Effect of Time to Treatment With Antiarrhythmic Drugs on Return of Spontaneous Circulation in Shock‐Refractory Out‐of‐Hospital Cardiac Arrest

Abstract

Background The effects of amiodarone and lidocaine on the return of spontaneous circulation (ROSC) in relation to time to treatment in patients with out‐of‐hospital cardiac arrest is not known. We conducted a post hoc analysis of the ROC ALPS (Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo) randomized controlled trial examining the association of time to treatment (drug or placebo) with ROSC at hospital arrival. Methods and Results In the trial, adults with nontraumatic out‐of‐hospital cardiac arrest with initial refractory ventricular fibrillation or pulseless ventricular tachycardia after at least 1 defibrillation were randomly assigned to receive amiodarone, lidocaine, or placebo. We used logistic regression to examine the association of time to treatment (911 call to study drug administration) with ROSC. An interaction term between treatment and time to treatment was included to determine the potential effect of time on treatment effects. Overall, 1112 (36.7%) patients had ROSC at hospital arrival (350 in the amiodarone arm, 396 in the lidocaine arm, and 366 in the placebo arm). The proportion of patients who had ROSC decreased as time to drug administration increased, in patients treated with amiodarone (odds ratio, 0.92; 95% CI, 0.90–0.94 per minute increase), lidocaine (odds ratio, 0.95; 95% CI, 0.93–0.96), and placebo (odds ratio, 0.95; 95% CI, 0.93–0.96). With shorter times to drug administration, the proportion with ROSC was higher in amiodarone versus placebo recipients. Conclusions The probability of ROSC decreased as time to drug administration increased. The effect of amiodarone but not lidocaine to restore ROSC declined with longer times to drug administration, potentially attributable to its adverse hemodynamic effects.

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

“…A recent study found that shorter time from 9‐1‐1 call to amiodarone had a higher probability of ROSC at ED arrival than placebo 11 . This study also reported that delayed administration of amiodarone was associated with lower probabilities of ROSC compared to placebo.…”

“…These previous analyses had limitations, including varied time cutoffs, a lack of controlling for dispatch to EMS arrival times or routes of drug administration, and not accounting for the resuscitation time bias. A recent secondary analysis of the ALPS data suggested that earlier time from 9‐1‐1 call to antiarrhythmics was associated with greater odds of ROSC, with a significant interaction with time of drug administration, when comparing amiodarone to placebo 11 . However, this study did not evaluate survival outcomes, control for route of drug administration, or assess the ideal time interval from EMS arrival to drug delivery.…”

“…Six studies have noted that early, compared to late, amiodarone or lidocaine was associated with improved patient outcomes, including greater odds of return of spontaneous circulation (ROSC) 11,12 as well as survival to admission, 13,14 to discharge, 15 and with good neurologic status (functional survival) 16 when using 9‐1‐1 call or dispatch to drug administration time cutoffs of 15, 2 16, 13 20, 16 and 24 min 17 . These previous analyses had limitations, including varied time cutoffs, a lack of controlling for dispatch to EMS arrival times or routes of drug administration, and not accounting for the resuscitation time bias.…”

Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest

“…For example, one strategy might use the algorithm to provide earlier or higher-dose antiarrhythmic treatment or a lower or delayed dose of a vasopressor such as epinephrine (given its potential proarrhythmic effects) for those at high risk of refractory VF. [8][9][10][11][12][13][14][15] The algorithm might also be used to inform which patients could be considered for modified shock delivery strategies (vector change or double sequential defibrillation) or early transport for advanced hospital care such as an emergent coronary artery intervention or extracorporeal CPR. [16][17][18][19][20][21]…”

“…[5][6][7] Hence, the ability to predict refractory VF in advance of repeated shock failure could enable preemptive interventions targeted at improving the relatively poor outcomes of the refractory VF subgroup. Such therapies might include earlier or increased antiarrhythmic dose administration, [8][9][10][11][12] reconsideration of epinephrine use or dosage, [13][14][15] changes in how shocks are administered, 16 or expedited invasive interventions. [17][18][19][20][21] By contrast, empiric treatment of all patients with VF OHCA using such strategies may unnecessarily expose patients who achieve best outcomes under the current protocol, introducing potential risk among those unlikely to benefit.…”