Aneurysmal Subarachnoid Hemorrhage: Impact on Phenytoin Permeability across the Blood-Brain Barrier.

Abstract

Phenytoin (PHT) is a routinely prescribed prophylactic antiepileptic following aneurysmal subarachnoid hemorrhage (aSAH). However, its prophylactic use in aSAH is controversial as emerging evidence suggests worsening of the neurological and functional outcomes. In addition, there is profound damage to the blood-brain barrier (BBB) in aSAH, posing uncertainty about the permeability of PHT across BBB in these patients. This pilot study was designed to evaluate the alteration in PHT permeability across BBB in aSAH patients. For conducting the study, 20 patients (control n = 10; aSAH (grade 3 or 4) n = 10) were recruited from a tertiary care hospital. The patients undergoing cranial surgery for pathology with intracerebral mass lesions on MRI were chosen as control for aSAH group. Both groups were administered PHT loading dose (20 mg/kg), infused in 5% dextrose, at a rate not more than 50 mg/min, followed by a maintenance dose (5 mg/kg). Quantification of PHT concentration was performed in brain tissue, plasma, and cerebrospinal fluid (CSF) by LC-MS/MS. The median PHT concentration in brain was found to be significantly decreased (64.8%) in aSAH group (3.78 μg/g) as compared to control (10.73 μg/g), P = 0.010. Similarly, median PHT brain concentration as fraction of plasma was significantly decreased in aSAH group (36.72%) compared to that of control (89.55%), P = 0.003. There was no significant difference in PHT concentration in plasma, CSF, and CSF as a fraction of plasma between both the groups. There is a definite decrease in the penetration of PHT to the brain in patients with grade 3 and 4 aSAH.