Phenobarbital Compared with Phenytoin for the Treatment of Neonatal Seizures
Michael J. Painter, M.D., Mark S. Scher, M.D., Aryeh D. Stein, Ph.D., Stacey Armatti, M.A., Zhiming Wang, Ph.D., Joseph C. Gardiner, Ph.D., Nigel Paneth, M.D., Beth Minnigh, Ph.D., and John Alvin, Ph.D.
Background Seizures occur in 1 to 2 percent of neonates admittedto an intensive care unit. The treatment is usually with eitherphenobarbital or phenytoin, but the efficacy of the two drugshas not been compared directly.
Methods From 1990 to 1995, we studied 59 neonates with seizuresthat were confirmed by electroencephalography. The neonateswere randomly assigned to receive either phenobarbital or phenytoinintravenously, at doses sufficient to achieve free plasma concentrationsof 25 µg per milliliter for phenobarbital and 3 µgper milliliter for phenytoin. Neonates whose seizures were notcontrolled by the assigned drug were then treated with bothdrugs. Seizure control was assessed by electroencephalographiccriteria.
Results Seizures were controlled in 13 of the 30 neonates assignedto receive phenobarbital (43 percent) and 13 of the 29 neonatesassigned to receive phenytoin (45 percent; P=1.00). When combinedtreatment is considered, seizure control was achieved in 17(57 percent) of the neonates assigned to receive phenobarbitalfirst and 18 (62 percent) of those assigned to receive phenytoinfirst (P=0.67). The severity of the seizures was a strongerpredictor of the success of treatment than was the assignedagent. Neonates with mild seizures or with seizures that weredecreasing in severity before treatment were more likely tohave their seizures end, regardless of the treatment assignment.
Conclusions Phenobarbital and phenytoin are equally but incompletelyeffective as anticonvulsants in neonates. With either drug givenalone, the seizures were controlled in fewer than half of theneonates.
Source Information
From the Departments of Pediatrics and Neurology (M.J.P., M.S.S.) and Pharmacology (J.A.), University of Pittsburgh, Pittsburgh; Children's Hospital of Pittsburgh and Magee Women's Hospital of Pittsburgh, Pittsburgh (M.J.P., M.S.S.); the Departments of Epidemiology (A.D.S., S.A., Z.W., J.C.G., N.P.) and Statistics and Probability (Z.W., J.C.G.), Michigan State University, East Lansing; and Pharmakon Laboratories, Pittsburgh (B.M.).
Address reprint requests to Dr. Painter at the Children's Hospital of Pittsburgh, 1 Children's Pl., Pittsburgh, PA 15213, or at paintem{at}chplink.chp.edu.
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