(582) Effect of Midazolam Weight-Based Infusion on Seizure Recurrence in Adults With Status Epilepticus

Introduction: There is limited data on the safety and efficacy of weight-based continuous infusion midazolam (WBCI-MDZ) in critically ill adults with status epilepticus (SE). The purpose of this study was to compare the impact of non-weight-based continuous infusion midazolam (NWBCI-MDZ) to WBCI-MDZ following a protocol change on successful weaning of continuous infusion anti-epileptic drugs without seizure recurrence in critically ill adult patients. It was hypothesized that there would be a reduction in seizure recurrence with WBCI-MDZ.

Methods: This single-center, retrospective study included adult patients admitted to the intensive care unit (ICU) with SE on continuous infusion midazolam (CI-MDZ). The primary outcome was successful wean of all continuous infusion anesthetics without seizure recurrence. Secondary outcomes, determined by a neurologist’s review of the electroencephalogram, included resolution of seizure, time to resolution of seizures, and achievement of burst suppression. Other secondary outcomes were time from SE diagnosis to initiation of CI-MDZ wean, ICU and hospital length of stay (LOS), duration of mechanical ventilation (MV), and discharge disposition. The safety outcome was rate of hypotension after CI-MDZ initiation.

Results: Of the 898 patients screened, 42 and 55 patients were included in the NWBCI-MDZ and WBCI-MDZ arm, respectively. The primary outcome of seizure recurrence remained similar between the NWBCI-MDZ and WBCI-MDZ arms (90.5% vs 98.2%; p=0.163). Achievement of burst suppression occurred more frequently in the WBCI-MDZ arm (23.8% vs 45.5% p=0.034). Patients in the WBCI-MDZ arm had significantly increased duration of MV (5 vs 8 days; p=0.004) and ICU LOS (7 vs 10 days; p=0.042). Incidence of hypotension remained similar (23.8% vs 18.2%; p=0.497).

Conclusions: In critically ill adult patients with SE who received NWBCI-MDZ versus WBCI-MDZ, there was no difference observed in successful wean of all continuous infusion anesthetics without seizure recurrence, despite the WBCI-MDZ arm more frequently achieving burst suppression. Patients in the WBCI-MDZ arm had significantly higher exposure to MDZ which explains the longer MV duration and ICU LOS. The results of this study raise the question of optimal CI-MDZ titration goals as well as optimal dosing for SE patients.