A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation

N Engl J Med. 2004 Jan 8;350(2):105-13. doi: 10.1056/NEJMoa025431.


Background: Vasopressin is an alternative to epinephrine for vasopressor therapy during cardiopulmonary resuscitation, but clinical experience with this treatment has been limited.

Methods: We randomly assigned adults who had had an out-of-hospital cardiac arrest to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine, followed by additional treatment with epinephrine if needed. The primary end point was survival to hospital admission, and the secondary end point was survival to hospital discharge.

Results: A total of 1219 patients underwent randomization; 33 were excluded because of missing study-drug codes. Among the remaining 1186 patients, 589 were assigned to receive vasopressin and 597 to receive epinephrine. The two treatment groups had similar clinical profiles. There were no significant differences in the rates of hospital admission between the vasopressin group and the epinephrine group either among patients with ventricular fibrillation (46.2 percent vs. 43.0 percent, P=0.48) or among those with pulseless electrical activity (33.7 percent vs. 30.5 percent, P=0.65). Among patients with asystole, however, vasopressin use was associated with significantly higher rates of hospital admission (29.0 percent, vs. 20.3 percent in the epinephrine group; P=0.02) and hospital discharge (4.7 percent vs. 1.5 percent, P=0.04). Among 732 patients in whom spontaneous circulation was not restored with the two injections of the study drug, additional treatment with epinephrine resulted in significant improvement in the rates of survival to hospital admission and hospital discharge in the vasopressin group, but not in the epinephrine group (hospital admission rate, 25.7 percent vs. 16.4 percent; P=0.002; hospital discharge rate, 6.2 percent vs. 1.7 percent; P=0.002). Cerebral performance was similar in the two groups.

Conclusions: The effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiopulmonary Resuscitation*
  • Drug Therapy, Combination
  • Emergency Medical Services
  • Epinephrine / therapeutic use*
  • Female
  • Heart Arrest / drug therapy*
  • Heart Arrest / mortality
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Survival Rate
  • Sympathomimetics / therapeutic use*
  • Vasoconstrictor Agents / therapeutic use*
  • Vasopressins / therapeutic use*
  • Ventricular Fibrillation / drug therapy


  • Sympathomimetics
  • Vasoconstrictor Agents
  • Vasopressins
  • Epinephrine