The enteral feeding of surgical patients began as supportive therapy to correct nutritional deficiencies in severely ill patients. More recently, the therapeutic effects of select nutrients have been recognized. These agents are now being used in dosages greater than those required to correct nutritional deficiencies as part of active nutritional pharmacology, or immunonutrition. A review by Alexander discusses the evidence for using the most common pharmaconutrients (arginine, glutamine, and long-chain fatty acids) in selected conditions.

Pharmaconutrients have been studied most extensively in patients following complex upper gastrointestinal surgery. Use of a macronutrient formula called Impact in critically ill surgical patients was associated with a 70 percent reduction in wound complications and a 22 percent reduction in length of hospital stay. The early studies have been confirmed with a meta-analysis of 11 randomized trials that included more than 1,000 patients.

Overall, Impact was associated with a significant reduction in infections and a 2.5–day reduction in average hospital stay. The greatest benefit occurred in patients who had some degree of malnutrition and those who received the formula for at least five days.

Adding arginine and fish oil supplements to enteral feeding of burn and trauma patients was reported to reduce total infections by 67 to 78 percent, resulting in a 31 percent decrease in hospital stay. Studies of specific conditions report a 75 percent reduction in wound infections and significant reductions in abdominal abscess, multiple organ failure, pneumonia, bacteremia, and inflammatory response syndrome. Studies of patients in surgical intensive care units showed a 40 percent reduction in sepsis and a 20 percent reduction in hospital stays associated with use of a pharmaconutrient formula.

In a meta-analysis of studies involving 1,482 critically ill patients, significant reductions were demonstrated in ventilator dependency, infection rate, and hospital stay. Overall mortality in critically ill patients was not reduced in two earlier studies but was significantly reduced (from 32 to 19 percent) in a subsequent prospective, randomized trial of 128 patients with sepsis in intensive care units.

Transplantation surgery is the other area in which pharmaconutrients have been studied. The Impact formula and studies of arginine and fish oil independently show prolongation of graft survival. More recent studies have reported that the combination of arginine and canola oil was associated with a 50 percent reduction in rates of rejection. The greatest benefits occurred in cadaveric transplants and in black patients.

The apparently paradoxic action of reducing infection and rejection rates cannot yet be fully explained. The authors suggest that pharmaconutrients down-regulate inflammatory responses and reduce production of cytokines, which inhibit multiple organ failure and complications of infections. They may also change the predominant form of inflammatory response, thus reducing the rate and severity of rejection.

The physiologic and pharmacologic actions of individual pharmaconutrients are incompletely understood (see accompanying table). In high concentrations, arginine induces several hormones, including pituitary growth hormone, insulin, vasopressin, adrenal catecholamines, and somatostatin. Arginine also acts directly on the immune system, and when it is metabolized, it produces several physiologically significant products, including nitric oxide, creatine, citrulline, and ornithine. Even though glutamine is the most abundant amino acid, it may still have strong pharmacologic effects because it is well recognized as the preferred fuel for enterocytes, lymphocytes, and neutrophils. All three types of long-chain fatty acids play significant roles in cell membrane function and the regulation of the metabolic pathways of inflammation. Known actions of the long-chain fatty acids include reduction in inflammatory mediators, production of cytokines, and immune responses.