Cachexia, which means “poor condition” in Greek, is a multidimensional set of adaptations encompassing a variety of alterations that range from physiologic to behavioral. Adverse consequences of cachexia have been documented in patients with cancer, congestive heart failure, acquired immunodeficiency disease and other diseases. Accelerated loss of skeletal muscle in the context of chronic inflammation is a characteristic feature of cachexia. Many chronic diseases feature some nutritional changes of cachexia such as weight loss, negative nitrogen balance, hypoalbuminemia, hyperinsulinemia, hypertriglyceridemia and hypocholesterolemia. Cachexia may develop in some elderly persons without obvious disease. Kotler reviewed the literature about cachexia and discussed recent advances in the understanding of the condition.

Cachexia and starvation are the two major forms of malnutrition. Starvation is pure caloric deficiency, and the resultant changes can be reversed by appropriate feeding. In contrast, cachexia is associated with inflammatory or neoplastic conditions causing an acute-phase response, and feeding does not reverse the resultant changes (see accompanying table). Body weight is considered the major determinant of nutritional status, with excessive declines in weight defined as abnormal. Measurement of body weight cannot distinguish between lean tissue or fat. Current nutritional analysis uses a body compartment analysis that distinguishes fat from fat-free mass. Fat-free mass is further separated into body cell mass and extracellular mass. Persons with cachexia lose roughly equal amounts of fat and fat-free mass but maintain extracellular volume. Acute-phase reactants responding to inflammation or neoplasm and regulated by proinflammatory cytokines require the consumption of body stores of amino acids, driving the loss of skeletal muscle.

Hypermetabolism, an elevation in resting energy expenditure, is an important feature of cachexia. This is thought to be the major cause of weight loss in these patients, but anorexia resulting from proinflammatory cytokine activity, including altered gastric emptying, a decrease in intestinal blood flow and bowel motility alterations, has also been reported.

Cachexia resulting from a rise in acute-phase reactants can occur with cancer, infection, rheumatologic disease, congestive heart failure, end-stage renal disease, chronic obstructive pulmonary disease and other inflammatory conditions. Various treatments can help mitigate the morbidity of the condition. The use of hypercaloric feedings is generally not successful in overcoming protein degradation. Appetite stimulants, such as megestrol, may increase calorie intake but generally increase fat, not fat-free mass. Anabolic therapies, such as human growth hormone and anabolic steroids, that promote protein synthesis or inhibit protein breakdown also have been used. In one study, anabolic steroids resulted in an increase in fat-free mass in HIV-infected patients. Anabolic steroids have also been used with some success in patients with alcoholic hepatitis and end-stage renal disease. Exercise training has nutritional benefits in patients with congestive heart failure and HIV infection. Anticytokine therapies, including pentoxifylline and thalidomide, are being tested. Anti-inflammatory agents, such as prednisolone and indomethacin, may have greater impact in nonmalignant cachexia conditions such as rheumato-logic disease.

The author concludes that although the severity of the underlying disease is a better predictor of disease outcome than cachexia itself, further development of nutritional therapies could help preserve skeletal muscle mass and maintain functional capacity.

editor's note: Cachexia is usually evident in the clinical evaluation but can also exist in cancer patients with only slight weight changes. Minimal baseline testing should include weight loss (greater than 5 percent per month being severe) and serum albumin level (less than 2.4 g per dL [24 g per L] being severe). Assessments of lean body mass and fat deposits are less reliable indicators. Metabolic abnormalities can also cause anorexia and asthenia. Corticosteroids and progestational drugs can improve appetite, increase food intake and enhance the sense of well-being, as well as increase weight gain. Hydralazine has been used in some situations but does not appear to be useful in the treatment of cancer cachexia. Megestrol acetate has been used widely to treat cachexia in patients with cancer and AIDS. Maximal weight gain occurs within eight weeks but is due mainly to an increase in fat mass and partly to edema. No improvement is noted on the Karnovsky index. Thalidomide and melatonin are being tested because of their effect on tumor necrosis factor-alpha and beta₂-adrenoreceptor agonists because of their effects on muscle metabolism. Parenteral nutrition can facilitate chemotherapy but is not as efficient a route for managing cachexia as is a functioning gastrointestinal tract. Optimal management of cachexia is waiting for effective anticytokine drug development.—r.s.