BACKGROUND. Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive. METHODS. To study further the effectiveness of phenytoin (Dilantin) in preventing post-traumatic seizures, we randomly assigned 404 eligible patients with serious head trauma to treatment with phenytoin (n = 208) or placebo (n = 196) for one year in a double-blind fashion. An intravenous loading dose was given within 24 hours of injury. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 mumol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat. RESULTS. Between drug loading and day 7, 3.6 percent of the patients assigned to phenytoin had seizures, as compared with 14.2 percent of patients assigned to placebo (P less than 0.001; risk ratio, 0.27; 95 percent confidence interval, 0.12 to 0.62). Between day 8 and the end of year 1, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures; at the end of year 2, the rates were 27.5 percent and 21.1 percent, respectively (P greater than 0.2 for each comparison; risk ratio, 1.20; 95 percent confidence interval, 0.71 to 2.02). This lack of a late effect could not be attributed to differential mortality, low phenytoin levels, or treatment of some early seizures in patients assigned to the placebo group. CONCLUSIONS. Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.
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Department of Neurological Surgery, University of Washington, Seattle 98104.
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[Full Text]
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[Abstract]
Schierhout, G., Roberts, I.
(1998). Prophylactic antiepileptic agents after head injury: a systematic review. J. Neurol. Neurosurg. Psychiatry
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[Abstract][Full Text]
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[Abstract][Full Text]
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[Abstract]
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8: 29-38
[Abstract]
Chadwick, D.
(1995). Controversies in Management: Case for early treatment is not established. BMJ
310: 177-178
[Full Text]
Roujeau, J. C., Stern, R. S.
(1994). Severe Adverse Cutaneous Reactions to Drugs. NEJM
331: 1272-1285
[Full Text]
Smith, K. R. Jr, Goulding, P. M., Wilderman, D., Goldfader, P. R., Holterman-Hommes, P., Wei, F.
(1994). Neurobehavioral Effects of Phenytoin and Carbamazepine in Patients Recovering From Brain Trauma: A Comparative Study. Arch Neurol
51: 653-660
[Abstract]
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(1994). Employment Following Traumatic Head Injuries. Arch Neurol
51: 177-186
[Abstract]
Seifert, C. F., Lee McGoodwin, P., Allen, L. V. JR
(1993). Phenytoin Recovery From Percutaneous Endoscopic Gastrostomy Pezzer Catheters After Long-Term In Vitro Administration. JPEN J Parenter Enteral Nutr
17: 370-374
[Abstract]
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(1991). Neurobehavioral Effects of Phenytoin Prophylaxis of Posttraumatic Seizures. JAMA
265: 1271-1277
[Abstract]
(1990). PHENYTOIN PREVENTS EARLY SEIZURES AFTER HEAD TRAUMA. JWatch General
1990: 1-1
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