Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis

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Object. The goals of this study were to determine if the use of phenytoin to prevent early posttraumatic seizures following head injury was associated with significant adverse side effects and also to determine if the reduction in early posttraumatic seizures after phenytoin administration was associated with a change in mortality rates in head-injured patients.

Methods. The authors performed a secondary analysis of the data obtained in a prospective double-blind placebo-controlled study of 404 patients who were randomly assigned to receive phenytoin or placebo for the prevention of early and late posttraumatic seizures. The incidence of adverse drug effects during the first 2 weeks of treatment, however, was low and not significantly different between the treated and placebo groups. Hypersensitivity reactions occurred in 0.6% of the patients in the phenytoin-treated group compared with 0% in the placebo group (p = 1.0) during week 1, and in 2.5% of phenytoin-treated compared with 0% of placebo-treated patients (p = 0.12) for the first 2 weeks of treatment. Mortality rates were also similar in both groups. Although the mortality rate was higher in patients who developed seizures, this increase was related to the greater severity of the injuries sustained by these patients at the time of the original trauma.

Conclusions. The results of this study indicate that the incidence of early posttraumatic seizure can be effectively reduced by prophylactic administration of phenytoin for 1 or 2 weeks without a significant increase in drug-related side effects. Reduction in posttraumatic seizure during the 1st week, however, was not associated with a reduction in the mortality rate.

Article Information

Address reprint requests to: David W. Newell, M.D., Department of Neurological Surgery, Harborview Medical Center, 325 9th Avenue, Seattle, Washington 98104. email: DWN@u.washington.edu.Address for Dr. Haltiner: Swedish Medical Center, Seattle, Washington.

© AANS, except where prohibited by US copyright law.

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Figures

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    Graph showing cumulative mortality as a function of assigned treatment. Forty-two deaths occurred in the placebo group and 50 in the phenytoin group (p = 0.67). The Kaplan—Meier estimates are shown through 3 months because more than 90% of the deaths had occurred by that time.

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    Graph showing that cumulative mortality was significantly higher in patients with delayed early seizures (occurring after drug loading but within the first 7 days posttrauma) based on the Cox model without adjustment for patient age or head injury severity (p = 0.03).

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    Graph showing that cumulative mortality did not differ significantly as a function of the occurrence of delayed early seizures after adjustment for patient age or head injury severity (p = 0.3 by using Cox's proportional-hazards regression).

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