Objectives Antioxidant depletion is common in critically ill patients. This study was designed to determine the effects of PN, with or without glutamine (Gln) supplementation, on systemic antioxidant status in adult patients after major surgery who required parenteral nutrition (PN) in the surgical intensive care unit (SICU) setting. Methods Fifty-nine SICU patients who required PN following pancreatic surgery or cardiac, vascular or colonic (non-pancreatic) surgery were randomized in a double-blind study to receive standard PN (Gln-free) or Gln-supplemented PN (Gln-PN) in which Gln was provided as alanyl-Gln dipeptide. Conventional PN vitamin and mineral doses were administered to all subjects. Plasma concentrations of the antioxidant glutathione (GSH) and the anti-oxidant nutrients α-tocopherol, vitamin C and zinc were determined at baseline (initiation of study PN) and again after 7 days of study PN. Data were analyzed for the total study cohort and within the pancreatic surgery and non-pancreatic (cardiac, vascular and colonic) surgery patient subgroups. Results Mean plasma antioxidant concentrations were within or slightly below the normal ranges at baseline. However, a high percentage of patients demonstrated below normal baseline plasma concentrations of GSH (59%), vitamin C (59%) and zinc (68%), respectively. A lower percentage of patients exhibited below normal plasma α-tocopherol levels (21%). Study PN significantly improved plasma zinc levels in the entire study group and each surgical subgroup. Gln-PN significantly improved the change in plasma reduced GSH from baseline to day 7 in the non-pancreatic surgery patients (PN: −0.27 µM vs Gln-PN: +0.26 µM; p<0.03). Conclusions Low plasma levels of key antioxidants were common in this group of SICU patients despite administration of PN containing conventional micronutrients. Compared to standard PN, Gln-supplemented PN improved plasma GSH levels in SICU patients after cardiac, vascular or colonic operations.

Background Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. Objectives We studied metabolic effects of intravenous (IV) alanyl-Gln dipeptide (AG) supplementation and enteral (EN) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. Methods In a double-blind, pilot clinical trial, forty-four medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), EN AG (n=15) or IV AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 to 8. Results Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the IV AG (565±119 μM, mean±SEM) vs the EN AG (411±27μM) group by day 9 (P=0.039); however, subjects in the IV AG group received a higher dose of AG (IV AG 0.50 versus EN AG 0.32±0.02 g/kg/day; P<0.001). EN AG subjects showed a significant increase in plasma γ-tocopherol levels over time and maintained plasma γ-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. Conclusions This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Background Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. Methods This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. Results Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). Conclusions Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin- and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin + LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products.

Carotenoids, vitamin A and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A and tocopherols in SBS patients undergoing an intensive 12-week intestinal rehabilitation program. Twenty-one PN-dependent adult SBS patients were enrolled in a 12-week intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive either s.c. placebo (n=9) or human growth hormone (GH, 0.1 mg/kg/day). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A and tocopherols were determined at baseline and at weeks 4 and 12. Results showed that a significant % of subjects exhibited low serum concentrations for carotenoids and α-tocopherol at study entry, while a few subjects had low concentrations of retinol (5%). Serum α-tocopherol concentration was negatively associated with PN lipid dose (r = - 0.34, p < 0.008). We conclude that SBS patients are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum α-tocopherol concentrations.

Background and Aims Little data are published on habitual home oral diet of short bowel syndrome (SBS) patients living in the United States. Methods We assessed habitual macro-and micronutrient intake from oral food and beverages in 19 stable patients with severe SBS who live in the Southeastern United States. Intestinal absorption of energy, fat, nitrogen (N) and carbohydrate (CHO) was determined in a metabolic ward setting. Results We studied 12 women and 7 men, age 48±3 years (mean±SE) receiving chronic PN for 31±8 months following massive small bowel resection (118±25 cm residual small bowel). Patients had intact (N=5), partial (N=9), or no residual colon (N=5). The subjects demonstrated severe malabsorption of energy (59±3% of oral intake), fat (41±5%), N (42±5%) and CHO (76±3%). Average oral energy intake was 2656±242 kcal/day (39±3 kcal/kg/day) and oral protein intake was 1.4 ±0.1 g/kg/d. Oral food/beverage intake constituted 49±4% of total (enteral + parenteral) daily fluid intake, 66±4% of total daily kcal and 58±5% of total daily N intake. Oral fat intake averaged 92±11g/day (≈ 35% of total oral energy). Oral fluid intake averaged 2712±240 ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars comprised 42±3% of oral CHO intake. Usual dietary intake of multiple micronutrients were below the Recommended Dietary Allowances (RDA) in a large percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%), vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%). Only 7 patients (37%) were taking oral multivitamin-mineral supplements and only 6 subjects (37%) were taking oral iron and calcium supplements, respectively. Conclusions In these SBS patients living in the Southeastern United States, oral diet provides a significant proportion of daily nutrient intake. However, the types of foods and fluids consumed are likely to worsen malabsorption and increase PN requirements. Oral intake of essential micronutrients was very low in a significant proportion of this cohort of SBS patients.