This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Mokhtarani, M. Articles by Sessler, D. I. Search for Related Content PubMed PubMed Citation Articles by Mokhtarani, M. Articles by Sessler, D. I. Related Collections Pharmacology

---

ANESTHETIC PHARMACOLOGY

Buspirone and Meperidine Synergistically Reduce the Shivering Threshold

Masoud Mokhtarani, MD^*, Adel N. Mahgoub, MD^*, Nobutada Morioka, MD^*, Anthony G. Doufas, MD^*, Michael Dae, MD, Thomas E. Shaughnessy, MD^*, Andrew R. Bjorksten, PhD, and Daniel I. Sessler, MD

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.

This article has been cited by other articles:

				D. I. Sessler Defeating Normal Thermoregulatory Defenses: Induction of Therapeutic Hypothermia Stroke, November 1, 2009; 40(11): e614 - e621. [Abstract] [Full Text] [PDF]

				T. Masamune, H. Sato, K. Okuyama, Y. Imai, H. Iwashita, T. Ishiyama, T. Oguchi, D. I. Sessler, and T. Matsukawa The Shivering Threshold in Rabbits with JM-1232(-), a New Benzodiazepine Receptor Agonist Anesth. Analg., July 1, 2009; 109(1): 96 - 100. [Abstract] [Full Text] [PDF]

				B. P. Meloni, K. Campbell, H. Zhu, and N. W. Knuckey In Search of Clinical Neuroprotection After Brain Ischemia: The Case for Mild Hypothermia (35{degrees}C) and Magnesium Stroke, June 1, 2009; 40(6): 2236 - 2240. [Abstract] [Full Text] [PDF]

				R. Kollmar, P. D. Schellinger, T. Steigleder, M. Kohrmann, and S. Schwab Ice-Cold Saline for the Induction of Mild Hypothermia in Patients With Acute Ischemic Stroke: A Pilot Study Stroke, May 1, 2009; 40(5): 1907 - 1909. [Abstract] [Full Text] [PDF]

				O. Kimberger, C. Held, K. Stadelmann, N. Mayer, C. Hunkeler, D. I. Sessler, and A. Kurz Resistive Polymer Versus Forced-Air Warming: Comparable Heat Transfer and Core Rewarming Rates in Volunteers Anesth. Analg., November 1, 2008; 107(5): 1621 - 1626. [Abstract] [Full Text] [PDF]

				B. P. Meloni, F. L. Mastaglia, and N. W. Knuckey Review: Therapeutic applications of hypothermia in cerebral ischaemia Therapeutic Advances in Neurological Disorders, September 1, 2008; 1(2): 75 - 98. [Abstract] [PDF]

				T. M. Hemmen and P. D. Lyden Induced Hypothermia for Acute Stroke Stroke, February 1, 2007; 38(2): 794 - 799. [Abstract] [Full Text] [PDF]

				T. Pretorius, G. K. Bristow, A. M. Steinman, and G. G. Giesbrecht Thermal effects of whole head submersion in cold water on nonshivering humans J Appl Physiol, August 1, 2006; 101(2): 669 - 675. [Abstract] [Full Text] [PDF]

				R. M. Zweifler, M. E. Voorhees, M. A. Mahmood, and M. Parnell Magnesium Sulfate Increases the Rate of Hypothermia Via Surface Cooling and Improves Comfort Stroke, October 1, 2004; 35(10): 2331 - 2334. [Abstract] [Full Text] [PDF]

				M. A. De Georgia, D. W. Krieger, A. Abou-Chebl, T. G. Devlin, M. Jauss, S. M. Davis, W. J. Koroshetz, G. Rordorf, and S. Warach Cooling for Acute Ischemic Brain Damage (COOL AID): A feasibility trial of endovascular cooling Neurology, July 27, 2004; 63(2): 312 - 317. [Abstract] [Full Text] [PDF]

				L. G. Futterman and L. Lemberg The Significance of Hypothermia in Preserving Ischemic Myocardium Am. J. Crit. Care., January 1, 2004; 13(1): 79 - 84. [Full Text] [PDF]

				K. Okuyama, T. Matsukawa, M. Ozaki, D. I. Sessler, T. Nishiyama, M. Imamura, and T. Kumazawa Doxapram Produces a Dose-Dependent Reduction in the Shivering Threshold in Rabbits Anesth. Analg., September 1, 2003; 97(3): 759 - 762. [Abstract] [Full Text] [PDF]

				A. G. Doufas, A. Wadhwa, C.-M. Lin, Y. M. Shah, K. Hanni, and D. I. Sessler Neither Arm nor Face Warming Reduces the Shivering Threshold in Unanesthetized Humans Stroke, July 1, 2003; 34(7): 1736 - 1740. [Abstract] [Full Text] [PDF]

				A. G. Doufas, C.-M. Lin, M.-I. Suleman, E. B. Liem, R. Lenhardt, N. Morioka, O. Akca, Y. M. Shah, A. R. Bjorksten, and D. I. Sessler Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold in Humans Stroke, May 1, 2003; 34(5): 1218 - 1223. [Abstract] [Full Text] [PDF]

				S. R. Dixon, R. J. Whitbourn, M. W. Dae, E. Grube, W. Sherman, G. L. Schaer, J. S. Jenkins, D. S. Baim, R. J. Gibbons, R. E. Kuntz, et al. Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1928 - 1934. [Abstract] [Full Text] [PDF]