title: Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia.
abstract: BACKGROUND
  Midazolam is used as an anticonvulsant in neonatology, including newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect the safety and effectiveness of midazolam in these patients.
  
  
  OBJECTIVE
  The objective was to evaluate the anticonvulsant effectiveness and hemodynamic safety of midazolam in hypothermic newborns and to provide dosing guidance.
  
  
  METHODS
  Hypothermic newborns with perinatal asphyxia and treated with midazolam were included. Effectiveness was studied using continuous amplitude-integrated electroencephalography. Hemodynamic safety was assessed using pharmacokinetic-pharmacodynamic modeling with plasma samples and blood pressure recordings (mean arterial blood pressure) under hypothermia.
  
  
  RESULTS
  No effect of therapeutic hypothermia on pharmacokinetics could be identified. Add-on seizure control with midazolam was limited (23% seizure control). An inverse relationship between the midazolam plasma concentration and mean arterial blood pressure could be identified. At least one hypotensive episode was experienced in 64%. The concomitant use of inotropes decreased midazolam clearance by 33%.
  
  
  CONCLUSIONS
  Under therapeutic hypothermia, midazolam has limited add-on clinical anticonvulsant effectiveness after phenobarbital administration. Due to occurrence of hypotension requiring inotropic support, midazolam is less suitable as a second-line anticonvulsant drug under hypothermia.
authors.affiliation: Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Marcel P H
authors.initials: MP
authors.lastname: van den Broek
authors.forename: Henrica L M
authors.initials: HL
authors.lastname: van Straaten
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: Toine
authors.initials: T
authors.lastname: Egberts
authors.forename: Mona C
authors.initials: MC
authors.lastname: Toet
authors.forename: Linda S
authors.initials: LS
authors.lastname: de Vries
authors.forename: Karin
authors.initials: K
authors.lastname: Rademaker
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D062186:Arterial Pressure; D001238:Asphyxia Neonatorum / Q000188:drug therapy*; D004569:Electroencephalography; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D007036:Hypothermia, Induced; D007231:Infant, Newborn; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D008874:Midazolam