Definition of major obstetric haemorrhage

Postpartum haemorrhage is usually defined as the loss of more than 500 mL of blood after vaginal delivery and 1000 mL of blood after caesarean delivery. These amounts are exceeded in 1:20 deliveries . Massive haemorrhage (MOH) is defined as the loss of more than 2500 mL of blood and is associated with significant morbidity, including the need for obstetric hysterectomy and critical care. Other definitions of MOH include a fall in haemoglobin to ≥4 g/dL, the need for transfusion of ≥5 units of packed red blood cells (RBCs), or the need to treat coagulopathy or perform an invasive procedure. The incidence of MOH is approximately 6:1000 deliveries . In the latest mortality reports, MOH was one of the leading causes of maternal mortality, contributing to approximately 50% of maternal deaths worldwide ; in the UK, it accounts for approximately 10% of all direct deaths . Maternal deaths from primary PPH in France are two times higher than those in the Netherlands and four times higher than those in the UK . In the period spanning from 2009 to 2012, in the UK and Ireland, there were 17 deaths by MOH, with an incidence of 0.49 per 100,000 maternities, and a case fatality rate of 1:1200 women. Currently, MOH is the third leading direct cause of maternal deaths. Many of these deaths are considered potentially avoidable . The main recommendations of ‘Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK)’ are described in Table 1 .

Management of PPH

Blood loss in a maternity setting may be rapid and readily apparent, intermittent and difficult to quantify, or completely concealed. In all cases, without prompt attention, the mother may become critically and dangerously hypovolemic, leading to cardiovascular collapse. Because of physiological adaptations in pregnancy, women may show few cardiovascular signs until 30%–50% of the circulating blood volume has been lost. Delayed treatment may lead to significant end-organ damage, coagulopathy and even death. Early identification and treatment are highlighted in the current UK Royal College of Obstetricians and Gynaecologist Green-top guidelines, which recommend that with a blood loss of 500–1000 mL, clinicians should undertake ‘basic measures of monitoring’ and ‘readiness for resuscitation,’ and after more than 1000 mL, a ‘full protocol … to resuscitate, monitor and arrest bleeding’ should be employed. The major problem, however, is early identification of women who may be bleeding .

In a large PPH preparedness survey, the Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN) PPH Project, in the US performed in 2013–2014, large variations were identified in the definitions of PPH, methods of identifying PPH, notification of team members, composition of the resuscitation team and the availability of medication and equipment. Less than 50% of the hospitals had a MOH protocol, performed risk assessments and drills, or routinely measured blood loss. It was considered that this lack of standardisation contributed to variation in rates of serious morbidity relating to PPH .

In one institution, a prescriptive approach to PPH management using quality improvement methodology was implemented; PPH was categorised into four stages based on the estimated blood loss (EBL): 0- risk assessment Table 2 , 1-EBL >500 mL, 2-EBL between 1000 and 1500 mL and 3-EBL >1500 mL . A prescriptive approach to management was developed for each stage, including measuring the blood loss at the time of delivery and delineating the personnel who should be informed and present at the mother’s bedside at each stage. The use of this protocol led to a reduction in the incidence of major haemorrhage and a reduction in blood product use across a whole region in the US . Similarly, another US-based quality improvement programme instigated an early prescriptive approach to PPH management with blood loss measurement and mandated that an obstetrician and obstetric anaesthetist attend the mother’s bedside once 1000-mL blood loss had been measured/estimated or suspected. This group also reported a reduction in the incidence of major haemorrhage, a reduction in blood product use and reduced ICU admissions (personal communication, teleconference to AWHONN: B Bateman, R Byfield; June 2016). A similar trend has been identified in a large city UK maternity hospital where measuring blood loss and early protocolised care led to a fall in major haemorrhage events, ICU admission and hysterectomy, far more than the effect of a study intervention, which was being conducted during this time period .

A key development in all programmes was the initiation of regular blood loss measurements as soon as abnormal bleeding had been identified. In clinical practice, blood loss during PPH is often estimated visually, especially if bleeding occurs outside the operating theatre. Measurement practice may also vary depending on whether the delivery is caesarean or vaginal. Of concern, studies have shown that visual estimation of blood loss is associated with significant underestimation of the actual blood loss, especially for large-volume blood loss in which underestimation may be as high as 30%–50% . This underestimation may also account for the discrepancies in the incidence of PPH reported in the literature. For example, the incidence of blood loss >1000 mL was estimated at 3.9/1000 (95% CI 3.3–4.5) in one study , whereas in another study, the incidence of blood loss >2500 mL was estimated at 4.3/1000 (95% CI 3.8–4.8) . Delivery units that have moved from visual estimates to the quantitative measurement of blood loss have noted a marked increase in the incidence of PPH (personal communication: G Lilley, Abergavenny delivery suite, UK 2016), although blood product use has not increased, indicating that the actual rate of PPH had not changed.

An article described improvements in estimating blood loss during simulated training sessions by using visual aids; pictures of known volumes of artificial blood were provided and were compared with the current scenario . Although impressive in training sessions, and a possible tool to improve early identification of abnormal bleeding, implementation into clinical practice and assessment against a standard outcome, such as a fall in haemoglobin, has not been performed. In another study, simulated PPH scenarios were performed with volumes of artificial blood ranging from 420 to 2480 mL . The mean error in identifying the volume by visual estimation was 34%; both over- and underestimation of the blood loss occurred. When the swabs and bed linen were weighted using a simple gravimetric subtraction technique using weighing scales ubiquitously found in a delivery suite, the error measurement in the volume of EBL was only 3% . An animated video of the technique is available from the AWHONN website . After adopting the gravimetric measurement of blood loss, the fall in haemoglobin correlated with the measured blood loss at delivery ( r = 0.8) when the blood loss was greater than 1500 mL, indicating that this approach is both feasible and practical in clinical practice .

Simulation training in the obstetric setting has been shown to improve safety for the mother and neonate . Specific training in PPH has been shown to improve adherence to guidelines and communication and is effective among diverse settings and provider types, including non-academic centres, midwives and in low-resource settings where the mother may be attended by medical officers . The importance of multidisciplinary training has been emphasised during the implementation of standardised protocols for the management of PPH .

Management of PPH

Blood loss in a maternity setting may be rapid and readily apparent, intermittent and difficult to quantify, or completely concealed. In all cases, without prompt attention, the mother may become critically and dangerously hypovolemic, leading to cardiovascular collapse. Because of physiological adaptations in pregnancy, women may show few cardiovascular signs until 30%–50% of the circulating blood volume has been lost. Delayed treatment may lead to significant end-organ damage, coagulopathy and even death. Early identification and treatment are highlighted in the current UK Royal College of Obstetricians and Gynaecologist Green-top guidelines, which recommend that with a blood loss of 500–1000 mL, clinicians should undertake ‘basic measures of monitoring’ and ‘readiness for resuscitation,’ and after more than 1000 mL, a ‘full protocol … to resuscitate, monitor and arrest bleeding’ should be employed. The major problem, however, is early identification of women who may be bleeding .

In a large PPH preparedness survey, the Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN) PPH Project, in the US performed in 2013–2014, large variations were identified in the definitions of PPH, methods of identifying PPH, notification of team members, composition of the resuscitation team and the availability of medication and equipment. Less than 50% of the hospitals had a MOH protocol, performed risk assessments and drills, or routinely measured blood loss. It was considered that this lack of standardisation contributed to variation in rates of serious morbidity relating to PPH .

In one institution, a prescriptive approach to PPH management using quality improvement methodology was implemented; PPH was categorised into four stages based on the estimated blood loss (EBL): 0- risk assessment Table 2 , 1-EBL >500 mL, 2-EBL between 1000 and 1500 mL and 3-EBL >1500 mL . A prescriptive approach to management was developed for each stage, including measuring the blood loss at the time of delivery and delineating the personnel who should be informed and present at the mother’s bedside at each stage. The use of this protocol led to a reduction in the incidence of major haemorrhage and a reduction in blood product use across a whole region in the US . Similarly, another US-based quality improvement programme instigated an early prescriptive approach to PPH management with blood loss measurement and mandated that an obstetrician and obstetric anaesthetist attend the mother’s bedside once 1000-mL blood loss had been measured/estimated or suspected. This group also reported a reduction in the incidence of major haemorrhage, a reduction in blood product use and reduced ICU admissions (personal communication, teleconference to AWHONN: B Bateman, R Byfield; June 2016). A similar trend has been identified in a large city UK maternity hospital where measuring blood loss and early protocolised care led to a fall in major haemorrhage events, ICU admission and hysterectomy, far more than the effect of a study intervention, which was being conducted during this time period .

A key development in all programmes was the initiation of regular blood loss measurements as soon as abnormal bleeding had been identified. In clinical practice, blood loss during PPH is often estimated visually, especially if bleeding occurs outside the operating theatre. Measurement practice may also vary depending on whether the delivery is caesarean or vaginal. Of concern, studies have shown that visual estimation of blood loss is associated with significant underestimation of the actual blood loss, especially for large-volume blood loss in which underestimation may be as high as 30%–50% . This underestimation may also account for the discrepancies in the incidence of PPH reported in the literature. For example, the incidence of blood loss >1000 mL was estimated at 3.9/1000 (95% CI 3.3–4.5) in one study , whereas in another study, the incidence of blood loss >2500 mL was estimated at 4.3/1000 (95% CI 3.8–4.8) . Delivery units that have moved from visual estimates to the quantitative measurement of blood loss have noted a marked increase in the incidence of PPH (personal communication: G Lilley, Abergavenny delivery suite, UK 2016), although blood product use has not increased, indicating that the actual rate of PPH had not changed.

An article described improvements in estimating blood loss during simulated training sessions by using visual aids; pictures of known volumes of artificial blood were provided and were compared with the current scenario . Although impressive in training sessions, and a possible tool to improve early identification of abnormal bleeding, implementation into clinical practice and assessment against a standard outcome, such as a fall in haemoglobin, has not been performed. In another study, simulated PPH scenarios were performed with volumes of artificial blood ranging from 420 to 2480 mL . The mean error in identifying the volume by visual estimation was 34%; both over- and underestimation of the blood loss occurred. When the swabs and bed linen were weighted using a simple gravimetric subtraction technique using weighing scales ubiquitously found in a delivery suite, the error measurement in the volume of EBL was only 3% . An animated video of the technique is available from the AWHONN website . After adopting the gravimetric measurement of blood loss, the fall in haemoglobin correlated with the measured blood loss at delivery ( r = 0.8) when the blood loss was greater than 1500 mL, indicating that this approach is both feasible and practical in clinical practice .

Simulation training in the obstetric setting has been shown to improve safety for the mother and neonate . Specific training in PPH has been shown to improve adherence to guidelines and communication and is effective among diverse settings and provider types, including non-academic centres, midwives and in low-resource settings where the mother may be attended by medical officers . The importance of multidisciplinary training has been emphasised during the implementation of standardised protocols for the management of PPH .

Guidelines

Many national guidelines for the management of PPH exist. Although they differ in a number of aspects, some basic concepts common to the majority should be noted. The World Health Organisation (WHO) guide, 2012 edition, stands out as a consensus document formulated by an international committee with representation from low-, middle- and high-resource countries. One of its strengths is its organisation into practical sections: prevention, treatment and care. It has 31 evidence-based recommendations . An update is expected in 2017.

In the US, a very practical national consensus guide has been published. The first step focusses on the available institutional resources, with emphasis on routine risk assessment and the quantification of blood loss. The second step focusses on communication with the bleeding patient and response to haemorrhage using standard protocols. Of note, family and staff support is emphasised in the document. The final step includes monitoring, evaluation and routine debriefing, and analysis of serious events with the goal of learning and improving future care .

In the UK, the ‘RCOG Green-top Guideline No. 52’ addresses PPH in a broad and comprehensive manner based on published evidence and the results of the Confidential Enquiries into Maternal and Child Health, which summarise detailed reports of cases of maternal death . These details give an added value to the analysis of results and the importance of continuous improvement. In addition, the Guideline provides intervention tools and highlights anaesthetic management and the admission to high-dependency or intensive care units. These aspects of care are rarely mentioned in other PPH guidelines . The Association of Anaesthetists of Great Britain and Ireland Consensus Guidelines on the use of blood and blood components highlights the importance of early recognition and treatment of coagulopathy and recommends point-of-care (POC) testing of critical laboratory values and coagulation assessment . The Guidelines also note the importance of early administration of plasma, fibrinogen and tranexamic acid (TXA) .

The European guidance on severe peri-operative bleeding includes important references to PPH . Written in 2013, it highlights the role of POC tests as guides to treatment and the important contribution of hypofibrinogenemia to obstetric haemorrhage and thus the necessity of early replacement of fibrinogen (threshold value: 2 g/L). In addition, it includes a section regarding pre- and post-natal treatment of anaemia with intravenous iron . A new edition is currently under review and is planned to be published in 2017.

In France, the latest guidelines were published in 2016 by a large multidisciplinary team including obstetricians, anaesthesiologists, epidemiologists and haematologists, although the guidelines are focussed towards obstetric rather than anaesthesia care. Their strengths are the gradation of performance times (<30 min, >30 min), differentiation between primary and secondary PPH, and haemorrhage following vaginal delivery and during and after caesarean delivery. Algorithms with defined actions are suggested, and specific guidelines for the care of patients with placentation anomalies and clarification on the timing of transfer of the patient to another level of care are included .

A recently published qualitative systematic review summarised guidelines for the treatment of PPH from professional organisations in high-resource countries . The authors analysed the pros and cons of each guideline, including the inconsistencies among obstetric and non-obstetric guidelines. These inconsistencies may have a negative impact on the proper treatment of PPH. The authors suggested that standardised evidence analysis, assessment of cost-effectiveness of interventions and guidance as to whether guidelines for non-obstetric haemorrhage should be extrapolated to obstetric haemorrhage would be helpful. Finally, the authors also note the importance of conflicts of interest and regular updating of guidelines in guideline development .

Aetiology of major obstetric haemorrhage (MOH)

Uterine atony and trauma during caesarean delivery or after vaginal birth account for 80% of MOH. Identifying other causes of bleeding, however, is important because it can influence treatment. The rule of the 4 T’s is a widely used pneumonic (Tone, Trauma, Tissue and Thrombin) .

Uterotonic agents

Because uterine atony is the most common cause of PPH, first-line measures commonly focus on improving uterine tone. These measures include the removal of retained placenta fragments, uterine massage and bimanual compression, and concurrent use of uterotonic agents. Optimisation, preparation, the rational use of resources and protocols improve outcome in patients with uterine atony .

Oxytocin is the drug most commonly used in the treatment of MOH. The recommended dose varies among institutions, but its use is associated with vasodilatation, increased cardiac output, tachycardia and hypotension, especially when administered as a bolus. Myocardial ischaemia associated with its use has been documented. Thus, rapid administration of oxytocin should be avoided. If uterine tone is not adequate, additional oxytocin can be administered by infusion . Carbetocin is a long-acting oxytocin analogue that does not seem to provide additional benefits to oxytocin in terms of prevention or treatment of PPH but is considerably more expensive .

Ergot alkaloids may be administered as an intramuscular drug with oxytocin as a first-line uterotonic or alone as a second-line treatment (e.g. methylergonovine 0.2 mg). These drugs cause intense vasoconstriction because of adrenergic stimulation and are relatively contraindicated in patients with hypertension, preeclampsia, ischaemic heart disease or pulmonary hypertension .

If methylergonovine is not effective or is contraindicated, the next available drug is carboprost or other prostaglandins (misoprostol). This drug is injected intramuscularly at a dose of 0.25 mg and may be repeated every 15–30 min, up to a maximum dose of 2 mg. It is contraindicated in women with asthma because it can cause bronchospasm . Misoprostol can be administered sublingually, orally, vaginally or rectally. The usual dose is 600–1000 mcg. Adverse effects include pyrexia, shivering, nausea, vomiting and diarrhoea. A 2014 meta-analysis concluded that adding misoprostol to oxytocin for the treatment of PPH did not improve outcomes .

Surgical measures

Interventional radiology

In recent years, arterial embolisation has become a standard treatment to avoid hysterectomy and preserve fertility. The success of this procedure is over 80%, with a rate of complications under the 10%. In some high-risk cases with placenta accreta or percreta, prophylactic intra-arterial balloons have been placed (in the common iliac or internal iliac arteries) with the intention of using them after delivery if necessary. The use of occlusion intra-arterial balloons may not be useful in all cases because of anatomical variations in blood supply to the uterus .

Placing prophylactic intra-aortic balloons, just below the renal arteries, completely blocks the blood flow to the pelvic area. Immediate and late complications include thrombosis, ischaemia, necrosis of the bladder and neurological damage. The most common complication after arterial occlusion is arterial thrombosis, although the prognosis is good with early diagnosis and treatment. Ischaemia-reperfusion injury, vascular dissection or rupture may also occur. Hypertension is common after aorta occlusion, especially if the balloon inflation is abrupt. It is recommended that inflation be performed slowly (1.5 mL/s) .

The use of intravascular occlusion devises or embolisation for the treatment of PPH requires a haemodynamically stable and successfully resuscitated patient in addition to the availability of necessary technical and human resources. Not all hospitals are able to easily provide interventional radiology services; thus, the role of these procedures in the treatment of PPH remains unclear, and alternative treatment strategies are being sought .

Haemostatic impairment

The mother at term has an increase in all pro-coagulant factors except factor XI. The increase in fibrinogen concentration is especially marked (pregnant values normally range from 4 to 6 g/L, whereas non-pregnant values range from 2 to 4 g/L). The concentrations of von Willebrand factor and FVIII increase by 100%. These changes are reflected in shorter prothrombin times (PT) and activated partial thromboplastic times (aPTT) and an increase in the maximum clot firmness in viscoelastic testing. The concentration of natural anti-coagulants such as protein S fall, contributing to the prothrombotic state of pregnancy. The changes in the coagulation system contribute to an increased risk of thromboembolic disease but may protect women from PPH .

Although strategies to treat the coagulopathy associated with MOH have traditionally used a formulaic fixed ratio of RBC and FFP during PPH, there is increasing evidence that the haemostatic impairment associated with bleeding in the pregnant population is different from trauma-induced haemorrhage. Although current guidelines do not do so, strategies for the management of PPH should consider the prothrombotic starting point of the pregnant woman and differentiate between the different causes of obstetric haemorrhage .

There is currently a divergence of opinion: in the US, recently published PPH protocols encourage the early use of formulaic plasma and the UK Royal College of Obstetricians and Gynaecologist (RCOG) Green-top guidelines advocate the use of formulaic plasma/red blood cell (RBC) ratios if clotting studies are not available . In parts of Europe, factor concentrates have become popular, and some hospitals now only use blood products if indicated by POC testing. There is, however, increasing evidence that a PPH-specific approach should be adopted.

In a large consecutive cohort, in whom routine clotting studies were performed, the PT and aPTT remained normal in most patients until the EBL reached 4.5–5 L . Thus, either these tests are insensitive to coagulation failure in these circumstances or the intrinsic and extrinsic pathways of coagulation remain intact. In contrast, the fibrinogen concentration nadir was directly related to the EBL and fibrinogen concentration fell below the normal range for pregnancy well before the prolongation of PT and aPTT were noted.

The type, severity and rapidity of the onset of coagulopathy seems to vary with the aetiology of PPH. Uterine atony and surgical and genital tract trauma are often associated with no significant coagulopathy, even with relatively large blood loss, whereas in the setting of placental abruption, coagulopathy is common . These differences can also be seen in a study of women who required at least eight units of packed RBC . Although overall, 80% of PPH are associated with atony and trauma, in this study, only 50% of the haemorrhage cases were attributed to these causes and less common causes of haemorrhage, such as abruption and placental accreta, were over represented.

The underlying coagulation disorder during PPH seems to have two distinct initial aetiologies. Most PPH is caused by atony and trauma, and if early intervention to control haemorrhage is delayed or fails, a predominantly dilutional coagulopathy may evolve.

In contrast, placental abruption may be associated with a severe and rapid consumptive coagulopathy characterised by hypofibrinogenemia and thrombocytopenia; major deficiencies in other factors are not initially observed . In these settings, the severity of the haemostatic impairment may be severe despite the minimal initial blood loss. Amniotic fluid embolus (AFE) is associated with a severe and rapid disseminated intravascular coagulation (DIC) with widespread micro-emboli formation .

In a cohort of patients in whom haemorrhage was caused by uterine atony, genital and surgical trauma, and retained or adherent placenta, coagulation was assessed when the EBL was between 1000 and 1500 mL . The average fibrinogen concentration was 3.9 g/L, and PT and aPTT were normal in 98.4% and 98% of the cases, respectively. In contrast, during the early recognition period of haemorrhage from placental abruption, the average fibrinogen was lower at 2.2 g/L, but PT and aPTT were normal in all cases. These findings suggest that different aetiologies have variable effects on fibrinogen concentration but not other coagulation factors. Charbit et al. classified patients into severe or non-severe PPH groups and found that the only difference in coagulation tests were the fibrinogen levels, whereas the aPTT and INR were similar and generally changed little over the course of haemorrhage .

A dilutional coagulopathy develops secondary to resuscitation when coagulation factors are replaced by crystalloid solutions. The resulting dilution of all coagulation factors affects thrombin generation and leads to a fall in fibrinogen and affects clot strength . The use of colloid solutions, especially the hydroxyethyl starches, may further interfere with fibrin clot strength. This negative effect on coagulation has led to a decline in the use of starch-based colloids during volume resuscitation in obstetric and non-obstetric haemorrhage .

True consumption is uncommon in obstetric haemorrhage and results from the dysregulated activation of coagulation and a fall in coagulation factors, especially fibrinogen and platelets. Although PPH is commonly thought to be associated with DIC, DIC, as defined by international criteria, is uncommon . The consumptive coagulopathies described in PPH seem to be localised to the placental bed and caused by the local consumption of coagulation factors within the uterine clot. The most typical example of this is the concealed bleeding between the placenta and uterus that occurs in the setting of placental abruption . It may also occur with retained blood clot associated with retained products of conception and uterine atony. True DIC is seen with AFE; in some cases of severe preeclampsia or haemolysis, elevated liver enzymes, low platelets syndrome; sepsis and, occasionally, with the most severe cases of placental abruption. Consumption leads to critically low levels of coagulation factors, especially fibrinogen, earlier than would occur with haemodilution alone. Local activation of the fibrinolytic system at the time of delivery contributes to a reduction in stable clot formation , and ongoing bleeding is rapidly exacerbated by the dilution of coagulation factors with the risk of catastrophic haemorrhage.