Original Article| Volume 40, P14-23, November 2019

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Carbetocin reduces the need for additional uterotonics in elective caesarean delivery: a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials


      • Carbetocin is superior to oxytocin against postpartum hemorrhage in mixed populations.
      • Data were analysed only from patients having elective caesarean deliveries.
      • Trial sequential analysis showed carbetocin reduced need for additional uterotonics.
      • Additional trials are needed to show the effect of carbetocin on bleeding-related outcomes.



      Carbetocin has been found to be superior to oxytocin in terms of need for additional uterotonics and prevention of postpartum haemorrhage at caesarean delivery. However, this is based on combined data from labouring and non-labouring parturients and it remains unclear how effective carbetocin is in the purely elective setting. The aim of this review was to compare carbetocin to oxytocin in elective caesarean delivery.


      Medline, Embase, CINAHL, Web of Science, and the Cochrane databases were searched for randomised controlled trials in any language. The primary outcome was need for additional uterotonics. Secondary outcomes were mean blood loss, need for blood transfusion and incidence of postpartum haemorrhage >1000 mL.


      Nine studies with a total of 1962 patients were included. Trial sequential analysis confirmed that the information size (n=1692) had surpassed that required (n=1166) in order to demonstrate a statistically significant reduction in the use of additional uterotonics. Need for additional uterotonics was reduced by 53% with carbetocin compared to oxytocin (OR 0.47, 95% CI 0.34 to 0.64; P <0.001, I2=63.5). The number needed-to-treat was 11. The risk of bias, data heterogeneity and inconsistency in reporting bleeding outcomes made it difficult to reach definite conclusions about prevention of PPH.


      Carbetocin is associated with a reduced need for additional uterotonics when compared with oxytocin at elective caesarean delivery. Standardisation of bleeding-related outcomes in studies is necessary to facilitate synthesis of data in future analyses.


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        • Say L.
        • Chou D.
        • Gemmill A.
        • et al.
        Global causes of maternal death: a WHO systematic analysis.
        Lancet Glob Heal. 2014; 2: 323-333
        • Anderson J.M.
        • Etches D.
        Prevention and management of postpartum hemorrhage.
        Am Fam Physician. 2007; 75: 875-882
        • Westhoff G.
        • Cotter A.
        • Tolosa J.
        Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage (Review).
        Cochrane Database Syst Rev. 2013; 10: CD001808
        • Mousa H.
        • Blum J.
        • El Senoun A.
        • Shakur H.
        • Alfirevic Z.
        Treatment for primary postpartum haemorrhage (Review).
        Cochrane Database Syst Rev. 2014; 13: CD003249
        • Fahmy N.G.
        • Yousef H.M.
        • Zaki H.V.
        Comparative study between effect of carbetocin and oxytocin on isoflurane-induced uterine hypotonia in twin pregnancy patients undergoing cesarean section.
        Egypt J Anaesth. 2016; 32: 117-121
        • Boucher M.
        • Horbay G.L.
        • Griffin P.
        • et al.
        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; 18: 202-207
        • Boucher M.
        • Nimrod C.A.
        • Tawagi G.F.
        • Meeker T.A.
        • White R.E.R.
        • 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; 26: 481-488
        • Borruto F.
        • Treisser A.
        • Comparetto C.
        Utilization of carbetocin for prevention of postpartum hemorrhage after cesarean section: A randomized clinical trial.
        Arch Gynecol Obstet. 2009; 280: 707-712
        • Dansereau J.
        • Joshi A.K.
        • Helewa M.E.
        • et al.
        Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section.
        Am J Obstet Gynecol. 1999; 180: 670-676
        • Su L.
        • Chong Y.
        • Samuel M.
        Carbetocin for preventing postpartum haemorrhage (Review).
        Cochrane Database Syst Rev. 2012; 4: CD005457
        • Jin B.
        • Du Y.
        • Zhang F.
        • Zhang K.
        • Wang L.
        • Cui L.
        Carbetocin for the prevention of postpartum hemorrhage: a systematic review and meta-analysis of randomized controlled trials.
        J Matern Neonatal Med. 2016; 29: 400-407
        • Gallos I.
        • Williams H.
        • Price M.
        • et al.
        Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis (Review).
        Cochrane Database Syst Rev. 2018; 12: CD011689
        • Wetterslev J.
        • Jakobsen J.C.
        • Gluud C.
        Trial sequential analysis in systematic reviews with meta-analysis.
        BMC Med Res Methodol. 2017; 17: 39
        • Nunnally M.E.
        • Tung A.
        Meta-analysis, medical reversal, and settled science.
        Anesth Analg. 2018; 126: 739-740
        • Imberger G.
        • Thorlund K.
        • Gluud C.
        • Wetterslev J.
        False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review.
        BMJ Open. 2016; 6e011890
        • Imberger G.
        • Gluud C.
        • Boylan J.
        • Wetterslev J.
        Systematic reviews of anesthesiologic interventions reported as statistically significant: Problems with power, precision, and type 1 error protection.
        Anesth Analg. 2015; 121: 1611-1622
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        J Clin Epidemiol. 2009; 62: 1006-1012
        • Hozo S.P.
        • Djulbegovic B.
        • Hozo I.
        Estimating the mean and variance from the median, range, and the size of a sample.
        BMC Med Res Methodol. 2005; 5: 13
        • Thiessen Philbrook H.
        • Barrowman N.
        • Garg A.X.
        Imputing variance estimates do not alter the conclusions of a meta-analysis with continuous outcomes: a case study of changes in renal function after living kidney donation.
        J Clin Epidemiol. 2007; 60: 228-240
        • Chowdhry A.K.
        • Dworkin R.H.
        • McDermott M.P.
        Meta-analysis with missing study-level sample variance data.
        Stat Med. 2016; 35: 3021-3032
        • Higgins J.P.T.
        • Altman D.G.
        • Gotzsche P.C.
        • et al.
        The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Guyatt G.
        • Oxman A.
        • Vist G.
        • et al.
        GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
        • Attilakos G.
        • Psaroudakis D.
        • Ash J.
        • et al.
        Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following caesarean section: the results of a double-blind randomised trial.
        Br J Obstet Gynaecol. 2010; 117: 1665
        • Moertl M.G.
        • 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.
        Br J Obstet Gynaecol. 2011; 118: 1349-1356
        • el Sharkwy I.A.E.
        Carbetocin versus sublingual misoprostol plus oxytocin infusion for prevention of postpartum hemorrhage at cesarean section in patients with risk factors: a randomized, open trail study.
        Arch Gynecol Obstet Germany. 2013; 288: 1231-1236
        • Rosseland L.A.
        • Hauge T.H.
        • Grindheim G.
        • Stubhaug A.
        • Langesaeter E.
        Changes in blood pressure and cardiac output during Cesarean delivery: the effects of oxytocin and carbetocin compared with placebo.
        Anesthesiology. 2013; 119: 541-551
        • Elbohoty A.E.H.
        • Mohammed W.E.
        • Sweed M.
        • Bahaa Eldin A.M.
        • Nabhan A.
        • Abd-El-Maeboud K.H.I.
        Randomized controlled trial comparing carbetocin, misoprostol, and oxytocin for the prevention of postpartum hemorrhage following an elective cesarean delivery.
        Int J Gynecol Obstet. 2016; 134: 324-328
        • Mannaerts D.
        • der Veeken L.
        • Coppejans H.
        • Jacquemyn Y.
        Adverse effects of carbetocin versus oxytocin in the prevention of postpartum haemorrhage after caesarean section: a randomized controlled trial.
        J Pregnancy. 2018 Jan 2; 2018 (1374150)
      1. CROWN Initiative. Core outcome sets in women’s and newborn health [Internet]. 2017. Available at: Accessed March 19, 2019.

        • Meher S.
        • Cuthbert A.
        • Kirkham J.J.
        • et al.
        Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study.
        Br J Obstet Gynaecol. 2019; 126: 83-93
        • Foley A.
        • Gunter A.
        • Nunes K.J.
        • Shahul S.
        • Scavone B.M.
        Patients undergoing cesarean delivery after exposure to oxytocin during labor require higher postpartum oxytocin doses.
        Anesth Analg. 2018; 126: 920-924
        • Nguyen-Lu N.
        • Carvalho J.C.A.
        • Farine D.
        • Seaward G.
        • Ye X.Y.
        • Balki M.
        Carbetocin at Cesarean delivery for labour arrest: a sequential allocation trial to determine the effective dose.
        Can J Anesth. 2015; 62: 866-874
        • Khan M.
        • Balki M.
        • Ahmed I.
        • Farine D.
        • Seaward G.
        • Carvalho J.C.
        Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose.
        Can J Anesth. 2014; 61: 242-248