Vasopressin vs. Epinephrine in ACLS Resuscitation

Abstract & Commentary

Source: Stiell IG, et al. Vasopressin versus epinephrine for in-hospital cardiac arrest: A randomized, controlled trial. Lancet 2001;358:105-109.

The American Heart Association’s (AHA) most recent Advanced Cardiac Life Support (ACLS) guidelines recommend vasopressin as an alternative to epinephrine in the treatment of cardiac arrest.1 Stiell and colleagues conducted a triple-blind, randomized, controlled trial comparing vasopressin with epinephrine as the initial vasopressor in the treatment of 200 in-patient cardiac arrests. The primary outcomes were survival to hospital discharge, survival to one hour, and neurologic function.

Patients in the emergency departments (EDs), critical care units, and wards of three Canadian teaching hospitals were eligible if they had a cardiac arrest and required epinephrine according to AHA/ACLS protocols for asystole, pulseless electrical activity, or refractory ventricular fibrillation. Patients received one dose of vasopressin 40 U or epinephrine 1 mg intravenously as the initial vasopressor. All patients who failed to respond to the study intervention were given standard doses of epinephrine every 3-5 minutes as rescue therapy. Of the 200 patients, 104 received vasopressin and 96 received epinephrine. The study patients overall had a mean age of 70 years, 64% were male, and the arrest was witnessed in 81% of cases. The most common initial rhythm was pulseless electrical activity (48%), followed by asystole (31%) and ventricular fibrillation (18%).

Outcomes did not differ in the vasopressin and epinephrine groups for one-hour survival (39% vs 35%, P = 0.66; absolute difference 3.1%, 95% CI -10.5%-17.3%) or survival to hospital discharge (12% vs 14%, P = 0.67; absolute difference -2.0%, 95% CI -11.6%-7.8 %). There were no differences between the two groups for any secondary survival outcomes, including any return of pulse, survival for 24 hours or for 30 days, or in adverse outcomes. Even in the subgroups of myocardial ischemia/infarction or ventricular fibrillation/tachycardia, no modest trend favoring vasopressin was detected. The neurologic state and quality of life of survivors in both groups were good, with similar median mini-mental state examination scores and median cerebral performance category scores.

Comment by Stephanie B. Abbuhl, MD, FACEP

This study puts a significant damper on the enthusiasm that had been generated by a few previous, smaller studies. One study in particular was a randomized trial comparing vasopressin with epinephrine in 40 pre-hospital patients.2 Many more patients were alive after 24 hours (60% vs 20%, P < 0.05) in the vasopressin group.

There are several potential explanations for these apparent contradictions. It is possible that differences do exist between vasopressin and epinephrine but that a larger study would be required to detect a smaller, but significant, difference. The sample size of 200 patients used in this study was chosen to detect a 20% absolute difference in survival to one hour. It also is possible that the value of vasopressin is fundamentally different in pre-hospital patients compared to in-patients. It may be that the differences between vasopressin and epinephrine are only to be found in important subgroup analyses, which only a much larger study would have enough power to detect. Finally, it also is possible that there are truly no differences between the two drugs and that the initial promise shown by vasopressin simply will not be fulfilled when put to the test of larger, randomized, controlled trials involving more diverse patients.

The authors conclude that they "strongly disagree" with the AHA decision to recommend vasopressin as an alternative to epinephrine. It is not entirely clear to me why the authors came down so strongly against this recommendation. While the results of this study failed to show any advantage for vasopressin over epinephrine, it failed to show any worse outcomes or harm. In an accompanying editorial,3 the important point is made that epinephrine itself has never been shown to be more beneficial than placebo for cardiac resuscitation in human beings.


1. International Consensus on Science, American Heart Association. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2000;102(Supp):I1-I384.

2. Lindner KH, et al. Randomized comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997;349:535-537.

3. Morley D. Vasopressin or epinephrine: Which initial vasopressor for cardiac arrests (editorial). Lancet 2001; 385:85-86.