Effect of intravenous GLutamine supplementation IN Trauma patients receiving enteral nutrition study protocol (GLINT Study): a prospective, blinded, randomised, placebo-controlled clinical trial.
ABSTRACT: Background Trauma patients are characterised by alterations in the immune system, increased exposure to infectious complications, sepsis and potentially organ failure and death. Glutamine supplementation to parenteral nutrition has been proven to be associated with improved clinical outcomes. However, glutamine supplementation in patients receiving enteral nutrition and its best route are still controversial. Previous trials have been limited by a small sample size, use of surrogate outcomes or a limited period of supplementation. The aim of this trial is to investigate if intravenous glutamine supplementation to trauma patients receiving enteral nutrition is associated with improved clinical outcomes in terms of decreased organ dysfunction, infectious complications and other secondary outcomes. Methods/design Eighty-eight critically ill patients with multiple trauma receiving enteral nutrition will be recruited in this prospective, triple-blind, block-randomised, placebo-controlled clinical trial to receive either 0.5 g/kg/day intravenous undiluted alanyl-glutamine or intravenous placebo by continuous infusion (24 h/day). Both groups will be receiving the same standard enteral nutrition protocol and the same standard intensive care unit care. Supplementation will continue until discharge from the intensive care unit, death or a maximum duration of 3 weeks. The primary outcome will be organ-dysfunction evaluation assessed by the pattern of change in sequential organ failure assessment score over a 10-day period. The secondary outcomes are: the changes in total sequential organ failure assessment score on the last day of treatment, infectious complications during the ICU stay, 60-day mortality, length of stay in the intensive care unit and body-composition analysis. Discussion This study is the first trial to investigate the effect of intravenous alanyl-glutamine supplementation in multiple trauma patients receiving enteral nutrition on reducing severity of organ failure and infectious complications and preservation of lean body mass. Trial registration number This trial is registered at http://www.clinicaltrials.gov. NCT01240291.
Project description:Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5?g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.
Project description:<h4>Introduction</h4>The potential benefit of parenteral glutamine (GLN) supplementation has been one of the most commonly studied nutritional interventions in the critical care setting. The aim of this systematic review was to incorporate recent trials of traditional parenteral GLN supplementation in critical illness with previously existing data.<h4>Methods</h4>All randomized controlled trials of parenterally administered GLN in critically ill patients conducted from 1997 to 2013 were identified. Studies of enteral GLN only or combined enteral/parenteral GLN were excluded. Methodological quality of studies was scored and data was abstracted by independent reviewers.<h4>Results</h4>A total of 26 studies involving 2,484 patients examining only parenteral GLN supplementation of nutrition support were identified in ICU patients. Parenteral GLN supplementation was associated with a trend towards a reduction of overall mortality (relative risk (RR) 0.88, 95% confidence interval (CI) 0.75, 1.03, P?=?0.10) and a significant reduction in hospital mortality (RR 0.68, 95% CI 0.51, 0.90, P?=?0.008). In addition, parenteral GLN was associated with a strong trend towards a reduction in infectious complications (RR 0.86, 95% CI 0.73, 1.02, P?=?0.09) and ICU length of stay (LOS) (WMD -1.91, (95% CI -4.10, 0.28, P?=?0.09) and significant reduction in hospital LOS (WMD -2.56, 95% CI -4.71, -0.42, P?=?0.02). In the subset of studies examining patients receiving parenteral nutrition (PN), parenteral GLN supplementation was associated with a trend towards reduced overall mortality (RR 0.84, 95% CI 0.71, 1.01, P?=?0.07).<h4>Conclusions</h4>Parenteral GLN supplementation given in conjunction with nutrition support continues to be associated with a significant reduction in hospital mortality and hospital LOS. Parenteral GLN supplementation as a component of nutrition support should continue to be considered to improve outcomes in critically ill patients.
Project description:Glutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. However, recent large-scale trials have suggested harm associated with GLN supplementation. Recently, systematic reviews on the use of parenteral GLN have been published; however, less information is available on the role of enteral GLN. Therefore, the aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness.We identified randomized controlled trials conducted from 1980 to 2014 with enterally administered GLN in adult critically ill patients. Studies of parenteral GLN only or combined enteral-parenteral GLN were excluded. The methodological quality of studies was scored, and trial data were statistically combined. We examined a priori the treatment effects in subgroups of trials of burn and trauma patients.A total of 11 studies involving 1079 adult critically ill patients and enteral GLN supplementation were identified. Enteral GLN supplementation was not associated with a reduction of hospital mortality (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.65-1.36; p = 0.74), infectious complications (RR 0.93, 95% CI 0.79-1.10; p = 0.39) or stay in the intensive care unit (weighted mean difference [WMD] -1.36 days, 95% CI -5.51 to 2.78; p = 0.52). However, there was a significant reduction in hospital stay (WMD 4.73 days, 95% CI -8.53 to -0.90; p = 0.02). In the subset of studies of patients with burns, enteral GLN supplementation was associated with significant reductions in hospital mortality (RR 0.19, 95% 0.06-0.67; p = 0.010) and hospital stay (WMD -9.16, 95% CI -15.06 to -3.26; p = 0.002). There was no effect in trauma patients.Enteral GLN supplementation does not confer significant clinical benefit in critically ill patients, with the exception of reduced hospital stay. There may be a significant benefit in patients with burns, but data are sparse and larger randomized trials are warranted to confirm this effect.
Project description:The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with ?-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.Twice-daily enteral supplementation of n-3 fatty acids, ?-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.Ventilator-free days to study day 28.The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001).Twice-daily enteral supplementation of n-3 fatty acids, ?-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.clinicaltrials.gov Identifier: NCT00609180.
Project description:Nosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population.Randomized, double-blinded, comparative effectiveness trial.Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.Two hundred ninety-three long-term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care.Patients were stratified according to immunocompromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat.There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011).Compared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune-competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient.
Project description:Objective. Evaluating the efficacy and safety of arginine and glutamine supplementation in decreasing the incidence of NEC among preterm neonates. Methods. Prospective case-control study done on 75 preterm neonates ?34 weeks, divided equally into L-arginine group receiving enteral L-arginine, glutamine group receiving enteral glutamine, and control group. Serum L-arginine and glutamine levels were measured at time of enrollment (sample 1), after 14 days of enrollment (sample 2), and at time of diagnosis of NEC (sample 3). Results. The incidence of NEC was 9.3%. There was no difference in the frequency of NEC between L-arginine and control groups (P > 0.05). NEC was not detected in glutamine group; L-arginine concentrations were significantly lower in arginine group than control group in both samples while glutamine concentrations were comparable in glutamine and control groups in both samples. No significant difference was found between groups as regards number of septic episodes, duration to reach full oral intake, or duration of hospital stay. Conclusion. Enteral L-arginine supplementation did not seem to reduce the incidence of NEC. Enteral glutamine may have a preventive role against NEC if supplied early to preterm neonates. However, larger studies are needed to confirm these findings. This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01263041).
Project description:Background:Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. Materials and Methods:This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. Results:No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Conclusion:Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.
Project description:The amount of enteral nutrition patients with acute lung injury need is unknown.To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding.The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol.Ventilator-free days to study day 28.Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P < .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days.In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance.clinicaltrials.gov Identifiers: NCT00609180 and NCT00883948.
Project description:Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg(-1)·d(-1)) from d 4 to 8 of life (n = 5-8). Whole-body respiratory calorimetry and (13)C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (?500 ?mol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath (13)CO2 enrichments, (13)CO2 production, percentage of (13)CO2 recovery/h, and cumulative percentage recovery of (13)C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2.
Project description:Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n = 31) or placebo supplemented (n = 29) preterm infants. Term peers (n = 30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p < 0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33 to 4.09 wt% or 2.88 to 3.55 mol%, p < 0.0001) while placebo-supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35 to 3.32 wt% or 2.91 to 2.87 mol%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97 wt% or 4.31 mol%) at discharge (p = 0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.