Medline ® Abstract for Reference 94
of 'Convulsive status epilepticus in adults: Treatment and prognosis'
High-dose midazolam infusion for refractory status epilepticus.
Fernandez A, Lantigua H, Lesch C, Shao B, Foreman B, Schmidt JM, Hirsch LJ, Mayer SA, Claassen J
Neurology. 2014 Jan;82(4):359-65. Epub 2013 Dec 20.
OBJECTIVE: This study compares 2 treatment protocols allowing low vs high continuous IV midazolam (cIV-MDZ) doses.
METHODS: We 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.
RESULTS: Median 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).
CONCLUSIONS: High-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 EVIDENCE: This 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.
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.