• Introduction [link]
• Breathlessness trajectories [link]
• Mechanisms of breathlessness [link]
• Assessment of breathlessness [link]
• Principles of management of breathlessness [link]
• Non-pharmacological interventions [link]
• Oxygen therapy [link]
• Pharmacological management [link]
• Cough [link]
• Further reading [link]
Breathlessness, the uncomfortable awareness of the need to breathe, is the most common symptom that troubles dying patients with end-stage respiratory disease. Prevalence is said to reach 90% in patients with advanced lung cancer, and at least 70% in those with COPD and ILD. Clinical management achieves imperfect control and present palliative techniques are certainly less effective than those used in the management of somatic cancer pain.
Nonetheless, there have been significant advances in breathlessness management in the last 10 years, and it is imperative that clinicians who care for patients with respiratory disease at the end of life are familiar with the multi-faceted approach that can improve care. In addition, specialist palliative care services, such as hospices and community teams, are recognizing that they need to provide services to meet the needs of patients with non-malignant disease, of which respiratory disease forms the largest proportion.
Breathlessness is a complex sensation. Physical and psychological components are inextricably linked, so that anxiety and depression at the end of life or associated with the underlying illness can both precipitate and exacerbate episodes of breathlessness. The definition of breathlessness (dyspnoea) most commonly cited is that of the American Thoracic Society (1999):
The presence of breathlessness is associated with:
• Greater need for sedation to achieve symptom control at the end of life.
• Greater likelihood of hospital admission at this time.
• High levels of distress and exhaustion in family and other informal carers.
Breathlessness is a distressing, frightening sensation and, at the end of life, it is often only possible to reduce its impact, rather than reduce the absolute level of breathlessness.
‘Best practice’ in the management of breathlessness requires employment of a range of pharmacological and non-pharmacological interventions, tailor-made for the individual, and support for the family and other carers. All this needs to be remembered when planning end of life care; a process that needs to begin once the disease is advanced and progressive, even if this is some months or years before death.
Breathlessness tends to follow a different pattern in malignant and non-malignant respiratory disease.
Dyspnoea in malignant disease
Patients with lung cancer (either primary or secondary) or mesothelioma may have felt relatively well until shortly before the diagnosis was made. Having been used to being active, such patients and their families often find the descent into breathlessness on the slightest exertion extremely frightening and disturbing. Their housing and lifestyle will tend not to be already organized to accommodate ill-health.
However, since such patients may have been working or very active until recently, they are less likely to be impoverished, and may have many social contacts able to help them manage the practical difficulties of the illness (such as transport to hospitals, shopping etc.).
Dyspnoea in non-malignant disease
Patients with COPD will typically have been breathless for many years, and many will have had to retire on ill-health grounds. They are likely to have had to withdraw from their social life (through lack of energy but also embarrassment and a sense of stigma). Their spouse or partner will have had to shoulder many extra burdens as well as often losing their own work and financial independence in the process.
As such patients tend to be unable to maintain friendships and social activities (such as churchgoing or being members of clubs or organizations), they often have few friends to help with practical tasks and the end of life phase can lead rapidly to a state of mental and physical exhaustion. Alternatively, such patients and their families may have already moved to a bungalow or started living downstairs or, if living alone, moved to a residential home. All these considerations influence the management of the end of life phase.
Patients with ILD tend to follow the pattern of those with cancer.
Respiration is controlled by a centre within the bulbopontine area of the brainstem, which maintains blood gas and pH values within physiological limits, irrespective of changes in metabolic demand. The respiratory centre receives afferent feedback from a range of chemoreceptors and mechanoreceptors (including lung stretch receptors), which feed into a final common efferent pathway that adjusts respiratory rate and rhythm. Signals from higher centres of the brain (suprapontine areas including the motor cortex and cerebellum) can modify or override these signals. Examples of this include intentional control (e.g. recitation), emotional influences (e.g. anger, fear, laughter), and protective reflexes such as cough.
A schematic model demonstrating the pathophysiology of breathlessness, suitable for use by clinicians, is shown in Figure 5.1. It illustrates that central to an understanding of breathlessness is the recognition that it is a complex sensation influenced, like pain, by the higher centres i.e. thoughts, feelings, and reactions to emotions. This diagram can be a useful aid to explaining breathlessness to patients. It helps demonstrate that psychosocial interventions may be helpful in reducing the impact of breathlessness, even when somatic afferent signals cannot be improved.
If a patient has been living with breathlessness for many years, managing against the odds, and a clinician introduces the concept of psychological interventions, the patient may feel slighted, interpreting the suggestion as implying that he or she is not ‘coping’. When psychological interventions are, however, put in the same context as other physical or ‘medical’ treatments, they may be more easily accepted. It can be explained that a psychological influence, such as fear or anxiety, sends a signal or ‘chemical messenger’ to the brain, in a similar way to a low oxygen or high carbon dioxide level. Importantly, ‘altering central perception’ does not imply an inability to ‘cope’ with the difficulties of breathlessness. It removes the stigma from psychological factors, enabling patients and families to consider dispassionately the possibility of using psychological interventions to help breathlessness.
The perception of breathlessness as a sensation is still poorly understood. The present consensus is that the brain perceives breathlessness when afferent information reporting the demand for breathing is not matched by afferent information reporting the current level of ventilation. This is called the ‘mismatch’ theory. The genesis of breathlessness is well reviewed in Booth et al. (2009) and O’Donnell et al. (2007) (see [link]).
Breathlessness is composed of qualitatively different sensations, much like pain, but as yet the distinction between these, such as between ‘air hunger’ and ‘work of breathing’, have not been found to be useful in defining aetiology. There is, however, a growing understanding that ‘air hunger’ is more distressing than increased work of breathing.
1. Moosavi S. Pathophysiology of breathlessness. In: Cambridge Breathlessness Intervention Service Manual. Cambridge University Hospitals NHS Foundation Trust. www.cuh.org.uk/btreathlessness
It is very important that, even at the end of life, a careful history and diagnosis is made of each symptom. This does not mean that a patient at home, hospital, or in a hospice should be subjected to a spiral CT or bronchoscopy in their last days. It is, however, only possible to give the best symptom control and end of life care to patients once the most appropriate treatment has been selected. This, in turn, can be done only when the underlying cause of breathlessness has been considered and investigated, in a manner that is, of course, consistent with an individual's situation and expressed wishes.
Change in pattern of breathlessness
A change in pattern of the symptom must lead to reassessment of the working diagnosis. New onset or rapid progression of breathlessness may mean that a reversible cause of breathlessness has developed, in addition to the intractable disease. Specialist investigation may give the best ‘risk benefit ratio’ (perhaps more accurately considered as ‘short-term discomfort versus longer-term comfort ratio’), even near the end of life.
In situations where further investigation is inappropriate, a good history, coupled where necessary with specialist advice on the probability of each differential diagnosis, is likely to give that patient the best chance of effective symptom control. In contrast, a ‘catch-all’ diagnosis of ‘dying from respiratory disease’ combined with the prescription of ‘broad brush’ pharmacological treatment will never be in a patient's best interests.
Discussion of treatment options
It is vital to discuss the options for the diagnosis and treatment of potential complications with patients, to determine their preferences and to record and communicate these widely (letters to GP, Preferred Priorities of Care document etc.). This level of communication should be instigated early and then maintained (see Chapter 8 [link]–[link]). This will make it much more likely that a patient with a life-threatening illness is given the type of care they would prefer, rather than interventions chosen as a reaction to a given clinical state, resulting, for example, in unwanted invasive treatment such as ventilation.
Collaboration with colleagues
• Respiratory specialists and general practitioners (GPs) may be fortunate enough to have a relationship with their patients over many years. This is usually tremendously valuable as the end of life approaches. It may, however, occasionally be hazardous as symptoms can be automatically ascribed to previously experienced conditions, rather than reconsidered anew.
• It is important that non-respiratory specialists, for example in palliative medicine or general practice, do not neglect to seek advice from respiratory physicians. The converse is also true.
• Telephone consultations can be of great value, for example when a very ill patient at home or in a hospice is unable to attend a hospital outpatient appointment.
Although there is, as yet, no perfect assessment tool for breathlessness, the recently developed Dyspnoea-12 shows great promise. It is short and therefore not burdensome for breathless patients with limited ability to concentrate, and has been carefully designed using modern understanding of questionnaire development. It has been widely validated in patients with non-malignant disease, and further work is currently being undertaken in patients with cancer.1
Table 5.1 Dyspnoea-12 questionnaire
This questionnaire is designed to help us learn more about how your breathing is troubling you. Please read each item and then tick in the box that best matches your breathing these days. If you do not experience an item tick the ‘none’ box. Please respond to all items. (Score 0–3 for each item, maximum score 36)
1. My breath does not go in all the way
2. My breathing requires more work
3. I feel short of breath
4. I have difficulty catching my breath
5. I cannot get enough air
6. My breathing is uncomfortable
7. My breathing is exhausting
8. My breathing makes me feel depressed
9. My breathing makes me feel miserable
10. My breathing is distressing
11. My breathing makes me agitated
12. My breathing is irritating
The multidimensional pathophysiology of dyspnoea gives scope to a wide range of potential approaches to palliate the symptom. Interventions act in a number of ways, including reversing the underlying cause, reducing ventilatory demand, optimizing the mechanics of ventilation, and modifying the central perception of breathlessness.
Principles of symptom management are outlined first below, followed by more detail on non-pharmacological and pharmacological approaches.
Reversal of underlying cause(s)
This is not always possible in patients with advanced and incurable disease. However, potentially reversible conditions causing or exacerbating the symptom should always be considered and, if appropriate, searched for. Common examples of reversible causes of deteriorating breathlessness in such patients include:
• pulmonary embolism
• pleural effusion.
A degree of anxiety is inevitably present in patients suffering from breathlessness. Eliciting and addressing patients’ concerns and fears compassionately can be very effective as an initial management strategy. Patients (and their carers) may have seen many different clinicians over the years, and never yet had the chance to ‘tell the full story’ of the impact of breathlessness on their lives. Even for patients to understand that, although feeling breathless is extremely unpleasant, it does not actually harm the patient, can be extremely helpful; it is this fear that causes patients to remain inactive to avoid provoking breathlessness, therefore becoming deconditioned.
These tend to be the most useful interventions in breathless patients with advanced but not end-stage disease. The techniques are safe, can be very effective, and give patients a sense of control of their symptom. However, any non-pharmacological approach needs regular practice to be effective and to remain so, and patients in the last weeks and days of life usually lack the energy or time to do this. The success of these interventions depends largely on the extent to which a patient engages with them. (See [link]–[link].)
Drugs such as opioids and benzodiazepines have an important role in palliating breathlessness in patients with advanced disease and at the end of life, who may benefit less from non-drug measures (see [link]–[link]).
Oxygen tends to be overused in this patient group. A small proportion of patients may gain relief of breathlessness. An individual clinical assessment is often necessary, as there are no reliable criteria to help predict which patients may benefit (see [link]–[link]). Most patients, however, regardless of whether or not they are hypoxaemic, will gain benefit from using a fan (see [link]).
Table 5.2 Management of chronic intractable breathlessness
Non-pharmacological treatments: suitable for all breathless patients
Pharmacological treatment: more important in the severely breathless
Palliative treatment: oral opioids reduce breathlessness by about 20% in many patients, start low and increase slowly to reduce incidence of adverse effects. More useful in patients with severe breathlessness.
Oral benzodiazepines (e.g. lorazepam) or phenothiazines may be helpful if patients cannot use non-pharmacological anxiety-reducing strategies.
At the end of life: prescribe continuous subcutaneous infusion of morphine/diamorphine and midazolam.
Oxygen In patients with advanced disease and chronic intractable breathlessness, there is no evidence that oxygen is better than a fan, unless the patient desaturates below 90% on exercise.
Both non-pharmacological and pharmacological interventions have their place in the treatment of breathlessness. When a patient is first diagnosed with advanced respiratory disease a range of non-pharmacological interventions should be instituted. These can include exercise, a fan, anxiety reduction techniques, and other psychological interventions. Encouraging mental and social activity, although not widely recognized as a health intervention, can have a positive impact on well-being. As the patient becomes less well, pharmacological therapy is likely to be needed.
It is important to understand that pulmonary rehabilitation is not an intervention just for patients with a longer prognosis. There is evidence that rehabilitation can benefit patients with the most advanced disease, including those that are too breathless to leave the house (MRC dyspnoea score 5), and even patients that are dependent on invasive ventilation.1 , 2 In addition, there is gathering evidence that short, low-intensity, and home-based programmes can lead to benefit.3
Some patients will need support or encouragement to accept pulmonary rehabilitation and sometimes a home visit or attendance at a hospice breathlessness clinic will give patients the confidence to participate.
Exercise outside pulmonary rehabilitation
Exercise is one of the most effective non-pharmacological interventions for breathlessness and is based on the greatest evidence base. Although patients with far advanced disease may be too unwell to join a formal exercise or rehabilitation programme, it is still vital to encourage activity. Simple activity such as getting up out of a chair and walking to the television in the ‘advert breaks’ (for example) has many benefits, including:
• maintenance of independence
• reduction of burden on carers
• increased confidence and self-efficacy
• reduction in the ‘humiliation’ (which many feel) of being dependent on others
• generation of a rare sense of progress or improvement.
It is particularly important in patients with advanced progressive disease that exercise is not viewed as compulsory, with the insinuation that it may improve prognosis. Exercise may, therefore, be best described as ‘activity’. Psychosocial activity, such as attending a hospice day centre, may be just as important.
Patients may have withdrawn from social life partly because they feel stigmatized by breathlessness, coughing, or their oxygen equipment, or because it drains too much energy. Once they understand that activity may do more good than harm, they may feel more able to re-engage with the outside world, relieving to some extent the tedium of chronic ill-health and reducing stress in the home.
Transcutaneous neuromuscular electrical stimulation (NMES) leads to passive exercise by electrical stimulation of muscle groups, such as the quadriceps. There is consistent evidence in patients with COPD that it can increase muscle strength and exercise capacity, and reduce dyspnoea during activities of daily living.4 Research evaluating the role of NMES in palliation of breathlessness in advanced cancer is currently being undertaken.
Although not yet in widespread use, NMES has the potential to be a useful intervention in patients with far advanced disease:
• Treatment is home-based and feasible for patients who are chair-bound by severe breathlessness.
• The intervention is very well tolerated.
• Physiotherapists are generally trained in the use of NMES.
• Equipment is relatively inexpensive.
The handheld fan
• This simple, cheap, and portable piece of equipment is an immensely valuable tool in reducing breathlessness and improving self-efficacy.
• Its use is supported by evidence from healthy volunteer studies, and emerging evidence in cardiopulmonary disease.5
• It is thought that the cooling of nasal receptors and parts of the face innervated by the 2nd and 3rd branches of the trigeminal cranial nerve transmits a signal to the brainstem respiratory complex, which alters the central perception of breathlessness.
• The handheld fan is usually much preferred by patients to bedside fans, which can cause discomfort from excessive draught.
• It is easy to use even for patients with end-stage disease and, unlike oxygen, does not stigmatize its user or have any known adverse effects.
• Handheld fans with three or more rotating blades seem to be most effective.
It is important never simply to hand the fan to patients without explanation as they will tend not to believe that such an ‘everyday object’ could be helpful. Its use should always be demonstrated, and the following points can be made to enhance the psychological impact of its use.
Instructions for use of handheld fan
• Use it whenever you feel yourself becoming breathless.
• Try to adopt a comfortable position, such as sitting leaning forward slightly, and hold the fan approximately 30cm (12in) from your face.
• Aim the draught of air towards the central part of your face so that you feel it around the sides of your nose and above your top lip.
• You should feel the benefit within a few minutes.
• It will not alter the disease or the cause of breathlessness, but will shorten attacks of breathlessness.
• There is scientific evidence to support its use.
• Try to take a fan with you when you are out, and also have one in different parts of your house, so that you do not have to search for one when breathless.
• By having a way of reducing breathlessness and regaining a degree of control, you are no longer simply waiting helplessly for another breathlessness attack. This is helpful in itself.
A video demonstrating the use of the handheld fan and a patient information sheet can be accessed at http://www.cuh.org.uk/breathlessness.
• A specialist physiotherapist can analyse and suggest changes to patients’ respiratory patterns, and recommend more comfortable positions for breathing and for recovering from episodes of breathlessness.
• All clinicians helping breathless patients need to be able to demonstrate abdominal breathing, although a physiotherapist or occupational therapist may do this more skilfully than others.
• Techniques need to be practised to have maximum impact. Practice during pulmonary rehabilitation or hospice day therapy can be helpful.
Instructions to reduce respiratory rate and prolong expiration
• Position yourself comfortably. Relax your body and mind.
• Inhale deeply and smoothly for four units of time. Fill your lungs completely, and feel your abdomen distend.
• Hold your breath for a count of two units of time and then exhale for a count of seven.
• Concentrate on a smooth (not ‘snatched’) in-breath, and a long and relaxed out-breath. Focus on the out breath.
Some patients find visualization helpful. Consider visualizing blowing into a balloon, the balloon steadily expanding on breathing out, and sucking in on breathing in. Alternatively, imagine breathing in ‘good things’ and breathing out the ‘bad or harmful things’ from the body.
• Sit in your most comfortable position, and put one hand on your chest and one on your stomach.
• Slowly inhale through your nose or through pursed lips. As you inhale, feel your stomach expand with your hand.
• Slowly exhale through pursed lips to regulate the release of air.
• Rest and repeat.
There are other breathing techniques that may be useful, including positions to adopt that improve the mechanical efficiency of breathlessness (such as sitting up, leaning forward slightly). Patients must have an individual assessment from an experienced respiratory physiotherapist to gain maximum benefit. Further information is available on the Breathlessness Intervention Service website (http://www.cuh.org.uk/breathlessness) and in the associated Breathlessness Manual.6
Many breathless patients continue to expect to achieve as much as they could before they were ill and at the same rate. Many will admit to feeling impatient, frustrated, and angry at the restrictions imposed by the illness and express disbelief at the degree to which their daily activities are limited.
Occupational therapists are particularly helpful in helping patients pace their activities and conserve energy for more enjoyable pursuits. They may also be able to recommend useful equipment. Walking aids, for example, have been shown to reduce the impact of breathlessness4.
The following advice and guidance can be helpful for patients:
• It is necessary to accept the reality of the illness (‘Yes, this is happening. Yes, people can sometimes feel breathless merely on dressing.’).
• Adopting a slower pace can sometimes allow one to achieve more.
• Try to rest between periods of activity.
• Spread out activities over a week rather than over a day.
• It is important to try to continue being active, even in the face of discouragement.
• It may be necessary to ask for help or support, such as using a wheelchair at social events or hiring a hotel room rather than travelling to an event on the day.
• Early and detailed planning of ambitious social outings can be very helpful.
• Energy can be considered to be contained in an energy tank rather like a petrol tank; it is helpful to be reminded not to run ‘on empty’.
Anxiety increases breathlessness, which in turn contributes to the anxiety, leading to a deteriorating vicious cycle. Anxiety associated with chronic intractable breathlessness appears to be even more common than depression, and possibly more long lasting.
Anxiety reduction techniques are a skill that can help with many of the vicissitudes of chronic, advancing illness. However, learning them is time-consuming and requires commitment. They should be taught and practised as early as possible in the course of respiratory disease, as
learning new techniques becomes increasingly difficult with advancing ill-health. The technique should be chosen for and tailored to the individual patient. This may take some trial and error. The range of techniques includes:
• progressive muscular relaxation
• visualization or guided imagery
• cognitive behavioural therapy (CBT)
• breathing pattern recognition and modification
• distraction e.g. by music
Some techniques are particularly useful at the time of a breathless attack (e.g. visualization, CBT), and others are of value in reducing background levels of stress and anxiety (e.g. yoga, mindfulness). A practical approach to some of these techniques is contained in the box on [link].
Ritual for crises
One of the most important aspects of caring for a breathless patient is to listen to exactly what the patient is experiencing when breathless. Talking through typical episodes from inception to resolution can reveal unhelpful thoughts or ideas that may be exacerbating the anxiety associated with breathlessness. Carers should be involved in this process as it is natural to feel particularly helpless and frightened watching a family member suffering with breathlessness. Some report literally ‘not knowing what to do’ when their loved one becomes breathless.
Designing a ‘ritual for crises’ may help to avert out of hours hospital admission. It may encompass such very simple ideas as ‘When you become breathless, sit down. Your wife can give you the fan and switch it on, and you may find it helpful if she puts her hand on your arm.’
Patients and carers should be taught how to detect exacerbations early. Reinforcing or ‘role playing’ these scenarios can help prevent a crisis developing.
NIV is most commonly used to increase survival and palliate symptoms in patients with acute, potentially reversible respiratory failure (e.g. infective exacerbation of COPD) and in those with respiratory failure due to neuromuscular or chest wall conditions.
It is, however, increasingly being recognized as a potential method for palliating breathlessness, particularly in patients with intolerable adverse effects from drugs such as opioids.7 Use of NIV is described in more detail in Chapter 2 [link]–[link], including its role in ‘buying time’ at the very end of life, when a patient wishes to achieve a specific goal.
The patient actively tenses and relaxes specific parts of the body in a progressive order.
Start with tensing and relaxing the whole body, and then move progressively through the body, for example, jaw (clench), tongue (stick out), shoulders (hunched), hands (fists) etc.
It is helpful if the clinician guides the patient through the exercise, pacing and modelling the technique.
‘I wonder if you can lift up your shoulders, lift them up to your ears, hold them there, squeeze them tightly, and then let them drop down, just let them flop… then once more hunch them up, hold it… then let them go, feel all the tight tension in your shoulders just drain away… Now, clench your hands into fists…’ and so on.
One form of imagery is for a patient, relaxed and with their eyes shut, to be guided to think of a place or an activity where he or she has felt safe and happy in the past.
The patient is encouraged to recall the details of the scene, using all five senses: sight, sound, smell, feel, and taste.
The clinician may choose to elaborate on the description of the patient, contributing to the experience of distraction and relaxation.
‘You can feel the granules of sand under your feet as you step steadily along the beach… the ripples of water sooth your feet and sound musical and you can feel the sun making your skin warm… the smell of clean sea air is refreshing you… you feel free…’ and so on.
Principles of cognitive behavioural therapy
Formal CBT can only be provided by a qualified practitioner. However, all professionals can encourage patients to describe their thoughts, feelings, behaviours, and physical symptoms and explore how they may be linked.
Revealing a vicious cycle can be a powerful way of explaining problems to patients, for example, how fear of dying can lead to anxiety, which worsens breathlessness, making the fear of dying even greater.
Writing down pertinent thoughts, feelings etc. and using arrows to graphically demonstrate the links can be helpful, both through acknowledging their existence and showing their interrelationships.
Mindfulness and mindful breathing
Mindfulness is derived from the Buddhist practice of meditation. With practice, individuals learn to develop a non-judging awareness and acceptance of the present moment. It can reduce rumination on the past and anxiety about the future.
Mindful breathing focuses on the present physical sensation of breathing, helping patients to live with and accept their experience of breathing, rather than fearing or avoiding thinking about it.
Following a CD describing mindful techniques can be very helpful for patients.
1. Evans R, Singh S, Collier R, Williams JE, Morgan MD (2009) Pulmonary rehabilitation is successful for COPD irrespective of MRC dyspnoea grade. Respir Med; 103 (7): 1070–1075.
2. Martin U, Hincapie L, Nimchuk M et al. (2005) Impact of whole-body rehabilitation in patients receiving chronic mechanical ventilation. Crit Care Med; 33 (10): 2259–2265.
3. Sachs S, Weinberg R (2009) Pulmonary rehabilitation for dyspnoea in the palliative care setting. Curr Opinion Supp Pall Care; 3: 112–119.
4. Bausewein C, Booth S, Gysels M, Higginson I. Non-pharmacological interventions for breathlessnesss in advanced stages of malignant and non-malignant disease. Cochrane Database SystRev 2008 Issue 2 CD005623.
5. Galbraith S, Fagan P, Perkins P, Lynch A, Booth S (2010) Does the use of a handheld fan improve chronic dypsnoea? A randomized controlled cross-over trial. J Pain Sy Manage; 39: 831–838.
6. Booth S, Burkin J, Moffat C (2010) Cambridge Breathlessness Intervention Service Manual. Cambridge University Hospitals NHS Foundation Trust www.cuh.org.uk/breathlessness
Long-term oxygen therapy (LTOT)
Use of continuous oxygen for 15 or more hours each 24 hours is well established in severely hypoxic patients with COPD (see Chapter 2 [link]–[link]). Although LTOT is used primarily because of its benefit on survival, there is also evidence that it improves quality of life and reduces severity of breathlessness.
The prescription of oxygen concentrators for long-term use is now undertaken by specialist respiratory clinics in the UK and follows strict guidelines.
Short-burst oxygen therapy (SBOT)
The role of oxygen in the palliation of breathlessness is still controversial in both malignant and non-malignant disease. Current controlled trial evidence suggests the following:
• A draught of cool air is helpful in reducing breathlessness.
• Oxygen tends to be no more effective than a flow of cool air, irrespective of a patient's initial level of hypoxaemia or nonmoxaemia.
• A few patients may benefit from SBOT, particularly when used during exertion (ambulatory oxygen).
• There is no way of predicting, without an individual clinical assessment, which patients will gain benefit.
It is now standard specialist palliative care practice to offer a fan first (see [link]). Oxygen is only prescribed when there are other indicators, such as significant desaturation on exercise. An individual clinical assessment is always necessary to determine which patients will benefit from oxygen.
The burdens of oxygen therapy are considerable:
• A degree of psychological dependence is inevitable, and some patients become acutely anxious during even a short interruption in oxygen supply.
• Cumbersome and heavy equipment can restrict movement, activities within the home, and excursions outside the home.
• An oxygen mask can impair communication between a patient and their family.
• Some patients feel a sense of social stigma and embarrassment, further compounding social isolation.
• It is both expensive and highly combustible.
There is some evidence that Heliox 28 (72% helium and 28% oxygen) may help reduce dyspnoea and increase oxygenation in conditions where there is increased work of breathing, such as with COPD or asthma.
One small feasibility trial compared Heliox with oxygen-enriched air in 12 patients with lung cancer, and showed an improvement in breathlessness on exertion and exercise tolerance.1 However, stronger evidence is needed before Heliox can be recommended as standard treatment for the palliation of breathlessness. Furthermore, the logistical challenges of administration, including access to gas and equipment as well as significant costs, would make routine use in end of life care difficult.
Although once feared as a cause of respiratory depression, oral morphine is the mainstay of pharmacological treatment for intractable breathlessness. Its use is supported by the greatest weight of evidence and extensive clinical experience.
• Opioids seem to give approximately a 20% improvement in breathlessness from baseline in those whom they help.
• They seem to work best in the most severely breathless patients.
• There is still uncertainty in a number of areas including the most effective opioid, route, and formulation (e.g. immediate or modified release).
• Oral morphine is the opioid most widely used for breathlessness. Fentanyl may have a role because of its rapid onset of action (for example, sublingual or intranasal). However, its use is not recommended without specialist advice and probably inpatient observation, in those unused to prescribing it.
Commencing opioids in breathless patients
For opioid naıïve patients in the community, opioids should be commenced at a very low dose, morphine sulphate immediate release (IR) 0.5–1.5mg bd, with the same dose as required as a ‘top up’. This can be increased each week by 1mg per day, until a daily dose of 10mg has been reached. At this point the patient can be converted to morphine sulphate modified release (MR) 5mg bd.
The use of low doses and slow titration makes this regimen suitable for patients with COPD. Patients with interstitial lung disease (ILD) may particularly benefit from opioids, as they often have stimulation of their respiratory centres (with hypoxaemia but rarely hypercapnia). Again, opioids can be commenced in the community using this regimen.
Patients already on opioids (for example with cancer and pain) can use the same ‘as required’ dose for breathlessness as they do for pain. The regular opioid dose may need to increase. The choice of timing of ‘as required’ doses can give patients a sense of control and self-efficacy, and contribute to the benefit experienced.
All patients should be reassessed at weekly intervals, in person or by telephone. Simple quantitative measures of effectiveness can be used even during telephone consultations, for example, a numerical rating scale (NRS) with anchors such as ‘no breathlessness’ and ‘breathlessness as bad as can be’, or a BORG scale of ‘average breathlessness over last week’.
High-risk patients, such as those with previous episodes of CO2 retention during exacerbations or with type II respiratory failure, should generally be admitted to the local hospice or respiratory unit for observation, allowing a more rapid titration period.
Concerns about opioids
• Patients should be warned about adverse effects. Nausea tends to settle in a few days and can be treated with anti-emetics. All patients on
• Patients with non-malignant disease may fear that prescription of opioids implies the presence of cancer. Both patients and relatives may need specific reassurance.
• Clinicians tend to be concerned about the possibility of respiratory depression. There has been no evidence to date that clinically significant respiratory depression does occur, and oral opioids started at a low dose and slowly titrated are very safe. Patients can be alerted to the potential risk and advised that respiratory depression would be preceded by sedation (with slow titration), providing a ‘built-in’ safety mechanism. Patients should be told not to take the next opioid dose if excessively sleepy, and to seek medical advice. Written information for patients and close communication with the community team can both be very helpful.
Benzodiazepines (BDZ) are regularly prescribed in breathless patients with advanced disease. The theoretical basis for their use is clear; they are anxiolytic drugs, and anxiety can precipitate or exacerbate breathlessness. However, there is little research evidence to support their use, and rigorous controlled trials are urgently needed.1
BDZ are rarely used in patients with non-malignant disease and a potentially long prognosis because of their potential to create dependency. Non-pharmacological interventions for breathlessness are generally favoured. However, patients with cancer frequently use BDZ, as the risk of dependency is of less concern.
Lorazepam (sublingual) and midazolam (subcutaneous) are the BDZ most commonly used in this context. Diazepam can also be used, but it has a particularly long half-life with active metabolites that persist for even longer, which can lead to accumulation and prolonged sedation. Please see Chapter 6 [link] for further details of these drugs.
There is a small amount of evidence that buspirone may reduce anxiety and breathlessness in patients with COPD. However, its usefulness is limited by the fact that it takes 2–4 weeks to work. See Chapter 6 [link] for further details.
Whereas in the UK BDZ tend to be used to supplement opioids, in Canada and the USA the phenothiazine, levomepromazine, is more commonly used for the pharmacological treatment of anxiety. Levomepromazine has a broad spectrum of receptor activity, which leads to a range of benefits (including anti-emetic effect) as well as adverse effects (including sedation, dysphoria, and hypotension). There is little published evidence to support the use of phenothiazines in breathlessness. The major tranquillizer effect suggests that it would be most useful in patients experiencing real terror associated with breathlessness.
Depression is prevalent in advanced respiratory disease, and is frequently under-diagnosed (see Chapter 6 [link]–[link]). It is well recognized that mood states and emotional factors influence the central perception of breathlessness, and there are some data to suggest that there are serotonergic pathways in the brainstem respiratory centre.
Although there is very limited evidence for the efficacy of anti-depressants in breathlessness, the use of anti-depressants to improve low mood may be helpful for breathlessness because of the significant impact of mood on symptom perception.
• Antidepressants tend to take at least 2 weeks to develop a therapeutic effect. They would be of very little value in escalating breathlessness near the very end of life.
• Selective serotonin reuptake inhibitors are the most commonly used first-line anti-depressant e.g. citalopram 10–20mg od. Fluoxetine should be avoided as it may increase anxiety.
• Mirtazapine, a centrally active presynaptic α2 adrenergic receptor antagonist, is being increasingly used in patients with advanced disease. As well as its antidepressant effect, it has a range of benefits including reduction in anxiety, improvement of sleep, and treatment of neuropathic pain. Start with a dose of 15mg at night (this dose has an anxiolytic effect equivalent to 15mg diazepam).
Several small studies have investigated the possible effectiveness of inhaled furosemide in dyspnoea after anecdotal reports of remarkable relief in some patients. There is not enough evidence to recommend its use outside clinical trials or specialist centres at present.
Intractable cough is a challenging symptom that is not easily treated. It can cause many problems including sleep disturbance, embarrassment, precipitation of episodes of breathlessness, muscle strain, rib fractures, urinary incontinence, vomiting, and retinal haemorrhage. It has a significantly negative impact on quality of life.
Chronic cough is highly prevalent in patients with advanced respiratory disease, and rates of up to 80% have been reported, both in patients with COPD and in those with lung cancer.
In COPD, there is evidence that cough is triggered by airway inflammation. Some inflammatory mediators, such as prostaglandins, are known to be tussive agents. Mucus hypersecretion and impaired ciliary clearance also contribute, particularly in smokers. Smoking cessation reduces the prevalence of cough in patients with COPD significantly.
Malignant lung disease may trigger cough through airway infiltration, distortion, or obstruction.
Co-morbidities frequently contribute to cough:
• Post-nasal drip.
• Chest infection/bronchiectasis.
• Gastro-oesophageal reflux.
• Cardiac failure.
• Vocal cord paralysis (malignant recurrent laryngeal nerve involvement).
Medical intervention can also cause cough, in particular ACE inhibitors, β-blockers, methotrexate, and radiotherapy-induced pneumonitis or fibrosis.
The following key questions must be answered:
• What is causing the cough?
• Are any of the potential causes reversible?
• Is the cough ‘wet’ or ‘dry’?
Correct reversible causes
This is the most effective treatment of cough. Treatment of underlying infection is vital. Sub-clinical gastro-oesophageal reflux disease (GORD) is common. Simple anti-reflux measures, such as wearing loose clothing and avoiding precipitating foods, and a trial of acid suppression (e.g. proton pump inhibitor therapy) should be considered.
Keeping the throat moist and coated with sugar (for example with sweets or hot sugary drinks) may reduce the hyper-reflexivity of the cough reflex. Simple linctus (e.g. 5mL tds), a soothing demulcent, can also be used. Although there is sparse research evidence to support their use, these simple interventions do appear to help.
Expectoration of sputum should be encouraged in patients with a wet cough. Physiotherapy, nebulized saline, or steam inhalation can all be helpful. Patients can be taught to ‘huff’, forcing expiration from a low–medium lung volume, to help clear secretions. A mucolytic drug that can reduce the viscosity of secretions, such as carbocysteine 750mg tds, can benefit some patients.
The only time a wet cough should be suppressed is in an imminently dying patient, where the cough is too weak to expectorate sputum (see below).
A dry cough serves no physiological purpose and can be suppressed. Opioids can provide centrally acting cough suppression and appear to be the most effective intervention. Use can be limited by adverse effects, and opioids may be of particular value in breathless patients who would anyway benefit from opioids. Examples of drugs and doses include:
• codeine linctus 15mg (5mL) tds to qds
• morphine sulphate IR solution 2.5mg qds and prn.
There is evidence of some benefit from inhaled sodium cromoglicate from one small trial in patients with lung cancer. Further definitive studies are needed.
• Sodium cromoglicate 10mg qds (inhaled via spacer).
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