The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest

Abstract

Objectives: Examining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome. Design: Post hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial. Setting: Emergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites. Patients: Adults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included. Interventions: None. Measurements and Main Results: We used logistic regression to examine the association of time to treatment with survival to hospital discharge and favorable neurologic status at discharge (modified Rankin Scale ≤ 3) for the three treatment groups including an interaction term between treatment and time to treatment to determine the effect of time on treatment effects. Time to treatment data were available for 2,994 out of 3,026 patients (99%). The proportion of patients who survived to hospital discharge decreased as time to drug administration increased, in amiodarone (odds ratio [OR], 0.91; 95% CI, 0.90–0.93 per min), lidocaine (OR, 0.93; 95% CI, 0.91–0.96), and placebo (OR, 0.91; 95% CI, 0.90–0.93). Comparing amiodarone to placebo, there was improved survival at all times of drug administration (OR, 1.32; 95% CI, 1.05–1.65). Comparing lidocaine to placebo, survival was not different with shorter times to drug administration (< 11 min), whereas survival was higher with lidocaine at longer times to drug administration with an interaction between treatment effect and time to treatment (p = 0.048). Survival with good neurologic outcome showed similar results for all analyses. Conclusions: Survival and favorable neurologic outcomes decreased with longer times to drug administration. Amiodarone improved survival at all time points whereas lidocaine improved survival only at later time points, compared with placebo.