Comparison of short-duration levetiracetam with extended-course phenytoin for seizure prophylaxis after subarachnoid hemorrhage

Background: The optimal regimen for seizure prophylaxis after subarachnoid hemorrhage (SAH) remains uncertain. Based on data suggesting that a short course may be adequate, coupled with an association between phenytoin exposure and poor cognitive outcome, our institution modified their seizure prophylaxis protocol for patients with SAH from an extended course of phenytoin to 3 days of levetiracetam. This study sought to compare the incidence of seizures before and after this change to evaluate whether a short course of levetiracetam would be as effective in preventing in-hospital seizures. Methods: This study analyzed 442 consecutive patients admitted with SAH between January 2003 and January 2008, including 297 patients treated before the protocol change (PHT group) and 145 treated afterward (LEV group). Occurrence of all seizures was extracted from a prospectively collected intensive care unit database and further review of medical records. In-hospital seizures were divided into early (occurring on or before day 3, all patients on prophylaxis) and those occurring late (after day 3, LEV group off prophylaxis). Results: In-hospital seizures occurred in 3.4% of the PHT group and 8.3% of the LEV group (P = 0.03). Although the rate of early seizures was not different (1.4% PHT vs. 2.8% LEV, P = 0.45), there was a higher rate of late seizures (2% PHT vs. 5.5% LEV, P = 0.05). Conclusions: The use of short-duration levetiracetam for seizure prophylaxis after SAH was associated with a higher rate of in-hospital seizures than an extended course of phenytoin, mainly related to an increase in late seizures, when the levetiracetam had been discontinued. This suggests that a longer duration of prophylaxis may be required to minimize seizures in patients with SAH, although confirmatory studies are required.