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Departments of *Anesthesia and Radiology, University of California, San Francisco; Department of Anaesthesia, Royal Melbourne Hospital, Parkville, Australia; Outcomes Research Institute, Department of Anesthesiology, University of Louisville, Kentucky; and the Ludwig Boltzmann Institute, University of Vienna, Austria
Address correspondence and reprint requests to Daniel I. Sessler, University of Louisville, Abell Administration Center, Room 217, 323 E. Chestnut St., Louisville, KY 40202-3866. Address e-mail to sessler{at}louisville.edu
Mild hypothermia (i.e., 34°C) 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°C 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 µg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 µg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer’s solution at 4°C. The control shivering threshold was 35.7°C ± 0.2°C. The threshold was 35.0°C ± 0.8°C during large-dose buspirone and 33.4°C ± 0.3°C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4°C ± 0.7°C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased 
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.
IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.
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