Comparing Non-Weight-Based Versus Weight-Based Midazolam Infusion in Refractory Status Epilepticus

Introduction: Refractory status epilepticus (RSE) has a high risk of mortality. The Neurocritical Care Society recommends a treatment goal of seizure control within 60 minutes. Thus, weight-based (WB) dosing of a midazolam continuous infusion (CI) may be considered to optimize control. Research to evaluate a WB dosing strategy has primarily occurred in pediatrics and is limited in adults. Therefore, optimal continuous midazolam therapy in RSE has not been well defined. The primary objective is to compare seizure duration between WB (0.05-2 mg/kg/hr) and non-weight-based (NWB) (1-10 mg/hr) midazolam CI.


Methods: This was a retrospective review of patients with RSE at a community teaching hospital over 5 years. Patients were excluded if under 18 years old, pregnant, incarcerated, had a preceding cardiac arrest, a life expectancy of less than 48 hours, received pentobarbital, or incomplete documentation. Secondary outcomes compared the cumulative dose, duration of administration, and length of stay. Safety outcomes include incidence of renal and hepatic injury. The Fisher’s Exact Test was used for qualitative and count variables with Mann-Whitney and Wilcoxon rank sum exact test used for quantitative variables.


Results: 15 patients were included with 7 WB and 8 NWB midazolam CI. Background characteristics were compared with only a significant difference in the number of patients with a history of seizures. The primary endpoint found a nonsignificant difference in average seizure duration (37 vs 61 hours). There were significant differences in total midazolam dose (p < 0.001), total duration (p=0.054), and number of patients requiring vasopressors (p=0.041). Safety endpoints were not significantly different between the groups.


Conclusions: The difference in seizure duration was not statistically significant but a 24 hour decrease in seizure activity is clinically significant. Neurocritical Care Society guidelines link longer seizure duration to worse patient outcomes with the goal of emergent seizure cessation. The results were limited by the retrospective nature, reliance on clinician documentation, small sample size, and changing practice patterns. These findings suggest further prospective research is needed with larger sample sizes, detailed timelines, and consistent practice patterns.