title: Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage.
abstract: OBJECTIVE
  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 > or =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 > or =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.
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Ill, USA. a-naidech@northwestern.edu
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Naidech
authors.forename: Kurt T
authors.initials: KT
authors.lastname: Kreiter
authors.forename: Nazli
authors.initials: N
authors.lastname: Janjua
authors.forename: Noeleen
authors.initials: N
authors.lastname: Ostapkovich
authors.forename: Augusto
authors.initials: A
authors.lastname: Parra
authors.forename: Christopher
authors.initials: C
authors.lastname: Commichau
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Mayer
authors.forename: Brian-Fred M
authors.initials: BF
authors.lastname: Fitzsimmons
mesh_terms: D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010672:Phenytoin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012640:Seizures / Q000209:etiology / Q000517:prevention & control; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010672:Phenytoin