Parenteral Glutamine Supplementation Research Articles

ESPEN Guidelines on Parenteral Nutrition: Pancreas

Assessment of the severity of acute pancreatitis (AP), together with the patient's nutritional status is crucial in the decision making process that determines the need for artificial nutrition. Both should be done on admission and at frequent intervals thereafter. The indication for nutritional support in AP is actual or anticipated inadequate oral intake for 5-7 days. This period may be shorter in those with pre-existing malnutrition. Substrate metabolism in severe AP is similar to that in severe sepsis or trauma. Parenteral amino acids, glucose and lipid infusion do not affect pancreatic secretion and function. If lipids are administered, serum triglycerides must be monitored regularly. The use of intravenous lipids as part of parenteral nutrition (PN) is safe and feasible when hypertriglyceridemia is avoided. PN is indicated only in those patients who are unable to tolerate targeted requirements by the enteral route. As rates of EN tolerance increase then volumes of PN should be decreased. When PN is administered, particular attention should be given to avoid overfeeding. When PN is indicated, a parenteral glutamine supplementation should be considered. In chronic pancreatitis PN may, on rare occasions, be indicated in patients with gastric outlet obstruction secondary to duodenal stenosis or those with complex fistulation, and in occasional malnourished patients prior to surgery.

The Effects of Parenteral Glutamine Supplementation on Immunological Modulation in Extensive Burn Injury Patients

Background: Glutamine is an important energy source for immune cells. Several clinical trials have supported that glutamine supplementation in severely burned patients can maintain the immunologic function and improve the outcome. Aim and Objectives: The aim of this clinical study was to observe the effects of glutamine supplementation on immunologic modulation in extensive burn injury patients from the alternations of T cell and B cell lymphocytes counts and their differentiated ratios. Materials and methods: From July 2006 to September 2007, seven patients with extensive burn (total burn surface area 65.57±13.59%, range: 50%-90%) were enrolled in this prospective clinical trial. Patients received parenteral glutamine in doses of 20 g/day for 7 days. Alterations in immunologic function indices including T cell, B cell, CD4+ cell counts (μL^(-1)), differentiated count ratios (%), and the changes of CD4/CD8 ratio were determined on the 1st day and the 8th day from the initiation of glutamine treatment. The pre-treatment data on the 1st day was then compared with the post-treatment data on the 8th day. Results: There were no significant changes between the T cell (721±571 and 361±124 μL^(-1), P=0.149) and B cells counts (311±210 and 190±155 μL^(-1), P=0.267) after glutamine therapy. The T cell differentiated count ratio after glutamine supplementation was significantly higher than before treatment (59.77±16.72% and 71.27±10.94%, P=0.009). We especially observed a greater increase in patients with lower initial T cell differentiated count ratio. However, there was a decrease in B cell differentiated count ratios (29.24±12.96% and 19.93±12.08%, P=0.154). Although the CD4+ cell counts did not increase significantly after parenteral glutamine supplementation, (357±275 and 252±110 μL^(-1), P=0.437), we found the CD4+ differentiated count ratio increased significantly after glutamine therapy (30.93±7.99% and 43.96±3.21%, P=0.01). Conclusion: Parenteral glutamine supplementation in extensive burn patients increases the Tlymphocyte and CD4+ cell differentiated count ratios, as well as modulate the cellular immunologic function rather than the humoral response. The possible process is first to stimulate the helper T (CD4+) cells, which play the most important role in initiation of immunologic function and regulation.

Effects of parenteral glutamine supplementation on modulating the immune response in rats undergoing a total gastrectomy

The present study investigated the effect of parenteral glutamine (Gln) supplementation on cellular adhesion molecule expression and release of chemokines responsible for inflammatory cell recruitment in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to one control group and two experimental groups and received total parenteral nutrition (TPN). A total gastrectomy was performed in the experimental groups, whereas the control group received a sham operation (Sham). The TPN solutions were isonitrogenous and identical in nutrient composition except that the Sham group and one of the experimental group received conventional (Conv) TPN solution, whereas the other experimental group received 25% of the amino acid nitrogen as Gln. Half of the rats in each group were killed 1 or 3 d after surgery or the Sham to examine their immune response. The results showed that the surgery produced higher polymorphonuclear leucocyte CD11b/CD18 expressions, and Gln supplementation lowered CD11b/CD18 expressions compared with the Conv group post-operatively. The levels of monocyte chemotactic protein-1 and macrophage inflammatory protein-2 in peritoneal lavage fluid were higher in the Gln group than those in the Conv group 1 d post-operatively; these chemotactic proteins had returned to the levels comparable with those in the Sham group on post-operative day 3. These results suggest that Gln supplementation attenuated polymorphonuclear leucocyte integrin expression. In addition, Gln-enriched parenteral nutrition induced an earlier more intensive and rapid immune response to injury than the Conv parenteral nutrition after a total gastrectomy.

Role of parenteral glutamine supplementation on patient outcome in the surgical ICU

During the excessive organ/tissue demand of glutamine (Gln) in episodes of stress following major surgery, endogenous Gln production may not be sufficient to meet the increased requirements. The aim of the study was to evaluate the effect of parenteral Gln supplementation on the outcome of surgical cancer patients after major surgery [1].

Human Milk Intake and Retinopathy of Prematurity in Extremely Low Birth Weight Infants

OBJECTIVES. Our goal was to analyze the association between human milk intake and severe retinopathy of prematurity in extremely low birth weight infants. PATIENTS AND METHODS. This study is a secondary analysis of data collected for a trial of glutamine supplementation in extremely low birth weight infants (birth weight <1000 g). Among the 1433 participants in that trial, data are available regarding human milk intake and the occurrence of severe retinopathy of prematurity (defined in this study as retinopathy of prematurity treated surgically) for 1057 infants. The volume of human milk intake was expressed as the mean volume (milliliters per kilogram per day) and the mean proportional volume (proportion of total nutritional intake) from birth to discharge or transfer. Using logistic regression, we estimated odds ratios and 95% confidence intervals for any human milk intake and, among infants who received human milk, for each 10 mL/kg per day and each 10% increase in volume. RESULTS. Of the 1057 infants included in this cohort, 788 infants (75%) received at least some human milk. Among these milk-fed infants, the median volume of human milk intake was 30 mL/kg per day (interquartile range: 6-83 mL/kg per day), and the median proportional volume of human milk intake was 0.18 (interquartile range: 0.03-0.66). One hundred sixty-three infants (15%) developed severe retinopathy of prematurity. CONCLUSIONS. In extremely low birth weight infants, human milk intake was not associated with a decreased risk of severe retinopathy of prematurity.

Enteral glutamine supplementation impairs intestinal blood flow in rats

Background Clinical studies have shown that enteral immune-enhancing diets (IEDs) containing l-glutamine decrease septic complications and length of stay in some patient populations. Animal studies suggest IED benefits might include augmented gut blood flow. We hypothesized that enteral glutamine supplementation modulates gastrointestinal blood flow. Methods Blood flow was measured in male Sprague-Dawley rats via the colorimetric microsphere technique at baseline, 60, and 120 minutes. Four groups were studied: (1) control diet (CD) + enteral glutamine; (2) CD + enteral glycine; (3) CD + enteral saline; and (4) CD + intravenous glutamine. Results There were no differences in blood pressure or heart rate in any group. Group 1 blood flow was decreased at 120 minutes compared with controls (groups 2 and 3) in small intestine, colon, spleen, and pancreas, whereas the intravenous glutamine group (group 4) had no effect on blood flow. Conclusions Enteral glutamine supplementation (as in IEDs) appears to impair gastrointestinal blood flow. Because glutamine provides energy directly to active enterocytes, enteral glutamine availability might diminish metabolic stimuli of absorptive hyperemia. This finding might partially explain the benefits observed with parenteral versus enteral glutamine supplementation in clinical studies (such as bone-marrow–transplant patients).

Immunonutrition

Immunonutrition describes the enteral or parenteral administration of certain substrates (arginine, omega-3 fatty acids, nucleotides, glutamine and antioxidants) with a putative immunomodulating function. Thus far, with the exception of glutamine and antioxidants, these immunomodulating substrates have not been examined separately but only in various combinations to establish their clinical efficacy. In critically ill patients who predominantly require parenteral nutrition, there is evidence from large meta-analyses that parenteral glutamine supplementation may significantly lower septic morbidity and mortality. Therefore, parenteral glutamine supplementation is currently part of all concepts and recommendations addressing nutritional issues in critical care. With respect to selective parenteral or enteral application of arginine or omega-3 fatty acids, there are still insufficient data on clinical effects or side effects to allow a definitive conclusion for nutritional care in the critically ill. Only one metaanalysis addressed the clinical importance of a selective antioxidant therapy. It was concluded that such a therapy lowered mortality rates by about one third. However, this effect was unrelated to an improvement of infectious morbidity. Still, parenteral antioxidant supplementation (especially of selenium) is currently considered beneficial in critically ill patients. At the moment, two different substrate mixtures of various immunomodulating compounds are commercially available. One type contains arginine, omega-3 fatty acids, and antioxidants ± glutamine (classic mixture), the other omega-3 fatty acids, dihomogamma linoleic acid and antioxidants (modified mixture). Due to the mixture concept, only summary effects can be examined clinically, and interactions between different substrates cannot be excluded. According to large metaanalyses, there are neither beneficial nor detrimental effects of the classic mixture when used in unselected cohorts of critically ill patients. In patients with severe sepsis, negative side effects of the classical mixture may possibly exist (enhancement of immunosuppression in the specific immune system). Therefore, use of the classical mixture is not recommended in the latter patients. On the other hand, there is increasing evidence for beneficial clinical effects of the modified mixtures in critically ill and also in septic patients. The modified mixture improved pulmonary function and outcome in ventilated patients significantly, and is currently incorporated into nutritional recommendations of various societies.

Effect of parenteral glutamine supplementation in premature infants

Glutamine, proposed to be conditionally essential for critically ill patients, is not added routinely to parenteral amino acid formulations for premature infants and is provided in only small quantities by the enteral route when enteral feeding is low. Parenteral feeding is the basic way of nutrition in the first days of life of premature infants. In this study, we evaluated the effects of glutamine supplemented parenteral nutrition for premature infants on growth and development, feeding toleration, and infective episodes. From December 2002 to July 2006, 53 premature infants were given either standard or glutamine supplemented parenteral nutrition for more than 2 weeks. Twenty-eight infants were in glutamine supplemented group, whose gestational age (31.4 +/- 2.0) weeks, birth weight range (1386 +/- 251) g; twenty-five infants were in control group, gestational age (31.1 +/- 1.7) weeks, with birth weight range (1346 +/- 199) g. There were no differences between the two groups. Various growth and biochemical indices were monitored throughout the duration of hospital stay. Data between groups were analyzed with Student's t test. Nonparametric data were analyzed using a Chi-square test. A two-tailed P value < 0.05 was considered statistically significant. The level of serum albumin was lower in the glutamine groups on the second week (3.0 vs 3.2 g/dl, P = 0.028), and blood urea nitrogen was higher in glutamine groups on the fourth week (8.1 vs 4.9 mg/dl, P = 0.014), but normal. Glutamine group infants took fewer days to regain birth weight (8.1 vs 10.4 days, P = 0.017), required fewer days on parenteral nutrition (24.8 vs 30.8 days, P = 0.035), with shorter stays in hospital (32.1 vs 38.6 days, P = 0.047). Episodes of hospital acquired infection in glutamine supplemented infants were lower than that in control group (0.96 vs 1.84 times, P = 0.000). Parenteral glutamine supplementation in premature infants can shorten days on parenteral nutrition and length of stay in hospital, and decrease hospital acquired infection episodes.

Glutamine Supplementation in Critical Illness: Evidence, Recommendations, and Implications for Clinical Practice in Burn Care

Glutamine is considered a conditionally essential amino acid in metabolic stress. Depletion of plasma and muscle glutamine is observed in acute burn injury and contributes to muscle wasting, weight loss, and infection. In critical illness, supplementation has been shown in patients to minimize these effects and reduce the rate of mortality and length of stay. The evidence for glutamine use and its implications for burn care practice are considered here. Work published to February 2006, which investigated enteral and parenteral glutamine supplementation in burns and critical care, is reviewed. Randomized controlled trials in burns, systematic reviews, and nutrition support practice guidelines are considered. Randomized controlled trials in burns suggest significant clinical benefit in terms of morbidity, mortality, and length of stay but are limited by sample size. Parenteral glutamine studies are under-represented. Systematic reviews and practice guidelines generally support glutamine supplementation in critical illness but vary in the level of recommendations for its use in burns. There also are features unique to burn injury that require consideration. Patients with severe burns or inhalation injury may have a prolonged critical illness phase. In large burns, inflammation and hypermetabolism may persist well beyond 4 weeks of injury. The justification and safety of long-term glutamine supplementation is yet to be established. The outlook for glutamine therapy in burns is promising. However, to strengthen recommendations for routine therapy in burns, further research focusing on larger-scale enteral glutamine studies, parenteral glutamine supplementation, and long-term use of the substrate is necessary.

Immunomodulation Part IV: Glutamine

Glutamine, a nonessential amino acid that appears to be conditionally essential during periods of physiologic stress, plays important physiologic roles in the immune system. However, neither enteral nor parenteral glutamine supplementation makes a difference in the rate of systemic infection or of NEC in very low birth weight infants. Thus, the search for agents to enhance the neonate's immune system and to serve as safe and effective adjuvants to antibiotics continues. Part V, the final article in this immunomodulation series, will explore the use of probiotics to support the neonatal immune system.

Glutamine in critical care: current evidence from systematic reviews

Glutamine, the most abundant amino acid in the body, is thought to become conditionally essential in critical illness. Some of the important roles for glutamine are as a carrier for inter-organ N, a preferred fuel for enterocytes and cells of the immune system, a substrate for renal NH3 formation and a precursor for glutathione. Mechanisms by which glutamine could improve recovery include attenuating oxidant damage and inflammatory cytokine production, reducing gut bacterial translocation and improving N balance. The present systematic review has found trends to suggest that parenteral and enteral glutamine supplementation reduce mortality, the development of infection and organ failure in critical illness. Trials of parenteral nutrition containing glutamine with patients after elective surgery also suggest reduction of infection, but it is unlikely that glutamine-containing parenteral nutrition would be used for such patients. The evidence base is limited by the quality of the reported trials and the suggestion that there is publication bias, with trials suggesting reduced infection being more likely to be published.

Metabolic effects of enteral versus parenteral alanyl‐glutamine (AG) dipeptide in critically ill tube‐fed patients

Enteral and parenteral glutamine (Gln) supplementation is being investigated in critically ill patients, but metabolic effects of different routes of administration are unknown. Methods This double-blind, randomized study compared enteral versus parenteral AG (EN-AG vs IV-AG) on plasma Gln, plasma antioxidants, intestinal permeability to lactulose/mannitol and nitrogen (N) balance over a 8-day period in 44 ICU patients requiring tube feeding. Subjects each received an identical, Gln-free, isocaloric tube feeding 24 h/day and randomized to control (no AG, n=12), EN-AG (n=16) or IV-AG (n=16) groups (AG at 0.5 g/kg/day). Results APACHE II scores were similar at entry in all groups as was energy and N delivery during study. Plasma Gln rose significantly in the IV-AG group. EN-AG subjects showed a significant increase in α-tocopherol (α-toc) levels over time (day 1, 1155±105 vs day 9, 1272±133 μg/dL; p=0.019) and maintained γ-tocopherol (γ-toc) levels. In contrast, α-toc levels were unchanged and γ-toc levels fell significantly in IV-AG and control groups. There were no differences between groups in levels of vitamin C and glutathione, intestinal permeability or N balance. In conclusion, this study shows that enteral Gln may maintain or increase plasma tocopherols in ICU patients. Route of Gln administration does not influence plasma vitamin C or glutathione levels, gut permeability or N balance in ICU patients over an 8-day period. Supported by NIH RO3 DK54823.

Effect of glutamine and growth hormone on adaptation in short bowel syndrome

To assess the effects of parenteral glutamine and growth hormone supplementation on gut adaptation for patients with short bowel syndrome. Twenty-six patients [male 15, female 11, aged (39 +/- 23) years] with short bowel syndrome received parenteral nutrition (PN) 3-52 months after surgical resection. The median length of remnant small intestine was 42.5(0-100)cm. All patients received growth hormone (0.10+/- 0.06) mg.kg(-1).d(-1) plus glutamine (0.30 +/- 0.17) mg.kg(-1).d(-1) for two or three weeks. Among the 26 patients, PN was not required soon after treatment in 34.6% (n=9) of the patients, the frequency and volume of PN decreased from (6.0 +/- 1.0) d to (4.2 +/- 1.0) d, from (13.6 +/- 5.2) L per week to (8.2 +/- 3.3) L per week respectively in 30.8% (n=8) of the patients,while 34.6% (n=9) still required PN after treatment. The combined administration of glutamine and growth hormone can promote remnant intestinal adaptation in short bowel patients.

Differentiation stage‐dependent preferred uptake of basolateral (systemic) glutamine into Caco‐2 cells results in its accumulation in proteins with a role in cell–cell interaction

Glutamine is an essential amino acid for enterocytes, especially in states of critical illness and injury. In several studies it has been speculated that the beneficial effects of glutamine are dependent on the route of supply (luminal or systemic). The aim of this study was to investigate the relevance of both routes of glutamine delivery to in vitro intestinal cells and to explore the molecular basis for proposed beneficial glutamine effects: (a) by determining the relative uptake of radiolabelled glutamine in Caco-2 cells; (b) by assessing the effect of glutamine on the proteome of Caco-2 cells using a 2D gel electrophoresis approach; and (c) by examining glutamine incorporation into cellular proteins using a new mass spectrometry-based method with stable isotope labelled glutamine. Results of this study show that exogenous glutamine is taken up by Caco-2 cells from both the apical and the basolateral side. Basolateral uptake consistently exceeds apical uptake and this phenomenon is more pronounced in 5-day-differentiated cells than in 15-day-differentiated cells. No effect of exogenous glutamine supply on the proteome was detected. However, we demonstrated that exogenous glutamine is incorporated into newly synthesized proteins and this occurred at a faster rate from basolateral glutamine, which is in line with the uptake rates. Interestingly, a large number of rapidly labelled proteins is involved in establishing cell-cell interactions. In this respect, our data may point to a molecular basis for observed beneficial effects of glutamine on intestinal cells and support results from studies with critically ill patients where parenteral glutamine supplementation is preferred over luminal supplementation.

Effect of parenteral glutamine supplementation on lymphocyte subpopulations in critically ill patients receiving glutamine enriched enteral nutrition

Effect of parenteral glutamine supplementation on lymphocyte subpopulations in critically ill patients receiving glutamine enriched enteral nutrition

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants

Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.

Nutrition artificielle et greffe de cellules souches hématopoı̈étiques

Nutritional support becomes essential after bone marrow transplantation. Nutritional assessment must be systematic before and after transplantation. This assessment could allow for the rapid replacement of an inefficient oral nutrition by artificial nutrition. Parenteral nutrition seems to be preferentially used, but enteral nutrition is well tolerated. Energetic and protein supply could be the same to that recommended in other acute stress situations. In the last decade, several publications have shown that parenteral glutamine supplementation could reduce infectious risk, length of stay and hospital cost, especially after allogenic transplantation. But glutamine isn't effective to reduce mortality. Results with other immunonutrients, like medium-chain triglycerides or branched-chain amino-acids, are insufficient to recommend their prescription. Practical recommendations and new data about enteral nutrition could enable to optimize nutritional management of bone marrow transplantation patients.

Parenteral glutamine supplementation enhances liver but not gut glutamine consumption.

s of the Netherlands Society of Gastroenterology and the Netherlands Society of Hepatology: Spring Meeting, 15–16 March 2001

Glutamine supplementation for preventing morbidity in preterm infants.

The amino acid glutamine is the preferred respiratory fuel for rapidly proliferating cells under normal conditions. Recent research has suggested a number of roles for glutamine during critical illness. This research has been largely performed in experimental animals and in adults in a variety of disease settings. There is little information on the role of glutamine in children and infants, or whether glutamine supplementation is beneficial in preterm babies. To determine the effects of glutamine supplementation on morbidity and weight gain in preterm babies. Searches were made using Medline and Embase electronic databases and specific handsearching in the English language. The search strategy followed the guidelines of the Neonatal Cochrane Review Group. Randomised controlled trials comparing glutamine supplementation to no glutamine supplementation in preterm babies at any time from birth to discharge from hospital. Data regarding clinical outcomes including duration of parenteral nutrition, time to full enteral nutrition, rate of weight gain, rate of positive blood cultures and duration of hospital stay were extracted by both reviewers. Analysis was performed by the primary reviewer (TRJT) in accordance with the standards of the Cochrane Neonatal Review Group. Three trials met the selection criteria. Data on proportion of babies having one or more of positive blood cultures were available from all three studies. Meta-analysis showed no significant difference between glutamine-supplemented and non-supplemented babies; RR = 0.73 (95% CI 0.44, 1.23), RD = -8.8% (95% CI -23.2, 5.5). Data for other outcome variables were pooled from two studies. There were no significant differences between glutamine-supplemented and non-supplemented babies for days to full enteral nutrition (WMD 0.42, 95% CI -3.0, 3.8), rate of weight gain (WMD 0.6 g/kg/d, 95% CI -1.6, 2.8) or days of hospital stay (WMD -2.4, 95% CI -14.9, 10.2). There is no evidence to support the routine use of parenteral or enteral glutamine supplementation in preterm babies. A large randomised controlled trial should be performed to determine whether or not glutamine supplementation enhances gut integrity and reduces sepsis rate.

Glutamine supplementation in catabolic patients.

To evaluate the safety and efficacy of parenteral and enteral glutamine supplementation in patients who are catabolic. English-language clinical trials and review articles identified by MEDLINE searches (January 1970-December 1997) and from bibliographies of selected articles were considered for possible inclusion. Key words used in the search strategy were glutamine, critical illness, stress, catabolism, injury, enteral nutrition, and parenteral nutrition. Inclusion was restricted to pertinent studies that evaluated the safety of glutamine supplementation, as well as effects of glutamine on amino acid metabolism, immune function, and patient outcome. Data from 18 clinical trials and multiple review articles were compiled into a review format. Glutamine is an important metabolic fuel for intestinal enterocytes, lymphocytes and macrophages, and metabolic precursors such as purines and pyrimidines. Although originally considered a nonessential amino acid, experimental work suggests that glutamine is essential for maintaining intestinal function, immune response, and amino acid homeostasis during periods of severe stress. In the past decade, clinical trials conducted in metabolically stressed patients indicate that glutamine improves nitrogen balance, increases cellular proliferation, decreases the incidence of infection, and shortens hospital stay in some catabolic patients. Glutamine has been studied extensively over the past decade for its role during critical illness. Clinical trials conducted in humans demonstrate glutamine to be well tolerated without adverse consequences, even during times of stress. Although glutamine has shown promise in select groups of catabolic patients, additional studies are needed to define which patient populations derive the greatest benefit from supplemental glutamine and the mechanisms by which these effects are exerted.