Effect of Co-administration of Carbetocin and Calcium Chloride on Uterine Tone in Patients Undergoing Elective Cesarean Delivery

Effect of Co-administration of Carbetocin and Calcium Chloride on Uterine Tone in Patients Undergoing Elective Cesarean Delivery: a Double-blind Randomized Control Trial

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality, and its severity has been increasing globally, including in high-income countries. The most common cause of PPH is uterine atony occurring in about 70% of cases. Uterotonic agents, like oxytocin, are key in managing the third stage of labour to prevent PPH. Oxytocin is a short-acting medication and requires frequent dosing, however, carbetocin, a longer-acting analogue that can be administered as a single dose, provides sustained uterotonic activity. Calcium chloride is a readily available, inexpensive medication that has been studied as an adjunct to primary uterotonics due to its role in uterine contractility. A randomized trial found no overall reduction in blood loss with calcium chloride and oxytocin, but a subgroup analysis suggested it may reduce bleeding in cases of uterine atony. This study was conducted in the US where carbetocin is not readily available. The investigators propose a double-blind randomized trial investigating if co-administering calcium chloride with carbetocin during scheduled cesarean deliveries reduces PPH secondary to uterine atony.

Inclusion Criteria:

1. Scheduled CD for patients ≥ 37 weeks excluding high risk factors for uterine atony
2. Neuraxial anesthesia as the primary anesthetic where intrathecal medications are the primary anesthetic

Exclusion Criteria:

1. Risk factors for uterine atony including:

   1. Overdistended uterus due to fetal macrosomia reported on prenatal ultrasound >90th centile or > 4000 gm, multiple gestation, grand multiparity (≥5 births at ≥ 20 weeks gestation), polyhydramnios
   2. History of uterine atony/PPH (documented with blood loss > 2000 ml, blood transfusion, use of surgical methods such as Bakri balloon, B-Lynch sutures, uterine artery ligation or embolization)
   3. Obesity with body mass index (BMI) > 40 kg/m2
   4. Placenta previa and/or placenta accreta

2. Digoxin therapy within 14 days (hypercalcemia can exacerbate digoxin toxicity)

3. Patients needing intraoperative IV ceftriaxone or tetracycline.

4. Kidney disease including Stage 3 chronic kidney disease, serum creatinine above 120 mmol/L or GFR <60 ml/min (to prevent hypercalcemia due to reduced creatinine clearance in those with impaired kidney function as calcium is renally excreted)

5. Calcium channel blockade within 24 hours (opposing effect)

6. Known history of cardiac disease including arrhythmias, ischemia, and congenital heart disease (to avoid attributing cardiac symptoms to study drugs)

7. Preexisting hypertension, preeclampsia or persistent elevated blood pressure above 160/100 mmHg requiring treatment

8. Emergency cesarean deliveries or women in labor

9. Planned general anesthetic for patients where neuraxial is contraindicated.