PATHOPHYSIOLOGY

Two important points to recognise in treating obstetric patients are:

Table 56.1 Changes in physiological variables during late pregnancy

CARDIOPULMONARY RESUSCITATION¹⁰

Cardiac arrest is rare in pregnancy and estimated to occur once in every 30 000 deliveries.

At more advanced gestation, one must consider potential fetal viability and recognise that the aetiology of cardiac arrest may include particular obstetric complications, such as AFE or drug toxicity from magnesium sulphate and local anaesthetics. As soon as the cardiac arrest call is activated, an obstetrician should be notified and preparations made for perimortem caesarean delivery if appropriate (see below).

Normally, external cardiac massage produces only 30% of cardiac output and this is reduced further if there is vena caval compression. After about 20 weeks’ gestation it becomes increasingly necessary to relieve aortocaval compression during basic life support (BLS). Left lateral tilt decreases the efficiency of closed-chest compression, but a wedge providing an angle of 27° gives significant relief of vena caval obstruction while allowing 80% of the maximal force for chest compression.¹¹ During BLS, aortocaval compression may be minimised by manually displacing the uterus using a wedge, or positioning the pregnant patient’s back on the rescuer’s thighs. Chest compression should be performed with a slightly higher hand position (slightly above centre of sternum). Early tracheal intubation after cricoid pressure will facilitate ventilation and decrease the risk of acid aspiration. During advanced life support (ALS), drugs are given and defibrillation performed according to the normal protocols. Apical placement of the paddle may be difficult because of position and breast enlargement, and adhesive defibrillation pads are preferred.

Fetal or uterine monitors should be removed before defibrillation.

Case reports at advanced gestation indicate that both maternal and fetal survival from cardiac arrest may depend on prompt caesarean delivery to relieve the effects of aortocaval compression. The European Resuscitation Council Guidelines¹² and International Liaison Committee on Resuscitation (ILCOR) advisory statement¹³ suggest that, if there is no immediate response to ALS, perimortem caesarean delivery should be considered. The decision must be made quickly because the surgery should start within 4 minutes of the arrest, with the aim of delivering the infant within 5 minutes of the arrest. There is no need to perform the delivery if the fetus is less than 20 weeks because aortal caval compression is not problematic then.

There is now some experience with somatic support after brain death to allow the fetus to mature.¹⁰

TRAUMA

Trauma occurs in approximately 6–7% of all pregnancies but only requires hospital admission in 0.3–0.4% of pregnancies. Trauma is the leading non-obstetric cause of maternal mortality and survivors have a high rate of fetal loss.¹⁴ Head injuries and haemorrhagic shock account for most maternal deaths, while placental abruption and maternal death are the most frequent causes of fetal death.¹⁵ Most injuries occur as the result of motor vehicle accidents, but other common causes are suicide (usually postpartum), falls and assaults.

Initial resuscitation should follow the normal plan of attention to airway, breathing and circulation.¹⁶ Oxygen 100% should be given and cricoid pressure applied during tracheal intubation. Blood volume is increased during pregnancy and hypotension may not be evident until 35% or more of total blood volume is lost. Uterine blood flow is not autoregulated and may be decreased despite normal maternal haemodynamics, so that slight overhydration may be preferred to underhydration. Excessive resuscitation with crystalloids or non-blood colloids may increase the mortality from severe haemorrhage.

Treatment of hypotension always includes positioning or manual uterine displacement to avoid aortocaval compression. Drug treatment of modest hypotension can be started with ephedrine, but more potent vasopressors should be used if necessary. AFE has been reported after blunt abdominal trauma.

Assessment of trauma should note the increased significance of pelvic fractures for uterine injury and retroperitoneal haemorrhage.

Necessary radiological investigations should be performed as indicated because radiation hazard to the fetus is very unlikely, except in the early first trimester, where exposure to more than 50–100 mGy is a cause for concern. A chest X-ray delivers less than 5 mGy to the lungs and very little to the shielded abdomen. The fetal radiation dose from abdominal examinations can range from 1 mGy for a plain film, up to 20–50 mGy for an abdominal pelvic computed tomography (CT) with fluoroscopy.¹⁷

Cardiotocographic monitoring is considered essential, but there is wide variation in practice and in the recommended duration of monitoring. Premature labour and placental abruption may not be diagnosed unless regular monitoring is continued for at least 6 hours and even 24 hours if indicated.¹⁸ Rh immune globulin 300 µg should be considered for all Rh D-negative within 72 hours of injury. The Kleihauer–Betke test can be used to detect fetal blood in the maternal circulation and give an estimate of the volume of transplacental haemorrhage.

BURNS

Serious burns during pregnancy are seen more commonly in the developing world. Although the women are usually young and healthy, pregnancy is already a hypermetabolic state and the fetus is at great risk from many complications.¹⁹

Patients of advanced gestation should not be kept supine and nutritional support for the fetus is necessary early. Topical povodine-iodine solution should be avoided because the iodine may be absorbed and affect fetal thyroid function. Premature delivery may have to be considered, especially with extensive burns.

SEVERE OBSTETRIC HAEMORRHAGE

Severe bleeding is the most important cause of maternal death worldwide. Peripartum haemorrhage contributes to 15% of maternal deaths, but if one includes ectopic pregnancy, 25% of maternal deaths are a result of haemorrhage. It seems obvious that the treatment of massive haemorrhage requires sufficient intravenous access and the logistic capability to replace circulating volume quickly with warmed fluids, blood and clotting factors. Adequate preparation may even require the use of cell saver technology and operating in the angiography suite after the placement of catheters in preparation for embolisation. Unfortunately, many deaths have occurred because blood loss was often underestimated and volume replacement delayed. Conversely, excessive resuscitation with crystalloids or non-blood colloids when blood is required may increase the mortality from severe haemorrhage.

Antepartum haemorrhage is mostly from placenta praevia or placental abruption and both are ultimately managed by delivery. In placenta praevia, the placenta implants in advance of the presenting part and classically presents as painless bleeding during the second or third trimester. Placenta praevia is relatively common (1 in 200 pregnancies) but severe haemorrhage is relatively rare. In placental abruption, a normally implanted placenta separates from the uterine wall. The incidence of placental abruption is low (0.5–2%) but perinatal mortality may be as high as 50%. Several litres of blood may be concealed in the uterus as a retroplacental clot. Bleeding may continue after delivery for a variety of reasons, including:

Postpartum haemorrhage is usually from uterine atony or placenta accreta. In an emergency, the aorta can be compressed against the vertebral column by a fist pressed on the abdomen above the umbilicus. The control of haemorrhage allows time for resuscitation and more definitive surgical treatment.

Uterine atony is managed initially with bimanual compression, uterine massage and intravenous oxytocin given intravenously by bolus (5 units) or infusion (20 units). Oral misoprostol (0.6–1.0 mg) can also be used, while methylergonovine (0.2 mg) or 15-methyl-prostaglandin F_2α (0.25 mg) is given intramuscularly or intramyometrially for persistent atony. Recombinant factor VIIa has also been used but the place of this therapy is still unclear.^38,39 If bleeding persists, tamponade techniques using gauze packs or balloons may be useful. Otherwise specific invasive management such as angiographic arterial embolisation, surgical ligation of the uterine, ovarian or internal iliac arteries or hysterectomy may be required.²⁰

With massive bleeding and transfusion, there should be no need to wait for a coagulation profile before giving coagulation factors. Disseminated intravascular coagulation still develops in 10–30% of cases, partly because tissue thromboplastin is released during abruption. Blood should be sent for measurement of fibrinogen and fibrin degradation products and blood component therapy, and cryoprecipitate given as appropriate.

SEPSIS AND SEPTIC SHOCK^21,22

Although sepsis is a major problem in intensive care, maternal sepsis and septic shock are relatively uncommon and the prognosis is usually better than in the general population. The most common sources of infection are chorioamnionitis, postpartum endometritis, urinary tract infections, pyelonephritis and septic abortion. The physiological changes of pregnancy may influence the course and presentation of septic shock. Animal studies suggest that pregnancy increases the susceptibility to endotoxin, and that metabolic acidosis and cardiovascular collapse occur earlier.

Management of septic shock follows normal guidelines with eradication of the infectious source, although the normal range for haemodynamic variables may be different. Gram-negative organisms are the frequent causative organisms but streptococci and Bacteroides may also be present. Antimicrobial therapy is dependent on hospital prevalence and susceptibility patterns, but empirical broad-spectrum therapy should be started early. Typical combinations are ampicillin, gentamicin and clindamycin, or imipenem, cilastatin and vancomycin. Tetracyclines and quinolones should not be used in pregnancy.

Newer approaches such as insulin therapy, corticosteroids and activated protein C have not been properly evaluated in pregnancy.²

VENOUS THROMBOEMBOLISM²³

Pulmonary thromboembolism is a common cause of maternal death, accounting for 15–25% of maternal mortality. Pregnancy is associated with a fivefold increase in thromboembolism because of:

Patients with acquired and hereditary thrombophilias have an even greater risk.

Accurate diagnosis of venous thromboembolism is crucial because of the long-term implications for therapy. Symptoms of dyspnoea or pain in the leg or chest require accurate diagnosis, especially in the immediate postpartum period. Although contrast venography is the gold-standard test for diagnosing deep-vein thrombosis, the radiation exposure and invasive nature of the test mean that duplex Doppler ultrasonography is the usual first choice. D-dimer testing may also be useful but a positive test must be interpreted in the clinical context because D-dimer values normally increase throughout pregnancy. Venography, perfusion lung scanning, pulmonary angiography and helical CT scan should not be avoided if indicated.²

There are various reviews summarising the guidelines for anticoagulant therapy during pregnancy.^24,25 Although LMWH has gradually replaced unfractionated heparin for the prophylaxis and treatment of deep-venous thrombosis and pulmonary embolism in pregnancy, there is not adequate evidence for a definitive recommendation in pregnancy. Patients with suspected or proven deep-vein thrombosis or pulmonary embolus should be given full anticoagulant therapy that is continued throughout pregnancy. Warfarin should not be used before delivery so heparin is continued until labour begins and restarted in the postpartum patient for at least 6–12 weeks.

With life-threatening massive pulmonary embolus, surgical treatment or thrombolysis must be considered. Thrombolysis was thought to be relatively contraindicated during pregnancy because of the risk of maternal and fetal haemorrhagic complications. No controlled trials are feasible and outcome data must be extracted from case reports. A recent review found that thrombolytic therapy was associated with a low maternal mortality rate of 1%, with a 6% rate of fetal loss and 6% rate of premature delivery.²⁶ The fetal risks appear to be lower than that obtained with surgical intervention in pregnant patients, and maternal risks lower than reported risks for surgery, thrombolysis or transvenous filters in non-pregnant patients. Although heparin remains the treatment of choice, thrombolysis appears to be a viable option except during the immediate postpartum period.

AMNIOTIC FLUID EMBOLISM

AFE remains largely an unpredictable and unpreventable disease of uncertain pathophysiology.^27,28 Most of the information about AFE has been derived from case reports, maternal mortality reviews and reports from national registries of AFE, such as those in the USA²⁹ and UK.³⁰ The incidence of AFE varies between 1 in 8000 and 1 in 80 000 deliveries, although there must be undetected and unsuspected cases where minimal amounts of amniotic fluid produce few symptoms. AFE is the cause of 5–10% of maternal deaths, and 25–50% of patients with suspected or proven AFE die within the first hour. The overall maternal mortality has been as high as 86% in symptomatic patients, with a perinatal and neonatal mortality up to 40% and significant neurological problems in surviving neonates. However, recent figures of 26–37% mortality are more encouraging and this may be the result of early suspicion of AFE and early intensive care support.

AFE was thought to be associated with vigorous labour and the use of oxytocics, but it may occur in any parturient. The exact pathogenic factors for the syndrome of AFE remain unclear.³¹ Amniotic fluid is thought to enter the maternal circulation through endocervical or uterine lacerations, uterine veins at the site of placental separation or placental abruption. Amniotic fluid normally contains prostaglandins, leukotrienes, endothelin and fetal debris that can cause complement activation, pulmonary vasoconstriction and physical blockage of pulmonary capillaries, with resultant damage and release of further mediators. By these mechanisms, AFE has more in common with anaphylaxis and septic shock than other embolic diseases.

The initial diagnosis of AFE is made on clinical grounds and is often one of exclusion. Classically, patients may present with severe dyspnoea, cyanosis, sudden cardiovascular collapse, coma or convulsions during labour but AFE may occur earlier during pregnancy, during delivery or in the early puerperium. Some patients may present with bleeding and most patients eventually develop a coagulopathy.

Animal studies indicate that AFE causes a biphasic haemodynamic response. The early phase probably lasts less than half an hour and is characterised by severe hypoxia and right heart failure as a result of pulmonary hypertension from vasoconstriction or vessel damage. Patients who survive this first phase develop left ventricular failure with return of normal right ventricular function. Left ventricular failure may be a result of the initial hypoxia or the depressant effects of mediators. Disseminated intravascular coagulation is present in most patients but the mechanism is unknown. It could be caused by a specific activator of factor X, tissue factor or other substances, such as trophoblasts, in the amniotic fluid. Traditionally, AFE is confirmed by detection of squamous cells and fetal debris in the pulmonary circulation either at autopsy or in blood samples from a pulmonary artery catheter, but squamous cells are a contaminant that can be found in other parturients and even in non-pregnant patients.

No specific therapy is available. Immediate cardiopulmonary resuscitation and 100% oxygen are necessary. Assessment of central venous pressure may be misleading, and early pulmonary artery catheterisation has been advocated in a series reporting 100% survival in 5 patients by treating left ventricular failure aggressively.³² The differential diagnoses must be evaluated quickly because urgent delivery of the fetus by caesarean section may improve resuscitation and prevent further AFE. Patients who survive the first few hours will continue to require supportive treatment for their acute lung injury. Blood component therapy is given as necessary to manage the coagulopathy. Cryoprecipitate has sometimes provided significant improvement in patient oxygenation, and recombinant factor VIIa has also been used. Survivors of AFE regain normal cardiorespiratory function but may have neurological sequelae.

ACUTE RESPIRATORY FAILURE

Asthma is the commonest respiratory condition complicating pregnancy but specific concerns are mainly related to the possibility of fetal toxicity from pharmacologic therapy. However there is no evidence that systemic corticosteroids or short-term use of beta-agonists are associated with adverse fetal outcomes.⁶

Pulmonary oedema is more likely in the pregnant patient (1:1000 pregnancies) because of the increased cardiac output and blood volume, and the decreased plasma oncotic pressure. The principles of treatment are relatively straightforward in terms of determining the cause of the oedema and improving oxygenation, although it can be difficult to distinguish between hydrostatic and permeability oedema.^2,7

The prevalence of acute respiratory distress syndrome during pregnancy has been estimated at 16–70 cases per 100 000 pregnancies, with mortality rates from 23 to 50%.^5,7 Some of the recommended strategies for managing this condition may be problematic. Low tidal volumes make it difficult to maintain the increased ventilatory requirements of pregnancy, and higher tidal volumes and alveolar plateau pressures up to 35 cmH₂O (0.34 kPa) may be necessary. Transfer of CO₂ across the placenta requires a gradient of 10 mmHg (1.33 kPa). Permissive hypercapnia may cause fetal respiratory acidosis that will reduce the ability of fetal haemoglobin to bind oxygen, and PaCO₂ should probably be kept below 45 mmHg (6.0 kPa) and PaO₂ above 70 mmHg (9.3 kPa).⁵ If conventional ventilation fails, the effectiveness of alternative strategies is unknown. There are no data on the prone position and only a few reports of inhaled nitric oxide.

Unlike in other obstetric-related conditions, delivery of the fetus does not appear to result in marked improvement of maternal respiratory failure.

ACID ASPIRATION (MENDELSON’S SYNDROME)

Obstetric patients are at increased risk of acid aspiration because of decreased gastric emptying, increased gastric acidity and volume and increased intra-abdominal pressure. Aspiration of acidic material will cause acute lung injury, the severity being related to the amount, content and acidity of the aspirate.

The initial presentation is hypoxaemia and bronchospasm. Chemical pneumonitis and increased permeability pulmonary oedema develop over several hours.

Treatment includes standard respiratory support. Rigid bronchoscopy may be required to remove large food particles. Bronchoalveolar lavage and steroids are not useful and antibiotics should only be given for proven infection.

TOCOLYTIC THERAPY AND PULMONARY OEDEMA³³

Pulmonary oedema is an uncommon (1 in 400 pregnancies) but serious complication of tocolytic therapy with beta-adrenergic agonists. The underlying mechanism for pulmonary oedema is unclear, but it is probably related to fluid overload and the cardiovascular effects of beta-adrenergic agonists leading to increased pulmonary capillary hydrostatic pressure. The initial management of pulmonary oedema is discontinuation of the beta-adrenergic agonist and oxygen therapy, with further monitoring, diuretics and respiratory support as necessary. This problem should disappear as alternative tocolytics such as nifedipine and atosiban are used.

COCAINE TOXICITY³⁴

Cocaine abuse during pregnancy has become a significant problem in the USA, affecting more than 30 million people, with 90% of the women of child-bearing age. Cocaine has local anaesthetic and sympathomimetic actions and can cause:

Patients commonly present with chest pain. cardiovascular complications or placental abruption and fetal distress. Acute toxicity may also mimic pre-eclampsia by presenting with cerebral haemorrhage or convulsions.

For the treatment of hypertension, the drug of choice is controversial. Although hydralazine is often used in obstetrics to treat maternal hypertension, labetalol is also widely used. However, concerns about beta-blockers allowing unopposed alpha-adrenergic stimulation may also apply to a lesser extent with labetalol, and calcium-channel antagonists and nitroglycerine have also been advocated. Nitroglycerine and benzodiazepines have been recommended for the treatment of cocaine-related myocardial ischaemia and infarction.

OVARIAN HYPERSTIMULATION SYNDROME³⁵

Ovarian hyperstimulation syndrome (OHSS) remains a significant but unpredictable and incompletely understood complication of ovarian stimulation. The syndrome is typically associated with:

The pathophysiology of OHSS has not been fully determined. A likely mediator is vascular endothelial growth factor, but many interacting cytokines and endocrine factors may be involved.

OHSS is most severe at several days to a week after a stimulated cycle, but early signs and symptoms can often be seen during the stimulatory phase. Fertility clinics will have their own protocols to try and minimise the incidence of OHSS and to detect its early stages. In general, symptoms resolve spontaneously over 2 weeks, in parallel with the decline in hCG from the last doses given. However, a successful pregnancy implantation will increase endogenous hCG and may temporarily worsen OHSS. Although subclinical OHSS may be found in most patients, only a small percentage require ward admission for careful fluid management to restore circulating volume with saline or albumin, prevention of thrombosis with heparin, and treatment of ascites by ultrasound-guided paracentesis as necessary. Severe OHSS may cause renal failure, respiratory failure or thromboembolism, which requires supportive intensive care therapy. Invasive monitoring is essential for fluid management.