Abstracts

Rationale: Last year, a pilot trial of midazolam administered intravenously (IV) was implemented as first line therapy for status epilepticus (SE) in a pediatric Epilepsy Monitoring Unit (EMU) with the primary objective of improving the time from start of seizure to administration of rescue medication. Currently, data of midazolam administered IV as first line therapy for SE in a pediatric EMU is being compared with retrospective data of lorazepam administered IV as first line therapy for SE in the same pediatric EMU, with the primary objective of decreasing the time from drug administration to start of next seizure in order to facilitate higher yield EMU studies. In line with evidence-based guidelines, lorazepam 0.1 mg/kg (up to 4 mg) IV for SE was the first line therapy prior to these studies. However, delays in administering lorazepam occurred. Midazolam was suggested as an alternative because it does not require refrigeration, nor dilution, and is available as a 1 mg/mL injection, which simplifies dose calculations. In the previous study performed, midazolam was shown to be administered in a reasonable and safe amount of time for SE. Additionally, it was effective in terminating SE and seizure clusters with a single dose. Another added benefit of midazolam is that it has a shorter half-life than lorazepam, thus a shorter duration of action and quicker patient recovery time, which may facilitate the recording of more seizures and overall higher yield studies in the EMU. Methods: This single-center study included patients at Texas Children’s Hospital’s (TCH) EMU, who received either IV midazolam or IV lorazepam as rescue therapy for SE, defined as a single seizure lasting 5 minutes or longer, or seizure cluster, defined as 3 or more seizures within 30 minutes. The midazolam dose, as determined by the faculty in the Comprehensive Epilepsy Program based on prior literature, pharmacokinetic properties, and dosing of midazolam in other indications, was 0.2 mg/kg (max 5 mg/dose) slow IV push every 3 minutes as needed for up to 2 doses. The lorazepam dose, in line with evidence-based guidelines, was 0.1 mg/kg (max 4 mg/dose) slow IV push every 5 minutes as needed for up to 2 doses. The primary endpoint was defined as the time from drug administration to start of next seizure. Results: Preliminary results for 10 patients who received IV midazolam had 15 rescue medication administrations. For nine patients, there was recurrent seizure activity in less than 24 hours (range approximately one hour to approximately 20 hours) after the administration of IV midazolam. Seven of these patients received one dose of IV midazolam, while the other two received at least one additional dose of rescue medication. For one patient, there was no further seizure activity during the study after the administration of IV midazolam (study ended within approximately 48 hours after administration). This patient received one dose of IV midazolam. Preliminary results for 10 patients who received IV lorazepam also had 15 rescue medication administrations. For two patients, there was recurrent seizure activity within 48 hours (range approximately two hours to approximately 45 hours) after the administration of IV lorazepam. These patients each received one dose of IV lorazepam. For eight patients, there was no further seizure activity during the study after the administration of IV lorazepam (studies ended within approximately 48 hours after administration). Five of these patients received one dose of IV lorazepam, while the other three received at least one additional dose of rescue medication. Further clinical data related to AED management in this patient cohort is being evaluated. Conclusions: Our data thus far suggest that midazolam is more effective than lorazepam in producing a quicker patient recovery time with shorter time to next seizure, which potentially will facilitate the recording of more seizures and thus improve the yield of studies in the EMU.