Dexmedetomidine and meperidine additively reduce the shivering threshold in humans

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 mug/mL); ( 3) dexmedetomidine ( target plasma level 0.4 ng/mL); and ( 4) meperidine plus dexmedetomidine ( target plasma levels of 0.3 mug/mL and 0.4 ng/mL, respectively). Lactated Ringer's solution (approximate to4degreesC) was infused through a central venous catheter to decrease tympanic membrane temperature by approximate to2.5degreesC/h; mean skin temperature was maintained at 31 degreesC. 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 degreesC ( 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.