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热稳定型卡贝缩宫素与催产素预防阴道分娩后出血的比较
Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth


Mariana Widmer ... 妇产科和儿科 • 2018.08.23
NEJM 动画解读

卡贝缩宫素预防产后出血
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无须冷链运输的卡贝缩宫素控制产后出血

 

魏瑗,李蓉*

北京大学第三医院妇产科

*通讯作者

 

产后出血是最常见的孕产妇死亡原因。70%的产后出血与宫缩乏力有关,因此2012年WHO颁布的产后出血的规范1预防策略中强调缩宫素(即催产素,oxytocin)的规范使用。但由于缩宫素的储存条件要求较高,需要保存在2~8℃(冷藏)以保持稳定的效能,否则可能出现药效的下降。

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摘要


背景

产后出血是产妇死亡的最常见原因。催产素是预防产后出血的标准疗法,但需要冷藏,而许多国家没有冷藏条件。在一项大型试验中,我们对一种新型热稳定型卡贝缩宫素制剂和催产素进行了比较。

 

方法

在一项随机、双盲、非劣效性试验中,我们在10个国家的23个研究中心纳入了女性受试者,对阴道分娩后立即肌内注射热稳定型卡贝缩宫素(剂量为100 μg)和催产素(剂量为10 IU)进行了比较。两种药物均冷藏(2~8℃),以保持双盲。本研究有两项主要结局:失血≥500 mL或使用额外的子宫收缩剂的产妇比例,以及失血≥1,000 mL的产妇比例。这些结局的相对危险度的非劣效性界值分别为1.16和1.23。

 

结果

总共29,645名女性经随机分组。在卡贝缩宫素组和催产素组中,失血≥500 mL或使用额外的子宫收缩剂的发生率分别为14.5%和14.4%(相对危险度,1.01;95%置信区间[CI],0.95~1.06),这一发现符合非劣效性。在卡贝缩宫素组和催产素组中,失血≥1,000 mL的发生率分别为1.51%和1.45%(相对危险度,1.04;95% CI,0.87~1.25),置信区间跨越非劣效性界值。在额外的子宫收缩剂的使用、止血干预和不良反应方面,两组之间无显著差异。

 

结论

在预防失血≥500 mL或使用额外的子宫收缩剂方面,热稳定型卡贝缩宫素不劣于催产素。对于失血≥1,000 mL这一结局,本研究未证明非劣效性。这一结局的事件发生率低,因此降低了本试验的统计学功效(由默沙东资助;CHAMPION在澳大利亚新西兰临床试验注册号为ACTRN12614000870651;在EudraCT注册号为2014-004445-26;在印度临床试验注册号为CTRI/2016/05/006969)。





作者信息

Mariana Widmer, M.Sc., Gilda Piaggio, Ph.D., Thi M.H. Nguyen, Ph.D., Alfred Osoti, M.P.H., Olorunfemi O. Owa, M.D., Sujata Misra, M.D., Arri Coomarasamy, M.R.C.O.G., Hany Abdel-Aleem, M.D., Ashalata A. Mallapur, M.D., Zahida Qureshi, M.D., Pisake Lumbiganon, M.D., Archana B. Patel, Ph.D., Guillermo Carroli, M.D., Bukola Fawole, M.D., Shivaprasad S. Goudar, M.D., Yeshita V. Pujar, M.D., James Neilson, Ph.D., G. Justus Hofmeyr, D.Sc., Lin L. Su, M.R.C.O.G., Jose Ferreira de Carvalho, Ph.D., Uma Pandey, M.D., Kidza Mugerwa, M.D., Shobha S. Shiragur, M.D., Josaphat Byamugisha, Ph.D., Daniel Giordano, B.Sc., and A. Metin Gülmezoglu, Ph.D. for the WHO CHAMPION Trial Group*
From the Department of Reproductive Health and Research, World Health Organization (WHO), United Nations Development Program–United Nations Population Fund–UNICEF–WHO–World Bank Special Program of Research, Development, and Research Training in Human Reproduction, Geneva (M.W., T.M.H.N., A.M.G.); Statistika Consultoria, Campinas, Brazil (G.P., J.F.C.); the Department of Obstetrics and Gynecology, School of Medicine, University of Nairobi, Nairobi, Kenya (A.O., Z.Q.); the Department of Obstetrics and Gynecology, Mother and Child Hospital, Akure (O.O.O.), and the Department of Obstetrics and Gynecology, College of Medicine, University of Ibadan, Ibadan (B.F.) — both in Nigeria; Sriram Chandra Bhanja Medical College, Cuttack (S.M.), S. Nijalingappa Medical College and Hangal Shri Kumareshwar Hospital and Medical Research Center (A.A.M.), Karnatak Lingayat Education Academy of Higher Education and Research, Jawaharlal Nehru Medical College (S.S.G., Y.V.P.), and Shri B.M. Patil Medical College, Hospital and Research Center (S.S.S.), Karnataka, Lata Medical Research Foundation and Daga Women’s Hospital, Maharashtra (A.B.P.), and the Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi (U.P.) — all in India; the Institute of Metabolism and Systems Research, University of Birmingham, Birmingham (A.C.), and the Department of Obstetrics and Gynaecology, University of Liverpool, Liverpool (J.N.) — both in the United Kingdom; the Department of Obstetrics and Gynecology, Women’s Health Hospital, Faculty of Medicine, Assiut University, Assiut, Egypt (H.A.-A.); the Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand (P.L.); Centro Rosarino de Estudios Perinatales, Rosario, Argentina (G.C., D.G.); the Effective Care Research Unit, Universities of Witwatersrand–Johannesburg, Fort Hare–Alice, and Walter Sisulu–Eastern Cape, and the Eastern Cape Department of Health, Eastern Cape — all in South Africa (G.J.H.); the Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (L.L.S.); and the Department of Obstetrics and Gynecology, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda (K.M., J.B.). Address reprint requests to Dr. Gülmezoglu at the Department of Reproductive Health and Research, World Health Organization, Ave. Appia 20, Geneva 1201, Switzerland, or at gulmezoglum@who.int. *A complete list of investigators in the WHO CHAMPION Trial Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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