Postpartum Hemorrhage

Key and Emerging Evidence

This page includes a curated list of select resources presenting key evidence on uterotonic agents for the treatment of PPH, uterine balloon tamponade to treat PPH, the importance of ensuring medication quality, and PPH care bundles – with additional resources to be added on an ongoing basis.

Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage

Ioannis Gallos, D.M.S., M.D., Adam Devall, B.Med.Sci., Ph.D., James Martin, Ph.D., Lee Middleton, M.Sc., Leanne Beeson, B.Sc., Hadiza Galadanci, F.R.C.O.G., Fadhlun Alwy Al-beity, M.D., Ph.D., Zahida Qureshi, M.B., B.S., M.Med., G. Justus Hofmeyr, M.B., B.Ch., D.Sc., Neil Moran, B.M., B.Ch., Sue Fawcus, M.B., B.S., Lumaan Sheikh, F.C.P.S., M.R.C.O.G., et al.

This three-year, cluster-randomized trial involved teaching providers the early detection of PPH coupled with the proposed WHO first-response bundle for postpartum hemorrhage (PPH), and then evaluating the bundle—a sequence of care components delivered in total, in rapid succession, without waiting for any individual component to work.

Highlights

  • The WHO PPH first-response bundle includes massage, uterotonic, tranexamic acid, IV fluids, and examination. While each individual component had been studied in the past, the bundle approach had not.
  • The research project modeled the Helping Mothers Survive training approach—low-dose, high-frequency—to build the capacity of health care professionals through a single-day training for the PPH clinical bundle.
  • The E-MOTIVE trial demonstrated that after near-universal uptake of the bundle by providers, use of the bundle significantly reduced bleeding and improved maternal health outcomes related to PPH – a 60% reduction in severe PPH outcomes.
How to Use

This study is well positioned to help inform the WHO’s official recommendation about PPH, as well as potential endorsement of the capacity-building approach as the methodology to be used to implement the bundle.

Uterotonic Agents for First-Line Treatment of Postpartum Haemorrhage: A Network Meta-Analysis
Parry Smith WR, Papadopoulou A, Thomas E, Tobias A, Price MJ, Meher S, Alfirevic Z, Weeks AD, Hofmeyr GJ, Gülmezoglu AM, Widmer M, Oladapo OT, Vogel JP, Althabe F, Coomarasamy A, Gallos ID.
Cochrane Database of Systemic Reviews, 2020.

Authors conclude that the available evidence suggests that oxytocin used as first-line treatment of PPH is probably more effective than misoprostol with less side effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®. 

Key Takeaways (based on 7 hospital-based trials, involving 3738 women in 10 countries)

  • Misoprostol, as first‐line treatment uterotonic agent:
    • Probably increases the risk of blood transfusion compared with oxytocin.
    • May increase the incidence of additional blood loss of 1000 mL or more.
    • May result in increased risk of vomiting and fever compared with oxytocin.
  • Misoprostol plus oxytocin:
    • Makes little or no difference to the use of additional uterotonics and to blood transfusion compared with oxytocin.
    • Cannot rule out an important benefit of using the combination over oxytocin alone for additional blood loss of 500 mL or more, additional blood loss of 1000 mL or more, maternal mortality, or severe morbidity.
    • Increases the incidence of fever and vomiting compared with oxytocin alone.
    • The combination makes little or no difference to vomiting compared with misoprostol alone.
    • Probably reduces the risk of blood transfusion and may reduce the risk of additional blood loss of 1000 mL or more compared with misoprostol alone.
    • The combination is compatible with a wide range of treatment effects for additional blood loss of 500 mL or more, maternal mortality or severe morbidity, use of additional uterotonics, and fever compared to misoprostol alone.

Uterine Balloon Tamponade for the Treatment of Postpartum Hemorrhage: A Systematic Review and Meta-Analysis
Suarez S, Conde-Agudelo A, Borovac-Pinheiro, Suarez-Rebling D, et al. International Journal of Gynaecology & Obstetrics, 2020. 

This systematic review and meta-analysis was conducted to evaluate the efficacy, effectiveness, and safety of uterine balloon tamponade (UBT) for the management of PPH. Ninety-one studies, including 4729 women, met inclusion criteria (6 randomized trials, 1 cluster randomized trial, 15 nonrandomized studies, and 69 case series).

Key Findings

The overall pooled success rate of uterine balloon tamponade in the treatment of postpartum hemorrhage was 85.9%.

  • UBT has a high success rate for treating severe PPH and appears to be safe.
  • The success rate was higher in women with PPH due to uterine atony (87.1%) and placenta previa (86.8%) than in women with PPH due to placenta accreta spectrum (66.7%) or retained products of conception (76.8%).
  • UBT success rate was lower in caesarean deliveries (81.7%) than in vaginal deliveries (87.0%)
  • The frequency of complications associated with the use of uterine balloon tamponade was low (<6.5%).

The authors state that the evidence on UBT efficacy and effectiveness from randomized and nonrandomized studies is conflicting, with experimental studies suggesting no beneficial effect, while observational studies show effectiveness of UBT. To optimize maternal outcomes, they suggest high-quality implementation research is needed to determine the most effective programmatic and healthcare delivery strategies on UBT introduction and use, adequately integrating the intervention into systems of emergency care.

Quality of Medicines for Life-Threatening Pregnancy Complications in Low- and Middle-Income Countries: A Systematic Review
Torloni MR, Bonet M, Betrán AP, Ribeiro-do-Valle CC, Widmer M.
Plos ONE, 2020.

Research indicates that the quality of medicines to manage pregnancy complications can be a contributing factor to high rates of maternal mortality in low-and middle-income countries (LMIC). This systematic review identifies, critically appraises, and synthesizes findings on studies related to the quality of medicines in LMIC for the management of hemorrhage, pre-eclampsia/eclampsia and sepsis. Findings indicate that the problem with the quality of medicines available is more evident for uterotonics (nearly 50% failure rates), and critical for ergometrine (75% failure rates). In addition, 1 in 7 injectable antibiotics samples (13%) and 1 in 29 magnesium sulfate samples (3.4%) were found to be of low quality.  

Postpartum Hemorrhage Care Bundles to Improve Adherence to Guidelines: A WHO Technical Consultation
Althabe F, Therrien MNS, Pingray V, et al.  
International Journal of Gynaecology & Obstetrics, 2019.

This technical consultation was conducted to systematically develop evidence-based bundles for care of PPH. Based on 12 criteria agreed upon by experts to assess PPH care bundles, their definition, median relevance rates, and the level of agreement in accordance with the RAND (RAND/UCLA Appropriateness Method) relevance ratings, two care bundles were defined including: 1) “First response to PPH bundle” comprises uterotonics, isotonic crystalloids, tranexamic acid, and uterine massage. 2)“Response to refractory PPH bundle” comprises continuous administration of uterotonics and isotonic crystalloids, second dose of tranexamic acid, compressive measures (aortic or bimanual uterine compression), the non-pneumatic anti-shock garment (NASG), and intrauterine balloon tamponade (IBT).  The E-MOTIVE trial, led by the University of Birmingham and the WHO, is currently in  progress to establish evidence and strategies to improve guideline adherence for the early detection of PPH and treatment using the WHO ‘first response’ bundle to improve outcomes. 

Risk of Medication Errors with Tranexamic Acid Injection Resulting in Inadvertent Intrathecal Injection
WHO
March 2022

WHO recommends early use of intravenous Tranexamic Acid (TXA) within 3 hours of birth in addition to standard care for women with PPH. WHO is now alerting health care professionals about the risk of administration errors that can occur with Tranexamic Acid (TXA) injection (TXA has been mistaken for obstetric spinal anaesthesia used for caesarean deliveries resulting in inadvertent intrathecal administration).

TXA is a lifesaving medicine, however, this potential clinical risk should be considered and addressed. Review existing operating theatre drug handling practices to decrease this risk, i.e. store TXA away from the anaesthetic drug trolley, and preferably outside the theatre.

Key Takeaways

  • Intrathecal TXA is a potent neurotoxin, with refractory seizures and 50% mortality.
  • TXA should be administered at a fixed dose of 1g in 10 ml (100 mg/ml) IV at 1 ml per minute, with a second dose of 1g IV if bleeding continues after 30 minutes.
  • The presentation of some of local anesthetics is similar to TXA (transparent ampoule containing transparent solution), which can erroneously be administered instead of the intended intrathecal anesthetic resulting in serious adverse effects.
  • Obstetricians from several countries have reported inadvertent intrathecal TXA administration and related serious neurological injuries.
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