ALFENTANIL SLIGHTLY INCREASES THE SWEATING THRESHOLD AND MARKEDLY REDUCES THE VASOCONSTRICTION AND SHIVERING THRESHOLDS

Background: Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abu se. In most cases, hypothermia results largely from drug-induced inhib ition of normal thermoregulatory control. Although opioids are given t o a variety of patients, the thermoregulatory effects of opioids in hu mans remain unknown. Accordingly, the hypothesis that opioid administr ation impairs thermoregulatory control was tested. Methods: Eight volu nteers were studied, each on 3 days: (1) a target total plasma alfenta nil concentration of 100 ng/ml, (2) control (no drug), and (3) a targe t alfentanil concentration of 300 ng/ml. Each day, skin and core tempe ratures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and sh ivering. Mathematical compensations were made for changes in skin temp erature using the established linear cutaneous contributions to contro l of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfen tanil concentrations, the individual concentration-response relationsh ip was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrat ions. Results: In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C . ng(-1) . ml; r(2) = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C . ng(-1) . ml; r (2) = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- 0.03 7 degrees C . ng(-1) . ml; r(2) = 0.98 +/- 0.04). In terms of total al fentanil concentration (degrees C . ng(-1) . ml), the sweating thresho ld increased according to the equation: threshold (degrees C) = 0.0014 [alfentanil] + 37.2 (r(2) = 0.33). In contrast, alfentanil produced a Linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C)= -0.0049[alfentanil] + 36.7 (r(2) = 0.64). Simil arly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r(2) = 0.70). Conclusions: The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a sight increase in the sweatin g threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.