Elsevier

Resuscitation

Volume 45, Issue 3, 1 August 2000, Pages 161-166
Resuscitation

High dose versus standard dose epinephrine in cardiac arrest — a meta-analysis

https://doi.org/10.1016/S0300-9572(00)00188-XGet rights and content

Abstract

In the management of cardiac arrest there is ongoing controversy concerning the optimal dose of epinephrine. To obtain the best available evidence regarding the current optimal dose, we performed a meta-analysis. We searched the Medline database online and reviewed citations in relevant articles to identify studies that met preset inclusion criteria (prospective, randomized, double-blind). Five trials were identified. The pooled odds ratio for return of spontaneous circulation favours the experimental dose. The pooled odds ratio for hospital discharge failed to demonstrate a statistically significant beneficial effect of high and/or escalating doses of epinephrine in comparison with standard dose of epinephrine. The possibility that patients who have already sustained irreversible neurologic injury will be resuscitated carries potential adverse social and economic implications.

Introduction

Although epinephrine has been used as a standard first-line drug in cardiac arrest for several decades, the optimal dose of epinephrine for the three main categories of adult cardiac arrest (persistent ventricular fibrillation, pulseless electrical activity and asystole), has not yet been definitely determined. Animal studies and human case reports suggest that high dose epinephrine might be more effective than the doses recommended by the European Resuscitation Council, and the American Heart Association in maintaining coronary and cerebral perfusion pressure and in restoring spontaneous circulation [1], [2], [3]. These preliminary reports precipitated the introduction of epinephrine in large dose vials.

Moreover, the fact that high dose epinephrine might merely result in longer hospital stay, but no improvement in neurologic outcome or discharge rate from the hospital, is an additional area of growing concern [4], [5], [6], [7], [8], [9]. In an attempt to reach the best level of evidence regarding this issue, we conducted a meta-analysis concerning the usage of high dose epinephrine versus standard dose epinephrine in the management of cardiac arrest in humans.

Section snippets

Data abstraction

We searched the Medline database online, from January 1988 to December 1998, to identify all English-language articles with the medical subject headings; ‘epinephrine’ ‘high dose’–‘randomized, double blind, controlled trial’–‘human’.

Randomized controlled trials are recognized as the most valid assessment of the efficacy of a new treatment. All the potentially relevant original articles were reviewed. The authors of the primary studies were not contacted to identify additional studies. Only five

Results

Of the five studies, recruiting patients between 1989 and 1996 included, four were multi-centred, two were European and three were North American. The number of subjects per study ranged from 536 to 3327. The bolus dose of experimental epinephrine ranged from 5 to 15 mg. Hospital discharge ranged from 8.6 to 21.4% in the experimental group, and from 5.5 to 21% in the standard group.

Fig. 1, Fig. 2, Fig. 3 show the odds ratios and the 95% confidence intervals of, respectively, achieving ROSC,

Discussion

So far, the randomized studies of high or escalating dose epinephrine have shown no significant improvement in hospital discharge. If there is a trend, it favours standard doses [23], [24], [25].

Why human trials are not in accordance with animal studies remains unclear [26]. The slight differences in the experimental treatment (different dose regimes, e.g. a total of 5, 7 and 15 mg, and 0.2 mg/kg) together with the variability in the investigated population are generally considered as the major

Acknowledgements

We are indebted to M. Haspeslagh for assistance with statistical processing.

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