title: A Common Reference-Based Indirect Comparison Meta-Analysis of Buccal versus Intranasal Midazolam for Early Status Epilepticus.
abstract: BACKGROUND
  Intranasal and buccal midazolam have recently emerged as possible alternatives to intravenous or rectal diazepam or intravenous lorazepam in the treatment of early status epilepticus (SE). However, to date no randomized controlled trial (RCT) has directly compared intranasal midazolam with buccal midazolam.
  
  
  OBJECTIVE
  The aim of this study was to indirectly compare intranasal midazolam with buccal midazolam in the treatment of early SE using common reference-based indirect comparison meta-analyses.
  
  
  METHODS
  RCTs comparing intranasal or buccal midazolam versus either intravenous or rectal diazepam for early SE were systematically searched. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy and safety of intranasal or buccal midazolam versus either intravenous or rectal diazepam. Adjusted indirect comparisons were then made between intranasal and buccal midazolam using the obtained results.
  
  
  RESULTS
  Fifteen studies, with a total of 1662 seizures in 1331 patients (some studies included patients with more than one episode of SE) were included; 1303 patients were younger than 16 years. Indirect comparisons showed no difference between intranasal and buccal midazolam for seizure cessation (OR 0.98, 95% CI 0.32-3.01, comparator: intravenous diazepam; OR 0.87, 95% CI 0.46-1.64, comparator: rectal diazepam). For serious adverse effects, we found a large width and asymmetrical distribution of confidence intervals around the obtained OR of 2.81 (95% CI 0.39-20.12; comparator: rectal diazepam). No data were available for OR using intravenous diazepam as the comparator.
  
  
  CONCLUSIONS
  Indirect comparisons suggest that intranasal and buccal midazolam share similar efficacy in the treatment of early SE in children. Intranasal midazolam should be used with caution and under clinical monitoring of vital functions. RCTs directly comparing intranasal midazolam with buccal midazolam are required to confirm these findings.
authors: Section of Clinical Neurology, Department of Neurological and Movement Sciences, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. dr.francescobrigo@gmail.com.|Department of Neurology, Franz Tappeiner Hospital, Merano, Italy. dr.francescobrigo@gmail.com.
authors: Francesco
authors: F
authors: Brigo
authors: Department of Neurology, Franz Tappeiner Hospital, Merano, Italy.|Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria.
authors: Raffaele
authors: R
authors: Nardone
authors: Department of Neurology, Franz Tappeiner Hospital, Merano, Italy.
authors: Frediano
authors: F
authors: Tezzon
authors: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria.|Centre for Cognitive Neuroscience Salzburg, Salzburg, Austria.|Department of Public Health Technology Assessment, UMIT, University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria.
authors: Eugen
authors: E
authors: Trinka
mesh_terms: D000278:Administration, Buccal; D000281:Administration, Intranasal; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008874:Midazolam / Q000008:administration & dosage*; D012016:Reference Values; D013226:Status Epilepticus / Q000188:drug therapy*
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam