Comparative dose-response study on the infusion of norepinephrine combined with intravenous ondansetron versus placebo for preventing hypotension during spinal anesthesia for cesarean section: a randomised controlled trial

Background:Ondansetron has been reported to attenuate the incidence of spinal anaesthesia-induced hypotension (SAIH) and norepinephrine requirement during caesarean section. However, no quantitative study has evaluated the extent of this effect. This study aimed to determine the dose-response of prophylactic infusion of norepinephrine to prevent SAIH in parturients who received intravenous ondansetron or placebo before spinal anaesthesia for caesarean section. The median effective dose (ED50) and 90% effective dose (ED90) were compared to evaluate the effect of ondansetron versus placebo on the norepinephrine requirement.Materials and methods:One hundred fifty parturients undergoing caesarean section were randomized to receive either 0.1 mg/kg ondansetron (group O) or saline control (group C) 10 min before spinal anaesthesia. The parturients were randomly assigned to one of five different norepinephrine infusion groups: 0.02, 0.04, 0.06, 0.08 or 0.10 mu g/kg/min. An effective infusion dose of norepinephrine was defined as non-occurrence of hypotension during the study period. The values for ED50 and ED90 of norepinephrine infusion were determined using probit regression. Differences between the two groups were evaluated by comparing the relative median potency with 95% CIs.Results:The ED50 values were 0.033 (95% CIs, 0.024-0.043) mu g/kg/min in group C and 0.021 (95% CIs, 0.013-0.029) mu g/kg/min in group O. The ED90 values were 0.091 (95% CIs 0.068-0.147) mu g/kg/min in group C and 0.059 (95% CIs 0.044-0.089) mu g/kg/min in group O, respectively. The estimate of the relative median potency for norepinephrine in group C versus group O was 0.643 (95% CIs, 0.363-0.956). The incidence of side effects was comparable between groups. No significant difference in neonatal outcomes.Conclusion:Intravenous ondansetron 0.1 mg/kg before spinal anaesthesia significantly reduced the dose requirement of prophylactic norepinephrine infusion in parturients undergoing elective caesarean section. This finding is potentially useful for clinical practice and further research.