title: Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.
abstract: BACKGROUND
  Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans.
  
  
  METHODS
  This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41 degrees to 50 degrees C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model.
  
  
  RESULTS
  Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1 degrees C at baseline to 48.4 degrees and 49.1 degrees C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients gamma during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2 degrees C) and a decrease in the steepness of the curve (decreased gamma from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and gamma).
  
  
  CONCLUSIONS
  As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.
authors.affiliation: Human Pharmacology Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Luis I
authors.initials: LI
authors.lastname: Cortinez
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Hsu
authors.forename: Sam T
authors.initials: ST
authors.lastname: Sum-Ping
authors.forename: Christopher
authors.initials: C
authors.lastname: Young
authors.forename: John C
authors.initials: JC
authors.lastname: Keifer
authors.forename: David
authors.initials: D
authors.lastname: Macleod
authors.forename: Kerri M
authors.initials: KM
authors.lastname: Robertson
authors.forename: David R
authors.initials: DR
authors.lastname: Wright
authors.forename: Eugene W
authors.initials: EW
authors.lastname: Moretti
authors.forename: Jacques
authors.initials: J
authors.lastname: Somma
mesh_terms: D000328:Adult; D000465:Algorithms; D000700:Analgesics; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D017711:Nonlinear Dynamics; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D000077208:Remifentanil; D015656:Respiratory Mechanics / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D010880:Piperidines; D020927:Dexmedetomidine; D000077208:Remifentanil