Archives of Gynecology and Obstetrics

, Volume 298, Issue 2, pp 319–327 | Cite as

Intravenous carbetocin versus intravenous oxytocin for preventing atonic postpartum hemorrhage after normal vaginal delivery in high-risk singleton pregnancies: a triple-blind randomized controlled trial

  • Paweena Amornpetchakul
  • Tripop LertbunnaphongEmail author
  • Dittakarn Boriboonhiransarn
  • Jarunee Leetheeragul
  • Ratree Sirisomboon
  • Ratchada Jiraprasertwong
Maternal-Fetal Medicine



To compare the effectiveness of intravenous carbetocin to that of intravenous oxytocin for prevention of atonic postpartum hemorrhage (PPH) after vaginal delivery in high-risk singleton pregnancies.


This triple-blind randomized controlled trial included singleton pregnant women who delivered at Siriraj Hospital between August 2016 and January 2017 and who were 20 years or older, had a gestational age of at least 34 weeks, had a vaginal delivery, and had at least one risk factor for atonic postpartum hemorrhage. Immediately after vaginal delivery, participants were randomly assigned to receive either 5 U of oxytocin or 100 mcg of carbetocin intravenously. Postpartum blood loss was measured objectively in mL using a postpartum drape with a calibrated bag.


A total of 174 and 176 participants constituted the oxytocin and carbetocin groups, respectively. The baseline characteristics were comparable between the groups. The carbetocin group had less postpartum blood loss (146.7 ± 90.4 vs. 195.1 ± 146.2 mL; p < 0.01), a lower incidence of atonic PPH (0 vs. 6.3%; p < 0.01), less usage of additional uterotonic drugs (9.1 vs. 27.6%; p < 0.01), and a lower incidence of postpartum anemia (Hb ≤ 10 g/dL) (9.1 vs. 18.4%; p < 0.05) than the oxytocin group. No significant differences regarding side effects were evident between the groups.


Intravenous carbetocin is more effective than intravenous oxytocin for the prevention of atonic PPH among singleton pregnancies with at least one risk factor for PPH.

Clinical trial registration



Carbetocin High-risk pregnancy Obstetric delivery Oxytocin Postpartum hemorrhage 



The authors gratefully acknowledge Mr. Suthipol Udompunthurak for assistance with the statistical analysis. We are also grateful to a grant obtained from the Siriraj Research Development Fund, which is managed by the Routine to Research Project (R2R) and to 100 doses of carbetocin used in this study which were supported unconditionally by Ferring Pharmaceutical Ltd., Thailand.

Author contributions

TL: protocol/project development, data analysis and interpretation, manuscript writing/editing, final form of manuscript. PA: data collection and management, manuscript writing, funding management. DB: protocol/project development, data analysis and interpretation. JL: data collection and management. RS: data collection and management. RJ: data collection and management, funding management.


This study was funded by the Siriraj Research Development Fund, which is managed by the Routine to Research Project (R2R; Grant number 16OG00021/044/16). The one hundred doses of carbetocin used in this study were provided unconditionally by Ferring Pharmaceutical Ltd., Thailand. The funders had no role in the processes of the study design, data collection, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

Assistant professor Tripop Lertbunnaphong has received a speaker honorarium from Ferring Pharmaceutical Ltd., Thailand. Paweena Amornpetchakul, Dittakarn Boriboonhiransarn, Jarunee Leetheeragul, Ratree Sirisomboon and Ratchada Jiraprasertwong declare that they have no conflict of interest.

Research involving human participants and/or animals

Ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L (2014) Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2(6):e323–e333CrossRefPubMedGoogle Scholar
  2. 2.
    World Health Organization (2012) WHO recommendations for the prevention and treatment of postpartum haemorrhage. WHO Guidelines Approved by the Guidelines Review Committee, GenevaGoogle Scholar
  3. 3.
    Cordovani D, Carvalho JCA, Boucher M, Farine D (2012) Carbetocin for the prevention of postpartum hemorrhage. In: Arulkumaran S, Karoshi M, Keith LG, Lalonde AB, B-Lynch C (eds) A Comprehensive textbook of postpartum hemorrhage: an essential clinical reference for effective management, 2nd edn. Sapiens Publishing, London, pp 361–368Google Scholar
  4. 4.
    Westhoff G, Cotter AM, Tolosa JE (2013) Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage. Cochrane Database Syst Rev. CrossRefPubMedGoogle Scholar
  5. 5.
    Meshykhi LS, Nel MR, Lucas DN (2016) The role of carbetocin in the prevention and management of postpartum haemorrhage. Int J Obstet Anesth 28:61–69CrossRefPubMedGoogle Scholar
  6. 6.
    Samimi M, Imani-Harsini A, Abedzadeh-Kalahroudi M (2013) Carbetocin vs. syntometrine in prevention of postpartum hemorrhage: a double blind randomized control trial. Iran Red Crescent Med J 15(9):817–822CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bruyere M, Ait Hamou N, Benhamou D, Chousterman B, Boulard V, Charbit B (2014) QT interval prolongation following carbetocin in prevention of post-cesarean delivery hemorrhage. Int J Obstet Anesth 23(1):88–89CrossRefPubMedGoogle Scholar
  8. 8.
    Jacquenod P, Cattenoz M, Canu G, Bois E, Lieutaud T (2015) Acute coronary syndrome following a 100 microg carbetocin injection during an emergency Cesarean delivery. Can J Anaesth 62(5):513–517CrossRefPubMedGoogle Scholar
  9. 9.
    Su LL, Chong YS, Samuel M (2012) Carbetocin for preventing postpartum haemorrhage. Cochrane Database Syst Rev. CrossRefPubMedGoogle Scholar
  10. 10.
    Leduc D, Senikas V, Lalonde AB, Ballerman C, Biringer A, Delaney M, Clinical Practice Obstetrics Committee; Society of Obstetricians and Gynaecologists of Canada et al (2009) Active management of the third stage of labour: prevention and treatment of postpartum hemorrhage. J Obstet Gynaecol Can 31(10):980–993CrossRefPubMedGoogle Scholar
  11. 11.
    Maged AM, Hassan AM, Shehata NA (2016) Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women. J Matern Fetal Neonatal Med 29(4):532–536CrossRefPubMedGoogle Scholar
  12. 12.
    Gulmezoglu AM, Lumbiganon P, Landoulsi S, Widmer M, Abdel-Aleem H, Festin M, Carroli G, Qureshi Z, Souza JP, Bergel E, Piaggio G, Goudar SS, Yeh J, Armbruster D, Singata M, Pelaez-Crisologo C, Althabe F, Sekweyama P, Hofmeyr J, Stanton ME, Derman R, Elbourne D (2012) Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial. Lancet 379(9827):1721–1727CrossRefPubMedGoogle Scholar
  13. 13.
    Hunter DJ, Schulz P, Wassenaar W (1992) Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. Clin Pharmacol Ther 52(1):60–67CrossRefPubMedGoogle Scholar
  14. 14.
    Amsalem H, Aldrich CJ, Oskamp M, Windrim R, Farine D (2014) Postpartum uterine response to oxytocin and carbetocin. J Reprod Med 59(3–4):167–173PubMedGoogle Scholar
  15. 15.
    Silcox J, Schulz P, Horbay GL, Wassenaar W (1993) Transfer of carbetocin into human breast milk. Obstet Gynecol 82(3):456–459PubMedGoogle Scholar
  16. 16.
    Rosseland LA, Hauge TH, Grindheim G, Stubhaug A, Langesaeter E (2013) Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo. Anesthesiology 119(3):541–551CrossRefPubMedGoogle Scholar
  17. 17.
    Boucher M, Nimrod CA, Tawagi GF, Meeker TA, Rennicks White RE, Varin J (2004) Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery: a double-blind randomized trial. J Obstet Gynaecol Can 26(5):481–488CrossRefPubMedGoogle Scholar
  18. 18.
    Askar AA, Ismail MT, El-Ezz AA, Rabie NH (2011) Carbetocin versus syntometrine in the management of third stage of labor following vaginal delivery. Arch Gynecol Obstet 284:1359–1365CrossRefPubMedGoogle Scholar
  19. 19.
    Jin B, Du Y, Zhang F, Zhang K, Wang L, Cui L (2016) Carbetocin for the prevention of postpartum hemorrhage: a systematic review and meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med 29(3):400–407CrossRefPubMedGoogle Scholar
  20. 20.
    Widmer M, Piaggio G, Abdel-Aleem H, Carroli G, Chong YS, Coomarasamy A, Fawole B, Goudar S, Hofmeyr GJ, Lumbiganon P, Mugerwa K, Nguyen TM, Qureshi Z, Souza JP, Gulmezoglu AM (2016) Room temperature stable carbetocin for the prevention of postpartum haemorrhage during the third stage of labour in women delivering vaginally: study protocol for a randomized controlled trial. Trials 17(1):143CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    (2017) Prevention and management of postpartum haemorrhage: green-top guideline no. 52. BJOG 124(5):e106–e149.
  22. 22.
    Snelgrove JW (2009) Postpartum haemorrhage in the developing world a review of clinical management strategies. Mcgill J Med 12(2):61Google Scholar
  23. 23.
    Su LL, Rauff M, Chan YH, Mohamad Suphan N, Lau TP, Biswas A, Chong YS (2009) Carbetocin versus syntometrine for the third stage of labour following vaginal delivery—a double-blind randomised controlled trial. BJOG 116(11):1461–1466CrossRefPubMedGoogle Scholar
  24. 24.
    Chen CY, Su YN, Lin TH, Chang Y, Horng HC, Wang PH, Yeh CC, Chang WH, Huang HY (2016) Carbetocin in prevention of postpartum hemorrhage: experience in a tertiary medical center of Taiwan. Taiwan J Obstet Gynecol 55(6):804–809CrossRefPubMedGoogle Scholar
  25. 25.
    Lertbunnaphong T, Lapthanapat N, Leetheeragul J, Hakularb P, Ownon A (2016) Postpartum blood loss: visual estimation versus objective quantification with a novel birthing drape. Singap Med J 57(6):325–328CrossRefGoogle Scholar
  26. 26.
    Luni Y, Borakati A, Matah A, Skeats K, Eedarapalli P (2017) A prospective cohort study evaluating the cost-effectiveness of carbetocin for prevention of postpartum haemorrhage in caesarean sections. J Obstet Gynaecol 37(5):601–604CrossRefPubMedGoogle Scholar
  27. 27.
    van der Nelson HA, Draycott T, Siassakos D, Yau CW, Hatswell AJ (2017) Carbetocin versus oxytocin for prevention of post-partum haemorrhage at caesarean section in the United Kingdom: an economic impact analysis. Eur J Obstet Gynecol Reprod Biol 210:286–291CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Paweena Amornpetchakul
    • 1
  • Tripop Lertbunnaphong
    • 1
    Email author return OK on get
  • Dittakarn Boriboonhiransarn
    • 1
  • Jarunee Leetheeragul
    • 1
  • Ratree Sirisomboon
    • 1
  • Ratchada Jiraprasertwong
    • 1
  1. 1.Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand

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