Maintenance Infusion of Oxytocin Following Elective Cesarean Deliveries

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Oxytocin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Biased coin up-and-down design.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cesarean delivery, oxytocin, uterotonic, pregnancy