Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest

Abstract

Background: Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known.

Methods: In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration.

Results: Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06-1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5-9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02-1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7-8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66-1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74-1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant.

Conclusions: We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.

Keywords: amiodarone; antiarrhythmia agents; arrhythmias, cardiac; heart arrest.

Figure 1:

Stratification of patients who were eligible for study drug by intravenous or intraosseous route of vascular access, and their randomized treatment assignment to amiodarone, lidocaine or placebo.

Figure 2

Unadjusted and adjusted absolute differences in survival to hospital admission, survival to hospital discharge and functional status (modified Rankin Scale ≤3) at hospital discharge. The left side of the figure describes the unadjusted percentages of patients who achieved the described endpoints. The forest plot and numerical values on the right of each figure depict the adjusted absolute differences (with 95% confidence intervals) in the described endpoints. The upper forest plot depicts outcomes comparing IV amiodarone vs placebo and IO amiodarone vs placebo. The lower plot depicts outcomes comparing IV lidocaine vs placebo and IO lidocaine vs placebo. Significant differences in survival to hospital admission, to hospital discharge and favoring improved functional status at hospital discharge were observed in association with IV administration of amiodarone and lidocaine compared to placebo, but not when these drugs were administered IO. A statistically significant interation between the route of drug administration and outcome was not found.