• Andres Fernandez, Hector Lantigua, Christine Lesch, Belinda Shao, Brandon Foreman, J Michael Schmidt, Lawrence J Hirsch, Stephan A Mayer, and Jan Claassen.
• From the Department of Neurology (A.F., H.L., B.S., B.F., J.M.S., L.J.H., S.A.M., J.C.), Columbia University Medical Center; and Department of Pharmacy (C.L.), New York-Presbyterian Hospital, NY.
• Neurology. 2014 Jan 28; 82 (4): 359-65.

ObjectiveThis study compares 2 treatment protocols allowing low vs high continuous IV midazolam (cIV-MDZ) doses.MethodsWe compared adults with refractory status epilepticus treated with a protocol allowing for high-dose cIV-MDZ (n = 100; 2002-2011) with those treated with the previous lower-dose cIV-MDZ (n = 29; 1996-2000). We collected data on baseline characteristics, cIV-MDZ doses, seizure control, hospital course, and outcome.ResultsMedian maximum cIV-MDZ dose was 0.4 mg/kg/h (interquartile range [IQR] 0.2, 1.0) for the high-dose group and 0.2 mg/kg/h (IQR 0.1, 0.3) for the low-dose group (p < 0.001) with similar duration of infusion. Median time from status epilepticus onset to cIV-MDZ start was 1 day (IQR 1, 3) for the high-dose group and 2 days (IQR 1, 5) for the low-dose group (p = 0.016). "Withdrawal seizures" (occurring within 48 hours of discontinuation of cIV-MDZ) were less frequent in the high-dose group (15% vs 64%, odds ratio 0.10, 95% confidence interval 0.03-0.27). "Ultimate cIV-MDZ failure" (patients requiring change to a different cIV antiepileptic medication) and hospital complications were not different between groups. Hypotension was more frequent with higher cIV-MDZ doses but was not associated with worse outcome. Discharge mortality was lower in the high-dose group (40% vs 62%, odds ratio 0.34, 95% confidence interval 0.13-0.92 in multivariate analysis).ConclusionsHigh-dose cIV-MDZ treatment of refractory status epilepticus can be performed safely, is associated with a lower seizure rate after cIV-MDZ discontinuation, and may be associated with lower mortality than traditional lower-dose protocols.Classification Of EvidenceThis study provides Class III evidence that midazolam at higher infusion rates is associated with a reduction in seizure recurrence within 48 hours after discontinuation and may be associated with lower mortality.

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