A Comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation - Vasopressin vs. Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation


The goal of the trial was to evaluate the efficacy of vasopressin versus epinephrine in increasing survival to hospital admission among patients undergoing out-of-hospital cardiac arrest.

Study Design

Study Design:

Patients Screened: 5,967
Patients Enrolled: 1,219
Mean Follow Up: Hospital discharge
Mean Patient Age: Mean age 66 years
Female: 30%

Patient Populations:

Adults with an out-of-hospital cardiac arrest who presented with ventricular fibrillation, pulseless electrical activity, or asystole requiring cardiopulmonary resuscitation with vasopressor therapy


Successful defibrillation without the administration of a vasopressor, documented terminal illness, lack of intravenous access, hemorrhagic shock, pregnancy, cardiac arrest after trauma, age <18 years, and presence of a do-not-resuscitate order

Primary Endpoints:

Survival to hospital admission

Secondary Endpoints:

Survival to hospital discharge

Drug/Procedures Used:

Patients with an out-of-hospital cardiac arrest were randomized to two injections of either vasopressin (40 IU; n=589) or epinephrine (1 mg; n=597). Patients were treated with additional epinephrine if needed. The study was conducted in Austria, Germany, and Switzerland.

Principal Findings:

Survival to hospital admission did not differ significantly between the vasopressin arm and the epinephrine arm in the overall population (36.3% vs. 31.2%, p=0.06), or among patients with ventricular fibrillation (46.2% vs. 43.0%, p=0.48) or those with pulseless electrical activity (33.7% vs. 30.5%, p=0.65).

However, vasopressin use was associated with significantly higher rates of hospital admission in patients with asystole (29.0% vs. 20.3%, p=0.02). Likewise, there was no difference in survival to hospital discharge overall (9.9% each, p=0.99) or in the subgroups of patients with ventricular fibrillation (17.8% vs. 19.2%, p=0.70) or pulseless electrical activity (5.9% vs. 8.6%, p=0.47), but survival to hospital discharge was higher in patients with asystole in the vasopressin arm (4.7% vs. 1.5%, p=0.04).

In patients in whom spontaneous circulation was not restored with the two injections of the study drug (n=732), additional treatment with epinephrine in the vasopressin arm was associated with increased rate of survival to both hospital admission (25.7% vs. 16.4%, p=0.002) and hospital discharge (6.2% vs. 1.7%, p=0.002) compared to the epinephrine arm. Among patients who survived to discharge, there was no difference in cerebral performance by treatment group (good cerebral performance 32.6% vs. 34.8%, p=0.99).


Among patients undergoing out-of-hospital cardiac arrest, treatment with vasopressin was not associated with increased survival to hospital admission or discharge compared with treatment with epinephrine. Unlike prior animal studies, treatment with vasopressin was not more effective than epinephrine in the subgroup of patients with ventricular fibrillation and pulseless electrical activity. The only subgroup to show a significant benefit was patients with asystole.

The authors speculate that vasopressin may result in better coronary perfusion pressure during cardiac resuscitation because it may be a more effective vasopressor than epinephrine in patients with asystole. Another important subgroup finding was the increased survival in patients in the vasopressin arm who received an additional dose of epinephrine, suggesting the combination of the two drugs may be superior to epinephrine alone. However, the analysis was post hoc and further studies would be needed to validate the hypothesis.


Wenzel V, Krismer AC, Arntz RH, et al. A Comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation. N Engl J Med 2004;350:105-13.

Clinical Topics: Arrhythmias and Clinical EP, SCD/Ventricular Arrhythmias

Keywords: Vasopressins, Out-of-Hospital Cardiac Arrest, Epinephrine, Vasoconstrictor Agents, Cardiopulmonary Resuscitation, Ventricular Fibrillation

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