Key Point:

• Vasopressin is an acceptable alternative to epinephrine for vasopressor therapy during CPR in patients with out-of-hospital cardiac arrests.

INNSBRUCK, AUSTRIA—Ever since endogenous vasopressin levels were found to be higher in patients who could be resuscitated after out-of-hospital cardiac arrests than in those who died, there has been interest in using exogenous vasopressin as a first-line pressor agent during cardiopulmonary resuscitation (CPR). Laboratory data suggest that vasopressin improves blood flow to vital organs and oxygen delivery to the brain, thereby increasing patients’ chances of recovery.

Until recently, however, only one small clinical trial had compared the use of vasopressin and epinephrine—the current standard of care—in patients who suffered out-of-hospital cardiac arrest. Although that study suggested that vasopressin administration was associated with a higher rate of survival, its small size precluded widespread adoption of its findings.

However, a much larger study now supports vasopressin use during CPR. Volker Wenzel, MD, and colleagues[1] compared vasopressin to epinephrine in 1,219 adults who had suffered an out-of-hospital cardiac arrest. Vasopressin was found to be as good as epinephrine in some settings, and better than it is in others. “We now feel justified in saying that vasopressin is an alternative to epinephrine in CPR,” stated Dr. Wenzel, Director of the Research Laboratories at the Department of Anesthesiology and Critical Care Medicine at the Leopold-Franzens University in Innsbruck, Austria.

Forty-four emergency medical services units from 33 cities in three European countries took part in the prospective double-blind study. All patients enrolled in the study had had an out-of-hospital cardiac arrest and presented with ventricular fibrillation, pulseless electrical activity (PEA), or asystole requiring CPR with vasopressor therapy. The patients with PEA or asystole were immediately randomized to one of the two study drugs; those with ventricular fibrillation were randomized after three attempts to defibrillate them had failed.

Following randomization, the patients were injected intravenously with 1 mg of epinephrine or 40 IU of vasopressin, followed by 20 mL of normal saline. They received a second injection of the same drug and dose if the first one failed to restore spontaneous circulation within three minutes. If the second injection failed, additional vasopressor therapy with epinephrine was an option.

The results of an interim analysis, seen only by a data and safety monitoring committee, confirmed the study’s safety. The study’s final analysis focused on two end points: survival to hospital admission and survival to hospital discharge.

EFFICACY CONFIRMED

The two groups of patients had similar clinical characteristics. In addition, they had similar rates of witnessed arrests and a similar mean amount of time before basic and advanced life support was provided.

The overall rate of survival to hospital admission was 36.3% in the vasopressin group and 31.2% in the epinephrine group; however, this difference did not reach significance. The two groups had the same overall rate of survival to hospital discharge: 9.9%.

When the analysis was limited to the 472 patients with ventricular fibrillation, the vasopressin group had a 46.2% rate of survival to admission and a 17.8% rate of survival to discharge—similar to the 43.0% and 19.2% rates in the epinephrine group. Among the 192 patients with PEA, the two drugs were again comparable. Survival to admission was 33.7% with vasopressin and 30.5% with epinephrine; survival to discharge was 5.9% and 8.6%, respectively.

Among the 528 patients with asystole, however, survival was substantially better in the vasopressin group—29.0% of the patients in that group survived to admission, compared with 20.3% of those given epinephrine. Survival to discharge was 4.7% and 1.5%, respectively. Dr. Wenzel and his colleagues believe that vasopressin may be a more effective pressor agent than epinephrine in patients with asystole because it can cause vasoconstriction even in the setting of severe acidosis; catecholamines are less potent in this situation. As a result, vasopressin administration may produce better coronary perfusion pressure during CPR.

A total of 732 patients did not regain spontaneous circulation after two injections of their assigned vasopressor; in this group, another potential advantage of vasopressin use was seen. Among those initially treated with vasopressin who were then given an epinephrine injection, the rates of survival to hospital admission and discharge were 25.7% and 6.2%; however, these rates were only 16.4% and 1.7% in those given three injections of epinephrine.

Among the patients who survived to discharge, there was no significant difference between the groups in cerebral performance.

IMPACT ON GUIDELINES

The study findings could lead to guideline changes regarding vasopressor use during CPR—current US guidelines acknowledge only the increased interest in vasopressin. “Now we have shown that it is an option in asystole and pulseless electrical activity as well,” Dr. Wenzel said.

—Timothy Begany

Reference
1. Wenzel V, Krismer AC, Arntz HR, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350:105-113.

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