Abstracts

Rationale: There is high variability in lorazepam (LZP) dosing when used in the treatment of status epilepticus (SE), but little is known about how this dosing variability affects seizure duration. Methods: Using data from a multicenter prospective observational cohort of pediatric patients admitted with refractory SE between 2011-2016 in whom SE did not resolve after ≥2 AEDs, we assessed if a lower first dose of IV LZP when used as a first line AED was associated with (1) increased total seizure duration and (2) increased convulsive seizure duration. Three dosing groups were created with cutoffs based on current guidelines: lower dose ( < 0.05 mg/kg), medium dose (0.05 to < 0.1 mg/kg), and higher dose (≥0.1 mg/kg). We used Cox proportional hazards regression to quantify the association between the first dose of LZP and subsequent time to total and convulsive seizure resolution. Models accounted for potential clustering by study site and were adjusted for age, sex, presumed underlying seizure cause, seizure duration prior to LZP administration, home AED use, prior neurological conditions, and location of LZP administration. Direct adjusted survival curves were used to obtain median seizure durations for each dosing group accounting for covariates. Results: 103 patients were included in the analysis. Patients were a median of 4.5 years of age, 49/103 (48%) were female, and 45/103 (44%) were currently receiving a home AED. LZP was administered at a median of 20 minutes following seizure onset, with 29/103 (28%) receiving a lower dose, 44/103 (43%) a medium dose, and 30/103 (29%) a higher dose. Individuals in the higher dose group were significantly more likely to experience seizure resolution sooner than those in the medium and lower dose groups, with a hazard ratio (HR) of 1.62 (95% CI: 1.04, 2.53; p=0.0333) and 2.49 (95% CI: 1.43, 4.32; p=0.0012), respectively. Median time to total seizure resolution following LZP administration was 93 min (IQR: 56-300 min) in the higher dose group, 160 min (IQR: 69-1664 min) in the medium dose group, and 350 min (IQR: 93-5580 min) in the lower dose group. 97/103 (94%) patients had convulsive seizures at time of LZP administration. Those in the higher dose group were more likely to experience convulsive seizure resolution sooner than those in the lower dose group (HR: 1.89; 95% CI: 1.15, 3.11; p=0.0122). Median time to convulsive seizure resolution was 67 min (IQR: 30-150 min) in the higher dose group and 120 min (IQR: 56-495 min) in the lower dose group. 81/103 (79%) of patients required intubation during hospitalization, with no statistically significant difference between the dosing groups (p=0.6905). Conclusions: The first dose of LZP, when administered as a first-line AED for pediatric refractory SE, is under-dosed in the majority of pediatric patients. Doses lower than 0.1 mg/kg are associated with an increase in seizure duration, emphasizing the importance of following American Epilepsy Society SE guidelines for lorazepam dosing (0.1 mg/kg). (Funded by the Pediatric Epilepsy Research Foundation) Funding: Funded by the Pediatric Epilepsy Research Foundation