Failure of prophylactically administered phenytoin to prevent early posttraumatic seizures

Abstract

A randomized double-blind placebo-controlled study was carried out to determine whether phenytoin administered soon after injury lessens the incidence of epilepsy in the 1st week after severe head trauma. In this study, 244 patients were randomized into either a phenytoin or placebo group. The patients in the phenytoin group were administered phenytoin intravenously or intramuscularly within 24 hours of hospital admission. Patients in the placebo group received intravenous or intramuscular diluent. The patients were switched from parenterally administered phenytoin or placebo as soon as oral doses could be tolerated. Over 78% of the phenytoin patients had plasma concentrations of at least 10 micrograms/ml at 1, 3, and 7 days after injury. There was no significant difference in the percentage of patients having early seizures in the treated and placebo groups (p = 0.99). There was no significant difference in the interval from injury to first seizure between the treated and placebo groups (p = 0.41). The early administration of phenytoin did not lessen the occurrence of seizures in the 1st week after head injury. Since the effectiveness of seizure prophylaxis has not been established, the authors suggest that anticonvulsant drugs be administered only after an early seizure has occurred.

Practice parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury

“…11 The other class I study, which evaluated a similar phenytoin regimen in a smaller but similar cohort, found no significant difference. 10 The latter study, however, reported a rate of early seizures in the placebo group of only 3.7%, which is much lower than the rates seen in other studies. Because the absolute seizure rates are so low in this study, the 95% CI for the RR (0.27 to 3.58) is very wide.…”

“…In the class I study demonstrating no significant benefit of prophylaxis, more than 78% of patients maintained therapeutic levels through the first week, although only 60% of those who had an early seizure had a therapeutic level immediately afterward. 10 In the class II study evaluating carbamazepine, average serum AED levels in the first week were in the therapeutic range. 12 In the class III study, levels were checked and doses adjusted accordingly but specific figures were not reported.…”

“…[10][11][12][13] Two randomized placebo-controlled studies with masked assessment, both evaluating phenytoin given initially by IV load, were graded class I. 10,11 One study comparing carbamazepine to placebo was graded class II because treatment assignment was performed using a quasi-random method, based on patient birthdate. 12 One study comparing phenytoin to no treatment was graded class III because of nonmasked assessment.…”

“…Two of the early seizure studies 10,13 and four of the late seizure studies 13,15,16,18 allowed enrollment of patients below 14 to 16 years of age. However, only one of these studies specifically reported findings in the pediatric subgroup, in a separate publication.…”

Predictors of Posttraumatic Convulsions in Head-Injured Children

“…Posttraumatic convulsions not only aggravate secondary injury to the brain after initial insult by increasing the intracranial pressure and hypoxia, but also make monitoring the head injured patients more difficult due to postictal neurological deterioration. This might lead to delay in the treatment of intracranial mass lesion [3]. Posttraumatic seizures have been the subject of investigation in a number of studies, mainly concerned with adults [2, 3, 4, 5, 6].…”