Buspirone and meperidine synergistically reduce the shivering threshold

Mild hypothermia (i.e., 34 degreesC) may prove therapeutic for patients wit h stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidin e synergistically reduces the shivering threshold (triggering tympanic memb rane temperature) to at least 34 degreesC while producing little sedation o r respiratory depression. Eight volunteers each participated on four random ly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV me peridine (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 withou t drugs. Core hypothermia was induced by infusion of lactated Ringer's solu tion 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-do se buspirone and 33.4 degreesC +/- 0.3 degreesC during large-dose meperidin e. The threshold during the combination of the two drugs was 33.4 degreesC +/- 0.7 degreesC. There was minimal sedation on the buspirone and combinati on 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 a lone slightly reduced the shivering threshold. The combination of small-dos e buspirone and small-dose meperidine acted synergistically to reduce the s hivering threshold while causing little sedation or respiratory toxicity.