-------------------------------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.
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