Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: A comparative cohort study

摘要

Background: Refractory status epilepticus (RSE) is an emergency with high mortality requiring neurointensive care. Treatment paradigms include first-generation antiepileptic drugs (AEDs) and anesthetics. Lacosamide (LCM) is a new AED, holding promise as a potent treatment option for RSE. High-level evidence regarding safety and efficacy in the treatment of RSE is lacking. Objective: The objective of the study was to evaluate the safety profile and efficacy of intravenous (i.v.) LCM as an add-on treatment in adult RSE patients. Methods: All consecutive RSE patients treated in the intensive care units (ICUs) of an academic tertiary care center between 2005 and 2011 were included. Severity of status epilepticus (SE) was graded by the SE Severity Scale (STESS), and SE etiology was categorized according to the guidelines of the International League Against Epilepsy (ILAE). Outcomes were seizure control, RSE duration, and death. Results: Of 111 RSE patients, 53 % were treated with LCM. Twenty-five patients with hypoxic-ischemic encephalopathy were excluded. Mortality was 30 %. Mean number of AEDs, duration, severity, and etiology of SE, as well as critical medical conditions did not differ between patients with and without LCM. While age tended to be higher, critical interventions, such as the use of anesthetics and mechanical ventilation, tended to be less frequent in patients with LCM. Seizure control tended to be achieved more frequently in patients with LCM (odds ratio, OR 2.34, 95 % CI 0.5-10.1, p = 0.252). Among patients with LCM, 51 % received LCM as the last AED (including hypoxic-ischemic encephalopathy), allowing the reasonable assumption that LCM was responsible for seizure control, which was achieved in 91 %. Multivariable analysis revealed a decreased mortality in patients with LCM (OR 0.34, 95 % CI 0.1-0.9, p = 0.035). A possible confounder in this context was the implementation of continuous video-electroencephalography (EEG) monitoring 6 months prior to the first use of i.v. LCM. There were no serious LCM-related adverse events. Conclusion: LCM had a favorable safety profile as adjunctive treatment for RSE. Its use was associated with decreased mortality of RSE - a finding that might have been confounded by the implementation of continuous video-EEG monitoring in the ICU prior to the use of i.v. LCM, leading to heightened awareness as well as earlier diagnosis and treatment of SE. Randomized trials are warranted to further strengthen the evidence of efficacy of LCM for RSE treatment.