title: Intramuscular versus intravenous therapy for prehospital status epilepticus.
abstract: BACKGROUND
  Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.
  
  
  METHODS
  This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.
  
  
  RESULTS
  At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.
  
  
  CONCLUSIONS
  For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.).
authors.affiliation: Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48105, USA. robert.silbergleit@umich.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Silbergleit
authors.forename: Valerie
authors.initials: V
authors.lastname: Durkalski
authors.forename: Daniel
authors.initials: D
authors.lastname: Lowenstein
authors.forename: Robin
authors.initials: R
authors.lastname: Conwit
authors.forename: Arthur
authors.initials: A
authors.lastname: Pancioli
authors.forename: Yuko
authors.initials: Y
authors.lastname: Palesch
authors.forename: William
authors.initials: W
authors.lastname: Barsan
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004632:Emergency Medical Services; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage; D007223:Infant; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D008140:Lorazepam / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012008:Recurrence; D013226:Status Epilepticus / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D008140:Lorazepam; D008874:Midazolam