Dyspnoea in Palliative Medicine
Dysponea, common in advanced cancer patients, has many causes. Specific treatment of the cause is more effective than non-specific treatment only. A detailed assessment for the cause is therefore mandatory. Non-specifically, morphine is the drug of choice for relieving dyspnoea. Other respiratory sedatives, such as promethazine and chlorpromazine are helpful. Anxiolytics are given to anxious patients. Oxygen is helpful in certain conditions only. Non-drug management is equally important. Refractory dyspnoea in terminal stage can be managed by heavily sedating the patient to sleep.
Dyspnoea occurs in between one quarter and three quarters of patients with advanced diseases, not only in patients with cancers of respiratory organs. It is recorded in 70% of patients with advanced cancer during the last six weeks of life1. Continuous dyspnoea may be the most distressing and panicking suffering for both patient and family.
Table 1 shows the causes and their clinical features.
Hyperventilation of panic attack and tachypnoea with acidotic deep breathing in acidosis may mimic dyspnoea. Fatigue, fear and panic also exacerbate dyspnoea. Cachexia and weakness of the patient can present as dyspnoea on exertion.
A complete history and physical examination can already provide enough information for making the diagnosis of dyspnoea for most of the patients.
History
Ask for the nature, severity and duration of the dyspnoea. Has deterioration been rapid or slow? Take a history about the symptoms of the possible causes of dyspnoea as we would from an ordinary dyspnoeic patient. In addition, ask in detail what treatment the patient has had for his cancer. Is the dyspnoea related to eating or drinking? Is the difficulty of breathing more severe on inspiration or expiration? How does it affect the quality of life? Assess the psychological status of the patient and carers.
Physical Examination
Examine the patient as we would for a non-cancer patient. Look for signs of the possible causes shown in Table 1. The patient’s underlying COAD or asthma might have been exacerbated by some cancer related problems. Presence of ankle oedema, basal crepitations and raised jugular venous pressure do not necessarily indicate heart failure. Ankle oedema is quite common in advanced cancer patients. Basal crepitation can occur in lymphangitis carcinomatosis and raised jugular venous pressure may be caused by obstruction of superior vena cava with the associated oedema of the face and upper limbs. There may be localised rhonchi and crackles caused by localised obstruction or compression.
Look for signs of extrathoracic causes such as anaemia, uraemia and distended abdomen caused by enlarged organs, bowel obstruction or massive ascites. Look for signs of anxiety and panic disorder.
Chest x-ray helps in confirming the diagnosis of pneumonia, atelectasis, lymphangitis carcinomatosis, pleural effusion, heart failure and chronic pulmonary disease. In lymphangitis carcinomatosis, chest x-ray shows reticular markings radiating from the hilar region which may be widened by enlarged lymph nodes. Widespread or miliary markings can be due to mutiple metastases, infection, haemorrhage or drug toxicity.
X-ray with contrast swallow is helpful in diagnosing tracheo-oesophageal fistula which presents with cough and dyspnoea on drinking and eating.
Laryngoscopy and bronchoscopy may be done for suspicion of laryngeal growth with stridor as well as tracheobronchial compression or obstruction. Stent insertion or laser treatment may be done at the same time if indicated.
Full blood count, sputum culture, CT scan, spirometry, blood gas and ventilation-perfusion scanning may also be done if indicated.
|
Clinical Features |
Management |
|
Infection (bacterial/opportunistic) |
|
|
· Increased sputum volume |
· appropriate antibiotics |
|
· Yellow/greenish sputum +/- blood |
(except in terminal phase) |
|
· Tachycardia, sweating |
|
|
· Fever (may be absent) |
|
Loss of lung function |
|
Lymphangitis carcinomatosis/ Lung secondaries |
|
|
· Steady deterioration |
· Dexamethasone 8-12mg/day |
|
· Dyspnoea on exertion / later at rest · Unproductive cough |
¯ in a few days to maintenance dose |
|
· Basal crackles in the chest |
· Radiotherapy to centre of chest |
Result of cancer treatment |
|
|
· Pneumonectomy |
· Oxygen |
|
· Radiation-induced fibrosis |
· Steroid |
|
· Chemotherapy - bleomycin, adriamycin |
· Stop chemotherapy / Use steroid |
Lung Collapse |
|
Pleural effusion |
|
|
· Steady or rapid deterioration |
· drained through a small IV |
|
· Trachea deviated to opposite side |
cannula |
|
· Reduced tactile fremitus |
· Pleurodesis2 |
|
· Stony dull on percussion |
· palliative radiotherapy3 |
|
· Reduced breath sounds/vocal resonance |
|
Pneumothorax |
|
|
· Trachea deviated to opposite side |
· drainage |
|
· Reduced tactile fremitus |
· pleurodesis |
|
· Tympanic on percussion |
|
|
· Reduced breath sound/vocal resonance |
|
|
Obstruction |
|
Asthma |
|
|
· History of asthma |
· Bronchodilator |
|
· Sudden onset or chronic |
· Oxygen |
|
· More wheezing, effort and rhonchi on expiration |
· Steroid |
|
Chronic Obstructive Airway Disease |
|
|
· “Blue bloater” |
· Bronchodilator |
|
· “Pink puffer” |
· Oxygen |
|
|
· Chest physiotherapy |
|
|
· Steroid/antibiotics |
|
Tumour in trachea / main bronchus |
|
|
· Localised rhonchi |
· Radiotherapy/brachytherapy4 |
|
· Nature of the cancer |
· Laser therapy |
|
|
· Bronchial stent |
|
|
· chemotherapy |
|
|
· steroid |
|
Tracheo-oesophageal fistula |
|
|
· acute dyspnoea immediately after swallowing |
· oesophageal tube |
|
Tracheal compression |
|
|
· Stridor/wheeze on inspiration & expiration |
· Steroid, radiotherapy |
|
· Inspiratory and expiratory effort |
|
|
Epiglottis tumour |
|
|
· Marked inspiratory stridor |
· palliative radiotherapy |
|
· partially relieved by sitting forward |
· Steroid |
|
Cardiac |
|
Congestive heart failure |
|
|
· Tachycardia, Orthopnoea |
· oxygen |
|
· Ankle oedema may be absent |
· ACE inhibitor |
|
· Frothy white or pink sputum |
· Frusemide |
|
· Bilateral basal crepitation |
|
|
· Raised JVP, hepatomegaly · May have expiratory rhonchi |
|
Pericardial effusion/temponade |
· Aspiration |
|
Vascular |
|
Pulmonary embolism |
|
|
· Sudden deterioration |
· Oxygen |
|
· Chest pain present or absent |
· Anticoagulant (except in |
|
· Tachycardia |
terminal phase) |
|
· No chest sign, apyrexia |
|
Superior vena cava syndrome |
|
|
· Oedema of face and upper limb · Raised JVP and distended veins |
· Steroid, radiotherapy |
|
Musculoskeletal |
|
Chest wall weakness / deformity / general debility |
· Oxygen |
|
Chest wall pain |
· Analgesic |
|
Diaphragmatic paralysis |
· Oxygen |
|
Extrathoracic |
|
Anaemia |
|
|
· Marked pallor |
· Hb<10, consider transfusion |
|
· Marked tachycardia |
· dependent on length of life |
|
· Wide pulse pressure |
|
|
· Air hunger |
|
Abdominal distension |
|
|
· Massive ascites |
· Paracentesis |
|
· Hepatomegaly |
· Steroid |
|
· Bowel obstruction |
|
|
Central (neurogenic) |
|
|
· Anxiety/situational |
· Counselling/anxiolytic |
The rationale of some specific management shown in the table is obvious and similar to the management of the condition in non-malignant patients.
It has been shown that pleurodesis after drainage of pleural effusion in malignant condition is effective in retarding recurrence of effusion with dyspnoea2.
Small cell carcinoma of the lung is highly responsive to chemotherapy. Combination of new chemotherapy in non-small cell lung cancer has resulted in symptom relief5,6 and an increase in the median survival of non-small cell lung cancer by 6-8 weeks compared to untreated patients7,8,9. Radiotherapy gives effective palliation of symptoms with minimal side-effect to non-small cell carcinoma of the lung, but there is still no evidence that they can extend survival time10.
Stenting and/or laser resection of endobronchial tumour are effective to arrest dyspnoea for a period of time.
Antibiotic is of course the choice of treatment for bacterial chest infection. However, its use may not be indicated in terminal cancer patients. Similarly, whether to treat pulmonary embolism with anticoagulants also depends on the stage of the disease. Involve the patient and family in decision making.
The patient would be less dyspnoeic if the need for exertion is reduced, such as using home-helper and using wheelchair and bedside commode11.
The patient can be propped up with pillow or sleep in a chair. He can be distracted by reading or watching television. Although stopping smoking is too late to prevent cancer, smoking can exacerbate dyspnoea.
Open the window and use an electric fan for facial cooling which can relieve sensation of dyspnoea through stimulation of the receptors of the trigeminal nerve.
Physiotherapist can help by teaching the patient to do breathing exercise, deep breathing and coughing. He can also do the postural drainage of retained secretion, percussion, vibration and suction. Humidified air from steam or nebulised saline as well as mucolytic agents such as acetylcysteine or bromhexine can loose tenacious sputum1. Excessive secretion in the terminal stage can be reduced by anticholinergic drugs.
Wheezing caused by reactive bronchospasm in congestive heart failure or caused by retained secretions or tumour in the main bronchi can be relieved with nebulized bronchodilator.
ANXIOUS PATIENTS
For panicking or anxious patients, reassure and accompany them and respond to their questions. Emphasize that breathlessness can be relieved, becoming breathless is not dangerous and that they will not suffocate. Identify situational and psychological components. Teach him to do relaxation exercise, meditation and breathing exercise. Refer to music therapy, hypnotherapy, conventional or religious counseling. Hold the patient firmly during panic attacks.
Morphine and other opioids, has a direct effect on brain stem respiratory centre12,13. It reduces respiratory drive, alters central perception of breathlessness, decreases carotid body discharge, reduces metabolic rate and oxygen consumption. It also sedates the panicking patient but the patient may become very drowsy if not used for pain. It can be started with 2-4mg four-hourly orally and be increased daily by 2mg/dose until relief of dyspnoea or drowsiness occurs. It is unusual to require more than 2.5-5mg subcutaneously or 5-10mg orally every four hours11.
If the patient is already on morphine, it will have little benefit on dyspnoea until adequate analgesia has been achieved. The dosage can be increased by 10% increments beyond the pain management dosage. It may need to be increased up to 50% more than the original dosage. At this dosage, drowsiness is inevitable.
Morphine solution for injection can be administered via a nebulizer in the dosage of 10-40mg up to three hourly14. However, it may cause bronchospasm and its effect has not been supported by clinical trials. So, if it has to be tried as a last resort, bronchodilator inhaler or nebulising solution should be readily available and the dosage should be titrated upward from a low dose.
STEROID
Steroids can reduce peritumour oedema with improvement in obstruction. They may also improve lung stiffness due to parenchymal infiltration. As a result, they are indicated in obstructive dyspnoea and lymphangitis carcinomatosis where there are blockage of lymphatic drainage of the lung at the hilar lymph nodes resulting in lung stiffness and impaired oxygen diffusion through the alveoli. They are also useful for patients with acute exacerbation of chronic obstructive pulmonary disease15.
Dexamethasone can be started with 8-12mg daily and reduced at weekly intervals to a maintenance dose of around 2-4mg daily. Prednisone or prednisolone has more minerocorticoid side-effects than dexamethasone.
ANXIOLYTICS
Benzodiazepines such as lorazepam 0.5-1mg orally or sublingually can be used for short term relief. Diazepam has a longer half-life and can be used for long term anxiety. 5-10 mg can be given at bed-time orally and the dose be reduced if drowsiness occurs after several days and in elderly. Although diazepam is much cheaper, it has more potent depressant effect on the ventilatory response to carbon dioxide than opioids with negative changes in terms of exercise tolerance and blood gas16.
Midazolam has been recommended for panic associated with dyspnoea. It can be given subcutaneously or intravenously17.
OTHER DRUGS
Other recommended respiratory sedatives are alprazolam 0.5-4.5mg/day, chlorpromazine18 10-50mg nocte or promethazine19 12.5-25mg q12h.
Nabilone, a cannabinoid, at the dosage of 0.1-0.25mg bd-qid has bronchodilating effects and sedate without reducing respiratory drive. It is useful in patients with chronic obstructive airway diseases (COAD) and lymphangitis carcinomatosis.
The local anaesthetic agents, lignocaine and bupivacaine, can be administered by nebuliser and may improve dyspnoea14.
Most patients do not require continuous oxygen where there has been optimal management with morphine and anxiolytics. However, it should be made available if acute attacks are likely, e.g. in end-stage chronic airways limitation, cardiac failure or thromboembolism, or the patient remains extremely anxious despite efforts to counsel and control symptoms.
Oxygen is useful in COAD, congestive heart failure, recurrent pulmonary emboli, post-surgical pulmonary insufficiency and post-radiotherapy fibrosis20. It does little to relieve dyspnoea where there is collapsed area because of shunting of deoxygenated blood. It interferes with speech, eating and mobility21. Because it may fatally reduce hypoxic drive in COAD patient, it should be used in the lowest effective dose in COAD patients.
It is administered through nasal prongs or light comfortable plastic face mask attached to nebuliser to prevent dryness. Smoking is forbidden in the patient’s room. If available, use of oxygen concentrator is cheaper.
Ventilatory support is rarely indicated.
Semiconscious and unconscious patients who still appear dyspnoeic in the terminal phase can be treated with continuous morphine infusion. Relief of dyspnoea is more important than respiratory depression or sedation22. Restless patients can be sedated to sleep with parenteral morphine and clonazepam, midazolam or diazepam. The dosage of morphine depends on the patient’s usual dose, but is usually 30mg q4h or 2-3 times the dose that was being administered prior to deterioration.
Clonazepam can be given 2mg sublingually, subcutaneously, intramuscularly or intravenously and continued with 2-4mg/24hours. Alternatively, midazolam 5-10mg can be given subcutaneously or intravenously and then continued with subcutaneous infusion at a dose of 30-90mg/24 hours. Diazepam 10mg can be given intravenously. The aim is to keep the patient asleep and asymptomatic.
Intensify medical management with full investigation of the reasons for deterioration to give the patient a chance of improvement. When the patient is still distressfully dyspnoeic despite maximal therapy, use of morphine and anxiolytics as described above is appropriate if their renal and hepatic functions are normal. Commence treatment at the lowest dose and titrate until the desired effect is achieved. These patients, afterall, deserve good quality of life made possible by quality palliative care. However, in patients with non-malignant diseases, patient and family involvement with options and decision-making is particularly more important than in terminal cancer patients.
1. Specific treatment of the cause is more effective than non-specific treatment only.
2. A complete history and physical examination can already provide enough information for making the diagnosis of dyspnoea for most of the patients.
3. Morphine helps controlling dyspnoea. It can be started with 2-4mg four-hourly orally and be increased daily by 2mg/dose until relief of dyspnoea or drowsiness occurs.
4. The patient may be less dyspnoeic if the need for exertion is reduced, being propped up and distracted, cooling fan blowing on the face, retained airway secretion removed by physiotherapy or mucolytic and use of bronchodilator in bronchospasm.
5. Most patients do not require continuous oxygen where there has been optimal management with morphine, anxiolytics and respiratory sedatives.
6. Terminal patients with controlled distressing dyspnoea can be sedated to sleep with higher dose of morphine and midazolam or clonazepam.
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