Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation - Vasopressin and Epinephrine vs. Epinephrine Alone in CPR

Oct 12, 2008
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Programme Hospitalier de Recherche Clinique 2003 of the French Ministry of Health Research and the French Health Product Safety Agency and by the Research Delegation of the Hospices Civils de Lyon
Date Presented:
01/01/2007
Date Published:
01/01/2008
Date Updated:
10/12/2008
Original Posted Date:
10/12/2008
References

Description:

The goal of the trial was to evaluate treatment with vasopressin and epinephrine compared with epinephrine alone among patients with an out-of-hospital cardiac arrest.

Hypothesis:

Vasopressin and epinephrine will be more effective in improving survival.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patients Enrolled: 2,956
Mean Follow Up: 1 year
Mean Patient Age: 62 years
Female: 27

Patient Populations:

  • Adult patients with a cardiac arrest due to VF, pulseless electrical activity, or asystole

Exclusions:

  • Age less than 18 years
  • Successful defibrillation without the need for vasopressor therapy
  • Traumatic cardiac arrest
  • Known pregnancy
  • Documented terminal illness
  • Do-not-resuscitate order
  • Sign of an irreversible cardiac arrest

Primary Endpoints:

  • Survival to hospital admission. Survival was defined as a palpable pulse and measurable blood pressure upon arrival to an intensive care unit.

Secondary Endpoints:

  • Return of spontaneous circulation
  • Survival to hospital discharge
  • Good neurological recovery
  • Survival at 1 year

Drug/Procedures Used:

Patients with cardiac arrest were randomized to 40 IU vasopressin and 1 mg epinephrine (n = 1,442) versus placebo and 1 mg epinephrine (n = 1,452). Study drugs were re-administered if there was no return in spontaneous circulation within 3 minutes. Defibrillation was attempted up to 3 times before randomization among patients who presented with ventricular fibrillation (VF).

Principal Findings:

Overall, 2,956 patients underwent randomization. There were 62 patients excluded after randomization: 26 did not provide informed consent, 29 had traumatic cardiac arrest, and 7 did not meet other inclusion criteria. Baseline characteristics were well-matched, except that there were more men in the vasopressin and epinephrine group (75.4% vs. 71.7%, p = 0.03). The initial cardiac rhythm was VF in 9.2% versus 9.3%, pulseless electrical activity in 7.7% versus 8.3%, and asystole in 83.1% versus 82.4%, respectively. The time to arrival of emergency medical technicians was 7.2 minutes versus 6.8 minutes, and the total duration of advanced cardiac life support was 38.0 minutes versus 37.6 minutes, respectively.

The primary outcome, survival to hospital admission, occurred in 20.7% of the combination treatment group compared with 21.3% of the epinephrine alone group (p = 0.69). Return of spontaneous circulation occurred in 28.6% versus 29.5% (p = 0.62), survival to hospital discharge occurred in 1.7% versus 2.3% (p = 0.24), 1-year survival occurred in 1.3% versus 2.1% (p = 0.09), and good neurological recovery at hospital discharge occurred in 37.5% versus 51.5% (p = 0.29), respectively, for combination treatment versus epinephrine alone. Among patients who presented with pulseless electrical activity, survival to hospital discharge was 0% versus 5.8% (p = 0.02), respectively. There was no difference in this outcome among patients with VF or asystole.

Interpretation:

The prognosis among patients who suffer an out-of-hospital cardiac arrest, especially asystole, remains grim. The combination of vasopressin and epinephrine is not superior to epinephrine alone in improving clinical outcomes. Specifically, there was no difference in survival to hospital admission or discharge, return in spontaneous circulation, good neurological recovery, or 1-year survival between the treatment groups. The finding of decreased survival to hospital discharge among the combination treatment group should only be considered hypothesis generating.

References:

Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008;359:21-30.

Keywords: Vasopressins, Out-of-Hospital Cardiac Arrest, Advanced Cardiac Life Support, Epinephrine, Ventricular Fibrillation, Heart Arrest, Informed Consent


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