Abstracts

Rationale: Increased awareness of seizures after neurological injury and their contribution to secondary injury has supported use of prophylactic anti-epileptic drugs (AEDs). Intravenous (IV) Lacosmaide (LCM) is a newer option, but its relative safety and efficacy in the Neuro-ICU (NICU) setting has not been studied in a randomized trial. We report our findings from a prematurely aborted study comparing IV LCM with IV Fosphenytoin (fPHT) for seizure prevention after moderate or severe neurological injury. Methods: This was a prospective, randomized, single-blinded comparative trial of LCM vs. fPHT in patients with severe traumatic brain injury (sTBI) admitted to the NICU of an academic urban level I trauma center. Patients were randomized in a 2:1 ratio to receive either LCM or fPHT for 7 days. All patients underwent continuous EEG monitoring for the initial 72 hours to monitor for possible subclinical seizures. The study pharmacist made all medication dosage adjustments. Outcomes data were collected including initial and discharge Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), medication side effects, and Disability Rating Scale (DRS). This study was aborted prematurely because of low enrollment. Results: 11 patients were enrolled (fPHT=4; LCM=7). There were no differences between the fPHT and LCM groups in age, gender distribution, ICP monitoring, Licox insertion, craniotomy, hematoma evacuation or surgical decompression (all p>0.2). There were no differences in complications attributed directly to the treatment (all p>0.2). There were no differences in the initial GCS (field, emergency room, ICU admission) or the days 1-3 of ICU stay (all p>0.2). Starting with day 4 of ICU stay GCS started improving in LCM-treated patients when compared to fPHT-treated patients: day 4 (p=0.095), day 5 (p=0.11), day 6 (p=0.15) and day 7 (p=0.05). Long-term outcomes were not different between groups but also trended in the direction of better outcomes in the LCM treated group for discharge GCS 11 vs. 6 (higher is better; p=0.26); discharge GOS 3 vs. 2 (higher is better; p=0.18); 3 months GOS 3 vs. 2 (p=0.39) and DRS 7 vs. 9 (lower is better; p=0.38) . Conclusions: This first single-blinded, randomized study of LCM vs. fPHT in the NICU setting suggests that LCM should be studied further for seizure prevention in patients with TBI. Study support: UCB Pharma