ANESTHETIC PHARMACOLOGY INTERNATIONAL SOCIETY FOR ANAESTHETIC PHARMACOLOGY SECTION EDITOR JAMES G. BOVILL Neither Nalbuphine nor Atropine Posses Special Antishivering Activity Robert Greif, MD*†, Sonja Laciny, MD*†, Angela M. Rajek, MD*‡, Merlin D. Larson, MD*, Andrew R. Bjorksten, PhD§, Anthony G. Doufas, MD*, Maryam Bakhshandeh, MD*, Masoud Mokhtarani, MD*, and Daniel I. Sessler, MD *Department of Anesthesia and Perioperative Care, University of California–San Francisco, San Francisco, California; †Department of Anesthesiology and Intensive Care Medicine, Donauspital/SMZO-Vienna, Austria; ‡Department of Cardiothoracic and Vascular Anesthesia, University of Vienna, Vienna, Austria; §Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Australia; and Outcomes Research™ Institute and Department of Anesthesiology, University of Louisville, Kentucky, and Ludwig Boltzmann Institute, University of Vienna, Austria The special antishivering action of meperidine may be mediated by its  or anticholinergic actions. We therefore tested the hypotheses that nalbuphine or atropine de- creases the shivering threshold more than the vasocon- striction threshold. Eight volunteers were each evaluated on four separate study days: 1) control (no drug), 2) small- dose nalbuphine (0.2 g/mL), 3) large-dose nalbuphine (0.4 g/mL), and 4) atropine (1-mg bolus and 0.5 mg/h). Body temperature was increased until the patient sweated and then decreased until the patient shivered. Nalbuphine produced concentration-dependent de- creases (mean  sd) in the sweating (-2.5  1.7°C · g -1 · mL; r 2 = 0.75  0.25), vasoconstriction (-2.6  1.7°C · g -1 · mL; r 2 = 0.75  0.25), and shivering (-2.8  1.7°C · g -1 · mL; r 2 = 0.79  0.23) thresholds. Atropine significantly increased the thresholds for sweat- ing (1.0°C  0.4°C), vasoconstriction (0.9°C  0.3°C), and shivering (0.7°C  0.3°C). Nalbuphine reduced the vaso- constriction and shivering thresholds comparably. This differs markedly from meperidine, which impairs shiver- ing twice as much as vasoconstriction. Atropine increased all thresholds and would thus be expected to facilitate shivering. Our results thus fail to support the theory that activation of -opioid or central anticholinergic receptors contribute to meperidine’s special antishivering action. (Anesth Analg 2001;93:620 –7) C ore temperature in humans is well maintained because even small deviations trigger effective thermoregulatory defenses, such as sweating and vasoconstriction (1). Because the normal sweating and vasoconstriction thresholds differ by only 0.2°C (2), normal body temperature is sometimes referred to as a “set point.” Opioids (3), like general anes- thetics, impair thermoregulatory defenses, produc- ing a characteristic increase in the sweating thresh- old (triggering core temperature) combined with a synchronous reduction in the vasoconstriction and shivering thresholds. The result is a marked increase in the sweating-to-vasoconstriction interthreshold range— the temperatures between which autonomic thermoreg- ulatory defenses are not triggered. Meperidine is a far more effective treatment for shivering than pure -receptor agonists, such as mor- phine (4). The special efficacy of meperidine is mani- fested by a disproportionate reduction in the shivering threshold (5) without any reduction in the gain of shivering (6). Meperidine thus reduces the shivering thresholds twice as much as the vasoconstriction threshold at any given concentration (5). This is in distinct contrast to general anesthetics and pure -receptor opioids that comparably reduce the thresh- olds for each major cold defense (7). The special antishivering action of meperidine may in part be mediated by its agonist activity at  recep- tors;  activity constitutes approximately 10% of me- peridine’s total opioid action (8). A clinically impor- tant contribution of  receptors is supported by the observation that meperidine reduces the intensity of cold-induced shivering even in the presence of mod- erate doses of naloxone, which presumably block  receptors while having little effect on the relatively Supported by National Institutes of Health Grant GM58273 (Be- thesda, MD), the Joseph Drown Foundation (Los Angeles, CA), and the Commonwealth of Kentucky Research Challenge Trust (Louis- ville, KY). Mallinckrodt Anesthesiology Products, Inc. (St. Louis, MO), donated the thermocouples. Accepted for publication May 1, 2001. Address correspondence and reprint requests to Dr. Sessler, Uni- versity of Louisville, Abell Administration Center, Room 217, 323 East Chestnut St., Louisville, KY 40202-3866. Address e-mail to sessler@louisville.edu. ©2001 by the International Anesthesia Research Society 620 Anesth Analg 2001;93:620–7 0003-2999/01