THE EFFECT OF TIME TO TREATMENT WITH ANTIARRHYTHMIC DRUGS ON OUTCOMES IN SHOCK REFRACTORY OUT-OF-HOSPITAL CARDIAC ARREST: A SECONDARY ANALYSIS OF THE ALPS RANDOMIZED CONTROLLED TRIAL

Abstract

<h3>BACKGROUND</h3> The relationship between time to treatment in patients with out-of-hospital cardiac arrest (OHCA) and survival outcomes, and the interaction of time to treatment and antiarrhythmic drug effect, is not precisely known. We conducted a post-hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo (ROC ALPS) randomized controlled trial examining the association of time to treatment (drug or placebo) with survival and neurological outcome. A secondary objective was to determine whether this relationship was modified by treatment type (i.e., amiodarone versus lidocaine). <h3>METHODS AND RESULTS</h3> In the ROC ALPS trial, adults with non-traumatic OHCA and an initial rhythm of shock refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) after at least one defibrillation were randomized to receive amiodarone, lidocaine, or placebo. We used logistic regression to examine the association of time to treatment (defined as a 911 call to study drug administration interval) with survival at hospital discharge and favourable neurological status at discharge (Modified Rankin Scale ≤ 3) for the three treatment groups. Time to treatment data were available for 2994/3026 (99%) of the patients. The proportion of patients who survived at hospital discharge decreased as time to drug administration increased in amiodarone (OR 0.91, 95% CI:0.90–0.93 per min increase in time interval), lidocaine (OR 0.93, 95% CI:0.91-0.96), and placebo (OR 0.91, 95% CI:0.90-0.93) treated patients. With short times to drug administration, survival was not different in lidocaine versus placebo, whereas survival was higher with lidocaine than placebo at later times after drug administration (Fig). The odds of survival at hospital discharge in the lidocaine group (as compared to placebo) changed significantly in relation to the time of drug administration in an adjusted analysis (OR 1.04, 95% CI:1.01-1.09, p=0.048). Comparing amiodarone to placebo, there was improved survival at discharge at all times of drug administration; there was no significant effect of time to drug administration (adjusted OR 1.00, 95% CI:0.95-1.03, p=0.84; unadjusted OR 0.99, 95% CI:0.95-1.03, p=0.67). Survival with good neurological outcome showed the same trends for all analyses. <h3>CONCLUSION</h3> In a post-hoc analysis of the ROC ALPS study, the probability of survival and favourable neurological outcomes decreased with a longer interval from a 911 call to receipt of amiodarone, lidocaine, or placebo. The effect of lidocaine but not amiodarone in increasing the probability of survival at hospital discharge and favourable neurological outcome varied based on the interval from 911 call to receipt of the drug.