Published Online
on January 20, 2005

A more recent version of this article appeared on March 1, 2005

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Submitted on July 6, 2004
Accepted on July 22, 2004

Phenytoin Exposure Is Associated With Functional and Cognitive Disability After Subarachnoid Hemorrhage

Andrew M. Naidech MD, MSPH^*; Kurt T. Kreiter PhD; Nazli Janjua MD; Noeleen Ostapkovich MS; Augusto Parra MD, MPH; Christopher Commichau MD; E. Sander Connolly MD; Stephan A. Mayer MD; and Brian-Fred M. Fitzsimmons MD

From the Departments of Neurology and Critical Care (A.M.N.), Northwestern University, Chicago, Ill; and the Department of Critical Care and Vascular Neurology (K.T.K., N.J., N.O., A.P., C.C., S.A.M., B.-F.M.F.) and Department of Neurosurgery (E.S.C.), Columbia University, New York, NY.

^* To whom correspondence should be addressed. E-mail: a-naidech{at}northwestern.edu.

Background and Purpose--Phenytoin (PHT) is routinely used for seizure prophylaxis after subarachnoid hemorrhage (SAH), but may adversely affect neurologic and cognitive recovery.

Methods--We studied 527 SAH patients and calculated a "PHT burden" for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale 4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status.

Results--PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale 10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003).

Conclusions--Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH.

Key words: critical care • phenytoin • subarachnoid hemorrhage

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