Definition and Prevalence
Fatigue, defined as a persistent sense of tiredness which is not relieved by sleep or rest, is an extremely common problem amongst palliative care patients and causes significant distress. [1,10,13-16] A systematic review of symptoms in adult and paediatric patients with advanced cancer indicated that over half experienced fatigue. [10,17] The prevalence of fatigue is likely to be similar or indeed higher in patients with other life-limiting diseases, including HIV-AIDS, heart disease, chronic obstructive pulmonary disease, Parkinson’s disease and renal disease. [15,16,18,19] Careful assessment is needed to ensure appropriate differentiation of fatigue and other conditions such as depression.
Factors which may contribute to fatigue in palliative care patients, some of which can be treated or modified, include:
- Cachexia and nutritional deficiencies
- Hypothyroidism, hypogonadism, adrenal insufficiency
- Metabolic disorders
- Reduced activity and deconditioning
- Depression or emotional distress
- Chemotherapy and radiotherapy
- Adverse effects of medications.
It is likely that the presence and intensity of fatigue may increase as patients’ disease progresses. The negative impact on quality of life of patients and their caregivers can be substantial.  While fatigue is distressing and common in palliative care patients it is often inadequately assessed. [1-3] Cultural issues are important in understanding the significance of fatigue for a particular person. 
Simple self-report scales should be used to routinely assess fatigue.  In a recent review of available tools used to measure fatigue in cancer patients only four tools met the authors quality standards.  The Brief Fatigue Inventory (BFI), the Functional Assessment of Cancer Therapy (FACT-F), the Multidimensional Fatigue Inventory 20 (MFI-20) and the Piper Fatigue Scale (PFS) were found to have adequate psychometric properties. These tools have not been validated in the palliative care context but may be useful. Fatigue is one of the symptoms screened for by the Symptom Assessment Scale in the PCOC dataset, which is used by many palliative care services in Australia. It is also screened in the Edmonton Symptom Assessment Scale, which has been validated in the palliative care setting.  Validated assessment tools are available for adolescents. Younger children can be asked if they are 'tired or not tired'. [4,5]
Regular assessment, attention to reversible factors, and multidisciplinary approaches to treating fatigue are essential. [2,3,5] Interventions involving physical exercise (walking and multimodal exercise) [2,6] and psychosocial interventions (eg. stress management, counselling, and restorative approaches) show definite promise for cancer related fatigue [7,8] although studies of physical activity involving a defined palliative care population have not been conclusive. [9-11] Whilst guidelines for the management of cancer related fatigue are available  these do not specifically address the needs of palliative care patients, or those with non-malignant conditions. 
- Fatigue should be recognised as a major problem for palliative care patients and should therefore be routinely asked about. Fatigue is one of the symptoms screened for by the Symptom Assessment Scale in the PCOC dataset, which is used by many palliative care services in Australia. Other more detailed assessment tools are also available. [21,22]
- Validated assessment tools for measuring fatigue in cancer patients are available and may be useful in other patient groups.  Younger children can be asked if they are 'tired or not tired'. [4,5]
- A multidisciplinary approach allows clinicians to identify and manage the full range of issues for patients with fatigue. Strategies  may include:
- Activity enhancement / exercise
- Energy conservation and provision of aids and equipment
- Nutritional assessment and support
- Psychosocial support
- Distraction and concentration techniques
- Addressing sleeping problems.
- Exercise may benefit all patients and improve fatigue, but individual exercise programs are seen as the most beneficial. [23,24]
- There is little evidence from placebo control studies to guide pharmacological management of fatigue. Low dose methylphenidate appears to be potentially effective, based on small studies. Treatment of depression with antidepressants has not so far been shown to improve fatigue in randomised control trials. [1,25,26]
- Pharmacological approaches to managing fatigue are evolving. Of the psychostimulant agents, methylphenidate has been shown to be beneficial in small studies, [27-29] whilst modafinil shows promise. Progestational steroids  and donepezil  have so far not shown any benefit in trials. There is limited evidence to base recommendations on. 
- Erythropoiesis stimulating agents (epoetin alfa and darbepoetin alfa) have been shown to improve cancer related fatigue in patients with chemotherapy-induced anaemia.  However, recent safety concerns suggest they should now only be offered to patients during myelosuppressive chemotherapy where the goal of treatment is not cure. [26,30]
- Research on management of this symptom has mainly studied cancer related fatigue and HIV / AIDS. There is little specific evidence regarding the management of fatigue in other advanced non-malignant conditions. [16,19]
- Fatigue may be protective of the individual who is very close to death. Active treatment of fatigue, and encouragement to increase physical activity, are most often inappropriate at that point. 
- There is little evidence for the use of psychosocial interventions to manage fatigue. 
- Fatigue in palliative care patients has been identified as an important symptom for research.  The experience of fatigue amongst people with advanced progressive diseases may be different to cancer treatment related fatigue. Evidence from studies of cancer treatment related fatigue should be assessed for its relevance to individuals in palliative care.
- Cultural issues in assessment and treatment of fatigue have been recognised as important, with many European languages having no word for fatigue.  Other issues being studied include: mechanisms and causes, prevalence patterns, and outcomes of cancer related fatigue, and the social and economic impact on both patients and caregivers. There appears to be an overlap between fatigue and problems of psychological distress, reduced functional ability and pain; the causal links between these problems have not yet been clarified. 
- Research is required to establish validated screening and assessment tools of fatigue in palliative care.
- Randomised trials of methylphenidate are currently underway to identify those patients who are most likely to benefit, and to clarify the benefit versus the burden of treatment. Bupropion, androgen replacement therapy and L-carnitine  are also being studied as potential pharmacological agents for treating fatigue in palliative care patients and show promise.
- Trials are underway to clarify the risks associated with use of erythropoiesis stimulating agents (epoetin alfa and darbepoetin alfa) in cancer related fatigue associated with anaemia.
- New research on the benefits of melatonin in managing fatigue have not established a positive effect.