High-Dose Midazolam for Pediatric Refractory Status Epilepticus: A Single-Center Retrospective Study

Abstract

Objectives: We sought to describe the prevalence of midazolam treatment failure in children with refractory status epilepticus (RSE) and define a threshold dose associated with diminishing frequency of seizure cessation.

Design: Single center retrospective cohort study.

Setting: Single-center, quaternary-care PICU.

Patients: Children younger than 18 years old admitted to the PICU from 2009 to 2018 who had RSE requiring a continuous midazolam infusion.

Interventions: None.

Measurements and main results: We identified individuals with RSE through a data analytics inquiry. Receiver operating characteristic (ROC) curve analysis and Youden's index were used to assess the midazolam dose threshold associated with the highest sensitivity and specificity in identifying seizure cessation. A logistic regression model was used to determine if there was an association between maximum midazolam dose and seizure cessation. Of the 45 patients who met inclusion criteria for this study, 27 (60%) had seizure cessation with a midazolam infusion, whereas 18 (40%) required an additional pentobarbital infusion for seizure cessation. There was an association between maximum midazolam dose and seizure cessation, with patients more likely to fail treatment when midazolam was administered at higher doses. The maximum midazolam dose displayed high area under the ROC curve value for seizure cessation, and the Youden's J index cut-off point was 525 μg/kg/hr. Treatment above this dose was associated with diminishing frequency of seizure cessation. The median time spent titrating midazolam above 500 μg/kg/hr for those patients who required pentobarbital for seizure cessation was 3.83 hours (interquartile range, 2.28-5.58 hr).

Conclusions: In pediatric patients with RSE requiring high dose midazolam, considerable time is spent titrating doses in a range (above 500 µg/kg/hr) that is associated with diminishing frequency of seizure cessation.