Ondansetron does not reduce the shivering threshold in healthy volunteers

Background. Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans. Methods. Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P < 0.05 was taken as significant. Results. Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximate to 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4)degrees C, ondansetron 37.6 (0.3)degrees C, P=0.16), vasoconstriction (37.0 (0.5)degrees C vs 37.1 (0.3)degrees C; P=0.70), or shivering threshold (36.3 (0.5)degrees C vs 36.3 (0.6)degrees C; P=0.76). No sedation was observed on either study day. Conclusions. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.