Palliative Care and Pain Management at the End of Life ___________________________________________
The treatment of anemia as an underlying cause of fatigue (and other symptoms) is a complex issue. Many studies have provided evidence to recommend the use of erythropoiesis- stimulating agents (erythropoietin [Epogen], darbepoetin [Procrit]) for anemia in people with cancer, HIV/AIDS, chronic kidney disease, and heart failure because of benefit in increasing the hemoglobin level, improving exercise tolerance, reducing symptoms, and decreasing the need for blood transfu- sions [279; 290; 294; 295; 296]. However, safety concerns led the U.S. Food and Drug Administration (FDA) to require a boxed warning on the label of erythropoiesis-stimulating agents regarding the increased risk of several adverse events (death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recur- rence) among people with chronic kidney disease or cancer [297]. The FDA recommends using the lowest dose sufficient to avoid red blood cell transfusion [297]. Recommendations for these agents in these populations have been withdrawn or revised [87; 291; 298; 299]. A 2010 systematic review and meta-analysis (11 studies, 794 subjects) demonstrated benefit of erythropoiesis-stimulating agents among people with heart failure and mild anemia (>10 g/dL) with no increase in adverse events [296]. Most patients will try to manage fatigue by resting and/or sleeping more often, and many healthcare professionals will also recommend this strategy. However, additional rest and/ or sleep usually does not restore energy in patients who have fatigue related to a life-limiting disease; continued lack of exercise may even promote fatigue [279]. Regular aerobic exer- cise and strength training has been found to alleviate fatigue, although much of the research in this area has been conducted with cancer survivors [284]. For example, a meta-analysis (28 studies, 2,083 subjects) demonstrated a significant effect of exercise in the treatment of fatigue during and after cancer treatment [293]. An update to this review and meta-analysis supported the benefit of aerobic exercise for individuals with cancer-related fatigue and recommended further research to determine the optimal type, intensity, and timing of an exercise intervention [300]. Some small studies of fatigue have been done in the palliative care setting, and exercise was found to be beneficial [301; 302; 303]. Although an exercise program is recommended, decreasing activity to conserve energy is also encouraged [108; 187; 279]. Clinicians should talk to the patient and family about the importance of the patient conserving energy by adjusting daily activities to correspond to times of peak energy, setting priorities for activities, following a normal wake-sleep cycle, and using assistive devices, and delegating less important tasks [187; 279]. Encouraging adequate nutrition, stress reduction through meditation or relaxation techniques, and engage- ment in enjoyable activities can help restore energy [187; 279]. Counseling about setting realistic goals for activities and function may also help patients and family members adapt to new daily routines.
Pharmacologic treatment of fatigue should be undertaken only after potential causes of fatigue have been ruled out [187; 279]. The EAPC and the ASCO note that methylphenidate (Ritalin) and modafinil (Provigil) may reduce fatigue [279; 284]. The NCCN does not recommend modafinil due to limited evidence of benefit and recommends that methylphenidate be used cautiously and should be considered only after other causes of fatigue have been ruled out [278]. The recommenda- tions from the EAPC and the ASCO are based on systematic reviews showing a significant effect of methylphenidate for the treatment of fatigue in people with cancer or HIV/AIDS or for opioid-induced sedation [279; 290; 291; 292; 304]. An optimal dose of methylphenidate has not been defined, but an initial dose of 5–10 mg (given in the morning) has been used, with the dose titrated to 40–60 mg per day (given once in the morning and once at midday) [279]. Among the side effects are nervousness, jitteriness, agitation, arrhythmia, and tachycardia [279]. The initial recommended dose of modafinil is 200 mg per day [279]. Major side effects have included agitation, ner- vousness, sleep disturbances, nausea, and diarrhea. Since the publication of these recommendations, researchers conducting a systematic review concluded that the evidence was insufficient to recommend a specific drug for the treatment of fatigue in the palliative care setting [292]. The ASCO notes that evidence for their use is weak; others argue that an improper (too low) dose and short study duration leads to suboptimal effect in trials and that individual response to central nervous system stimulants is highly variable [284; 305]. Corticosteroids (prednisone and dexamethasone) have been used frequently to treat fatigue in the palliative care setting, but no research on their effectiveness is available [292]. These agents have provided short-term relief of fatigue and improved quality of life among people with cancer, but because of the toxicity associated with long-term use, they should be consid- ered only at the end life or to alleviate fatigue for a well-defined goal (such as allowing the patient to attend a special event) [187; 279]. DYSPNEA Dyspnea is a subjective sense of breathlessness (extreme short- ness of breath, the subjective awareness that “breathing is not working”) and ranges from breathlessness on exertion to persistent, distressing breathlessness at rest or for longer peri- ods of time. Patients may describe dyspnea as “smothering,” “suffocating,” or “drowning.” Dyspnea can have a substantial impact on a patient’s quality of life by restricting the patient’s activities as well as causing distress for both patients and their families. Prevalence The prevalence of dyspnea among adults with life-limiting disease ranges from 10% to 95%, with the highest rates among people with COPD, lung cancer, and heart failure, especially in the last week of life [54; 207; 209; 211; 213; 306; 307].
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MDCA1525
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