title: Pharmacokinetics of midazolam in resuscitated patients treated with moderate hypothermia.
abstract: BACKGROUND
  Patients who remain comatose after resuscitation are treated with moderate hypothermia. Little is known about the pharmacokinetics of drugs in patients who are treated with moderate hypothermia.
  
  
  OBJECTIVE
  We investigated the pharmacokinetics of midazolam in resuscitated patients treated with moderate hypothermia in comparison to normothermic and non-resuscitated patients.
  
  
  METHODS
  This study was performed on the ICU of a Dutch non-academic hospital. The study population consisted of nine patients in the hypothermic group and eight patients in the control group.
  
  
  METHODS
  The resuscitated patients were cooled to a target temperature of 33 °C and rewarmed 24 h after start of cooling. Midazolam was given as continuous infusion. The control group consisted of non-resuscitated ICU-patients who were treated with midazolam as sedative. Plasma concentration-time data were collected for midazolam and its metabolites.
  
  
  METHODS
  Non-linear mixed effect modelling was used to analyze midazolam population pharmacokinetics and identify possible covariates.
  
  
  RESULTS
  A two-compartment pharmacokinetic model best describes the data. The pharmacokinetic models of the investigated groups are not significantly different. Pharmacokinetic parameter estimates for midazolam for the hypothermic group are a body clearance (CL) of 12.6 l/h, an apparent volume of the central compartment (V1) of 19.1 l, an apparent volume of the peripheral compartment (V2) of 108 l and an intercompartmental clearance (Q) of 18.4 l/h. Estimated parameters for the control group are CL of 14.2 l/h, a V1 of 15.7 l, a V2 of 171 l and Q of 25.6 l/h. In the covariate analysis, body temperature did not significantly improve the model.
  
  
  CONCLUSIONS
  We found no significant difference in the pharmacokinetics of midazolam between resuscitated patients treated with hypothermia during 24 h and the control group.
authors.affiliation: Máxima Medical Centre, Eindhoven/Veldhoven, The Netherlands, d.bastiaans@akf.umcn.nl.
authors.forename: Diane E T
authors.initials: DE
authors.lastname: Bastiaans
authors.forename: Eleonora L
authors.initials: EL
authors.lastname: Swart
authors.forename: Jesse P
authors.initials: JP
authors.lastname: van Akkeren
authors.forename: Luc J J
authors.initials: LJ
authors.lastname: Derijks
mesh_terms: D000368:Aged; D003128:Coma / Q000628:therapy; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D007036:Hypothermia, Induced / Q000379:methods*; D007362:Intensive Care Units; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D008875:Middle Aged; D008954:Models, Biological; D009426:Netherlands; D017711:Nonlinear Dynamics; D011446:Prospective Studies; D012151:Resuscitation; D013696:Temperature; D014018:Tissue Distribution
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam