High dose versus standard dose epinephrine in cardiac arrest — a meta-analysis
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.
References (31)
CPR and high dose epinephrine
Resuscitation
(1993)High dose epinephrine
Am. J. Emerg. Med.
(1993)- et al.
Four case studies: high dose epinephrine in CA
Ann. Emerg. Med.
(1990) - et al.
Standard dose versus repeated high dose of epinephrine in cardiac arrest outside the hospital
Resuscitation
(1995) - et al.
High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest
Resuscitation
(1995) - et al.
High dose epinephrine improves the ROSC rates in human victims of CA
Ann. Emerg. Med.
(1991) - et al.
Prehospital administration of high-dose epinephrine
Ann. J. Emerg. Med.
(1994) - et al.
Adverse effect of early high dose adrenaline on outcome of VF
Lancet
(1988) - Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care. Recommendations of the 1992 National...
- European Resuscitation Council. Guidelines for Resuscitation, June...
Changes in the pharmacotherapy of CPR
Heart Lung
The next chapter in the high-dose epinephrine story: infavorable neurologic outcomes?
Ann. Intern. Med.
High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy
Pharmacotherapy
Potential complications of high dose epinephrine therapy in patients resuscitated from cardiac arrest
J. Am. Med. Assoc.
A comparison of repeated high dose and repeated standard dose of epinephrine for cardiac arrest outside the hospital
N. Engl. J. Med.
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