Dexmedetomidine and meperidine additively reduce the shivering threshold in humans

Stroke. 2003 May;34(5):1218-23. doi: 10.1161/01.STR.0000068787.76670.A4. Epub 2003 Apr 10.


Background and purpose: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adrenergic alpha-Agonists / adverse effects
  • Adrenergic alpha-Agonists / blood
  • Adrenergic alpha-Agonists / pharmacology*
  • Adult
  • Body Temperature / drug effects
  • Carbon Dioxide / blood
  • Depression, Chemical
  • Dexmedetomidine / adverse effects
  • Dexmedetomidine / blood
  • Dexmedetomidine / pharmacology*
  • Drug Synergism
  • Hemodynamics / drug effects
  • Humans
  • Hypothermia, Induced*
  • Male
  • Meperidine / adverse effects
  • Meperidine / blood
  • Meperidine / pharmacology*
  • Oxygen Consumption / drug effects
  • Partial Pressure
  • Receptors, Opioid, mu / agonists
  • Respiration / drug effects
  • Shivering / drug effects*
  • Skin Temperature
  • Tympanic Membrane
  • Vasoconstriction / drug effects
  • Wakefulness / drug effects


  • Adrenergic alpha-Agonists
  • Receptors, Opioid, mu
  • Carbon Dioxide
  • Dexmedetomidine
  • Meperidine