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Causes for extreme fatigue and weakness, the ringing cedars pdf - .

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Fatigue is sometimes referred to as asthenia, tiredness, lack of energy, weakness, and exhaustion. The causes of fatigue in an individual patient are often multiple, with many interrelated factors.
Decreased physical activity has been shown to cause deconditioning and decreased endurance to both exercise and normal activities of daily living.
In patients without cancer who present with fatigue, the final diagnosis is psychological (eg, depression, anxiety, and other psychological disorders) in almost 75% of patients. Low red blood cell count related to advanced cancer or chemotherapy has been associated with fatigue, and its treatment results in improvement of fatigue and quality of life in these patients. Both intrathecal and systemic opioid therapies, as well as cachexia and some antineoplastic therapies, can result in hypogonadotropic hypogonadism. Administration of chemotherapy and radiotherapy for malignancy causes a specific fatigue syndrome.
Comorbid conditions not necessarily related to cancer, such as renal failure and congestive heart failure, may coexist and contribute to the problem.
The fourth category in Table 1 is the most relevant for both clinical management and clinical trials in fatigue. In addition to the assessment of the intensity of fatigue, the clinical assessment of these patients requires clinicians to determine the impact of all factors on the presence of fatigue. To treat fatigue optimally, it is vital to identify and prioritize the different underlying factors in the individual patient. In patients with cancer treatment–related fatigue, it is important to exclude specific causes, such as hypothyroidism, hypogonadism, and anemia, and to consider other potential adverse effects of treatment.
Psychosocial interventions, such as CBT, have been found to be effective in improving cancer-related fatigue in cancer patients receiving treatment. Fatigue is also commonly associated with cancer treatment and occurs in up to 90% of patients undergoing chemotherapy.
It may be present early in the course of the illness, may be exacerbated by treatments, and is present in almost all patients with advanced cancer. Host cytokines such as tumor necrosis factor, interleukin (IL)-1, and IL-6 are capable of causing decreased food intake, loss of body weight, a decrease in synthesis of both lipids and proteins, and increased lipolysis. In terminally ill patients with advanced cancer, treatment of anemia may not resolve fatigue adequately because of the multifactorial nature of its etiology. Autonomic failure has also been documented in patients with severe chronic fatigue syndrome.
The pattern of fatigue reported by patients with cancer who receive myelosuppressive chemotherapy is cyclical.
It is often described as a “wave” that starts abruptly within a few hours after treatment and subsides shortly thereafter. Combined therapy with the two modalities appears to cause worse fatigue than does either modality given alone. In addition, commonly used medications, such as opioids and hypnotics, may cause sedation and fatigue. Other conditions include the chronic stress response (possibly mediated through the hypothalamic-pituitary axis), disrupted sleep or circadian rhythms, and hormonal changes (eg, premature menopause and androgen blockade secondary to cancer treatment). There is agreement that self-assessment should be the “gold standard.” Because of the complex nature of the symptoms of fatigue, an effort to identify a set of diagnostic criteria similar to those for depression has been attempted. The two most common scales, Eastern Cooperative Oncology Group and Karnofsky Performance Status, consist of a physician’s rating of the patient’s functional capabilities after a regular medical consultation.

Visual analog scales, numerical scales, the Brief Fatigue Inventory (BFI), and the Piper Fatigue Self-Report Scale have been validated. Thorough records, including recent treatment history, physical examination, and medication review, in addition to simple laboratory investigations, will help identify possible underlying causes. A number of effective pharmacologic and nonpharmacologic symptomatic treatments are available for these patients. There is substantial evidence that corticosteroids can reduce fatigue and other symptoms in cancer patients. Psychostimulants (eg, methylphenidate, 5 to 10 mg in the morning and at noon or 5 mg as needed) may be useful in treating fatigue in patients with advanced cancer. Based on a preliminary study that found significant improvement of cancer-related fatigue with a dose of 2,000 mg extract of ground root of American ginseng (Panax quinquefolius), Barton et al recently completed a double-blind trial of 2,000 mg of American ginseng vs placebo for 8 weeks in 364 fatigued cancer survivors.
When appropriate in patients with advanced cancer, physical therapy may encourage increased activity and provide active range of motion to prevent painful tendon retraction.
A recent controlled trial by Chandwani and Cohen et al assessed 163 breast cancer patients receiving radiation therapy who were randomized to a yoga group, a stretching group, or a waitlist group. A recent randomized controlled trial by Montogomery et al found that the benefits of CBT on cancer-related fatigue lasted long after the CBT was finished. Moreover, different studies of fatigue and asthenia have looked at different outcomes, ranging from physical performance to the purely subjective sensation. When injected into a rested subject, blood from a fatigued subject has produced manifestations of fatigue. The metabolic abnormalities involved in the production of cachexia and the loss of muscle mass resulting from progressive cachexia may cause profound weakness and fatigue. It should also be considered in younger cancer patients who are undergoing aggressive antineoplastic treatments such as radiation therapy and chemotherapy and who are nevertheless trying to maintain their social and professional activities. Although the association between fatigue and autonomic dysfunction has not been established in cancer patients, it should be suspected in patients with severe postural hypotension or other signs of autonomic failure. It begins within the first few days after therapy is started, peaks around the time of the white blood cell nadir, and diminishes in the week thereafter, only to recur again with the next cycle of chemotherapy. Fatigue has been noted to decrease in the first 2 weeks after localized treatment for breast cancer but then to increase as radiation therapy persists into week 4.
This syndromal approach has been useful to assess the presence or absence of the clinical syndrome of fatigue.
These functional tasks have limited value in cancer care, however, since they are very difficult for the advanced cancer patient to perform. A physical therapist completes the Edmonton Functional Assessment Tool and attempts to determine the functional status, as well as all the obstacles to clinical performance, of these patients. For instance, patients with anemia may experience symptomatic improvement with the administration of erythropoietic therapy (epoetin alfa [Epogen, Procrit] and darbepoetin alfa [Aranesp]) at the dose and administration schedule that best fit the patient’s need. However, long-term use is associated with weight (fluid) gain, adrenal insufficiency, and thromboembolic complications. In a study by Bruera et al, 141 advanced cancer patients were evaluated for a period of 15 days so as to compare the effects of methylphenidate and placebo. Studies suggest that moderate to intense (55% to 75% of maximum heart rate) aerobic exercise for 10 to 90 minutes, 3 to 7 days per week is safe and effective. In most patients, the etiology of fatigue or dyspnea is multifactorial, with many contributing interrelated abnormalities. The host production of cytokines in response to the tumor can also have a direct fatigue-inducing effect.

However, many abnormalities described in Figure 1 are capable of causing profound fatigue in the absence of significant weight loss.
Patients with an adjustment disorder or a major depressive disorder can have fatigue as their most prevalent symptom.
Fatigue tends to worsen with subsequent cycles of chemotherapy, which suggests a cumulative dose-related toxic effect. Their beneficial effects generally last between 2 and 4 weeks, and longer-term use carries the risk of serious adverse effects. The provision of ramps, walkers, wheelchairs, elevated toilets, and hospital beds may allow the patient to remain at home in a safe environment. However, patients in the yoga group had a greater improvement in physical functioning (Short Form 36 Health Survey), compared with the stretching and waitlist groups. In one study of patients with advanced cancer, fatigue was found to be significantly correlated with the intensity of dyspnea. Muscular or neuromuscular junction abnormalities are a possible cause of chemotherapy- or radiotherapy-induced fatigue. Compared with women who have no history of cancer, former patients with breast cancer who had received adjuvant chemotherapy reported more fatigue and worse quality of life due to this symptom. It is impossible to be certain whether one of these identified problems is a major contributor to fatigue or simply a coexisting problem in a given patient. The results of this study showed that there was no significant improvement in fatigue in the methylphenidate group compared with the placebo group. This chapter will discuss the mechanisms, clinical features, assessment, and management of both of these troublesome and often undertreated symptoms in cancer patients. Similar results have been noted in breast cancer patients who have been treated with high-dose chemotherapy and autologous stem cell support and in patients treated for lymphoma. Therefore, it is of great importance to measure the intensity of fatigue and the patient’s performance before and after treating any contributing factor. In a recent double-blind placebo controlled study of 84 advanced cancer patients with fatigue, oral dexamethasone at a standard dose of 8 mg daily for 2 weeks was associated with significant improvement in cancer-related fatigue. There was also no significant benefit from methylphenidate plus a nursing telephone intervention on cancer-related fatigue.
Counseling (more specifically, cognitive-behavioral therapy [CBT]) for stress management, depression, and anxiety may reduce distress and fatigue as well as improve mood. If the level of fatigue does not improve after correction of these abnormalities, it is clear then that further treatment will not result in improvement in the future. There were no significant differences in adverse events in patients in the dexamethasone and placebo group.
A 148-patient study by Moraska et al also found no significant improvement in cancer-related fatigue with long-acting methylphenidate compared with placebo. In a recent study by Spathis et al, 160 patients with advanced non–small-cell lung cancer were randomized to modafinil or placebo for 28 days. Similar to the previous studies of Bruera et al and Moraska et al, fatigue improved among patients treated with modafinil but there was no significant difference between the active and placebo treatments.
Based on these results, future studies of psychostimulants should be focused on a specific patient group, such as fatigued patients with depression or drowsiness.

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