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Original Article
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Volume 341:485-489 August 12, 1999 Number 7
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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.

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ABSTRACT

Background Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly.

Methods From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 µg per milliliter for phenobarbital and 3 µg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria.

Results Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment.

Conclusions Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.


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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