Abstracts

Early post-operative seizures are well recognized and antiepileptic drugs (AEDs) are commonly used despite limited evidence of a prophylactic or antiepileptogenic benefit. Phenytoin (PHT), the most commonly used AED, has well known adverse reactions. Levetiracetam (LEV) has a low incidence of serious reactions. However, its safety and efficacy in the perioperative period have not been evaluated., A research patient database was used to identify nonepileptic patients who had supratentorial neurosurgery at Brigham and Women[apos]s or Massachusetts General Hospitals, during a five year period (1/1999-12/2004) and were followed for at least 7 days. The electronic medical records of patients who received LEV monotherapy were analyzed. A control group consisting of PHT monotherapy patients (2:1 vs. LEV) was randomly selected. The following procedures were excluded: pressure measurement devices, external and internal ventricular drainage.
Records were reviewed for rate of seizures (at presentation, 1 week postoperatively, and development of epilepsy in those patients followed for at least one year). The other main outcome assessed was rate of adverse reactions during the postoperative period. Chi-square and Fisher[apos]s tests were used for intergroup comparisons., 105 LEV patients were identified. They were 39% male. Mean age was 55 (range 29-88). The 210 PHT patients were 47% male. Mean age was 64 (range 23-95). LEV dose ranged from 500 to 3000 mg/d, with 1000 mg/d used most frequently.
The LEV diagnoses were 41% glial tumors, 10% meningiomas, 11% metastases, 21% hemorrhages, 10% vascular malformations, 4% infections, and 3% other. The PHT diagnoses were 27% glial tumors, 17% meningiomas, 13% metastases, 24% hemorrhages, 7% vascular malformations, 2% infections, and 10% other.
Of the 105 LEV patients, 33 had presented with a seizure vs 57/210 PHT patients (p=0.26). 1 LEV patient (1%) had an early postoperative seizure (within the first 7 days), vs 9 PHT patients (4%) (p=0.28). Mean follow-up for the LEV group was 12 mo, vs 20 mo for PHT. 42 LEV patients were followed for one year or more and 11/42 (26%) developed epilepsy, vs 42/117 (36%) on PHT (p= 0.32).
Adverse reactions prompting a change in AED during the hospitalization occurred in 1/105 (1%) LEV patients (visual hallucinations), vs 38/210 (18%) PHT patients (p[lt]0.001). These reactions consisted of allergy (2), rash (22), fever (8), tremors (1), cytopenia (3), rhabdomyolysis (1),and cognitive change(1).
Of the LEV group with epilepsy followed for at least 12 months, 7/11 remained on levetiracetam (64%) vs 11/42 (26%) on phenytoin (p=0.025)., Both LEV and PHT are associated with a low risk of early post-operative seizures and a moderate risk of later epilepsy. LEV is associated with significantly fewer adverse reactions, an attractive feature particularly when an agent is being used prophylactically, as well as with a higher retention rate in patients who developed epilepsy., (Supported by UCB Pharma Young Investigators Award.)