Source: Ali MU, Fitzpatrick-Lewis D, Kenny M, et al. Effectiveness of antiarrhythmic drugs for shockable cardiac arrest: A systematic review. Resuscitation. 2018;132:63-72.
Study Population: 6,525 adults in 14 randomized controlled trials
Efficacy Endpoints: Survival to hospital discharge with favorable neurologic outcome, survival to hospital discharge, return of spontaneous circulation
Harm Endpoints: Not reported
Narrative: The International Liaison Committee on Resuscitation guidelines1 support the use of antiarrhythmics in patients with shock-resistant out-of-hospital cardiac arrest (OHCA), largely based on a systematic review and meta-analysis by Ali et al,2 the basis of this evidence summary.
Ali et al2 found 14 randomized trials (n=6525 subjects) on the use of antiarrhythmics in adult cardiac arrest. Upon meta-analysis, they found no significant difference with an antiarrhythmic agent compared to placebo in the patient-centered outcome of survival to hospital discharge: amiodarone (relative risk [RR] 1.1, 95% confidence interval [CI] 0.98-1.3; n=2530), lidocaine (RR 1.1, 95% CI, 0.96-1.3; n=2041), magnesium (RR 1.1, 95% CI 0.6-1.9; n=437), and bretylium (RR 4.3, 95% CI 0.6-30.3; n=29). The results were similar for survival to discharge with favorable neurologic outcome. However, there was a statistically increased return of spontaneous circulation associated with lidocaine (RR 1.2, 95% CI 1.0-1.3; n=2051).
Caveats: The systematic review by Ali et al2 is comprehensive, yet the results should be interpreted with caution. Ali et al noted risks of bias among included studies such as issues with randomization, improper allocation concealment and blinding, baseline imbalance, failure to adhere to intention-to-treat analysis, and industry funding. They therefore rated the evidence “very low to moderate certainty.”
Twelve of 14 trials were also performed before 2005, and there have since been revisions of guidelines and advancements in care including increases in bystander CPR, implementation of targeted temperature management, and greater use of post-arrest coronary catheterization.3 For instance in the 2016 ROC-ALPS trial,4 high proportions received targeted temperature management (74%) and coronary catheterization (56%), and the placebo group survival rate was 21%. In the 1999 Kudenchuk et al trial,5 such procedures were uncommon, and the placebo group survival rate was 13%. The inclusion of older trials may therefore limit the applicability of this meta-analysis to contemporary clinical practice.
The timing of drug administration may also help to explain the absence of meaningful benefit found in Ali et al.2 The likelihood of survival drops rapidly with time after cardiac arrest,6 and antiarrhythmic drugs may function best in the ‘metabolic’ phase, within ten minutes of arrest.7 This theory is supported by an analysis of a subgroup with witnessed arrest in Kudenchuk et al.4 In this subgroup (n=1934), for whom antiarrhythmic drug administration in the metabolic phase may have occurred more frequently, there was a statistically significant increase in survival to discharge with both amiodarone (27.7%) and lidocaine (27.8%) compared to placebo (22.7%). And while subgroup findings are, at best, hypothesis-generating, presumably drug administration occurred earlier in this group.
In summary, we assign a recommendation of Red (benefits do not outweigh harms) for antiarrhythmic administration in cardiac arrest with a shockable rhythm. There is no overall evidence of patient-centered benefit. There is, however, a signal that earlier administration of antiarrhythmics in patients with witnessed arrest may be beneficial, and we hope future studies will address this possibility.
Author: Robert Allen, MD; Peter Tepler, MD; Ian S. deSouza, MD
Supervising Editor: Shahriar Zehtabchi, MD
Published/Updated: June 18, 2020
The title bar is color-coded with our overall recommendation.