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Evidence reviews for pharmacological management of postpartum haemorrhage

Intrapartum care

Evidence review O

NICE Guideline, No. 235

London: National Institute for Health and Care Excellence (NICE); .
ISBN-13: 978-1-4731-5400-1

Pharmacological management of postpartum haemorrhage

Review question

What is the effectiveness of pharmacological treatments for the management of postpartum haemorrhage?

Introduction

Postpartum haemorrhage (PPH), defined as the loss of ≥500 mL of blood from the genital tract in the 24 hours following the birth of a baby, is one of the leading causes of maternal death globally and can also have a significant psychological impact on women. PPH can lead to the need for blood and blood product transfusion, further interventions, and even the need for hysterectomy.

Identifying the most effective pharmacological interventions or treatments that minimise blood loss, reduce mortality and improve women’s experience of birth is therefore important, but there is uncertainty about the most effective pharmacological treatments and dosage regimens for women who develop PPH. The most effective sequencing of pharmacological interventions is also uncertain.

This review aims to identify the most effective pharmacological interventions (including doses) to manage primary PPH.

Summary of the protocol

See Table 1 for a summary of the Population, Intervention, Comparison and Outcome (PICO) characteristics of this review.

Table 1. Summary of the protocol (PICO table).

Table 1

Summary of the protocol (PICO table).

For further details see the review protocol in appendix A.

Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document (supplementary document 1).

During guideline development, the BNF notation for oxytocin dose changed to ‘units’, so this has been reflected in the evidence report. The evidence tables in appendix D reflect the dose notations as defined by the original study.

Declarations of interest were recorded according to NICE’s conflicts of interest policy.

Effectiveness evidence

Included studies

Eleven publications were included for this review: 2 publications were Cochrane systematic reviews (Mousa 2014 and Shakur 2018) that included 10 randomised controlled trials (RCTs) (from Mousa 2014: Blum 2010, Hofmeyr 2004, Lokugamage 2001, Walraven 2004, Widmer 2010, Winikoff 2010, Zuberi 2008; from Shakur 2018: Ducloy-Bouthers 2011, Sahhaf 2014, Shakur 2017), and 9 publications were separate RCTs (Abbas 2019, Abbas 2020, Dallaku 2019, Diop 2020, Javadi 2012, Kumari 2022, Maged 2016, Wang 2020, Zeng 2022). One RCT (Dallaku 2019) was a sub-study of a larger RCT (Shakur 2017).

Six RCTs compared misoprostol to placebo (Abbas 2019, Abbas 2020, Hofmeyr 2004, Walraven 2004, Widmer 2010, and Zuberi 2008). Two RCTs compared misoprostol to intravenous (IV) oxytocin (Blum 2010 and Winikoff 2010). Two RCTs compared tranexamic acid (TXA) to placebo (Ducloy-Bouthors 2011 and Shakur 2017). One RCT compared TXA plus misoprostol to placebo plus misoprostol (Diop 2020). One RCT compared TXA plus oxytocin infusion plus ergometrine to oxytocin infusion plus ergometrine (Javadi 2015). One RCT compared misoprostol to syntometrine (intramuscular (IM) oxytocin and ergometrine) plus IV oxytocin (Lokugamage 2001). One RCT compared carbetocin to IV oxytocin (Maged 2016). Two RCTs compared TXA to misoprostol (Kumari 2022, Sahhaf 2014). One RCT compared carboprost plus oxytocin to oxytocin alone (Wang 2020). One RCT compared carbetocin to TXA.

The studies were from Afghanistan, Albania, Argentina, Bangladesh, Burkina Faso, Cameroon, China, Colombia, Cote d’Ivoire, Democratic Republic of Congo, Ecuador, Egypt, Ethiopia, France, Gambia, Ghana, India, Iran, Jamaica, Kenya, Nepal, Nigeria, Pakistan, Papua New Guinea, Senegal, South Africa, Sudan, Tanzania, Thailand, Turkey, United Kingdom, Uganda, Vietnam and Zambia.

The included studies are summarised in Table 2.

See the literature search strategy in appendix B and study selection flow chart in appendix C.

Excluded studies

Studies not included in this review are listed, and reasons for their exclusion are provided in appendix J.

Summary of included studies

Summaries of the studies that were included in this review are presented in Table 2.

Table 2. Summary of included studies.

Table 2

Summary of included studies.

See the full evidence tables in appendix D and the forest plots in appendix E.

Summary of the evidence

All comparisons – maternal death

Across the comparisons identified in this review that reported maternal death, there was no important difference between the interventions (misoprostol versus placebo, misoprostol versus oxytocin, TXA versus placebo, TXA plus misoprostol versus placebo plus misoprostol, and carbetocin versus oxytocin). However, there was an exception between TXA versus placebo when maternal deaths due to bleeding were analysed separately. In this case, TXA had an important benefit with fewer maternal deaths due to bleeding. Most of the evidence reporting maternal death was rated as high quality, with exceptions for TXA plus misoprostol versus placebo plus misoprostol, and carbetocin versus oxytocin, where the evidence was rated as low to moderate, with concerns around imprecision.

Misoprostol versus placebo

For the comparison of misoprostol versus placebo, there was no important difference for blood loss volume, need for additional pharmacological management or need for additional surgical management. Most of the evidence was rated high quality, with the exception of some outcomes rated very low to low due to concerns around imprecision, and some concerns for inconsistency and indirectness. All the evidence was from low/middle income countries.

Misoprostol versus oxytocin

When misoprostol was compared to oxytocin, high quality evidence showed that misoprostol had an important harm when compared to oxytocin in terms of need for additional pharmacological management, in all women and in women who did not receive oxytocin prophylaxis. However, in women who had received oxytocin prophylaxis there was no evidence of an important difference, with the quality of the evidence rated as low due to concerns over imprecision. There was no important difference or no evidence of an important difference for blood loss volume, or need for additional surgical management. The evidence was rated low to high quality with some concerns around imprecision. All the evidence was in low income countries.

TXA versus placebo

TXA was compared to placebo in studies conducted in low/middle and high income countries. One study was a multicentre study which provided data on low, middle and high income countries. The data from this study could not be stratified by low/middle versus high, and so has been analysed as mixed income. However, it was analysed separately from the study reporting in high income countries only. There was no evidence of an important difference, or no important differences for outcomes blood loss volume, occlusive/embolic events, coagulation, need for additional pharmacological management, or need for additional surgical management.

The quality of the evidence ranged from low to high. Apart from risk of bias due to reporting subjective outcomes for blood volume loss, all other concerns around quality were due to imprecision.

TXA plus misoprostol versus placebo plus misoprostol

TXA plus misoprostol was compared to placebo plus misoprostol in low/middle income countries. There was no important difference or no evidence of an important difference, between interventions for blood loss volume, need for additional pharmacological or surgical management. The evidence was mainly of moderate quality with concerns over imprecision.

TXA plus oxytocin plus ergometrine versus oxytocin plus ergometrine

When TXA plus oxytocin plus ergometrine was compared to oxytocin plus ergometrine, there was an important benefit favouring TXA plus oxytocin plus ergometrine in terms of the number of women with blood loss volume between 500 to 1000ml and 1000 to 2000ml, but no evidence of difference in the number of women with blood loss volume over 2000ml. The evidence was rated as very low to moderate. Very low quality evidence showed no important differences in terms of thromboembolism, and low quality evidence showed a possible important benefit favouring TXA plus oxytocin plus ergometrine in terms of need for additional surgical management. Most of the quality concerns were around risk of bias and some concerns around imprecision. The evidence was from a low/middle income country.

Misoprostol versus syntometrine plus oxytocin

Misoprostol was compared to syntometrine (IM oxytocin and ergometrine) plus IV oxytocin in a low/middle income country. Very low to low quality evidence showed an important benefit for misoprostol in terms of need for additional pharmacological and surgical management. There were concerns around the risk of bias and imprecision. The evidence did not report whether the women had received uterotonic prophylaxis.

Carbetocin versus oxytocin

Carbetocin was compared to oxytocin in a low/middle income country. There was no important difference between blood loss volume. However, there was an important benefit favouring carbetocin for need for additional pharmacological and surgical management. The quality of the evidence ranged from moderate to low and was downgraded due to concerns over imprecision.

TXA versus misoprostol

For the comparison of TXA versus misoprostol, there was data on blood loss volume which showed no important difference. The evidence came from a low/middle income countries and was rated low quality due to risk of bias concerns.

Carboprost plus oxytocin versus oxytocin alone

For the comparison carboprost plus oxytocin versus oxytocin alone, there was an important benefit favouring carboprost on blood loss volume at 2, 6 and 12 hours after birth but an important harm for blood loss volume at 24 hours after birth. All the evidence was of low quality due to concerns around risk of bias and indirectness of the data, as diagnosis of postpartum haemorrhage was unclear. The evidence came from low/middle income country.

Carbetocin versus TXA

For the comparison of carbetocin versus TXA, there was data on blood loss volume which showed an important benefit of carbetocin. The evidence came from a low/middle income country and was rated low to very low due to risk of bias and imprecision.

There was no evidence identified for the outcomes breastfeeding or women’s and partner’s experience and satisfaction of labour and birth and postnatal period.

See appendix F for full GRADE tables.

Economic evidence

Included studies

Two economic studies were identified which were relevant to this question (Sudhof 2019, Howard 2022).

See the literature search strategy in appendix B and economic study selection flow chart in appendix G.

Excluded studies

Economic studies not included in this review are listed, and reasons for their exclusion are provided in appendix J.

Summary of included economic evidence

See Table 3 for the economic evidence profile of the included study.

Table 3. Economic evidence profile of a systematic review of economic evaluations of pharmacological treatments for the management of postpartum haemorrhage.

Table 3

Economic evidence profile of a systematic review of economic evaluations of pharmacological treatments for the management of postpartum haemorrhage.

Economic model

No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.

Unit costs

ResourceUnit costsSource
Tranexamic acid£3.001BNF
Oxytocin£0.802BNF
Misoprostol£0.843BNF
Syntometrine (oxytocin and ergometrine)£1.574BNF
1

Based on dose of 1g and Tranexamic acid 1g/10ml solution for injection ampoules at £15.00 for 5 ampoules

2

Based on dose of 5 units and Oxytocin 5units/1ml solution for injection ampoules at £4.00 for 5 ampoules

3

Based on dose of 1,000 micrograms and 200 microgram misoprostol at £10.03 for 60 tablets

4

Based on dose of 1mL and Syntometrine 500 micrograms/1ml solution for injection ampoules at £7.87 for 5 ampoules

The committee’s discussion and interpretation of the evidence

The outcomes that matter most

Maternal death, blood loss volume and coagulation//coagulopathy/occlusive events/embolic events were prioritised as critical outcomes by the committee. Maternal death was prioritised as a critical outcome as postpartum haemorrhage can lead to maternal death if it is not controlled. Blood loss volume was also prioritised as this would be an indicator of the effectiveness of pharmacological treatments to reduce blood loss and consequently maternal deaths. Coagulation/coagulopathy and occlusive/embolic events were also prioritised as critical, as this could be a serious side effect of using pharmacological treatments for postpartum haemorrhage.

The committee agreed that as well as the critical outcomes, the need for additional pharmacological management of haemorrhage, and the need for additional surgical management of haemorrhage should be important outcomes. This would also give an indication of the effectiveness of the interventions as it would show whether they were effective enough to stop bleeding, or if further interventions had to be used. The committee also agreed that breastfeeding was an important outcome as women with high amounts of blood loss may find breastfeeding difficult. Women’s and partner’s experience and satisfaction of labour and birth and postnatal period was also chosen as an important outcome because postpartum haemorrhage can be a traumatic event for both the woman and her partner and the committee wanted to find out whether any of the interventions have an impact on satisfaction.

The quality of the evidence

The quality of the evidence for outcomes was assessed with GRADE and was rated as high to very low. The main reason why outcomes were downgraded was imprecision around the effect estimate. The risk of bias assessment indicated in some outcomes concerns over randomisation, blinding or participants and outcome assessors, subjective reporting of some outcomes, and lack of information on missing outcome data. There were also some concerns around inconsistency for some outcomes where subgroup analysis could not be performed. Some outcomes were downgraded due to unclear criteria for diagnosis of postpartum haemorrhage.

There was no evidence identified for the outcomes of breastfeeding or women’s and partner’s experience and satisfaction of labour and birth and postnatal period.

Benefits and harms

The committee discussed that PPH is a medical emergency which requires a coordinated team response and that pharmacological treatments form only a part of this response. Furthermore, a number of pharmacological treatments are often used in succession or in combination. The committee were aware that the 2014 version of the Intrapartum care guideline advised the use of oxytocin and ergometrine as first-line treatments, repeat doses of oxytocin, misoprostol or carboprost as second-line treatments, and tranexamic acid or clotting factors as adjuvant options. The committee discussed the fact that the choice of pharmacological treatments used to treat postpartum haemorrhage depended on the uterotonics that had been given previously for active management of the third stage of labour. For example, ergometrine cannot be repeated so if women had received ergometrine as part of active management of the third stage they could not receive it again for the management of postpartum haemorrhage. The committee agreed this had not been clear in the previous guideline and so reformulated the recommendations into a table which made this easier to describe.

The committee were aware that the NICE surveillance decision to review the evidence for the management of PPH was based primarily on the fact that new evidence was available for the benefits of tranexamic acid and so the committee reviewed all the evidence identified, but focused particularly on the role of tranexamic acid in the overall treatment pathway. However, the committee noted that the evidence presented did not provide any information regarding the ideal sequencing of pharmacological treatments for the management of PPH.

There was no evidence for the use of oxytocin compared to placebo or ergometrine compared to placebo, but the committee were aware from their own knowledge and experience that these agents were effective in practice and there was nothing in the evidence that suggested any harms and so they agreed not to change the recommendations to use these medicines for the treatment of PPH, depending on whether or not they had been used as part of active management. The committee were aware that the half-life of oxytocin was very short and that for the management of PPH it was preferable to set up an intravenous infusion of oxytocin to provide a more sustained effect.

The committee discussed the evidence for tranexamic acid, and agreed that there was a clear benefit compared to placebo in terms of maternal death due to bleeding. The committee discussed that, although the current recommendations advised tranexamic acid as adjuvant treatment after uterotonics have been tried first, due to the different mechanisms of actions, it would be logical if uterotonics and tranexamic acid could be given in combination. This use of combination therapy was reinforced by the evidence from the combination of tranexamic acid with oxytocin and ergometrine that showed benefits on blood loss volume and possible benefits on the need for additional surgical intervention, compared to oxytocin and ergometrine alone. The committee discussed the dose of tranexamic acid and noted that the recommended dose in the Summary of Product Characteristics is 1g given intravenously over 10 minutes. This can then be followed by an intravenous infusion. However, the committee discussed that in the case of ongoing postpartum haemorrhage it was more common practice to give a repeat injection after 30 minutes and that this was reflected in the international FIGO guidelines and the Welsh PPH guidelines.

The committee discussed the evidence for misoprostol and noted that although on its own it did not show any benefits compared to placebo, it showed equivalent efficacy to oxytocin alone and there was some evidence from a single study that when used in combination with oxytocin and ergometrine, it reduced the need for additional pharmacological and surgical treatment. The committee therefore agreed that misoprostol should remain one of the treatment options for PPH. The committee noted that misoprostol was given orally or rectally and therefore may be of particular benefit in home births, midwife-led settings or before intravenous access could be established to give other uterotonics.

The committee discussed the evidence which showed a benefit of carbetocin over oxytocin in terms of the need for additional pharmacological and surgical management and carbetocin over tranexamic acid, with a reduced blood loss seen with carbetocin. The committee noted that carbetocin was now recommended for active management of the third stage of labour in women having a caesarean birth (see Evidence review M). They highlighted that carbetocin could not be repeated, but agreed that it could be used as an option when additional uterotonics were needed in women who had not previously received carbetocin.

The committee finally discussed the evidence for carboprost. This had shown benefit in combination with oxytocin at reducing blood loss at 2, 6 and 12 hours, compared to oxytocin alone, but the committee noted that by 24 hours the oxytocin alone arm was more effective at reducing blood loss. The committee also discussed the low quality of the evidence, however they were aware from their own experience that carboprost is not associated with any harm, that in the majority of cases the bleeding would have resolved by 12 hours and that as carboprost was still a useful second-line treatment in addition to oxytocin for up to 12 hours after birth, they agreed to retain it as part of the recommendations.

The committee discussed that some of the evidence was in women who had received oxytocin prophylaxis (that is, an injection of oxytocin as part of the active management of the third stage of labour) and some was for women who had not received this. In the UK, the majority of women still receive active management of the third stage, although physiological management (where no oxytocin is administered) may be more common in women who give birth at home or in a midwife-led unit. In the studies where sub-group analysis was possible, there was no difference between the outcomes for women whether or not they had had oxytocin prophylaxis, except for one outcome in the comparison of misoprostol versus oxytocin: women receiving oxytocin had less need for additional pharmacological management than women receiving misoprostol when analysed in all women and in women who had no oxytocin prophylaxis, but no benefit was seen in women who had received oxytocin prophylaxis. This reinforced the committee’s view that the choice of agents to treat PPH should take into consideration the medication that has already been administered during the active third stage, and that giving women who had already received one dose of oxytocin another dose of oxytocin was unlikely to be the most effective strategy.

Cost effectiveness and resource use

The committee noted that the acquisition costs of all the medicines being recommended for the management of PPH were low and were likely to be far outweighed by the cost of a PPH, which if not treated promptly could lead to serious maternal consequences including ITU admission.

The evidence review identified 2 economic studies (Sudhof 2019, Howard 2022) in a United States setting which compared tranexamic acid to no tranexamic acid for women with postpartum haemorrhage. Whilst both studies found tranexamic acid to be cost-effective it was not possible for the committee to make recommendations for tranexamic acid as a first line treatment because its cost-effectiveness was not assessed against other uterotonics. Nevertheless, the committee believed it provided some cost-effectiveness justification to their recommendation to give tranexamic acid in combination with other uterotonic drugs to manage postpartum haemorrhage.

Other factors the committee took into account

The committee were disappointed that there was no evidence on breastfeeding or maternal experience or satisfaction and so made a research recommendation.

However, the committee did consider the use of the recommended drugs and the potential risk to babies who were breastfed after their mothers had received treatment for PPH. There are not considered any contraindications to breastfeeding for women who have received tranexamic acid, oxytocin, carbetocin or misoprostol, although additional monitoring of the baby may be considered.

Ergometrine may interfere with lactation although this is unlikely after short-term administration. Carboprost may be present in breast milk but is likely to be degraded in the baby’s gastrointestinal tract, and so will not lead to systemic effects in the baby.

Recommendations supported by this evidence review

This evidence review supports recommendations 1.10.34and 1.10.35 and a research recommendation. Other evidence supporting these recommendations can be found in the evidence review M on Uterotonics for the prevention of postpartum haemorrhage.

References – included studies

    Effectiveness

    • Abbas 2019

      Abbas, Dina F., Diop, Ayisha, Durocher, Jill et al. (2019) Using misoprostol to treat postpartum hemorrhage in home deliveries attended by traditional birth attendants. International Journal of Gynecology and Obstetrics 144(3): 290–296 [PubMed: 30582753]

    • Abbas 2020

      Abbas, Dina F., Durocher, Jill, Byrne, Meagan E. et al. (2020) Testing a home-based model of care using misoprostol for prevention and treatment of postpartum hemorrhage: Results from a randomized placebo-controlled trial conducted in Badakhshan province, Afghanistan. Reproductive Health 17(1): 88 [PMC free article: PMC7275481] [PubMed: 32503556]

    • Blum 2010

      Blum, Jennifer, Winikoff, Beverly, Raghavan, Sheila et al. (2010) Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial. The Lancet 375(9710): 217–223 [PubMed: 20060162]

    • Dallaku 2019

      Dallaku, Kastriot, Shakur-Still, Haleema, Beaumont, Danielle et al. (2019) No effect of tranexamic acid on platelet function and thrombin generation (ETAPlaT) in postpartum haemorrhage: a randomised placebo-controlled trial. Wellcome open research 4: 21 [PMC free article: PMC6556984] [PubMed: 31223662]

    • Diop 2020

      Diop, Ayisha, Abbas, Dina, Martin, Roxanne et al. (2020) A double-blind, randomized controlled trial to explore oral tranexamic acid as adjunct for the treatment for postpartum hemorrhage. Reproductive Health 17(1): 34 [PMC free article: PMC7060559] [PubMed: 32143721]

    • Ducloy-Bouthers 2011

      Ducloy-Bouthors, Anne-Sophie, Jude, Brigitte, Duhamel, Alain et al. (2011) High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Critical care (London, England) 15(2): r117 [PMC free article: PMC3219400] [PubMed: 21496253]

    • Hofmeyr 2004

      Hofmeyr, G. Justus, Ferreira, Sandra, Mangesi, Lindeka et al. (2004) Misoprostol for treating postpartum haemorrhage: A randomized controlled trial [ISRCTN72263357]. BMC Pregnancy and Childbirth 4: 16 [PMC free article: PMC514549] [PubMed: 15298718]

    • Javadi 2015

      Javadi E, Sadeghipour Z, Barikani A et al. (2015) Tranexamic Acid in the Control of Uterine Atony During Labor. Biotech Health Sci 2(2): e26898

    • Kumari 2022

      Kumari, A.; Rohatgi, R. et al; (2022) A Double Blinded Randomised Clinical Trial to Compare the Effect of Intravenous Tranexamic Acid and Misoprostol for Postpartum Haemorrhage. European Journal of Molecular and Clinical Medicine 9(1): 539–545

    • Lokugamage 2001

      Lokugamage, A. U., Sullivan, K. R., Niculescu, I. et al. (2001) A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. Acta obstetricia et gynecologica Scandinavica 80(9): 835–9 [PubMed: 11531635]

    • Maged 2016

      Maged, A. M.; Hassan, A. M.; Shehata, N. A. (2016) Carbetocin versus oxytocin in the management of atonic post partum haemorrhage (PPH) after vaginal birth: a randomised controlled trial. Archives of gynecology and obstetrics 293(5): 993–999 [PubMed: 26511939]

    • Mousa 2014

      Mousa, Hatem A., Blum, Jennifer, Abou El Senoun, Ghada et al. (2014) Treatment for primary postpartum haemorrhage. The Cochrane database of systematic reviews: cd003249 [PMC free article: PMC6483801] [PubMed: 24523225]

    • Sahhaf 2014

      Sahhaf, Farnaz, Abbasalizadeh, Shamsi, Ghojazadeh, Morteza et al. (2014) Comparison effect of intravenous tranexamic acid and misoprostol for postpartum haemorrhage. Nigerian medical journal : journal of the Nigeria Medical Association 55(4): 348–53 [PMC free article: PMC4124551] [PubMed: 25114373]

    • Shakur 2017

      Shakur, Haleema, Roberts, Ian, Fawole, Bukola et al. (2017) Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. The Lancet 389(10084): 2105–2116 [PMC free article: PMC5446563] [PubMed: 28456509]

    • Shakur 2018

      Shakur, H., Beaumont, D., Pavord, S. et al. (2018) Antifibrinolytic drugs for treating primary postpartum haemorrhage. Cochrane Database of Systematic Reviews [PMC free article: PMC6491317] [PubMed: 29462500]

    • Walraven 2004

      Walraven, Gijs, Dampha, Yusupha, Bittaye, Bubacarr et al. (2004) Misoprostol in the treatment of postpartum haemorrhage in addition to routine management: a placebo randomised controlled trial. BJOG : an international journal of obstetrics and gynaecology 111(9): 1014–7 [PubMed: 15327620]

    • Wang 2020

      Wang, Li; Jiang, Hong-Mei; Yang, Rui-Rui (2020) Carboprost tromethamine prevents caesarean section-associated postpartum hemorrhage. Tropical Journal of Pharmaceutical Research 19(4): 899–904

    • Widmer 2010

      Widmer M, Blum J, Hofmeyr GJ et al. (2010) Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: a multicentre, double-blind randomised trial. Lancet (London, England) 375(9728): 1808–1813 [PubMed: 20494730]

    • Winikoff 2010

      Winikoff, Beverly, Dabash, Rasha, Durocher, Jill et al. (2010) Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial. Lancet (London, England) 375(9710): 210–6 [PubMed: 20060161]

    • Zeng 2022

      Zeng, X.; Huang, D.; Luo, X.; Gong, H.; Wang, X.X.; Comparison of Clinical Effects of Intravenous Tranexamic Acid and Carbetocin in the Treatment of Postpartum Hemorrhage; Indian Journal of Pharmaceutical Sciences; 2022; vol. 84; 158–162

    • Zuberi 2008

      Zuberi, Nadeem F., Durocher, Jill, Blum, Jennifer et al. (2008) Misoprostol in addition to routine treatment of postpartum hemorrhage: A hospital-based randomized-controlled trial in Karachi, Pakistan. BMC Pregnancy and Childbirth 8: 40 [PMC free article: PMC2529259] [PubMed: 18718007]

    Economic

    • Sudhof 2019

      Sudoh, Leanna S., Shainker, Scott A., Einerson, Brett D. (2019). Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol 221(3) :275.e1–275.e12. doi: 10.1016/j.ajog.2019.06.030. Epub 2019 Jun 18. [PubMed: 31226298] [CrossRef]

    • Howard 2022

      Howard DC, Jones AE, Skeith A, et al. Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis. Am J Obstet Gynecol MFM 2022;4:100588 [PubMed: 35124299]

Appendices

Appendix I. Economic model

Economic model for review question: What is the effectiveness of pharmacological treatments for the management of postpartum haemorrhage?

No economic analysis was conducted for this review question.

Appendix J. Excluded studies

Excluded studies for review question: What is the effectiveness of pharmacological treatments for the management of postpartum haemorrhage?

Final

Evidence reviews underpinning recommendations 1.10.34 and 1.10.35 and a research recommendation in the NICE guideline

These evidence reviews were developed by NICE

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.

Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Copyright © NICE 2023.
Bookshelf ID: NBK596278PMID: 37856627

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