Isoflurane produces marked and nonlinear decreases in the vasoconstriction and shivering thresholds.

In summary, we present a new model for evaluating thermoregulatory effects of drug administration, pregnancy, illness, etc. Specifically, we experimentally manipulated both skin and core temperatures, and subsequently compensated for the changes in skin temperature using the relationships between skin and core contributions to thermoregulatory control. We thus were able to report our results for warm- and cold-responses in terms of calculated core-temperature thresholds at a single designated skin temperature. Advantages of this model include its being nearly noninvasive and requiring relatively little core temperature manipulation. Using this technique, we have shown that the shape and magnitude of thermoregulatory impairment produced by various anesthetic drugs differs. Propofol linearly increases the sweating threshold and linearly decreases the vasoconstriction and shivering threshold. In contrast, volatile anesthetics produce a nonlinear reduction in the major cold-response thresholds, reducing the vasoconstriction and shivering thresholds disproportionately at higher anesthetic concentrations. Midazolam not only produces a different magnitude of thermoregulatory impairment, but also a novel pattern of threshold changes. Anesthetic-induced thermoregulatory impairment thus depends both on anesthetic type and dose.