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Anorexia and Cachexia 

Anorexia and Cachexia
Chapter:
Anorexia and Cachexia
Author(s):

Robert Smeltz

DOI:
10.1093/med/9780190204747.003.0026
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Key Points

  • Because cachexia and anorexia syndrome is present in most advanced chronic and life-limiting illnesses, the palliative advanced practice registered nurse (APRN) should be vigilant in assessing for its presence.

  • Assessment of cachexia and anorexia syndrome requires subjective and objective measures and must take into account the multiple dimensions of the individual.

  • Treatment of cachexia and anorexia syndrome requires a multimodal approach using pharmacologic and nonpharmacologic interventions, treating both physical and psychosocial symptoms.

Introduction

This chapter defines anorexia and cachexia and their interplay as a syndrome, as seen in most advanced stages of disease. The assessment of anorexia and cachexia is fundamental in establishing an effective treatment plan. A first step in treatment of cachexia and anorexia is setting goals and educating patients and families on the limits of reversing anorexia and cachexia in advanced disease. The use of a multimodal approach with pharmacologic and nonpharmacologic measures delivered by an interdisciplinary care team geared at treating the whole person is the key strategy to addressing cachexia and anorexia syndrome.

Cachexia is defined as a

multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The pathophysiology is characterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism.1

Anorexia in cancer and advanced chronic illness is a decrease in nutritional intake, often accompanied by a loss of appetite. Cachexia and anorexia are often seen together, and this is referred to as cachexia and anorexia syndrome (CAS). CAS is seen in cancer, heart disease, kidney failure, chronic lung diseases, and HIV/AIDS. Weakness, weight loss, and anorexia are seen in 60%, 53%, and 46% of patients with advanced cancer, respectively. The prevalence increases to 86%, 74%, and 56%, respectively, in the last 1 to 2 weeks of life in advanced cancer.2 Cachexia is seen in 10.5% of patients with congestive heart failure.3 Anorexia is seen in 15% to 30% of elderly persons in the community.4

CAS is a difficult symptom to treat and often becomes refractory toward the end-of-life. Most pharmaceuticals have limits in terms of efficacy and/or side effects. Dietary counseling seems like a logical choice with no adverse effects, but it is not clear that outcomes are improved. This chapter discusses the role of the palliative APRN in treating CAS. The pathophysiology of CAS, identifying underlying causes, and the importance of using a multimodal approach to treatment are outlined. A review of the psychosocial assessment and how CAS affects the patient and family is offered. Finally, strategies the palliative APRN can offer as part of education and support are described.

Palliative APRN Considerations

The palliative APRN plays an important role in assessment, diagnosis, and treatment of anorexia and cachexia. This includes coordinating the patient’s interdisciplinary care, advocating for the patient, and educating the patient and family.5 The palliative APRN can identify the goals of care in terms of how they relate to addressing CAS and can help the family understand what is realistic within the limits of the disease at its current point in the disease trajectory. The palliative APRN can help the family explore pharmacologic and nonpharmacologic treatment measures and identify a regimen that takes into account the patient’s goals as well as caregiver burden.

Pathophysiology

CAS is produced by multiple factors, including decreased appetite, alterations in metabolism, and increased catabolism. The decrease in appetite is likely multifactorial as well, resulting from decreased drive to feed, early satiety, decreased intestinal motility, and nausea. Decreased food intake results in some of the weight loss but does not explain all of the wasting seen in CAS. There are also disturbances in metabolism resulting in loss of lean body mass and body fat.6 This is evidenced by visceral organs not showing the signs of wasting in CAS that are seen in starvation.7 Also, in CAS there is greater loss of lean body mass, unlike initial stages of starvation, where fat is lost.

CAS is believed to be caused, in part, by pro-inflammatory cytokines (interleukin [IL]-1, IL-2 and IL-6, interferon-gamma, and tumor necrosis factor-alpha [TNF-α‎]) in patients with cancer.8 There are other peptides and pathways that influence appetite and catabolism, which could also be affected by cancer.

TNF appears to increase lipolysis in rat models, but its impact on patients with cancer in terms of weight loss and decreased appetite is not clear.8 IL-6 is a pro-inflammatory cytokine, but like TNF and the other cytokines, it is difficult to understand the specific roles in CAS since there is overlap and redundancy. It is likely that the effects of several cytokines cause CAS, and inhibiting one cytokine has little to no effect on CAS.

Glucagon and other hormonal peptides and neuropeptides play a role in CAS. Specifically, glucagon administration has been shown to reduce food intake, and glucagonemia is associated with some cancers. Corticotropin-releasing factor (CRF) is seen in some cancers, and its presence decreases gastric emptying as well as food intake and appetite. There are several other neuropeptides that appear to affect feeding and weight, but their role in CAS and implications in the treatment of CAS are not known.8

Cancer cell metabolism may play a role in CAS. The uncontrolled metabolism and growth of cancer cells inhibit delivery of sufficient oxygen, which prevents creation of energy from the Krebs cycle; instead, the Cori cycle is used to create energy. This creates lactic acid, which needs to be processed in the liver, requiring further energy expenditure. This essentially helps to increase the resting energy expenditure.7

CAS is seen in several serious illnesses in addition to cancer. The process of aging likely contributes to CAS in the elderly population.4 Gastric emptying is decreased in older patients.9 Senses, including smell, taste, and sight, may be altered, which may have an impact on appetite. CAS in amyotrophic lateral sclerosis and dementia is not well understood. It is at least partially related to decreased mobility and decreased nutritional intake secondary to the progression of the neurologic disease.

CAS is also seen in advanced heart disease. Pro-inflammatory cytokines appear to be involved.10 Decreased circulation to the intestines can decrease motility and absorption, which can further contribute to anorexia and cachexia, respectively. There is an increase in muscle protein breakdown.11 Decreased insulin sensitivity could also play a role in CAS in patients with heart disease.12

Inflammatory responses appear to play a role in CAS in chronic obstructive pulmonary disease (COPD).13 The increased work of breathing likely increases energy expenditure, contributing to CAS. Impaired oxidative capacity in COPD appears to alter protein turnover, worsening CAS further.14

Assessment

The goal of assessment is to identify the presence of cachexia, weight loss, and/or anorexia. The presence of cachexia is identified with weight loss disproportionate to, or without, anorexia. Reversible causes of anorexia and cachexia should be sought.

The assessment of anorexia and cachexia includes the patient’s report of appetite, disturbances in taste and smell, early satiety, and nausea. Appetite can be assessed on a Likert scale.15 There are screening tools, but most of them are not practical for daily clinical practice, like the Mini-Nutritional Assessment tool. The Simplified Nutritional Appetite Questionnaire is more practical clinically, but it lacks the sensitivity and specificity of the lengthier assessment tools.16

The patient’s food intake should be assessed either through patient report or direct quantification of food eaten over a period of time.1 The number of meals the patient eats per day and the size or the percentage of the meals eaten should be recorded. A variety of tools can be used. The patient can keep a food diary or use applications on computers or handheld devices for tracking food consumption, or healthcare providers can do a calorie count.

Secondary causes of reduced food intake should be assessed. These include pain, stomatitis, constipation, dyspnea, depression and anxiety, and poor dietary habits. More information on the assessment and treatment of these symptoms can be found throughout this textbook.

The patient’s weight should be monitored. Fluid retention should be considered when evaluating weight changes. Muscle mass can be assessed through the mid-arm muscle area. Muscle strength can be assessed using handgrip, upper extremity, and lower extremity strength testing. More precise muscle strength can be achieved with upper-limb handgrip dynamometry.17

Laboratory tests and imaging can be used to measure nutritional status, inflammation, and body composition. Prealbumin is one of the better measures for assessing malnutrition. A low prealbumin level indicates low protein stores indicative of chronic anorexia. C-reactive protein (CRP) measures systemic inflammation, but cachexia can be present without an increase in CRP. Cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]), dual energy x-ray imaging (DEXA), anthropometry (mid-arm muscle area), and bioimpedance analysis are tests that can measure muscle mass. However, it is not clear how useful these tests are in treating CAS.1

The palliative APRN must assess the patient’s functional status. This can be accomplished through patient report on activities or provider assessment using the Karnofsky scale, the Palliative Performance Scale, or similar measures. In addition, the psychosocial effects of anorexia and cachexia should be assessed.

Cachexia and Anorexia Management

Identifying the goals of care and how they relate to management of CAS is important. The palliative APRN can initiate a goals of care discussion, so that he or she can inform the patient and family what is realistic, within the limits of the disease. The patient and family may want to treat CAS to increase body mass, weight, and functional status or to improve appetite for the sake of the pleasure of eating, or they may be simply looking for a way to help the patient. An understanding of the natural progression of disease and the pharmacologic and nonpharmacologic measures (Table 26.1) to treat CAS will help when counseling the patient and family to clarify and meet their goals.

Table 26.1 CAS Management

Intervention

Implementation

Comments

Pharmacologic

Megestrol

800 mg PO qd

Shown to improve appetite and weight. Increased risk of blood clots and increased mortality. Patients should be aware of this potential adverse effect before implementing.

Dronabinol

Starting dose is 2.5 mg PO bid (qd in elderly).

Treats anorexia in HIV/AIDS, treats therapy-related nausea in cancer patients

Glucocorticoids

Starting dose: 4 mg PO qd

Use of this regimen is limited due to side effects. Used often to treat anorexia and cachexia near the end-of-life.

Nonpharmacologic

Dietary counseling

Refer to dietitian in complex cases. Provide instruction to reduce size of meals but increase frequency.

No evidence that this will result in sustained weight gain or improved quality of life in advanced cancer patients. Patients with COPD did benefit from nutritional counseling in terms of increased oral intake, weight gain, and increased strength.

Oral care

Oral hygiene can prevent oral infection. Keeping the mouth moist can improve mastication and prevent infection.

Low-risk and low-cost interventions

Pharmacologic Management

Megestrol acetate (MA) is a synthetic progestin used as an antineoplastic agent and to stimulate appetite.18 The Cochrane Collaboration has done reviews of MA, the most recent in 2013.19 The meta-analysis considered outcomes like weight gain, improved quality of life, increased appetite, increased body mass, adverse effects, and death in patients with cancer, AIDS, or COPD and the elderly. The analysis found an increase in appetite and modest weight gain compared to placebo, but there was also an increase in thromboembolic events and mortality. There was no improvement in quality of life. Currently, MA is the most effective pharmaceutical for CAS, but patients should be aware of the side effects and limits of the drug before they start taking it.

The American Geriatric Society recommends avoiding MA in the elderly.20 One study found improved appetite and weight gain (mostly adipose tissue) with the use of MA over placebo in the elderly.21 This was a small, randomized, double-blind trial with 3 months of treatment and 3 months of follow-up without treatment and a 4-year survival analysis. Currently, MA is not recommended for patients with cardiac cachexia.12

The typical dosage of MA is 800 mg once a day, or 625 mg for the concentrated formulation.18 Other doses have been studied and showed some benefit; there is increased weight gain with higher doses.19 MA reaches peak plasma concentrations in 1 to 5 hours. It is metabolized by the liver and excreted by the kidneys and in the feces.

Dronabinol and other cannabinoids have been used to improve appetite in CAS resulting from multiple etiologies. Dronabinol, a synthetic cannabinoid, has been approved to treat anorexia related to HIV/AIDS.22,23 There is no evidence to support the use of dronabinol and cannabinoids in CAS related to cancer,24 but dronabinol is approved to treat cancer treatment-related nausea that is refractory to first-line antiemetics.23

The starting dose is 2.5 mg before lunch and supper; however, 2.5 mg once daily should be considered for geriatric patients and in patients who experience side effects with more frequent daily dosing. The maximum dosage is 20 mg per day in divided doses.23 The most common side effects involve the central nervous system and include feeling high, somnolence, and confusion. The initial half-life is 4 hours, but the terminal elimination half-life is 25 to 36 hours. Steady-state plasma levels are reached in 2 weeks.23

Glucocorticoids have shown some efficacy in improving appetite and weight gain, but no better than MA and with a worse toxicity profile.25 The toxicity may be limited if the drug is given for short periods of time; however, the beneficial effects wear off after the steroids are stopped.25 Glucocorticoids may be a better intervention for patients near the end-of-life. Doses as low as 4 mg per day of dexamethasone were used.26

Mirtazapine is known to produce increased appetite and weight gain as a side effect.27 Although it is being studied, there is currently insufficient evidence to support the clinical use of mirtazapine in treating CAS related to cancer or other chronic illnesses.28 Nonsteroidal anti-inflammatory drugs (NSAIDs) have been studied for their effectiveness in managing CAS. The drugs studied include celecoxib, ibuprofen, and indomethacin. Currently there is insufficient evidence to recommend their use in clinical practice.29

Thalidomide is thought to work by anti-inflammatory mechanisms, blocking cytokines or cytokine production and thereby treating the underlying causes of cachexia. Insufficient evidence exists to support the use of thalidomide, and its use is not recommended due to toxicities in the absence of efficacy.30

There currently is insufficient evidence to support the efficacy of eicosapentaenoic acid (EPA), an omega-3 fatty acid, but early studies show promise.31 Further research will need to be done to determine if EPA is effective. It is thought that EPA could inhibit tumor-induced lipolysis and muscle protein degradation by suppressing cytokines.

Ghrelin, a peripheral hormone that is secreted from the stomach, is being studied as a treatment for CAS. The release of ghrelin stimulates the release of growth hormone and stimulates orexigenic neurons in the hypothalamus, which is known to increase appetite. Ghrelin has been shown to increase appetite in healthy subjects.32 It has shown benefit in patients with renal failure, heart failure, and COPD.12,32,33 However, ghrelin is currently not approved by the U.S. Food and Drug Administration for any indication.

l-Carnitine given with celecoxib was compared with l-carnitine with celecoxib and MA. Both treatments were effective in increasing lean body mass and increasing physical daily activity. However, it was not compared to placebo, and the number of people finishing the study was less than 60.34 Another study looked at five types of treatment, with over 300 patients enrolled. The only group that showed a statistically significant increase in lean body mass was the one taking a combined medication regimen, including l-carnitine, MA, EPA, and thalidomide.35 Despite the problems of these studies, they suggest that multiple-drug regimens should be looked at more closely, but cannot yet be recommended for clinical practice.

Nonpharmacologic Management

Dietary counseling can play an important role in patients with anorexia and cachexia. Counseling has been shown to increase calorie intake in cancer patients in one study; however, the increase in weight did not reach statistical significance and appeared to be fat tissue.36 Dietary counseling includes education on modifying familiar or favorite foods to match patients’ changing tastes and needs, adding nutritional supplements, and decreasing the size and increasing the frequency of meals.

There is no conclusive evidence to support increased survival, significant weight gain, or improved quality of life with dietary counseling in cancer patients, but the risks are low and patients and families may value this kind of support. There is some evidence to support dietary counseling in patients with COPD. With therapy mainly in the form of nutritional supplements, patients with COPD experienced increased caloric intake, increased weight, and increased grip strength.13

Providing good oral care to reduce the risk of mucositis and oral mucosal infections can prevent these causes of decreased oral intake. This includes good oral hygiene. Patients at risk (those with reduced immunity, receiving radiation therapy, or receiving chemotherapy) or with mucositis should use a mouth rinse, like bicarbonate solution or chlorhexidine (alcohol-free) regularly. Using sucralfate-based saliva substitutes can provide needed moisture to the mouth to aid with mastication and prevent dryness. Using an antifungal or antibiotic agent in the presence of oral infection should be considered.

Exercise has shown some benefit in improving symptoms related to CAS.37 More evidence is needed to make recommendations on the types and quantity that work best, but it is likely this could be tailored to the patient. It is important for patients to avoid exercise that causes pain or is too strenuous; safety is always the first consideration.

Artificial Enteral and Parenteral Feeding

Parenteral feeding should be used only if the patient’s gastrointestinal tract is not functioning and the patient has a good prognosis.5 Parenteral feeding is often used temporarily prior to treating the gut dysfunction. Patients with advanced cancer likely will not see benefit from parenteral feeding and are apt to have more complications.38

Patients with advanced cancer receiving enteral feeding did not show significant benefit either.38 Tube feedings don’t improve survival in patients with advanced dementia.39 Artificial enteral feeding is often used in certain disease processes, such as severe dysphagia associated with stroke, when the patient’s quality of life is acceptable and it meets his or her goals of care. Also, patients with head and neck cancers who have lost the ability to swallow as a result of the disease or treatment can benefit from enteral feeding through a percutaneous endoscopic gastrostomy (PEG) tube.

Multimodal Approach

CAS is a syndrome with multiple components contributing to the symptoms, so it is reasonable to suspect that multiple modes of treatment, including pharmacologic, nonpharmacologic, and psychosocial measures, will be needed to address the CAS.40 There are no good studies that would allow recommendations to be made for specific treatment regimens; however, available evidence suggests a trend that a multimodal approach could help.40

Identifying the patient’s goals of care related to treating CAS is an initial step in using a multimodal approach. This will help tailor the interventions and will determine if using a pharmaceutical like MA is prudent. The goals will also inform the instructions provided during nutritional counseling. If patients want to maintain weight during disease-directed therapies, they should eat small meals several times a day, paying attention to the nutritional content of the food. However, if goals are geared toward comfort, instructing patients and families to focus on comfort feeding is important.

Existence of other symptoms and comorbidities will help to inform choices for a multimodal approach. For example, if patients are nauseated in addition to having CAS, antinausea agents with appetite-stimulating properties may be a wise choice. Patients who experience early satiety with nausea may benefit from metoclopramide. Patients with increased risk for thrombi should avoid MA. For patients who are depressed, mirtazapine may be considered.

Use of nutritional supplements like l-carnitine, EPA, protein, and vitamins should be explored with patients. There are few if any adverse reactions to these supplements, but caution should be used since there may be unknown drug interactions. There is not sufficient evidence to direct dosing recommendations. Patients should be aware of the limited efficacy these supplements could have on advanced diseases.

Nonpharmacologic measures should be part of a multimodal approach. The combination of pharmaceuticals, supplements, oral care, exercise, and dietary counseling should be directed by the patient’s goals.

Psychosocial Support

CAS not only affects the body but also has psychosocial implications for patients and families. Patients, who are already having to make psychosocial adjustments as a result of their underlying diseases, are also suffering from the social isolation caused by their anorexia and cachexia. They may avoid social situations to avert pressure to eat.41 The patient may have a desire to please, and eat when pressured, but this can strain relationships. Family members can also experience a sense of rejection, guilt, or helplessness when the patient refuses offers of food.

Food not only sustains life, but also plays a central role in most cultures, traditions, and celebrations. It is often a symbol of nurturing. Preparing food is one way we take care of the ones we love. Seeing patients eat less over time can be a reminder of the imminence of death.

Patients with CAS and their family members may express concern about the patient’s decreased appetite, changing appearance, prognosis, and changes in social interactions.42 Addressing these concerns is important to patients and families,43 but healthcare professionals may not have the knowledge or training to do so.44 APRNs specializing in palliative care need to develop expertise in addressing the physical and psychosocial sequelae of CAS.

The palliative APRN can arrange a family meeting to discuss the role of food in the patient’s care. This will create an opportunity for the patient and the family to discuss their views about eating food in light of the patient’s condition and disease. The APRN can establish goals of care as they relate to nutritional intake. This becomes a good time to educate both the patient and family on the impact that progressive illnesses have on appetite and weight loss.

End-of-Life Considerations

During the final hours to days of life, it is not uncommon for patients to eat and drink little to nothing. The patient or family may make requests at this time to address the patient’s poor nutritional intake or weight loss. This often includes requests for parenteral hydration. Simply discussing the options available to treat anorexia and cachexia misses an opportunity to explore what the patient and family really want. It is likely the family is seeking a way to provide care to their loved one. Finding meaningful ways for family members to do just that introduces hope that may not have been realized.

The goals of care discussion can be a great starting point to help the family identify more effective and meaningful ways of helping their loved one. When goals of care are directed toward treating symptoms and promoting comfort, educating the family about the difference between little or no intake of nutrients at the end-of-life and starvation is important. Starvation is what happens when someone who has the desire to eat is deprived of food; his or her body is otherwise capable of processing food and nutrients if they were available. When a patient does not eat at the end-of-life, it is due to the patient’s lack of desire to eat. The body also increasingly becomes unable to properly process food due to decreased motility and absorption in the intestines.

It is important for families to see the hope they provide to their loved one by their presence and commitment to care. Having some useful routines of care that family members can provide at the end-of-life goes a long way in comforting both the patient and the family. This includes an oral regimen of providing moisture through mouth swabs every couple of hours. Providing food to the patient should happen only if the patient desires it, taking into consideration the patient’s safety. Any food provided should be the right consistency, texture, and amount. Sometimes a taste is all that is needed; this is referred as to pleasure feeding or eating. If the sensation of taste is all that is desired, flavored ices can be effective. Safety always needs to be considered along with goals and comfort.

Case Study

MM was a 62-year-old male with recently diagnosed pancreatic cancer who opted to pursue chemotherapy. Before starting treatment for his cancer, he was hospitalized for failure to thrive. His appetite became very poor, and he was diagnosed with a partial post-outlet obstruction due to disease progression. He was made NPO for safety. This caused him discomfort, because, as he stated, he derived a lot of pleasure from eating. The palliative APRN was asked to evaluate him.

Physical assessment revealed bowel sounds. His abdomen was flat and there was no abdominal tenderness. At 5-foot-11 and 155 pounds, he had lost 15 pounds in the past month. He reported that he had passed gas and moved his bowels recently. He stated that for breakfast he had had a bite of toast and some milk but became full quickly. He drank a few sips of Ensure for lunch, with the same experience. He stated this had been typical for him over the past 2 weeks but had been getting worse recently. He denied pain, reported occasional nausea with vomiting, and denied shortness of breath, coughing, anxiety, and depression.

MM’s psychosocial history revealed that he was single with an adult daughter. He did not keep in contact with his daughter’s mother and did not have any significant or close relationships. He had been estranged from his daughter most of his daughter’s life, but he had been in contact with his daughter in recent years. He stated he lived in a studio apartment in an elevator building. He reported being raised Protestant but did not belong to a church community. Religion or spiritual beliefs and practices did not play a role in his life or his coping with his illness.

The palliative APRN held a goals of care conversation with the patient that revealed that eating was important to him. It was in fact one of his favorite things to do. He wanted to focus on doing what would allow him to eat better. He also stated that he would like to pursue disease-directed therapies, including chemotherapy. He wanted to be resuscitated with a trial of intubation. He appointed his daughter as his healthcare power of attorney. The palliative APRN prescribed metoclopramide 10 mg before meals for nausea and dexamethasone 4 mg three times a day. The APRN ordered physical activity for MM, and the nursing staff was directed to ensure he moved out of bed and ambulated in the hall at least three times a day.

His symptoms improved and he was discharged on this regimen, with a steroid taper after 1 week and follow-up in the palliative care clinic. He gained 2 pounds and reported eating 50% of the meals he received from the local senior meal delivery service.

Conclusion

CAS comprises a complex set of symptoms that are difficult to manage. The cause can be related to treatment, but as the end-of-life nears, it is almost always a manifestation of the progression of disease. Since reversal of this progression is often not possible, alleviating or slowing CAS is difficult, if not impossible. Identifying goals of care for nutrition and weight loss is important. Educating family members and primary care providers about CAS as part of the natural progression of disease is necessary. The palliative APRN can help the patient and family identify a regimen that will maximize the patient’s comfort. Though a palliative care focus cannot eliminate CAS, the palliative APRN can help improve some of the symptoms some of the time and can align care with the patient’s goals and optimize quality of life.

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