• Mahbod Rahimi, Paul Dorian, Sheldon Cheskes, Gerald Lebovic, and Steve Lin.
• Institutes of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
• Crit. Care Med. 2023 Jul 1; 51 (7): 903912903-912.

ObjectivesExamining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome.DesignPost hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial.SettingEmergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites.PatientsAdults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included.InterventionsNone.Measurements And Main ResultsWe 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.ConclusionsSurvival 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.Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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