Optimal timing for epinephrine administration in adult patients with out-of-hospital cardiac arrest: A retrospective observational study

Background: This study aimed to clarify the appropriate timing for epinephrine administration in adults with out-of-hospital cardiac arrest (OHCA), particularly those cases with nonshockable rhythms, by addressing resuscitation time bias.

Methods: We performed a retrospective observational study utilizing a multicenter OHCA registry involving 95 hospitals in Japan between June 2014 and December 2020. We included patients with OHCA and nonshockable rhythms who received epinephrine during resuscitation. The primary and secondary outcomes were favorable 30-day neurological status and survival, respectively. A favorable neurological outcome was defined as a cerebral performance category score of 1 or 2. The time from emergency medical service (EMS) personnel contact to epinephrine administration was categorized in 5-min intervals. We used the Fine-Gray regression to calculate the time-dependent propensity score in each group. After risk set matching, we employed a generalized estimating equation (GEE) to adjust for within-patient clustering.

Results: A total of 36,756 patients were included in the analysis. When involving timing variables and GEE, epinephrine administration significantly affected favorable 30-day neurological status at 1-5 and 6-10 min, with risk ratios (RR; 95% confidence intervals [CIs]) of 9.36 (1.19-73.7) and 3.67 (1.89-7.14), respectively. Epinephrine administration significantly affected 30-day survival at 1-5, 6-10, 11-15, and 16-20 min, with RRs (95% CIs) of 2.33 (1.41-3.85), 2.09 (1.65-2.65), 1.64 (1.32-2.05), or 1.70 (1.29-2.25), respectively.

Conclusions: Epinephrine administration within 10 min of EMS personnel contact may be associated with favorable neurological outcomes in patients with OHCA and nonshockable rhythms.