A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest
Article Outline
Perondi MB, Reis AG, Paiva EF, Nadkarni VM, Berg RA. N Engl J Med 2004;350:1722-30
Context When efforts to resuscitate a child after cardiac arrest are unsuccessful despite the administration of an initial dose of epinephrine, American Heart Association guidelines recommend that the next dose of epinephrine (ie, the rescue dose) should be the same (standard) dose or a higher dose.
Objectives To evaluate whether rescue therapy with high-dose epinephrine compared with continued use of the standard dose, would improve the rate of survival at 24 hours for children who had an in-hospital cardiac arrest.
Design Prospective, randomized, double-blind trial.
Setting Children's Institute of the University of São Paulo School of Medicine, a tertiary-care children's hospital that admits more than 6000 patients each year.
Participants 68 children who remained in cardiac arrest despite CPR and an initial standard dose of epinephrine.
Interventions High-dose epinephrine (0.1 mg/kg body weight) with standard-dose epinephrine (0.01 mg/kg) as rescue therapy.
Main outcome measure Survival 24 hours after the arrest.
Results The rate of survival at 24 hours was lower in the group assigned to a high dose of epinephrine as rescue therapy than in the group assigned to a standard dose: 1 of the 34 patients in the high-dose group survived for 24 hours compared with 7 of the 34 patients in the standard-dose group (unadjusted odds ratio for death with the high dose, 8.6; 97.5% CI, 1.0-397.0; P
=.05). After adjustment by multiple logistic-regression analysis for differences in the groups at the time of arrest, the high-dose group tended to have a lower 24-hour survival rate (odds ratio for death, 7.9; 97.5% CI, 0.9-72.5; P=.08). The two treatment groups did not differ significantly in terms of the rate of return of spontaneous circulation (which occurred in 20 patients in the high-dose group and 21 of those in the standard-dose group; odds ratio, 1.1; 97.5% CI, 0.4-3.0). None of the patients in the high-dose group compared with 4 of those in the standard-dose group survived to hospital discharge. Among the 30 patients whose cardiac arrest was precipitated by asphyxia, none of the 12 who were assigned to high-dose epinephrine were alive at 24 hours compared with 7 of the 18 who were assigned to a standard dose (P=.02).
Conclusions There is no benefit of high-dose epinephrine rescue therapy for in-hospital cardiac arrest in children after failure of an initial standard dose of epinephrine. The data suggest that high-dose therapy may be worse than standard-dose therapy.
Comment Perondi et al showed that rate of resuscitation from cardiac arrest was not different whether children received one or more doses of 0.1 mg/kg epinephrine or the customary amount (0.01 mg/kg), but those with the higher dose were more likely to die thereafter. Like any thoughtful study, the findings raise a number of important issues and provoke additional questions. Whether high- or low-dose epinephrine is superior in management of cardiac arrest in children has been debated without the direct data to derive firm conclusions. The compelling argument to study this question is the uniformly dismal survival rate reported in children with cardiac arrest. The rationale for not adopting information from much larger trials in adults relates to the presumption that a much higher fraction of children develop cardiac arrest consequent to asphyxia, which has a pathogenesis and management that is fundamentally different from ischemic coronary artery disease. With that said, one is now left with relatively few subjects on which to base conclusions, even thought this is a well-performed randomized controlled trial. Thus, the following questions arise: (1) Are these data sufficient to change policy: likely, because prior policy to offer high dose as an option was not based on strong evidence1., 2.; (2) Are these data sufficient to change practice: not clear, because there is a common compulsion to exceed recommendations in desperate situations, such as resuscitation; (3) Is it possible or ethical for other studies to be conducted to verify the findings now that these data are published: a formidable barrier, but one worth the effort before embracing a conclusion that is not yet fully substantiated; and (4) What is the putative mechanism for the findings: this is a challenging question but one that offers the best opportunity to improve practice further. It is intriguing to consider why a difference in dose of epinephrine, which may seem trivial, had an important effect on the dismal survival rates observed after cardiac arrest.3 Determining a mechanism might add validation to these findings.
References
- Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part VI. Pediatric advanced life support. JAMA. 1992;268:2262–2275
- . High-dose epinephrine improves outcome from pediatric cardiac arrest. Ann Emerg Med. 1991;20:22–26
- . Can resuscitation jeopardize survival. N Engl J Med. 2004;350:1708–1709
PII: S0022-3476(04)00755-3
doi:10.1016/j.jpeds.2004.08.036
© 2004 Elsevier Inc. All rights reserved.
