Survival by time-to-administration of amiodarone, lidocaine, or placebo in shock-refractory out-of-hospital cardiac arrest

Background: Amiodarone and lidocaine have not been shown to have a clear survival benefit compared to placebo for out-of-hospital cardiac arrest (OHCA). However, randomized trials may have been impacted by delayed administration of the study drugs. We sought to evaluate how timing from emergency medical services (EMS) arrival on scene to drug administration affects the efficacy of amiodarone and lidocaine compared to placebo. Method: This is a secondary analysis of the 10-site, 55-EMS-agency double-blind randomized controlled amiodarone, lidocaine, or placebo in OHCA study. We included patients with initial shockable rhythms who received the study drugs of amiodarone, lidocaine, or placebo before achieving return of spontaneous circulation. We performed logistic regression analyses evaluating survival to hospital discharge and secondary outcomes of survival to admission and functional survival (modified Rankin scale score <= 3). We evaluated the samples stratified by early (<8 min) and late administration groups (>= 8 min). We compared outcomes for amiodarone and lidocaine compared to placebo and adjust for potential confounders. Results: There were 2802 patients meeting inclusion criteria, with 879 (31.4%) in the early (<8 min) and 1923 (68.6%) in the late (>= 8 min) groups. In the early group, patients receiving amiodarone, compared to placebo, had significantly higher survival to admission (62.0% vs. 48.5%, p = 0.001; adjusted OR [95% CI] 1.76 [1.24--2.50]), survival to discharge (37.1% vs. 28.0%, p = 0.021; 1.56 [1.07--2.29]), and functional survival (31.6% vs. 23.3%, p = 0.029; 1.55 [1.04--2.32]). There were no significant differences with early lidocaine compared to early placebo (p > 0.05). Patients in the late group who received amiodarone or lidocaine had no significant differences in outcomes at discharge compared to placebo (p > 0.05). Conclusions: The early administration of amiodarone, particularly within 8 min, is associated with greater survival to admission, survival to discharge, and functional survival compared to placebo in patients with an initial shockable rhythm.