Optimizing pediatric status epilepticus management: The role of early midazolam infusion and adherence to clinical practice guidelines.

Abstract

Objective: This study was undertaken to describe a cohort of pediatric patients with status epilepticus (SE) in Italy over the past decade, focusing on the variability of treatment protocols among centers, adherence to guidelines, and potential predictors of refractoriness.

Methods: This is a multicenter retrospective observational cohort study including patients aged 1 month to 18 years who experienced convulsive SE (CSE) between January 2010 and June 2022. Variables analyzed included age at CSE onset, etiology, and treatment.

Results: We included 1374 CSE episodes in 1071 patients (median age = 3.3 years); 46% occurred in the first 3 years of life. The prominent etiology was remote symptomatic (32%). Resolution was obtained only with benzodiazepine administration in 19.2% of SE episodes. Phenytoin, phenobarbital, and midazolam by infusion were the drugs most frequently used. Maximum therapeutic response occurred with low-dose (<.2 mg/kg/h) midazolam infusion administered at an early stage, following a single dose of benzodiazepine or an antiseizure medication (ASM; 59%). Midazolam effectiveness decreased to 37% when it was used after multiple ASMs, even at high doses. CSE was refractory in 39% of cases. Predictors of refractoriness included nonadherence to current guidelines, type of CSE, and etiology.

Significance: This study emphasizes that low-dose midazolam infusion, not requiring endotracheal intubation and administered at an early phase, appears to be effective in permanently stopping seizure and preventing the evolution toward a refractory CSE. Given its proven efficacy and widespread use in many hospitals, early midazolam infusion could be considered in the management of pediatric CSE. Adherence to treatment protocols, specific etiologies, and type of CSE are correlated with refractoriness; thus, when facing SE in infants, these factors should guide treatment protocol selection, including medication choice and timing.