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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Postpartum Hemorrhage
• Intervention / Treatment: Drug: Oxytocin

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin 0.5IU; Patient is given 0.5IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin; Oxytocin administered intravenously, over 1 minute following delivery of the fetal head; Other Names: pitocin
Active Comparator: Oxytocin 1IU; Patient is given 1IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin; Oxytocin administered intravenously, over 1 minute following delivery of the fetal head; Other Names: pitocin
Active Comparator: Oxytocin 2IU; Patient is given 2IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin; Oxytocin administered intravenously, over 1 minute following delivery of the fetal head; Other Names: pitocin
Active Comparator: Oxytocin 3IU; Patient is given 3IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin; Oxytocin administered intravenously, over 1 minute following delivery of the fetal head; Other Names: pitocin
Active Comparator: Oxytocin 4IU; Patient is given 4IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin; Oxytocin administered intravenously, over 1 minute following delivery of the fetal head; Other Names: pitocin
Active Comparator: Oxytocin 5IU; Patient is given 5IU of oxytocin intravenously over 1 minute, immediately upon delivery of the fetal head.	Drug: Oxytocin; Oxytocin administered intravenously, over 1 minute following delivery of the fetal head; Other Names: pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine tone 2 minutes: questionnaire	Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 2 minutes after completion of the oxytocin injection.	2 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypotension: systolic blood pressure less than 80% of baseline	Systolic blood pressure < 80% of baseline, from drug administration until end of surgery	2 hours
Tachycardia: heart rate greater than 130% of baseline	Heart rate > 130% of baseline, from drug administration until end of surgery	2 hours
Bradycardia: heart rate less than 70% of baseline	Heart rate < 70% of baseline or a heart rate < 50bpm, from drug administration until end of surgery	2 hours
Presence of ventricular tachycardia: ECG	Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery	2 hours
Presence of atrial fibrillation: ECG	Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery	2 hours
Presence of atrial flutter: ECG	Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery	2 hours
Presence of nausea: questionnaire	The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient	2 hours
Presence of vomiting: questionnaire	The presence of vomiting and number of episodes, from drug administration until end of surgery	2 hours
Presence of chest pain: questionnaire	Any presence of chest pain, from drug administration until end of surgery, as reported by the patient	2 hours
Presence of shortness of breath: questionnaire	Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient	2 hours
Presence of headache: questionnaire	Any presence of headache, from drug administration until end of surgery, as reported by the patient	2 hours
Presence of flushing: questionnaire	Any presence of flushing, from drug administration until end of surgery	2 hours
Intraoperative requirement for additional uterotonic medication	A request made by the obstetrician performing the cesarean delivery for additional uterotonic medication, due to bleeding or poor uterine tone.	1 hour
Intravenous fluid administered during surgery	The total volume (ml) of fluid administered from entering the operating room to skin closure.	2 hours
Calculated estimate of blood loss	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	24 hours
Need for uterine massage: questionnaire	The obstetricians will be asked if there was any need for uterine massage beyond the initial 3 minute evaluation period following delivery.	20 minute

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2019
• Primary Completion (Actual): February 3, 2020
• Study Completion (Actual): February 4, 2020

Study Registration Dates

• First Submitted: May 17, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 21, 2019

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: obesity; oxytocin; pregnancy; postpartum hemorrhage; Cesarean delivery
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 19-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No