Oxytocin in Cesarean Delivery

Comparing Oxytocin and Oxytocin-ergometrine Combinations for Increasing Uterine Tone in Cesarean Delivery: a Pharmacokinetic-pharmacodynamic Study.

In this study the investigators hypothesize that infused combinations of oxytocin and ergometrine will exhibit fewer cardiac and neurological side effects than equipotent infusion of oxytocin alone. In order to perform this study the investigators perform the following steps:

1. The investigators validate a quantitative measure of uterine tone as our primary endpoint.
2. The investigators use this endpoint measure in order to determine equipotential doses of different tocotonic drug regimens, based on the ED50 for each.
3. Using equipontial ratios based on the ED50, the investigators compare hemodynamic and other side effects of these tocotonic drug regimes. Plasma levels of oxytocin will be measured.

Study Overview

• Status: Unknown
• Conditions: Post Partum Hemorrhage
• Intervention / Treatment: Drug: Oxytocin versus oxytocin-ergometrine

Detailed Description

Obstetric hemorrhage is associated with severe maternal morbidityש and maternal death. The use of tocotonic drugs following delivery is routine practice as part of the active management of the third stage of labor, to increase uterine tone and reduce blood loss. However, the use of these drugs is not without side effects and complications. Oxytocin causes profound vasodilatation, hypotension and increased cardiac output and has been associated with chest pain, reduced arterial oxygen saturation and ST segment changes on ECG. Ergometrine, on the other hand, causes systemic vasoconstriction and hypertension, and reduced cardiac output. As oxytocin and ergometrine are associated with opposing hemodynamic sequelae, there is a rationale to justify the co-administration of both of these drugs in an attempt to cancel out their side effects.

No clinical studies have attempted to titrate the dose of tocotonic drugs against a quantified measure of uterine tone. As a consequence, comparisons of the hemodynamic side effects of oxytocin and other tocotonic agents (particularly ergometrine) have not been based on a knowledge of equipotential doses, making the rational comparison of side effects impossible.

In this study we hypothesize that infused combinations of oxytocin and ergometrine will exhibit fewer cardiac and neurological side effects than equipotent infusion of oxytocin alone. In order to perform this study we perform the following steps:

1) We validate a quantitative measure of uterine tone as our primary endpoint. 2) We use this endpoint measure in order to determine equipotential doses of different tocotonic drug regimens, based on the ED50 for each. 3) Using equipontial ratios based on the ED50, we compare hemodynamic and other side effects of these tocotonic drug regimes. Plasma levels of oxytocin will be measured to enable pharmacokinetic-pharmacodynamic assessments to be made.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 93510
    • Hadassah Hebrew University Medical Center
    • Contact: Yehuda Ginosar, MBBS; Phone Number: +972-2-6722077; Email: yginosar@netvision.net.il
    • Principal Investigator: Yehuda Ginosar, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 80 healthy women presenting for elective repeat cesarean delivery under regional anesthesia.
• All women are ASA class 1-2, aged 18 - 45, with body weight 60-100 kg.

Exclusion Criteria:

• Obstetric risk factors: Pre-eclampsia, abnormalities of placentation (eg placenta accrete, placenta previa), amnionitis, multiple gestation, preterm delivery (< 37 completed weeks), more than three previous cesarean deliveries, previous history of ante-partum or post-partum hemorrhage.
• Maternal medical risk factors: Chronic hypertension, cardiac disease, intracranial pathology, known allergies to oxytocin or ergometrine, autoimmune disorders, SLE, coagulation defect or anticoagulation therapy, amnionitis.
• Women asking for cord blood donations are not included in this study due to the long elapsed time between delivery and the commencement of oxytocin.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin	Drug: Oxytocin versus oxytocin-ergometrine; Group 1: Oxytocin 0.1 I.U./kg/hr (plain) Group 2: Oxytocin 0.1 I.U./kg/hr with ergometrine 2 mcg/kg/hr co-administered Infusion rates determined to achieve equipotential doses based on an earlier PKPD study
Experimental: Oxytocin - ergometrine	Drug: Oxytocin versus oxytocin-ergometrine; Group 1: Oxytocin 0.1 I.U./kg/hr (plain) Group 2: Oxytocin 0.1 I.U./kg/hr with ergometrine 2 mcg/kg/hr co-administered Infusion rates determined to achieve equipotential doses based on an earlier PKPD study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine tone	Uterine tone as measured by tissue durometry	Up to 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of oxytocin		Up to 30 minutes
Subjective side effects	Headache, chest pain, shortness of breath	Up to 120 minutes

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): May 1, 2011
• Study Completion (Anticipated): May 1, 2011

Study Registration Dates

• First Submitted: September 27, 2010
• First Submitted That Met QC Criteria: November 5, 2010
• First Posted (Estimate): November 7, 2010

Study Record Updates

• Last Update Posted (Estimate): November 7, 2010
• Last Update Submitted That Met QC Criteria: November 5, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Pregnancy; Oxytocin; Postpartum hemorrhage; Uterine tone; Ergometrine; Pharmacokinetic-pharmacodynamic analysis
• 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; Ergonovine
• Other Study ID Numbers: oxytocined50-HMO-CTIL