Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined micro- and kappa-agonist) treats shivering better than equianalgesic doses of pure micro-opioid agonists. Meperidine's special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure micro-agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does.Methods
Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 micro gram/ml; and (3) a target plasma alfentanil concentration of 0.2 micro gram/ml. Skin temperatures were maintained near 31 [degree sign] Celsius, and core temperatures were decreased by central-venous infusion of cold lactated Ringer's solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression.Results
Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering.Conclusions
The authors could not confirm the hypothesis that meperidine reduces the gain or maximum intensity of shivering more than alfentanil does. These results suggest that meperidine's special antishivering effect is primarily mediated by a disproportionate reduction in the shivering threshold.