Maintenance Infusion of Oxytocin Following Elective Cesarean Deliveries

Maintenance Infusion of Oxytocin Following Elective Cesarean Deliveries: an Up-down Sequential Allocation Dose-response Study

This study is designed to determine the minimal effective oxytocin maintenance dose required during cesarean delivery to achieve the best effect. Oxytocin is a drug which is routinely used to help contract the uterus and keep it contracted after the delivery of the baby and placenta. The aim of oxytocin is to reduce the amount of blood that might be lost. In order to determine the minimal effective dose, the investigators will conduct a dose-finding study. The first patient will receive a set oxytocin infusion. If the uterus contracts well, this is considered satisfactory and the next patient will receive the same dose. If the uterus does not contract well, this is considered unsatisfactory and the next patient will receive a higher dose. The dose for the next patient will be determined based on the results of the uterine contraction of the previous patient.

The investigators hypothesize that the ED90 of an oxytocin infusion rate to maintain a satisfactory uterine tone during a cesarean delivery in non-laboring women, would be lower than that found in previous studies without an initial bolus (less than 16 IU/h).

Study Overview

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

Detailed Description

This study will be conducted as a prospective, double blinded clinical trial (patient, anesthesiologist and obstetrician blinded to the oxytocin dose), in an up-down sequential allocation fashion. The objective of the study is to determine the minimum effective dose of oxytocin infusion required to produce appropriate uterine contraction during and after cesarean delivery under neuraxial anesthesia in non-laboring women. For the purpose of this study, the minimum effective dose is defined to be that at which adequate response occurs in 90% of patients, i.e. ED90.

• Study Type: Interventional
• Enrollment (Actual): 40
• 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: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Elective uncomplicated cesarean delivery under neuraxial anesthesia
• >18 year-old with ASA status II or III, with a singleton gestation and a gestational age between 37 to 42 weeks Informed consent to participate in this study

Exclusion Criteria:

• Refusal to give written informed consent
• Allergy or hypersensitivity to oxytocin
• Body mass index ≥ 40 kg/m2on the day of admission
• A history of hypertension and/ or severe cardiac disease(s)
• Contra-indications for neuraxial anesthesia
• Conditions that predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, preeclampsia, macrosomia (≥ 4 kg), polyhydramnios, uterine fibroids in and near operating field, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin infusion rate 2 IU/h; The maintenance infusion rate of oxytocin will be 2 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 4 IU/h; The maintenance infusion rate of oxytocin will be 4 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 6 IU/h; The maintenance infusion rate of oxytocin will be 6 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 8 IU/h; The maintenance infusion rate of oxytocin will be 8 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 10 IU/h; The maintenance infusion rate of oxytocin will be 10 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 12 IU/h; The maintenance infusion rate of oxytocin will be 12 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 14 IU/h; The maintenance infusion rate of oxytocin will be 14 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin
Experimental: Oxytocin infusion rate 16 IU/h; The maintenance infusion rate of oxytocin will be 16 IU/h.	Drug: Oxytocin; Oxytocin will be prepared in a 1L bag of Ringer's lactate, to be infused at a rate of 125 ml/h.; Other Names: Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine tone upon discharge from the post anesthetic care unit (PACU): questionnaire	Uterine tone will be evaluated as satisfactory or unsatisfactory by the obstetrician throughout the surgery, starting at 5 minutes after the oxytocin infusion. It will also be measured at 10 minutes following the oxytocin infusion and every 10 minutes following that for the duration of the surgery. Unsatisfactory uterine tone at any time until discharge from the PACU will be considered a failure of the maintenance infusion.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculated blood loss	Estimated blood loss will be calculated using the difference in hematocrit values prior to surgery and 24 hours post surgery, using the following formula: Calculated blood loss (mL) = 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
Incidence of post partum hemorrhage	Incidence of post partum hemorrhage defined as a calculated blood loss >1L.	24 hours
Need for blood transfusion	Blood product administered.	24 hours
Episodes of bleeding postpartum	Number of episodes of bleeding postpartum up to 24 hours post delivery.	24 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.	2 hours
Requirement for additional uterotonic medication in the PACU	Any uterotonic medication administered while the patient is in PACU	2 hours
Requirement for additional uterotonic medication from discharge from the PACU until 24 hours postpartum.	Any uterotonic medication administered after the patient is discharged from PACU until 24 hours postpartum.	24 hours
Postoperative uterine position in the PACU	Postoperative uterine position (below or above the umbilicus) as determined by the PACU nurse. This is measured every 15 minutes for the first hour and then hourly until discharge to the postpartum unit.	3 hours
Hypotension: systolic blood pressure less than 80% of baseline	Systolic blood pressure < 80% of baseline, from drug administration until end of surgery	2 hours
Hypertension: systolic blood pressure greater than 120% of baseline	Systolic blood pressure > 120% 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

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 2, 2022

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): June 7, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: oxytocin; pregnancy; Cesarean delivery; uterotonic
• 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: 21-05

Drug and device information, study documents

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