CANCER PAIN: SPECIAL CONSIDERATIONS FOR PATIENTS WITH CANCER

Delirium in Patients With Cancer

Delirium is an acute state of confusion that frequently occurs in patients with advanced cancer and can lead to death. The condition is more common in the elderly. Delirium is easily reversible if recognized early in about two-thirds of patients, however, its presence denotes a poor outcome and as many as 30 percent of cancer patients die within a month of diagnosis. About 85 percent of cancer patients develop delirium before death. Delirium may be confused with other common medical conditions, such as anxiety, restlessness and insomnia. The onset of these common symptoms in a patient who has been otherwise stable should raise suspicion as to the presence of delirium, especially if associated with mood changes.

Major causes of reversible delirium include pain medications (opioids), infection, electrolyte imbalance, dehydration and some common medications. Medications for regulating sleep and mood are notorious for precipitating delirium, especially in patients taking opioids. Others may include steroids, allergy and over-the-counter medications. Constipation is a frequently forgotten cause of delirium in patients on pain medications. Family members may be the first to notice the changes of delirium. These changes frequently start at night, when the patient gets more confused and has difficulty falling sleep. The occurrence of vivid dreams and incoherent talk are not infrequent. The patient may start having memory problems and find it difficult to write or adjust finances. The normal sleep-wake cycle may get confused and the patient may have more tendencies to sleep during the day and lie awake at night. Patients with delirium may have periods where they are fully normal, interrupted with periods of confusion, several times during the day. The patient's expression of symptoms such as pain is greatly exaggerated during these periods of confusion and well-meaning relatives may provide more frequent pain or sleep medications to the patient, which can worsen the delirium.

It is very important for you and your family members and to know and understand the cause of and treatment for delirium. Treating delirium depends on reversing the cause for the delirium. Family members should notify your physician promptly if they notice symptoms suggestive of early delirium. Treatment can be as simple as changing the type of pain medication, giving an enema for constipation or fluids for dehydration. Simple measures such as lighting the patient's room, writing the date and the day in front of the patient, providing a calendar or having a family member stay with the patient are of great help in making many patients regain orientation.

Eating-related Issues in Patients With Advanced Incurable Illness

Anorexia, Cachexia and Wasting
Not eating enough is a common concern of many patients with advanced incurable illnesses and of their loved ones. These concerns are a normal reaction to weight loss and decreased appetite. In addition, these patients often loss their ability to do things and fatigue may become a significant problem. Family members intuitively undertake efforts to cook and provide sufficient amounts of the right types of food for the patients.

It is important to understand, however, that incurable illnesses, such as cancer or HIV infection can distort the normal processing of nutrients. Providing extra food or the right food is, unfortunately, not beneficial in these cases. Many patients are not able to get enough food into the body because of a damaged or dysfunctional gastrointestinal tract or severe symptoms such as pain. Providing extra food or giving food through a tube or intravenously may help those patients. Typically, it takes several weeks to decrease fatigue or improve function. Therefore, nutritional support needs to take into account the big picture.

Loss of Weight and Appetite: Mechanism and Causes
Advanced Incurable Illness
Most active tumors and uncontrolled HIV infections activate the metabolism and cause inflammation comparable to that of a chronic infection. Muscle and fat tissues are destroyed, and the liberated nutrients go to the liver to feed an increased production of proteins and other substances. This production is a normal reaction to an infection or other stress event. Because these substances do not help fight the cancer or HIV infection, their production is useless. Providing more food will only feed this cycle, rather than help build muscle. This phenomenon is called "primary cancer anorexia/cachexia syndrome" or "HIV wasting syndrome." Anorexia is a lack or loss of appetite that results in the inability to eat. Cachexia is a state of general poor health, malnutrition, weakness and emaciation.

Starvation, Infection or Prolonged Bed Rest
Starvation can be caused by impaired enteral (intestinal) intake due to alterations in the function or integrity of the gastrointestinal tract or by interfering symptoms or conditions that reduce a person's desire or ability to eat. Loss of proteins through body fluids or the feces also may lead to starvation. Improving nutritional intake by managing these causing factors or by providing nutritional therapy has been shown to increase weight and probably quality of life in a subgroup of cancer patients. For example, patients with bowel obstruction in the context of a slowly growing tumor or patients with severe pain or shortness of breath (i.e., dyspnea) who receive excellent symptom control usually can increase their food intake orally. The clinical reality, however, is that starvation related to secondary anorexia/cachexia is not diagnosed in many patients with advanced cancer or is not distinguishable from a concomitant primary anorexia/cachexia syndrome component. The inflammatory response, or metabolic distress, associated with acute or chronic infection also can impede metabolism of nutrients and lead to cachexia. Prolonged immobility can lead to loss of muscle tissue as a result of decreased muscle activity.

Assessment of Eating-related Issues
Your physician may use a few relatively simple measures to determine if you have eating-related issues. These assesments may include evalutating recent involuntary weight loss, recent impaired nutritional intake, changes in your perception of your body, chronic nausea, fatigue, and determining if you have cachexia or anorexia. Your physician may ask you to provide information about your weight and weight loss, how much food you are eating, if you are having problems that prevent you from eating, and your ability to perform activities of daily living.

If your cancer is in an advanced state, your physician should perform such assessments so he or she can prioritize the problems. Symptoms of anorexia/cachexia can be obscured by other symptoms such as anxiety or shortness of breath, and determining that could be critial in planning treatment. It is especially important to identify factors that may aggravate primary anorexia/cachexia. These factors (secondary anorexia and cachexia) may include pain, constipation, bowel obstruction, difficulty swallowing (dysphagia), taste abnormalities, dry mouth (xerostomia), nausea, cognitive impairment, dehydration, and infection. Your physician also should determine if treating anorexia and cachexia is important to you to determine what measures should be used. For example, if you are suffering from a perceived change in body image, you may appreciate receiving treatment leading to weight gain, even in the absence of symptomatic improvement.

Managing Anorexia and Cachexia in Patients With Cancer
Managing patients with advanced cancer who are suffering from anorexia, cachexia and related symptoms must be based on a careful multidimensional evaluation. Managing your symptoms and distress, as well as the distress of family members, often requires simultaneously addressing physical, psychosocial and existential issues to prioritize the issue of anorexia and cachexia compared to other problems in your situation. Your physician should present treatment options for the underlying illness and complications, so together you can choose which options are best for you. You and your physician should communicate and decide which options are best for based on your coping style, cultural background and preferences of decision making. Furthermore, your living situation and the available social and financial resources may influence decisions related to eating and nutrition.

In the comprehensive management approach, health care professionals try to reach an agreement with you and your family about treatment goals and meaningful outcomes. The purpose of the treatment may be to control a specific symptom (e.g., decreased food intake, sensation of anorexia, chronic nausea, or fatigue), to improve function, body image, or overall quality of life; or to prolong life expectancy.

It is important to detect and treat reversible causes of anorexia or cachexia (Table 1).

Table 1: Causes of Cancer-related Anorexia and Cachexia

A) Starvation/Malnutrition

Impaired oral intake

· An inflammatory condition of the mouth (stomatitis), taste alterations, zinc deficiency, dry mouth (xerostomia), dehydration

· Difficulty swallowing (dysphagia), a severe burning sensation while swallowing (odynophagia)

· Severe constipation, bowel obstruction, autonomic failure

· Vomiting, heartburn

· Severe pain, difficulty breathing (dyspnea), depression, cognitive impairment, delirium

· Social and financial obstacles

Impaired gastrointestinal absorption

· Malabsorption, exocrine pancreatic insufficiency, chronic severe diarrhea

Significant loss of proteins

· Frequent drainage of fluid in the abdomen (ascites) or pleural fluid punctures, nephrotic syndrome (an abnormal condition of the kidney)

B) Loss of muscle mass

· Prolonged immobility

· Growth hormone deficiency, hypogonadism, aging, sarcopenia

C) Other catabolic states than primary anorexia/cachexia syndrome

· Chronic and acute infections

· Treatment with proinflammatory cytokines

· Chronic heart failure (cardiac cachexia), lung disease, renal failure

· Poorly controlled diabetes mellitus, liver cirrhosis

· Hyperthyroidism

D) Primary anorexia/cachexia syndrome

· Anorexia, chronic nausea, early satiety, asthenia/fatigue

· Catabolic state with complex metabolic, neuroendocrine and anabolic alterations

Experts don't agree on whether nutritional support is helpful to patients with advanced cancer. Following is a practical approach for you and your physician to follow:

· Your physician should assess the relative importance of a starvation component.

· Your physician should investigate the probability of reversible inflammation (i.e., infection, primary anorexia/ cachexia syndrome).

· You and your physician should consider the likelihood of your survival and what nutritional support will provide for you.

· Your physician should check the integrity of your upper and lower gastrointestinal tract and evaluate your hydration status.

· Your physician should carefully discuss the goals of nutritional intervention with you and your family and you all should discuss and agree upon meaningful outcomes.

· Your health care team should provide dietary counseling.

· Your physician might consider enteral nutrition if you have symptoms of starvation and functioning bowel. Enteral nutrition is liquid nutrition provided directly to the stomach or intestine through a feeding tube.

· Your physician may consider parenteral nutrition (PEN). Parenteral nutrition involves delivering nutrients intravenously directly into the bloodstream. Your physician will consider PEN only if you have a predominant, starvation component, your physician is able to provide an accurate estimation of life expectancy, you have a good understanding of the individual indication and effects and side effects of PEN, and if you have obstacles for the use of enteral nutrition

Currently, corticosteroids, progestins and prokinetics are the only three therapies for anorexia/cachexia for which there is enough evidence to support their use in specific patients. In patients with a life expectancy of only a few weeks, who suffer from anorexia, asthenia and chronic nausea, a trial regimen of corticosteroids is preferable. Pain or shortness of breath is often another indication for the prescription of corticosteroids. The short-term side effects of corticosteroids are often minimal; however, symptomatic diabetes mellitus or steroid psychosis may develop. The corticosteroid regimen requires reevaluation after one week, and tapering should begin at the second day of treatment.

Progestins (megestrol acetate and medroxyprogesterone acetate) are a good choice for patients whose predominant symptoms are anorexia or change in body image and do not have a history of thromboembolic events. Progestins often improve appetite within a few days. A dose-response relationship has been shown, but side effects also increase with increasing dose. Metoclopramide is a good medication for patients whose predominant symptoms are early satiety or chronic nausea but may be of little help to patients whose dominant symptoms are anorexia, cachexia or fatigue.

Hydrazine sulphate, cyproheptadine and pentoxifylline were found to be of limited usefulness in patients with cancer-related anorexia and cachexia.

Several new medications are undergoing clinical evaluation but are not yet indicated for use outside of experimental settings. They include thalidomide, omega-3 fatty acids, growth hormone and insulin-like growth factors, androgenic anabolic steroids, cannabinoids, melatonin, beta 2- adrenergic mimetics, non-steroidal anti-inflammatory drugs and adenosine-tri-phosphate. These new agents have different mechanisms of action and eventually may be used in combination treatments.

It is also important to provide adequate education and counseling to patients and families. Your physician should carefully address your concerns and your family members concern that you are "starving to death." You and your family need to understand that, if you have primary anorexia/cachexia syndrome and because of the generally irreversible underlying abnormalities, giving you more food will not automatically result in fat or muscle gain. Reframing your perceptions can decrease emotional distress in both you and your family members and can help you maintain the social enjoyment of mealtimes.