[[ International SymposiumF03 ]]
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Kenneth A. Kudsk, M. D.
Professor of Surgery |
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The goals of specialized nutrition support are to: 1) replenish and support lean body mass and host defenses, 2) avoid complications of starvation-induced malnutrition without aggravating the clinical condition, and 3) significantly improve outcome. In times of stress, there is a massive mobilization of lean body mass from somatic protein depots into the amino acid pool. These amino acids are delivered to the liver for the production of acute phase proteins and albumin, to the healing wounds, and to the bone marrow for the production of white cells to fight infection. The body can only afford to lose approximately 40% of its lean body mass before developing a state of irreversible malnutrition. The main goal of nutrition support is to keep patients from developing progressive starvation-induced malnutrition. In 1992, our group randomized 98 patients to either early enteral or early parenteral nutrition using a standard enteral formula which had been on formulary for at least three years prior to the institution of the study and pair-fed trauma patients with a parenteral solution having similar concentrations of protein, carbohydrate, and fat. Severely injured patients with reoperation within 72 hours or Abdominal Trauma Indices greater than 40 were included in this study. These severely injured patients were excluded from the Denver studies. Just as the Denver studies showed, there was a significant reduction in pneumonias, intra-abdominal abscesses and infections in the patients randomized to enteral feeding, but the primary effect was in those patients who were the most severely injured. In patients with high Injury Severity Scale scores or high Abdominal Trauma Indices, if patients were randomized to TPN, their risk of infection was increased by anywhere from 6 to 11 times the rate of patients randomized to enteral feeding. Even within the most severely injured patient population, the incidence of pneumonia or abscess was much higher in the group randomized to parenteral nutrition. Enteral feeding was not without its complications, and two patients failed to tolerate even 50% of their nutrient goals by 1 week. Diarrhea was more common in the enterally fed patients, and there was one patient with a bowel obstruction secondary to the jejunostomy placement. The gastrointestinal tract has many functions including digestion, absorption, and an immunologic defense. Approximately 50% of the total immune system of the body lines the gastrointestinal tract, and 80% of the immunoglobulin produced by the body is secreted across the mucosa as a defense against the high bacterial concentrations within the lumen. In addition to the normal barriers of gastric acidity, normal motility, and an intact mucosa, IgA produced by committed plasma cells within the lamina propria maintain the normal balance of endogenous microflora. There is considerable experimental data to suggest that when the gastrointestinal tract is not fed, these mechanisms may fail. There have been multiple mechanisms proposed for the increased infections including an immunosuppression related to the TPN as well as intestinal factors such as mucosal atrophy increased intestinal permeability, or defects in the gut-associated lymphoid tissue. Data from our institution showed an increase in intestinal permeability following trauma in approximately one-third of patients within 48 hours of injury that returned to normal by 7-10 days using as a marker permeability to lactulose and mannitol. Subsequent studies, however, have not shown that there is an increase in bacterial translocation in trauma patients who account for the increased incidence of pneumonia and intra-abdominal abscesses that have been found in the clinical study. Recent attention has been addressed towards the gut-associated lymphoid tissue (GALT). In many experimental models, the basic consensus is that in situations where there is an increase in bacterial translocation, there is generally an overgrowth of bacterial flora and a reduction in intestinal lgA. Nutrition has been shown to have effects upon these three factors. Intravenous TPN or elemental diets appear to be associated with lower levels of lgA, bacterial overgrowth, and increases in bacterial translocation into the mesenteric lymph node. What has been ignored in these studies is the GALT which accounts for the lgA levels. GALT consists of both an affector arm which responds to an antigenic challenge as B cells home to Peyer's patches where they are sensitized to new antigenic challenges. These cells then traffic through the thoracic duct and serve as the effector arm in mucosal defense producing secretory lgA within the lamina propria. The secretory lgA is transported across the mucosa into the lumen where the lgA binds and agglutinates bacteria, viruses, et al. In animals randomized to TPN, there is a significant GALT atrophy within the Peyer's patches, the intraepithelial space, and in the lamina propria, but this atrophy is prevented by either administration of chow or a complex enteral diet. Within the lamina propria, a normal balance of helper to suppressor cells are maintained with complex enteral diet. It thus appears that the route and type of feeding affects the GALT dramatically exerting an effect upon generalized mucosal immunity in nonintestinal sites. This is significant because not only do the cells home back to the lamina propria, producing high levels of secretory lgA with the lumen of the gastrointestinal tract, they also home to lamina propria within the nasopharynx, the bronchus, and the bronchioles, producing an immunologic defense important in the defense against pneumonia. Current work just now being performed demonstrate that IV feeding significantly impairs mucosal defense to an infectious challenge. These effects can be partially reversed with glutamine or completely reversed with bombesin.
References: 2. Li J, Kudsk KA, Gocinski B, Dent D, Glezer J, Langkamp-Henken B: Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue. J Trauma 39(1): 44-52, 1995. 3. Kudsk KA, Li J, Renegar KB: Loss of upper respiratory tract immunity with arenteral feeding. Ann Surg 223(6):629-38, 1996.
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