title: Concentrations of remifentanil, propofol, fentanyl, and midazolam during rewarming from therapeutic hypothermia.
abstract: BACKGROUND
  The clearance of sedatives and analgesics may be reduced by therapeutic hypothermia. However, little is known about the concentrations of such drugs during rewarming. The aim of this study was to describe the serum concentrations of sedatives and analgesics during rewarming from therapeutic hypothermia.
  
  
  METHODS
  Blood samples were collected for quantification of drug concentrations in 22 patients given analgesia/sedation with either remifentanil/propofol or fentanyl/midazolam during rewarming from therapeutic hypothermia (33-34°C) after cardiac arrest. Samples for were drawn before (-2 h) and during rewarming (0-8 h). Linear mixed effects models were used to describe serum concentrations and adjust for rates of infusion during rewarming from therapeutic hypothermia.
  
  
  RESULTS
  Subjects with samples analyzed were remifentanil (n = 8), propofol (n = 14), fentanyl (n = 8), and midazolam (n = 8). Age, body mass index, and simplified acute physiology score II [mean (standard deviation)] were 64 (14.2) years, 27.3 (3.7) kg/m(2), and 69 (13.2), respectively. While the concentration of fentanyl was not significantly affected by temperature, concentrations of remifentanil, propofol, and midazolam decreased with core temperature by 16%, 12%, and 11% (mean values) from 33°C to 37°C after adjusting for rates of infusion, respectively.
  
  
  CONCLUSIONS
  Concentrations of remifentanil, propofol, and midazolam decreased during rewarming from therapeutic hypothermia when adjusting for rates of infusion. No changes were demonstrated for fentanyl.
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: T W
authors.initials: TW
authors.lastname: Bjelland
authors.forename: P
authors.initials: P
authors.lastname: Klepstad
authors.forename: B O
authors.initials: BO
authors.lastname: Haugen
authors.forename: T
authors.initials: T
authors.lastname: Nilsen
authors.forename: O
authors.initials: O
authors.lastname: Salvesen
authors.forename: O
authors.initials: O
authors.lastname: Dale
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000097:blood* / Q000493:pharmacokinetics; D015992:Body Mass Index; D001831:Body Temperature; D003131:Combined Modality Therapy; D005260:Female; D005283:Fentanyl / Q000097:blood* / Q000493:pharmacokinetics; D006323:Heart Arrest / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood* / Q000493:pharmacokinetics; D007036:Hypothermia, Induced; D008297:Male; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000097:blood* / Q000493:pharmacokinetics; D008875:Middle Aged; D008954:Models, Biological; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics; D015742:Propofol / Q000097:blood* / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D000077208:Remifentanil; D017694:Rewarming
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives; D010880:Piperidines; D000077208:Remifentanil; D008874:Midazolam; D005283:Fentanyl; D015742:Propofol