Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest

JAMA Netw Open. 2024 Feb 5;7(2):e2356863. doi: 10.1001/jamanetworkopen.2023.56863.


Importance: While epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest (OHCA), the optimal sequence of these interventions remains unclear.

Objective: To evaluate the association of the sequence of epinephrine administration and AAM with patient outcomes after OHCA.

Design, setting, and participants: This cohort study analyzed the nationwide, population-based OHCA registry in Japan and included adults (aged ≥18 years) with OHCA for whom emergency medical services personnel administered epinephrine and/or placed an advanced airway between January 1, 2014, and December 31, 2019. The data analysis was performed between October 1, 2022, and May 12, 2023.

Exposure: The sequence of intravenous epinephrine administration and AAM.

Main outcomes and measures: The primary outcome was 1-month survival. Secondary outcomes were 1-month survival with favorable functional status and prehospital return of spontaneous circulation. To control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions, propensity scores and inverse probability of treatment weighting (IPTW) were performed for shockable and nonshockable initial rhythm subcohorts.

Results: Of 259 237 eligible patients (median [IQR] age, 79 [69-86] years), 152 289 (58.7%) were male. A total of 21 592 patients (8.3%) had an initial shockable rhythm, and 237 645 (91.7%) had an initial nonshockable rhythm. Using IPTW, all covariates between the epinephrine-first and AAM-first groups were well balanced, with all standardized mean differences less than 0.100. After IPTW, the epinephrine-first group had a higher likelihood of 1-month survival for both shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms compared with the AAM-first group. For the secondary outcomes, the epinephrine-first group experienced an increased likelihood of favorable functional status and prehospital return of spontaneous circulation for both shockable and nonshockable rhythms compared with the AAM-first group.

Conclusions and relevance: These findings suggest that for patients with OHCA, administration of epinephrine before placement of an advanced airway may be the optimal treatment sequence for improved patient outcomes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Epinephrine / therapeutic use
  • Female
  • Humans
  • Intubation, Intratracheal
  • Male
  • Odds Ratio
  • Out-of-Hospital Cardiac Arrest* / therapy


  • Epinephrine