Re: Diagnosis and management of postpartum haemorrhage
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.