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 abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. Methods: Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control 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 alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. 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 +/- 0.037 degrees C . ng(-1) . ml; r(2) = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C . ng(-1) . ml), the sweating threshold 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). Similarly, 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 sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.