Association of postpartum oxytocin dose and postpartum bleeding outcomes in nulliparous patients at term

Postpartum hemorrhage is a leading cause of morbidity and mortality. The use of prophylactic oxytocin in the third stage of labor is globally accepted as standard of care for the prevention of postpartum hemorrhage; however, the most effective dose of oxytocin is unknown. While studies suggest a possible benefit of higher doses of postpartum prophylactic oxytocin, results are inconclusive, and data are limited.

Our objective was to compare rates of postpartum hemorrhage and the need for additional postpartum hemorrhage interventions between high-dose (80 international units) and low-dose (10-30 international units) postpartum oxytocin regimens.

Secondary analysis of a multicenter randomized control trial of 2404 nulliparous women with term singleton pregnancies that investigated immediate vs delayed pushing in women in the second stage of labor (5/2014-12/2017). Postpartum oxytocin regimens were ascertained from each of the 6 participating centers and categorized as high-dose (80 international units/500 mL over 1-4 hours after placental delivery) and low-dose (10-30 international units/500-1000 mL over 1-4 hours). The primary outcome was a composite of uterotonic use after initial postpartum oxytocin, any blood transfusion, and postpartum hemorrhage. Postpartum hemorrhage was defined as estimated blood loss >500 mL after vaginal delivery and >1000 mL after cesarean delivery. Secondary outcomes included individual composite components and select bleeding outcomes. Logistic regression using covariates identified as significant in parsimonious modeling were used to estimate adjusted odds ratios and 95% confidence intervals using the low-dose group as the reference. Dose effect analysis by total dose and effect modification by mode of delivery were also performed.

All 2404 patients from the primary trial were included: 455 (19%) in the high-dose group and 1949 (81%) in the low-dose group. Women in the high-dose group were more likely to be younger, African American, obese, have magnesium sulfate exposure, and achieve vaginal delivery. Compared to low-dose oxytocin, patients receiving high-dose oxytocin had lower odds of the primary composite outcome (adjusted odds ratio 0.53, 95% confidence interval 0.34-0.82), primarily driven by decreased odds of postpartum hemorrhage (adjusted odds ratio 0.44, 95% confidence interval 0.27-0.72). While frequencies of other secondary outcomes were lower in the high-dose group, there was no significant difference in odds of these outcomes after adjustment. Analysis of dose effect by total dose between low- (10-20 international units), moderate- (30 international units), and high- (80 international units) dose oxytocin revealed a decreased odds of the primary composite outcome with moderate- and high-dose (moderate-dose: odds ratio 0.57, 95% confidence interval 0.41-0.80; high-dose: odds ratio 0.39, 95% confidence interval 0.25-0.61; interaction P<.01).The effect of oxytocin dose on the primary outcome did not differ by delivery mode (interaction P=.35).

High-dose postpartum oxytocin was associated with lower rates of postpartum hemorrhage than lower oxytocin doses. Results appeared consistent for both vaginal and cesarean deliveries (at second stage given primary trial). Given the widespread use of oxytocin globally and its relatively low cost, future multicenter trials of postpartum oxytocin dose are warranted.