Combining Vasopressin and Epinephrine Does not Improve CPR Outcomes

Researchers at the University of Lyon (France) performed a large, randomized, clinical trial between May 2004 and April 2006 to prospectively test whether the combination of vasopressin and epinephrine is superior to epinephrine alone in out-of-hospital cardiac arrest. Investigators assigned 1,442 adults to 1 mg of epinephrine and 40 IU of vasopressin, and 1,452 adults to 1 mg of epinephrine alone, with the combination of drugs repeated if spontaneous circulation was not restored within three minutes after the first administration. Patients were subsequently given additional epinephrine alone if needed. The primary endpoint was survival to hospital admission; the secondary endpoints were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and one-year survival.

The researchers found that the combination therapy with vasopressin and epinephrine did not result in any significant improvement over epinephrine alone. The rates of survival to hospital admission, return of spontaneous circulation, survival to hospital discharge, survival at one year, and neurologic recovery at discharge were similar in both treatment arms. The researchers also looked at a number of predefined patient subgroups, among them the initial cardiac rhythm, the number of drug injections, and the time to resuscitation before drug injection, and found no benefit with the combination of vasopressin and epinephrine. The researchers noted that in a post hoc subgroup analysis, the results demonstrated that when the electrocardiographic rhythm was pulseless electrical activity, the rate of survival to hospital discharge was significantly higher in the epinephrine-only group. The study was published in the July 3, 2008, issue of the New England Journal of Medicine (NEJM).

"The lack of superiority of combination therapy over epinephrine alone, regardless of the patient subgroup, suggests it may be futile to add vasopressin to epinephrine during cardiopulmonary resuscitation with advanced cardiac life support,” concluded lead author Pierre-Yves Gueugniaud, M.D., Ph.D., and colleagues.

Although epinephrine remains the vasopressor agent of choice for CPR, the prognosis of patients with cardiac arrest is poor, regardless of the dose of epinephrine used. But when it was discovered that successfully resuscitated cardiac arrest patients had higher endogenous vasopressin levels than those patients who died, vasopressin was postulated as an alternative to epinephrine. Studies of CPR in animal models showed that vasopressin increased blood flow to vital organs and cerebral oxygen delivery, as well as improved short-term survival. However, limited clinical experience with the treatment has been documented; while one study suggested that vasopressin as an adjunctive therapy to epinephrine might be more effective than epinephrine alone in the treatment of asystolic cardiac arrest, other studies have shown ambivalent benefit with the two drugs.


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