Effect of Extracellular Calcium on Carbetocin Mediated Contractility in Human Myometrium

Effect of Extracellular Calcium on Carbetocin Mediated Contractility in Human Myometrium: An Ex-Vivo Study

Postpartum hemorrhage (PPH) continues to be an increasing problem globally. Uterotonics play an essential role in the pharmacological management of uterine atony. Carbetocin, a long acting analog of oxytocin has been recommended as a first line uterotonic for PPH prophylaxis at cesarean delivery. Considering many woman have associated comorbidities and are at high risk of PPH, finding alternative pharmacological agents is essential. Calcium is a key factor for myometrial contractions and calcium blood levels can be low at the end of pregnancy. Both hypocalcemia and hypercalcemia could lead to a decrease in myometrial contractions. It is already been demonstrated that in both desensitized and naïve myometrium, normocalcemia provides a better uterine tone compared to hypo and hypercalcemia when oxytocin is given as the first uterotonic drug.

Currently, the role of extracelullar calcium in carbetocin- induced contractility is unknown. This will be the first ex vivo study to test the effects of extracellular calcium on oxytocin pretreated and naive myometrium. The results of this study will provide evidence on the use of this safe drug in clinical practice, particularly in women with labour arrest, and provide alternative pharmacological strategies to both prevention and treatment of PPH, thus improving our clinical practice.

The investigators hypothesize that extracellular normocalcemia would provide superior carbetocin-mediated contractility in both naive and oxytocin-pretreated myometrium compared with hypercalcemia and hypocalcemia.

Inclusion Criteria:

• non-laboring women with gestational age between 37 to 41 weeks
• not exposed to exogenous oxytocin, scheduled for a primary or first repeat cesarean delivery under neuraxial anesthesia.

Exclusion criteria:

• patients requiring general anesthesia
• more than 1 previous cesarean delivery
• history of uterine atony
• emergency cesarean section in labor
• patients using medications that could affect myometrial contractility such as nifedipine, labetalol, or magnesium sulphate.
• patients with any condition of predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, severe preeclampsia, macrosomia, polyhydroamnios, large uterine fibroids, chorioamnionitis, previous history of postpartum bleeding.