Dorian, Gavin D. PerkinsJerry P. Nolan

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish (US)
Pages (from-to)381-393
Number of pages13
JournalCHEST
Volume164
Issue number2
DOIs
StatePublished - Aug 2023
Externally publishedYes

Keywords

  • critical care medicine
  • emergency medicine
  • epinephrine
  • out-of-hospital cardiac arrest
  • return of spontaneous circulation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine

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