3. Major Obstetric Haemorrhage 4. Uterotonics

1 Define major obstetric haemorrhage (MOH) and understand its epidemiology. 2 Initiate an appropriate strategy for resuscitation with fluids and blood products. 3 Explain the rationale for the medical, pharmacological and surgical treatment options for patients with MOH.

• Major obstetric haemorrhage (MOH) is the leading cause of global maternal morbidity and mortality, yet most deaths can be prevented. • Early recognition is key to the effective management of patients with MOH. • The choice and dose of uterotonic drug depend on the clinical context. • Massive transfusion protocols should be adopted locally, as deaths occur from inadequate volume replacement and failure to correct coagulopathy • Anaesthetists should be familiar with the range of mechanical and surgical options to treat postpartum haemorrhage.

However, MOH results in severe morbidity in all healthcare settings, including multiorgan failure, postpartum hysterectomy and long-term psychological trauma, contributing to enormous economic and social costs In the UK and Ireland’s most recent Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries (MBRRACE) report, deaths from haemorrhage were the second most common cause of direct maternal deaths with a rate of 0.64 (0.35e1.08) per 100,000. In resource-rich healthcare settings, an increase in the incidence of PPH has been primarily caused by an increasing incidence of uterine atony.7 Rates of severe PPH requiring interventions, such as blood transfusion and surgery, are also increasing in many countries

Definitions of what constitutes maternal haemorrhage are not universally agreed. Antepartum haemorrhage (APH) occurs from 24 weeks’ gestation, and occurs in between 3% and 5% of all pregnancies. Defined major APH as bleeding of 50-1000mL with no signs of shock, and massive APH as bleeding 1000 mL and/or bleeding of any volume with clinical signs of shock

Primary PPH occurs within the 24 h after delivery and secondary PPH occurs between 24 h and 12 weeks after delivery. The WHO defines PPH as 500 ml blood loss. However, it is recognised that using a definition with a higher threshold of 1000 ml may be more relevant clinically In the UK, the RCOG stratifies their definitions of PPH by severity. Major PPH may be defined as moderate (1000e2000 ml) or severe (2000 ml).

High-flow, low-resistance vascular bed and by term receives 25% of the cardiac output. Both plasma and red cell mass increase throughout pregnancy, leading to a 50% increase in maternal blood volume. volume is greater than red cell mass leading to a ‘physiological anaemia of pregnancy’, thereby offering an evolutionary advantage in which less red cell mass is lost per millilitre of blood during haemorrhage. Involution of the uterus and termination of the placental circulation after delivery results in autotransfusion of approximately 500 ml

Aetiology Early identification of women who are at risk of haemorrhage allows for safe birth planning and strategic mobilisation of resources; yet, risk stratification for maternal haemorrhage is fraught with difficulty as most women who present with PPH have no discernible risk factors.

Causes of APH include placenta praevia, placental abruption, uterine rupture and bleeding from the vulva, vagina or cervix, although a cause is often not found.

PPH is uterine atony, which accounts for approximately 80% of cases of primary PPH Trauma and injury to the genital tract, retained invasive placenta and coagulopathy are other common causes of PPH.

Endometritis or retained products of conception are the most common causes of secondary PPH

Placenta accreta spectrum (PAS) is a common cause of MOH, and the incidence of this condition is increasing placenta that is morbidly adherent to the myometrium (accreta vera), to that which invades into the myometrium (increta) through the myometrium into surrounding organs (percreta)

• A higher resting heart rate and a lower mean arterial blood pressure compared with the non-pregnant state may contribute to failure to detect signs of haemorrhage • Visual estimation of blood loss is variable and often underestimated. Quantitative blood loss measurement offers a more objective and scientific approach to visual assessment Quantitative blood loss can be used as part of an alert system with the aim of preventing the progression of minor bleeding to more severe bleeding, and has been successfully incorporated into the Welsh Obstetric Bleeding Strategy

This includes individual risk stratification, optimisation before delivery, and preparing obstetric units and healthcare staff for massive transfusion events. Bundles of care such as the Safe Motherhood Initiative (SMI) aid in both the planning and execution of safe management by delineating standards and minimising variability in care between obstetric units Early identification of haemorrhage risk in the antenatal period enables the effective mobilisation of healthcare resources In those with abnormal placentation, prior structured multidisciplinary planning can reduce blood loss, blood transfusions and emergency Caesarean delivery - appropriate site Women who may refuse blood products in an emergency, including Jehovah’s witnesses, should be identified early in the antenatal period and counselled appropriately. Screening for anaemia and the optimisation of haemoglobin in the antenatal period is essential to prevent unnecessary blood transfusion in cases of postpartum bleeding, as there are opportunities to maximise maternal red cell mass through improved nutrition, iron supplementation or the use of recombinant erythropoietin. multidisciplinary involvement including obstetrics, anaesthesia, midwifery, obstetric-trained nurses and transfusion medicine specialists. It is recommended that from the outset a senior clinician should supervise the overall management plan, in order to coordinate all aspects of care and avoid fragmentation of decision making

• The causes of haemorrhage should be considered and simultaneously investigated while being treated • The goal during resuscitation is restoration of blood volume and oxygen-carrying capacity. The SMI has categorised obstetric haemorrhage into four stages based on volume of blood loss, the presence of abnormal physiology and the requirement for transfusion. • Wide bore i.v. access should be established early in at least two sites and a high flow of warmed i.v. crystalloid fluid should be infused until blood products are available • Rapid infusion systems offer the possibility of very high flow rates. • Central venous access should be considered if you anticipate that vasopressors might be needed. • Left lateral tilt or uterine displacement is required in antepartum cases to optimise preload to the right side of the hear

• Management of the airway is the first priority followed by respiratory support if needed. High-flow oxygen via facemask should be started in all cases of MOH in awake patients. Tracheal intubation may be required to protect the airway in women with a reduced level of consciousness. • Blood should be sent for a full blood count, a coagulation screen and four units of blood should be cross-matched as a minimum • liver and renal function tests, electrolytes and fibrinogen concentrations. Point-of-care testing for haemoglobin and viscoelastic assays may be useful to detect and monitor ongoing losses • initial haemoglobin concentration may not reflect the amount of blood lost and therefore clinical judgement is paramount when initiating and calculating needs for blood transfusion • The body temperature should be measured frequently and active warming is mandatory. Extracorporeal membrane oxygenation (ECMO) may offer life-saving support for patients who fail to recover from reversible cardiocirculatory failure

• Major obstetric haemorrhage call * Mobilise obstetrics and anaesthesia * Summon senior help * Initiate massive transfusion protocol– laboratory + transport staff alerted: immediate issuance of blood components • Blood loss ≥1000 ml +/– signs of hypovolaemia • Immediate resuscitation * Airway: assessment * Breathing: 100% F2 * Circulation: wide bore IV access, warmed i.v. fluid or blood if available Interventions Clinical • • External uterine massage • • Bimanual uterine compression 3* Active warming • • If uterus contracted- transfer to theatre Pharmacological * Uterotonics * TXA Blood component therapy • • PRC • • FFP • • Cryoprecipitate/ fibrinogen conc. • • Platelet Assessment + investigation of bleeding • • Blood tests: X Match, FBC, Coag, Fibrinogen, U+E, LFTs • • Assess QBL 3 * Point-of-care echocardiography 4 * Thromboelastography 5 * Point-of-care Hb 6 * Consider invasive monitoring Transfer to operating theatre * Examination under anaesthesia * If uterine inversion: reduce * Genital tract trauma - repair +/– pack * Intrauterine balloon tamponade * Haemostatic compression sutures * Uterine artery ligation * Hysterectomy interventional radiology * Selective endovascular balloon occlusion • Selective radiological embolisation Post HDU * ICU

• Oxytocin • Carbetocin • Prostaglandins • Ergot alkaloids

First-line therapy Via oxytocin receptors on myometrial cell membrane After vaginal delivery: 5 IU i.v. slowly. Elective Caesarean delivery (CD): bolus 1 IU oxytocin; then infusion at 2.5-7.5 IU h1 . Intrapartum CD: 3 IU oxytocin over 30 s; then infusion at 7.5e15 IU h1 . If required after 2 min after initial bolus, give a further dose of 3 IU over 30 s. Extreme caution in context of haemodynamic instability or cardiovascular disease e deliver drug slowly

First-line therapy Via oxytocin receptors on myometrial cell membrane After vaginal delivery: 100 mg over 30 s. Elective CD: 100 mg over 30 s. Intrapartum CD: 100 mg over 30 s. Smaller doses may be sufficient at CD (as low as 20 mg) and may be repeated up to 100 mg. Do not exceed 100 mg in any setting. Extreme caution in context of haemodynamic instability or cardiovascular disease e deliver drug slowly

Second-line therapy: misoprostol may be used as first line where oxytocin/carbetocin unavailable Via prostaglandin receptors PGE1, PGE2, and PGF2a subtypes Misoprostol 400e600 mg: sublingual, rectal, vaginal, oral; repeat after 15 min if required, maximum dose 800 mg. Carboprost 250 mg: i.m. or intramyometrial (contraindicated i.v.); up to every 15 min if required, maximum eight doses. Asthma/obstructive lung disease

Second-line therapy Via dopamine, aadrenergic and 5-HT3 receptors Ergometrine (ergonovine) 200e500 i.m. or slow i.v. in exceptional circumstances; may be repeated after 2 h. Hypertension Myocardial ischaemia Cardiovascular disease

• More than 80% of cases of PPH are attributable to poor uterine tone after delivery. Traditionally, active management of the third stage of labour (AMTSL) is a • process in which expulsion of the placenta and membranes is achieved proactively with early cord clamping, controlled cord traction (CCT use of uterotonic drugs

• More than 80% of cases of PPH are attributable to poor uterine tone after delivery. Traditionally, active management of the third stage of labour (AMTSL) is a • process in which expulsion of the placenta and membranes is achieved proactively with early cord clamping, controlled cord traction (CCT use of uterotonic drugs = Reduce Incidence of primary PPH by 70% compared with expectant management delayed cord clamping has significant benefits for the neonate, and CCT may only be beneficial in the event of a delayed third stage. Uterotonic drug prophylaxis against PPH is required for all women, as many who suffer PPH have no identifiable risk factors.

uterine smooth muscle demonstrates considerable spontaneous electrical and contractile activity. Gap junctions between myometrial cells enhance the spread of electrical activity, and these junctions increase during pregnancy to provide a low resistance pathway. Depolarization takes place in response to the influx of sodium ions, while the availability of calcium ions enhances the response of uterine smooth muscle. These cross the cell membrane to stimulate further release of calcium from the sarcoplasmic reticulum. The uterus contains α1-adrenergic (excitatory), β2-adrenergic (inhibitory) and serotoninergic receptors, as well as specific excitatory receptors for oxytocin. These increase in number in late pregnancy (after 37 weeks’ gestation).