-------------------------------FATIGUE: OVERVIEW------------------------------- STATEMENT Fatigue is one of the most common complaints of cancer patients. In this population, fatigue can be a chronic problem resulting from a combination of physical, psychological, and situational factors. Whereas rest will completely restore the healthy individual to a normal level of functioning, this restorative capacity is diminished in the presence of neoplastic disease. FATIGUE: FATIGUE FACTORS Although a variety of treatment- and disease-related factors may contribute to the development of fatigue, the exact mechanisms of chronic fatigue in oncology patients are unknown. Disease factors Fatigue is a common prodrome of disease progression and is frequently one of the presenting signs for both pediatric and adult malignancies.[1] Tumors can influence fatigue indirectly as well by infiltrating the bone marrow, causing anemia, and by producing toxic metabolic substances that interfere with normal cellular processes. Marked increases in Cori cycle activity leading to excess lactate and hydrogen ion production have been reported in cancer patients.[2-4] Accumulation of these substances may produce fatigue by decreasing muscle contractility. Treatment factors Fatigue is a common symptom following treatment with both radiation and chemotherapy and may be associated with an accumulation of cell destruction end products, and, in the case of radiation, with increased energy requirements to repair damaged epithelial tissue.[5,6] Patients receiving interferons and other biological response modifiers also frequently experience fatigue as part of a symptom constellation that includes fever, anorexia, and weight loss.[7] The mechanism for this effect is also unknown. In some cases, fatigue may be produced by disorders in neurotransmission. Since peripheral fatigue symptoms and cognitive impairment (decreased concentration and ability to think clearly) have been reported anecdotally with the vinca alkaloids, drugs that cross the blood brain barrier or have neurotoxicities may be more likely to produce fatigue.[8] Additionally, many oncology patients may be concurrently receiving analgesics, hypnotics, antidepressants, antiemetics, or anticonvulsants. Because many of these drugs exert their effect on the central nervous system, they can significantly compound the problem of fatigue. Nutritional factors Fatigue often occurs when the energy requirements of the body exceed the supply of energy sources. In cancer patients, three major mechanisms may be involved: alteration in the body's ability to process nutrients efficiently, increase in the body's energy requirements, and decrease in intake of energy sources. Causes of nutritional alterations are listed in TABLE 1. TABLE 1: NUTRITIONAL/ENERGY FACTORS Mechanisms Causes ------------------ -------------- Altered ability to process nutrients Impaired glucose, lipid, and protein metabolism [9] Increased energy requirements Tumor consumption of and competition for nutrients Hypermetabolic state due to tumor growth Infection/fever Decreased intake of energy sources Anorexia Nausea/vomiting Diarrhea Bowel obstruction Psychological factors Numerous factors related to patients' moods, beliefs, attitudes, and reactions to stressors are thought to contribute to the development of chronic fatigue. Nonorganic causes comprise approximately 40-60% of the cases of fatigue in general medical populations, with anxiety and depression as the most common psychological disorders.[10] In hospitalized oncology patients, the incidence of moderate to severe depression can be as high as 42%.[11,12] The presence of depression, as manifested by loss of interest, difficulty concentrating, lethargy, and feelings of hopelessness can compound the physical causes for fatigue in these patients and persist long past the time when physical causes have resolved. Anxiety and fear associated with the diagnosis of cancer and its impact on the patient's physical, psychosocial, and financial well-being are a source of emotional stress. Situational factors Situational fatigue can occur in fairly transient circumstances that produce periods of extreme emotional or physiological stress. For patients with cancer, other situational factors that may contribute to the development of fatigue include: pain, nausea and vomiting, respiratory impairment, immobility, altered sleep patterns, anesthesia, analgesia, and infection.[13,14] References: 1. Waskerwitz MJ, Leonard M: Early detection of malignancy: from birth to twenty years. Oncology Nursing Forum 13(1): 50-57, 1986. 2. Burt ME, Aoki TT, Gorschboth CM, et al.: Peripheral tissue metabolism in cancer-bearing man. Annals of Surgery 198(6): 685-691, 1983. 3. Gold J: Cancer cachexia and gluconeogenesis. Annals of the New York Academy of Sciences 230: 103-110, 1974. 4. Nakamaru Y, Schwartz A: The influence of hydrogen ion concentration on calcium binding and release by skeletal muscle sarcoplasmic reticulum. Journal of General Physiology 59(1): 22-32, 1972. 5. Nerenz DR, Leventhal H, Love RR: Factors contributing to emotional distress during cancer chemotherapy. Cancer 50(5): 1020-1027, 1982. 6. Haylock PJ, Hart LK: Fatigue in patients receiving localized radiation. Cancer Nursing 2(6): 461-467, 1979. 7. Mayer D, Hetrick K, Riggs C, et al.: Weight loss in patients receiving recombinant leukocyte a interferon (IFLRA): a brief report. Cancer Nursing 7(1): 53-56, 1984. 8. Piper BF, Lindsey AM, Dodd MJ: Fatigue mechanisms in cancer patients: developing nursing theory. Oncology Nursing Forum 14(6): 17-23, 1987. 9. Lindsey AM: Cancer cachexia: effects of the disease and its treatment. Seminars in Oncology Nursing 2(1): 19-29, 1986. 10. Reich SG: The tired patient: psychological versus organic causes. Hospital Medicine 22(7): 142-154, 1986. 11. Petty F, Noyes R: Depression secondary to cancer. Biological Psychiatry 16(12): 1203-1220, 1981. 12. Burkberg J, Penman D, Holland JC: Depression in hospitalized cancer patients. Psychosomatic Medicine 46(3): 199-212, 1984. 13. Rhoten D: Fatigue and the postsurgical patient. In: Norris CM, Ed.: Concept Clarification in Nursing. Rockville, MD: Aspen Systems, 1982, pp 277-300. 14. Aistars J: Fatigue in the cancer patient: a conceptual approach to a clinical problem. Oncology Nursing Forum 14(6): 25-30, 1987. FATIGUE: ASSESSMENT Comprehensive assessment of the fatigued patient starts with obtaining a careful history to characterize the patient's fatigue pattern and identify all factors that contribute to its development. The following areas should be included in the initial assessment: 1. Fatigue pattern, including onset, duration, intensity and aggravating and alleviating factors. 2. Nutritional habits and any appetite or weight changes. 3. Effects of fatigue on activities of daily living and lifestyle. 4. Treatment history. 5. Incidence of treatment-related side effects. 6. Sleep/rest patterns/relaxation habits/customs/rituals. 7. Current medications. 8. Extent of disease. 9. Psychological profile. 10. Complete physical examination. A complete evaluation will provide information regarding both the physical and psychological factors producing fatigue in the individual, as well as identify possible resources that may be available to assist the patient in adapting or coping with the effects of fatigue on lifestyle. FATIGUE: INTERVENTIONS Much of the information regarding interventions for fatigue relates either to healthy subjects or patients where muscle fatigue is the primary etiology of their problem.[1-3] Without a determination of the mechanisms of fatigue in oncology patients, interventions must be directed to symptom management and emotional support. Although some recommendations for the management of fatigue in oncology patients have been made, these are theoretical or anecdotal in nature, and have, in general, not been the focus of scientific evaluation. Medical management focuses on treatable physiological causes of fatigue. Treatment of the underlying malignancy is the primary goal, since in many cases, anticancer therapy may decrease the sense of fatigue as the tumor responds. Patients should be advised that fatigue is a common problem during the course of treatment so that they will not necessarily attribute its onset to progressive disease. Symptom management includes red blood cell transfusions, nutritional support, and surgical decompression of gastrointestinal obstructions. Whenever possible, treatment side effects such as nausea, vomiting, and diarrhea should be minimized by adequate antiemetic therapy and early detection of treatment-related toxicities to avoid the additive effect that they may have on other predisposing factors. Assessment for depression should also be undertaken. Although developing a healthful daily routine should be encouraged in patients experiencing fatigue, rest alone is generally not effective in returning the patient with chronic fatigue to their previous level of functioning. A balanced diet, regular exercise, and adequate rest should be the minimum health habits for which the patient should strive. Any changes in routine require additional energy expenditure. Patients should be advised about setting priorities and maintaining a reasonable schedule. Health professionals may be of assistance by providing information regarding support services that might be available to help the patient with daily activities and responsibilities. Much of the management of patients with chronic fatigue involves promoting the patient's adaptation and adjustment to the condition. The possibility that fatigue may be a chronic disability should be discussed with the patient. Although it is frequently an expected, temporary side effect of treatment, the problem may persist if other factors continue to be present. Patients can work with health professionals to develop an activity/rest program based on assessment of their fatigue patterns that allows the patient to utilize their energy most effectively. References: 1. Gibson H, Edwards RH: Muscular exercise and fatigue. Sports Medicine 2(2): 120-132, 1985. 2. Hart LK: Fatigue in the patient with multiple sclerosis. Research in Nursing Health 1(4): 147-157, 1978. 3. Arendt J, Borbely AA, Franey C, et al.: The effects of chronic, small doses of melatonin given in the late afternoon on fatigue in man: a preliminary study. Neuroscience Letter 45(3): 317-321, 1984.