title: High-dose midazolam infusion for refractory status epilepticus.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Andres
authors.initials: A
authors.lastname: Fernandez
authors.forename: Hector
authors.initials: H
authors.lastname: Lantigua
authors.forename: Christine
authors.initials: C
authors.lastname: Lesch
authors.forename: Belinda
authors.initials: B
authors.lastname: Shao
authors.forename: Brandon
authors.initials: B
authors.lastname: Foreman
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schmidt
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Hirsch
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Mayer
authors.forename: Jan
authors.initials: J
authors.lastname: Claassen
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005260:Female; D006761:Hospitals; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use*; D008875:Middle Aged; D010351:Patient Discharge / Q000706:statistics & numerical data; D012189:Retrospective Studies; D013226:Status Epilepticus / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam