COMMON QUESTIONS IN THE MANAGEMENT OF PATIENTS WITH PAH IN SECONDARY CARE
PAH is a complex disease that can impact on all aspects of a patient’s life.1 Advances in knowledge and treatment mean that care has evolved, and patients are now living with a long-term condition.2
Patients receive specialist care at the pulmonary hypertension (PH) centres from a highly experienced, multidisciplinary team. This includes physicians, specialist nurses, radiologists and pharmacists.2
Patients may not necessarily live near the specialist centres and consequently both routine and emergency care will likely be provided by local primary and secondary care services.3 The prevalence of PAH is high in certain patient groups, such as those with systemic sclerosis, portal hypertension, congenital heart disease and HIV; this means patients may be seen more frequently in rheumatology, gastroenterology and cardiology departments.4 Good communication between the secondary care clinical teams and the PH centre is vital.
Ms Rachel Crackett
Newcastle upon Tyne
Ms Wendy Gin-Sing
Senior Clinical Nurse Specialist,
Mr Duncan Grady
This article was developed by Specialist PH Nurses, Ms Rachel Crackett and Ms Wendy Gin-Sing, and Thoracic Directorate Pharmacist, Mr Duncan Grady. Below is a list of questions they are commonly asked by doctors and nurses in secondary care about the management of patients with PAH. They have provided their guidance as well as suggesting resources for further reading. As with all conditions, the final decisions concerning an individual patient must be made by the responsible healthcare professional in consultation with the patient and caregiver as appropriate. Prescribing information can be found at the bottom of the page. Writing supported by NexGen Healthcare Communications. Funded by Actelion Pharmaceuticals UK Ltd.
Browse the questions by clicking on the topics below to read a short answer and find links to more resources.
WHO TO CALL?
The patient’s general practitioner is first line for general enquires. They are likely to be responsible for fine-tuning long-term medications, such as anticoagulants and diuretics.3 Local guidelines may differ but if in any doubt, or for issues specific to PAH, the specialist PH team can be contacted. Consultants, PH registrars, specialist nurses and pharmacists can all provide advice over the phone. Patients can also contact the service for support. In an emergency, as with any other patient, you should call an ambulance.
Click here to find the location and contact details of the PH services in the UK and Ireland. The PH Professionals website also provides information about the centres:
- PH Professionals: http://www.phprofessionals.org.uk
Hypotension in patients with PAH may have multiple causes and can be impacted by diuretic therapy.5
Diastolic dysfunction leads to limited right ventricular (RV) output, increased right-sided filling pressures and under-filling of the left ventricle, with an eventual decrease in systemic blood pressure.6 This means many patients with PAH have low blood pressure and will have adapted to this over several years.6 It is therefore important to know their usual systemic blood pressures before making changes to their management.
In instances when the blood pressure decreases below their normal levels, concomitant therapies should be checked and blood pressure medications should be reviewed. If patients are on diuretic therapy, fluid intake should be monitored. Patients with PAH are often placed on a 2 litre per day fluid restriction.5 Increased fluid intake may cause cardiac overload, and this must be promptly identified.5
Vasodilators used in PAH can cause low blood pressure and adjustments may be necessary.5 Consultation with the PH team should occur before any change to the targeted therapy.
Further information on volume management in PAH can be found here:
- Volume management in pulmonary arterial hypertension patients: an expert pulmonary hypertension clinician perspective. Hansen L, et al. Pulm Ther 2018;4:13–27. Available from: https://link.springer.com/article/10.1007/s41030-018-0052-z
Acute decompensated right heart failure in PH is a life-threatening condition requiring management in a specialist centre. It is a rapidly progressing syndrome with systemic congestion resulting from impaired RV filling and output, and is associated with a poor prognosis in the short term.7
Underlying precipitating factors should be identified and managed. Treatment should aim to restore oxygenation, perfusion of vital organs and treat fluid overload.7
Adapted from Savale L, et al. Eur Resp Rev 2017. RV, right ventricle
Chronic heart failure in PAH occurs when the RV is no longer able to maintain sufficient output. Symptoms include increased breathlessness and peripheral oedema.6
Treatment aims to relieve physical symptoms, such as breathlessness and pain, and emotional distress or anxiety. RV function is the major determinant of morbidity and mortality in the PH population; therefore, it is important that this is managed appropriately.8
Click here to read more about the treatment and prognosis of PAH. Please contact the specialist centre for further advice.
Click here to read more about the changes in the heart and how this is assessed on echo. Further information about the management of right heart failure can be found here:
- Management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology. Harjola VP, et al. Eur J Heart Fail 2016;18:226–41. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.478
Figure 1. Healthcare professional protocol for volume management in patients with PAH. Adapted from Hansen et al, 2018.5 NSAID, non-steroidal anti-inflammatory drug; RHF, right heart failure; RV, right ventricle
Nausea is not uncommon in PAH and can be due to the disease itself or as a treatment side effect.9,10
Nausea, early satiety and lack of appetite can be symptoms of worsening right heart failure or the result of an enlarged, congested liver compressing the stomach.11,12 In this instance, a prokinetic agent such as metoclopramide could be considered.13 Patients should be encouraged to sit up while eating and to stay upright afterwards rather than immediately lying down. Small, frequent meals are often better tolerated than large meals. Patients may find it helpful to snack on high-carb foods and avoid fatty foods and carbonated beverages.11
Nausea, as a treatment side effect, is commonly associated with the prostanoid family of medicines.11 It can be severe during up-titration of dosing but usually reduces, often completely, once the dose has stabilised.9 Medicines that can be helpful include 5-hydroxytryptamine 3 (5-HT3) antagonists, such as ondansetron, and prokinetic agents, such as metoclopramide.14,15 Cyclizine and prochlorperazine can also be useful but only if there is no sign of heart failure (see question below on ‘Which medications should be avoided in patients with PAH?’). Be aware that some anti-emetics (ondansetron, domperidone, prochlorperazine) have the potential for QT prolongation and this should be monitored appropriately.16
Non-drug treatments can also be utilised, for example, eating ginger.17
Further information on non-drug treatments of nausea can be found below:
- Pulmonary Hypertension Association. Managing Nausea: https://phassociation.org/patients/living-with-ph/diet-nutrition/managing-nausea/
LFTs are often performed in patients with PAH to assess for any damage caused by hepatic congestion.18 A pattern of LFT derangement – which includes raised alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) with or without raised bilirubin, or alanine aminotransferase (ALT) – should warn healthcare professionals to check for other signs of right heart failure and treat any fluid overload and cardiac insufficiency accordingly.18 Table 1 summarises the key laboratory abnormalities encountered in patients with heart failure.
Table 1. Key laboratory abnormalities encountered in patients with heart failure based on the primary mechanism18
LFT checks are also important for patients taking endothelin receptor antagonists (ERAs), such as bosentan, ambrisentan and macitentan. These medicines have a small risk of liver damage and the Medicines and Healthcare products Regulatory Agency/European Medicines Agency require all patients to undergo regular monitoring of LFTs when takings ERAs. Click on the following link for up-to-date information on the manufacturer’s summary of product characteristics: www.medicines.org.uk
For patients taking ERAs, an elevated aminotransferase (ALT or aspartate aminotransferase [AST]) level 3-times greater than the upper limit of normal requires action.19 If this occurs, the patient’s specialist PH centre can be contacted for advice and the test should be repeated to confirm the result.19 If ALT or AST is more than 5-times the upper limit of normal or the raised aminotransferase is accompanied by raised bilirubin 2-times the upper limit of normal, then the patient should immediately stop the medicine and contact their specialist centre for further advice and monitoring.19–21
Further information about blood tests performed in patients with PAH can be found below:
- Pulmonary Hypertension R.N. Routine blood tests for pulmonary hypertension patients:
Unfortunately, in acute illness, patients with PAH may deteriorate quickly.22 An infection places more demands on the already compromised cardiovascular system and can precipitate episodes of heart failure.3,22
If a patient with PAH is admitted to hospital with sepsis, fluid resuscitation should be undertaken with care if required. Owing to the right heart failure in these patients, excessive fluid may result in increased failure and compromise.22
Patients with a Hickman line to deliver intravenous (IV) prostanoid therapy are at increased risk of bacteraemia compared with the general public, and pyrexia should raise the suspicion of a line infection.23,24 In a patient with sepsis, it is recommended that the catheter is removed and a temporary line inserted.23 This alternative access should be obtained prior to discontinuing IV prostacyclin therapy to avoid any break in drug administration.23 Prostacyclin in the blood stream has a very short half-life (2–3 mins) and therefore patients may become compromised very quickly.25 Contact the patient’s PAH centre for specific instruction with regard to the cultures and further management of the patient.
Patients presenting with a suspected exit site infection will require the site to be swabbed.26 Empirical antibiotics can be commenced until swab results are available.27 Please seek further advice from your trust guidelines or the specialist PH centre on antibiotic choice and duration.
Further information about managing patients with PAH with infections can be found below:
- Management of pulmonary vasodilator therapy in patients with pulmonary arterial hypertension during critical illness. Muzevich K, et al. Crit Care 2014;18:523. Available from: https://ccforum.biomedcentral.com/articles/10.1186/s13054-014-0523-z
- Acute decompensated pulmonary hypertension. Savale L, et al. Eur Respir Rev 2017;26:170092. Available from: https://err.ersjournals.com/content/26/146/170092
There are several medicines and classes of medicines that should be used with caution in patients with PAH. Please note that the list below is not exhaustive; this is a selection of the most common medicines to be aware of. Please refer to the British National Formulary for further information.
Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. naproxen and ibuprofen: These are known to increase the risk of heart failure by increasing sodium and water retention, and can also blunt the effects of diuretics.28,29 In theory, NSAIDs also reduce the production of prostaglandin I2 (prostacyclin), which is a vasodilator in short supply in patients with PAH.29,30 Additionally, patients may be receiving anticoagulation due to the risk of venous thromboembolism in PAH or for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH).10 This increases the patient’s bleeding risk when used with NSAIDs.29
Beta-blockers, e.g. propranolol, bisoprolol: Unlike their clear beneficial effects in left heart failure, beta-blocker use in PH is controversial and has been associated with side effects.31
Vasoconstricting agents, e.g. pseudoephedrine, phenylephrine and triptans, such as sumatriptan: While commonly used for nasal congestion (pseudoephedrine, phenylephrine) and migraine (triptans), these medicines increase vasoconstriction.32,33 Little is known about the direct effects on the pulmonary vasculature and so, given the potential to counteract the vasodilator effects of targeted PAH therapies, they should be avoided in patients with PH.32,33
Cyclizine: Use with caution in patients with severe heart failure, as it is known to cause a fall in cardiac output and increases in mean arterial pressure and pulmonary wedge pressure.34
Steroids, e.g. prednisolone: These should be used with caution in patients with heart failure due to their propensity to increase oedema.35,36 Monitor for peripheral oedema, weight gain and signs of worsening right heart failure.
Pro-arrhythmic medicines and medicines that cause QT prolongation: The right ventricle remodelling that is common in patients with PAH leads to an increased risk of heart rhythm disturbances such as atrial flutter.10 There is also suggestion that women with PH have significantly prolonged QTc.37 Caution is required with any medicine that can cause QT prolongation (e.g. ondansetron, domperidone, amitriptyline, citalopram) or other cardiac arrhythmias (e.g. flecainide) in patients with cardiac conditions.38
Macrolide antibiotics e.g. erythromycin, clarithromycin: Can be used, but be aware of potential drug–drug interactions with therapies for PAH, such as sildenafil, tadalafil and bosentan.39
Nitrates, e.g. glyceryl trinitrate, isosorbide mononitrate: Contraindicated for patients taking sildenafil, tadalafil or riociguat. Can potentially cause a dangerous drop in systemic blood pressure when co-administered with these medicines.40
Gaviscon: This should be used sparingly for any patient on a restricted salt diet as the sodium load per 10 mL dose is approximately 4.6 mmol for Gaviscon Advance and 6 mmol for Gaviscon Liquid.41
For more information see below:
- The manufacturer’s summary of product characteristics from: www.medicines.org.uk
Due to their short half-lives, prostanoid infusions should not be stopped for any length of time.42 Cessation of these medications can result in patients becoming severely and rapidly symptomatic.9
In the event of interruption to a central venous infusion, for example due to removal or line failure, a temporary line should be inserted as quickly as possible, ideally prior to catheter removal.23 A basic cannula can be placed; however, prostaglandin medications can cause rapid extravasation in cannulas (Image 1).43 As such, a midline or peripherally inserted central catheter is preferable; however, in an emergency situation, any access is better than none.
Image 1. Extravasation injury to patients’ arm (image courtesy of Wendy Gin-Sing)
PAH is a progressive and ultimately fatal disease and therefore the need for palliative care is the same as in other long-term, life-limiting diseases.44
Palliative care should be introduced early and considered for all patients who still have symptoms that concern them despite being on optimal PH targeted therapies.44 Common symptoms such as breathlessness and anxiety can often be addressed by the specialist PH team. Referral to specialist palliative care should be made for complex patients with uncontrolled symptoms and those needing end-of-life care.44,45
Patients may have a high symptom burden both because of the disease and the side effects of therapy; consequently, there is an increasing need for a palliative care approach to improve the quality of life for this patient group. Medications can be continued indefinitely during the provision of palliative care.44
In a dying patient, the continuation of targeted therapy should be assessed on an individual basis.45 The effects of stopping IV prostaglandins will occur very quickly and will accelerate the patient’s demise.9 In our experience, the speed of decline varies among patients. Oral therapies can be continued as long as the patient is able or chooses to take them. Compared with parenteral formulations, oral prostaglandins have a relatively long half-life; however, less is known about the impact of stopping them.9
At the point when the burden or side effects of PH targeted therapies outweigh the symptomatic benefits, consideration should be made to stop them.10
For further information on palliative care in PAH:
- Palliative care in pulmonary arterial hypertension: an underutilised treatment. Khirfan G, et al. Eur Resp Rev 2018;27:180069. Available from: https://err.ersjournals.com/content/27/150/180069
- Palliative care in pulmonary arterial hypertension. Gin-Sing, W. Curr Opin Support Palliat Care 2017;11:7–11. Available from: https://journals.lww.com/co-supportiveandpalliativecare/Abstract/2017/03000/Palliative_care_in_pulmonary_arterial_hypertension.3.aspx
Most patients with PAH have a mild degree of hypoxaemia at rest, unless they have congenital heart disease (CHD) and pulmonary-to-systemic shunts, e.g. Eisenmenger physiology.10, In these situations, the degree of hypoxaemia will be greater as some of the blood entering the right side of the heart shunts directly to the left heart, bypassing the lungs and the opportunity to pick up oxygen.
Many patients with Eisenmenger syndrome have resting oxygen saturations of around 85%.46 This chronic cyanosis results in elevated renal production of erythropoietin, which promotes erythropoiesis and secondary erythrocytosis to compensate for the low oxygen saturation.47
Advice for using oxygen in patients with CHD
The use of oxygen in patients with CHD should only be considered in cases in which it produces a consistent increase in arterial oxygen saturation and reduces symptoms.10 For a small number of patients with CHD, long-term home oxygen therapy may improve symptoms but this has not been shown to modify survival, at least when given only at night.48 The continuous use of daytime and night-time oxygen may also lead to dependency and physical deconditioning through immobilisation and is therefore not recommended as routine care.49
Advice for using oxygen in patients with PAH but without CHD
Supplemental low-flow oxygen is recommended by treatment guidelines as supportive therapy for patients with PAH, based largely on expert opinion.50 It has been shown to significantly lower the risk of all-cause mortality in patients with a severely reduced diffusing capacity of the lungs for carbon monoxide (DLCO, <40% predicted).50 Use of long-term oxygen therapy (LTOT) in patients with PH is to improve tissue oxygenation and to prevent complications associated with hypoxaemia, such as worsening PH, rather than to afford a specific survival benefit.51 LTOT should be ordered for patients with PH, including idiopathic PAH, when the partial pressure of oxygen (PaO2) is ≤8 kPa.51
For further information about oxygen therapy in PH:
- Pulmonary Hypertension R.N. Oxygen Therapy for Pulmonary Hypertension: http://pulmonaryhypertensionrn.com/oxygen-therapy-in-the-treatment-of-pulmonary-hypertension/
- Read more about PAH in adult CHD here: https://actonpah.co.uk/articles-and-resources/adult-congenital-heart-disease/
SUPPORT FOR PATIENTS
As with all patients with long-term conditions, the work–life balance needs to be considered. Many patients are forced to give up work or reduce their working hours due to the impact of their condition, which can have a large impact on their quality of life and financial stability.1,52 To help address this, the PH team can provide support through liaising with employers to ensure that, where possible, adjustments are made to the patient’s working environment to enable them to continue at work.
Additionally, patients may be entitled to welfare support, such as benefits or grants. Turn2us, a charity that helps people in financial hardship to gain access to welfare benefits, has developed a benefits calculator: http://www.phauk.org/resources/turn2us/benefits-calculator/
Living with PAH can have a significant impact on a patient’s quality of life, especially their emotional wellbeing.44 While the PH team can provide advice, a local programme of support with regular reviews is important to patients and their carers.53 As such, access to psychological support should be discussed with the patient’s general practitioner; they will be able to facilitate referral to locally based psychologists.
Read more about the different ways in which PHA UK can support your patients here: https://actonpah.co.uk/articles-and-resources/pha-uk/
PHA UK has partnered with Anxiety UK to provide telephone and email support free of charge. Visit http://www.phauk.org/living-with-pulmonary-hypertension/emotional-support/ to find out more.
- Delcroix M and Howard L. Eur Respir Rev 2015;24:621–9
- Actelion Pharmaceuticals Ltd. A holistic approach to patient care in pulmonary arterial hypertension. 2016. Available from: http://www.phaeurope.org/wp-content/uploads/Holistic-Care-in-PAH-report-FINAL-25.01.16.pdf. Accessed July 2019
- Delcroix M and Naeije R. Eur Respir Rev 2010;19:204–11
- Kiely D, et al. BMJ 2013;346:f2028
- Hansen L, et al. Pulm Ther 2018;4:13–27
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- Savale L, et al. Eur Respir Rev 2017;26:170092
- Harjola VP, et al. Eur J Heart Fail 2016;18:226–41
- Farber HW and Gin-Sing W. Eur Respir Rev 2016;25:418–30
- Galiè N, et al. Eur Heart J 2016;37:67–119
- Pulmonary Hypertension Association. Managing nausea and vomiting. 2019. Available from: https://phassociation.org/patients/living-with-ph/diet-nutrition/managing-nausea/. Accessed June 2019
- Sundaram V and Fang JC. Circulation 2016;133:1696–703
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- Muzevich K, et al. Crit Care 2014,18:523
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