The Tibetan Uterotonic Zhi Byed 11: Mechanisms of Action, Efficacy, and Historical Use for Postpartum Hemorrhage

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 794164, 9 pages doi:10.1155/2012/794164 Review Article The Tibetan Uterotonic Zhi Byed 11: Mechanisms of Action, Efficacy, and Historical Use for Postpartum Hemorrhage Rebecca Lynn Coelius,1 Amy Stenson,2 Jessica L. Morris,3 Mingji Cuomu,4, 5 Carrie Tudor,6 and Suellen Miller7, 8, 9 1 School of Medicine, University of California, San Francisco, 50 Beale Street, Suite 1200, San Francisco, CA 94105, USA 2 Department of Obstetrics and Gynecology, David Geffen School of Medicine, Center for the Health Sciences, University of California, Los Angeles, 10,833 Le Conte Avenue, Los Angeles, CA 90095, USA 3 Safe Motherhood Program, University of California, San Francisco, 50 Beale Street, Suite 1200, San Francisco, CA 94105, USA 4 The Institute for Social and Cultural Anthropology, University of Oxford, 386 London Road, Headington, Oxford OX3 8DW, UK 5 Tibetan Medical College, Lhasa, Tibet 850000, China 6 School of Nursing, The Johns Hopkins University, 525 N. Wolfe Street, Baltimore, MD 21205, USA 7 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, 50 Beale Street, Suite 1200, San Francisco, CA 94105, USA 8 Safe Motherhood Programs, Bixby Center for Global Reproductive Health, School of Medicine, University of California, San Francisco, 50 Beale Street, Suite 1200, San Francisco, CA 94105, USA 9 Maternal Child Health Program, School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA Correspondence should be addressed to Rebecca Lynn Coelius, Received 9 February 2011; Revised 12 April 2011; Accepted 25 May 2011 Academic Editor: Raffaele Capasso Copyright © 2012 Rebecca Lynn Coelius et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To explore evidence for the traditional Tibetan medicine, Zhi Byed 11 (ZB11), for use as a uterotonic. Methods. The eleven ingredients in ZB11 were chemically analyzed by mass spectroscopy. A review was conducted of Western allopathic literature for scientific studies on ZB11’s individual components. Literature from Tibetan and other traditional paradigms were reviewed. Results. Potential mechanisms of action for ZB11 as a uterotonic include laxative effects, a dose-dependant increase in smooth muscle tissue peristalsis that may also affect the uterus smooth muscle, and chemical components that are prostaglandin precursors and/or increase prostaglandin synthesis. A recent RCT demonstrated comparable efficacy to misoprostol in reducing severe postpartum hemorrhage (PPH) (>1000 mL) and greater effect than placebo. Historical and anecdotal evidence for ZB11 and its ingredients for childbirth provide further support. Discussion. ZB11 and its ingredients are candidates for potentially effective uterotonics, especially in low-resource settings. Further research is warranted to understand the mechanisms of action and synergy between ingredients. 1. Introduction 1.1. Uterotonics for Prevention of Postpartum Hemorrhage (PPH). PPH is a leading cause of maternal morbidity and mortality worldwide. It is estimated that of the approximately 350,000 women who die annually from complications of pregnancy and childbirth, more than 25% die of obstetric hemorrhage [1]. This burden is unequally held by developing countries, where it occurs at a rate 100 times higher than in the developed world [2]. One key factor is that many women deliver at home without skilled delivery attendance, where complications often go unrecognized and untreated. By the time a problem is identified and the woman is transported to an appropriate facility, it may be too late. Women can deteriorate so rapidly that even if they arrive at an appropriate medical facility alive, they may already be in irreversible shock and/or have developed disseminated intravascular coagulopathy (DIC) [3]. The third stage of labor is the time period between the birth of the infant and delivery of the placenta and 2 membranes. Failure or delay of the uterus to appropriately contract after delivery can lead to rapid and massive hemorrhage. Shortening the third stage of labor and ensuring that the uterus is well contracted during this time has the potential to decrease blood loss and the incidence of hemorrhage. The World Health Organization (WHO), the International Federation of Gynecology and Obstetrics (FIGO), and the International Confederation of Midwives (ICM) advocate the use of a uterotonic to decrease postpartum bleeding by up to 50%–70% [4]. A uterotonic is a substance that increases the tone (causes contraction) of the uterus, an organ composed of smooth muscle tissue. In both allopathic and traditional and herbal medicine, substances that are called uterotonics often have laxative, purgative, diarrheagenic, cathartic, abortifacient, and emmenagoguic effects. Some uterotonics are biochemically synthesized hormones, such as oxytocin, that act on distant hormone receptors or upstream from other hormones in the body to induce uterine contractions. Others may be synthetic prostaglandins or prostaglandin precursors. Prostaglandins are lipid compounds derived enzymatically from fatty acids and serve as locally acting messenger molecules performing important functions in the body such as regulating the contraction and relaxation of smooth muscle [5]. Since 2007, the WHO PPH Prevention Guidelines have stated that the uterotonic of choice for prophylaxis of PPH is 10 IU of oxytocin delivered intramuscularly [6]. Oxytocin (pitocin and syntocinon) is a hormone produced in the hypothalamus that plays a critical role in labor and delivery by stimulating uterine contraction, and in lactation by causing milk letdown. However, there are barriers to its use in low-resource settings. To maintain the highest potency, oxytocin requires refrigeration. It is only effective if given parenterally [4], thus safe administration of oxytocin requires staff trained in intravenous or intramuscular administration techniques, sterile needles, and safe disposal for injection equipment. These are frequently unavailable or too costly during births in low-resource settings. The uterotonic ergometrine has similar efficacy to oxytocin but has more side effects, which makes it the preferred option only when oxytocin is not available [6]. Like oxytocin, its utility in lowresource settings is lessened by special storage requirements and parenteral administration [7]. The uterotonic misoprostol has been recommended as an alternative to oxytocin and ergometrine for the prevention of PPH in low-resource settings, primarily due to its greater ease of administration and storage [8]. Misoprostol (Cytotec) is a synthetic prostaglandin E1 analogue that has been shown to significantly decrease (...truncated)