Elsevier

The Lancet

Volume 358, Issue 9276, 14 July 2001, Pages 105-109
The Lancet

Articles
Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(01)05328-4Get rights and content

Summary

Background

Survival rates for cardiac arrest patients, both in and out of hospital, are poor. Results of a previous study suggest better outcomes for patients treated with vasopressin than for those given epinephrine, in the out-of-hospital setting. Our aim was to compare the effectiveness and safety of these drugs for the treatment of in-patient cardiac arrest.

Methods

We did a triple-blind randomised trial in the emergency departments, critical care units, and wards of three Canadian teaching hospitals. We assigned adults who had cardiac arrest and required drug therapy to receive one dose of vasopressin 40 U or epinephrine 1 mg intravenously, as the initial vasopressor. Patients who failed to respond to the study intervention were given epinephrine as a rescue medication. The primary outcomes were survival to hospital discharge, survival to 1 h, and neurological function. Preplanned subgroup assessments included patients with myocardial ischaemia or infarction, initial cardiac rhythm, and age.

Findings

We assigned 104 patients to vasopressin and 96 to epinephrine. For patients receiving vasopressin or epinephrine survival did not differ for hospital discharge (12 [12%] vs 13 [14%], respectively; p=0·67; 95% CI for absolute increase in survival –11·8% to 7·8%) or for 1 h survival (40 [39%] vs 34 [35%]; p=0·66; –10·9% to 17·0%); survivors had closely similar median mini-mental state examination scores (36 [range 19–38] vs 35 [20–40]; p=0·75) and median cerebral performance category scores (1 vs 1).

Interpretation

We failed to detect any survival advantage for vasopressin over epinephrine. We cannot recommend the routine use of vasopressin for inhospital cardiac arrest patients, and disagree with American Heart Association guidelines, which recommend vasopressin as alternative therapy for cardiac arrest.

Introduction

There are an estimated 300 000 cardiac arrests yearly in patients in hospital throughout Canada and USA.1 We have previously recorded2 that the survival rate of hospital patients who required epinephrine was only 6%. Results of clinical trials have failed to show improved survival with high doses of epinephrine and other adrenergic agents (phenylephrine and methoxamine). Because of the high drug concentrations required and the potential side-effects of adrenergic agents, non-adrenergic vasoactive drugs are sought to maintain vascular tone and blood flow during cardiac arrest.

Several laboratory and clinical studies have documented high concentrations of endogenous vasopressin during cardiac arrest.3, 4 Additionally, Lindner and colleagues5 showed that arginine vasopressin increased arterial and coronary pressures as well as myocardial and cerebral blood flows compared with standard doses of epinephrine in experimental models of cardiac arrest. In two small case series,6, 7 patients failed standard epinephrine therapy but survived after receiving vasopressin. In one randomised controlled clinical trial,8 the investigators compared the effect of 40 U vasopressin with 1 mg epinephrine in 40 prehospital patients who had not responded to three countershocks. Compared with epinephrine, the group that received vasopressin had a 50% increase in the number of admitted patients and a 66% increase in patients alive at 24 h.

The American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) guidelines9 recommend vasopressin as an alternative to epinephrine for treatment of cardiac arrest. This recommendation could lead to use of vasopressin for millions of cardiac arrests worldwide. We did a randomised controlled clinical trial of vasopressin or epinephrine as the initial vasopressor, to compare survival outcomes and safety for patients who had cardiac arrest in hospital.

Section snippets

Patients

We did our study in the emergency departments, critical care units, and general wards of two tertiary-care hospitals affiliated with the University of Ottawa, Ottawa, Canada, and with one tertiary hospital affiliated with the University of Western Ontario in London. Patients were eligible if they were admitted to hospital, had a cardiac arrest, and required epinephrine according to AHA ACLS protocols for asystole, pulseless electrical activity, or refractory ventricular fibrillation. We

Results

From July 3, 1997, to Nov 30, 1998, we enrolled and successfully followed up 200 patients (figure). During the trial, a further 50 eligible patients were not entered into the study by attending clinicians because of the urgency and stress of treating an immediately life-threatening condition. Clinical and demographic characteristics of these individuals were closely similar to those of the enrolled patients. Furthermore, 74 ineligible patients received the study drug and were excluded

Discussion

We failed to show any improvement with vasopressin compared with epinephrine for either short-term or long-term survival. Furthermore, in several clinically important subgroups, vasopressin was not associated with improved outcomes. We recognise that, because of our small sample size and the wide confidence intervals around the treatment effect estimates, our results do not exclude the possibility of a clinically important benefit for vasopressin. Nevertheless, we detected no trends favouring

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