Factors predicting a successful outcome after pharmacologic bowel compensation.

OBJECTIVES: The authors determined those factors that predict a successful outcome in patients who receive pharmacologic agents to promote bowel absorption after massive intestinal resection. SUMMARY BACKGROUND DATA: Patients with the short bowel syndrome are maintained on long-term total parenteral nutrition (TPN) or more frequently considered for intestinal transplantation as part of their treatment program. The authors have administered a combination of trophic agents and a specialized diet to further enhance intestinal compensation and optimize nutrient absorption in patients with intestinal failure. METHODS: Forty-five TPN-dependent adults with a jejunal-ileal remnant < or = 50 cm and a portion of colon in continuity were treated with growth hormone, glutamine, and a modified diet for 4 weeks and observed for an average of 1.8 years. RESULTS: The average age of the patients was 43 years, the average jejunal-ileal length was 23 cm, and the average length of time the patient received TPN was 4.3 years. After 4 weeks of therapy, 26 (58%) were free of TPN support. Predictors of a favorable response included greater bowel length, lower body weight, and greater bowel length-body weight ratio. At follow-up, the percentage of patients who were not receiving TPN had fallen to 40%. CONCLUSIONS: Approximately half of a group of patients, thought to have absorptive surface area inadequate to be independent of TPN support, can maintain themselves on enteral feedings after this intestinal rehabilitation program. Because of the risk, costs, and alterations in lifestyle associated with long-term TPN or intestinal transplantation or both, it seems prudent to consider a program of bowel rehabilitation with an individual patient before embarking on another therapeutic plan.

A new treatment for patients with short-bowel syndrome. Growth hormone, glutamine, and a modified diet.

OBJECTIVE: The purpose of this study was to initially determine if growth hormone or nutrients, given alone or together, could enhance absorption from the remnant small bowel after massive intestinal resection. If clinical improvement were observed, this therapy would then be used to treat patients with the short-bowel syndrome over the long term. SUMMARY BACKGROUND DATA: Patients who undergo extensive resection of the gastrointestinal tract frequently develop malabsorption and require long-term parenteral nutrition. The authors hypothesized that the administration of growth factors and/or nutrients could enhance further compensation of the remnant intestine and thereby improve absorption. Specifically, animal studies have shown that there is enhanced cellularity with the administration of growth hormone (GH) or glutamine (GLN), or a fiber-containing diet. METHODS: Initially, 17 studies were performed in 15 total parenteral nutrition (TPN)-dependent short-bowel patients over 3 to 4 weeks in the clinical research center; the first week served as a control period, and during the next 1 to 3 weeks, the specific treatment was administered and evaluated. Throughout the study, food of known composition was provided and all stool was collected and analyzed to determine absorption across the remaining bowel. The effect of a high-carbohydrate, low-fat diet (DIET), the amino acid glutamine (GLN) and growth hormone (GH) administered alone or in combination with the other therapies (GH + GLN + DIET) was evaluated. The treatment was expanded to 47 adults (25 men, 22 women) with the short-bowel syndrome, dependent on TPN for 6 +/- 1 years. The average age was 46 +/- 2 years, and the average jejunal-ileal length was 50 +/- 7 cm (median 35 cm) in those with all or a portion of colon and 102 +/- 24 cm (median 102 cm) in those with no colon. After 28 days of therapy, the patients were discharged on only GLN + DIET. RESULTS: The initial balance studies indicated improvement in absorption of protein by 39% accompanied by a 33% decrease in stool output with the GH + GLN + DIET. In the long-term study, 40% of the group remain off TPN and an additional 40% have reduced their TPN requirements, with follow-up averaging a year and the longest being over 5 years. CONCLUSION: GH + GLN + DIET offers a potential method for providing cost-effective rehabilitation of surgical patients who have the short-bowel syndrome or other complex problems of the gastrointestinal tract. This therapeutic combination also may be useful to enhance bowel function in patients with other gastrointestinal diseases and those requiring extensive intestinal operations, including transplantation.

Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome.

BACKGROUND: Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid, electrolytes, and other nutrients. Although the remaining bowel undergoes morphological and functional adaptation, often these changes are inadequate to support the individual by enteral feedings, and parenteral nutrition is required to prevent dehydration, electrolyte disturbances, and malnutrition. Substances such as growth hormone, glutamine, and fiber exert bowel-specific trophic effects and either directly or indirectly influence nutrient absorption. This study was undertaken to determine whether the co-administration of exogenous growth hormone, supplemental glutamine, and a modified fiber-containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection. METHODS: Ten patients (5 men, 5 women, aged 43 +/- 4 years) with short bowel syndrome were studied 6 +/- 1 years after surgical resection. All patients were admitted to the Clinical Research Center for a 28-day period; the first week served as a control period when nutritional (enteral and parenteral) and medical management simulated usual home therapy. Thereafter, eight patients received exogenous growth hormone, supplemental glutamine, and a modified high-carbohydrate, high-fiber diet. Two patients were treated with the modified diet alone. The efficiency of net nutrient absorption (percent absorbed) for total calories, protein, fat, carbohydrate, water, and sodium was calculated from the measured nutrient intake and stool losses. RESULTS: Three weeks of treatment with growth hormone, glutamine, and a modified diet increased total caloric absorption from 60.1 +/- 6.0% to 74.3 +/- 5.0% (p < or = .003), protein absorption from 48.8 +/- 4.8% to 63.0 +/- 5.4% (p < or = .006), and carbohydrate absorption from 60.0 +/- 9.8% to 81.5 +/- 5.3% (p < or = .02). Fat absorption did not change (61.0 +/- 5.3% to 60.3 +/- 7.9%, p = NS). Water and sodium absorption increased from 45.7 +/- 6.7% to 65.0 +/- 7.3% (p < or = .002) and from 49.0 +/- 9.8% to 69.6 +/- 6.5% (p < or = .04), respectively. These absorptive changes resulted in a decrease in stool output (1,783 +/- 414 g/d control period vs 1,308 +/- 404 g/d third week of treatment, p < or = .05). Treatment with diet alone did not influence nutrient absorption or stool output. CONCLUSIONS: The combined administration of growth hormone, glutamine, and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection. These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients. This therapy may offer an alternative to long-term dependence on total parenteral nutrition for patients with severe short bowel syndrome.

Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring nutritional rehabilitation.

OBJECTIVE: The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the composition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy. SUMMARY BACKGROUND DATA: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein. METHODS: Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n = 4) or, in addition, received GH 0.14 mg/kg/day (n = 10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and nonmineral-containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition. RESULTS: The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311 +/- 0.6 kg vs. 1.988 +/- 0.2 kg, p < or = 0.03) and more protein (1.417 +/- 0.3 kg vs. 0.086 +/- 0.1 kg, p < or = 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004 +/- 0.3 kg vs. 0.129 +/- 0.2 kg, p < 0.05). GH administration altered substrate oxidation (respiratory quotient = 0.94 +/- 0.02 GH vs. 1.17 +/- 0.05 STD, p < or = 0.0002) and the use of available energy, resulting in a 66% increase in the efficiency of protein deposition (13.37 +/- 0.8 g/1000 kcal vs. 8.04 g +/- 3.06 g/1000 kcal, p < or = 0.04). CONCLUSIONS: GH administration accelerated protein gain in stable adult patients receiving aggressive nutritional therapy without a significant increase in body fat or a disproportionate expansion of ECW. GH therapy accelerated nutritional repletion and, therefore, may shorten the convalescence of the malnourished patient requiring a major surgical procedure.