[Lancet Global Health在线发表]:WHO有关静脉氨甲环酸治疗产后出血的推荐意见 | 中国病理生理学会危重病医学专业委员会
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[Lancet Global Health在线发表]:WHO有关静脉氨甲环酸治疗产后出血的推荐意见
2018年01月11日 指南导读, 进展交流 暂无评论

Updated WHO recommendation on intravenous tranexamic acid for the treatment of post-partum haemorrhage

Joshua P Vogel, Olufemi T Oladapo, Therese Dowswell, et al

Lancet Global Health 2017 Published Online October 31, 2017

http://dx.doi.org/10.1016/ S2214-109X(17)30428-X

Post-partum haemorrhage is the leading cause of maternal mortality globally.1 The majority of deaths resulting from post-partum haemorrhage occur during the rst 24 h after birth, most of which could be avoided by routine prevention through active management of the third stage of labour and prompt and e ective management of post-partum haemorrhage, including the use of uterotonics and uid replacement. Tranexamic acid, an antifibrinolytic drug, was identified as a promising candidate to be included in recommended packages for treatment of post-partum haemorrhage, since it has shown efficacy in reducing blood loss and mortality following surgical trauma.2 This hypothesis led to the conduct of the largest trial of tranexamic acid for the treatment of post-partum haemorrhage to date, the World Maternal Anti brinolytic (WOMAN) trial, which was published in April, 2017.3 The WOMAN trial was a randomised, double-blind, placebo-controlled trial in which women with a clinical diagnosis of post-partum haemorrhage (regardless of mode of birth) were randomly assigned to a regimen of intravenous tranexamic acid or placebo. Nearly 200 hospitals in 21 high-income, middle-income, and low-income countries participated, recruiting over 20 000 women. The investigators concluded that early use (within 3 h of birth) of intravenous tranexamic acid reduces maternal death due to bleeding in women with clinically diagnosed post-partum haemorrhage, and that early treatment appears to optimise benefits.

In response to the WOMAN Trial, a new Cochrane review was rapidly initiated to assess the effect of antifibrinolytic drugs (in additional to standard care) compared with standard (or usual) care alone for treatment of post-partum haemorrhage (Shakur H, unpublished). This review includes only two trials in which tranexamic acid was compared with standard care. Evidence from the WOMAN trial dominates the findings.3 The other trial was conducted in eight obstetric units in France, and randomly assigned 152 women with post-partum haemorrhage (defined as more than 800 mL of blood lost) after vaginal birth to treatment with tranexamic acid or placebo.4 An individual participant-data meta-analysis of 40 138 bleeding patients,5 that includes participants from both the WOMAN3 and CRASH-2 trials,6 is an important complement to the findings of the Cochrane review.

WHO recommendations are regularly updated to reflect the latest scientific evidence, particularly when new evidence that could affect the strength or direction of existing recommendations becomes available. With a view to updating the existing WHO recommendation, a Guideline Development Group (GDG) was convened in August, 2017, to review and consider the updated analysis, values, and preferences of stakeholders, resource requirements, cost-effectiveness, acceptability, feasibility, and equity with respect to treatment of post-partum haemorrhage with tranexamic acid. WHO has now published an updated recommendation on the use of tranexamic acid for treatment of post-partum haemorrhage,7 which supersedes the 2012 recommendation.8

WHO strongly recommends early use of intravenous tranexamic acid (within 3 h of birth), in addition to standard care for women with clinically diagnosed post-partum haemorrhage following vaginal birth or caesarean section. On the basis of the dosing regimen used in the WOMAN trial, the GDG supports treatment with tranexamic acid at a fixed dose of 1 g (100 mg/mL) intravenously at 1 mL/min (ie, given over 10 min), with a second dose of 1 g intravenously if bleeding continues after 30 min, or if bleeding restarts within 24 h of completing the first dose. In the context of this recommendation, “clinically diagnosed postpartum haemorrhage” refers to a clinically estimated blood loss of more than 500 mL after vaginal birth or 1000 mL after caesarean section, or any blood loss that is sufficient to compromise haemodynamic stability.3 The GDG remarked that tranexamic acid should be given in all cases of post-partum haemorrhage, regardless of whether the bleeding is thought to be due to genital tract trauma or for other reasons, including uterine atony. This updated recommendation is broader than the previous recommendation of 2012, which advised that tranexamic acid be given for treatment of post-partum haemorrhage only if oxytocin and other uterotonics fail to stop bleeding, or if it is thought that the bleeding could be partly due to trauma.

The GDG panel considered the benefits and potential harms of tranexamic acid, and emphasised the 3 h threshold (following birth), after which it should not be given. This judgment was based on the individual participant data meta-analysis of the effects of timing of administration,5 which indicates that delay in treatment appears to reduce benefit, decreasing by 10% for every 15 min delay, and with no benefit seen after 3 h. Giving tranexamic acid to women with post-partum haemorrhage beyond 3 h after birth is suspected to be potentially harmful. Importantly, giving the drug earlier after birth appears to increase benefit; hence it should be given as soon as possible for treatment of post-partum haemorrhage.

Giving tranexamic acid should be considered as part of the standard treatment packages for post-partum haemorrhage, in accordance with WHO guidelines.7,8 This package includes fluid replacement, treatment with uterotonics, monitoring of vital signs, and non-surgical (eg, bimanual compression, intrauterine balloon tamponade, non-pneumatic antishock garment, external aortic compression) and surgical interventions (eg, brace sutures, arterial ligation, or hysterectomy). The sequential use of these interventions should start with less invasive interventions, moving towards more invasive interventions as required. Health facilities in which emergency obstetric care is provided need to have the necessary supplies and the necessary training for staff who attend births, so that tranexamic acid can be given safely by intravenous infusion. Treatment with tranexamic acid should be avoided in women with a clear contraindication to antifibrinolytic therapy (eg, a known thromboembolic event during pregnancy). This updated recommendation7 applies to giving the drug intravenously only, since the benefits and potential harms of other routes of administration are not yet known and are a research priority. Wide and effective implementation of this recommendation would require all health systems, regardless of their level of resources, to recognise tranexamic acid as a life-saving intervention that should be made readily available for the management of post-partum haemorrhage wherever emergency obstetric care is provided.

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