Efficacy and safety of continuous midazolam infusion in the treatment of acute repetitive seizures in non‐intensive settings: A multicenter retrospective real‐world data study

Seizures, when prolonged or repeated, leading to status epilepticus (SE), represent a medical emergency, requiring prompt treatment. In these conditions, the use of continuous midazolam (MDZ) infusion is often reserved for established or refractory SE and considered an anesthesiologic treatment, while evidence on its early use in non-intensive settings is still limited. To verify this approach in daily practice, we retrospectively collected data on about 42 episodes of pediatric SE or acute repetitive seizures (ARSs), treated with continuous MDZ infusion in non-intensive setting. Collected data include demographical information, previous history of epilepsy, instrumental examinations (electroencephalography [EEG] and brain magnetic resonance imaging [MRI]), comorbidities, anti-seizure medications (ASMs), information about the event, other treatments (first- and second-line), information about MDZ infusion, and need for other third-line treatment and/or intensive care unit (ICU) transfer. Infusion durations and rates varied widely, but in most cases (38/42) low dose (<.23 mg/kg/h) were employed. The treatment was effective in 84.2% of cases, achieving both clinical and EEG response. No adverse events (AEs) were reported. The need for a second-line treatment (particularly levetiracetam [LEV] and phenobarbital [PB]) was associated with a worse outcome. Another third-line treatment was needed in 9.5% of cases. Patients (21.4%) were transferred to ICU; a higher risk of ICU admission was reported in patients with precipitating factors (infection, surgery, hypertension and suboptimal anti-seizure medication [ASM] serum levels), and those receiving MDZ infusion at higher rates and/or co-treated with PB. Overall, our study suggests that low-dose continuous MDZ infusion is an effective and safe strategy for treatment of pediatric SE and ARSs in non-intensive settings.