Thomas R. Ziegler

Clinical and Metabolic Efficacy of Glutamine-supplemented Parenteral Nutrition after Bone Marrow Transplantation: A Randomized, Double-Blind, Controlled Study

OBJECTIVEnTo determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation.nnnDESIGNnDouble-blind, randomized, controlled clinical trial.nnnSETTINGnUniversity teaching hospital.nnnPATIENTSnForty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies.nnnINTERVENTIONnParenteral nutrition was initiated the day after bone marrow transplantation (day 1). The experimental solution was supplemented with L-glutamine (0.57 g/kg body weight per day) and provided estimated requirements for energy and protein. The control solution was a standard, glutamine-free, isonitrogenous, isocaloric formula.nnnMEASUREMENTSnNitrogen balance was determined between days 4 and 11 in the initial 23 patients. The incidence of clinical infection and microbial colonization, time until bone marrow engraftment, indices of clinical care, and other data related to hospital morbidity were recorded for all patients.nnnRESULTSnThe glutamine-supplemented patients (n = 24) were clinically similar to the controls (n = 21) at entry. Nutrient intake was similar in both groups; however, nitrogen balance was improved in the glutamine-supplemented patients relative to the controls (-1.4 +/- 0.5 g/d compared with -4.2 +/- 1.2; P = 0.002). Fewer experimental patients developed clinical infection (three compared with nine in the control group; P = 0.041), and the incidence of microbial colonization was also significantly reduced. Hospital stay was shortened in patients receiving glutamine supplementation (29 +/- 1 d compared with 36 +/- 2 d; P = 0.017).nnnCONCLUSIONnPatients receiving glutamine-supplemented parenteral nutrition after bone marrow transplantation had improved nitrogen balance, a diminished incidence of clinical infection, lower rates of microbial colonization, and shortened hospital stay compared with patients receiving standard parenteral nutrition. These effects occurred despite no differences between groups in the incidence of fever, antibiotic requirements, or time to neutrophil engraftment.

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

ObjectiveThe 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 DataPatients 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. MethodsInitially, 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. ResultsThe 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.

Parenteral Nutrition in the Critically Ill Patient

A 67-year-old woman with type 2 diabetes mellitus undergoes extensive resection of the small bowel and right colon with a jejunostomy and colostomy because of mesenteric ischemia. In the surgical intensive care unit, severe systemic inflammatory response syndrome with possible sepsis develops. The patient is treated with volume resuscitation, vasopressor support, mechanical ventilation, broad-spectrum antibiotics, and intravenous insulin infusion. Low-dose tube feedings are initiated postoperatively through a nasogastric tube. However, these feedings are discontinued after the development of escalating vasopressor requirements, worsening abdominal distention, and increased gastric residual volume, along with an episode of emesis. The hospital nutritional-support service is consulted for feeding recommendations. A discussion with the patient’s family reveals that during the previous 6 months, she lost approximately 15% of her usual body weight and decreased her food intake because of abdominal pain associated with eating. Her preoperative body weight was 51 kg (112 lb), or 90% of her ideal body weight. The physical examination reveals mild wasting of skeletal muscle and fat. Blood tests show hypomagnesemia, hypophosphatemia, and normal hepatic and renal function. Central venous parenteral nutrition is recommended.

Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study.

Glutamine (Gln) is an important nutrient substrate for lymphocytes and macrophages in vitro. This pilot study evaluated effects of Gln supplementation on circulating lymphocytes and lymphocyte subsets after allogeneic bone marrow transplantation (BMT). Adult patients received either parenteral nutrition supplemented by L-Gln (Gln-PN) or standard Gln-free PN after BMT. Leukocyte and total lymphocyte counts were determined during hospitalization, and flow cytometry studies of peripheral mononuclear cells were performed 1 to 2 weeks after hospital discharge. The Gln-PN group demonstrated a higher percentage of blood lymphocytes during hospitalization. At flow cytometry, patients who received Gln-PN had an increased total lymphocyte count (332 +/- 50 versus 590 +/- 71 cells/microL, P = 0.010); greater numbers of total T lymphocytes (54 +/- 19 versus 229 +/- 70 cells/microL, P = 0.030); and higher CD4+ and CD8+ T-lymphocyte counts in peripheral blood compared with controls. Gln-PN may support lymphocyte recovery after BMT.

A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients

OBJECTIVEnIn a randomized, double-blind, prospective clinical trial, we evaluated the metabolic effects of glutamine-supplemented parenteral nutrition in patients with bone marrow transplants. We compared hospital charge and cost data for the two groups of patients in the trial.nnnDESIGNnRetrospective review.nnnSETTINGnBone Marrow Transplant Unit, Brigham and Womens Hospital, Boston, Mass.nnnSUBJECTSnForty-three patients admitted to the Bone Marrow Transplant Unit were assigned randomly to receive either standard parenteral nutrition or an isocaloric, isonitrogenous parenteral nutrition solution containing glutamine starting on day 1 after bone marrow transplant. The two groups were well matched for diagnosis, antineoplastic treatment, and sex.nnnMEASURESnThe primary clinical end points evaluated were nitrogen balance, length of hospitalization, incidence of infection, and results of microbial culture. After completion of the study, we compared the hospital charges for the categories of room and board, surgery, laboratory, pharmacy, radiology, ancillary, and miscellaneous between the two groups of patients.nnnSTATISTICAL ANALYSIS PERFORMEDnThe two groups were compared using the unpaired t test or Mann-Whitney test for nonparametric measurements. A P value of < .05 was considered significant.nnnRESULTSnNitrogen balance improved in the glutamine-supplemented group compared with control subjects (-1.4 +/- 0.5 g/day vs 4.2 +/- 1.2 g/day, respectively; P = .002). Length of hospitalization was significantly shorter in the glutamine-supplemented group than in the control group (29 +/- 1 day vs 36 +/- 2 days, respectively; P = .017). The incidence of positive microbial cultures and clinical infection was also significantly lower with glutamine supplementation. Hospital charges were

Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood

21,095 per patient less in the glutamine-supplemented group compared with charges for patients who received standard therapy. Room and board charges were significantly different:

Insulin-like growth factor-I improves mucosal structure and function in transplanted rat small intestine.

51,484 +/- 2,647 for the glutamine-supplemented group vs

Potential role of glutamine supplementation in nutrition support

61,591 +/- 3,588 in the control group (P = .02).nnnCONCLUSIONnThis intervention study using a new therapy demonstrated clinical and nutritional benefits to patients and cost savings to the hospital.

Nutrition Support in Critical Illness — Bridging the Evidence Gap

Nutritional effects have traditionally focused on outcomes, such as nitrogen balance, wound healing, or muscle strength. Little emphasis has been placed on how biochemical or physical improvements translate into functional changes as perceived by the patient. Because glutamine (GLN)-supplemented nutrition promotes protein synthesis and improves nitrogen balance, we assessed the mood of individuals participating in a randomized controlled blinded trial receiving GLN solutions. Patients (n = 23) undergoing marrow transplantation were randomized by the research pharmacist to receive either standard total parenteral nutrition (TPN) (control) or GLN-containing TPN (40 g of glutamine total). The solutions were isocaloric and isonitrogenous and were administered until the patient was eating 50% of estimated requirements. Before TPN and on admission to the hospital, the patient completed the Profile of Mood States questionnaire, a standardized test quantifying the degree of tension, depression, anger, vigor, fatigue, and confusion. The patient completed the questionnaire again at the end of TPN near discharge. The tests were scored and the change from baseline for each mood for both groups of patients was calculated at the completion of TPN. The scores for vigor in the control group (delta scores) decreased over the course of hospitalization as would be expected with a serious illness. The group receiving glutamine TPN, however, essentially showed little change in vigor from baseline and the delta score was significantly different from the control group (delta vigor score -0.85 +/- 2.1 in the glutamine group vs. -5.90 +/- 1.7 in the control group; p = .07).(ABSTRACT TRUNCATED AT 250 WORDS)

Glutamine Is Essential for Epidermal Growth Factor-Stimulated Intestinal Cell Proliferation

The transplanted small intestine develops significant mucosal atrophy, impaired nutrient and water absorption, and increased bacterial translocation to mesenteric lymph nodes in rats maintained on elemental diets or total parenteral nutrition. This study determined the effects of administration of an peptide growth factor (insulin-like growth factor-I[IGF-I]) on the mucosal structure and barrier function of rat small bowel isografts. Thirty-six adult Lewis rats underwent either resection of the distal 60% of the small bowel and proximal colon followed by a 40-cm orthotopic jejunal isograft or proximal small bowel transection and distal small bowel resection to leave an analogous length of small intestine in control animals. All rats received an isocaloric, isonitrogenous, polymeric diet (200 kcal/kg/day, 2 gN/kg/day) by gastrostomy and were infused with either IGF-I (2.4 mg/kg/day) or vehicle by osmotic pumps subcutaneously. After 10 days of treatment, jejunal crypt cell production, mucosal morphometric indices, glucose and water absorption, body weight, and bacterial translocation to mesenteric lymph nodes (MLN) were measured. Jejunal mRNA content for IGF-I, IGF-I receptor, and IGF-binding proteins 3 and 4 (IGFBP-3,4) were determined by Northern blotting. Crypt cell production, villus height, crypt depth, and villus surface area were significantly increased in control and transplanted jejunum of rats infused with IGF-I when compared to animals given vehicle alone. Additionally, jejunal glucose absorption and water absorption were significantly improved in both IGF-I groups when compared with their respective vehicle controls. IGF-I infusion increased body weight in transplanted and control animals and markedly reduced bacterial translocation to MLN after small bowel transplantation. Jejunal levels of IGF-I mRNA were significantly increased in transplanted animals when compared to transected controls. IGF-I treatment significantly increased IGFBP-3 tissue mRNA levels in both transected and transplanted animals. These results demonstrate that IGF-I administration, after small bowel transplantation, improves mucosal structure and absorptive function and reduces bacterial translocation to MLN. IGF-I may have important effects in transplanted small bowel both as an endogenous and administered growth factor.