CLONIDINE COMPARABLY DECREASES THE THERMOREGULATORY THRESHOLDS FOR VASOCONSTRICTION AND SHIVERING IN HUMANS

Background. Clonidine stops postoperative shivering, but its underlying mechanism of action is unknown. Clonidine may impair central control of thermoregulation or act on peripheral receptors. Accordingly, the authors tested the hypothesis that clonidine reduces both the vasoconstriction and shivering thresholds, a pattern consistent with central thermoregulatory impairment. Methods. Seven healthy volunteers participated in the study. Thermoregulatory vasoconstriction was evaluated using forearm minus fingertip, skin-temperature gradients; values exceeding 4-degrees-C were considered to be significant vasoconstriction. Systemic oxygen consumption (VO2) was measured with a canopy system. In addition, shivering was qualitatively evaluated using a simple scale, graduated from 0 (no shivering) to 2 (intense shivering). The tympanic membrane temperatures triggering significant vasoconstriction and grade 1 shivering were considered to be the thresholds for the two thermoregulatory responses. Measurements were performed after a 10-min steady state period and during cooling by central venous infusion of Ringer's lactate solution at 4-degrees-C. Each subject was evaluated at two sessions, separated by at least 48 h. They were randomly and blindly assigned to received either an intravenous bolus of 75 mug clonidine or a placebo before cooling. When the shivering score equaled 2, 75 mug clonidine was injected intravenously, and repeated if necessary, to completely stop shivering. Results: Clonidine significantly decreased the thermoregulatory threshold for shivering by 0.6 +/- 0.3-degrees-C (mean +/- SD). Similarly, the threshold for cutaneous vasoconstriction was significantly reduced by 0.5 +/- 0.2-degrees-C. Additional clonidine administration always stopped shivering, at whatever temperature it occurred. Conclusions: This study confirms that clonidine administration stops shivering, and suggests that it acts by impairing central thermoregulatory control. That an additional dose of clonidine stops shivering in subjects already given one dose, indicates that the effect of clonidine is dose dependent.