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, [email protected] 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 women deliver at home without skilled delivery attendance, where complications often go unrecognized and untreated. 1.1. Uterotonics for Prevention of Postpartum Hemorrhage By the time a problem is identified and the woman is trans- (PPH). PPH is a leading cause of maternal morbidity and ported to an appropriate facility, it may be too late. Women mortality worldwide. It is estimated that of the approxi- can deteriorate so rapidly that even if they arrive at an ap- mately 350,000 women who die annually from complications propriate medical facility alive, they may already be in irre- of pregnancy and childbirth, more than 25% die of obstetric versible shock and/or have developed disseminated intravas- hemorrhage [1]. This burden is unequally held by developing cular coagulopathy (DIC) [3]. countries, where it occurs at a rate 100 times higher than The third stage of labor is the time period between in the developed world [2]. One key factor is that many the birth of the infant and delivery of the placenta and 2 Evidence-Based Complementary and Alternative Medicine membranes. Failure or delay of the uterus to appropriately dose dependant; malignant hyperpyrexia has been reported contract after delivery can lead to rapid and massive hemor- at 800 mcg orally [10, 12], with potentially dangerous rhage. Shortening the third stage of labor and ensuring that outcomes such as uterine rupture, abruption, fetal demise, the uterus is well contracted during this time has the poten- and maternal death if used inappropriately during the active tial to decrease blood loss and the incidence of hemorrhage. phase of labor at doses above 50 mcg [13, 14]. Another bar- The World Health Organization (WHO), the International rier is that misoprostol is not approved for obstetric or gy- Federation of Gynecology and Obstetrics (FIGO), and the necologic indications in many countries [15], and thus may International Confederation of Midwives (ICM) advocate not be widely available. Where use is restricted because of the use of a uterotonic to decrease postpartum bleeding by concerns for its use as an abortifacient, it may only be found up to 50%–70% [4]. on the black market, causing concern for its purity and A uterotonic is a substance that increases the tone safety. Due to misoprostol’s side effects and inconsistent out- (causes contraction) of the uterus, an organ composed of comesacrossstudies[16], the search for an alternative oral smooth muscle tissue. In both allopathic and traditional and uterotonic for low-resource settings continues. herbal medicine, substances that are called uterotonics often The ideal uterotonic for prevention of PPH at the home have laxative, purgative, diarrheagenic, cathartic, abortifa- or community level is one that is simultaneously efficacious, cient, and emmenagoguic effects. Some uterotonics are bi- affordable, widely available, does not require electricity or ochemically synthesized hormones, such as oxytocin, that technology for effective storage, has a low side effect profile act on distant hormone receptors or upstream from other and high safety level, and is compatible with local beliefs and hormones in the body to induce uterine contractions. Others traditional practices. There may be alternatives to current may be synthetic prostaglandins or prostaglandin precursors. allopathic medicines within traditional medical systems that Prostaglandins are lipid compounds derived enzymatically would fit these ideals for the prevention of PPH. from fatty acids and serve as locally acting messenger mol- Since at least 1500 BC traditional medical practices have ecules performing important functions in the body such as taken advantage of the uterotonic properties of local herbs regulating the contraction and relaxation of smooth muscle to promote uterine contractions and/or control PPH. These [5]. systems include but are not limited to US-based midwifery, Since 2007, the WHO PPH Prevention Guidelines have African traditional, Ayruveda, Chinese traditional, and Ti- stated that the uterotonic of choice for prophylaxis of PPH betan medicine. The history of ergometrine is an example is 10 IU of oxytocin delivered intramuscularly [6]. Oxytocin of how a naturally occurring substance was discovered to be (pitocin and syntocinon) is a hormone produced in the hy- a uterotonic and became widely used in Western allopathic pothalamus that plays a critical role in labor and delivery medicine. Ergometrine is derived from the naturally occur- by stimulating uterine contraction, and in lactation by caus- ring substance ergot, the alkaloid-containing product of the ing milk letdown. However, there are barriers to its use in fungus, Claviceps purpurea, which grows on grain. References low-resource settings. To maintain the highest potency, oxy- to ergot date as far back as 600 BC, and its effects on preg- ff tocin requires refrigeration. It is only e ective if given par- nancy were identified in the 16th century by midwives who enterally [4], thus safe administration of oxytocin requires ff noted an increased rate of miscarriage during epidemics of sta trained in intravenous or intramuscular administration “ergotism”, a disease caused by eating contaminated rye techniques, sterile needles, and safe disposal for injection bread [17]. In 1935, the active substance was identified and equipment. These are frequently unavailable or too costly named ergometrine, effectively initiating the modern era of during births in low-resource settings. The uterotonic er- allopathic uterotonics [18, 19]. gometrine has similar efficacy to oxytocin but has more In the USA, Chumash Native American communities in side effects, which makes it the preferred option only when California have used Trichostema lanatum and lanceolatum oxytocin is not available [6]. Like oxytocin, its utility in low- resource settings is lessened by special storage requirements leaves in a decoction to pass the afterbirth (placenta) [20]. and parenteral administration [7]. Midwives frequently use herbal preparations that are pur- The uterotonic misoprostol has been recommended as an ported to increase uterine tone (red raspberry leaf), act as alternative to oxytocin and ergometrine for the prevention of an emmenagogue to provoke menstruation (penny royal), or PPH in low-resource settings, primarily due to its greater ease induce labor contractions (blue