Does Single Dose Epinephrine Improve Outcomes for Patients with Out-of-Hospital Cardiac Arrest by Sex or Race?

INTRODUCTION: Recent evidence suggests that survival to hospital discharge in patients with out-of-hospital cardiac arrest (OHCA) is similar among patients receiving a single dose epinephrine protocol compared to a multi-dose epinephrine protocol. However, it is unknown whether survival to hospital rates differ for single dose vs. multi-dose epinephrine within sex and race subgroups. Our objective in this study was to determine whether survival to hospital discharge rates varied for single dose vs. multi-dose epinephine protocols among men, women, White, and non-White patients. METHODS: We conducted a pre-post Single Dose Epinephrine Implementation Study from November 1,2016 - October 29, 2019 at five North Carolina emergency medical services (EMS) systems, involving patients ≥ 18 years old with non-traumatic OHCA. Data on race, sex, and the primary outcome of survival to hospital discharge were determined from the Cardiac Arrest Registry to Enhance Survival and from EMS records. We performed intention-to-treat analysis. We compared survival to hospital discharge rates between single dose vs multi-dose epinephrine protocols within sex and race subgroups using generalized estimating equations with a logit link to account for clustering among EMS agencies and to adjust for age, witnessed arrest, automated external defibrillator availability, EMS response interval, the presence of a shockable rhythm, receiving bystander cardiopulmonary resuscitation, and sex or race. In the model, we evaluated interactions between epinephrine protocol and race and sex. RESULTS: Of the 1,690 patients included, (899 multi-dose, 791 single dose), 38.7% (657/1,690) were female and 74.7% (1,262/1,690) were White. Survival to hospital discharge occurred in 13.6% (122/899) of patients in the multi-dose group and 15.4% (122/791) in the single dose epinephrine group (OR 1.19, 95%CI 0.89-1.59). Single dose epinephrine was associated with increased survival to hospital discharge rates in White patients (adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] 1.05-1.30). However, the rates were similar for single dose vs. multi-dose epinephrine among men (aOR 1.03, 95% CI 0.93-1.14), women (aOR 1.23, 95% CI 0.97-1.56), and non-White patients (aOR 1.08, 95% CI 0.78-1.51). Interactions between epinephrine protocol and subgroups were not significant. CONCLUSION: Rates of survival to hospital discharge were similar in the single dose and multi-dose epinephrine strategies regardless of sex. Single dose epinephrine was associated with increased survival to hospital discharge among White patients but not in non-White patients, which may be due to unmeasured confounding or inadequate power.