The efficacy and safety of carbetocin<i>versus</i>oxytocin on the prevention of postpartum hemorrhage for women undergoing vaginal delivery: a meta-analysis _Chinese Journal of Evidence-Based Medicine

Authors：

TAN Yaqing , LIU Shujun , CAO Shiyu , WANG Tingting ,  CHEN Lizhang

Department of Epidemiology and Health Statistics, School of Xiangya Public Health, Central South University, Changsha, 410078, P.R.China;

Corresponding author：

CHEN Lizhang, Email: chenliz@csu.edu.cn

Keywords：

Carbetocin; Oxytocin; Vaginal delivery; Postpartum hemorrhage; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.201802014

Video：

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Objectives To systematically review the efficacy and safety of carbetocinversusoxytocin on the prevention of postpartum hemorrhage (PPH) for women undergoing vaginal delivery. Methods PubMed, The Cochrane Library, Web of Science, CBM, WanFang Data, CNKI and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on carbetocinversusoxytocin on the prevention of PPH for women undergoing vaginal delivery from inception to January 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 and Stata 12.0 software. Results A total of 16 RCTs including 2 537 patients were included. The results of meta-analysis showed that: compared to oxytocin, carbetocin could reduce the amount of blood loss within 24h (MD=–107.68, 95%CI–130.21 to –85.15, P<0.000 01) and 2h (MD=–85.98, 95%CI–93.37 to –78.59,P<0.000 01), hemoglobin (Hb) within 24h after delivery (MD=–5.63, 95%CI–6.82 to –4.43,P<0.000 01), the occurrence of PPH (RR=0.46, 95%CI 0.32 to 0.66,P<0.000 01) and the requirement for additional uterotonic agents (RR=0.63, 95%CI 0.48 to 0.84,P=0.002). There was no significant difference in the risk of adverse effects between two groups. Conclusions Current evidence shows that carbetocin is superior to oxytocin in the prevention of PPH for women undergoing vaginal delivery, without increasing the adverse effects. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above the conclusion.

Citation： TAN Yaqing, LIU Shujun, CAO Shiyu, WANG Tingting, CHEN Lizhang. The efficacy and safety of carbetocinversusoxytocin on the prevention of postpartum hemorrhage for women undergoing vaginal delivery: a meta-analysis . Chinese Journal of Evidence-Based Medicine, 2018, 18(10): 1093-1100. doi: 10.7507/1672-2531.201802014 Copy

1.	刘兴会, 陈锰. 全球产后出血指南异同. 中国实用妇科与产科杂志, 2017, 33(6): 556-559.
2.	Gulmezoglu AM, Souza JP, Chou D, et al. WHO guidelines for the management of postpartum haemorrhage and retained placenta. Geneva: World Health Organization, 2009.
3.	Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health, 2014, 2(6): e323-e333.
4.	Meshykhi LS, Nel MR, Lucas DN. The role of carbetocin in the prevention and management of postpartum haemorrhage. Int J Obstet Anesth, 2016, 28: 61-69.
5.	刘兴会, 张力, 张静. 《产后出血预防与处理指南 (草案)》(2009) 及《产后出血预防与处理指南 (2014 年版)》解读. 中华妇幼临床医学杂志 (电子版), 2015, 11(4): 433-447.
6.	Du Vigneaud V. Trail of sulfur research: from insulin to oxytocin. Science, 1956, 123(3205): 967-974.
7.	李健和, 曹俊华, 周冬初, 等. 长效催产素受体激动剂卡贝缩宫素的药理作用与临床应用. 中国新药与临床杂志, 2012, 31(3): 134-138.
8.	Su LL, Chong YS, Samuel M. Carbetocin for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews, 2012, (4): CD005457.
9.	许杨鹏, 喻亚宇, 付文杰, 等. Meta 分析中缺失标准差换算与标准化均数差估计方法简介. 中国循证心血管医学杂志, 2016, 8(12): 1412-1415.
10.	Boucher M, CarlNimrod, GeorgesTawagi. Carbetocin IM injection vs. oxytocin IV infusion for prevention of postpartum hemorrhage in women at risk following vaginal delivery. Am J Obstet Gynecol, 2001, 185(6): S216.
11.	Boucher M, Nimrod CA, Tawagi GF, et al. 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(5): 481-488.
12.	王林, 陈必良, 辛晓燕, 等. 卡比托辛减少阴道分娩后出血的随机对照研究. 山西医科大学学报, 2008, 39(1): 78-80.
13.	范丽. 卡贝缩宫素预防和治疗宫缩乏力性产后出血临床观察. 中国现代药物应用, 2012, 6(1): 72-73.
14.	张晶, 宋伟夫. 卡贝缩宫素预防产后出血的临床研究. 山西医药杂志, 2013, 42(15): 936-937.
15.	张国荣. 卡贝缩宫素预防宫缩乏力性产后出血的疗效观察. 中国煤炭工业医学杂志, 2013, 16(4): 579-580.
16.	李慧敏, 封亦兵, 陈爱増, 等. 卡贝缩宫素预防宫缩乏力性产后出血的临床研究. 中国妇幼健康研究, 2013, 24(3): 353-355.
17.	李桂莲. 卡贝缩宫素预防宫缩乏力性产后出血的临床观察. 中国地方病防治杂志, 2014, 29(2): 237.
18.	王秀梅. 卡贝缩宫素预防宫缩乏力性产后出血的临床观察. 检验医学与临床, 2014, 11(5): 672-673.
19.	仇艺, 谢涵. 卡贝缩宫素对阴道分娩产后出血的预防作用. 复旦学报 (医学版), 2014, 41(1): 102-105.
20.	Kabir N, Akter D, Daisy TA, et al. Efficacy and safety of carbetocin in comparison to oxytocin in the active management of third stage of labour following vaginal delivery: an open label randomized control trial. Bangladesh J Obstet Gynaecol, 2015, 30(1): 3-9.
21.	耿雪梅. 卡贝缩宫素预防产后出血的临床效果研究. 中国妇幼健康研究, 2015, 26(5): 1073-1074.
22.	李娅娜. 卡贝缩宫素对阴道分娩产后出血的预防作用. 中外女性健康研究, 2015, (10): 170.
23.	屈小洁, 庞妮妮, 赵娜. 卡贝缩宫素对高危产妇阴道分娩产后出血的预防作用. 安徽医学, 2016, 37(11): 1351-1354.
24.	Maged AM, Hassan AM, Shehata NA. Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women. J Matern Fetal Neonatal Med, 2016, 29(4): 532-536.
25.	童慧华. 卡贝缩宫素对阴道分娩产后出血的预防效果观察. 医学理论与实践, 2017, 30(15): 2285-2286.
26.	Carroli G, Cuesta C, Abalos E, et al. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol, 2008, 22(6): 999-1012.
27.	Sweeney G, Holbrook AM, Levine M, et al. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in non-pregnant women. Curr Ther Res ClinExper, 1990, 47: 528-539.
28.	Rydén G, Sjöholm I. Half-life of oxytocin in blood of pregnant and non-pregnant women. Acta Endocrinol (Copenh), 1969, 61(3): 425-431.
29.	Fabian M, Forsling ML, Jones JJ, et al. The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability. J Physiol, 1969, 204(3): 653-668.
30.	Del Angel-Garcia G, Garcia-Contreras F, Constantino-Casas P, et al. Economic evaluation of carbetocin for the prevention of uterine atony in patients with risk factors in Mexico. Value in Health, 2006, 9: A254.

1. 刘兴会, 陈锰. 全球产后出血指南异同. 中国实用妇科与产科杂志, 2017, 33(6): 556-559.
2. Gulmezoglu AM, Souza JP, Chou D, et al. WHO guidelines for the management of postpartum haemorrhage and retained placenta. Geneva: World Health Organization, 2009.
3. Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health, 2014, 2(6): e323-e333.
4. Meshykhi LS, Nel MR, Lucas DN. The role of carbetocin in the prevention and management of postpartum haemorrhage. Int J Obstet Anesth, 2016, 28: 61-69.
5. 刘兴会, 张力, 张静. 《产后出血预防与处理指南 (草案)》(2009) 及《产后出血预防与处理指南 (2014 年版)》解读. 中华妇幼临床医学杂志 (电子版), 2015, 11(4): 433-447.
6. Du Vigneaud V. Trail of sulfur research: from insulin to oxytocin. Science, 1956, 123(3205): 967-974.
7. 李健和, 曹俊华, 周冬初, 等. 长效催产素受体激动剂卡贝缩宫素的药理作用与临床应用. 中国新药与临床杂志, 2012, 31(3): 134-138.
8. Su LL, Chong YS, Samuel M. Carbetocin for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews, 2012, (4): CD005457.
9. 许杨鹏, 喻亚宇, 付文杰, 等. Meta 分析中缺失标准差换算与标准化均数差估计方法简介. 中国循证心血管医学杂志, 2016, 8(12): 1412-1415.
10. Boucher M, CarlNimrod, GeorgesTawagi. Carbetocin IM injection vs. oxytocin IV infusion for prevention of postpartum hemorrhage in women at risk following vaginal delivery. Am J Obstet Gynecol, 2001, 185(6): S216.
11. Boucher M, Nimrod CA, Tawagi GF, et al. 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(5): 481-488.
12. 王林, 陈必良, 辛晓燕, 等. 卡比托辛减少阴道分娩后出血的随机对照研究. 山西医科大学学报, 2008, 39(1): 78-80.
13. 范丽. 卡贝缩宫素预防和治疗宫缩乏力性产后出血临床观察. 中国现代药物应用, 2012, 6(1): 72-73.
14. 张晶, 宋伟夫. 卡贝缩宫素预防产后出血的临床研究. 山西医药杂志, 2013, 42(15): 936-937.
15. 张国荣. 卡贝缩宫素预防宫缩乏力性产后出血的疗效观察. 中国煤炭工业医学杂志, 2013, 16(4): 579-580.
16. 李慧敏, 封亦兵, 陈爱増, 等. 卡贝缩宫素预防宫缩乏力性产后出血的临床研究. 中国妇幼健康研究, 2013, 24(3): 353-355.
17. 李桂莲. 卡贝缩宫素预防宫缩乏力性产后出血的临床观察. 中国地方病防治杂志, 2014, 29(2): 237.
18. 王秀梅. 卡贝缩宫素预防宫缩乏力性产后出血的临床观察. 检验医学与临床, 2014, 11(5): 672-673.
19. 仇艺, 谢涵. 卡贝缩宫素对阴道分娩产后出血的预防作用. 复旦学报 (医学版), 2014, 41(1): 102-105.
20. Kabir N, Akter D, Daisy TA, et al. Efficacy and safety of carbetocin in comparison to oxytocin in the active management of third stage of labour following vaginal delivery: an open label randomized control trial. Bangladesh J Obstet Gynaecol, 2015, 30(1): 3-9.
21. 耿雪梅. 卡贝缩宫素预防产后出血的临床效果研究. 中国妇幼健康研究, 2015, 26(5): 1073-1074.
22. 李娅娜. 卡贝缩宫素对阴道分娩产后出血的预防作用. 中外女性健康研究, 2015, (10): 170.
23. 屈小洁, 庞妮妮, 赵娜. 卡贝缩宫素对高危产妇阴道分娩产后出血的预防作用. 安徽医学, 2016, 37(11): 1351-1354.
24. Maged AM, Hassan AM, Shehata NA. Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women. J Matern Fetal Neonatal Med, 2016, 29(4): 532-536.
25. 童慧华. 卡贝缩宫素对阴道分娩产后出血的预防效果观察. 医学理论与实践, 2017, 30(15): 2285-2286.
26. Carroli G, Cuesta C, Abalos E, et al. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol, 2008, 22(6): 999-1012.
27. Sweeney G, Holbrook AM, Levine M, et al. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in non-pregnant women. Curr Ther Res ClinExper, 1990, 47: 528-539.
28. Rydén G, Sjöholm I. Half-life of oxytocin in blood of pregnant and non-pregnant women. Acta Endocrinol (Copenh), 1969, 61(3): 425-431.
29. Fabian M, Forsling ML, Jones JJ, et al. The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability. J Physiol, 1969, 204(3): 653-668.
30. Del Angel-Garcia G, Garcia-Contreras F, Constantino-Casas P, et al. Economic evaluation of carbetocin for the prevention of uterine atony in patients with risk factors in Mexico. Value in Health, 2006, 9: A254.

Chinese Journal of Evidence-Based Medicine

The efficacy and safety of carbetocinversusoxytocin on the prevention of postpartum hemorrhage for women undergoing vaginal delivery: a meta-analysis

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