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

TLDR

Phenytoin is routinely used for seizure prophylaxis after subarachnoid hemorrhage but may impair neurologic and cognitive recovery. The study aimed to determine whether the cumulative burden of phenytoin exposure predicts functional and cognitive outcomes after SAH. Researchers calculated a phenytoin burden by multiplying average serum level by exposure days up to 14 days, then measured functional outcome with the modified Rankin scale at 14 days and 3 months and cognitive outcome with a telephone interview for cognitive status. Higher phenytoin burden was associated with poorer functional outcome at 14 days and worse cognitive scores at discharge and 3 months, even after adjusting for clinical confounders, while seizures alone were only linked to functional disability in univariate analysis.

Abstract

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.