Pulmonary arterial hypertension in pregnancy

Learning objectives.

By reading this article you should be able to:

• •Discuss the pathophysiology of pulmonary arterial hypertension (PAH) in relation to pregnancy.
• •Identify pregnant women at risk of PAH.
• •Describe the management of an acute intrapartum pulmonary hypertensive crisis.

Key points.

• •PAH in pregnancy is a high-risk condition associated with increased morbidity and mortality.
• •Advancements in targeted therapies and better understanding of the pathophysiology have led to improved outcomes.
• •Pregnant women with PAH should be managed in an expert centre by a multidisciplinary team.
• •Mortality is highest immediately postpartum.
• •A comprehensive management plan for elective and emergency delivery is required.

Background

Pulmonary arterial hypertension (PAH) is a high-risk pathology, associated with a 3-yr mortality of 55%.^1,2 The condition is rare with no cure and disproportionately affects women, particularly of child-bearing age.^1,3 Cardiac disease in pregnancy is increasing, and remains one of the most common causes of maternal death in higher income countries.^4,5 In a recent review of cardiac disease in pregnancy, PAH accounted for only 1% of cases, but was associated with the highest morbidity and mortality.⁶ Advancements in pulmonary vasodilator therapies, and early recognition and management of conditions such as congenital heart disease (CHD) have resulted in increased life expectancy, with more women reaching adulthood and child-bearing age.^1,5

The World Health Organization (WHO) classifies PAH as class IV maternal cardiac risk (mWHO IV) and avoidance of pregnancy is strongly recommended.^2,7 Right heart failure is the most common cause of death in these patients because they are unable to compensate for the physiological changes of pregnancy.^1,6 Maternal risks also include other major adverse cardiac events and an increased incidence of pre-eclampsia, thrombotic events and postpartum haemorrhage (PPH).⁶

Fetal and neonatal complications include prematurity, stillbirth, intrauterine growth restriction and an associated mortality of 0–30%.⁷ Despite counselling to avoid pregnancy, some patients will opt to embark on and continue pregnancy for a variety of personal reasons. There are also women who are previously undiagnosed and who present for the first time in pregnancy.

The risk for an individual woman depends on the severity of their PAH. One review found 25% mortality in women with right ventricular (RV) systolic pressures >70 mmHg compared with 0% in low-to-moderate systolic pressures.⁵ Another series found poorer outcomes in women with an average mean pulmonary artery pressure (mPAP) of 71 compared with an mPAP of 36 mmHg.⁸ Early reviews reported mortality rates of 30–56% in pregnant patients with PAH.^9,10 More recently, a number of case series and reviews have reported improved mortality rates of 10–33%.^7,8,11, 12, 13, 14, 15 Three case series published since 2020 reported no mortality.^14,15 Although mortality rates are still prohibitively high, the improving survival is likely to result from better understanding of the pathophysiology, evolving targeted therapies and skilled multidisciplinary team (MDT) management in specialist centres.^1,10,14,16 These patients require care in specialist high-risk obstetric centres with experience in managing patients with PAH.^1,7 Anaesthetists play a significant role as part of the MDT. These patients present complex anaesthetic challenges that require a good understanding of the pathophysiology and treatment options available. This article focuses on the pathophysiology of PAH in pregnancy and the considerations for the anaesthetist.

Classification and definition

The WHO classifies pulmonary hypertension (PH) into five groups, differentiated by clinical characteristics, pathophysiology and treatment options, with PAH being group 1.¹⁷ A revised classification of aetiologies by the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) guidelines in 2015 is shown in Table 1.¹⁷ The aetiology and pathophysiology is important to understand, because it determines the most appropriate therapy for a particular group. PAH is further subdivided by aetiology, including idiopathic (IPAH), PAH associated with CHD, human immunodeficiency virus (HIV) and connective tissue disorders. PAH secondary to Eisenmenger’s syndrome is associated with the highest mortality in pregnancy, followed by IPAH.^1,10

Table 1.

Classification of pulmonary hypertension (adapted from ESC/ERS guidelines 2015)¹⁷.

Group 1 Pulmonary arterial hypertension (PAH) 1.1. Idiopathic 1.2. Heritable 1.2.1. BMPR2 mutation 1.2.2. Other mutations 1.3. Drugs and toxins induced (e.g. serotonin reuptake inhibitors, amphetamines) 1.4. Associated with: 1.4.1. Connective tissue disorders 1.4.2. Human immunodeficiency virus (HIV) infection 1.4.3. Portal hypertension 1.4.4. Congenital heart disease (CHD) 1.4.4.1. Eisenmenger's syndrome 1.4.4.2. PAH associated with prevalent systemic-pulmonary shunt 1.4.4.3. PAH with small or coincidental defects, usually ventricular septal defect <1 cm and atrial septal defect <2 cm 1.4.4.4. PAH after defect corrected 1.4.5. Schistosomiasis 1.5. PAH secondary to pulmonary veno-occlusive disease, pulmonary capillary haemangiomatosis, or both 1.6. Persistent pulmonary hypertension of the newborn Group 2 Pulmonary hypertension caused by left heart disease Group 3 Pulmonary hypertension resulting from lung disease, hypoxia, or both Group 4 Chronic thromboembolic pulmonary hypertension Group 5 Pulmonary hypertension with unclear, multifactorial, or both mechanisms

The 6th World Symposium on Pulmonary Hypertension (WSPH) defines PH as an mPAP ≥20 mmHg.17, 18, 19 Precapillary PH secondary to pulmonary vascular disease is further defined by a pulmonary vascular resistance (PVR) of >3 wood units (WU) and a pulmonary artery wedge pressure <15 mmHg.17, 18, 19

Pathophysiology

There are three main processes that result in increased PVR. These are sustained pulmonary vasoconstriction; cellular proliferation in the intimal, medial and adventitial layers of the pulmonary vessels; and localised thrombi formation further obstructing pulmonary capillary flow.^3,20 The resulting vascular remodelling exhausts the availability of endogenous vasodilators nitric oxide and prostacyclin, whilst upregulating endothelin-1, a potent vasoconstrictor.³ These changes results in RV strain, increased afterload and abnormal ventricular remodelling. Eventually, this culminates in RV dysfunction and failure, the primary determinant of survival in PAH.^3,20

Physiological changes in pregnancy and PAH

Pregnancy is a high cardiac output and hypermetabolic state. In the early first trimester, an increase in the hormones progesterone, oestrogen and relaxin mediate vasodilation of the vasculature causing a reduction in systemic vascular resistance (SVR) contributing to uteroplacental blood flow and fetal growth. This in turn activates the renin–angiotensin system to promote salt and water retention. By the third trimester the plasma volume has increased by 50%, with an extracellular fluid volume of ∼6–8 L, contributing to an increased stroke volume and cardiac output.⁶

The physiological effects of pregnancy on the pulmonary circulation are similar to those seen within the systemic circulation. Normally, increased progesterone levels promote pulmonary vasodilation and recruitment of non-perfused pulmonary arterioles. In PAH, the normally thin walled and distensible pulmonary vasculature is thickened and chronically vasoconstricted. The non-compliant pulmonary arteries are unable to accommodate for the increased cardiac output and plasma volume, leading to further increases in PVR and RV strain. The right ventricle becomes highly vulnerable to ischaemia and failure. The left ventricle is then compromised because of interventricular interdependence and compression from septal bowing. Before labour, the most hazardous period in PAH is between 20 and 30 weeks when cardiac output peaks.^1,21

During labour the sympathetic stimulation from pain, fluid shifts and changes in intrathoracic pressure from the Valsalva manoeuvre during the second stage increase PVR further. These induce rapid changes in the preload-dependent right ventricle, which can lead to catastrophic cardiovascular collapse. Immediately postpartum, the autotransfusion of ∼500 ml of blood from the uterine contraction and shifts of extracellular fluid into the intravascular compartment can lead to sudden RV overload.^1,6 The highest risk for mortality in PAH is immediately postpartum, with physiological changes taking 3–6 months to normalise.^1,2,6

Pregnancy is a hypercoagulable state. This, coupled with the histological picture of microthrombi in the pulmonary arterioles in PAH, increases the risk of thrombotic events in pregnant patients with PAH.³ Idiopathic pulmonary arterial hypertension in particular has an increased risk of thrombosis and evidence suggests better survival outcomes when these patients are anticoagulated; conversely, patients with Eisenmenger’s syndrome are at increased risk of haemorrhage as a result of intrinsic deficiencies of vitamin K-dependent clotting factors and the risk of thrombocytopenia.^7,22 Anticoagulation in the pregnant patient with PAH will therefore require careful consideration depending on the individual risk assessment.

Presentation and diagnosis

Most patients present with a prenatal diagnosis of PAH, although a small number will present during pregnancy. Diagnosing PAH can be difficult, as signs and symptoms are often non-specific and subtle leading to a delayed diagnosis. Particular attention should be given to pregnant women with a family history or those with associated conditions such as CHD, HIV and connective tissue disorders. There should be a high index of suspicion in a pregnant patient presenting with excessive exertional dyspnoea, fatigue or signs of right heart failure and they should be referred for further investigation (Table 2). The ECG may be normal, particularly in mild PAH. In more severe disease, the ECG may show RV strain or supraventricular arrhythmias such as atrial fibrillation or flutter, with ventricular arrhythmias rare in PAH.¹⁷ Essential components of the investigation are determining the presence, severity and aetiology of the PH and assessing the degree of right heart dysfunction.

Table 2.

Signs and symptoms of pulmonary hypertension—often subtle and non-specific.

Symptoms	Signs	Auscultation	ECG changes
•Exertional dyspnoea • Fatigue • Syncope • Chest pain • Dry cough • Peripheral oedema • Haemoptysis (rare)	• Tachycardia/arrhythmias • Raised jugular venous pressure • Hepatomegaly • Ascites • Mottled extremities • Hypoxia	• Systolic murmur indicating tricuspid regurgitation • Diastolic murmur indicating pulmonary regurgitation • Accentuated pulmonary valve component (P2) • Right ventricular S3 and S4 sounds	• P pulmonale • RV strain • RV hypertrophy • Right axis deviation • Right bundle branch block • QRS/Qtc prolongation suggests severe disease

Transthoracic echocardiography (TTE) is the first-line non-invasive investigation when PH is suspected.¹⁷ Doppler measurements and the modified Bernoulli equation are utilised to calculate the tricuspid regurgitation velocity and estimate PAP in suspected PH (Table 3).¹⁷ In addition to tricuspid velocity, TTE signs are used to assess the probability of PH (Table 4). Echocardiography signs from at least two different categories (A/B/C) in Table 4 should be present to estimate the probability of PH as per ESC/ESR guidelines.¹⁷ Structural changes seen on TTE in severe PAH include RV hypertrophy and right atrial (RA) dilatation (Fig. 1), tricuspid regurgitation (Fig. 2) and ventricular septal displacement (Fig. 3). Echocardiography enables further differentiation of PH into PAH with features of CHD present and excluding evidence of left heart disease (group 2). Spirometry and either a ventilation perfusion scan or CT pulmonary angiogram should be performed to exclude lung (group 3) and thromboembolic (group 4) disease.¹⁶

Table 3.

Echocardiographic probability of PH in symptomatic patients with suspicion of PH (ESC/ESR guidelines)¹⁷.

Peak tricuspid regurgitation velocity (m s−1)	Presence of other echocardiographic signs of PH∗	Probability of PH by echocardiography
≤2.8 Or not measurable	No	Low
≤2.8 Or not measurable	Yes	Intermediate
2.9–3.4	No
2.9–3.4	Yes	High
>3.4	Not required

∗See Table 4.

Table 4.

Echocardiographic signs suggesting PH to assess probability in addition to tricuspid regurgitation velocity measurement (ESC/ESR guidelines)¹⁷.

A: The ventricles	B: Pulmonary artery (PA)	C: Inferior vena cava and right atrium
Right ventricle/left ventricle basal diameter ratio >1.0	Right ventricular outflow Doppler acceleration time <105 ms, mid-systolic notching, or both	Inferior cava diameter >21 mm with decreased inspiratory collapse (<50% with a sniff or <20% with quiet inspiration)
Flattening of the interventricular septum (left ventricular eccentricity index >1.1 in systole, diastole, or both	Early diastolic pulmonary regurgitation velocity >2.2 m s-1	Right atrial area (end-systole) >18 cm2
	PA diameter 25 mm

Figure 1.

A TTE image showing RA dilatation and RV hypertrophy in PAH. RV focused four-chamber apical view. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.

Figure 2.

A TTE image of tricuspid regurgitation in PAH. Apical four-chamber view. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.

Figure 3.

A TTE image highlighting a D-shaped LV secondary to RV volume overload in PAH. Parasternal short-axis view. RV, right ventricle; LV, left ventricle.

The ‘gold standard’ for the diagnosis of PAH is right heart catheterisation (RHC).¹⁷ Right heart catheterisation establishes the diagnosis, grade severity and guide therapeutic interventions. It is especially useful in patients who have PH of mixed aetiology, which is not uncommon particularly in patients with CHD. Complications from RHC in pregnancy are low when performed at expert centres and may be considered when the diagnosis is unclear after TTE.^17,23 To reduce fetal radiation exposure, considerations include external shielding, confining the X-ray beam to focused areas and a radial artery approach instead of femoral to avoid the pelvis.^17,23

Antenatal management

Once PAH is suspected or diagnosed, patients should be referred to an expert centre for further investigation and management. The MDT should consist of maternal–fetal medicine (MFM) obstetricians, midwifery, cardiology and an obstetric anaesthetist. Input will be required from haematologists and cardiac anaesthetists, intensive care, neonatology and extracorporeal membrane oxygenation (ECMO) services when planning delivery.

Anaesthetic antenatal management should include comprehensive documentation of elective and emergency delivery plans.

Termination of pregnancy is recommended and considered safest in the first trimester. It should also be considered up to viability in the second trimester, but it becomes more perilous as gestation increases.^1,6 Medical termination is considered safest and recommended with mifepristone.¹ It is imperative that during the counselling process the woman has autonomy and is part of the shared decision-making process.

Women choosing to continue with pregnancy will require assessment on a regular basis by their cardiologist and MFM obstetrician, increasing in frequency as the pregnancy progresses. Functional status is a critical part of the assessment. The WHO functional class (WHO-FC) is the best prognostic indicator of survival in PAH and any deterioration in functional status should prompt immediate investigation.^6,7,17 Other prognostic indicators include the 6-min walk test (6MWT), which is easy to perform and interpret. It is recommended to assess effort with the Borg scale at the end of the test.¹⁷

Brain natriuretic peptide (BNP/NT-proBNP) is the most commonly used biochemical marker in PAH. Brain natriuretic peptide concentrations routinely double in pregnancy but remain within normal limits and BNP is therefore a useful indicator of worsening cardiac function.⁶ Currently there is no specific biochemical marker for PAH, but BNP is the most widely accepted and is a strong prognostic indicator.¹⁷

Regular TTE is essential to assess the sequelae of PAH, such as RA and RV function, severity of tricuspid valve regurgitation, septal bowing and left ventricular impairment. This will enable guidance on therapies and planning mode of delivery as part of a comprehensive assessment. At our institution women will have a TTE each trimester as a minimum. The frequency will usually increase in the last trimester depending on the underlying functional status and is guided by the cardiologist.

Specific therapies in PAH

Targeted therapies have contributed to improved survival and life expectancy of patients with PAH. These therapies target three biological pathways. Endothelin-1 causes vasoconstriction of smooth muscle when bound to endothelin-A receptors.^3,24 Bosentan, ambrisentan and macitentan are widely used endothelin receptor antagonists. However, they are contraindicated because of teratogenicity and are labelled category X in pregnancy.¹

The nitric oxide and prostacyclin (PGI₂) pathways are diminished in PAH, which leads to a decrease in production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), respectively, amplifying vasoconstriction and abnormal cell proliferation.³ Phosphodiesterase 5 (PDE5) inhibitors target the nitric oxide pathway. Sildenafil, an oral selective PDE5 inhibitor, is recommended as the first-line agent in pregnant patients with WHO-FC I/II and normal RV function. Studies show that sildenafil improves exercise capacity and haemodynamics, and it is also available in parenteral form.^1,17 Riociguat, a newer agent that works on the nitric oxide pathway, is contraindicated in pregnancy.⁶

Prostacyclin analogues target the PGI₂ pathway. These can be given parenterally (epoprostenol), inhaled (iloprost) or subcutaneously (treprostinil). Studies have shown that epoprostenol improves symptoms, exercise capacity and mortality in non-pregnant patients with IPAH.¹⁷ The decision to commence these will be guided and initiated by the cardiologist with the primary goal to protect RV function. Epoprostenol has a short half-life (3–5 min) with rebound effects if stopped abruptly.¹⁶ Treatment requires long-term tunnelled venous access and care must be taken to prevent line sepsis and malfunction of the delivery system. Nebulised iloprost has been used successfully in pregnancy, but it needs to be given several times daily and can be extremely onerous for the patient.^12,17 Another potential issue with epoprostenol is an increased risk of bleeding because platelet aggregation is inhibited. There have been case reports of wound haematomas and thrombocytopenia, with severe PPH associated with epoprostenol use in PAH and pregnancy. However, there are no reports of neuraxial haematoma after regional anaesthesia.²⁵

In addition to targeted therapies, antenatal care includes a risk assessment regarding anticoagulation. Patients already taking warfarin or direct oral anticoagulants require transition to low molecular weight heparin and careful planning of cessation of these before delivery, in consultation with a haematologist. Euvolaemia is targeted by restricting intake of fluids and salt. If required, diuretic therapy is used judiciously to avoid adverse effects on the fetus. Furosemide should be first line because spironolactone has teratogenic effects.^1,6 Iron deficiency is common in PAH and pregnancy; anaemia should be corrected and monitored to optimise the blood oxygen-carrying capacity.¹⁷

Planning mode, timing and place of delivery

Consensus guidelines recommend Caesarean section as the preferred mode of delivery for PAH in pregnancy, but there is limited evidence to support this.^1,13 The advantages of Caesarean section include avoiding the physiological impact of labour, particularly pain-induced catecholamine release and Valsalva manoeuvre with maternal expulsive effort. These issues can be avoided with an effective epidural and passive descent during the second stage, followed by a planned instrumental delivery. Vaginal delivery is associated with decreased infection, bleeding and thrombotic events.⁷ There have been a number of case series reporting successful vaginal deliveries in patients with PAH.^4,10,13,21 Vaginal delivery is most likely to be successful in multiparous patients who are at term gestation where the cervix is more favourable. Careful consideration should be given to the risk of maternal decompensation during a prolonged induction in a primiparous woman with severe PAH.¹³ Overall the mode of delivery will be governed by obstetric and fetal indications, institutional practices and maternal preferences as part of the shared decision-making process. If vaginal delivery is planned, induction should be clearly scheduled as this allows MDT planning for cessation of anticoagulation, monitoring, neuraxial anaesthesia and contingency planning for intrapartum Caesarean section if required.

The optimal place for delivery should be considered. Many of the medications and monitors are unfamiliar on the maternity unit, whilst transfer from the intensive care unit may be slow in the event of sudden fetal compromise. At our institution the highest risk women are induced and delivered in an operating theatre to allow rapid commencement of Caesarean section or medical therapy including ECMO if required.

Timing of delivery is recommended at 34 weeks, but the optimum time is unknown.^1,12 PAH in pregnancy is associated with preterm labour and increased neonatal complications.^2,11,21 Timing of delivery is a balance between the risk of maternal deterioration and improved neonatal outcomes with longer gestation.²⁶ At our institution, the approach to mode and timing of delivery has been on an individual basis. In our experience of seven deliveries, all proceeded to 37 weeks and five delivered vaginally. Two delivered by Caesarean section because one had placenta previa and the other had severe PAH. Mortality was zero in our case series.¹⁵

Anaesthesia for intrapartum management

Haemodynamic goals

The intrapartum haemodynamic goals are to prevent increases in PVR and RV afterload, whilst maintaining SVR. Avoidance of hypoxia, hypercapnia, acidosis, high airway pressures and pain is paramount to prevent increases in PVR.²⁷ Non-pharmacological strategies include supplemental oxygenation and careful fluid balance to avoid fluid overload. Oxytocin for induction should be concentrated to avoid giving excessive volumes of fluids.

Analgesia and anaesthesia

Neuraxial anaesthesia is the recommended method for vaginal and Caesarean deliveries in PAH with successful outcomes in a number of case series.^1,4,11, 12, 13^,21 Slowly titrated epidural analgesia for vaginal delivery before induction minimises haemodynamic compromise, provides effective analgesia and the ability to convert to regional anaesthesia for intrapartum Caesarean section if required. Alternative pain relief methods such as nitrous oxide and opioid-based patient-controlled analgesia should be avoided because of the potential to increase PVR and worsen hypoxia and hypercapnia.

Adequate regional anaesthesia for Caesarean section requires a dermatomal block to the level of T5. A single-shot spinal anaesthesia is regarded as being contraindicated for patients with PAH to avoid rapid haemodynamic changes, in particular vasodilation, which will compromise RV perfusion.^1,28 Epidural anaesthesia allows careful titration, but it may not deliver the adequate sensory block required for Caesarean section. The combined spinal–epidural technique is a favourable method as a low-dose spinal anaesthetic will achieve a denser block without risking rapid haemodynamic instability.^1,4,21 Maxwell and colleagues described the use of hyperbaric bupivacaine 0.75%, 3–6 mg intrathecally, supplemented with lidocaine 2% (5–22 ml) epidurally with good outcomes.⁴ Our practice is intrathecal hyperbaric bupivacaine to a maximum dose of 5 mg with additional fentanyl and morphine. The epidural is then dosed incrementally with either lidocaine 2% with adrenaline for speed, or ropivacaine 0.75% for density. Removal of the epidural and initiation of anticoagulation will need to be planned to avoid the risk of neuraxial haematoma.

General anaesthesia (GA) may be required in the event of cardiopulmonary decompensation, an inability to lie flat or with ongoing anticoagulation. The risks of GA include depressed cardiac contractility, increased sympathetic drive associated with laryngoscopy, reduced preload and increased PVR from positive pressure ventilation. General anaesthesia further reduces the functional residual capacity and causes atelectasis, which can exacerbate hypoxia and hypercarbia. A systematic review by Bedard and colleagues found that patients with PAH in pregnancy who received GA were four times more likely to die compared with those who received regional anaesthesia.¹⁰ In contrast, Bonnin and colleagues commented on case series showing favourable outcomes with GA, although the numbers were small.²¹

Monitoring

Continuous ECG and pulse oximetry should be routine throughout labour and delivery. Invasive monitoring should include central venous access and intra-arterial blood pressure.¹ The use of pulmonary artery catheters (PACs) is controversial as they have known associated risks; there are no consensus recommendations regarding their use.¹ There have been case series describing the use of a PAC without complications in pregnant patients with PAH, allowing direct measurement of pulmonary pressures and guidance of therapies.^11,21 Insertion of PACs can be challenging in the presence of RV dilation or history of CHD and should not be wedged in PAH. The use of PACs depends on institutional preferences and experience; it can be beneficial in selected cases.

Uterotonic agents

Bolus doses of oxytocin can cause increased PVR, reduced SVR and tachycardia, which could precipitate acute cardiovascular collapse in those with PAH. The ED₉₀ of oxytocin is only 0.35 IU to achieve adequate uterine contraction in elective Caesarean delivery, and large bolus doses should be avoided.^1,29 Oxytocin should be diluted and given by slow i.v. infusion with continuous cardiovascular monitoring until the desired uterine tone is achieved.¹ Curry and colleagues commented on two deaths associated with oxytocin boluses and describe the use of 0.1 IU boluses or a slow infusion postpartum with good outcomes.³⁰ Carboprost, a prostaglandin F_2α analogue, increases PVR and should be avoided in PAH. Ergometrine should also be avoided because of its hypertensive effects, but avoiding these uterotonic agents must be balanced against the risk of bleeding.⁶ Misoprostol is considered safe but is less effective for PPH. The use of specific uterotonics should be planned in advance in event of a PPH with early consideration for hysterectomy.

Haemodynamic support

The choice of haemodynamic support is governed by institutional preferences, with the primary goal of minimising pulmonary pressures and supporting the right ventricle during the peripartum period. This must be carefully planned and available before delivery. Pulmonary vasodilator drugs such as prostacyclin analogues must be continued throughout labour and delivery, in consultation with a cardiologist. Low-dose dobutamine is used at our institution and other centres as additional inotropic support; adverse effects include peripheral vasodilation and tachyarrhythmias.^1,12 Milrinone has inodilator effects, but is less easy to titrate. Adverse effects include vasoplegia and accumulation in renal failure.²⁷ At low doses, adrenaline (epinephrine) enhances RV contractility but can cause increased myocardial oxygen consumption and tachyarrhythmias at higher doses. Noradrenaline (norepinephrine) is used to maintain RV perfusion by counteracting the vasodilatory effects of neuraxial and inodilator therapy. At low doses, noradrenaline has minimal effects on the pulmonary vasculature and favourable fetal outcomes compared with other vasopressors. Phenylephrine has the potential to worsen PVR and should be avoided in PAH.²⁷ Vasopressin has potent systemic vasoconstrictor properties with minimal effect on the pulmonary vasculature; it has been used successfully in cases of postpartum deterioration with IPAH.^27,31 Care must be exercised when vasopressin is given before delivery because of its potential uterotonic effects.

Consideration for ECMO

There are no consensus guidelines for ECMO in pregnant patients with PAH. Consideration of ECMO depends on factors such as the degree of right heart dysfunction and functional status, and institutional preferences. ECMO should be discussed within the MDT as part of planning for acute decompensation and as a bridging therapy for heart–lung transplant. In the event of decompensation, venoarterial ECMO is most likely to be used when right heart failure is present. This could involve the placement of ECMO with a micropuncture cannula before attempting vaginal delivery with ECMO on standby for acute decompensation, in which case the delivery plan would change to a Caesarean section. If ECMO is required, the need for heparinisation will potentially complicate neuraxial anaesthesia. Other risks include thrombosis, bleeding and lower limb ischaemia and difficulties in catheter placement with a gravid uterus. In one case series, ECMO was used in six patients with PAH and none survived beyond 3 months postpartum.¹³ A more recent systematic review reported a 50% survival rate in 28 patients with PAH, but publication bias may be a confounding factor.³² There are very small numbers described in the literature and so it is difficult to provide recommendations for ECMO. However patients with PAH should be delivered in centres with ECMO services available.

Management of intrapartum acute pulmonary hypertensive crisis

An acute pulmonary hypertensive crisis is most likely to present immediately after delivery, but constant vigilance throughout delivery is required. The onset of chest pain, dyspnoea, wheeze, desaturation, hypotension or syncope should alert the anaesthetist that right heart failure is the most likely differential in this scenario. Prompt management includes:

• (i)Correct any precipitants—hypoxia, hypercapnia, acidosis, high airway pressures, arrhythmias and pain.
• (ii)Pulmonary vasodilator therapy—prostacyclin analogues (e.g. nebulised iloprost 10 μg or epoprostenol via ultrasonic nebuliser, i.v. epoprostenol). Nitric oxide if available.
• (iii)Support the right ventricle—dobutamine, milrinone.
• (iv)Maintain RV perfusion—noradrenaline, vasopressin.
• (v)Reduce RV overload—diuretics.

A specific management plan for acute decompensation should be made in advance with emergency drugs and specialised equipment prepared before delivery.

Postpartum management

The highest risk period is immediately postpartum and mortality is highest within the first month after delivery, with right heart failure being the most common cause of death. Patients need to be monitored in intensive care for a minimum of 24–48 h and may require ongoing RV support.^1,2,5 Although RV failure is the most common cause of death, other differentials for a low cardiac output state should be sought, including sepsis, thrombosis and bleeding. Patients with PAH are particularly at risk of thromboembolic events postpartum and anticoagulation is usually established with oral anticoagulants. Counselling regarding contraception is provided and patients are subsequently encouraged to avoid pregnancy.

Conclusions

PAH in pregnancy is rare and associated with high morbidity and mortality, but recent reports suggest improvement in survival. Recent revised definitions of PH, and the increased life expectancy of women with associated conditions may increase the prevalence in pregnancy. These patients present complex challenges to the anaesthetist that require a holistic and highly individualised approach to achieve successful outcomes.

Acknowledgements

We wish to acknowledge the assistance of MFM consultant Dr Roshini Nayyar, Cardiologist Dr David Tanous and our cardiac anaesthesia colleagues in the preparation of this manuscript, and caring for these patients.

Declaration of interests

The authors declare that they have no conflicts of interest.

Biographies

Sameeka Kariyawasam FRCA FANZCA MSc is a fellow in high-risk obstetric anaesthesia at Westmead Hospital, Sydney, Australia.

Jane Brown FANZCA is a consultant anaesthetist at Westmead Hospital with a special interest in cardiac disease and pregnancy. She is currently co-chair of the Australian and New Zealand College of Anaesthetists' obstetric special interest group.

Matrix codes: 1A01, 1A02, 2A03, 2B05, 2B06, 3B00

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