Are Antiarrhythmics Effective in Out-of-Hospital Cardiac Arrest?

Resuscitation medicine has been lacking high-quality, evidence-based standards. Despite the existence of concrete guidelines such as the American Heart Association’s Advanced Cardiac Life Support recommendations, few pharmacologic interventions have been tested in a sufficient methodological manner to establish efficacy and safety.

Previous literature has largely relied on surrogate markers of safety and efficacy such as return of spontaneous circulation and survival to hospital admission. While these endpoints are useful, they don't demonstrate an intervention’s ability to improve survival to hospital discharge.

There’s debate on whether the difference between survival to hospital admission and survival to hospital discharge is significant. When considering these outcomes simplistically, however, more patients would rather leave the hospital alive.

Fortunately, new data is emerging to help improve the decision-making process when considering pharmacologic interventions for patients who have experienced out-of-hospital cardiac arrest (OHCA). For instance, a new study from the Resuscitation Outcomes Consortium compared amiodarone, lidocaine, and placebo in OHCA with an initial rhythm of refractory ventricular fibrillation/ventricular tachycardia (rVF/VT).

Patients were enrolled if they were at least 18 years old and had a nontraumatic OHCA with rVF/VT, meaning persistent VF/VT despite at least 1 defibrillation, or a return of VF/VT after defibrillation causing successful termination. Patients were excluded if they had already received open-labeled amiodarone or lidocaine, or had known hypersensitivity to these drugs.

The study drugs were supplied in identical kits dispensed to emergency medical services (EMS), and patients were randomized once EMS personnel opened the kit. Each kit contained 3 syringes of study drug dosed depending on weight.

The amiodarone used was a non-polysorbate 80-containing product, so that no unblinding of the drug would occur from foaming or hypotension. Standard resuscitation measures were permitted, excluding open-label lidocaine or amiodarone.

Importantly, the primary outcome of this study was survival to hospital discharge among the amiodarone group compared with placebo. Secondary outcomes included survival comparisons in lidocaine recipients versus placebo and amiodarone versus placebo. Survival to discharge with favorable neurologic outcome was also a secondary outcome.

There was no difference in survival to hospital discharge among the amiodarone (24.4%), lidocaine (23.7%) and placebo groups (21.0%). The absolute risk difference for survival to hospital discharge between amiodarone and placebo was 3.2 with a 95% CI of -0.4 to 7.0; p=0.08. Survival to discharge with favorable neurologic outcome was similarly non-significantly different among the groups.

Although it appears that there’s no benefit in administering either amiodarone or lidocaine in this patient population, a subgroup analysis shed light on where these antiarrhythmics agents are still important. Among patients with witnessed OHCA, the survival rate was higher with amiodarone (27.7%) and lidocaine (27.8%) compared with placebo (22.7%). When patients with non-witnessed OHCA were examined, however, there was no difference among the study groups.

While this finding merits further investigation, it makes sense that the earlier cardiopulmonary resuscitation (CPR) is performed and the earlier defibrillation occurs, the better the chance that antiarrhythmic agents will be beneficial.

The importance of early recognition, early CPR, and early defibrillation are still the most critical interventions for any OHCA patient. However, antiarrhythmic agents still play a role in OHCA, and they’re most beneficial when given early in conjunction with early intervention.

Reference

Kudenchuk PJ, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016 Apr 4. [Epub ahead of print]