Combination vasopressin/epinephrine does not improve cardiac-arrest outcomes

July 02, 2008

Lyon, France - The combination of vasopressin and epinephrine in cardiopulmonary resuscitation (CPR) does not improve clinical outcomes, including survival to hospital admission or survival to the return of spontaneous circulation, compared with epinephrine alone, a new study has shown[1]. Investigators say there was no benefit of vasopressin treatment on any of the predefined subgroups and that the therapy is not likely to provide benefit when used in the resuscitation of patients who have cardiac arrest.

"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," write Dr Pierre-Yves Gueugniaud (University of Lyon, France) and colleagues in the July 3, 2008 issue of the New England Journal of Medicine.

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. As previously reported by heart wire , vasopressin was postulated as an alternative to epinephrine when it was discovered that successfully resuscitated cardiac-arrest patients had higher endogenous vasopressin levels than those patients who died.

Although vasopressin is a possible alternative to epinephrine during CPR, limited clinical experience with the treatment has been documented. 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, while other studies have shown equivocal benefit with the two drugs. Studies of CPR in animal models, Gueugniaud and colleagues write, showed that vasopressin increased blood flow to vital organs and cerebral oxygen delivery, as well as improved short-term survival.

For this reason, the French investigators performed a large, randomized, clinical trial to prospectively test whether the combination of vasopressin and epinephrine is superior to epinephrine alone in out-of-hospital cardiac arrest. Investigators assigned 1442 adults to 1 mg of epinephrine and 40 IU of vasopressin and 1452 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 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.

Survival data in the intention-to-treat analysis

End point Combination treatment , n=1442 (%) Epinephrine only, n=1452 (%) Relative risk (95% CI)
Survival to hospital admission 20.7 21.3 1.01 (0.97-1.05)
Survival to return of spontaneous circulation 28.6 29.5 1.01 (0.97-1.06)
Survival to hospital discharge 1.7 2.3 1.01 (1.00-1.02)
One-year survival 1.3 2.1 1.01 (1.00-1.02)
Good neurologic recovery at discharge * 37.5 51.5 1.29 (0.81-2.06)
*Good neurologic recovery defined as cerebral performance category 1 (patient conscious with normal function or only slight disability)

Investigators also looked at a number of predefined patient subgroups, among them witnessed vs unwitnessed cardiac arrest, 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.

In 2005, the writing group of the International Consensus of Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations concluded: "There is insufficient evidence to support or refute the use of vasopressin as an alternative to or in combination with adrenaline in any cardiac-arrest rhythm." However, Gueugniaud and colleagues point out that very few patients in their study had ventricular fibrillation—less than 10% in both treatment arms—and this "precludes a definitive conclusion against the use of vasopressin."


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