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Glutamine supported early enteral therapy for severe acute pancreatitis: A systematic review and meta-analysis.
Jiang, X, Pei, LY, Guo, WX, Qi, X, Lu, XG
Asia Pacific journal of clinical nutrition. 2020;(2):253-261
Abstract
BACKGROUND AND OBJECTIVES Several studies have shown that glutamine (Gln) may play an important role in energy metabolism, inflammatory reactions, and immune processes in patients with severe acute pancreatitis (SAP). Nevertheless, the results of individual randomized controlled trials (RCTs) on Gln nutrition support for SAP are contradictory. This systematic review and meta-analysis evaluated the clinical benefit of Gln-supported early enteral nutrition (G+EEN) in patients with SAP. METHODS AND STUDY DESIGN Cochrane Library, PubMed, Embase, CNKI, Wan Fang, and Chinese Biomedical Literature Database were searched for relevant studies published before December 2018. RCTs of G+EEN versus standard early enteral nutrition (EEN) for SAP were selected, with both started within 48 h of admission. RESULTS Seven clinical RCTs including a total of 433 patients (EEN group: 218 patients; G+EEN group: 215 patients) were included. Compared with EEN, G+EEN increased serum albumin (standard mean difference [SMD]=0.74; 95% confidence interval [CI], 0.33-1.15; p<0.01), reduced serum hypersensitive C-reactive protein (SMD=-1.62; 95% CI, -1.98 to -1.26; p<0.01) and risks of mortality risk (risk ratio= 0.38; 95% CI, 0.16-0.90; p=0.03) and multiple organ dysfunction syndrome (MODS)(risk ratio=0.37; 95% CI, 0.15-0.94; p<0.01), and shortened length of hospital stay (SMD=-1.19; 95% CI, -1.88 to 0.49; p<0.01); moreover, it did not significantly increase the incidence of infection-related complications, operative interventions, or APACHE II scores. CONCLUSIONS G+EEN is beneficial in SAP management.
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Glutamine supplementation to prevent morbidity and mortality in preterm infants.
Moe-Byrne, T, Brown, JV, McGuire, W
The Cochrane database of systematic reviews. 2016;(4):CD001457
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BACKGROUND Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. SELECTION CRITERIA Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. AUTHORS' CONCLUSIONS The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.
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Glutamine supplementation to prevent morbidity and mortality in preterm infants.
Moe-Byrne, T, Brown, JV, McGuire, W
The Cochrane database of systematic reviews. 2016;(1):CD001457
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Abstract
BACKGROUND Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. SELECTION CRITERIA Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. AUTHORS' CONCLUSIONS The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.
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Efficacy of Glutamine-Enriched Nutrition Support for Patients With Severe Acute Pancreatitis: A Meta-Analysis.
Yong, L, Lu, QP, Liu, SH, Fan, H
JPEN. Journal of parenteral and enteral nutrition. 2016;(1):83-94
Abstract
BACKGROUND Plasma glutamine (Gln) level has been negatively correlated with the severity of severe acute pancreatitis (SAP). Although Gln is widely used today, the results of individual randomized controlled trials of Gln-enriched nutrition support for patients with SAP are conflicting. METHODS PubMed, EMBASE, HighWire, Cochrane Central Register of Controlled Trials, Wanfang, China Journals Full-Text Database, and the Chinese Biomedical Literature Database were searched. Literature published before June 2014 was searched. Randomized controlled trials investigating the comparison of conventional and Gln-enriched nutrition support were included; a random effect model using Rev Man 5.2 software was chosen to complete this meta-analysis. The count data were analyzed using the risk ratio (RR) and 95% confidence interval (CI), and the measurement data were analyzed using the standard mean difference or weighted mean difference and 95% CI. Heterogeneity analyses were conducted by I(2) test; publication bias analyses were conducted by Begg test. RESULTS Ten studies were eventually chosen for analysis, including 218 patients who received conventional methods (control group) and 215 patients who received Gln-enriched nutrition support (experimental group). Compared with the control group, Gln is helpful in elevating the albumin level, decreasing C-reaction protein (standard mean difference = 1.01, -1.89; 95% CI: 0.50 to 1.51, -3.23 to -0.56; P < .05), decreasing the incidence of infectious complication and mortality (RR = 0.62, 0.36; 95% CI: 0.46 to 0.83, 0.16 to 0.83; P < .05), and shortening the hospital stay length (weighted mean difference [WMD] = -3.89; 95% CI: -4.98 to -2.81; P < .05) without increasing expenses (WMD = -0.16; 95% CI: -1.34 to 1.02; P > .05). Intravenous infusion manifested more advantages by decreasing the incidence of infectious complications and mortality. CONCLUSIONS Gln-enriched nutrition support is superior to conventional methods for SAP, and intravenous infusion may be a better choice for drug administration.
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Efficacy of glutamine-enriched enteral feeding formulae in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.
Mottaghi, A, Yeganeh, MZ, Golzarand, M, Jambarsang, S, Mirmiran, P
Asia Pacific journal of clinical nutrition. 2016;(3):504-12
Abstract
Critically ill patients usually suffer from catabolic stress that could lead to malnutrition and nutritional support therefore is essential to maintain lean body mass, improve metabolic and immune response and decrease rate of mortality and comorbidity in these patients. This meta-analysis was aimed to evaluate effect of glutamineenriched enteral nutrition in critically ill patients. In order to obtain randomized clinical trial studies (RCTs), international databases including MEDLINE and Google scholar and also electronic resources in Iran, including IRAN MEDEX, IRAN DOC, SID, Magiran were systematically searched without language and publication restriction before December 2014. The final included number of studies for meta-analysis was 10. The methodological quality of eligible studies was assessed by four investigators using the Jadad 5-point scale, a scale containing three items describing randomization, blinding and fate of participants. We analyzed data from the included studies using STATA version 12.0, and calculated a pooled odds ratio for dichotomous data and mean differences for continuous data with 95% confidence intervals (CIs). There was no significant difference in mortality in elevated pooled odds ratios (p-value=0.070). A funnel plot was drawn for evaluation of publication bias, but none was found. The fixed effect model shows significant reduction in gut permeability in who received enteral feeding enriched with glutamine (-0.84, 95% CI=-1.25 to -0.44), moreover the funnel plot did not show publication bias. Based on the available data, our meta-analysis showed that enteral glutamine (Gln) supplementation increased mortality rate, though non-significantly, but decreased gut permeability significantly.
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Parenteral immunonutrition in patients with acute pancreatitis: a systematic review and meta-analysis.
Jafari, T, Feizi, A, Askari, G, Fallah, AA
Clinical nutrition (Edinburgh, Scotland). 2015;(1):35-43
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BACKGROUND & AIMS Acute pancreatitis is a systemic immunoinflammatory response to auto-digestion of the pancrease and peri-pancreatic organs. Patients with acute pancreatitis can rapidly develop nutritional deficiency; hence nutritional support is important and critical. Sometimes parenteral nutrition (PN) is inevitable in acute pancreatitis. Due to immunosuppressive and inflammatory nature of the disease, it seems that immunonutrients like glutamine and omega-3 fatty acids (ω-3 FAs) added to parenteral formulas may improve the conditions. We conducted a meta-analysis to evaluate the effects of parenteral immunonutrition on clinical outcomes (infectious complications, length of hospital stay (LOS) and mortality) in patients with acute pancreatitis. METHODS A computerized literature search on four databases (PubMed, Cochrane, ISI Web of Science, and Iran Medex) was performed to find all the randomized controlled trials (RCTs) assessed the effects of parenteral immunonutrition in acute pancreatitis. Necessary data were extracted and quality assessment of RCTs was performed with consensus in the study team. Fixed effects model was used to conduct the meta-analysis. RESULTS One hundred and ninety four references were found via our search in which 7 articles matched our criteria for enrolling the meta-analysis. Parenteral immunonutrition significantly reduced the risk of infectious complications (RR = 0.59; 95% CI, 0.39-0.88; p ≤ 0.05) and mortality (RR = 0.26; 95% CI, 0.11-0.59; p ≤ 0.001). LOS was also shorter in patients who received immunonutrition (MD = -2.93 days; 95% CI, -4.70 to -1.15; p ≤ 0.001). CONCLUSION Immunonutrients like glutamine and ω-3 FAs added to parenteral formulas can improve prognoses in patients with acute pancreatitis.
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Effect of glutamine enriched nutrition support on surgical patients with gastrointestinal tumor: a meta-analysis of randomized controlled trials.
Kang, K, Shu, XL, Zhang, YS, Liu, XL, Zhao, J
Chinese medical journal. 2015;(2):245-51
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BACKGROUND Associations between glutamine (Gln) enriched nutrition support and surgical patients with gastrointestinal (GI) tumor remain controversy. The purpose of this meta-analysis was to assess the effect of Gln enriched nutrition support on surgical patients with GI tumor in term of relevant biochemical indices, immune indices, and clinical outcomes. METHODS Six databases were systematically searched to find eligible randomized controlled trials (RCTs) from 1966 to May 2014. When estimated the analysis indexes, the relative risk (RR) was used as the effect size of the categorical variable, while the weighted mean difference (MD) was used as the effect size of a continuous variable. Meta-analysis was conducted with Rev Man 5.2. RESULTS Thirteen RCTs, involving 1034 patients, were included in the meta-analysis. The analysis showed that Gln enriched nutrition support was more effective in increasing serum albumin (MD: 0.10; 95% confidence interval [CI]: 0.02-0.18; P < 0.05), serum prealbumin (MD: 1.98; 95% CI: 1.40-2.55; P < 0.05) and serum transferring (MD: 0.35; 95% CI: 0.12-0.57; P < 0.05), concentration of IgG (MD: 1.26; 95% CI: 0.90-1.63; P < 0.05), IgM (MD: 0.18; 95% CI: 0.11-0.25; P < 0.05), IgA (MD: 0.22; 95% CI: 0.10-0.33; P < 0.05), CD3 + (MD: 3.71; 95% CI: 2.57-4.85; P < 0.05) and CD4/CD8 ratio (MD: 0.27; 95% CI: 0.12-0.42; P < 0.05). Meanwhile, it was more significant in decreasing the incidence of infectious complications (RR: 0.67; 95% CI: 0.50-0.90; P < 0.05) and shortening the length of hospital stay (MD: -1.72; 95% CI: -3.31--0.13; P < 0.05). CONCLUSIONS Glutamine enriched nutrition support was superior in improving immune function, reducing the incidence of infectious complications and shortening the length of hospital stay, playing an important role in the rehabilitation of surgical GI cancer patients.
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The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials.
Chen, QH, Yang, Y, He, HL, Xie, JF, Cai, SX, Liu, AR, Wang, HL, Qiu, HB
Critical care (London, England). 2014;(1):R8
Abstract
INTRODUCTION Glutamine supplementation is supposed to reduce mortality and nosocomial infections in critically ill patients. However, the recently published reducing deaths due to oxidative stress (REDOX) trials did not provide evidence supporting this. This study investigated the impact of glutamine-supplemented nutrition on the outcomes of critically ill patients using a meta-analysis. METHODS We searched for and gathered data from the Cochrane Central Register of Controlled Trials, MEDLINE, Elsevier, Web of Science and ClinicalTrials.gov databases reporting the effects of glutamine supplementation on outcomes in critically ill patients. We produced subgroup analyses of the trials according to specific patient populations, modes of nutrition and glutamine dosages. RESULTS Among 823 related articles, eighteen Randomized Controlled Trials (RCTs) met all inclusion criteria. Mortality events among 3,383 patients were reported in 17 RCTs. Mortality showed no significant difference between glutamine group and control group. In the high dosage subgroup (above 0.5 g/kg/d), the mortality rate in the glutamine group was significantly higher than that of the control group (relative risk (RR) 1.18; 95% confidence interval (CI), 1.02 to 1.38; P = 0.03). In 15 trials, which included a total of 2,862 patients, glutamine supplementation reportedly affected the incidence of nosocomial infections in the critically ill patients observed. The incidence of nosocomial infections in the glutamine group was significantly lower than that of the control group (RR 0.85; 95% CI, 0.74 to 0.97; P = 0.02). In the surgical ICU subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.70; 95% CI, 0.52 to 0.94; P = 0.04). In the parental nutrition subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.83; 95% CI, 0.70 to 0.98; P = 0.03). The length of hospital stay was reported in 14 trials, in which a total of 2,777 patients were enrolled; however, the patient length of stay was not affected by glutamine supplementation. CONCLUSIONS Glutamine supplementation conferred no overall mortality and length of hospital stay benefit in critically ill patients. However, this therapy reduced nosocomial infections among critically ill patients, which differed according to patient populations, modes of nutrition and glutamine dosages.
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Glutamine supplementation for critically ill adults.
Tao, KM, Li, XQ, Yang, LQ, Yu, WF, Lu, ZJ, Sun, YM, Wu, FX
The Cochrane database of systematic reviews. 2014;(9):CD010050
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BACKGROUND Glutamine is a non-essential amino acid which is abundant in the healthy human body. There are studies reporting that plasma glutamine levels are reduced in patients with critical illness or following major surgery, suggesting that glutamine may be a conditionally essential amino acid in situations of extreme stress. In the past decade, several clinical trials examining the effects of glutamine supplementation in patients with critical illness or receiving surgery have been done, and the systematic review of this clinical evidence has suggested that glutamine supplementation may reduce infection and mortality rates in patients with critical illness. However, two recent large-scale randomized clinical trials did not find any beneficial effects of glutamine supplementation in patients with critical illness. OBJECTIVES The objective of this review was to:1. assess the effects of glutamine supplementation in critically ill adults and in adults after major surgery on infection rate, mortality and other clinically relevant outcomes;2. investigate potential heterogeneity across different patient groups and different routes for providing nutrition. SEARCH METHODS We searched the Cochrane Anaesthesia Review Group (CARG) Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 5); MEDLINE (1950 to May 2013); EMBASE (1980 to May 2013) and Web of Science (1945 to May 2013). SELECTION CRITERIA We included controlled clinical trials with random or quasi-random allocation that examined glutamine supplementation versus no supplementation or placebo in adults with a critical illness or undergoing elective major surgery. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS Two authors independently extracted the relevant information from each included study using a standardized data extraction form. For infectious complications and mortality and morbidity outcomes we used risk ratio (RR) as the summary measure with the 95% confidence interval (CI). We calculated, where appropriate, the number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH). We presented continuous data as the difference between means (MD) with the 95% CI. MAIN RESULTS Our search identified 1999 titles, of which 53 trials (57 articles) fulfilled our inclusion criteria. The 53 included studies enrolled a total of 4671 participants with critical illness or undergoing elective major surgery. We analysed seven domains of potential risk of bias. In 10 studies the risk of bias was evaluated as low in all of the domains. Thirty-three trials (2303 patients) provided data on nosocomial infectious complications; pooling of these data suggested that glutamine supplementation reduced the infectious complications rate in adults with critical illness or undergoing elective major surgery (RR 0.79, 95% CI 0.71 to 0.87, P < 0.00001, I² = 8%, moderate quality evidence). Thirty-six studies reported short-term (hospital or less than one month) mortality. The combined rate of mortality from these studies was not statistically different between the groups receiving glutamine supplement and those receiving no supplement (RR 0.89, 95% CI 0.78 to 1.02, P = 0.10, I² = 22%, low quality evidence). Eleven studies reported long-term (more than six months) mortality; meta-analysis of these studies (2277 participants) yielded a RR of 1.00 (95% CI 0.89 to 1.12, P = 0.94, I² = 30%, moderate quality evidence). Subgroup analysis of infectious complications and mortality outcomes did not find any statistically significant differences between the predefined groups. Hospital length of stay was reported in 36 studies. We found that the length of hospital stay was shorter in the intervention group than in the control group (MD -3.46 days, 95% CI -4.61 to -2.32, P < 0.0001, I² = 63%, low quality evidence). Slightly prolonged intensive care unit (ICU) stay was found in the glutamine supplemented group from 22 studies (2285 participants) (MD 0.18 days, 95% CI 0.07 to 0.29, P = 0.002, I² = 11%, moderate quality evidence). Days on mechanical ventilation (14 studies, 1297 participants) was found to be slightly shorter in the intervention group than in the control group (MD - 0.69 days, 95% CI -1.37 to -0.02, P = 0.04, I² = 18%, moderate quality evidence). There was no clear evidence of a difference between the groups for side effects and quality of life, however results were imprecise for serious adverse events and few studies reported on quality of life. Sensitivity analysis including only low risk of bias studies found that glutamine supplementation had beneficial effects in reducing the length of hospital stay (MD -2.9 days, 95% CI -5.3 to -0.5, P = 0.02, I² = 58%, eight studies) while there was no statistically significant difference between the groups for all of the other outcomes. AUTHORS' CONCLUSIONS This review found moderate evidence that glutamine supplementation reduced the infection rate and days on mechanical ventilation, and low quality evidence that glutamine supplementation reduced length of hospital stay in critically ill or surgical patients. It seems to have little or no effect on the risk of mortality and length of ICU stay, however. The effects on the risk of serious side effects were imprecise. The strength of evidence in this review was impaired by a high risk of overall bias, suspected publication bias, and moderate to substantial heterogeneity within the included studies.
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A meta-analysis of trials using the intention to treat principle for glutamine supplementation in critically ill patients with burn.
Lin, JJ, Chung, XJ, Yang, CY, Lau, HL
Burns : journal of the International Society for Burn Injuries. 2013;(4):565-70
Abstract
BACKGROUND During critical illness, the demand for glutamine may exceed that which can be mobilized from muscle stores. Infections increase mortality, morbidity, length-of-stay, antibiotic usage and the cost of care. This is a major health care issue. METHODS RCTs were identified from the electronic databases: the Cochrane Library, MEDLINE, PubMed web of knowledge and hand searching journals. The trials compared the supplementation with glutamine and non-supplementation in burn. Statistical analysis was performed using RevMan5.1 software, from Cochrane Collaboration. RESULTS 216 papers showed a match, in the keyword search. Upon screening the title, reading the abstract and the entire article, only four RCTs, involving 155 patients, were included. For both the glutamine group and control group, total burn surface area (TBSA) (MD=2.02, 95% CI -2.17, 6.21, p=0.34) was similar. Glutamine supplementation was associated with a statistically significant decrease in the number of patients with gram-negative bacteremia (OR 0.27, 95% CI 0.08-0.92, p=0.04) and hospital mortality (OR=0.13, 95% CI 0.03, 0.51, p=0.004), however, no statistical difference was noted between groups, for the other results. CONCLUSION Glutamine supplemented nutrition can be associated with a reduction in mortality in hospital, complications due to gram-negative bacteremia in burn patients. Further larger and better quality trials are required, in order to determine whether any differences are statistically and clinically important.