composed of easy fatigue, weakness, lack of energy, anorexia, early satiety, weight loss, dry mouth, and taste changes [285]. Fatigue has often been reported to be the symptom that causes patients the most distress [286]. Prevalence A sense of fatigue and weakness is one of the most common symptoms near the end of life, and patients often consider this symptom to be more troublesome than pain [287; 288]. The prevalence of fatigue has been reported to range from 12% to 97% of patients with life-limiting diseases, and the prevalence is fairly consistent across disease settings [211; 279]. Cancer-related concurrent syndromes and comorbidities such as anaemia, cachexia, fever, infections or metabolic disorders as well as sedative drugs for symptom control can produce secondary fatigue. reported by the patient concomitantly. 52 As with depression, these symptoms represent distinct entities and efforts should be made to assess and treat them separately. However, it has been suggested that investigation of symptom clusters involving fatigue instead of fatigue as an isolated symptom may be the next step in research in symptom control. 53,54 Pathophysiology of fatigue Primary fatigue is hypothesized to be related to the tumour itself. This may either be through peripheral mechanisms such as energy depletion or by central mechanisms such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis or serotonin metabolism. These mechanisms may ulti- mately be related to high levels of cytokines.
Prevention Ensuring adequate management of symptoms related to fatigue may help in preventing the condition. Clinicians should advise the patient to conserve energy as much as possible, to follow a normal sleep cycle, and to engage in aerobic exercise [108; 278; 279; 286]. In advanced cancer, many factors are likely to contribute to fatigue. The relative contribution of each cause will fluctuate throughout the disease trajectory, thus challenging too simplistic primary and secondary concepts in clinical practice. In a quantitative review of 18 studies with 1037 participants, significant positive correlations were found between fatigue and circulating levels of inflammatory markers. However, 31 out of a total of 58 correlation estimates in these studies were not significant. 56
Palliative Care and Pain Management at the End of Life ___________________________________________
Etiology Among the most common contributors to fatigue in people with advanced life-limiting diseases are medications, anemia, dehydration, direct tumor effects on energy consumption and supply, infection, metabolic disturbances, fluid and electrolyte imbalance, dyspnea, sleep apnea, depression, and loss of skel- etal muscle due to cachexia [108; 278; 279]. Assessment Assessing fatigue can be a challenge, but as with pain, the patient’s report of how he or she is feeling is the gold standard in the assessment. For patients who speak a language other than English, questions about fatigue should include such words and phrases as “tired,” “weak,” and “lack of energy,” as the word “fatigue” may translate differently in some languages [279]. Several tools are available to assess fatigue, but because it usually occurs in a cluster of symptoms, many of these tools are multidimensional instruments, often involving several questions, which can be impractical [279; 284]. In assessing patients for fatigue, the clinician should ask such questions as “Do you feel unusually tired or weak?” or “How tired/weak are you?” [279]. ALGORITHM FOR THE DIAGNOSIS OF FATIGUE IN PATIENTS RECEIVING PALLIATIVE CARE The pathophysiology of cancer-related fatigue is not fully understood. In most patients, throughout the disease trajec- tory, many different causes will contribute to the develop- ment of fatigue. 55 For a systematic approach, the expert group suggests a differentiation between primary fatigue, probably related to high cytokine load and secondary fatigue High cytokine concentrations have been reported in asso- ciation with fatigue in patients undergoing radio- and chemotherapy as well as in cancer survivors. 57,58 However, another study with women with uterine cancer receiving curative external radiation therapy found no correlation of fatigue intensity and levels of interleukin-1 (IL-1) and tumour necrosis factor (TNF) and even a negative correlation between fatigue and interleukin-6 (IL-6) level. 59 Simple assessment of circulating cytokine concentrations alone may not be sufficiently reliable. In one study, signifi- cantly higher serum levels of markers associated with proin- flammatory cytokine activity were found in fatigued breast cancer survivors compared with nonfatigued survivors. These markers included IL-1 receptor antagonist (IL-1ra), soluble TNF receptor type II (sTNF-RII) and neopterin as a
Screening (single question)
“I feel unusually weak/tired.”
Figure 1 Algorithm for diagnosis of fatigue in palliative care patients.
ACTH = adrenocorticotropic hormone, Ca = calcium, CRP = C-reactive protein, Mg = magnesium, NRS = numerical rating scale, Phos = phosphate, TSH = thyroid-stimulating hormone. Source: [279] Reprinted, with permission from Radbruch L, Strasser F, Elsner F, et al. Fatigue in palliative care patients—an EAPC approach. Palliat Med. 2008;22(1):13-32. Figure 9
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MDCA1525
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