Diagnosis and management of postpartum haemorrhageBMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3875 (Published 27 September 2017) Cite this as: BMJ 2017;358:j3875
All rapid responses
Chandraharan and Krishna’s clinical update (1) suggests that misoprostol may be used as a second line pharmacological therapy in the management of postpartum haemorrhage (PPH). This guidance echoes the recent RCOG and NICE guidelines in the UK. (2, 3)
Trials comparing PPH treatments are rare, but we are fortunate that there are some large, well-conducted randomised control trials to guide the pharmacological management of PPH with misoprostol. One of the largest is that of Widmer et al (4) where 1422 women with PPH were randomised to receive oxytocin along with either misoprostol or placebo. The clinical outcomes were identical, with 14% of women having further blood loss of 500ml within 1 hour in both groups. The rate of side effects, however, differed markedly with 65% of women experiencing shivering and 43% with a fever in the misoprostol arm, compared to 32% and 15% respectively in the placebo arm. This result is consistent with the two other large randomised trials of misoprostol use for PPH treatment where it was compared directly to oxytocin. These showed that, in women not receiving oxytocin prophylaxis, oxytocin treatment was more effective than misoprostol. (5) However, where oxytocin prophylaxis was used, misoprostol treatment was clinically equivalent to oxytocin. (6) In both situations, women given misoprostol were more likely to suffer from side effects.
The implications are clear: if oxytocin is available, misoprostol provides no additional benefit but increases side effects. However, it can be useful in settings where oxytocin is unavailable or inappropriate due to heat instability. (7)
Global norms for PPH treatments were clearly revealed in the recent WOMAN study, (8) a randomised, double-blind, placebo-controlled study of 20,000 women, conducted in 193 hospitals in 21 countries. In this study of tranexamic acid, women also received standard therapy. We were surprised to see that 99% of women received oxytocin treatment for their PPH, but 67% also received misoprostol, whilst ergometrine (a WHO first line therapy (9)) was given to only 43% of the participants.
This global snapshot shows that although the benefits of misoprostol are only seen in women who do not receive oxytocin, it is currently being widely used alongside oxytocin to treat PPH. Furthermore, UK guidelines seem also to have ignored the results of the massive Widmer study, and are continuing to recommend its use alongside oxytocin. The reasons are unclear, but it is disappointing to see clinicians and policy-makers being seduced by a new therapy, even when a large WHO trial has disproved its efficacy. What happened to evidence-based medicine?
1. Chandraharan E, Krishna A. Diagnosis and management of postpartum haemorrhage. BMJ 2017;358:j3875.
2. Mavrides E, Allard S, Chandraharan E, Collins P, Green L, Hunt BJ, Riris S, Thomson AJ on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG 2016;124:e106-e149.
3. National Institute for Health and Care Excellence (2014). Intrapartum care for healthy women and babies. NICE Guideline CG190: updated February 2017.
4. Widmer M, Blum J, Hofmeyr GJ, Carroli G, Abdel-Aleem H, Lumbiganon P, et al. Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: a multicentre, double-blind randomised trial. Lancet 2010;375:1808-13.
5. Winikoff B, Dabash R, Durocher J, Darwish E, Nguyen TN, Leon W, et al. 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 2010;375:210-6.
6. Blum J, Winikoff B, Raghavan S, Dabash R, Ramadan MC, Dilbaz B, et al. Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial. Lancet 2010;375:217-23.
7. Elati A, Weeks A. Misoprostol for the management of postpartum haemorrhage. BMJ 2011;342:d2877.
8. WOMAN Trial Collaborators. 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. Lancet 2017;389:2105-16.
9. World Health Organization. WHO recommendations for the prevention and treatment of postpartum haemorrhage. WHO, 2012.
Competing interests: Andrew Weeks is Director of a WHO Collaborating Centre and is the inventor of the PPH Butterfly, a uterine compression device to treat postpartum haemorrhage (see www.liv.ac.uk/pph-butterfly). He is the Chief Investigator of the NIHR HTA COPE study to compare oxytocin and carboprost for the treatment of PPH. He has also received funding from Gynuity Health Projects to attend conferences and conduct misoprostol research.
We would like to thank Chandraharan and Krishna for their recent article highlighting the challenges of postpartum haemorrhage (PPH). The article provided a comprehensive review of the causes of PPH and the pharmacological and surgical interventions that may be required. However, we felt that the article did not adequately address the importance of early recognition of PPH and multidisciplinary team working that together make a difference to outcome; nor did the article reflect the recent RCOG guidance and research that has increased our understanding of coagulation changes which occur during PPH.
The management of postpartum haemorrhage requires a well-trained, effective multidisciplinary team with a defined escalation strategy. Team working and training is essential to achieve an optimal outcome in a rapidly deteriorating clinical situation (1). In Wales we have developed a national quality improvement project working to improve the care of women experiencing postpartum haemorrhage (OBS Cymru (2)). Our key themes are multidisciplinary team working, risk assessment, measurement of blood loss and point of care testing to guide blood product administration. None of these issues were addressed adequately in the review, yet we feel that they are the cornerstones of successful PPH management.
The authors describe the inaccuracy of estimating blood loss which can lead to underestimation of large blood loss and overestimation of smaller bleeds. Both situations have a significant impact on the care of a bleeding mother. We have found that the gravimetric measurement of blood loss after all deliveries is easy to perform, requires minimal equipment and reflects the fall in postpartum haemoglobin in larger bleeds (3). When undertaken cumulatively during a bleed this technique allows the clinical teams to escalate appropriately and act in a timely fashion. Measuring blood loss is often said to be difficult or impractical, yet we now have an 80% compliance rate after all vaginal deliveries and 90% after Caesarean deliveries across the 12 consultant led delivery units in Wales.
Our additional concern was the recommendation that red blood cells should be replaced in a 1:1 ratio with fresh frozen plasma (FFP). This is not in-line with current RCOG guidance and does not reflect the recent research that has increased our understanding of the coagulation changes occurring during PPH (4,5).
The RCOG guidance now specifies that if no haemostatic results are available and bleeding is continuing, then, if bleeding is continuing after 4 units of red blood cells have been given then 15 ml/kg of FFP should be infused until haemostatic test results are known. The RCOG only advise early FFP administration if haemostatic tests are not available for conditions such as placental abruption or amniotic fluid embolism where coagulopathy is an early feature. There is a clear recommendation not to give 1:1 plasma to red cell transfusion for all bleeding. 1:1 resuscitation is a practice supported by data derived from studies in major non obstetric trauma and there is no data that support its use during PPH. We have recently published a study reporting on the use of point of care visco-elastometric testing of coagulation during severe PPH. Women were stratified during the bleed based on their fibrinogen levels. It was found that a rapid point of care test of coagulation was practical and that very few women needed coagulation product support based on the results of the bedside test. Point of care testing of coagulation is described in the RCOG guidance and we have found that if used, very few women receive FFP, thus avoiding the many unnecessary infusions that would have resulted from 1:1 resuscitation (6).
1. Siassakos D, Fox R, Crofts JF, Hunt LP, Winter C, Draycott TJ. The management of a simulated emergency: better teamwork, better performance. Resuscitation 2011; 82(2): 203-6.
3. Lilley G et al. Measurement of blood loss during postpartum haemorrhage. Int J Obst Anesth 2015; 24(1): 8-14.
4. Mavrides E,Allard S,Chandraharan E,Collins P,Green L,Hun tBJ,RirisS,Thomson AJ on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage. BJOG 2016; 124: e106–e149.
5. Collins PW et al. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. BJA 2017; 119(3): 411-421.
6. Collins PW et al. Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study. BJA 2017; 119(3):422-434.
Competing interests: OBS Cymru is an all Wales Quality Improvement Project sponsored by Welsh Government, 1000 Lives and Werfen.
I was disappointed by the lack of reference to Interventional Radiology (IR) in the above clinical update by Edwin Chandraharan and Archana Krishna BMJ 2017; 358: j3875 Published 27 Sep 2017. IR plays a major role in the prevention and treatment of post partum haemorrhage (PPH) and the need for early involvement of interventional radiology in the management of patients with PPH is stressed in the Royal college of obstetricians and gynaecologists good practice guidelines (1-19). Uterine artery embolisation should be mentioned in the “What you need to know” panel and the need for early involvement of IR described explicitly in the text. This review fails to recognise that IR is a specialty in its own right.
I would draw your attention to multiple publications (1-13) describing the benefit of IR techniques in PPH and a health care commission report (14) which highlights the potential of IR to save lives.
Arterial balloon occlusion and embolisation performed by an interventional radiologist in an IR suite can prevent major blood loss acutely reducing the need for blood transfusion and hysterectomy. The technique involves percutaneous femoral artery access with incisions of 1-2mm and using X-ray guidance to access either the anterior division of the internal iliac artery or more selectively the uterine artery to prevent or arrest acute haemorrhage. A variety of different embolic agents can be used including gelfoam, glue, coils and particles. A similar technique is also commonly used as part of a prophylactic strategy in abnormal placentation.
It is crucial that your readers are made aware of the potential benefit of early involvement of interventional radiology in the management of a patient with PPH and not denied potentially life saving treatments.
Dr R Uberoi
President of the British Society of Interventional Radiologists
Royal College of Radiologists
Lincoln Inn Fields
1. Heaston DK, Mineau DE, Brown BJ et al (1979) Transcatheter arterial embolization for control of persistent massive puerperal hemorrhage after bilateral surgical hypogastric artery ligation AJR Am J Roentgenol 133:152–154
2. Pelage JP, Le Dref O, Mateo J et al (1998) Life-threatening primary postpartum hemorrhage: treatment with emergency selective arterial embolization. Radiology 208:359–362
3. Deux JF, Bazot M, Le Blanche AF et al (2001) Is selective embolization of uterine arteries a safe alternative to hysterectomy in patients with postpartum hemorrhage? AJR Am J Roentgenol 177:145–149
4. Ratnam LA, Gibson M, Sandhu C et al (2008) Transcatheter pelvic arterial embolisation for control of obstetric and gynaecological haemorrhage. J Obstet Gynaecol 28:573–579
5. Boulleret C, Chahid D, Gallot D et al (2004) Hypogastric arterial selective and superselective embolization for severe postpartum hemorrhage: a retrospective review of 36 cases. Cardiovasc Intervent Radiol 27:334–348
6. Ojala K, Perala J, Kariniemi J et al (2005) Arterial embolization and prophylactic catheterization for the treatment of severe obstetric hemorrhage. Acta Obstet Gynecol Scand 84:1075–1080
7. Tsang ML, Wong WC, Kun KY et al (2004) Arterial embolisation in intractable primary post-partum haemorrhage: case series. Hong Kong Med J 10:301–306
8. Tourne G, Colleta F, Seffert P et al (2003) Place of embolization of the uterine arteries in the managementof post-partum haemorrhage:a study of 12 cases. Eur J Obstet Gynecol Reprod Biol110:29–34
9. Tixier H, Loffroy R, Guiu B et al (2009) Complications and failure of uterine artery embolisation for intractable postpartum haemorrhage. BJOG 116:55–61
10. Deux JF, Bazot M, Le Blanche AF, Tassart M, Khalil A, Berkane N, Uzan S, Boudghe`ne F (2001) Is selective embolization of uterine arteries a safe alternative to hysterectomy in patients with postpartum hemorrhage ? AJR Am J Roentgenol 177:145–149
11. Soyer P etal, Transcatheter Arterial Embolization for Postpartum Hemorrhage: Indications, Technique, Results, and Complications CVIR Feb 2015 Oct;38(5):1068-81
12. Multidisciplinary approach to manage antenatally suspected placenta percreta: updated algorithm and patient outcomes.Lee PS, Kempner S, Miller M, Dominguez J, Grotegut C, Ehrisman J, Previs R, Havrilesky LJ, Broadwater G, Ellestad SC, Secord AA. Gynecol Oncol Res Pract. 2017 Aug 22;4:11.
13. Endovascular management of massive post-partum haemorrhage in abnormal placental implantation deliveries. Rebonato A, Mosca S, Fischer M, Gerli S, Orgera G, Graziosi L, Maiettini D, Di Renzo GC, Epicoco G, Krokidis M, Rossi M, Scialpi M. Eur Radiol. 2016 Jun;26(6):1620-30.
14. Investigation into 10 maternal deaths at, or following delivery at, Northwick Park Hospital, North West London Hospitals NHS Trust, between April 2002 and April 2005. Health care Commission
15. Royal College of Obstetricians and Gynaecologists (2007) The role of emergency and elective interventional radiology in postpartum hemorrhage. Royal College of Obstetricians and Gynaecologists Good Practice Guideline No. 6. Royal College of Obstetricians and Gynaecologists, London. Available at: http://www.rcog.org.uk/ womens-health/clinical-guidance/role-emergency-and-electiveinterventional- radiology-postpartum-haem.
16. Royal College of Obstetricians and Gynaecologists 2011; Placenta Praevia, Placenta Praevia Accreta and Vasa Praevia - .Royal College of Obstetricians and Gynaecologists Good Practice Guideline No. 27. Royal College of Obstetricians and Gynaecologists https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_27.pdf
17. Royal College of Obstetricians and Gynaecologists (2016)Prevention and management of post partum haemorrhage .Royal College of Obstetricians and Gynaecologists Good Practice Guideline No. 52. Royal College of Obstetricians and Gynaecologists, London. Available at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg52/
Competing interests: No competing interests
Dear Sir or Madam:
A new hypothesis in the management of post-partum haemorrhage
Chandraharan and Krishna are to be congratulated on their very clear Clinic Update on the management of post-partum haemorrhage (PPH) (1).
Our therapeutic options for uterine atony (the principal cause of PPH) fall into just three types of intervention; hyperstimulation of the myometrium, correcting clotting disturbances, and the application of direct pressure. But given that the myometrium, in many cases of PPH, is exhausted, might there be some mileage in ‘myometrial resuscitation’?
Glucose is the principal fuel for myometrium activity. If the myometrium is exhausted of its glycogen reserve, and glucose uptake from the circulation compromised by general exhaustion, it would not seem unexpected that flogging the myometrium with ever more potent stimulatory drugs is likely to fail. Without fuel (glucose) the myometrium just cannot respond.
A brief search of the literature yielded just one paper mentioning (briefly) the use of glucose in PPH (2). We also found references to glucose therapy during acute myocardial ischaemia (sometimes enhanced with potassium and insulin to facilitate cellular glucose uptake), but nothing in the current obstetric literature. It may be that glucose supplementation may have a role not just in treating uterine atony, but perhaps too in its prevention. We would be interested in the views of your readers.
Miriam Barclay ST1 LAS, Obstetrics and Gynaecology, Colchester Hospital
Chris Barclay, Locum GP, Aldeburgh, Suffolk
1 – Diagnosis and management of postpartum haemorhage. Chandraharan
E, Krishna A. BMJ 2017;358:494-495
2 - The Principles of Treatment of Post-Partum Haemorrhage. Hunter W. Postgraduate Med J 1937 Nov;13(145):419-422. Accessed at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2476739/?page=1
Competing interests: No competing interests
Discussion of postpartum haemorrhage, and its ideal management, is made difficult as the resources available vary widely from developing to developed countries.
What is not difficult to comprehend is the vast, largely needless waste of human life that goes on day after day, year after year, from postpartum haemorrhage. There are around 125,000 deaths each year from postpartum haemorrhage - which equates to 42 equivalent 9/11 events. Whilst every year the anniversary of 9/11 is marked and tributes paid to the dead, the deaths of 2,000,000 women who have died from postpartum haemorrhage since 9/11 took place, are only acknowledged and grieved by their families. Because almost all of the deaths are in developing countries. This surely speaks volumes of where priorities lie for us in the devoloped world
Competing interests: No competing interests
Chandraharan and Krishna define postpartum haemorrhage (PPH) as blood loss over 500mL from the female genital tract. What is often not considered is the fact that visual estimation of blood loss following both vaginal and Caesarean section delivery may be grossly inaccurate and therefore of limited clinical use (1). Specifically, significant underestimation in three key areas (floor spillages, surgical swab capacity and massive PPH) were identified by Bose et al in all professional groups (2), with resultant clinical care implications. Overestimation of blood volume losses may result in unnecessary cross matching and care in the high dependency unit. Bose et al suggest a pictorial algorithm may be useful to increase the accuracy of visual blood loss estimation, along with clinical reconstruction and simulation training.
Furthermore, whilst hysterectomy may be definitive management in massive post-partum haemorrhage as suggested by Chandraharan and Krishna, stepwise uterine devascularisation, internal iliac artery ligation and selective arterial occlusion or embolisation by interventional radiology may also be other measures to be considered, where expertise and facilities allow, thereby preserving the uterus where fertility is desired (3).
In addition to considering acute management of PPH, the RCOG greentop guidelines outline the importance of identifying high risk patients who may experience post-partum haemorrhage in the antenatal period. This allows treatment to be administered where correctable factors such as anaemia are noted in good time, or preparation for prevention of PPH by the use of an active third stage.
Given that PPH remains a common emergency, antenatal assessment and counselling together with regular multidisciplinary training remains key to minimising its impact on our patients.
1. Dildy GA III, Paine AR, George NC, Velasco C. Estimating blood loss: can teaching significantly improve visual estimation? Obstet Gynecol 2004;104:601–6.
2. Bose P, Regan F, Paterson-Brown S. Improving the accuracy of estimated blood loss at obstetric haemorrhage using clinical reconstructions. BJOG 2006; 113:919–924.
3. Mavrides E, Allard S, Chandraharan E, Collins P, Green L, Hunt BJ, Riris S, Thomson AJ on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage.
Competing interests: No competing interests