Abstract
Fatigue is the most common symptom experienced by patients with chronic progressive illnesses such as cancer, chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS). While it is normal to feel fatigue when the body or mind has been exerted, pathological fatigue is pervasive, may occur with little or no exertion and may not be relieved by sleep or rest. Fatigue has both physical and psychological components. It may manifest physically as a feeling of weakness or psychologically as mental tiredness, lack of motivation and reduced concentration.
The GP curriculum and lethargy in palliative care
The ability to function as both leader and member of cancer care teams, as required
Knowledge of the principles of palliative care and how it applies to non-cancer illnesses such as cardiovascular, neurological, respiratory and infectious diseases
Knowledge of the management of hypercalcaemia (palliative)
Knowledge of their own personal attitudes and experiences that can affect their attitude towards patients with cancer or who are dying
The ability to define and apply evidence-based care in patients with cancer
The ability to manage cancer and non-cancer symptomatology in the same patient
The ability to attend to the full range of physical, social and spiritual needs of the patient and carer(s)
The ability to communicate effectively with the patient and carer(s) regarding difficult information about the disease, its treatment or its prognosis
This article aims to give you an understanding of how to manage fatigue in palliative care. While concentrating on cancer-related fatigue (CRF), the principles may be used in managing fatigue from any chronic progressive illness.
Definitions
The proposed International Classification of Disease (ICD-10) criteria for diagnosis of CRF appear in Box 1 (Cella et al., 1998). These criteria will appear in the next revision of ICD-10 due for release in 2010. These criteria may also be used to describe fatigue due to most chronic progressive illnesses if item C is ignored.
ICD-10 criteria for diagnosis of CRF
Six or more of the following 11 symptoms, with one being ‘significant fatigue’, have been present daily or nearly daily over a 2 week period during the past month:
Significant fatigue, diminished energy or increased need to rest, disproportionate to a recent change in activity level
Generalized weakness or limb heaviness
Diminished concentration or attention
Reduced motivation or interest to engage in usual activities
Insomnia or hypersomnia
Experience of sleep as unrefreshing or non-restorative
Perceived need to struggle to overcome inactivity
Marked emotional reactivity, for example, sadness, frustration, irritability to feeling fatigued
Difficulty completing daily tasks due to fatigue
Perceived problems with short-term memory
Post-exertional malaise lasting several hours
The symptoms cause clinically significant distress or impairment in important areas of functioning
The symptoms result from cancer or cancer treatment
The symptoms are not primarily due to co-morbid psychiatric disorders
As attested by the numerous assessment scales and definitions available, there is often confusion surrounding the definition of fatigue. I prefer the European Association of Palliative Care definition of fatigue: ‘Fatigue is a subjective feeling of tiredness, weakness or lack of energy’ (Radbruch et al., 2008).
The World Health Organization (WHO) definition of palliative care appears in Box 2. Palliative care is commonly said to start when the aim of treatment is no longer curative. Good palliative care relies on the whole primary team working together, often with the support of the hospice-based palliative care team. It is also important to adopt a patient-centred holistic approach (NICE, 2004).
WHO definition of palliative care
Palliative care is an approach that improves the quality of life of patients and their families facing the problem 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.
A complex problem
CRF is often multifactorial in origin (Fig. 1). Its prevalence varies but may be as high as 84% (Radbruch et al., 2008). Cytokine release, anorexia and cachexia, metabolic disturbance, hypoxia and poor tissue perfusion may all lead to fatigue. Cancer treatment often has fatigue as an unwanted side effect. Examples are chemotherapy and opioid analgesia. The causes of fatigue may vary depending on what chronic illness the patient is suffering from, but the principles of management remain the same.
Causes of fatigue.
Anorexia—cachexia syndrome
The anorexia—cachexia syndrome may be found in cancer and many chronic diseases such as rheumatoid arthritis, CHF and COPD. Anorexia is loss of appetite, and cachexia is an involuntary loss of more than 10% of pre-morbid weight. Lean muscle mass and fat are not replenished, therefore patients lose weight, become malnourished and may ultimately die. It may be the sole cause of death in up to 20% of patients with cancer. This syndrome is closely linked with fatigue. The pathophysiology is summarized in Box 3 (Del Fabbro et al., 2006).
Anorexia—cachexia syndrome
Tumour by-products such as proteolysis-inducing factor produced
Host cytokines stimulated: interleukin 1+ 6, tumour necrosis factor and interferon
Liver produces cytokines in preference to protein synthesis and lipid storage
Neuroendocrine malfunction further increases anorexia
Muscles waste away as no new protein. Fat stores are used and no new ones laid down
Not just in cancer but also in CHF, COPD, rheumatoid arthritis and other chronic inflammatory states
Nutritional support unable to reverse the process
History
It is important to appraise what the patient and family already know about the situation. The doctor must find out what they know about the likely course of the illness, including how rapidly the patient's condition may deteriorate. Asking these difficult questions can help forge the therapeutic relationship between physician, patient and family. Education about terminal illness is recommended by the National Comprehensive Cancer Network guidelines (NCCN, 2009) as a way of reducing anxiety and distress during cancer treatment and palliative care. The patient with terminal illness may be glad to talk about issues around death and dying. The discomfort felt by physicians discussing these issues is often due to their own feelings, rather than those of the patient.
There is evidence that fatigue is under-recognized by physicians treating cancer. Box 4 shows some barriers to diagnosing fatigue in patients receiving palliative care (Passik et al., 2002).
Ten patient concerns about CRF
Patient perception that the fatigue is not treatable
Patient fear that fatigue is an ominous sign of disease progression
Desire to be a ‘good patient’ and not bother the doctor or other health professional
Fear of distracting doctor from primary cancer treatment
Lack of patient concern over fatigue as a symptom
Fear of stigma and association with depression
Desire to limit medications for fear of side effects, drug interactions and addiction
Preference for non-medication interventions
Fear of jeopardizing cancer treatment
Lack of physician initiated discussion
The history must concentrate on the patient's perception of the problem and how it affects his or her activities of daily living. Attention should be paid to the onset, severity and duration of symptoms. It is worth noting that perception of fatigue will change as the illness progresses. At first, fatigue that is severe enough to prevent a trip to the shops, or to take the dog for a walk, may be enough to cause distress.
A good question to start with is: ‘What do you think is wrong?’. Do not be afraid to take time to explore the patient's hopes, fears and ideas about the illness. Ask about the patient's view of the future too. Patients often associate increasing fatigue with death and dying, so may welcome the chance to talk openly about their symptoms. Suitable questions include
‘What have you been told about the illness?’
‘What do you think about the future?’
Clarify what the patient means by fatigue. Is it sleepiness, weakness, lack of motivation or breathlessness? Define it in terms of what the patient can and cannot do:
‘I'm too weak to lift my head off the pillow’
‘I'm not able to climb the stairs anymore’
‘I can just about walk to the toilet but it makes me breathless’
Several scales are available to assess quality of life and multiple symptoms in palliative care. A useful approach suggested by the NCCN (2009) is to give the fatigue a score out of 10, with 10 being the worst fatigue imaginable and zero being no fatigue. This could also be used to help record how the severity of the symptom changes over time.
A common cause of fatigue is sleep disturbance, which may be due to pain, anxiety or drug treatments. Ask about recent changes in medication, particularly analgesia. Ask about ‘as required’ medication usage. Has the patient been using too much? Have there been any recent changes? Find out about recent chemotherapy and radiotherapy, both of which can cause extreme fatigue. Are there other symptoms to guide you? Coughing foul sputum or dysuria may indicate infection. Breathlessness may indicate hypoxia or anaemia.
Finally, enquire about the patient's mental state. Depression and anxiety are common in palliative care and may present through lack of motivation, broken sleep or lack of energy. It is important to enquire about the mental well-being of the patient's family and carers, as well as their concerns about the patient.
Examination
A good history and examination should identify most common causes of fatigue. The main points are summarized in Box 5. A laboratory workup may be appropriate depending on the stage of the disease. A reasonable set of blood tests would be:
Full blood count
Ferritin
Sodium, potassium, urea and creatinine
Calcium, albumin and phosphate
Glucose
Inflammatory markers
Liver function tests
Consideration may be given to checking thyroid, testosterone and adrenal hormone levels if appropriate.
Clinical examination
Level of consciousness
Muscle wasting
Respiratory rate
Temperature, blood pressure and pulse
Pupils (pinpoint?)
Conjunctiva for anaemia
Mucous membranes for hydration
Focal signs of infection: chest, urine and pressure sores
Mobility and general function
Mood and psychological state
Management
Treatment of fatigue may be extremely difficult and requires a pragmatic and holistic approach. Reversible causes should be identified and treated. The level of fatigue should be reassessed regularly to gauge the response to treatment.
Much research has been done in treating CRF. The most recent guidelines are written by the NCCN in USA (NCCN, 2009). There has also been a Cochrane review (Cramp and Daniel, 2008).
Education
The NCCN guidelines recommend education as a mainstay of treating fatigue. It is important for patients and their carers to understand the reasons behind fatigue and to learn how to cope with worsening physical abilities. Energy conservation, sleep hygiene and the dying process are all topics that may be covered. Simply taking time to explore the patient's ideas, hopes and fears may be enough to improve perception of fatigue.
Exercise
There is lots of evidence that increasing exercise improves fatigue during cancer treatment (Cramp and Daniel, 2008). Exercise is also thought to be beneficial in COPD, CHF and MS. Exercise builds muscle mass and can lift the mood. Conservation of muscle mass is important, as once anorexia—cachexia sets in, it is difficult to reverse. Resting is counterproductive as muscles are lost and functional ability decreases, leading to a vicious circle of decline.
Practical support
In the early stages of palliative care, practical support may mean giving information on benefits and sources of support or information. Patients may need time off work while undergoing treatment. As a patient's condition progresses, his or her needs may change. This is an area where the social worker, physiotherapist, occupational therapist, community nurses and palliative care team can all work with the GP to provide a package of care tailored to the patient.
In the last weeks or days of the illness, when patients may be chair- or bed-bound, the focus shifts to energy conservation. Priorities and goals should be set to allow patients to use what energy they have effectively. Social input may be helpful to conserve energy. For example, help with washing and dressing or the provision of a commode. It is important for patients and their families to make practical plans as fatigue and dependency increase. As well as aids, adaptations and a care package, respite at the hospice or in a nursing home may be offered. It is also possible to move beds downstairs, to provide hoists, hospital beds and support for the family. This support may come from many sources, including charities such as Marie Curie and Macmillan cancer care.
Although most deaths occur in hospital or hospices, it is possible for terminal care to happen at home. The GP, community nurses, Macmillan nurses and palliative care team work together to achieve this. Coordination may be shared between the GP and palliative care team. Tools such as the Gold Standards Framework and Liverpool Care Pathway may be useful here; links are included at the end of the article.
Look for reversible causes of fatigue
If sleep is disturbed, the underlying cause must be sought: is lack of sleep resulting from pain, anxiety or perhaps medication? Normal sleep hygiene advice should be given. Insomnia may be managed by the use of a hypnotic, for example, zopiclone or temazepam. This should be balanced against the risk of fatigue as a side effect of the medication. A sedating antidepressant such as mirtazapine may be tried if there is the possibility of co-morbid depression. Often the sedating properties of anti-emetics such as haloperidol and levomepromazine are also used to aid sleep. When oral medication is not tolerated any more, it is still possible to give subcutaneous sedation via a syringe driver.
Biochemical imbalance, for example, hyponatraemia or hypercalcaemia, and anaemia are other possible causes of fatigue. Correcting biochemical imbalance and anaemia can be a quick and easy way to improve fatigue. Some common abnormalities and their treatments are shown in Table 1.
Common biochemical causes of fatigue
Many medications in palliative care may cause sedation. Sedation is often desirable, and medicines can fulfil two roles at once. An example is levomepromazine, a potent anti-emetic and sedative. When over-sedation is an issue, a balancing act must take place between symptom control and sedation. This must be discussed with the patient, and, if appropriate with the patient's family. A compromise can be negotiated, in line with the patient's hopes, fears and expectations regarding the illness. Good communication between the GP, community nurses and palliative care team is essential. This may be facilitated by a patient-held record.
Treatment of depression can often improve the perception of fatigue and increase motivation. Depression is common in all chronic disease states. It is, therefore, common during the palliative care of these diseases. A recent Bandolier review suggests that the exact prevalence of depression is uncertain and changes depending on how it is measured. The prevalence was as broad as 10–60% in this review (Bandolier 102). It is possible that depression, much the same as fatigue, is under-diagnosed in palliative care. Fatigue and depression may be difficult to differentiate. It is reasonable to initiate a trial treatment with an antidepressant medication as it can always be discontinued if there is no response after a few weeks.
Adequate nutrition is important to make sure the patient's physical condition is as good as possible before the patient deteriorates and develops the anorexia—cachexia syndrome. In the terminal stages of illness, food is taken purely for pleasure and makes little difference to the outcome.
Medical treatment
Many treatments may be tried; however, they should not be continued longer than necessary if they are found to be ineffective. Once the terminal phase of the illness has been reached, unnecessary treatments and investigations should be avoided. Drugs that may be tried include:
Corticosteroids: Such as dexamethasone. These have some benefit in treating fatigue in patients with advanced cancer. A short trial, for a week or two, may increase appetite and general well-being. Use is limited by side effects such as oedema, dyspepsia and insomnia.
Steroid hormones: There is no conclusive evidence that progesterone is beneficial, but it may be tried to stimulate appetite.
Methylphenidate: The Cochrane collaboration looked at methylphenidate as a treatment in patients undergoing chemotherapy. They found that it gave a significant improvement in fatigue. It is currently used rarely in selected palliative care cases, when other interventions have failed (Minton et al., 2008).
Erythropoietin, iron and blood transfusion
Blood loss, direct effects of the tumour, chemotherapy and radiotherapy may all cause anaemia. If low iron levels are found, oral or intravenous iron may be enough to return the heamoglobin levels to normal. Chronic renal failure may lead to reduced erythropoietin production. Chronic inflammation can also cause anaemia, for example, in rheumatoid arthritis.
The Cochrane collaboration found erythropoietin and darbopoietin both improved fatigue in anaemic patients with cancer (Minton et al., 2008). In palliative care, treatment should be guided by how symptomatic the patient is rather than absolute values. It is not uncommon to see patients tolerate extremely low levels of haemoglobin with minimal symptoms. This occurs when the drop in haemoglobin is gradual. Patients with bone marrow failure, for example, from myelofibrosis, may live for many years receiving ‘top-up’ blood transfusions. During radiotherapy and chemotherapy, it is normal practice to try and maintain a reasonable haemoglobin level to reduce patient suffering and speed recovery.
Psychological treatment
There is no body of evidence that supports routine use of cognitive behavioural therapy (CBT) or relaxation therapy in the treatment of fatigue or pain in palliative care. They may, however, be useful where anxiety or depression is present.
Complementary therapy
There is no evidence that any complementary therapy decreases fatigue, although ‘touch treatments’ such as aromatherapy may increase general well-being. The GP should work with the patient and family to make sure treatments offered are tailored to their health beliefs.
Spiritual support
As patients approach death, psychological and emotional fatigue may be most prominent. At this time, spiritual support from an appropriate person may be more important than any other treatment. Spirituality is not synonymous with religion or faith and may take many forms. This may be as simple as having family close or there may be faith-specific rituals to observe.
Summary
Fatigue is a common cause of morbidity in patients with chronic progressive diseases. It is often multifactorial and under-diagnosed. The aim of management is to identify treatable causes and optimize the patient's condition.
Key points
Fatigue is extremely common in the palliative care of many chronic progressive illnesses, although under-diagnosed
It has physical and psychological components
Search hard for a treatable cause; for example, undiagnosed depression
Review the medication for iatrogenic causes
Muscle mass may be preserved by optimal nutrition and exercise
Anaemia may respond to iron, erythropoietin or transfusion
Education and practical support are extremely important for both the carers and the patient
A trial of corticosteroid is often used in advanced cancer
Methylphenidate may be initiated by palliative care specialists in selected cases