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E001466.Full.Pdf Editorial BMJ Glob Health: first published as 10.1136/bmjgh-2019-001466 on 11 April 2019. Downloaded from WHO recommendations on uterotonics for postpartum haemorrhage prevention: what works, and which one? Joshua P Vogel, 1,2 Myfanwy Williams,3 Ioannis Gallos,4 Fernando Althabe,1 Olufemi T Oladapo1 To cite: Vogel JP, THE GLOBAL BURDEN OF POSTPARTUM trials of tranexamic acid for PPH treatment Williams M, Gallos I, et al. HAEMORRHAGE and a heat-stable formulation of carbetocin WHO recommendations on 6–12 uterotonics for postpartum Obstetric haemorrhage, especially post- for PPH prevention. The increasing haemorrhage prevention: partum haemorrhage (PPH), was responsible number of PPH prevention and management what works, and which for more than a quarter of the estimated 303 options makes it challenging for providers one?BMJ Glob Health 000 maternal deaths that occurred globally in and health system stakeholders to choose 2019;4:e001466. doi:10.1136/ 2015.1 PPH—commonly defined as a blood where and how to invest limited resources in bmjgh-2019-001466 loss of 500 mL or more within 24 hours after order to optimise health outcomes. birth—affects about 6% of all women giving Multiple uterotonics have been eval- Handling editor Seye Abimbola birth.1 Uterine atony is the most common uated for PPH prevention over the past Received 4 February 2019 cause of PPH, but it can also be caused by four decades, including oxytocin receptor Revised 10 March 2019 genital tract trauma, retained placental tissue agonists (oxytocin and carbetocin), prosta- Accepted 16 March 2019 or maternal bleeding disorders. The majority glandin analogues (misoprostol, sulprostone, of women who experience PPH have no iden- carboprost), ergot alkaloids (such as ergo- tifiable risk factor, meaning that PPH preven- metrine/methylergometrine) and combina- tion programmes rely on universal use of PPH tions of these (oxytocin plus ergometrine, © Author(s) (or their prophylaxis for all women in the immediate or oxytocin plus misoprostol). Trial evidence employer(s)) 2019. Re-use postpartum period. Active management of for each of these options has been meta-an- permitted under CC BY-NC. No the third stage of labour involves prophylactic alysed through multiple separate Cochrane http://gh.bmj.com/ commercial re-use. See rights administration of a uterotonic agent prior to systematic reviews that compared one utero- and permissions. Published by BMJ. delivery of the placenta, as well as delayed tonic option against several other options or 1UNDP/UNFPA/UNICEF/WHO/ cord clamping and controlled traction of the placebo/no treatment. However, subtle but World Bank Special Programme umbilical cord (in settings where skilled birth important methodological differences have of Research, Development attendants are available).2 The uterotonic is emerged between these reviews. For example, and Research Training in the most important component in terms of there are differences in trial eligibility criteria, on September 28, 2021 by guest. Protected copyright. Human Reproduction (HRP), preventing PPH.3 4 In 2012, WHO recom- review outcomes and subgroup comparisons. Department of Reproductive Health and Research, World mended oxytocin (10 IU, intravenously or Some uterotonic comparisons (eg, oxytocin vs Health Organization, Geneva, intramuscularly) as the uterotonic of choice misoprostol) appear in more than one review. Switzerland for PPH prevention at birth for all women.5 Cochrane review standards have evolved over 2 Maternal and Child Health time, meaning more recent reviews may have Program, Burnet Institute, higher methodological rigour. Melbourne, Victoria, Australia 3Cochrane Pregnancy and RECENT INNOVATIONS IN PPH PREVENTION AND These problems were largely resolved Childbirth, University of TREATMENT RESEARCH by a recent Cochrane review and network Liverpool, Liverpool, United There have been major new developments meta-analysis (NMA) of 140 trials (88 947 Kingdom 4 in PPH prevention and treatment in the last women) that considered multiple utero- Institute of Metabolism and tonic drug options (single or combination) Systems Research, University decade, including technological advance- of Birmingham, Birmingham ments (such as inhalational oxytocin and and placebo or no treatment, first published 13 Women's Hospital Foundation the non-pneumatic antishock garment), new in April 2018. A single review of multiple Trust, Birmingham, United treatment strategies (such as advance distri- options meant standardisation of trial eligi- Kingdom bution of prophylactic misoprostol for self-ad- bility, risk of bias assessment and outcome Correspondence to ministration after birth, administration of reporting. The NMA also reported on compar- Dr Joshua P Vogel; oxytocin via Uniiject and care bundles for PPH isons of all options based on the full evidence vogeljo@ who. int management), as well as large multicountry network, providing estimates of effect even Vogel JP, et al. BMJ Glob Health 2019;4:e001466. doi:10.1136/bmjgh-2019-001466 1 BMJ Global Health BMJ Glob Health: first published as 10.1136/bmjgh-2019-001466 on 11 April 2019. Downloaded from Table 1 WHO recommendations on uterotonics for PPH prevention Context Recommendation Efficacy and safety of 1. The use of an effective uterotonic for the prevention of PPH during the third stage of uterotonics for PPH prevention labour is recommended for all births. To effectively prevent PPH, only one of the following uterotonics should be used: ► Oxytocin (recommendation 1.1). ► Carbetocin (recommendation 1.2). ► Misoprostol (recommendation 1.3). ► Ergometrine/methylergometrine (recommendation 1.4). ► Oxytocin and ergometrine fixed dose combination (recommendation 1.5). 1.1 The use of oxytocin (10 IU, IM/IV) is recommended for the prevention of PPH for all births. 1.2 The use of carbetocin (100 µg, IM/IV) is recommended for the prevention of PPH for all births in contexts where its cost is comparable to other effective uterotonics. 1.3 The use of misoprostol (either 400 µg or 600 µg, PO) is recommended for the prevention of PPH for all births. 1.4 The use of ergometrine/methylergometrine (200 µg, IM/IV) is recommended for the prevention of PPH in contexts where hypertensive disorders can be safely excluded prior to its use. 1.5 The use of oxytocin and ergometrine fixed-dose combination (5 IU/500 µg, IM) is recommended for the prevention of PPH in contexts where hypertensive disorders can be safely excluded prior to its use. 1.6 Injectable prostaglandins (carboprost or sulprostone) are not recommended for the prevention of PPH. Choice of uterotonics for PPH 2. In settings where multiple uterotonic options are available, oxytocin (10 IU, IM/IV) is the prevention recommended uterotonic agent for the prevention of PPH for all births. 3. In settings where oxytocin is unavailable (or its quality cannot be guaranteed), the use of other injectable uterotonics (carbetocin, or if appropriate ergometrine/methylergometrine or oxytocin and ergometrine fixed-dose combination) or oral misoprostol is recommended for the prevention of PPH. 4. In settings where skilled health personnel are not present to administer injectable uterotonics, the administration of misoprostol (400 µg or 600 µg PO) by community healthcare workers and lay health workers is recommended for the prevention of PPH. IM, intramuscular; IV, intravenous; PO, per oral; PPH, postpartum haemorrhage. http://gh.bmj.com/ in the absence of a direct comparison (‘head-to-head’) settings where oxytocin is unavailable (or its quality trial. The NMA was closely followed by important new cannot be guaranteed), the use of other injectable utero- findings from a WHO-led, multicountry PPH prevention tonics (carbetocin, or if appropriate ergometrine/meth- trial in June 2018.11 This trial randomised nearly 30 000 ylergometrine or oxytocin and ergometrine fixed-dose on September 28, 2021 by guest. Protected copyright. women in 10 countries to either oxytocin (the recom- combination) or oral misoprostol is recommended for mended standard of care) or a heat-stable formulation the prevention of PPH. In those settings where skilled of carbetocin, and found that heat-stable carbetocin health personnel are not present to administer injectable was non-inferior to oxytocin for the prevention of PPH uterotonics, the administration of misoprostol (400 µg (defined as blood loss of at least 500 mL), and the use or 600 µg orally) by community healthcare workers and of additional uterotonic agents. What should clinicians lay health workers is recommended for the prevention make of these important new findings? It was in this of PPH. context that the Executive Guideline Steering Group on It should be noted that the uterotonic options Maternal and Perinatal Health advised WHO to prioritise containing ergometrine (ergometrine alone, and the updating of its recommendations on uterotonics for 14 oxytocin–ergometrine fixed-dose combination) are PPH prevention. context-specific recommendations, on account of the need to exclude the presence of hypertensive disor- UPDATED WHO RECOMMENDATIONS ON UTEROTONICS FOR ders prior to its use. This condition may limit their use PPH PREVENTION in those settings where there is lack of screening for In December 2018, WHO issued new recommendations hypertensive disorders in pregnancy. WHO also made a on uterotonics for PPH prevention (table 1).15 Oxytocin context-specific recommendation regarding the use of (10 IU, intravenously or intramuscularly) remains the carbetocin for PPH prevention (use
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