Published Online
on April 10, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on December 5, 2002
Accepted on December 10, 2002

Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold in Humans

Anthony G. Doufas MD, PhD^*; Chun-Ming Lin MD; Mohammad-Irfan Suleman MD; Edwin B. Liem MD; Rainer Lenhardt MD; Nobutada Morioka MD; Ozan Akça MD; Yunus M. Shah MD; Andrew R. Bjorksten PhD; and Daniel I. Sessler MD

From the Outcomes Research Institute and the Department of Anesthesiology (A.G.D., C.-M.L., M.-I.S., E.B.L., R.L., N.M., O.A., Y.M.S., D.I.S.), Louisville, Ky; the Department of Anesthesiology (C.-M.L.), Chang Gung Memorial Hospital, Taipei, Taiwan; the Department of Anesthesia, Tokyo Women's Medical College (N.M.), Tokyo, Japan; the Department of Anaesthesia (A.R.B.), Royal Melbourne Hospital, Parkville, Australia; and the Ludwig Boltzmann Institute (D.I.S.), University of Vienna, Vienna, Austria.

^* To whom correspondence should be addressed. E-mail: agdoufas{at}louisville.edu.

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 µg/mL); (3) dexmedetomidine (target plasma level 0.4 ng/mL); and (4) meperidine plus dexmedetomidine (target plasma levels of 0.3 µg/mL and 0.4 ng/mL, respectively). Lactated Ringer's solution (4°C) was infused through a central venous catheter to decrease tympanic membrane temperature by 2.5°C/h; mean skin temperature was maintained at 31°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°C; dexmedetomidine, 36.0±0.5°C (P<0.001 from control); meperidine, 35.5±0.6°C (P<0.001); and meperidine plus dexmedetomidine, 34.7±0.6°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.

Key words: body temperature regulation • dexmedetomidine • hypothermia • meperidine • stroke • temperature

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