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ANESTHETIC PHARMACOLOGY

Doxapram Only Slightly Reduces the Shivering Threshold in Healthy Volunteers

Ryu Komatsu, MD^*, Papiya Sengupta, MD^*, Grigory Cherynak, MD, Anupama Wadhwa, MD^*, Daniel I. Sessler, MD^*, Jin Liu, MD, Harrell E. Hurst, PhD, and Rainer Lenhardt, MD^*

*Outcomes Research^TM Institute, University of Louisville; and Departments of Anesthesiology & Perioperative Medicine, and Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky

Address correspondence and reprint requests to Daniel I. Sessler, MD, Outcomes Research Institute, 501 East Broadway, Suite 210, Louisville, KY 40202. Address e-mail to sessler{at}louisville.edu. On the worldwide web: www.or.org.

We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on 2 days: control and doxapram (IV infusion to a plasma concentration of 2.4 ± 0.8, 2.5 ± 0.9, and 2.6 ± 1.1 µg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t-tests and presented as mean ± sd; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (control: 37.5° ± 0.4°C, doxapram: 37.3° ± 0.4°C; P = 0.290) or the vasoconstriction threshold (36.8° ± 0.7°C versus 36.4° ± 0.5°C; P = 0.110). However, it significantly reduced the shivering threshold from 36.2° ± 0.5°C to 35.7° ± 0.7°C (P = 0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug’s efficacy for treatment of postoperative shivering; however, a reduction of only 0.5°C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole drug.

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