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

This large multinational clinical trial from the European Resuscitation Council, led by Volker Wenzel at the University of Innsbruck, was one of the definitive studies on the use of vasopressin (argipressin) in out-of-hospital cardiopulmonary resuscitation (CPR). The context was the search for alternatives to epinephrine, the standard CPR vasopressor that has potentially deleterious cardiac effects (tachycardia, myocardial ischemia, post-resuscitation arrhythmias).

The study randomized 1186 adult patients with out-of-hospital cardiac arrest to receive repeated injections of vasopressin 40 IU or epinephrine 1 mg during CPR. Primary endpoints were return of spontaneous circulation and survival to hospital discharge.

In patients with ventricular fibrillation, there were no significant differences between groups. However, in the asystole subgroup (worst prognostic rhythm), vasopressin was superior: higher rate of survival to hospital admission (29.0% vs 20.3%, p = 0.02) and higher survival to hospital discharge (4.7% vs 1.5%, p = 0.04). Even more notably, in patients who did not respond to the initial drug, the sequence vasopressin followed by epinephrine was superior to epinephrine alone (survival 25.7% vs 16.4%, p = 0.002).

This work consolidated vasopressin as a viable therapeutic option in cardiac arrest, particularly in asystole and as rescue therapy after epinephrine failure. Although subsequent guidelines (ILCOR 2015, AHA 2020) simplified protocols focusing solely on epinephrine, the Wenzel study retains historical value by demonstrating that arterial vasopression physiology does not depend exclusively on catecholamines, paving the way for combined therapies used today in the ICU (vasopressin + norepinephrine in vasodilatory shock).