Time to Abandon Epinephrine for OHCA?

This is part of a recurring series examining landmark articles in Emergency Medicine, in the style of ALiEM’s 52 Articles.

Discussing: Wenzel, K. et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350(2):105-113.

Main Points:

  1. For out-of-hospital cardiac arrest (OHCA), vasopressin was similar to epinephrine in patients with ventricular fibrillation or pulseless electrical activity, with regards to survival to hospital admission and survival to hospital discharge. Vasopressin was noted to be superior, in both outcomes, for patients with asystole.
  1. In patients with refractory cardiac arrest and no ROSC, vasopressin followed by epinephrine may be more effective than epinephrine alone.


With more than 600,000 sudden death in North America and Europe annually, optimization of CPR is crucial to improve a patient’s chance of survival. Epinephrine use has become controversial as it induces increased myocardial consumption and ventricular arrhythmias post-resuscitation. Endogenous vasopressin levels have been known to be elevated in successfully resuscitated patients. In small prior studies, vasopressin has been associated with higher rate of short term survival and improved blood flow to vital organs when compared to epinephrine. Current guidelines recommend the use of epinephrine during cardiac resuscitation, with vasopressin as a secondary alternative.


This study was a double-blind, prospective randomized clinical trial, conducted in 44 Emergency Medical Service units in three European countries, including those with OHCA unresponsive to defibrillation. 1186/1219 patients with OHCA were included in the trial with randomization to two injections of either 40 IU of vasopressin or 1 mg epinephrine, followed by additional treatment with epinephrine at the discretion of the emergency physician managing the resuscitation. Average age 66 years, 70% men, 61% attributed to cardiac causes, 78% arrests witnessed. 33 patients were excluded due to a missing study drug code. The rates of hospital admission were similar between the two treatment groups for patients with ventricular fibrillation (46.2 vs 43%, p=0.48) and pulseless electrical activity (33.7 vs 30.5%, p=0.65). Patients with asystole treated with vasopressin were more likely to survive to hospital admission (29.0 vs 20.3%, p=0.02) and hospital discharge (4.7 vs 1.5%, p=0.04). Among 732 patients without ROSC, additional treatment with epinephrine resulted in improvement in rates of survival to hospital admission (25.7 vs 16.4%, p=0.002) and discharge (6.2 vs 1.7%, p=0.002) in the vasopressin group, but not the epinephrine group.

Level of Evidence:

ACEP Clinical Policy level I


– In those who needed additional treatment after no ROSC, the group of patients initially treated with vasopressin, followed by epinephrine had an increase in the number of comatose patients, indicating that the combination of vasopressin and epinephrine may have effectively restored cardiac function, but took too long to restore neurologic function.

– Authors report benefit of initial vasopressin over initial epinephrine among patients requiring additional doses of epinephrine after 2 doses of study drug in those with failure of ROSC. However, these patients are not prospectively identifiable, and therefore this clinical outcome is of little practical significance.

– Of note, this past October the 2015 ACLS Guidelines changed the stance on vasopressin use, in that it has been removed entirely from the algorithm. See below:


Relevant articles:

Callaway CW, et al. Am J Cardiol 2006. Usefulness of vasopressin administered with epinephrine during out-of-hospital cardiac arrrest.

Lindner KH, et al. Lancet 1997. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation.

Wyer PC, et al. Ann Emerg Med 2006. Vasopressin or epinephrine for out-of-hospital cardiac arrest.

Source Articles:

Wenzel V, et al. N Engl J Med 2004. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation.

Resident Review: Dr. Anatoly Kazakin
Faculty Review: Dr. Matt Siket

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