Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2.

PURPOSE: The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED95) undergoing elective Cesarean delivery under spinal anesthesia.

METHODS: One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 μg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects.

RESULTS: Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin.

CONCLUSIONS: In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 μg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 μg. This trial was registered at www.clinicaltrials.gov (NCT01428817).