Postpartum Hemorrhage

Color profile: Generic CMYK printer profile Composite Default screen 27 STANDARD MEDICAL THERAPY F. Breathnach and M. Geary INTRODUCTION successful until the early 20th century, when Barber and Dale isolated ergotoxine in 19062. Failure of the uterus to contract and retract Initially thought to be a pure substance, this following childbirth has for centuries been agent was subsequently found to comprise four recognized as the most striking cause of post- alkaloids and in 1935 Moir and Dudley were partum hemorrhage. Uterine atony is a condi- credited for isolating ergometrine, the active tion which, in spite of the presence of effective aqueous extract ‘to which ergot rightly owes medical interventions, still claims thousands of its long-established reputation as the pulvis maternal lives. In the developing world, lack of parturiens’5,6. Moir reported on its clinical use access to uterotonic therapies that have been in 1936, stating6: available for almost a century represents one of the most glaring disparities in obstetric care ‘. the chief use of ergometrine is in the preven- today. tion and treatment of postpartum haemorrhage. In the 19th century, uterine atony was Here the ergometrine effect is seen at its best. If after the delivery of the placenta the uterus is treated by intrauterine placement of various unduly relaxed, the administration of ergo- agents with the aim of achieving a tamponade metrine, 1 mg by mouth or 0.5 mg by injection, effect. ‘A lemon imperfectly quartered’ or ‘a will quickly cause a firm contraction of the organ. large bull’s bladder distended with water’ were If severe haemorrhage has already set in, it is employed for this purpose, with apparent suc- highly recommended that the drug should be cess. Douching with vinegar or iron perchloride given by the intravenous route. For this purpose was also reported1,2. Historically, the first utero- one-third of the standard size ampoule may be tonic drugs were ergot alkaloids, followed by injected or, for those who wish accurate dosage, oxytocin and, finally, prostaglandins. a special ampoule containing 0.125 mg is manu- Ergot, the alkaloid-containing product of the factured. An effect may be looked for in less than fungus Claviceps purpurea that grows on rye, was one minute.’ recognized for centuries as having uterotonic Oxytocin, the hypothalamic polypeptide hor- properties and is the substance referred to by mone released by the posterior pituitary, was John Stearns in 1808 as ‘pulvis parturiens’ (a discovered in 1909 by Sir Henry Dale7 and syn- powder [for] childbirth), at which time it was thesized in 1954 by du Vigneaud8. The develop- used as an agent to accelerate labor3. By the end ment of oxytocin constituted the first synthesis of the 19th century, however, recognition of the of a polypeptide hormone and gained du potential hazards associated with ergot use in Vigneaud a Nobel prize for his work. labor, namely its ability to cause uterine hyper- The third group of uterotonics comprises stimulation and stillbirth, had tempered enthu- the ever-expanding prostaglandin family. The siasm for its use. Focus was diverted toward prostaglandins were discovered in 1935 by a its role in preventing and treating postpartum group led by Swedish physiologist Ulf von hemorrhage at a time when, according to an Euler9 who found that extracts of seminal vesi- 1870 report, maternal mortality in England cles or of human semen were capable of causing approached one in 20 births4. Attempts to iso- contraction of uterine tissue and lowering blood late the active alkaloids from ergot were not pressure. The term ‘prostaglandin’ evolved 256 278 Z:\Sapiens Publishing\A5211 - Postpartum Hemorrhage\Make-up\Postpartum Hemorrhage - Voucher Proofs #T.vp 30 August 2006 14:21:33 Color profile: Generic CMYK printer profile Composite Default screen Standard medical therapy from von Euler’s belief that the active material Ta bl e 1 Risk factors for uterine atony came exclusively from the prostate gland. This Factors associated with uterine overdistension family of ‘eicosanoids’, 20-carbon fatty acids, Multiple pregnancy was subsequently found to be produced in a Polyhydramnios variety of tissues and capable of mediating a Fetal macrosomia myriad of physiologic and pathologic processes. Prostaglandins, by virtue of their ability to cause Labor-related factors strong myometrial tetanic activity, are increas- Induction of labor Prolonged labor ingly being employed as adjunctive therapy Precipitate labor to standard oxytocin and ergometrine to treat Oxytocin augmentation postpartum hemorrhage resulting from uterine Manual removal of placenta atony (see Chapter 12). This chapter is devoted to critical evaluation Use of uterine relaxants of the standard pharmacological methods avail- Deep anesthesia (especially halogenated anesthetic able to overcome uterine atony, with particular agents) Magnesium sulfate focus on agent selection based on effectiveness, safety profile, ease of administration, cost and Intrinsic factors applicability in low-resource settings. Previous postpartum hemorrhage Antepartum hemorrhage (abruptio or previa) Obesity UTERINE ATONY Age > 35 years Powerful efficient contractions of the myo- metrium are essential to arrest blood loss after delivery. The resultant compression of the uter- hemorrhage confers a 2–4-fold increased risk of ine vasculature serves to halt the 800 ml/min hemorrhage compared to women without such blood flow in the placental bed. Recognition of a history12,13. a soft, boggy uterus in the setting of a post- It is appropriate that women with these pre- partum bleed alerts the attendant to uterine disposing risk factors should deliver in a hospital atony. The contribution that uterine atony with adequate facilities to manage postpartum makes toward postpartum hemorrhage is so hemorrhage. Prophylactic measures adopted well-known that a universal reflex action when include appropriate hospital booking for women faced with excessive postpartum bleeding is at risk, active management of the third stage of to massage a uterine contraction. Prompt labor, intravenous access during labor and recognition of this condition and institution of ensuring the availability of cross-matched uterotonic therapy will effectively terminate the blood. However, it is noteworthy that uterine majority of cases of hemorrhage. Once effective atony occurs unpredictably in women with uterine contractility is assured, persistent bleed- no identifiable predisposing risk factors. This ing should prompt the search for retained underpins the need for strict protocols for the placental fragments, genital tract trauma or a management of postpartum hemorrhage to be bleeding diathesis (see Chapters 9 and 25). in place in every unit that provides obstetric Astute risk assessment is crucial in identify- care. ing women at increased risk of uterine atony, thereby allowing for preventive measures to OXYTOCIN be instituted and for delivery to take place where transfusion and anesthetic facilities are With timely and appropriate use of uterotonic available. The established risk factors associated therapy, the majority of women with uterine with uterine atony are outlined in Table 1. It is atony can avoid surgical intervention. Stimula- worth noting that multiparity, hitherto believed tion of uterine contraction is usually achieved in to be a significant risk factor, has not emerged the first instance by bimanual uterine massage as having an association with uterine atony and the injection of oxytocin (either intra- in recent studies10-12. Previous postpartum muscularly or intravenously), with or without 257 279 Z:\Sapiens Publishing\A5211 - Postpartum Hemorrhage\Make-up\Postpartum Hemorrhage - Voucher Proofs #T.vp 30 August 2006 14:21:33 Color profile: Generic CMYK printer profile Composite Default screen POSTPARTUM HEMORRHAGE ergometrine. The mode of action of oxytocin of action of 2–5 min. Metabolism is via the involves stimulation of the upper uterine seg- hepatic route and the mean plasma half-life ment to contract in a rhythmical fashion. Owing is 30 min. Nonetheless, the clinical effect of to its short plasma half-life (mean 3 min), a ergometrine persists for approximately 3 h. The continuous intravenous infusion is required in co-administration of ergometrine and oxytocin order to maintain the uterus in a contracted therefore results in a complementary effect, with state14. The usual dose is 20 IU in 500 ml oxytocin achieving an immediate response and of crystalloid solution, with the dosage rate ergometrine a more sustained action. adjusted according to response (typical infusion Common side-effects include nausea, vomit- rate 250 ml/h). When administered intra- ing and dizziness and these are more striking venously, the onset of action is almost instanta- when given via the intravenous route. As a result neous and plateau concentration is achieved of its vasoconstrictive effect via stimulation after 30 min. By contrast, intramuscular admin- of α-adrenergic receptors, hypertension can istration results in a slower onset of action occur. Contraindications to use of ergometrine (3–7 min) but a longer lasting clinical effect (up therefore include hypertension (including to 60 min). pre-eclampsia), heart disease and peripheral Metabolism of oxytocin is via the renal and vascular disease. If given intravenously, where hepatic routes. Its antidiuretic effect, which its effect is seen as being almost immediate, it amounts to 5% of the antidiuretic effect of should be given over 60 s with

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