Breathlessness: A palliative care perspective
Breathlessness is a difficult symptom to control in palliative care. Knowledge of the underlying mechanism has not had the same impact on the management of dyspnoea as has understanding of pain pathways on pain, or clarification of receptors and neurotransmitters on the management of nausea and vomiting.
This article describes a systematic approach to management of breathlessness in adult patients with malignant disease, but the principles can be applied to many of non-malignant diseases as well.
Dyspnoea is defined as an unpleasant subjective awareness of difficulty in breathing. It should not be confused with objective signs such as tachypnoea and hyperventilation. In healthy individuals, dyspnoea may be physiologically appropriate on exertion and often needs no intervention, but in disease states it arises with little or no external provocation.
In patients with advanced cancer the prevalence of dyspnoea increases from the time of referral to palliative care services to the last week of life. 24% patients had dyspnoea at initial referral as compared to 64% in the last week of life.
Dyspnoea is ranked in the top ten symptoms of advanced cancer. Surveys document an incidence of 70% in the last six weeks of life. It is the most frequently reported symptom in patients with lung cancer, occurring in up to 75% of patients. Breathlessness is an independent indicator of prognosis, second only to performance status.
There is little definitive knowledge about the neurophysiologic mechanisms involved in the central processing of dyspnoea. Functional imaging studies with positron emission tomography showed brain activation that correlated with respiratory discomfort during laboured breathing. Brain activation was characterised by a significant increase in regional cerebral blood flow. In this model at least, the perception of dyspnoea occurs in the right anterior insula where neural activity is proportional to the stimulus, whereas the intensity of the perception is modulated in the right posterior cingulate gyrus where other neural inputs come into play. Modulating factors might include emotions, cognitive factors and treatments such as facial cooling which appear to reduce dyspnoea without affecting the breathing pattern.
It is reasonable to hypothesize that exogenous opioids reduce dyspnoea by acting on receptors in the right posterior cingulate gyrus to modulate the perception of dyspnoea without necessarily altering either the drive to ventilation or the ventilation response itself. [Table - 1]
A good history is essential in the assessment of patients with dyspnoea. Specific points in history must include time and nature of onset, diurnal variation, exacerbating and relieving factors and associated symptoms such as pain, cough, sputum, wheezing haemoptysis and features of hyperventilation. The history should also explore what breathlesness means to the patient; his coping strategies, response to medication and significant past medical illnesses. Clinical monitoring of the severity of breathlessness and functional ability should be undertaken, preferably using simple verbal or numerical rating scales, which can be can be used for serial measurements if necessary.
One must pay particular attention to the posture of the patient for e.g. orthopnoea in heart failure and leaning forward with pursed lip breathing in chronic obstructive airways disease. It is important to check for pallor, cyanosis, bronchospasm, pulmonary collapse or consolidation, pleural effusion and signs of heart failure. Observing the patient during an episode of dyspnoea may reveal a panic attack/hyperventilation.
Investigations should be kept to a minimum in palliative care, particularly because many patients find it difficult to travel to to different hospital departments. Investigations should be restricted to those that might alter management. The most commonly performed tests are full blood count and chest radiographs. It may occasionally be necessary to perform CT or MRI of the thorax to elucidate pulmonary, cardiac or mediastinal abnormalities detected on chest radiography or ultrasound.
If available, pulse oximetry is a very useful bedside non-invasive quick test that allows simple assessment of oxygenation. One should be aware of its limitations as readings can be inaccurate in peripheral vascular shut down or in hypercapnoeic respiratory type II failure.
Chest ultrasound may occasionally be necessary to differentiate collapse from an effusion or to localise effusion before aspiration. Ventilation/perfusion scans have very limited use in palliative care settings. Pulmonary function tests may be helpful in patients with a prognosis of months to identify reversible bronchospasm. In patients with an expected survival of a few days to weeks, clinical assessment and a therapeutic trial of bronchodilators is usually sufficient.
It is important to explain the underlying mechanisms and likely treatment in simple terms to both patient and carer. This often does much to reduce the psychological impact of the symptom on the sufferer.
Before embarking on any specific intervention for breathlessness in palliative care, the following should be checked:
Physical, psychological, social and spiritual factors all play a part and the concept of "total respiratory distress" can be useful. It is important to understand the symptom as not merely the manifestation of disease; it is also about the problems that arise from experiencing symptoms. Breathlessness can lead to restricted mobility, loss of independence, financial handicap, sleep disturbance, anxiety, depression etc.
A broader, interdisciplinary team approach must be employed tailored to the needs of the individual patient. In the early stages of disease, non-pharmacological treatment is as important as pharmacological, but in frail and terminal patients who are breathless at rest, the emphasis tends to be on pharmacological interventions.
Chemotherapy should be considered for patients with lung cancer or lymphoma. Chemotherapy has also been tried when breast cancer has spread to the pulmonary lymphatics causing lymphangitis carcinomatosa.
Radiotherapy is better at relieving haemoptysis and chest pain than breathlessness or cough.
Although airflow obstruction in COPD is largely irreversible, bronchodilators used individually or in combination are the mainstay of treatment.
If anxiety is a significant component, small doses of short acting benzodiazapines can be offered; e.g., lorazepam 0.5-1 mg 8-12 hourly and prn initially. Long acting drugs such as diazepam should be avoided. In acute exacerbations, subcutaneous infusions or bolus doses of midazolam can be given (starting dose 10 mg over 24 hours as infusion or 2.5 to 5 mg as subcutaneous bolus prn).
Opioids reduce the sensation of breathlessness by reducing the CO2 sensitivity in medullary respiratory center. Patients who are breathless on exertion or on lying down only may gain more benefit from as-required opioids than from regular dosing, at an initial dose of morphine 2.5-5 mg orally in opioid-na´ve patients (smaller dose in the very elderly and in renal failure). Patients who require more than three as-required doses per day should be considered for regular therapy e.g. with 12 hourly slow release oral morphine. A dyspnoeic patient who is already taking opioids for pain can be offered extra as-required doses of opioids. A laxative must be prescribed to prevent constipation.
A recent systematic review supports the use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were similar to the results of the main analysis. Four studies measured arterial blood gases and showed no deleterious effects with opioids. Oxygen saturation was measured in nine studies, which showed no significant change with opioids. Results from included studies do not support the use of nebulized opioids.
A recent study of morphine for refractory dyspnoea in community setting, concluded that sustained release oral morphine at low dosage provides significant symptomatic improvement in dyspnoea.
If cardiac failure is responsible for breathlessness, the patient should be treated with standard antifailure treatment including diuretics.
There is good evidence for the use of corticosteroids in asthma and COPD but one must be aware of the adverse effects of long term use. The risk of oral candidiasis with inhaled route should not be underestimated. Corticosteroids have also been used in cases of stridor, superior vena caval obstruction and lymphangitis carcinomatosa. In these cases steroids must be used on a short trial basis and discontinued promptly if there is no benefit.
Oxygen therapy is not always necessary in patients with dyspnoea. Both patient and family can become emotionally dependent on oxygen. If the patient is hypoxic at rest (SaO2 < 90% on pulse oximetry), it is appropriate to offer oxygen as required.
Patients who become hypoxic only on exertion should use oxygen only for brief periods after activity. Care should be taken to reduce the oxygen flow rate in those who are hypercapnoeic or at risk of hypercapnia.
Only a small proportion of patients should require continuous oxygen. For others, explanation combined with non-specific drug measures especially anxiolytics and possibly a bedside or hand-held fan can have dramatic effects.
Intraluminal laser therapy can help recanalise an occluded bronchus and restore airflow. If the patient has already received maximal external beam radiation to the primary bronchial lesion, recurrence can be treated endo-bronchially using intraluminal radiation (brachytherapy). However endobronchial therapy is limited in availability.
This can open a recently closed major bronchus, and can also help keep the trachea patent in patients with proximal tumours. Expandable wire stents are most commonly used, though the tumour may eventually grow through these. Stents can be placed under minimal sedation using a fibre-optic bronchoscope.
In palliative care, most effusions are malignant in origin, but they can also be caused by cardiac failure or secondary to infection e.g. tuberculosis. Asymptomatic patients can be kept under observation. Patients who remain symptom free after initial thoracentesis, can also be followed up without further intervention. However, most patients have recurrence of symtoms within one month of therapeutic aspiration. Frail patients with a limited life expectancy, and others who are unwilling for inpatient admission and pleurodesis may be treated with repeated therapeutic thoracoentesis. The volume of fluid removed during initial thoracentesis should be limited to 1.5 litres. There is a risk of re-expansion pulmonary oedema with removal of large amounts of pleural fluid when there is co-existing endobronchial obstruction. Care should also be taken to avoid a pneumothorax as the lung may be resistant to re-expansion because of endobronchial obstruction.
Patients with rapidly reaccumulating malignant pleural effusions with reasonable life expectancy will benefit from pleurodesis.
The pleural space has to be drained using an intercostal tube. Small bore (10-14 F) intercostal catheters should be the initial choice for effusion drainage as they cause less patient discomfort. Large pleural effusions must be drained in a controlled fashion to reduce the risk of re-expansion pulmonary oedema. A chest radiograph is taken to check that the lung has expanded (implying that the parietal and viscera pleura are in contact). It is not necessary to wait till fluid drainage is less than 150 ml per day before proceeding with pleurodesis. The most important requirement for successful pleurodesis is satisfactory apposition of the parietal and visceral pleura, confirmed radiologically. In the majority of patients this will occur in less than 24 hours. If only partial pleural apposition can be achieved, chemical pleurodesis can still be attempted and may provide symptomatic relief.
The intercostal tube should be clamped for one hour after sclerosant instillation. The tube can be removed within 12- 72 hours if the lung remains exapnded and drainage is less than 250 ml. Repeated pleurodesis can be considered if drainage remains more than 250 ml. To date there is no ideal sclerosing agent. Talc is the most effective sclerosant available. A small number of patients (<1%) may develop acute respiratory failure following talc administration. Tetracycline is modestly effective, has few severe side effects, and is the preferred sclerosant to minimize adverse event rates. Bleomycin is an alternative sclerosant with a modest efficacy rate but is expensive. Pleuritic chest pain and fever are the most common side effects of sclerosant administration. Lignocaine (3 mg/kg; maximum 250 mg) should be administered intrapleurally just prior to sclerosant administration. Premedication should be considered to alleviate anxiety and pain associated with pleurodesis. Intrapleural instillation of fibrinolytic drugs is recommended for the relief of distressing dyspnoea due to multiloculated malignant effusion resistant to simple drainage.
Long term indwelling catheters are beng investigated as an alternative to repeated thoracosentesis or pleurodesis in selected patients., 
A recent systematic review of complementary therapies found research-based evidence of benefit to cancer and/or COPD patients from several complementary therapies including acupuncture.
As with any symptom in palliative care, an understanding of the underlying mechanism will improve management. A rational approach to the management of breathlessness demands that the causes are determined whenever possible, using the minimum of invasive investigations.
It is important to choose investigations and treatment that are appropriate to the prognosis and include specific drug as well as general and non-drug measures. A systematic review supports the use of systemic opioids for breathlessness in patients with advanced disease.
[Table - 1]