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

Samuel Lunenfeld Research Institute, Mount Sinai Hospital120 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

120

Conditions

Postpartum Hemorrhage (Primary)

Interventions

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Uterine Tone 10 minutes

The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 10 minutes post-fetal delivery, utilizing a verbal numeric rating scale of 0-10.

Time frame: 10 minutes

Secondary Outcomes

Uterine Tone baseline

The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician after delivery of the placenta, utilizing a verbal numeric rating scale of 0-10.

Time frame: 1 minute

Uterine Tone 5 minutes

The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 10 minutes post-fetal delivery, utilizing a verbal numeric rating scale of 0-10.

Time frame: 5 minutes

Uterine Tone 15 minutes

The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 15 minutes post-fetal delivery, utilizing a verbal numeric rating scale of 0-10.

Time frame: 15 minutes

Uterine Tone 20 minutes

The intensity of uterine tone as evaluated by palpation of the uterus by the obstetrician at 20 minutes post-fetal delivery, utilizing a verbal numeric rating scale of 0-10.

Time frame: 20 minutes

Additional uterotonic agents required intraoperatively

The number of patients who are administered additional uterotonic agents intraoperatively will be recorded

Time frame: 90 minutes

Additional uterotonic agents required post-operatively

The number of patients who are administered additional uterotonic agents post-operatively will be recorded

Time frame: 24 hours

Semi-quantitative blood loss (SQBL)

Blood loss measured in the operating room by volume (ml)

Time frame: 90 minutes

Incidence of postpartum hemorrhage

The number of patients with blood loss greater than or equal to 1000ml

Time frame: 24 hours

Presence of blood transfusion

Number of units of blood product administered post-delivery

Time frame: 24 hours

Number of patients with conservative surgical methods to manage post partum hemorrhage

Bakri balloon/B-Lynch sutures used intraoperatively

Time frame: 2 hours

Number of patients with radiological methods used to manage post partum hemorrhage

Uterine artery embolization used intraoperatively.

Time frame: 2 hours

Obstetric Quality of Recovery-10 (ObsQoR-10) score 24 hours

ObsQoR-10 score at 24 hours. There are 10 questions, and the results are tabulated out of 100. The higher the overall score out of 100, the better quality of recovery a patient is experiencing.

Time frame: 24 hours

Number of patients with hypotension defined as systolic blood pressure less than 80% of baseline

Systolic blood pressure \< 80% of baseline, at any time during surgeryTime

Time frame: 2 hours

Number of patients with hypertension defined as systolic blood pressure greater than 120% of baseline

Systolic blood pressure \> 120% of baseline, at any time during surgery

Time frame: 2 hours

Number of patients with tachycardia defined as heart rate greater than 130% of baseline

Heart rate \> 130% of baseline, at any time during surgery

Time frame: 2 hours

Number of patients with bradycardia defined as heart rate less than 70% of baseline

Heart rate \< 70% of baseline, at any time during surgery

Time frame: 2 hours

Presence of atrial fibrillation: ECG

Presence of atrial fibrillation as recorded by ECG, at any time during surgery

Time frame: 2 hours

Presence of atrial flutter: ECG

Presence of atrial flutter as recorded by ECG, at any time during surgery

Time frame: 2 hours

Presence of nausea: questionnaire

The presence of nausea at any time during surgery, as reported by the patient

Time frame: 2 hours

Presence of vomiting: questionnaire

The presence of vomiting at any time during surgery, as reported by the patient

Time frame: 2 hours

Number of patients with chest pain: questionnaire

Any presence of chest pain, at any time during surgery, as reported by the patient

Time frame: 2 hours

Number of patients with irritation at the intravenous site: questionnaire

Any presence of irritation, including pain or burning, at the intravenous site, at any time during surgery, as reported by the patient.

Time frame: 2 hours

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts