Efficacy of Low Dose Levetiracetam for Seizure Prophylaxis in Traumatic Brain Injury

Abstract

Objectives: Guidelines from the Brain Trauma Foundation recommend that after traumatic brain injury (TBI) patients should be given seizure prophylaxis for up to seven days. Currently, phenytoin is the first line therapy for this indication. However, levetiracetam is increasingly being used as an alternative because it does not require serum concentration monitoring and has a desirable safety profile. Studies evaluating levetiracetam have used a loading dose, followed by a maintenance dose of 1000 mg every 12 hours. The primary objective of this study was to evaluate the efficacy of low-dose (500 mg every 12 hours) levetiracetam for seizure prophylaxis after TBI. Methods: This was a retrospective cohort study conducted in a tertiary care, academic institution that is designated as a level 1 trauma center. Institutional review board approval was obtained prior to data collection. Consecutive patients with TBI between 2010 and 2012, who received levetiracetam for seizure prophylaxis, were included. Patients who met at least one of the following criteria were included: cortical contusion on computerized tomography scan, subdural hematoma, epidural hematoma, intracerebral hematoma, depressed skull fracture, penetrating head injury, or Glasgow Coma Scale (GCS) of 10 or less. Patients were excluded if they were less than 16 years of age, had a previous head injury, previous neurosurgery, history of seizure, or anti-seizure medication, or were given a loading dose of levetiracetam, or given a maintenance dose greater than 500 mg every 12 hours. The primary outcome was the occurrence of a seizure within seven days of TBI. A one-sample test of proportions was used to compare the rate of seizures while being treated with levetiracetam to a hypothesized value of 3.6 percent (from previous trials), using an a priori alpha for 0.05. Results: There were a total of 146 patients included in the study, who were treated with levetiracetam 500 mg every 12 hours. The median age was 51 years (interquartile range 31 to 65 years), 110 (75 percent) were male, and the median GCS on admission was 11 (interquartile range 5 to 14). The mechanisms of injury were fall (n equals 49), motor vehicle or motorcycle collisions (n equals 42), pedestrian or bicyclist (n equals19), assault (n equals16), suicide attempt (n equals 2), and other (n equals18). The median time to first dose of levetiracetam was 4 hours after injury (interquartile range 1 to 13 hours). After initiation of levetiracetam, there were 5 (3.4 percent) patients who had a seizure within seven days. This was not significantly different than the hypothesized population value (p equals 0.910). The median length of stay was 13 days (interquartile range 9 to 21) and 7 (4.8 percent) patients died during hospitalization. Conclusions: A low-dose of levetiracetam 500 mg every 12 hours after TBI was effective for early seizure prevention. This regimen may be an appropriate alternative to phenytoin or traditional dose levetiracetam for this indication. Future, prospective studies are needed to confirm these findings.