Buspirone and meperidine synergistically reduce the shivering threshold

Mild hypothermia (i.e., 34 degreesC) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degreesC while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 mug/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 mug/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degreesC. The control shivering threshold was 35.7 degreesC +/-0.2 degreesC. The threshold was 35.0 degreesC +/-0.8 degreesC during large-dose buspirone and 33.4 degreesC +/- 0.3 degreesC during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degreesC +/- 0.7 degreesC. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal Pco(2) increased similar or equal to 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity.