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Oxytocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2

Not Applicable
Completed
Conditions
Postpartum Hemorrhage
Obesity
Interventions
Registration Number
NCT03957083
Lead Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Brief Summary

Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and mortality. Uterotonic drugs are used to improve the muscle tone of the uterus after birth, and these are effective at reducing the incidence of PPH. Oxytocin is the most commonly used uterotonic drug to prevent and treat PPH. Large doses of this drug are asociated with adverse effects like low blood pressure, nausea, vomiting, abnormal heart rhythms and changes on ECG. Various international bodies recommend varying and high doses of oxytocin in elective cesarean sections. A study performed at Mount Sinai Hospital showed that a much smaller dose of oxytocin is required (ED95 being 0.35IU). However, most of the women included in this study were below a body mass index (BMI) of 40kg/m2.

The investigators seek to find the best dose for patients with a BMI\>40kg/m2, as a higher dose may be needed in this population to contract the uterus adequately.

Detailed Description

Postpartum hemorrhage (PPH) is one of the leading causes of death during childbirth and accounts for an estimated 140,000 deaths per year worldwide. The World Health Organization (WHO) recommends active management of the third stage of labor to prevent PPH, even in low risk patients. Prophylactic uterotonic drugs administered after delivery are the main element of active management of the third stage and have been demonstrated to reduce the incidence of PPH by up to 40%. Oxytocin is the most commonly used uterotonic in North America, however it has a very short duration of action and requires a continuous infusion to achieve sustained effect, with large doses associated with adverse effects like low blood pressure, nausea, vomiting, abnormal heart rhythms and changes on ECG.

The prevalence of obesity is increasing in young women and some studies have shown that obese women have higher rates of caesarean delivery compared to non-obese women. Other studies have demonstrated an increased risk of hemorrhage due to poor uterine tone in obese women. Laboratory studies show that BMI alone appears to contribute to blunted uterine muscle responses and therefore contraction responses to oxytocin in obese women.

Previous dose finding studies have excluded those women with a BMI of ≥40kgm2. Therefore, the investigators wish to perform a double-blind dose finding study using the biased coin up-and-down sequential allocation technique to determine the ED90 of oxytocin at cesarean section in those women with a BMI\>40.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
30
Inclusion Criteria
  • BMI ≥40kg/m2
  • Elective cesarean delivery under regional anesthesia
  • Gestational age ≥ 37 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 (other than high BMI) that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, severe preeclampsia (as defined by SOGC guidelines (21)), eclampsia, polyhydramnios, uterine fibroids, previous history of uterine atony resulting in PPH, or bleeding diathesis.
  • Hepatic, renal, and vascular disease
  • Use of general anesthesia prior to the administration of the study drug

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oxytocin 1IUOxytocinPatient is given 1IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.
Oxytocin 2IUOxytocinPatient is given 2IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.
Oxytocin 0.5IUOxytocinPatient is given 0.5IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.
Oxytocin 3IUOxytocinPatient is given 3IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.
Oxytocin 5IUOxytocinPatient is given 5IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.
Oxytocin 4IUOxytocinPatient is given 4IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.
Primary Outcome Measures
NameTimeMethod
Uterine tone 2 minutes: questionnaire2 minutes

Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 2 minutes after completion of the oxytocin injection.

Secondary Outcome Measures
NameTimeMethod
Intraoperative requirement for additional uterotonic medication1 hour

A request made by the obstetrician performing the cesarean delivery for additional uterotonic medication, due to bleeding or poor uterine tone.

Intravenous fluid administered during surgery2 hours

The total volume (ml) of fluid administered from entering the operating room to skin closure.

Presence of ventricular tachycardia: ECG2 hours

Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery

Need for uterine massage: questionnaire20 minute

The obstetricians will be asked if there was any need for uterine massage beyond the initial 3 minute evaluation period following delivery.

Presence of vomiting: questionnaire2 hours

The presence of vomiting and number of episodes, from drug administration until end of surgery

Calculated estimate of blood loss24 hours

Blood loss will be calculated through the difference in hematocrit values assessed prior to and at the end of 48 hours after the cesarean delivery, according to the following formula:

Calculated blood loss = EBV ((Pre-op Htc-Post-op Htc)/pre-op Htc). EBV (estimated blood volume) in ml: patient's weight in kg x 85

Bradycardia: heart rate less than 70% of baseline2 hours

Heart rate \< 70% of baseline or a heart rate \< 50bpm, from drug administration until end of surgery

Presence of nausea: questionnaire2 hours

The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient

Presence of headache: questionnaire2 hours

Any presence of headache, from drug administration until end of surgery, as reported by the patient

Hypotension: systolic blood pressure less than 80% of baseline2 hours

Systolic blood pressure \< 80% of baseline, from drug administration until end of surgery

Tachycardia: heart rate greater than 130% of baseline2 hours

Heart rate \> 130% of baseline, from drug administration until end of surgery

Presence of atrial fibrillation: ECG2 hours

Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery

Presence of atrial flutter: ECG2 hours

Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery

Presence of shortness of breath: questionnaire2 hours

Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient

Presence of flushing: questionnaire2 hours

Any presence of flushing, from drug administration until end of surgery

Presence of chest pain: questionnaire2 hours

Any presence of chest pain, from drug administration until end of surgery, as reported by the patient

Trial Locations

Locations (1)

Mount Sinai Hospital

🇨🇦

Toronto, Ontario, Canada

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