World Health Organization. WHO recommendations: uterotonics for the prevention of postpartum haemorrhage; 2018. Available from URL: https://www.who.int/publications/i/item/9789241550420 (accessed March 2025).

Heesen M, Carvalho B, Carvalho JC, et al. International consensus statement on the use of uterotonic agents during Caesarean section. Anaesthesia 2019; 74: 1305–19. https://doi.org/10.1111/anae.14757

Article  CAS  PubMed  Google Scholar 

Mavrides E, Allard S, Chandraharan E, et al. Prevention and management of postpartum haemorrhage. BJOG 2016; 75: 875–82. Available from URL: https://amogsobgy.com/content/GTG%2052%20PPH%20BJOG%202016.pdf (accessed March 2025).

Hunter DJ, Schulz P, Wassenaar W. Effect of carbetocin, a long-acting oxytocin the postpartum uterus analog. Clin Pharmacol Ther 1992; 52: 60–7. https://doi.org/10.1038/clpt.1992.103

Article  CAS  PubMed  Google Scholar 

Nguyen-Lu N, Carvalho JC, Farine D, Seaward G, Ye XY, Balki M. Carbetocin at Cesarean delivery for labour arrest: a sequential allocation trial to determine the effective dose. Can J Anesth 2015; 62: 866–74. https://doi.org/10.1007/s12630-015-0375-2

Article  PubMed  Google Scholar 

Cordovani D, Balki M, Farine D, Seaward G, Carvalho JC. Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose. Can J Anesth 2012; 59: 751–7. https://doi.org/10.1007/s12630-012-9728-2

Article  PubMed  Google Scholar 

Drew T, Balki M, Farine D, Ye XY, Downey K, Carvalho JC. Carbetocin at elective Caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women. Anaesthesia 2020; 75: 331–7. https://doi.org/10.1111/anae.14944

Article  CAS  PubMed  Google Scholar 

Tabl S, Balki M, Downey K, et al. Uterotonics in elective Caesarean delivery: a randomised non-inferiority study comparing carbetocin 20 μg and 100 μg. Anaesthesia 2019; 74: 190–6. https://doi.org/10.1111/anae.14480

Article  CAS  PubMed  Google Scholar 

Khan M, Balki M, Ahmed I, Farine D, Seaward G, Carvalho JC. Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose. Can J Anesth 2014; 61: 242–8. https://doi.org/10.1007/s12630-013-0082-9

Article  PubMed  Google Scholar 

McDonagh F, Carvalho JC, Abdulla S, et al. Carbetocin vs. oxytocin at elective Caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens. Anaesthesia 2022; 77: 892–900. https://doi.org/10.1111/anae.15714

Article  CAS  PubMed  Google Scholar 

Ibrahim ZM, Sayed Ahmed WA, Abd El-Hamid EM, Taha OT, Elbahie AM. Carbetocin versus oxytocin for prevention of postpartum hemorrhage in hypertensive women undergoing elective Cesarean section. Hypertens Pregnancy 2020; 39: 319–25. https://doi.org/10.1080/10641955.2020.1768268

Article  CAS  PubMed  Google Scholar 

Nucci B, Aya AGM, Aubry E, Ripart J. Carbetocin for prevention of postCesarean hemorrhage in women with severe preeclampsia: a before-after cohort comparison with oxytocin. J Clin Anesth 2016; 35: 321–5. https://doi.org/10.1016/j.jclinane.2016.08.017

Article  CAS  PubMed  Google Scholar 

Reyes OA, Gonzalez GM. Carbetocin versus oxytocin for prevention of postpartum hemorrhage in patients with severe preeclampsia: a double-blind randomized controlled trial. J Obstet Gynaecol Can 2011; 33: 1099–104. https://doi.org/10.1016/s1701-2163(16)35077-0

Article  PubMed  Google Scholar 

Bahr MH, Alkhatip AA, Ahmed AG, Elgamel AF, Abdelkader M, Hussein HA. Hemodynamic effects of oxytocin and carbetocin during elective Cesarean section in preeclamptic patients under spinal anesthesia: a randomized double-blind controlled study. Anesth Pain Med 2023; 13: e128782. https://doi.org/10.5812/aapm-128782

Article  PubMed  PubMed Central  Google Scholar 

Chen YT, Chen SF, Hsieh TT, Lo LM, Hung TH. A comparison of the efficacy of carbetocin and oxytocin on hemorrhage-related changes in women with Cesarean deliveries for different indications. Taiwan J Obstet Gynecol 2018; 57: 677–82. https://doi.org/10.1016/j.tjog.2018.08.011

Article  PubMed  Google Scholar 

von Schmidt auf Altenstadt JF, Hukkelhoven CW, van Roosmalen J, Bloemenkamp KW. Pre-eclampsia increases the risk of postpartum haemorrhage: a nationwide cohort study in The Netherlands. PLoS One 2013; 8: 2–11. https://doi.org/10.1371/journal.pone.0081959

Article  CAS  Google Scholar 

Anandakrishnan S, Balki M, Farine D, Seaward G, Carvalho JC. Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2. Can J Anesth 2013; 60: 1054–60. https://doi.org/10.1007/s12630-013-0028-2

Article  PubMed  Google Scholar 

Lavoie A, McCarthy RJ, Wong CA. The ED90 of prophylactic oxytocin infusion after delivery of the placenta during Cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study. Anesth Analg 2015; 121: 159–64. https://doi.org/10.1213/ane.0000000000000781

Article  CAS  PubMed  Google Scholar 

American College of Obstetricians and Gynecologists. Gestational hypertension and preeclampsia. Obstet Gynecol 2020; 135: E237–60. https://doi.org/10.1097/aog.0000000000003891

Article  Google Scholar 

Dixon WJ, Mood AM. A method for obtaining and analyzing sensitivity data. J Am Stat Assoc 1948; 43: 109–26. https://doi.org/10.1080/01621459.1948.10483254

Article  Google Scholar 

Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a precis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology 2007; 107: 144–52. https://doi.org/10.1097/01.anes.0000267514.42592.2a

Article  PubMed  Google Scholar 

Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics 2002; 58: 171–7. https://doi.org/10.1111/j.0006-341x.2002.00171.x

Article  PubMed  Google Scholar 

Tyagi A, Mohan A, Singh Y, Luthra A, Garg D, Malhotra RK. Effective dose of prophylactic oxytocin infusion during Cesarean delivery in 90% population of nonlaboring patients with preeclampsia receiving magnesium sulfate therapy and normotensives: an up-down sequential allocation dose-response study. Anesth Analg 2022; 134: 303–11. https://doi.org/10.1213/ane.0000000000005701

Article  CAS  PubMed  Google Scholar 

Fan X, Xu T, Ding H, et al. DNA methylation-reprogrammed oxytocin receptor underlies insensitivity to oxytocin in pre-eclamptic placental vasculature. J Cell Mol Med 2019; 23: 4118–26. https://doi.org/10.1111/jcmm.14299

Article  CAS  PubMed  PubMed Central  Google Scholar