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.
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.
patients requiring general anesthesia
more than 1 previous cesarean delivery
history of uterine atony
emergency cesarean section in labor
Parallel
Oxytocin
DrugOxytocin 10-5M will be added to 3 groups of myometrial strips for 2 hours to induce desensitization.
Carbetocin
DrugIncreasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-10 M to 10-5 M
Calcium
DrugCalcium chloride in the following concentrations:1.25mM, 2.5mM and 5.0mM.
6
Treatment groupsSee each treatment group below.
Motility index
Motility index (MI) is a calculated outcome, based on the formula: frequency/(10 x amplitude). Frequency and amplitude are secondary outcome measures as described below. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
Amplitude of contraction
The maximum extent of uterine muscle contraction, measured in grams (g). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
Frequency of contraction
The number of contractions in uterine muscle (myometrium) over 10 minutes, spontaneously and in response to an agonist. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
Integrated area under response curve (AUC)
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