A randomised controlled trial of glutamine-enriched neonatal parenteral nutrition in Malaysia. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study) A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates. Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood. Parenteral nutrition is not superior to replacement fluid therapy for the supportive treatment of chemotherapy induced oral mucositis in children. [Total enteral nutrition versus mixed enteral and parenteral nutrition in patients at an intensive care unit]. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants. The effects of glutamine-supplemented parenteral nutrition in premature infants. Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial. The favorable effect of early parenteral feeding on survival in head-injured patients. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6). Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. 2004 MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. [Effects of glutamine supplemented parenteral nutrition on the incidence of necrotizing enterocolitis, nosocomial sepsis and length of hospital stay in very low birth weight infants]. Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism. Enteral glutamine supplementation for very low birth weight infants decreases morbidity. Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after a standard stress. Effect of oral glutamine supplementation during bone marrow transplantation. Improvement of nutritional measures during preoperative parenteral nutrition in patients selected by the prognostic nutritional index: a randomized controlled trial. Nutrition support with glutamine dipeptide in patients undergoing liver transplantation. Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial. Hyperalimentation in autologous bone marrow transplantation for solid tumors. Comparison of total parenteral versus partial parenteral plus enteral nutrition. The effect of nutritional support on outcome from severe head injury.
The addition of glutamine to parenteral nutrition (PN) in neonates has not shown significant benefits as compared to adults thus far. This study aimed to determine the potential benefits of the addition of glutamine to neonatal PN in a tertiary hospital in a middle-income country.
                This was a double-blinded randomised controlled trial. Babies who were admitted to the neonatal intensive care unit (NICU) and who required PN were eligible for inclusion in the study. The subjects were randomised to receive either glutamine-added PN (intervention) or standard PN (control). The most important outcomes included time to full enteral nutrition, incidence of sepsis and necrotising enterocolitis (NEC), clinical or culture-proven sepsis.
                Out of 270 subjects, 132 were randomised to the intervention group and 138, to the control group. Baseline data were comparable in both groups. The median time taken to reach full enteral nutrition was similar for both intervention and control groups (six days in each group, p-value is 0.52). The incidences of NEC, clinical sepsis and culture-proven sepsis did not differ significantly in the intervention and control groups (5.8 vs. 7.1 percent, p-value is 0.68; 15.7 percent vs. 10.2 percent, p-value is 0.21 and 16.5 percent vs. 15.7 percent, p-value is 0.38, respectively). Other outcomes such as duration of ventilation, duration of NICU stay and a subgroup analysis for preterm and term babies also showed no statistically significant differences.
                Addition of glutamine to neonatal PN was not shown to improve outcome. In a paper by Ziegler et al (Ann Intern Med 116: 821-828, 1992), total parenteral nutrition supplemented with L-glutamine (TPN/GLN) was reported beneficial in patients receiving bone marrow transplantation (BMT) for hematologic malignancies. By using a similar protocol, we studied 29 patients with both hematologic malignancies and solid tumors, and with both allogeneic and autologous BMTs. In a double-blind, randomized approach, patients were given isocaloric, isonitrogenous TPN after BMT until they consumed 50% of their required diet orally. Total body water and extracellular water were measured before and after TPN in 10 patients. Total body water increased in patients receiving standard TPN and decreased significantly in patients receiving TPN/GLN. Length of hospital stay after BMT was significantly (5.8 days) less in patients receiving TPN/GLN. Incidence of positive bacterial cultures, clinical infections, and mortality did not differ significantly between the two groups. When the groups were subdivided into patients with hematologic malignancies and those with solid tumors, there were no significant differences in the above variables associated with TPN/GLN. In 17 of 30 additional hospitalized patients receiving standard TPN, substitution of TPN/GLN did not have discernible clinical or laboratory effects but appeared to be safe. Inclusion of patients with solid tumors and a higher mortality in our patients may have obscured beneficial effects of TPN/GLN observed by others. The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates.
                Randomized controlled trial.
                Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18).
                There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups.
                Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN. 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) Many paediatric oncology centres apply parenteral nutrition (PN) in children with severe oral mucositis after chemotherapy. However, no convincing data exist to support this treatment strategy. The aim of our study was to elucidate a possible advantage of PN versus intravenous replacement fluid therapy (FT). In a prospective randomized study, 30 children with mucositis WHO grade IV were assigned to receive either PN or intravenous replacement FT. Weight, total body water, fat-free mass (measured by impedance analysis) and peripheral white blood cells were assessed daily. For aspects of quality of life and economics, the length of hospital stay, the incidence of infections, the days on intravenous antibiotics and delay of scheduled chemotherapy were examined. Children with PN gained body weight significantly compared to baseline and to FT due to an augmentation of fat mass while total body water and fat-free mass significantly decreased. In children with FT, body weight remained stable while total body water and fat-free mass significantly increased, thereby loosing fat mass. We observed no differences in recovery of peripheral white blood cells (WBC), incidence of infections, hospitalization time, days on intravenous antibiotics, days on opioid analgesics and delay of the next scheduled chemotherapy cycle. Although children with PN gained weight in form of fat mass, this did not translate into a clinical benefit for the patients such as earlier recovery of WBC counts, shorter hospitalization time, a decreased use of analgesics or less delay of the next scheduled chemotherapy cycle. Our findings therefore do not support the hypothesis that PN is superior to FT when used for less than 10 days for oral mucositis. To compare metabolic, nutritional and epidemiological data in two groups of patients, one receiving total enteral nutrition, via nasoenteric tube, and one receiving both enteral and parenteral nutrition.
                A prospective, randomized study.
                A general ICU, with both medical and surgical patients, in a big regional University and National Health Service hospital.
                24 patients requiring Intensive Care after major surgery or because suffering from severe head injury or major neurological impairment.
                All patients initially received total parenteral nutrition: after 4 days 12 patients were "weaned" to total enteral nutrition and 12 stayed on mixed parenteral and enteral nutrition. LABORATORY INVESTIGATIONS AND OBSERVATIONAL DATA: Blood levels of albumin, prealbumin, transferrin, ALT, AST, bilirubin, blood urea, blood glucose, total linfocite count, and nutritional and epidemiological data such as nitrogen balance, calorie intake, diarrhea incidence, blood and sputum cultures and radiologic evidence of pneumonia are analysed.
                At T1, NET patients were able to reduce their nitrogen losses (0.27.1 g/kg +/-0.12 vs 0.35 +/- 0.13 at TO; p < 0.05) and improve nitrogen balance (-9 +/- 7 vs -2 +/- 6 at T0; p < 0.05); they also had a better total linfocite count (2034 +/- 304 vs. 1413 +/- 360 of the MISTA group; p < 0.05), and a lower incidence of pneumonia as documented by sputum cultures and radiograms.
                Patients fed with both parenteral and enteral nutrition did no better than those on total enteral nutrition as far as nutritional and metabolic indices were concerned; they also seemed more prone to infections than those on total enteral nutrition, indicating that mixed nutrition may result in more stable feeding, but this does not seem to have any beneficial nutritional, immunological and metabolic effect. To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation.
                Double-blind, randomized, controlled clinical trial.
                University teaching hospital.
                Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies.
                Parenteral 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.
                Nitrogen 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.
                The 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).
                Patients 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. Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known.
                We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis.
                Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation.
                Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population. Glutamine (GLN) is the primary fuel for rapidly dividing cells, yet it is not a constituent of parenteral nutritional formulas administered to newborns. The aims of this prospective, randomized, double-blind trial were (1) to confirm the safety of glutamine supplementation for premature infants and (2) to examine the effects of glutamine-supplemented parenteral nutrition on length of stay, days on total parenteral nutrition (TPN), days on the ventilator, and other clinical outcomes.
                Premature infants received either standard or glutamine-supplemented TPN and were monitored throughout length of stay for various health and biochemical indices. The group was examined as a whole (n = 44; birth weight range: 530 to 1250 g) and in two weight subgroups, < 800 and > or = 800 g.
                Serum ammonia, blood urea nitrogen, and glutamate tended to be higher in the GLN groups, but the levels were well within normal limits. In the < 800-g cohort (n = 24), glutamine-supplemented infants required fewer days on TPN (13 vs 21 days, p = .02), had a shorter length of time to full feeds (8 vs 14 days, p = .03), and needed less time on the ventilator (38 vs 47 days, p = .04). There was a tendency toward a shorter length of stay in the NICU (73 vs 90 days, NS). These findings were not observed in the infants > or = 800 g (n = 20).
                Glutamine appears to be safe for use in premature infants and seems to be conditionally essential in premature infants with extremely low birth weights. Larger multicenter trials are needed to confirm these observations and further evaluate the efficacy of GLN in these high-risk premature infants. To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery.
                Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results.
                Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources.
                Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects.
                In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise. This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury. Total enteral nutrition (TEN) within 48 h of admission has recently been shown to be safe and efficacious as part of the management of severe acute pancreatitis. Our aim was to ascertain the safety of immediate TEN in these patients and the effect of TEN on systemic inflammation, psychological state, oxidative stress, plasma glutamine levels and endotoxaemia.
                Patients admitted with predicted severe acute pancreatitis(APACHE II score >5) were randomised to total enteral (TEN; n = 8) or total parenteral nutrition (TPN; n = 9). Measurements of systemic inflammation (C-reactive protein), fatigue (visual analogue scale), oxidative stress (plasma thiobarbituric acid-reactive substances), plasma glutamine and anti-endotoxin IgG and IgM antibody concentrations were made on admission and repeated on days 3 and 7 thereafter. Clinical progress was monitored using APACHE II score. Organ failure and complications were recorded.
                All patients tolerated the feeding regime well with few nutrition-related complications. Fatigue improved in both groups but more rapidly in the TEN group. Oxidative stress was high on admission and rose by similar amounts in both groups. Plasma glutamine concentrations did not change significantly in either group. In the TPN group, 3 patients developed respiratory failure and 3 developed non-respiratory single organ failure. There were no such complications in the TEN group. Hospital stay was shorter in the TEN group [7(4-14) vs. 10 (7-26) days; p = 0.05] as was time to passing flatus and time to opening bowels [1 (0-2) vs. 2 (1-5)days; p = 0.01]. The cost of TEN was considerably less than of TPN.
                Immediate institution of nutritional support in the form of TEN is safe in predicted severe acute pancreatitis. It is as safe and as efficacious as TPN and may be beneficial in the clinical course of this disease. Total parenteral nutrition (TPN) supplemented with glutamine (GLN) has been reported to be effective for patients with bone marrow transplantation (BMT). Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT.
                For evaluation of GLN in BMT, 66 patients with 43 hematologic and 23 solid malignancies (21 breast carcinomas), were randomized, double-blinded, to either oral GLN (n = 35) or glycine-control (GLY) (n = 31), 10 g three times daily. When TPN became necessary, patients who received GLN orally were given TPN with GLN (0.57 g/kg). Those who received GLY received standard TPN, isocaloric and isonitrogenous. Patients with hematologic malignancies received high-dose chemotherapy, total body irradiation, and either allogeneic (ALLO) BMT (n = 18) or autologous (AUTO) stem cell transplantation (n = 25). Patients with solid malignancies (n = 23) received AUTO.
                There were 14 in-hospital deaths without relationship to GLN administration. For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups, there were no significant differences in hospital stay, duration of stay after BMT, TPN days, neutrophil recovery >500/mm3, incidence of positive blood cultures, sepsis, mucositis, and diarrhea. Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo (p > .05). Possible reduction in need for TPN and a suggestion of improved long-term survival were associated with GLN.
                Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies. Further study of long-term effects of GLN in BMT seems warranted. In 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.
                Retrospective review.
                Bone Marrow Transplant Unit, Brigham and Women's Hospital, Boston, Mass.
                Forty-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.
                The 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.
                The two groups were compared using the unpaired t test or Mann-Whitney test for nonparametric measurements. A P value of < .05 was considered significant.
                Nitrogen 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 $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: $51,484 +/- 2,647 for the glutamine-supplemented group vs $61,591 +/- 3,588 in the control group (P = .02).
                This intervention study using a new therapy demonstrated clinical and nutritional benefits to patients and cost savings to the hospital. The optimal route of nutrition in severe pancreatitis is controversial. Parenteral nutrition (PN) is preferred, but enteral nutrition (EN) promises to attenuate inflammation and prevent sepsis. We hypothesized that EN was at least equivalent to PN in reducing inflammation, providing effective nutrition and being cost-effective.
                We conducted a randomized controlled trial comparing PN to EN in pancreatitis in an academic, multi-institutional, tertiary care health system. We screened 728 consecutive patients. Twenty-eight patients with a Ranson's score greater than 2 who did not tolerate clear fluids 4 days after admission were randomized: 18 to PN and 10 to EN. Both groups were provided daily 105 kJ (25 kcal)/kg and 1.5 g/kg of protein, respectively, until they could tolerate a regular diet.
                C-reactive protein in EN patients was reduced by 50% 5 days faster than PN patients (Wilcoxon test, p = 0.09). Both groups received a similar number of kilojoules and achieved near normal prealbumin and 24-hour urinary nitrogen values. Neither regimen caused a change in cholecystokinin levels. Overall mortality was 4.9% (3 patients in the PN group). In 5 patients (4 PN, 1 EN) there were infected pancreatic collections. Nine EN patients dislodged the nasojejunal tube. EN had an average cost of dollar 1375 per patient compared with dollar 2608 for PN (p = 0.08). After sensitivity analysis, EN cost dollar 957 compared with dollar 2608 for PN (p = 0.03).
                EN or PN is safe and provides adequate nutrition in severe pancreatitis. EN shows a trend toward faster attenuation of inflammation, with fewer septic complications and is the dominant therapy in terms of cost-effectiveness. This study favours EN for nutritional support in severe pancreatitis. Parenteral feeding is the basic way of nutrition in the first day of life in infants with very low birth weight. Due to its instability glutamine is not included in aminoacid solutions used for parenteral nutrition. Meanwhile glutamine is an important aminoacid, which plays a major role in the maturation of the gastrointestinal tract as well as the immunological system.
                The aim of our study was to estimate if glutamine supplementation of parenteral nutrition in neonates with the very low birth weight can decrease the incidence of necrotizing enterocolitis -- NEC (> 1 degree according to the Bell criteria), nosocomial sepsis, and shorten the total length of hospitalization.
                Prospective, randomized study included 55 neonates born between 26 and 32 weeks of gestation, with birth weight range of 580 g to 1250 g. On the third day of life patients were randomized into 2 groups. Each group was fed with a different aminoacid solution. Group 1 consisted of patients who received a standard aminoacid solution with an addition of glutamine dipeptide (20% of total amount of aminoacids). Group 2 (acknowledged as the control group) including 30 patients received a standard aminoacid solution. Glutamine and glutaminic acid levels were checked in the cord blood, and on the 3rd and 14th day of life. Venous samples were taken at 8 a.m. and were estimated using HPLC. The Ethics Committee of the Warsaw Medical University had approved the research.
                In group 1 nosocomial sepsis had occurred in 7/25 neonates, and in the control group in 11/30; NEC was diagnosed in none of the 25 neonates in group 1 and in 5/30 of the control group; the total length of hospitalization in group 1 was 75 days (median 70) versus 73 in the control group (median 70). The lowest glutamine concentration was noted in cord blood samples, and increased on the third day of life in both groups. There were a statistically significant difference among the levels of glutamine concentration between the cord sample and the sample on the day three (p<0.01). On the 14th day of life glutamine concentration increased in both groups, but it was about 30% higher in group 1. This was statistically significant.
                Glutamine supplemented parenteral nutrition from day 4 to day 14 among neonates with very low birth weight, decreased the incidence of necrotizing enterocolitis, but it did not influence the incidence of hospital acquired sepsis, as well as the length of stay in the intensive care unit, and the total time of hospitalization. Further research is needed to estimate the role of glutamine in preventing gastrointestinal complications observed during sepsis. The effects of total parenteral nutrition (TPN) versus enteral nutrition (TEN) were studied in 34 patients following major neurosurgery. Measurements were made of resting energy expenditure (REE), urea production rate (UPR), visceral proteins, parameters of liver and pancreas function, as well as gastrointestinal absorption. To predict nutritional status, nutritional index (NI) was calculated. UPR revealed no significant differences between the groups. After 12 days of TEN, however, synthesis of visceral proteins increased significantly. In addition, NI improved after TEN (p < 0.05), whereas it remained unchanged after TPN. Thrombocyte and lymphocyte counts rose predominately during enteral nutrition. Only in the TEN group was REE increased by 18% and Glasgow Coma Scale (GCS) enhanced from Day 6 on. Exogenous insulin demand was enhanced in the parenterally fed group, and bilirubin (p < 0.05), amylase (p < 0.05), and lipase (p < 0.01) rose significantly, as did gamma-glutamyl-transferase (p < 0.0005) and alkaline phosphatase (p < 0.0005). After 12 d of TPN, vitamin A absorption was significantly attenuated, indicating reduced fat absorption compared to TEN. Carbohydrate absorption did not show significant changes between the groups. Only during TPN did mean values of xylose absorption remain below the normal range. Therefore, enteral nutrition following neurosurgical procedures is associated with an accelerated normalization of nutritional status and an improved substrate tolerance. TEN opposes early postoperative absorption disturbances of the small intestine. Glutamine, described as a "conditionally essential" amino acid for critically ill patients, has not been routinely added to parenteral amino acid formulations for critically ill neonates and is provided in only small quantities by the enteral route when enteral intake is low. We conducted a blinded, randomized study of enteral glutamine supplementation in 68 very low birth weight neonates randomly assigned to receive glutamine-supplemented premature formula versus premature formula alone between days 3 and 30 of life. Primary end points consisted of hospital-acquired sepsis, tolerance to subsequent enteral feedings (days with no oral intake), and duration of hospital stay. Hospital acquired sepsis was 30% (control group) and 11% (glutamine group). Logistic regression with birth weight as a covariate showed that: (1) feeding group was significant (p = 0.048) in determining the probability of developing proven sepsis over the course of hospitalization and (2) the estimated odds of developing sepsis were 3.8 times higher for infants in the control group than for those treated with glutamine. Glutamine-supplemented infants had better tolerance to enteral feedings as measured by percent of days on which feedings needed to be withheld (mean percentage of 8.8 vs 23.8, p = 0.007). Analysis of T cells demonstrated a blunting of the rise in HLA-DR+ and CD16 subsets in glutamine-supplemented infants. There were no differences in growth; in serum ammonia, urea, liver transaminase, or prealbumin concentrations; or in mean hospital stay. This study provides evidence for decreased morbidity in very-low-birth-weight neonates who receive enteral glutamine supplementation. A double-blind, randomized controlled trial was performed to determine the effect of glutamine (GLN)-enriched intravenous feedings on the volume and distribution of body fluids in catabolic patients. Subjects with hematologic malignancies in remission underwent a standard treatment of high-dose chemotherapy and total body irradiation before bone marrow transplantation. After completion of this regimen, they were randomized to receive either standard parenteral nutrition (STD, n = 10) or an isocaloric, isonitrogenous nutrient solution enriched with crystalline L-glutamine (0.57 g/kg/day, GLN, n = 10). Extracellular water (ECW) and total body water (TBW), determined by bromide and heavy water dilution techniques, were measured before the conditioning treatment and after termination of the intravenous feedings that were administered for 27 +/- 1 days. In addition electrical resistance (R, in ohms, omega) and reactance (Xc, omega) of the body to a weak alternating current were measured at these time points. Both study groups were comparable for age, weight, height, sex, and diagnosis. Initial TBW was highly related to electrical resistance (r = -0.93, p less than 0.001). After conditioning therapy, bone marrow infusion, and intravenous feedings, a 20% expansion in ECW was observed in the STD group (ECW: 18.0 +/- 1.1 L vs. 14.9 +/- 1.0, p = 0.012), and this fluid retention was associated with a marked decrease in electrical resistance (R: 514 +/- 28 omega vs. 558 +/- 26, p less than 0.05). In contrast the extracellular fluid compartment in patients receiving GLN-supplementation did not change (ECW: 15.8 +/- 0.9 L vs. 15.4 +/- 0.8, p = 0.49), and the body's resistance was maintained (R: 552 +/- 27 omega vs. 565 +/- 23, p = 0.42). Expansion of ECW could not be related to differences in fluid or sodium intake, or to the use of diuretics or steroids. Patients receiving the STD solution, however, exhibited a greater number of positive microbial cultures (p less than 0.01) and a higher rate of clinical infection compared with the GLN patients (5/10 vs. 0/10, p less than 0.05); the fluid expansion in infected STD patients was greater compared with uninfected individuals (delta ECW: + 5.0 +/- 1.4 vs. 0.7 +/- 0.5, p = 0.007). In this model of catabolic stress, fluid retention and expansion of the extracellular fluid compartment commonly observed after standard total parenteral nutrition can be attenuated by administering glutamine-supplemented intravenous feedings, possibly by protecting the host from microbial invasion and associated infection. Because all patients receiving bone marrow transplant (BMT) and peripheral blood progenitor cell transplant (PBPCT) experience gastrointestinal (GI) toxicity from the preparative regimen of chemotherapy, with or without radiation, oral glutamine was administered during the preparatory regimen and after transplant to maintain GI structure and function.
                To evaluate effects of oral glutamine on nutritional status and overall outcome, a prospective, randomized, double-blinded study was performed on 58 autologous and allogeneic BMT patients. Patients received 30 g of oral glutamine or placebo daily.
                The trends of decreased median length of stay and the median number of days of total parenteral nutrition (TPN) were seen in the group supplemented with the >0.285-g/kg (the recommended dosage) dose of glutamine; however, there was no statistically significant difference in the nutritional status and overall patient outcome as assessed by days receiving TPN, number of days required until oral intake resumed, length of hospitalization, number of days and highest grade of mucositis, and quantity and number of days of diarrhea.
                This study does not support the hypothesis that oral glutamine may offer benefit. Further investigation is required regarding clinical tools for determining effectiveness, administration for tolerance and compliance, dosage, and potential of oral glutamine usage. Patients undergoing major gastrointestinal surgery who had a prognostic nutritional index (PNI) score of greater than 30% were randomized to receive a preoperative course of 10 days of intravenous nutrition or to undergo surgery at the next convenient operation list. Two groups of 17 patients were well matched for age, sex, and nutritional status. Although they underwent diverse operations, the extent of these was similar: 12 +/- 3 days of parenteral nutrition resulted in weight gain, 3.2 +/- 2.3 kg p less than 0.01; increased triceps skinfold, 0.6 +/- 1.2 mm p less than 0.05; improved immunological state, p less than 0.02; and improved PNI, 5.5 +/- 10.1% p less than 0.05. The changes in serum albumin and transferrin were not significant. There were only three major complications with one death in the treatment group but this was not significantly different from the control group which had six major complications and three deaths. This study suggests that patients with demonstrable nutritional depletion who require major gastrointestinal surgery will benefit from a preoperative course of parenteral nutrition, but to conclusively prove this a large and probably multicentre study will be required. The effect of total parenteral nutrition (TPN) support supplemented with alanyl-glutamine (Ala-Gln) dipeptide was investigated in a randomized, controlled clinical trial.
                Sixty-five patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma admitted for orthotopic liver transplantation were randomly divided into 3 groups: diet group (n = 21), TPN group (n = 22), and Gln group (n = 22). Patients in the TPN and Gln groups received isocaloric and isonitrogenous TPN for 7 days. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery; we performed routine pathologic tests.
                Compared with the results on day 9 in the TPN group, there was a significant increase in the prognostic nutrition index and in prealbumin among the Gln group. Aspartate aminotransferase improved significantly by Gln treatment compared with traditional TPN support (P < .05). The pathologic results also showed Gln supplementation to reduce hepatic cell injury. A significant decrease in postoperative hospital stay was observed in the Gln group.
                Posttransplant TPN support greatly improved protein metabolism and nutritional state of patients. TPN with Ala-Gln helped to improve synthetic function and to reduce the injury to a transplanted liver. Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease.
                This was a randomized, double-masked, controlled clinical trial.
                Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake.
                In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements. Recipients of autologous bone marrow transplantation (ABMT) for solid tumors need nutritional support to maintain their body weight (BW). Severe BW-reduction (9.9%) was noticed retrospectively in ten ABMT patients fed orally, despite intensive counseling or occasional tube feeding. A prospective, randomized study of hyperalimentation (25 g nitrogen (N) and 3400 nonprotein kilocalories) with total parenteral nutrition (TPN) or partial parenteral plus enteral nutrition by tube feeding (PPN/EN) was done in 22 patients. Nutritional assessment included balance measurements of N, Na, K, Cl, P, Ca, Mg, Cu, and Zn, and serial measurements of BW, serum albumin, prealbumin, and transferrin. Both regimens were effective in maintaining BW (maximum percent of change, 2.5) and N-balance. Blood products accounted for an additional N-intake of 13% in both groups. The TPN group had a higher dietary N-intake versus PPN/EN, a positive K balance but negative Ca, Mg, Cu, and Zn balances. More mineral supplementation was given in the PPN/EN group where positive K, Mg, and Zn balances were seen. Visceral proteins and IgG, IgA, and IgM levels were decreased on days 7, 14, and 21. Creatinine clearance increased significantly in both groups. Compared with TPN, the PPN/EN group showed a twofold number of patients with a positive blood culture, although this observation did not reach statistical significance and patients had fewer days of diarrhea (31.1% versus 54.3%, P less than 0.01). Hyperalimentation with PPN/EN is an acceptable alternative to TPN in the nutritional support of ABMT recipients. Fifty-one brain-injured patients with peak 24-hour admission Glasgow Coma Scale (GCS) scores of 4 to 10 were prospectively randomly assigned to receive total parenteral (TPN) or enteral (EN) nutrition. Patients were studied from hospital admission to 18 days postinjury. Outcome was assessed by the Glasgow Outcome Scale at 3 months, 6 months, and 1 year postinjury. The TPN group received a significantly higher cumulative mean intake of protein than the EN group (mean +/- standard error of the mean: 1.35 +/- 0.12 vs. 0.91 +/- 0.9 gm/kg/day; p = 0.004). Mean cumulative caloric balance was also significantly higher in the TPN than in the EN group (75.6% +/- 5.13% vs. 59% +/- 4.26%; p = 0.02). Nitrogen balance was significantly more negative in the EN group during the 1st week postinjury (p = 0.002). The incidence of pneumonia, urinary tract infections, septic shock, and infections was not significantly different between groups. Classic nutritional assessment parameters such as anergy screens, total lymphocyte counts, and albumin levels were not significantly different between groups. The 11 patients in the EN group who did not tolerate tube feedings for 1 week postinjury had a significantly higher incidence of septic shock (p = 0.008). The change over time in GCS scores between groups was significantly different, with the TPN group showing a mean four-point increase in GCS score compared with a three-point increase in the EN group (p = 0.02). At 3 months the TPN group had a significantly higher percentage of favorable outcomes (43.5% vs. 17.9%, respectively; p = 0.05). At 6 months, 43.5% of the TPN group had a favorable outcome while 32.1% of the EN group had a favorable outcome (p = 0.29). By 1 year, 47.8% of the TPN group and 32.1% of the EN group had a favorable outcome (p = 0.20). In conclusion, more calories and protein usually can be administered to acute brain injury patients via the TPN route than by EN feedings via nasogastric or nasoduodenal routes. Traditional parameters for nutritional assessment are not useful in studying the efficacy of nutritional support during the first 2 weeks after head injury. Neurological recovery from head injury occurs more rapidly in patients with better early nutritional support.
In this update an additional study that compared PN and Glutamine versus standard PN showed that the certain benefits of parenteral nutrition with added glutamine compared to standard PN for reducing hospital stay are no longer definite. When PN with glutamine is compared with standard PN, patients may not leave hospital earlier, but do have reduced incidence of positive blood cultures, than those receiving standard PN. Where possible use of intravenous fluids and oral diet should be considered as a preference to parenteral nutrition, however, in the event of a patient suffering severe gastrointestinal failure even with a trial of enteral feeding, PN with the addition of glutamine could be considered.