Dyspnoea in Palliative Care

Dyspnoea is the distressing awareness of the process of breathing - either the frequency or the effort involved. It is very frightening and occurs in about a third of all patients receiving palliative care.¹ A search of the literature found it in 21 to 78.6% of patients with advanced cancer² and over 50% patients with end-stage AIDS, COPD, heart disease and renal disease will also experience this disabling symptom.³ It is important to realise it is not limited to those with cancer or respiratory disease. Indeed, many patients with neuromuscular diseases have a normal ventilatory drive but low ventilation due to abnormalities in muscle function and neuromuscular transmission: this feeling of paralysis preventing ventilation is particularly frightening.

Palliative care has been defined by WHO as "an approach that improves the quality of life of individuals and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual".⁴ Congestive heart failure, COPD and advanced neurological or muscular disease are all highly likely to cause dyspnoea as a main symptom, and are amenable to a palliative approach.

Agitation, anxiety and insomnia can produce a vicious cycle of behavioural disturbance and distress for both the patient and their family and carers.

The drive to breathe and the stimulus for dyspnoea is quite complex and multifactorial:

• The main driving force of blood gases is pCO₂ rather than pO₂ (the exception being in COPD) although significant hypoxia can augment the hypercapnic drive.
• Mechanical stimuli such as pulmonary stretch and proprioceptive input from the chest wall and diaphragm are also important.
• Proprioception in the lungs and chest wall provide additional stimulus.
• Pyrexia stimulates the thalamus and can cause tachypnoea.
• Emotions (anxiety, fear, anger etc.) and arousal state can also modulate breathing.

It is important to distinguish potentially reversible causes from those which are fixed and irreversible.

Breathlessness is subjective and, especially in these circumstances, may correlate poorly with objective assessment of lung function including blood gas analysis and airways obstruction. Dyspnoea does not necessarily imply respiratory failure. How the patient feels is important - dyspnoea can be a major problem in terminal illness with remarkably normal blood gases.

History

Should include information about:

• Previous or pre-existing conditions (co-morbidities may exacerbate symptoms)
• Recent treatments e.g. radiotherapy
• Recent medication changes

Questions regarding the breathlessness should include:

• Rapidity of onset (insidious and relentless vs. sudden)
• Associated symptoms
• Relationship to exercise
• Impact on simple daily activities e.g. washing, toileting, dressing
• Role of carers
• Episodes of panic
• Impact on quality of life and any mood disturbance
• Any known relieving factors

Examination

Including:

• Assess effort and efficacy of breathing (e.g. depth of breathing, use of of accessory muscles of respiration, expectoration of secretions)
• Observe the patient at rest and, where appropriate, walking or undertaking a small task
• Assessment of degree of anxiety (e.g. Hospital Anxiety and Depression scale). Chest breathing (as opposed to abdominal breathing, with use of the diaphragm) may be a clinical sign of anxiety.
• Cardiac status (heart rate, rhythm, cardiac murmurs, signs of cardiac failure)
• Clinical signs of infection, effusion, anaemia or cyanosis*
• Examination of the respiratory system based on known disease, looking for signs of stridor and progressive disease

*Central cyanosis means that there is at least 5 g unsaturated haemoglobin per 100 ml. Hence there may be cyanosis in very modest hypoxia with polycythaemia but no cyanosis with marked desaturation in anaemia.

Investigations

Clinical Knowledge Summaries recommend the following:⁵

• CXR
• Spirometry
• ECG to exclude arrhythmia
• FBC to exclude anaemia
• Pulse oximeter

Blood gas analysis is not usually available outside hospital but a pulse oximeter may be a useful tool in the community.⁶

General

Try to address breathlessness as soon as distress becomes apparent and not wait until it is well established. To relieve the anxiety that will alway accompany the symptom, start by explaining the current situation and discussing management options. Explore ongoing fears (fears of suffocation, choking, dying in sleep are common). Someone should stay with an acutely distressed patient to give reassurance and possibly distraction. Outside the home this may need to be a member of staff as relatives can be very frightened too. If left alone a call bell should be available.
Useful strategies include:

• Positioning - the most comfortable position is usually sitting upright with support.
• Moving air from a fan (hand held or stationary) or open window helps provides psychological relief.
• Teaching and use of breathing exercises and relaxation methods.
• Encourage modification of lifestyle in reducing non-essential activities, whilst trying to maintain mobility and independence as far as possible.
• Dietary modifications with small frequent drinks and meals being best tolerated. Patients with cancer or end-stage respiratory disease are frequently cachexic and advice from a dietician may be helpful.
• Mouth breathing dries the mouth and oxygen will be very dry unless it has been humidified so attention to oral hygiene is important.
• Complementary therapies such as aromatherapy, hypnosis and acupuncture may be helpful to some patients but the evidence base is weak.⁷

A breathing management programme can help people to learn how to control their breathing. These are usually accessible via a 'Breathlessness clinic' (where they exist) or from specialist respiratory nurses or physiotherapists. After a full assessment, various techniques are demonstrated and advice given. There is evidence that working with both patients and carers significantly improves control and satisfaction.⁸Typical areas covered are:

• Breathing retraining exercises
• Advice about managing attacks of breathlessness with possible panic attacks using CBT techniques
• Coping with activities of daily living
• Relaxation techniques
• Emotional support for both the patient and those around

Medical interventions

Physical interventions may help to relieve or even reverse the cause of the dyspnoea. The degree of intervention desired by the patient will vary and management decisions should be made with them and their families. Discussing possible eventualities can help patients make important, informed decisions about their future care such as the need for emergency hospital admissions, use of artificial ventilation and aggressive treatment of infections.

• Anaemia can exacerbate dyspnoea on exertion, and blood transfusion can be justified on this basis. One study looking at practice in 6 British hospices found that patients received blood transfusions in about 6% of all hospice admissions.⁹
• Tapping ascites can relieve pressure on the diaphragm and improve ventilation.
• Pleural effusion tapping also improves lung function. For recurrent effusion, pleurodesis is often effective, but it is a painful procedure. Some centres are pioneering the use of implantable access devices for recurrent tapping.¹⁰
• Infections will aggravate dyspnoea and whilst pneumonia may be "the old man's best friend", treatment of the infection will improve matters where he is not strictly terminal.
• Heart failure management where appropriate, offers some relief.
• Lymphangitis carcinomatosa can result in the malignant blockage of mediastinal lymphatics causing lymphoedema in the lung. Treatment is with steroids, and occasionally radiotherapy or chemotherapy, but response is often poor and the condition carries a poor prognosis.
• Superior vena caval (SVC) obstruction can arise from compression of the SVC by mediastinal tumour. In ¾ of cases it is from primary lung tumours but intra-luminal thrombosis may also occur. There is dyspnoea and gross venous congestion and oedema of the head, neck and upper limbs. High dose steroids with radiotherapy or chemotherapy may help. Dilatation, stenting and anticoagulants may also be tried.
• Tumour may impinge on the tracheal or bronchus causing collapse of a segment or complete lung. Treatments include steroids, external radiotherapy, chemotherapy (for small cell cancer of the lung) and endobronchial treatments such as laser, radiotherapy, stenting, cryotherapy and balloon dilatation.¹¹
• Pulmonary embolism and pneumothorax may justify admission to hospital for active treatment.

Drugs¹¹

In some situations, physical interventions may not be possible. This is especially true of neuromuscular disease. Nonetheless, medication (including oxygen) may be useful in reducing symptoms.

Opiates

Reticence about the use of morphine for palliation of dyspnoea is common, especially in non-malignant disease (COPD in particular), for fear of causing respiratory depression. Oral and parenteral opiates can provide good symptom relief,¹² and the risk of significant respiratory depression is much less than anticipated.¹³

• Oral morphine is widely used to manage dyspnoea, although the mechanism of action is not fully understood. Morphine can be used safely in cancer patients without producing any changes in pCO₂.¹⁴ The anxiolytic and anti-tussive effects of diamorphine make it ideal for lung cancer.
• Expert opinion is that oral morphine can be used safely for the management of dyspnoea, even with COPD, if the patient is started on a low dose, and it is titrated according to response and side effects. Patients not already receiving morphine should start at doses of 2.5 to 5 mg 4 hourly/prn. For those already on morphine, whether for pain or dyspnoea, the overall dose may need to be increased by 30 to 50%.
• In extreme dyspnoea and distress intravenous or subcutaneous diamorphine is often used for more rapid relief than by the oral route.
• When the oral route is no longer available administration by continuous subcutaneous infusion is acceptable. It can even be combined with a benzodiazepine.
• Evidence for the use of nebulised opioids for dyspnoea comes largely from uncontrolled or small trials and is of poor quality.^15,16

Anxiolytics

There is as much reason to be cautious about respiratory depression with benzodiazepines as with opiates but they are commonly used to treat dyspnoea in palliative care, although they fail to work in 4 trials out of 5.²

• Diazepam, lorazepam and midazolam are most frequently used:
• Diazepam is usually given in oral form, and because of its long duration of action, it can often be given as a single bedtime dose of 2 to 5 mg to relieve ongoing breathlessness and anxiety.
• Lorazepam is much shorter acting and is preferred by some patients to cover brief episodes. It is often prescribed as 0.5 mg (½ a tablet). It can be swallowed or it can be crushed between the molars and put between gum and cheek or under the tongue for rapid absorption. This technique is very effective but should not be taught in other situations as the swift response predisposes to addiction.
• Midazolam has an injectable preparation that mixes better with other drugs than diazepam injection. It can be given by subcutaneous infusion with opioids such as diamorphine if necessary. The dose range is from 5 to 10 mg stat to 10 to 60 mg over 24 hours via a subcutaneous infusion. The combination of midazolam and diamorphine is particularly helpful in the terminal phase of
  disease. However, it can also be a useful adjunct to morphine for dyspnoea prior to this.¹⁷

Oxygen therapy

The role of oxygen therapy for palliation of dyspnoea is unclear.¹⁸

• There is conflicting evidence, particularly with lung cancer patients who are not significantly hypoxaemic. The few published studies do not clearly demonstrate that oxygen relieves dyspnoea in these patients. The consensus amongst respiratory physicians is that supplemental oxygen should not be used when the resting oxygen saturation is normal.
• Patients with significant hypoxaemia should derive some benefit. A pulse oximeter is more useful than clinical cyanosis in the situation where repeated blood gas analyses is not available or not desirable.
• Dyspnoeic patients with oxygen saturations below 90% may benefit from a trial of oxygen. Below 80% the individual is likely to be severely compromised, and so require oxygen. The use of oxygen in COPD requires care as patients may be dependent upon their hypoxic respiratory drive, and should therefore be given 24% oxygen with repeat assessment. For others, 28 to 40% may be required, according to response.
• Either a mask or nasal cannulae may suit patient preference and comfort. Patients need to be encouraged not to become dependent upon their oxygen supply, as this may severely limit their lifestyle.
• Humidified oxygen may be more acceptable to some patients, particularly those with an already dry mouth.

Bronchodilators

Where an element of bronchoconstriction is contributing to breathlessness, it is worth reinforcing and optimising use of bronchodilators. There are a variety of devices for asthma but delivery of salbutamol by nebuliser or spacer device is simple and effective where breath control is poor.

Tricyclic antidepressants and SSRIs may be helpful, especially for panic attacks.