EBM COMMENTARY:

1) Statistical versus clinical significance: The study authors did not demonstrate a statistical difference in their primary outcome. However, there is a difference between statistical significance and clinical significance. The observed approximately 3 percent difference in survival to hospital discharge with treatment, if true, would translate into 1,800 lives saved yearly in North America for OHCA. They would have needed to enroll about 9,000 patients to establish if the 3 percent difference was statistically significant.

2) Intention-to-treat versus per-protocol analysis: The primary endpoint of this study was based on a per-protocol analysis of the cohort, which can introduce bias and make the treatment look better. They excluded 1,627 patients for a number of reasons. When they did an intention-to-treat analysis, the trend toward improvement became even less.

• Survival to hospital discharge: amiodarone 19 percent, lidocaine 18.4 percent, and placebo 17.6 percent
• Favorable neurologic function at discharge: amiodarone 14.4 percent, lidocaine 13.5 percent, and placebo 13.8 percent

3) Subgroup analysis: There were statistical differences observed in some prespecified subgroups. These should be viewed with caution and considered observational by nature. It is also important to remember that subgroup analysis can easily be misleading because the risk of type 1 error (incorrect rejection of a true null hypothesis) increases as the investigator makes more observations.

BOTTOM LINE: In adult OHCA patients with refractory ventricular fibrillation or pulseless ventricular tachycardia, amiodarone or lidocaine is unlikely to provide a clinically important benefit.

CASE RESOLUTION: The patient has a return of spontaneous circulation but does not survive to hospital discharge.

Thank you to Dr. Rory Spiegel from EM Nerd for his help with this review. Dr. Spiegel is a clinical instructor at the University of Maryland and a recent graduate of Stony Brook’s resuscitation fellowship.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References

1. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S444-S464.
2. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 1999;341(12):871-878.
3. Dorian P, Cass D, Schwartz B, et al. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med. 2002;346(12):884-890.