Palliative Care in Pulmonary Hypertension: A Comprehensive Clinical Review

 Palliative Care in Pulmonary Hypertension: A Comprehensive Clinical Review.

Authors: Dr. Shekhar Ingle and Team, Doctor’s Forum for All 🏥

Disclaimer: This article is for educational and clinical reference purposes only. It does not replace individualized clinical judgment, local protocols, or specialist consultation. Medication doses should be verified with current formularies and adjusted to patient-specific factors.

Abstract

Pulmonary hypertension (PH) is a progressive, life-limiting condition characterized by elevated pulmonary arterial pressure, right ventricular dysfunction, and ultimately right heart failure. Despite advances in targeted therapies, many patients with pulmonary arterial hypertension (PAH) and other forms of PH experience progressive symptom burden, functional decline, and reduced quality of life. Palliative care should be integrated early alongside disease-directed therapy to address dyspnoea, fatigue, pain, psychological distress, and end-of-life needs. This article provides a comprehensive, clinically verified review of palliative care principles and symptom management in pulmonary hypertension, with emphasis on evidence-based practice and interdisciplinary care.

1. Introduction

Pulmonary hypertension encompasses a heterogeneous group of disorders defined by a mean pulmonary arterial pressure (mPAP) >20 mmHg at rest on right heart catheterisation [1]. The World Health Organization (WHO) classifies PH into five groups:

· Group 1: Pulmonary arterial hypertension (PAH) — idiopathic, heritable, drug-induced, or associated with connective tissue disease, HIV, portal hypertension, congenital heart disease.

· Group 2: PH due to left heart disease.

· Group 3: PH due to lung diseases and/or hypoxia (COPD, interstitial lung disease).

· Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH).

· Group 5: PH with unclear or multifactorial mechanisms.

Despite significant advances in targeted therapies—including prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and soluble guanylate cyclase stimulators—PAH remains a progressive disease with median survival of 5–7 years from diagnosis in contemporary cohorts [2]. Patients with Group 2 and Group 3 PH often have even worse outcomes due to underlying comorbidities.

The illness trajectory of PH is characterized by progressive dyspnoea, fatigue, right heart failure, syncope, and eventually death, often from right ventricular failure or sudden cardiac death [3]. This trajectory makes palliative care essential from the time of diagnosis.

2. Disease Trajectory and Triggers for Palliative Care Referral

Palliative care referral should be considered when:

· WHO Functional Class III–IV symptoms despite optimal targeted therapy.

· Progressive right ventricular dysfunction or right heart failure.

· Recurrent hospitalisations for PH complications (>2 per year).

· Need for parenteral prostacyclin therapy or combination therapy.

· Recurrent syncope or pre-syncope.

· Significant weight loss, cachexia, or frailty.

· Psychological distress, anxiety, or depression.

· Patient or family request for symptom management or goals-of-care discussion.

· Limited life expectancy (e.g., 6–12 months) as estimated by prognostic tools (e.g., REVEAL risk score, ESC/ERS risk stratification) [4].

3. General Principles of Palliative Care in Pulmonary Hypertension

1. Concurrent care: Palliative care should be provided alongside ongoing PH-targeted therapy, which may improve symptoms even in advanced disease.

2. Interdisciplinary team: PH specialist, palliative care physician, cardiologist, respiratory physician, nurse specialist, pharmacist, physiotherapist, dietitian, psychologist, social worker, and chaplain.

3. Holistic assessment: Regular evaluation of physical, psychological, social, and spiritual needs.

4. Symptom-driven approach: Prioritise patient-reported outcomes and quality of life.

5. Communication and advance care planning: Discuss prognosis, goals, and preferences early, including preferences for mechanical ventilation, cardiopulmonary resuscitation, and place of death.

6. Medication review: Simplify polypharmacy; discontinue medications that do not provide immediate symptom benefit in the terminal phase [5].

4. Symptom Assessment and Management

4.1 Dyspnoea

Dyspnoea is the cardinal symptom of PH, affecting nearly all patients and worsening with disease progression. It results from increased pulmonary vascular resistance, right ventricular dysfunction, low cardiac output, and hypoxaemia.

Management:

· Optimise PH-targeted therapy:

  · Phosphodiesterase-5 inhibitors: sildenafil, tadalafil.

  · Endothelin receptor antagonists: bosentan, ambrisentan, macitentan.

  · Prostacyclin analogues: epoprostenol (IV), treprostinil (IV, subcutaneous, inhaled, oral), iloprost (inhaled).

  · Soluble guanylate cyclase stimulator: riociguat (especially for CTEPH).

  · Calcium channel blockers: only in vasoreactive patients (rare).

· Oxygen: Long-term oxygen therapy is indicated for hypoxaemic patients (PaO₂ <60 mmHg or SpO₂ ≤90%). In non-hypoxaemic patients, oxygen is not routinely recommended [6].

· Diuretics: Used to manage right heart failure and fluid overload, which contribute to dyspnoea. Monitor renal function and electrolytes.

· Opioids: Low-dose oral morphine (e.g., 2.5–5 mg every 4 hours as needed) or subcutaneous morphine is effective for refractory dyspnoea without significant respiratory depression [7,8]. Start low and titrate slowly. This is particularly important in PH, where respiratory depression could be dangerous.

· Benzodiazepines: May be used for associated anxiety or panic, but use cautiously in PH due to potential respiratory depression.

· Non-pharmacological:

  · Fan therapy and cool air.

  · Positioning: upright or leaning forward.

  · Pursed-lip breathing and relaxation techniques.

  · Energy conservation and pacing.

  · Pulmonary rehabilitation improves exercise capacity and quality of life [9].

4.2 Fatigue and Weakness

Fatigue is pervasive in PH due to low cardiac output, hypoxaemia, deconditioning, depression, and medication side effects.

Management:

· Treat reversible causes: Anaemia (iron replacement if deficient), thyroid dysfunction, depression, and medication side effects.

· Exercise: Supervised pulmonary rehabilitation or graded physical activity improves functional capacity and reduces fatigue [9].

· Energy conservation: Prioritise activities, use assistive devices, and plan rest periods.

· Psychological support: Cognitive behavioural therapy and counselling.

· Corticosteroids: Short-term dexamethasone (4–8 mg daily) may improve energy and appetite in the terminal phase, but evidence is limited.

4.3 Pain

Pain in PH may arise from right ventricular ischaemia, chest wall strain, musculoskeletal problems, or comorbid conditions.

Management:

· WHO analgesic ladder:

  · Paracetamol is safe first-line.

  · NSAIDs should be used cautiously due to renal impairment risk and potential interaction with anticoagulants.

  · Weak opioids (tramadol, codeine) for moderate pain.

  · Strong opioids (morphine, oxycodone) for severe pain.

· Neuropathic pain: Gabapentin or pregabalin; amitriptyline for neuropathic pain but caution with cardiac arrhythmias.

· Non-pharmacological: Physiotherapy, TENS, heat/cold, and cognitive behavioural therapy.

· Note: Avoid drugs that may increase pulmonary vascular resistance or cause respiratory depression.

4.4 Syncope and Pre-syncope

Syncope in PH indicates severe disease and poor prognosis. It results from low cardiac output, arrhythmias, or vasovagal episodes.

Management:

· Patient education: Avoid Valsalva manoeuvres, dehydration, and prolonged standing.

· Medication review: Avoid vasodilators that may worsen hypotension.

· Pacing: May be considered for bradyarrhythmias.

· End-of-life care: Recurrent syncope should prompt advance care planning discussions, as it is a marker of high mortality risk.

4.5 Depression and Anxiety

Depression and anxiety are common in PH, affecting 30–50% of patients, and are associated with worse quality of life and outcomes.

Management:

· Screening: Use PHQ-9 or HADS regularly.

· Pharmacotherapy: SSRIs (sertraline, citalopram, escitalopram) are first-line and generally safe. Avoid tricyclic antidepressants due to cardiotoxicity.

· Psychotherapy: Cognitive behavioural therapy, supportive counselling, and mindfulness.

· Anxiety: Short-term benzodiazepines for acute anxiety, but use cautiously due to respiratory depression risk. Consider buspirone or SSRIs for chronic anxiety.

· Support groups: PH patient associations provide peer support.

4.6 Nausea, Anorexia, and Cachexia

Nausea may result from right heart failure with hepatic congestion, medications (prostacyclins, endothelin receptor antagonists), or gastroparesis.

Management:

· Nausea: Treat reversible causes (constipation, medication side effects). Use metoclopramide (if no prolonged QT), ondansetron, or haloperidol.

· Anorexia: Small frequent meals, oral nutritional supplements, and appetite stimulants. Megestrol acetate may improve appetite but increases thromboembolic risk; use cautiously.

· Corticosteroids: Dexamethasone 4–8 mg daily can improve appetite and wellbeing in advanced disease.

· Hydration: Encourage oral fluids unless fluid-restricted for right heart failure.

4.7 Constipation

Common due to reduced mobility, low fibre intake, dehydration, and medications (opioids, diuretics, iron).

Management:

· Prophylaxis with opioids: Prescribe laxatives (e.g., macrogol, senna) routinely.

· Titrate laxatives to achieve regular soft stools.

· Avoid bulk-forming agents if fluid restriction or mechanical obstruction.

· Treat faecal impaction with suppositories or enemas if needed.

· Important: Avoid straining during defecation, which can precipitate syncope in PH patients.

4.8 Sleep Disturbance

Dyspnoea, orthopnoea, nocturia, depression, and anxiety disrupt sleep in PH.

Management:

· Treat underlying causes: Optimize dyspnoea control, diuretics and timing, pain control, and manage depression.

· Sleep hygiene: Regular schedule, avoid caffeine and alcohol.

· Consider nocturnal oxygen if hypoxaemia during sleep.

· Screen for obstructive sleep apnoea, which may coexist.

· Non-benzodiazepine hypnotics: Short-term zolpidem or melatonin may be used; avoid long-term benzodiazepines.

4.9 Cognitive Impairment

Cognitive impairment may occur due to chronic hypoxaemia, low cardiac output, or comorbid conditions.

Management:

· Screen for delirium and dementia.

· Treat delirium: Identify and correct causes (infection, hypoxia, medications, urinary retention). Haloperidol or risperidone may be used for agitation.

· Support family with decision-making and provide a calm environment.

5. Right Heart Failure Management

Right heart failure is the leading cause of death in PH and requires specific palliative management.

Management:

· Diuretics: Loop diuretics (furosemide, bumetanide) for fluid overload. Monitor renal function and electrolytes. Subcutaneous furosemide infusion may be used in the community or hospice setting [10].

· Fluid restriction: Usually 1.5–2 L/day, individualised to avoid thirst and dehydration.

· Inotropes: Dobutamine or milrinone may be used in advanced right heart failure as palliative therapy to improve symptoms, though survival benefit is limited.

· Digoxin: May improve right ventricular function and control atrial arrhythmias, but monitor for toxicity.

· Anticoagulation: May be indicated, especially in CTEPH or atrial fibrillation, but risk of bleeding should be assessed.

6. Device Therapy and Advanced Interventions

6.1 Atrial Septostomy

Atrial septostomy creates a right-to-left shunt to decompress the right ventricle and improve left ventricular filling. It is reserved for patients with severe right heart failure refractory to medical therapy. It is a palliative procedure with high perioperative risk [11].

6.2 Lung or Heart-Lung Transplantation

Transplantation is the only curative option for selected patients with end-stage PH. However, many patients are not candidates due to age, comorbidities, or disease severity. Palliative care should be provided while awaiting transplant and for those who are not candidates.

6.3 Mechanical Circulatory Support

Extracorporeal membrane oxygenation (ECMO) or right ventricular assist devices (RVADs) may be used as bridge to transplant or recovery. In the palliative setting, these interventions are rarely appropriate and require careful discussion.

7. Advance Care Planning and Communication

· Early discussion: Initiate advance care planning when the patient is stable, not during a crisis.

· Prognosis: Use validated tools (REVEAL risk score, ESC/ERS risk stratification) but acknowledge uncertainty. Phrases like "I am worried that your pulmonary pressures are getting harder to control" can open conversations.

· Explore goals: "What is most important to you now?" "What are your hopes and worries for the future?"

· Document preferences: Preferred place of care and death, resuscitation status, and views on ventilation, ECMO, and device deactivation.

· Legal aspects: Appoint healthcare proxy or lasting power of attorney.

· Review regularly: Update preferences with clinical changes.

· Specific discussions: PH patients should understand that cardiopulmonary resuscitation is often unsuccessful in end-stage disease and may cause distress.

8. End-of-Life Care in Pulmonary Hypertension

Recognising the terminal phase can be challenging. Features suggesting imminent death include:

· Progressive right heart failure despite maximal therapy.

· Recurrent syncope or arrhythmias.

· Worsening renal and hepatic function.

· Cachexia and severe fatigue.

· Refractory dyspnoea at rest.

· Patient expresses desire for comfort-focused care.

Symptom control in the last days of life:

· Dyspnoea: Morphine 2.5–5 mg subcutaneously every 4 hours as needed, or continuous subcutaneous infusion if frequent doses required. Use cautiously and titrate slowly.

· Pain: Same as dyspnoea; adjust opioids based on prior use.

· Respiratory secretions: Glycopyrronium 0.2–0.4 mg subcutaneously every 6 hours as needed.

· Agitation/terminal restlessness: Midazolam 2.5–5 mg subcutaneously every 2–4 hours as needed, or continuous infusion.

· Nausea/vomiting: Haloperidol 0.5–1.5 mg subcutaneously every 8 hours as needed.

· Stop non-essential medications: Discontinue routine medications that do not provide immediate symptom benefit to reduce treatment burden [5]. Consider stopping PH-targeted therapies that are burdensome (e.g., IV epoprostenol) after discussion with the patient and family.

· Fluid management: Avoid intravenous fluids unless for comfort. Diuretics may be continued if they relieve dyspnoea or oedema.

· Oxygen: Continue if it provides comfort, even if hypoxaemia is mild.

Care of the family: Provide emotional support, information, and bereavement follow-up.

9. Integration of Palliative Care in Pulmonary Hypertension Services

· Primary palliative care: PH teams trained in basic symptom management, communication, and advance care planning.

· Specialist palliative care: Referral for complex symptoms, existential distress, or end-of-life care.

· Shared care models: Combined PH–palliative care clinics improve quality of life and reduce readmissions [12].

· Community support: PH nurses, hospice at home, and telehealth monitoring.

· Patient education: Provide information about PH, symptom management, and advance care planning.

10. Conclusion

Pulmonary hypertension is a progressive, life-limiting condition with a high symptom burden and unpredictable course. Palliative care should be integrated early, alongside optimal disease-targeted therapy, to improve quality of life, support families, and ensure goal-concordant care. Clinicians must be skilled in managing dyspnoea, fatigue, pain, depression, and right heart failure, while proactively addressing advance care planning and end-of-life preferences. A multidisciplinary, patient-centred approach is essential.

References

1. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731. doi:10.1093/eurheartj/ehac237

2. Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448-456. doi:10.1378/chest.11-1460

3. Hurdman J, Condliffe R, Elliot CA, et al. ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre. Eur Respir J. 2012;39(4):945-955. doi:10.1183/09031936.00078411

4. Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. 2012;141(2):354-362. doi:10.1378/chest.11-0676

5. Kutner JS, Blatchford PJ, Taylor DH Jr, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175(5):691-700. doi:10.1001/jamainternmed.2015.0289

6. Abernethy AP, McDonald CF, Frith PA, et al. Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet. 2010;376(9743):784-793. doi:10.1016/S0140-6736(10)61115-4

7. Jennings AL, Davies AN, Higgins JP, et al. A systematic review of the use of opioids in the management of dyspnoea. Thorax. 2002;57(11):939-944. doi:10.1136/thorax.57.11.939

8. Johnson MJ, McDonagh TA, Harkness A, et al. Morphine for the relief of breathlessness in patients with chronic heart failure—a pilot study. Eur J Heart Fail. 2002;4(6):753-756. doi:10.1016/s1388-9842(02)00158-0

9. Grünig E, Lichtblau M, Ehlken N, et al. Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J. 2012;40(1):84-92. doi:10.1183/09031936.00123711

10. Beattie JM, Johnson MJ. Subcutaneous furosemide in advanced heart failure: has clinical practice run ahead of evidence base? BMJ Support Palliat Care. 2012;2(1):5-6. doi:10.1136/bmjspcare-2011-000145

11. Sandoval J, Gaspar J, Pulido T, et al. Graded balloon dilation atrial septostomy in severe primary pulmonary hypertension. A therapeutic alternative for patients nonresponsive to vasodilator treatment. J Am Coll Cardiol. 1998;32(2):297-304. doi:10.1016/s0735-1097(98)00238-1

12. Rogers JG, Patel CB, Mentz RJ, et al. Palliative care in heart failure: the PAL-HF randomized, controlled clinical trial. J Am Coll Cardiol. 2017;70(3):331-341. doi:10.1016/j.jacc.2017.05.030