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 (trigging core temperatures) in humans.
Ten healthy volunteers were studied on two days: Control and Ondansetron (intravenous infusion to plasma concentrations of 278 (57) ng mL−1, 234 (55) ng mL−1, and 243 (58) ng mL−1at the sweating, vasoconstriction, and shivering thresholds, respectively); this corresponded to ≈50 mg of ondansetron which is roughly ten times the dose used for postoperative nausea and vomiting. 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 analyzed with paired t tests and presented as means (SD)s; P<0.05 was statistically significant.
Ondansetron did not change the sweating (Control: 37.4 (0.4)°C, Ondansetron: 37.6 (0.3)°C, P=0.16), vasoconstriction (37.0 (0.5) vs. 37.1 (0.3)°C; P=0.70), or shivering threshold (36.3 (0.5) vs. 36.3 (0.6)°C; P=0.76). No sedation was observed on either study day.
Ondansetron, therefore, appears to have little potential for facilitating induction of therapeutic hypothermia.