A prospective, multicenter, uncontrolled, open-label study of the efficacy and safety of intravenous midazolam in Japanese adults/adolescents with status epilepticus (MiSES-J)

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Purpose: In Japan, intravenous (IV) midazolam (MDL) is recommended as first-line therapy for pediatric patients with status epilepticus (SE) if venous access is possible. However, few studies have investigated its use in adults/adolescents with SE. This prospective, uncontrolled, open-label study investigated the efficacy and safety of bolus or continuous IV MDL in adults/adolescents with convulsive SE.Methods: Patients aged ≥15 years who satisfied the diagnostic criteria for SE with convulsive seizures lasting ≥5 min were enrolled. Patients first received bolus IV MDL (0.15 mg/kg). If the seizures continued, additional doses (0.1‒0.3 mg/kg) were administered (maximum cumulative dose: 0.6mg/kg). Patients with a high likelihood of recurrent convulsive seizures were subsequently administered continuous IV MDL (0.1 mg/kg/h). The dose was increased until seizure cessation (maximum: 0.4 mg/kg/h) and administration continued for 24 h from seizure cessation. The primary efficacy endpoint was convulsive seizure cessation after bolus IV. Safety endpoints included adverse events (AEs) and adverse drug reactions (ADRs).Results: Twenty-one patients (aged 18.0‒89.0 years) with SE were enrolled. The convulsive seizure cessation rate after bolus IV MDL was 100.0% (21/21 patients), which was statistically significant (P < 0.001) in one-sample testing (binomial distribution). The most common AE/ADR was hypotension (four patients [19.0%]). There were no deaths, serious AEs/ADRs, or AEs/ADRs leading to discontinuation of MDL. Respiratory depression occurred in two patients (9.5%). None of the patients required mechanical ventilation/endotracheal intubation.Discussion: Bolus IV MDL achieved a high seizure cessation rate in patients with convulsive SE, with minimal effects on respiratory or cardiovascular functions and no major safety issues.