Prophylactic oxytocin infusion rate and adequate uterine tone in repeat cesarean delivery: a randomized dose-response trial

Background The dose-response relationship of an infusion-only prophylactic oxytocin regimen in women undergoing repeat cesarean delivery remains uncertain. We evaluated adequate uterine tone at six dose levels (saline placebo at 0 IU/h and five active infusion rates of 4–20 IU/h) and estimated the originally targeted ED90. Methods In this single-center, randomized, double-blind dose-finding trial, 120 women aged 21–34 years undergoing elective repeat cesarean delivery before labor were assigned to saline placebo (0 IU/h) or oxytocin infusion at 4, 8, 12, 16, or 20 IU/h immediately after fetal delivery, without an initial bolus. The primary outcome was adequate uterine tone (score ≥ 7 on a 0–10 scale) at 3 min, assessed before rescue uterotonics. Logistic regression was the primary dose-response model; probit regression, an asymmetric complementary log-log model, isotonic regression, and assumptions for the two missing primary outcomes were examined in additional analyses. Results Primary outcome data were available for 118 women. The observed adequate-tone rate increased from 5.3% (1/19) in the placebo (0 IU/h) group to 90.0% (18/20) at 20 IU/h. In the primary logistic analysis, the estimated ED50 was 9.92 IU/h (95% confidence interval [CI], 7.72–12.09 IU/h), and the post hoc ED80 was 16.62 IU/h (95% CI, 13.93–20.80 IU/h). The logistic model-estimated ED90 was 20.54 IU/h (95% CI, 17.00–26.50 IU/h), with a point estimate above the highest tested rate of 20 IU/h. The requirement for rescue oxytocin decreased with increasing infusion rate ( P < 0.001). Estimated blood loss and recorded potential oxytocin-related adverse events did not differ significantly among groups; this trial was not powered for hemorrhage or uncommon adverse events. Conclusion In this selected population, adequate uterine tone increased across the tested dose levels of 0–20 IU/h. The model-estimated ED90 point estimate lay outside the tested range and depended on extrapolation. An infusion rate around 20 IU/h should be viewed as a candidate for further evaluation, not a definitive recommended dose. Findings should not be extrapolated to bolus-plus-infusion regimens or laboring and emergency cesarean deliveries. Clinical Trial Registration https://www.chictr.org.cn/showproj.html?proj=39583 , Chinese Clinical Trial Registry, ChiCTR1900023469, registered on May 30, 2019.