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.	劉興會, 陳錳. 全球產后出血指南異同. 中國實用婦科與產科雜志, 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.	劉興會, 張力, 張靜. 《產后出血預防與處理指南 (草案)》(2009) 及《產后出血預防與處理指南 (2014 年版)》解讀. 中華婦幼臨床醫學雜志 (電子版), 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, 曹俊華, 周冬初, 等. 長效催產素受體激動劑卡貝縮宮素的藥理作用與臨床應用. 中國新藥與臨床雜志, 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.	許楊鵬, 喻亞宇, 付文杰, 等. Meta 分析中缺失標準差換算與標準化均數差估計方法簡介. 中國循證心血管醫學雜志, 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, 陳必良, 辛曉燕, 等. 卡比托辛減少陰道分娩后出血的隨機對照研究. 山西醫科大學學報, 2008, 39(1): 78-80.
13.	范麗. 卡貝縮宮素預防和治療宮縮乏力性產后出血臨床觀察. 中國現代藥物應用, 2012, 6(1): 72-73.
14.	張晶, 宋偉夫. 卡貝縮宮素預防產后出血的臨床研究. 山西醫藥雜志, 2013, 42(15): 936-937.
15.	張國榮. 卡貝縮宮素預防宮縮乏力性產后出血的療效觀察. 中國煤炭工業醫學雜志, 2013, 16(4): 579-580.
16.	李慧敏, 封亦兵, 陳愛増, 等. 卡貝縮宮素預防宮縮乏力性產后出血的臨床研究. 中國婦幼健康研究, 2013, 24(3): 353-355.
17.	李桂蓮. 卡貝縮宮素預防宮縮乏力性產后出血的臨床觀察. 中國地方病防治雜志, 2014, 29(2): 237.
18.	王秀梅. 卡貝縮宮素預防宮縮乏力性產后出血的臨床觀察. 檢驗醫學與臨床, 2014, 11(5): 672-673.
19.	仇藝, 謝涵. 卡貝縮宮素對陰道分娩產后出血的預防作用. 復旦學報 (醫學版), 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. 卡貝縮宮素預防產后出血的臨床效果研究. 中國婦幼健康研究, 2015, 26(5): 1073-1074.
22.	李婭娜. 卡貝縮宮素對陰道分娩產后出血的預防作用. 中外女性健康研究, 2015, (10): 170.
23.	屈小潔, 龐妮妮, 趙娜. 卡貝縮宮素對高危產婦陰道分娩產后出血的預防作用. 安徽醫學, 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.	童慧華. 卡貝縮宮素對陰道分娩產后出血的預防效果觀察. 醫學理論與實踐, 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, Sj?holm 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. 劉興會, 陳錳. 全球產后出血指南異同. 中國實用婦科與產科雜志, 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. 劉興會, 張力, 張靜. 《產后出血預防與處理指南 (草案)》(2009) 及《產后出血預防與處理指南 (2014 年版)》解讀. 中華婦幼臨床醫學雜志 (電子版), 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, 曹俊華, 周冬初, 等. 長效催產素受體激動劑卡貝縮宮素的藥理作用與臨床應用. 中國新藥與臨床雜志, 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. 許楊鵬, 喻亞宇, 付文杰, 等. Meta 分析中缺失標準差換算與標準化均數差估計方法簡介. 中國循證心血管醫學雜志, 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, 陳必良, 辛曉燕, 等. 卡比托辛減少陰道分娩后出血的隨機對照研究. 山西醫科大學學報, 2008, 39(1): 78-80.
13. 范麗. 卡貝縮宮素預防和治療宮縮乏力性產后出血臨床觀察. 中國現代藥物應用, 2012, 6(1): 72-73.
14. 張晶, 宋偉夫. 卡貝縮宮素預防產后出血的臨床研究. 山西醫藥雜志, 2013, 42(15): 936-937.
15. 張國榮. 卡貝縮宮素預防宮縮乏力性產后出血的療效觀察. 中國煤炭工業醫學雜志, 2013, 16(4): 579-580.
16. 李慧敏, 封亦兵, 陳愛増, 等. 卡貝縮宮素預防宮縮乏力性產后出血的臨床研究. 中國婦幼健康研究, 2013, 24(3): 353-355.
17. 李桂蓮. 卡貝縮宮素預防宮縮乏力性產后出血的臨床觀察. 中國地方病防治雜志, 2014, 29(2): 237.
18. 王秀梅. 卡貝縮宮素預防宮縮乏力性產后出血的臨床觀察. 檢驗醫學與臨床, 2014, 11(5): 672-673.
19. 仇藝, 謝涵. 卡貝縮宮素對陰道分娩產后出血的預防作用. 復旦學報 (醫學版), 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. 卡貝縮宮素預防產后出血的臨床效果研究. 中國婦幼健康研究, 2015, 26(5): 1073-1074.
22. 李婭娜. 卡貝縮宮素對陰道分娩產后出血的預防作用. 中外女性健康研究, 2015, (10): 170.
23. 屈小潔, 龐妮妮, 趙娜. 卡貝縮宮素對高危產婦陰道分娩產后出血的預防作用. 安徽醫學, 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. 童慧華. 卡貝縮宮素對陰道分娩產后出血的預防效果觀察. 醫學理論與實踐, 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, Sj?holm 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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