MCI RESEARCH PROJECTS EVALUATES A NEW EMERGENCY TREATMENT FOR POSTPARTUM HAEMORRHAGE



BACKGROUND

Postpartum Haemorrhage (PPH) is one of the leading causes of maternal mortality in the developing world, in particular in rural areas. At present a medication that can be used safely, easily and effectively, to control severe haemorrhage by non-trained health care providers, traditional birth attendants (TBAs), who provide most of the maternity care, does not exist. A medication that could be used safely by them in the villages in life threatening situations, when specialised help is not available, would be a major breakthrough in reducing mortality. An oral medication has been identified and MCI has conducted three clinical trials to prove its safety and efficacy.

In developed countries at the time of delivery mothers are given an injection of a medication known as an oxytocic, which is to cause the uterus to contract thus preventing continued bleeding after the baby has been born. These medications are not always suitable for use in tropical countries since they can have serious associated side effects, deteriorate due to the heat and thus has to be stored and protected from light in a refrigerator which is frequently not possible in rural centres without electricity and have to be given by injection which a TBA is not able to give.

Until recently there was no proven effective alternative. The World Health Organisation (WHO), established a special committee the Postpartum Haemorrhage Technical Working Group (1989), which made the strong recommendation that;

“the practice of the active management of the third stage, including the intramuscular administration of oxytocin should be followed at the most peripheral/lowest level of the maternal health care system, as possible”. (1)

Most women in Africa are delivered by TBAs in their homes where there is no access to skilled care should it prove to be necessary. It is under these circumstances that the majority of deaths from haemorrhage occur.

WHO has recommended that special attention be given to the management of the 3rd stage of labour by TBAs. Some programmes have trained them in various interventions which can be life saving, e.g. the rubbing up of a contraction, putting the baby to the breast soon after delivery or by stimulating the nipple, both of which can induce the release of endogenous oxytocin, resulting in uterine contractions. A few programmes have trained TBAs in the use of oral ergometrine.

There is presently no established method of treating severe PPH at the TBA level. The WHO, PPH technical group however recommends that;

“ high priority be given to any research proposals that sets out to investigate the effectiveness of formulations of different oxytocic drugs suitable for oral, rectal or vaginal delivery. Such formulations would have significant advantages over those for parental administration currently available, which are only suitable for use by extensively trained attendants.” (1) The group concludes;

“It is vital that clinical trials to assess the safety, efficacy, reliability, availability and feasibility of new oxytocics are needed, which could be used at the most peripheral level by TBAs.” (1)

CURRENT KNOWLEDGE

Recently Misoprostol has been identified as an important oxytocic. It is an inexpensive and stable synthetic prostaglandin E1 analogue, marketed as an oral tablet for the treatment of non-steroidal, anti-inflammatory, drug induced, gastric ulcers. Its use in pregnancy has only recently been appreciated. Studies have evaluated this prostaglandin and have shown that it can be used safely and effectively for the induction of labour. In addition a number of studies have shown that it can also be used effectively when given orally and rectally, in the management of the third stage of labour. (2) (3) (4) (5) (6) (8) It has therefore been suggested that misoprostol could potentially be lifesaving in the presence of severe post-partum haemorrhage.(7)

There have been a number of studies evaluating misoprostol including a WHO multi-centred trial comparing the use of misoprostol with oxytocin, which has to be given by i/m injection, however, none of the centres are in the developing world.

THE RESEARCH

Purpose

A multi-phased study to evaluate an oral prostaglandin misoprostol as a possible safe, effective, stable and simply administered alternative oxytocic for the management of postpartum haemorrhage has been developed to be conducted in an African country.

Phase 1 objective

To compare oral misoprostol with i/m oxytocin for the management of the third stage of labour with patients at low risk for post-partum haemorrhage.

A double blind, placebo controlled clinical trial comparing 400 micrograms of oral misoprostol with 10 units i/m or oxytocin for the management of the third stage of labour was carried out with the assistance of the department of Obstetrics and Gynaecology at Korle- Bu Teaching Hospital, University of Ghana. The results of this study showing that misoprostol was as good as i/m oxytocin for the management of the third stage was published in the British Journal of Obstetrics and Gynaecology in September 2000. (9)

Significance of the study;

A complicated research study was conducted successfully in an African country.

It was conducted in a developing country, where PPH is the leading cause of maternal mortality.

It provided the department of obstetrics and gynaecology and the consulting, resident and nursing staffs at a west African university, with the opportunity of conducting an important piece of research.

Misoprostol has been shown to be safe and effective and has the additional advantages of being stable in a hot climates, and is inexpensive.

As a result of these findings a second phase has been developed

Phase II objectives

Two randomised trials comparing 800 micrograms of oral or rectal misoprostol with 10 i/u of i/m oxytocin in the management of the third stage of labour are being conducted by nurse/midwives, in maternity departments of two rural district hospitals in Brong - Ahafo region of Ghana.

Significance of these studies are;

They are being carried out in two district hospitals which are closer to the peripheral setting of the village where many deaths from PPH frequently occur, as requested by the World Health Organisation.

They are being conducted by nurse/midwives.

Should these studies prove the efficacy and safety of misoprostol by nurses, then a third phase will be developed.

Phase III objectives

To develop protocols for the use of misoprostol as a safe, effective, and simply administered oxytocic which could be used by traditional birth attendants in villages for the treatment of life threatening postpartum haemorrhage, when medical assistance is not immediately available.

REFERENCES

World Health Organisation. The prevention and Management of Postpartum Haemorrhage; Report of a Technical Working Group 1989.

El-Refaey H, O’Brien P, Morafa W, Walder J, Rodeck C. Use of oral misoprostol in the prevention of postpartum haemorrhage. Br J Obstet Gynaecol 1997; 104: 336-9.

El-Refaey H, Nooh R, O’Brien P, Abdalla M, Geary M., Walder J, et al. The misoprostol third stage of labour study: a randomised controlled comparison between orally administered misoprostol and standard management. Br J Obstet Gynaecol 2000; 107: 1104-10.

O’Brien P, El-Refaey H, Gordon A, Geary M, Rodeck CH. Rectally administered misoprostol for the treatment of postpartum haemorrhage unresponsive to oxytocin and ergometrine: a descriptive study. Obstet Gynecol 1998; 92: 212-4.

Bamigboye AA, Hofmeyr J, Merrell DA. Rectal misoprostol in the prevention of postpartum haemorrhage: a placebo-controlled trial. Am J Obstet Gynecol 1998; 179: 1043-6.

Editorial: The Lancet, Vol 358; September 1, 2001. Misoprostol: a boon to safe motherhood…or not?

Sami G., Karkanis, MD, David Caloia, MD, Mary ellen Salenieks, RN, John Kingston, MD, Mark Walker, MD, Filomena Meffe, MD, Rory Windrim, MD, MSc. Randomized Controlled Trial of Rectal Misoprostol Versus oxytocin in third stage management. J Obstet Gynaecol Can 2002; 24 (2): 149-54.

A Metin Gulmezoglu, Jose Villar, Nguyen Thi Nhu Ngoc, Gilda Piaggio, Guillermo Carroli, Lekan Adetoro, Hany Abdel-Aleem, Linan Cheng, G Justus Hofmeyr, Pisake Lumbiganon, Christian Unger, Walter Prendiville, Alain Pinol, Diana Elbourne, Hazem El-Refaey, Kenneth F. Schulz, for the WHO Collaborative Group to Evaluate Misoprostol in the Management of the Third Stage of Labour. WHO multicentre randomised trial of misoprostol in the management of the third stage of labour. Editorial: The Lancet, Vol. 358; September 1, 2001.

Walley RL, Wilson JB, Crane JMG, Matthews K, Sawyer E, Hutchens D. A double-blind placebo controlled randomised trial of misoprostol and oxytocin in the management of the third stage of labour. Br J Obstet and Gynaecol 2000: 107:1111 15.

R. L. Walley, FRCSC., FRCOG., MPH(Harvard)
Principle Investigator
Professor of Obstetrics and Gynaecology
Faculty of Medicine,
Memorial University of Newfoundland, Canada
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