Randomized Double-Blinded Clinical Trial of Oxytocin Bolus versus Infusion in Elective Cesarean (INBOX Trial)

Oxytocin is the most widely used uterotonic for postpartum hemorrhage prevention, yet high-quality data comparing bolus versus infusion administration are limited. Given the very high uterine blood flow at term, rapid achievement of uterine tone is critical to minimize blood loss. We hypothesized that bolus administration leads to a greater likelihood of attaining adequate uterine tone at 2 minutes.

In this randomized, double-blinded clinical trial, 121 patients undergoing elective cesarean delivery under spinal anesthesia were randomized 1:1 to receive oxytocin by bolus or infusion after cord clamping. Masked study drugs were prepared by the investigational pharmacy to maintain blinding of the anesthesiologist, obstetrician, and study personnel. The primary end point was adequate uterine tone at 2 minutes. Secondary end points included patient satisfaction, time to adequate uterine tone, quantitative blood loss, postpartum hemorrhage (blood loss greater than 1000 mL), and safety measures (heart rate, blood pressure, phenylephrine dose, chest pain, nausea/vomiting, additional uterotonic use, and intensive care unit admission).

Of 121 patients enrolled, 115 were analyzable (6 screen failures received no study drug); 114/115 received oxytocin per protocol. Baseline characteristics were similar between groups. Adequate uterine tone at 2 minutes (primary end point) was similar in bolus (50/60, 83.3%) vs infusion (43/55, 78.2%), P = .483. Patient satisfaction scores were also not significantly different (P = .495) between the two arms, with both the bolus and infusion arms having medians and interquartile range (IQRs) of (10 [IQR 10-10]). Median blood loss was slightly lower with bolus (558 mL [IQR 429-733]) vs infusion (687 mL [IQR 480-826], P = .0438; Hodges-Lehmann estimate of 82 mL [95% confidence interval {CI}, 2-168 mL]). Phenylephrine dosage and rates of postpartum hemorrhage, nausea, and additional uterotonic use were similar between groups (all P > .28). Rates of postpartum hemorrhage, hypotension, phenylephrine use, nausea, and additional uterotonic use were similar.

There was no statistically significant difference in the frequency of achieving adequate uterine tone at 2 minutes between oxytocin given by infusion or bolus. Although the bolus group demonstrated statistically lower blood loss, the magnitude of this difference was small (upper confidence limit of 168 mL) and is unlikely to be clinically significant. Both methods showed comparable safety profiles.