Time to amiodarone administration and survival outcomes in refractory ventricular fibrillation

Abstract

Objective International guidelines recommend amiodarone for out‐of‐hospital cardiac arrest (OHCA) in refractory ventricular fibrillation (VF). While early appropriate interventions have been shown to improve OHCA survival, the association between time to amiodarone and survival remains to be established. Methods Included were adult OHCA in refractory VF, between January 2015 and December 2019, who received a resuscitation attempt with amiodarone from Queensland Ambulance Service paramedics. Patient characteristics and survival outcomes were described. Factors associated with survival were investigated, with a focus on time from arrest to amiodarone administration. Optimal time window for amiodarone administration was determined, and factors influencing whether amiodarone was given within the optimal time window were examined. Results A total of 502 patients were included. The average (range) time from arrest to amiodarone was 25 (4–83) min. Time to amiodarone was negatively associated with survival (adjusted odds ratio 0.93 for event survival; 95% confidence interval 0.89–0.97). The optimal time window for amiodarone was within 23 min following arrest. Patients receiving amiodarone within the optimal time had significantly better survival than those receiving it outside this window (event survival 38.3% vs 20.6%, P < 0.001; discharge survival 25.5% vs 9.7%, P < 0.001; 30‐day survival 25.1% vs 9.7%, P < 0.001). Paramedic response time (adjusted odds ratio 0.96; 95% confidence interval 0.92–0.99) and time from arrest to intravenous access (0.71; 0.67–0.76) were independent factors determining whether patients received amiodarone within the optimal time. Conclusions Earlier amiodarone administration was associated with improved survival. Strategies aimed at reducing delay to amiodarone administration have the potential to improve outcome.

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

“…Our study independently confirms the importance of early amiodarone, and we further show clear associations with greater survival to discharge and functional survival for early amiodarone compared to placebo. Our results also agree with published retrospective studies finding reduced odds of survival with each 1‐min delay in amiodarone administration (aOR 0.93 15 vs. 0.80 in our study) and neurologic outcomes (unadjusted OR 0.89 16 vs. aOR 0.77 in our study). We also provide reassuring evidence that there is no association with worse survival to discharge or functional outcomes for late amiodarone administration compared to placebo.…”

“…To facilitate comparison to prior studies on the association between the timing of antiarrhythmics and outcomes in OHCA that did not have a data set with a placebo arm for comparison, 12,15,16 we evaluated the impact of delays to delivery among patients receiving each study drug. After multivariable analyses, the odds (95% CI) for survival to admission, survival to discharge, and functional survival were significantly lower per 1‐min delay in drug administration for placebo (0.94 [0.90–0.98], 0.92 [0.87–0.97], and 0.90 [0.84–0.96]), lidocaine (0.91 [0.87–0.95], 0.89 [0.85–0.94], and 0.86 [0.80–0.92]), and amiodarone (0.87 [0.83–0.91], 0.80 [0.74–0.86], and 0.77 [0.71–0.84]), respectively, with the greatest magnitude of decreased odds per 1‐min delay in the amiodarone group (Figure 5).…”

“…Finally, we sought to evaluate the impact of delays to drug administration timing on each individual drug to itself rather than comparing amiodarone or lidocaine to placebo to put our results in context of prior published analyses of antiarrhythmic timing that did not have a placebo arm for comparison. 12,15,16 Due to the resuscitation time bias, we anticipated that these comparisons would show significantly better outcomes with early drug administration compared to late drug administration in unadjusted analysis, even when comparing early placebo to late placebo. Thus, our primary focus was on multivariable logistic regression evaluating the impact of early compared to late drug administration with adjustment for potential confounders.…”

“…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.…”

Temporal Changes in Epinephrine Dosing in Out-of-Hospital Cardiac Arrest: A Review of EMS Protocols across the United States

“…Although less robustly studied, amiodarone has also been associated with increased survival with earlier administration and thus this is an area of clinical equipoise. 12 Rhode Island allows for an epinephrine infusion in place of epinephrine bolus dosing. Studies to support this are lacking, but there are several theoretical benefits such as simplifying the resuscitation process and producing a more consistent serum epinephrine level.…”