Abstracts

Rationale: Status epilepticus (SE) is an underdiagnosed life-threatening medical emergency, but limited data is available to guide management. Lorazepam is the accepted first line therapy, with most prior studies supporting Fosphenytoin as second line. Although multiple other anti-epileptic (AEDs) are available, only 2-7% of SE will be stopped with a third line agent or beyond. Lacosamide (LCS) is an AED with a novel mechanism of action and approved as adjunctive therapy for partial seizures in adults. LCS has shown efficacy in mouse models of SE and an intravenous (IV) formulation is available but not FDA approved for SE. Only a single case report has reported the use of IV LCS in stopping nonconvulsive SE. This case series investigates safety profile and potential efficacy of IV LCS in patients with refractory SE on video electroencephalography (EEG). Methods: Charts were retrospectively reviewed per IRB-approved protocol for patients with continuous EEG-confirmed SE and were treated with LCS during SE. Primary outcomes were cessation of electrographic seizures after administration of IV LCS, as well as safety profile measures. Statistical analysis was performed on SPSS 10.0. Results: Twenty-seven patients had SE and were treated with LCS, of which 88.9% had nonconvulsive SE. No prior seizure history was found in 59.3%. Only two patients had prior SE. Main etiologies of SE was acute hemorrhage (6), stroke (5), and medically refractory epilepsy (5). Cessation of SE after LCS occurred in nine patients (33.3%) within 4 hours and 21 patients (77.8%) within 24 hours. LCS was given a mean of 20.8 hours after SE onset for those who had SE cessation within 4 hours and 22.2 hours in the overall group (p=0.308). Mean number of IV AEDs given prior to LCS was 3.3 (range 1-5). Nineteen patients (70.3%) were given an IV AED with sodium-channel mechanism. Mean SE cessation time from end of LCS infusion was 0.78 hours in those who responded within 4 hours and 8.37 hours in those who responded within 24 hours. Patients with no prior history of seizures had a higher responder rate to LCS (p=0.001). SE etiology was not a useful predictor for response. Serial blood pressures (BP) were obtained in 25 patients. Only two patients had a decrease in BP without significant hypotension. Serial EKGs showed an increase in PR interval in 11 of 16 patients with a mean increase of 24.5 ms in those patients, a mode of 16 ms, and a range of 4-80 ms. One patient had an increase in PR interval >200 ms without clinical symptoms. Serial liver function tests were obtained in 28 patients. Seven patients had an asymptomatic increase in AST and/or ALT. Serial serum creatinine showed a nonsignificant increase in 2 of 26 patients. SE was resolved in 21 patients, while the 6 others expired. Conclusions: IV LCS is a promising new adjunct agent for the treatment of refractory SE with a favorable safety profile in critically ill population. Prospective studies would better determine the efficacy and potential role of IV LCS in the treatment of SE.