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.
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.
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.