carbetocin at elective cesarean deliveries: a dose-finding study in women with twin pregnancy.

Conditions: Postpartum Hemorrhage; Twin

Summary: poor uterine tone after the birth of a baby can cause excess bleeding (called postpartum hemorrhage or pph). this is a major cause of maternal death worldwide. uterotonic drugs are used to improve the muscle tone of the uterus after birth, and these are effective at reducing the incidence of pph. the society of obstetricians and gynecologists of canada (sogc) has recommended a single dose of 100 mcg of carbetocin at elective cesarean delivery to promote uterine contraction. in a study performed at mount sinai hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. in these dose-finding studies, women with multiple pregnancies have been excluded. because women with multiple pregnancy have a higher risk of severe pph, uterine atony, hysterectomy, prolonged hospital stay and death, it is plausible that a higher dose of carbetocin is required. this question remains unanswered. the hypothesis is that the ed90 of carbetocin in women with twin pregnancy undergoing elective cesarean delivery under regional anesthesia is greater than 20 mcg but less than 100 mcg.

there is a lack of consensus as to what the optimal uterotonic regime is globally. furthermore, variability in the international guidelines regarding the choice of first line uterotonic in prevention of pph adds to the confusion. with the widespread availability of carbetocin in some developed countries, including canada, the question of which uterotonic to adopt and at which dose becomes even more difficult to ascertain. studies that have currently been published suggest the ed90 doses of carbetocin and oxytocin provide adequate uterine contraction with possibly fewer side effects associated with the lower dose regimens. there is evidence to suggest that lower doses of both carbetocin provide equivalent uterine contractions with a better side effect profile in patients with a singleton pregnancy. however, there is no clinical dosing data specifically for patients with twin pregnancy. the results of our study will provide guidance to obstetric and anesthetic providers worldwide when deciding what dose of carbetocin to use in women with twin pregnancy.

Eligibility criteria:
inclusion criteria: * twin pregnancy * elective cesarean delivery under regional anesthesia * gestational age ≥ 36 weeks * no known additional risk factors for postpartum hemorrhage * written informed consent to participate in this study exclusion criteria: * refusal to give written informed consent * allergy or hypersensitivity to oxytocin * conditions that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, severe preeclampsia (as defined by sogc guidelines (25)), polyhydramnios, uterine fibroids, previous history of uterine atony resulting in pph, or bleeding diathesis and obesity, defined as pre-pregnancy bmi \>40 * hepatic, renal, and vascular disease * use of general anesthesia prior to the administration of the study drug

Keywords: pregnancy twins postpartum hemorrhage carbetocin uterotonic cesarean delivery