Hemodynamic Effects of Continuous Intravenous Midazolam in Refractory Status Epilepticus

The primary objective of this study was to determine the proportion of patients who developed hemodynamic compromise (HDC) while receiving continuous intravenous midazolam (cIV-MDZ) for refractory status epilepticus (RSE). Secondary objectives included comparing cIV-MDZ and ketamine exposures, baseline and treatment characteristics, and clinical outcomes in patients that developed HDC to those that did not.

This retrospective nested case-control study included patients receiving cIV-MDZ for RSE at a tertiary academic medical center. Descriptive statistics and univariate analyses were used to compare exposures and outcomes in patients who developed HDC, defined as the initiation or escalation of vasopressors, to those who did not.

Of 112 patients included, 76 (67.9%) developed HDC and 36 (32.1%) did not. Patients who developed HDC received higher mean maximum doses of cIV-MDZ (0.88 mg/kg/h [standard deviation (SD) ± 0.58] vs. 0.55 mg/kg/h [SD ± 0.45], P < 0.001) and longer median durations of cIV-MDZ (2.5 days [interquartile range (IQR), 1.6-3.6] vs. 1.5 days [IQR, 0.7-2.1], P < 0.001). Patients who developed HDC also had longer intensive care unit (ICU) length of stay (13.7 days [IQR, 7.7-19.6] vs. 8.9 days [IQR, 4.7-16.6], P = 0.05) and hospital admissions (21.2 days [IQR, 14.8-30.5] vs. 13.3 days [IQR, 8-23.5], P < 0.01). Seizure recurrence (HDC vs. no HDC, 34.2% vs. 25%; P = 0.33) and mortality (HDC vs. no HDC, 23.7% vs. 19.4%; P = 0.62) were similar between groups.

The majority of patients receiving cIV-MDZ for RSE developed HDC. These results may help guide further studies seeking optimal cIV-MDZ doses for efficacy while minimizing adverse effects.