Haemodynamic Effects of Oxytocin and Carbetocin

Haemodynamic Assessment at Primary Caesarean Section After Administration of Carbetocin Versus Oxytocin: a Doubleblind Randomized Trail

The purpose of this study is to evaluate the immediate effects of carbetocin and oxytocin on maternal hemodynamic parameters (heart rate and blood pressure) in a non-invasive setup (TaskeForce®-Monitor) during primary Caesarean section.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Cesarean Section; Complications; Adverse Reaction to Oxytocic Agents

Detailed Description

As there is a trend toward childbearing in later life, pre-existing maternal cardiovascular problems may become more frequent during pregnancy and at delivery. In addition the increasing number of women with congenital or acquired cardiac diseases may not tolerate the induced haemodynamic changes as well as healthy patients. Therefore uterotonic drugs must be safe for the cardiovascular system.

Currently oxytocin is used as a common uterotonic agent in obstetrics. The use of this drug in uterotonic reasons can cause serious haemodynamic side effects which has been shown by several investigators.

Preliminary clinical observations of maternal heart rate and blood pressure suggest that that the use of carbetocin causes less hemodynamic changes than oxytocin.

Primary objective(s):

To evaluate the effect of carbetocin on maternal hemodynamic parameters (heart rate, blood pressure, systemic vascular resistance, cardiac output, stroke volume, heart rate variability, and blood pressure variability) in a non-invasive setup (TaskeForce®-Monitor) during primary Caesarean section.

To compare the haemodynamic changes of carbetocin versus oxytocin.

Secondary objective(s) To evaluate the need of additional drugs and methods to control uterine tone.

• Study Type: Observational
• Enrollment (Actual): 84

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University Graz, Dept. of Obstetrics and Gynecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Women undergoing elective caesarean section after regional anesthesia at an University hospital providing intrapartum care.

Description

Inclusion Criteria:

• Healthy pregnant women undergoing elective caesarean section with regional anesthesia

Exclusion Criteria:

---Women with

• placenta praevia
• placental abruption
• multiple gestation
• pregnancy related complications and disorders (i.e. preeclampsia, gestational diabetes)
• pre-existing diseases (e.g. insulin-dependent diabetes, cardiovascular or renal diseases, thyroid disease
• taking medication with known impact on the cardiovascular system
• undergoing caesarean section with general anesthesia
• secondary caesarean section

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Carbetocin; Women undergoing elective caesarean sectio in regional anesthesia randomised to receive 100 ug Carbetocin (the clinical standard dose) following delivery of the baby.
Oxytocin; Women undergoing elective caesarean sectio in regional anesthesia randomised to receive 5 IU oxytocin (the clinical standard dose) following delivery of the baby.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immediate hemodynamic effects of carbetocin and oxytocin	Maternal heart rate, blood pressure, stroke volume, cardiac output, and systemic vascular resistance will be measured non-invasively. Measurements will be performed starting immediately following administration of the study medication.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects	Number of participants with adverse events as a measure of safety and tolerability	2 day
Uterotonic effect	Impact of both drugs on uterine tone	1 day
Estimation of blood loss	Measurement of pre- and postoperative hemoglobin levels (routine clinical blood sample).	2 day

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Manfred G Mörtl, MD, Medical University Graz, Dept. of Obstetrics and Gynecology

Publications and helpful links

General Publications

• Boucher M, Horbay GL, Griffin P, Deschamps Y, Desjardins C, Schulz M, Wassenaar W. Double-blind, randomized comparison of the effect of carbetocin and oxytocin on intraoperative blood loss and uterine tone of patients undergoing cesarean section. J Perinatol. 1998 May-Jun;18(3):202-7.
• Dansereau J, Joshi AK, Helewa ME, Doran TA, Lange IR, Luther ER, Farine D, Schulz ML, Horbay GL, Griffin P, Wassenaar W. Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section. Am J Obstet Gynecol. 1999 Mar;180(3 Pt 1):670-6. doi: 10.1016/s0002-9378(99)70271-1.
• Pinder AJ, Dresner M, Calow C, Shorten GD, O'Riordan J, Johnson R. Haemodynamic changes caused by oxytocin during caesarean section under spinal anaesthesia. Int J Obstet Anesth. 2002 Jul;11(3):156-9. doi: 10.1054/ijoa.2002.0970.
• Su LL, Chong YS, Samuel M. Oxytocin agonists for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD005457. doi: 10.1002/14651858.CD005457.pub2.
• Chong YS, Su LL, Arulkumaran S. Current strategies for the prevention of postpartum haemorrhage in the third stage of labour. Curr Opin Obstet Gynecol. 2004 Apr;16(2):143-50. doi: 10.1097/00001703-200404000-00008.
• Westhoff G, Cotter AM, Tolosa JE. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage. Cochrane Database Syst Rev. 2013 Oct 30;(10):CD001808. doi: 10.1002/14651858.CD001808.pub2.
• Sweeney G, Holbrook AM, Levine M, Yip M, Alfredsson K, Cappi S, et al. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in nonpregnant women. Curr Ther Res 1990;47:528-40
• Thomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing Caesarean section. Br J Anaesth. 2007 Jan;98(1):116-9. doi: 10.1093/bja/ael302. Epub 2006 Dec 2.
• Boucher M, Nimrod CA, Tawagi GF, Meeker TA, Rennicks White RE, Varin J. Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery:a double-blind randomized trial. J Obstet Gynaecol Can. 2004 May;26(5):481-8. doi: 10.1016/s1701-2163(16)30659-4.
• Atke A, Vilhardt H. Uterotonic activity and myometrial receptor affinity of 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin. Acta Endocrinol (Copenh). 1987 May;115(1):155-60. doi: 10.1530/acta.0.1150155.
• Hunter DJ, Schulz P, Wassenaar W. Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. Clin Pharmacol Ther. 1992 Jul;52(1):60-7. doi: 10.1038/clpt.1992.103.
• Moertl MG, Friedrich S, Kraschl J, Wadsack C, Lang U, Schlembach D. Haemodynamic effects of carbetocin and oxytocin given as intravenous bolus on women undergoing caesarean delivery: a randomised trial. BJOG. 2011 Oct;118(11):1349-56. doi: 10.1111/j.1471-0528.2011.03022.x. Epub 2011 Jun 14. Erratum In: BJOG. 2011 Nov;118(12):1549.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ACTUAL): July 1, 2008
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: January 13, 2011
• First Submitted That Met QC Criteria: January 14, 2011
• First Posted (ESTIMATE): January 17, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 17, 2011
• Last Update Submitted That Met QC Criteria: January 14, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Caesarean section; Oxytocin; Cardiovascular effects; Postpartum hemorrhage; Carbetocin
• Other Study ID Numbers: CARBOXY-005498-78-Graz; 2007-005498-78 (EUDRACT_NUMBER)