title: Dexmedetomidine and meperidine additively reduce the shivering threshold in humans.
abstract: OBJECTIVE
  Hypothermia might prove to be therapeutically beneficial in stroke victims; however, even mild hypothermia provokes vigorous shivering. Meperidine and dexmedetomidine each linearly reduce the shivering threshold (triggering core temperature) with minimal sedation. We tested the hypothesis that meperidine and dexmedetomidine synergistically reduce the shivering threshold without producing substantial sedation or respiratory depression.
  
  
  METHODS
  We studied 10 healthy male volunteers (18 to 40 years) on 4 days: (1) control (no drug); (2) meperidine (target plasma level 0.3 microg/mL); (3) dexmedetomidine (target plasma level 0.4 ng/mL); and (4) meperidine plus dexmedetomidine (target plasma levels of 0.3 microg/mL and 0.4 ng/mL, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused through a central venous catheter to decrease tympanic membrane temperature by approximately 2.5 degrees C/h; mean skin temperature was maintained at 31 degrees C. An increase in oxygen consumption >25% of baseline identified the shivering threshold. Sedation was evaluated by using the Observer's Assessment of Sedation/Alertness scale. Two-way repeated-measures ANOVA was used to identify interactions between drugs. Data are presented as mean+/-SD; P<0.05 was statistically significant.
  
  
  RESULTS
  The shivering thresholds on the study days were as follows: control, 36.7+/-0.3 degrees C; dexmedetomidine, 36.0+/-0.5 degrees C (P<0.001 from control); meperidine, 35.5+/-0.6 degrees C (P<0.001); and meperidine plus dexmedetomidine, 34.7+/-0.6 degrees C (P<0.001). Although meperidine and dexmedetomidine each reduced the shivering threshold, their interaction was not synergistic but additive (P=0.19). There was trivial sedation with either drug alone or in combination. Respiratory rate and end-tidal Pco2 were well preserved on all days.
  
  
  CONCLUSIONS
  Dexmedetomidine and meperidine additively reduce the shivering threshold; in the small doses tested, the combination produced only mild sedation and no respiratory toxicity.
authors.affiliation: Outcomes Research Institute and the Department of Anesthesiology, Louisville, KY, USA. agdoufas@louisville.edu
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Doufas
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Lin
authors.forename: Mohammad-Irfan
authors.initials: MI
authors.lastname: Suleman
authors.forename: Edwin B
authors.initials: EB
authors.lastname: Liem
authors.forename: Rainer
authors.initials: R
authors.lastname: Lenhardt
authors.forename: Nobutada
authors.initials: N
authors.lastname: Morioka
authors.forename: Ozan
authors.initials: O
authors.lastname: Akça
authors.forename: Yunus M
authors.initials: YM
authors.lastname: Shah
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Bjorksten
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003864:Depression, Chemical; D020927:Dexmedetomidine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008614:Meperidine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D017450:Receptors, Opioid, mu / Q000819:agonists; D012119:Respiration / Q000187:drug effects; D012768:Shivering / Q000187:drug effects*; D012881:Skin Temperature; D014432:Tympanic Membrane; D014661:Vasoconstriction / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D017450:Receptors, Opioid, mu; D002245:Carbon Dioxide; D020927:Dexmedetomidine; D008614:Meperidine