Abstracts

Rationale: Seizures are a common and often dangerous complication of aneurysmal subarachnoid hemorrhage, leading to shifts in blood pressure and the risk of re-bleeding. As a result, the standard of care has been the use of seizure prophylaxis in these critically ill patients. However, the choice of a particular anti-epileptic drug (AED) and duration of treatment has yet to be clearly defined. The older generation AEDs have long been the mainstay of treatment due to their IV availability and familiarity. However, there has been a recent increase in the use of levetiracetam (LEV) in the neuro-intensive care unit (NICU) due to the lack of drug-drug interactions or significant adverse effects. We sought to compare the safety and efficacy of fosphenytoin (FOS)/phenytoin (PHT) versus LEV in patients with aneurysmal subarachnoid hemorrhage.Methods: We retrospectively identified all NICU admissions with a diagnosis of subarachnoid hemorrhage from January 1, 2006 through December 15, 2006. Patients were divided into three groups, one treated with FOS/PHT alone, a second group initially loaded and treated with FOS/PHT and then transitioned to LEV within 72 hours of admission (Transition Group), and a third group treated only with LEV. Safety was assessed by documenting serious adverse reactions reported in the hospital chart (hypotension, arrhythmias, rash). Efficacy was determined by the number of clinical or subclinical (electrographic) seizures recorded. Secondary endpoints included the presence of interictal epileptiform abnormalities, the presence of periodic discharges on continuous EEG (cEEG), and frequency of vasospasm. Vasospasm was selected due to nimodipine’s metabolism via cytochrome P450 enzymes and the known induction of these enzymes by FOS/PHT.Results: Of the 126 patients identified, 58 were treated with FOS/PHT, 53 were transitioned to LEV, and 15 were treated with LEV only. There were no adverse events identified in any group. One patient in both the FOS/PHT group and the transition group had a clinical seizure. A total of 32 patients had cEEG monitoring (15 FOS/PHT, 11 transition, 6 LEV). Periodic discharges were rare in all 3 groups, but interictal abnormalities occurred more frequently in the FOS/PHT group (53%) than in either the transition group (9%) or the LEV group (16%). Using a Fisher’s Exact Test, the differences seen in interictal abnormalities reaches statistical significance (p=0.04). Vasospasm occurred in 50% or FOS/PHT group, 51% of the transition group, and 33% of the LEV only group, a difference that is not statistically significant. (Table 1)Conclusions: Seizure prophylaxis with PHT and LEV is equally safe and effective at preventing early/acute seizures in patients with aneurysmal subarachnoid hemorrhage. The difference in interictal abnormalities favors the use of LEV. This study is limited by its small sample size. Larger prospective studies are needed to further evaluate use of PHT and LEV as seizure prophylaxis in subarachnoid hemorrhage. (Sources of funding include Young Investigator's Research Program Grant from UCB)