You are the nursing coordinator of the Thoracic Oncology Clinic at a large outpatient cancer center. In your role, you oversee the symptom management of patients at all stages of their illness including the initiation and continuation of palliative care throughout the cancer trajectory.
Anna, a 58-year-old woman with limited-stage small-cell lung cancer, presents to the thoracic oncology clinic for a follow-up visit after completing three cycles of cisplatin and etoposide. She is scheduled to receive her fourth cycle immediately following today's visit. After checking her vital signs, the clinical assistant informs you that Anna would like to talk to you about discontinuing her chemotherapy. When you enter the room and ask Anna how she is doing, she responds, "I don't think I want to go on with these treatments. I'm not sure it is worth it to feel like this every day." When you ask Anna to explain, she hesitates, but her husband responds, "She has no energy. We used to go to the lake every weekend; now, she can't do it. She can't even tolerate a visit with our granddaughter. Some days she doesn't even get out of bed."
Cancer-related fatigue (CRF) is defined by the National Comprehensive Cancer Network (NCCN) as "a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning."1 Cancer-related fatigue is a complex, multifactorial phenomenon with physical, emotional, and cognitive effects and is described by the patient as feelings of tiredness, lack of energy, weariness, loss of vigor, and physical and mental exhaustion.2 It differs from tiredness in the general population as it is not associated with increased or decreased physical activity, nor is it relieved by rest. Subjective descriptions of the symptom, its effects on daily activities, and its resistance to rest can serve to differentiate CRF from normal tiredness experienced in the general population.3
Anna is not alone in her battle with fatigue. Cancer-related fatigue is the most commonly reported cancer-related symptom, occurring in more than 90% of patients with the disease.4-8 Cancer-related fatigue can have a devastating effect on quality of life and is considered the most distressing of all symptoms experienced by cancer patients, even surpassing pain and nausea.9 Some evidence suggests that CRF has been associated with decreased survival.10 While CRF can occur in any cancer patient, several studies have demonstrated that the incidence and severity of CRF are greatest in patients who receive aggressive interventions including chemotherapy, biological therapy, radiation therapy, bone marrow transplantation, surgery, or a combination of treatments.7,11-15 Cancer-related fatigue can become so bothersome to patients that chemotherapy regimens are decreased-or in some instances discontinued altogether-in an effort to mitigate the intensity of the symptom.5,16 A higher incidence of fatigue has been found with specific cancers9; patients with cancer of the lung17,18 or prostate are more likely to report CRF lasting longer than 6 months and resulting in some level of disability.17 Cancer-related fatigue is often clustered with other symptoms19-21 including pain, changes in sleep patterns, and emotional distress, making it even more devastating to the patient. Left unchecked, CRF can result in significant disability,22,23 leading to financial losses due to decreased employment and increased dependency,7,24 role loss, and related decline in meaningful family relationships.22
Cancer-related fatigue is a multidimensional syndrome that can be affected by physiologic, psychological, and/or situational factors.25 While not clearly understood, causal mechanisms are thought to include factors directly related to or induced by the tumor, cachexia, anemia, dehydration, decreased oxygen saturation, insomnia or other sleep-related disturbances, neurological alterations, psychological disorders, metabolic disorders, liver metastasis, and the adverse effects of anticancer treatments.26
While CRF has received more attention in the research literature, cancer is not the only disease accompanied by fatigue. In a literature review of symptom prevalence in end-stage chronic disease, Solano et al27 found that fatigue also occurred in patients with AIDS (54%-85%), heart disease (69%-82%), chronic obstructive pulmonary disease (68%-80%), and renal disease (73%-87%). Almost all patients with multiple sclerosis experience fatigue to some degree, and as many as 40% have described it as the single, most debilitating symptom, even more troublesome than the neurosensory deficits commonly associated with the disease.28 Fatigue is also associated with systemic lupus erythematosus and rheumatoid arthritis.25 The frequency of fatigue in elderly persons with chronic disease ranges from 47% to 99%,29 and in palliative care, the prevalence ranges from 48% to 78%.30,31 The symptom of fatigue in these other disease states is similar to that experienced by cancer patients and should be assessed and managed accordingly.
For Anna, CRF has led her to consider refusing the treatments that could prolong her survival. She would rather have energy so she can enjoy life. While CRF can significantly impair a patient's quality of life, not all disease-related fatigue is detrimental. In some chronic infectious states, fatigue is thought to be a beneficial adaptive response that facilitates needed rest. At the end of life, fatigue is considered a natural stage of the dying process and may serve to protect the patient against suffering.32 A thorough assessment is therefore essential to determine any treatable causes.
Anna frowns at her husband and says, "I told you not to bring that up. The doctors and nurses have more important things to do than listen to my complaints. There's nothing anyone can do about it anyway-it's just part of the disease and its treatment. It is much worse than I expected."
Despite the prevalence of CRF and the availability of practice guidelines issued more than a decade ago33 and updated annually1 by the NCCN, it is rarely addressed in the clinic setting. Patient-, clinician-, and system-related barriers can result in failure to report, diagnose, or treat fatigue.
Like Anna, many cancer patients do not voluntarily report the presence or impact of fatigue on their daily lives.1,33 Patients' reasons for not communicating about their fatigue include not wanting to divert the oncologist's attention away from primary cancer treatment, perception that fatigue is a "normal" adverse effect of cancer and its treatment and must be endured, personal association of fatigue with depression, lack of awareness of available treatments, fear the presence of fatigue may indicate disease progression, and fear of having to take additional medication.34
Clinicians who do not inquire about fatigue are often unaware of its presence or significance for the patient.1 Other clinician-related barriers to diagnosis and treatment of fatigue include a view of fatigue as a "normal" adverse effect of the disease and treatment, a belief that it would take too much time to assess and treat fatigue, a focus on symptoms perceived as being more important or having more clinical impact, and lack of knowledge about interventions to mitigate CRF. While most oncologists believe their patients suffer from fatigue, they tend to give it less attention than other symptoms, that is, pain.14
System barriers, including an absence of fatigue (or its descriptors) as components of documentation forms or computer programs and a related lack of policies or procedures addressing the phenomenon, also contribute to inadequate assessment and management of CRF.35-38 This lack of practice standards and accountability measures has limited focused quality improvement efforts.
"It is true that cancer patients often experience fatigue," you tell Anna. "But there may be something we can do to help. First of all, I need you to tell me more. I want to know about your tiredness…. I understand that it is keeping you from the activities you usually enjoy…. Is it always present?…What seems to help relieve it? How does it affect your day-to-day activities? What does it mean to you?"
Using active listening skills and allowing ample time between questions for Anna to respond, you learn that Anna has been having increasing difficulty performing self-care. She tells you she must complete her bath in stages and rest before she can dress herself. "It's unlike anything I have ever experienced. I do nothing, and yet, I have never felt so exhausted." She states she must "plan ahead" to go to the bathroom as she doesn't have the energy. "Even thinking about it wears me out." She is able to stand but reports, "My legs feel like rubber. I don't know how much longer they will hold me up." She spends nearly all of her time in a recliner because she does not want to be in the bed any more than necessary. She states it has become difficult to focus on a television program or a book: "I know it sounds crazy, but I am too tired to even read the newspaper." She also reports she has trouble focusing on conversations with family and friends and frequently loses her train of thought. "It's just as well; the visits wear me out anyway." Her husband reports she sleeps nearly all of the time, even dozing off while sitting up in a chair at the kitchen table.
As CRF is primarily a subjective, complex, whole-body experience, most experts agree the patient self-report provides the best evidence of the intensity and severity of the symptom as well as its impact on a patient's quality of life.1,32,33,39,40 Individualized characteristics of the fatigue experience should be assessed and include timing, exacerbating and relieving factors, impact on routine daily activities, meaning to the individual, and any cultural factors that may affect descriptions.33,40 Assessment tools useful for evaluation include a complete medical history, physical examination, laboratory testing, and family and caregiver reports.33 Since fatigue is not stable, but prone to variations, it should be assessed as a condition or a phenomenon2,41,42 and not a one-time symptom that could be easily addressed.
You note what Anna is telling you about the personal impact of her fatigue. As you continue, you ask her, "On a scale of 0 to 10, with 0 being not fatigued at all and 10 being the most fatigued you can imagine, can you rate your fatigue?" Anna is thoughtful for a minute and then replies, "I would rate it around a 9. I guess it could get worse, but I can't imagine how! My whole body feels heavy, and some days it takes all my energy just to sit up on the side of the bed."
According to the NCCN's practice guidelines for CRF, all patients should be initially screened for the presence of fatigue at the first clinical visit and routinely thereafter, well into the survivorship period.28,29 If fatigue is identified, the severity of the fatigue should then be determined. The NCCN guidelines suggest that the use of a simple 0- to 10-point numerical rating scale (NRS) is feasible and sufficient to determine initial severity. If the intensity level is moderate or severe (a score of 4 on the NRS), a focused history and physical examination are indicated, and additional measurement is recommended. If fatigue is not present at the initial visit or is reported to be mild (a score of 0-3 on the NRS), patients and families should receive education about fatigue management. Rescreening and evaluation should then occur at regular intervals.
There are several tools available for measuring CRF when measurement beyond intensity level is warranted (as with a score of 4 on the NRS). Minton and Stone43 reviewed 14 scales previously validated in cancer populations. Based on their study, they recommended three scales: two unidimensional scales measuring physical functioning-European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy Fatigue (FACT-F)-and one multidimensional scale measuring physical and mental functioning-the Chalder Fatigue Scale or Fatigue Questionnaire. Of the three, the unidimensional scales were considered the easiest to administer and the most feasible for a clinic setting. In addition, both could be used to monitor the effects of treatment.43 The EORTC QLQ-C30 and the FACT-F have 3- and 13-item fatigue-specific subscales, respectively, which have been independently validated for use with CRF,43,44 making them less burdensome for the patient and attractive tools for the busy clinician.
"In order to further understand your fatigue and what might be causing it, I need to ask you more questions about how you've been feeling. I think the doctor will also want to evaluate your lab work," you inform Anna. You proceed to ask her about her pain, how she's been sleeping, what she eats during a normal day, and how much time she is spending in bed.
Once fatigue is detected, the first assessment priority is to identify treatable underlying causal or contributing factors,25 sometimes called the "gang of 7"38-anemia, pain, altered sleep cycles, nutritional deficits, physical deconditioning, emotional distress (depression/anxiety), and the presence of comorbidities (hypothyroidism, pulmonary or heart disease, diabetes, etc). A thorough medication history should be conducted to determine the presence of any medications, especially those known to produce sedation,1 which may contribute to fatigue. Causative factors should be assessed and managed whenever possible. However, prior to initiating any treatment, consideration should be given to the patient's physical condition and prognosis.32 Balancing the benefits and risks of any treatment will guide the nurse to identify a treatment plan that is individualized to the patient.
When assessing Anna's fatigue, you consider her chemotherapy regimen. You understand fatigue is more prevalent with certain chemotherapy agents, such as cisplatin. However, based on Anna's treatment goal-to try and beat the disease-and her cell histology and prognosis, it is in Anna's best interest to try and remain at her current dose.
According to Anna's verbal responses, her pain is well managed on a low dose of oxycodone; she is eating a well-balanced diet, which is supplemented by a protein shake twice daily, and her weight has remained stable since starting treatment. You realize that she is sleeping excessively, spending much of the day in bed, which is probably deconditioning her body. You think a little exercise might help but decide to proceed with your assessment before recommending any interventions.
"Have you been feeling unusually sad?" you ask the patient. Anna responds, "I am sad. I don't know what this means. I'm afraid it is a sign that my cancer is growing and that I am getting worse every day. It means I can't be a good wife, mother, or grandmother-the very things that have meant so much to me." Her husband adds that he often finds her in tears. "She cries a lot, but I guess anyone in this situation would."
Because some of the manifestations of depression are also present in fatigue, it is possible to misdiagnose fatigue as depression. While depression can occur as a comorbid condition along with fatigue, it is not necessarily so. Care must be taken to differentiate the diagnosis.40,45 Depressed patients often present with complaints of tiredness; patients with fatigue often complain of feeling down. Depression, however, may also present with feelings of intense sadness, hopelessness, loss of self-worth, and, possibly, recurrent thoughts of dying. These latter symptoms are not present in patients suffering from fatigue. In addition, fatigued persons suffer from postexertional malaise-also not present in depression.45
After completing your assessment, you excuse yourself to confer with the oncologist. A review of Anna's laboratory work reveals her serum chemistry, complete blood count, and thyroid function tests are within normal limits. The two of you agree that further evaluation for depression is indicated. Anna might benefit from psychostimulants, education, and a physical exercise program.
You and her medical oncologist meet with Anna and her husband and agree on the following treatment plan:
• Refer to the psycho-oncologist for further evaluation of possible depression
• Begin on methylphenidate (Ritalin) 5 mg PO twice a day; increase until desired effect is achieved or until adverse effects prohibit.
You educate Anna and her husband regarding fatigue and possible management strategies. She is sent home with an informational brochure and a written plan that includes a teaching sheet on fatigue management (Figure 1) and suggestions for light exercise.
According to the Hospice and Palliative Nurses Association, fatigue treatment interventions fall into one of three categories: reduction of causative factors and pharmacological and nonpharmacological.46
Reduction of Causative Factors
If feasible, treatment should focus first on alleviating any identified causal factor or comorbidity.1,33 As causal therapy may require time before the patient notices improvement, symptomatic treatment should also be initiated.25
Looking back at the "gang of 7," anemia, pain, nutritional deficits, and comorbid conditions such as hypothyroidism and infection are ruled out as causes of Anna's fatigue. Anna requires only a small dose of oxycodone hydrochloride (OxyContin) to manage her pain; therefore, this is not likely to contribute to her fatigue. Physical deconditioning, hypersomnia, emotional distress, and, possibly, depression are identified as treatable causes to be addressed in her plan of care (Table 1).
When no identifiable cause is found, symptomatic treatment becomes the primary focus. Because fatigue is likely to be related to multiple factors, most patients suffering from fatigue benefit from a combination of pharmacological and nonpharmacological interventions.32
A variety of medications have been studied to determine their effectiveness in managing symptoms associated with CRF. Donepezil, a centrally active, acetylcholinesterase inhibitor-generally prescribed to treat dementia in patients with Alzheimer disease-has been tested in CRF, but was not shown to be better than placebo in lessening fatigue.47 Early research on psychostimulants has demonstrated their ability to counteract the manifestations of CRF as well as alleviate some contributing factors. These effects are attributed to their stimulatory effects on the central nervous system.48 Modafinil, a nonamphetamine that increases wake-time in patients with narcolepsy, has been used successfully to mitigate fatigue in patients with multiple sclerosis28 and to a limited degree in cancer.49
In Anna's case, the physician prescribed methylphenidate. This amphetamine-like drug, commonly prescribed for attention-deficit/hyperactivity disorder and the symptomatic management of narcolepsy,50 has been supported by research as reducing fatigue in cancer patients.51 It increases dopamine concentrations in the brain by blocking dopamine transport or carrier proteins.52 Hanna et al51 reported that methylphenidate significantly reduced fatigue in patients receiving aggressive treatment for breast cancer. Methylphenidate has demonstrated efficacy in reducing the somnolence and mental clouding associated with opioid use53 and may enhance the analgesic effects of opioids.54 Methylphenidate has also been associated with increased physical activity55 and has shown promise as a short-acting antidepressant,26,56 making this especially attractive for use with someone like Anna, who is possibly experiencing depression, which is contributing to her fatigue.
Use of corticosteroids, that is, methylprednisolone and dexamethasone, has been anecdotally supported to improve fatigue symptoms in cancer patients.32,57 A few clinical trials have associated corticosteroid administration with increased appetite,58 strength,59 sense of well-being,60 and quality of life60,61 in cancer patients. However, the positive effects are reportedly short lived.58 Long-term use of corticosteroids has been associated with muscle wasting.62 Therefore, use of corticosteroids is recommended only for brief periods, such as to allow a patient to get through an important holiday or event.32
A number of nonpharmacological interventions have been studied to determine their effects on fatigue and its associated symptoms in cancer and other chronic illnesses. While the results have varied among studies, there is a growing body of evidence supporting efforts that aim to increase a patient's knowledge63-65 and/or to increase or enhance a patient's physical mobility.32,33
Educational and counseling interventions offered at the outset of cancer treatment have been associated with better health outcomes, including reduction of fatigue65 and symptom burden,66 and improved quality of life.66,67 According to the NCCN guidelines,1 all patients and their families should receive preparatory educational and counseling interventions. These interventions should inform patients about the probability of developing fatigue1 and counsel them regarding self-management strategies likely to improve coping, such as energy conservation techniques, and stress and activity management.64,65 Any education program should reassure patients that fatigue may occur as an adverse effect of treatment, and its presence need not indicate that the cancer is progressing.1 Educating patients about fatigue and arming them with self-management strategies allow more control over their disease and provide accurate expectations, thereby reducing the stress response.1,2
Three weeks later, Anna returns to the clinic for follow-up. She states her energy level is starting to return. She is not sleeping as much as before and is getting by with a daily nap. She has also begun to enjoy her television programs and is looking forward to having dinner with her daughters on Sunday. The psycho-oncologist's report indicates that Anna is not clinically depressed and recommends continued use of methylphenidate as tolerated.
You suggest that she might now enjoy a light exercise program sponsored by the clinic's resource center. She refuses, saying she is now taking a short walk with her husband each evening. You encourage her to continue, as exercise is important to her conditioning and rebuilding her energy level. You suggest she might try using some light weights and doing strengthening exercises.
While intuition may lead patients like Anna to believe that resting more will alleviate their fatigue, the opposite is actually true. Rest will often neither restore nor increase energy levels; rather, prolonged physical inactivity and the resulting muscular deconditioning will actually promote fatigue.32 Fatigue is thought to occur because of sedentary movement (patient lying around ill) coupled with the toxic effects of therapies, resulting in lost capacity for physical functioning.68 As a result, greater effort and energy must be utilized to perform routine activities. Exercise training decreases functional loss and improves functional capacity, thereby decreasing the amount of physical effort needed to do everyday tasks.68
Exercise interventions have been studied in a variety of populations, including patients at the end of life, and appear to be the most promising of all nonpharmacological interventions at improving levels of fatigue.1,69 Several studies have reported the level of physical activity to be inversely related to the level of fatigue.70 Exercise, particularly aerobic exercise, has been reported to reduce fatigue in cancer patients receiving treatment,71,72 in palliative care patients with a short life expectancy,73 and in cancer survivors.74 Studies have also supported the use of resistance training or "anabolic" exercise to improve muscle and bone tissue in cancer patients.75
If exercise is initiated, muscle strength may improve in a matter of days.76 Any recommended exercise program should be individualized to the patient, taking into consideration the patient's physical capabilities, disease status, and any comorbid conditions.1,42,68 In Anna's case, walking with her husband is more appealing than attending a class.
Anna continues on her methylphenidate with slight increases every few weeks. She continues to exercise. Eight weeks after her last chemo treatment, she contacts the clinic stating she has begun experiencing shortness of breath and coughing up blood. Subsequent scans demonstrate growth and expansion of the tumor, and she is now diagnosed with extensive-stage small-cell lung cancer. Administration of topotecan (Hycamtin) was started. She completes two doses of chemotherapy, but misses the third and does not call to reschedule.
When you call Anna's home, her husband informs you that Anna is "just too tired to come in to the clinic." "She says she just wants to rest." He reports Anna quit taking the methylphenidate last week, because it was making her too jittery, and she was having trouble sleeping. He states Anna called a family meeting and told them she was ready to stop the chemo. He says his daughters are taking turns staying with them.
"Will it hurt her to stop the methylphenidate?" he asks you. "She seems so content to just sleep now. I think we should let her rest. She has fought so hard, and she says she is now ready to die." You respond, "No, stopping the medicine won't hurt her in any way. If she seems uncomfortable, be sure to call me, and we'll see what might be helpful to her." You suggest that he consider a referral to the local hospice program as they can visit, assess her condition, manage her symptoms, and provide support to the family.
"That might be helpful. I know they were a big help to my brother," replies her husband. You assure him that you will make the referral, and they should call him soon to set up an admission visit.
As with all symptom management in palliative care, treatment goals for fatigue should be based on the stage of the patient's illness and the patient's wishes. Other important factors to consider include extent of the disease, other symptoms, age, and emotional "place" of the patient.77 Identifying the point at which aggressive management of fatigue should be ended is important to the patient's comfort and quality of life. As death approaches, fatigue is a natural occurrence and may protect the patient from further distress.32 Providing aggressive treatment during this time could force the patient to experience anew the effects of her disease, leaving her to cope with the intense suffering associated with an advanced stage of disease in an even more frail and progressively weakened physical and emotional state.32 Anna's preference for no further treatment for her fatigue coupled with disease progression and a shortened prognosis are signs that aggressive management is no longer indicated.
Anna receives hospice care for the next month. The hospice nurse calls the clinic to report that she had a peaceful death and was comfortable for the last weeks of her life.
Cancer-related fatigue is a serious problem for many palliative care patients with cancer. Cancer-related fatigue can limit communication, prevent patient involvement in social interactions, disrupt daily life, and prevent the important work of closure at the end of life.78,79 It can be the most troublesome of symptoms for palliative care patients.78 Because it is a subjective experience and is often thought to be an unavoidable symptom in chronic illness, it may go ignored. Therefore, assessing and treating fatigue should be an essential component of all palliative nursing care.
The authors thank Anne Elizabeth Small, BSN, RN, OCN, for her expertise and valuable suggestions to our case study.
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