High-Dose Epinephrine in Children: No Benefit, Maybe Harmful

Abstract & Commentary

Source: Perondi MB, et al. A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest. N Engl J Med 2004; 350:1722-1730.

The authors of this Brazilian study enrolled children sustaining witnessed, in-hospital cardiac arrests from any cause. Patients who remained in cardiac arrest despite cardiopulmonary resuscitation and an initial standard dose of epinephrine (0.01 mg/kg) received either standard dose epinephrine (0.01 mg/kg) or high-dose epinephrine (0.1 mg/kg) for the second and any subsequent doses of drug. The resuscitation otherwise proceeded in the usual fashion. Study group assignment was determined in a randomized, double-blind fashion. The main study endpoint was survival at 24 hours after the arrest.

Sixty-eight patients were enrolled during a 23-month period. Protocol violations–usually incorrect doses of epinephrine–were noted in 18 patients, and analyses were performed on an intent-to-treat basis. While seven of 34 patients in the standard-dose epinephrine group survived at 24 hours, only one of 34 in the high-dose group met this endpoint (odds ratio for death in the high-dose group, 8.6). This effect persisted after adjustment for inter-group differences. Among patients sustaining cardiac arrest as a result of asphyxia, 24-hour survival was noted in seven of 18 in the standard-dose epinephrine group, compared with none of 12 in the high-dose group. Four children who had received standard-dose epinephrine survived to hospital discharge—two of whom had normal neurologic function at six months, and two of whom returned to their abnormal baseline functional status—while no patient receiving high-dose epinephrine survived to discharge. No children with shockrelated cardiac arrest survived to discharge.

Commentary by David J. Karras, MD, FAAEM, FACEP

High-dose epinephrine currently is considered a treatment option for pediatric victims of cardiac arrest. Data supporting the use of high-dose epinephrine is limited, and largely consists of a non-randomized study using historical controls.1 Recent studies have failed to show a benefit over standard-dose therapy in adult resuscitations. This study provides powerful evidence that high-dose epinephrine offers no advantage in the resuscitation of children. While stronger conclusions are limited by the relatively small sample size, it appears that patients in the high-dose epinephrine group actually fared worse than those receiving standard-dose therapy. Further analyses showed that the protocol violations were unlikely to have biased the results—if anything, more patients received high-dose therapy—and the authors caution that their results may not apply to children sustaining unwitnessed, out-of-hospital arrests.

Reference

1. Goetting MG, Paradis NA. High-dose epinephrine improves outcome from pediatric cardiac arrests. Ann Emerg Med 1991;20:22-26.

Dr. Karras, Associate Professor of Emergency Medicine, Associate Chair for Academic Affairs, and Research Director, Department of Emergency Medicine, Temple University School of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.