Minimum effective dose of carbetocin for preventing uterine atony during Cesarean delivery in patients with and without preeclampsia: a biased sequential allocation study.

Purpose: The aggregate data for successful use of carbetocin in patients at high risk of postpartum hemorrhage is fairly large. Nevertheless, there are scant data evaluating carbetocin in patients with preeclampsia and no established optimal dose. Therefore, we aimed to determine the minimum effective dose (the dose effective in 90% of the studied population [ED₉₀]) of carbetocin to prevent intraoperative uterine atony in patients with preeclampsia undergoing Cesarean delivery.

Methods: We based this nonrandomized triple-blinded dose finding study on biased coin sequential allocation design. We enrolled all consenting nonlabouring parturients aged > 18 yr with singleton pregnancy posted for Cesarean delivery under spinal anesthesia (with and without preeclampsia). Doses of carbetocin included 10 μg, 20 μg, 40 μg, 60 μg, 80 μg, 100 μg, or 120 μg, with 20 μg for the first patient of either group and then successively decided by response to the bolus in the previous patient in the respective group. After a "failed" dose of carbetocin bolus, the subsequent patient in that group received the next highest dose. In the case of a "successful" dose, we decreased it to the lower dose with a probability of 1/9; otherwise, it remained unchanged. The determinant of a successful dose was satisfactory uterine tone at 2 min after carbetocin, along with no need for any additional uterotonic intraoperatively.

Results: The ED₉₀ of carbetocin for patients with and without preeclampsia was 96 µg (95% confidence interval [CI], 59 to 114) vs 68 µg (95% CI, 46 to 76).

Conclusion: The dose requirement of carbetocin to prevent intraoperative uterine atony in patients with preeclampsia is 1.5 times greater than in those without the disease.