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Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

ABSTRACT: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients.GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients.A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5?g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n?=?75) received standard GLN-free PN (STD-PN); the GLN group (n?=?75) received PN containing alanyl-GLN dipeptide (0.5?g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints.Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P?=?0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P?=?0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P?=?0.73). Other clinical outcomes and adverse events were similar.PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

SUBMITTER: Ziegler TR

PROVIDER: S-EPMC4877187 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

Ziegler Thomas R TR May Addison K AK Hebbar Gautam G Easley Kirk A KA Griffith Daniel P DP Dave Nisha N Collier Bryan R BR Cotsonis George A GA Hao Li L Leong Traci T Manatunga Amita K AK Rosenberg Eli S ES Jones Dean P DP Martin Gregory S GS Jensen Gordon L GL Sax Harry C HC Sax Harry C HC Kudsk Kenneth A KA Galloway John R JR Blumberg Henry M HM Evans Mary E ME Wischmeyer Paul E PE

Annals of surgery 20160401 4

<h4>Objective</h4>To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients.<h4>Summary background data</h4>GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients.<h4>Methods</h4>A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN ...[more]

PMID: 26501700

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Project description:BackgroundNutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited.ObjectiveExplore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations.MethodsSecondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up.ResultseHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN.ConclusionOur results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.

Project description:IntroductionPrevious studies and a meta-analysis in surgical patients indicate that supplementing parenteral nutrition regimens with n-3 polyunsaturated fatty acids (PUFAs), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with improved laboratory and clinical outcomes in the setting of hyper-inflammatory conditions. Refined or synthetic fish oils are commonly used as a source of EPA and DHA. The objective of the present meta-analysis was to evaluate n-3 PUFA-enriched parenteral nutrition regimens in elective surgical and intensive care unit (ICU) patients.MethodsMedline was searched for randomized controlled trials comparing n-3 PUFA-enriched lipid emulsions with standard non-enriched lipid emulsions (i.e. soybean oil, MCT/LCT or olive/soybean oil emulsions) in surgical and ICU patients receiving parenteral nutrition. Extracted data were pooled by means of both random and fixed effects models, and subgroup analyses were carried forward to compare findings in ICU versus non-ICU patients.ResultsA total of 23 studies (n = 1502 patients: n = 762 admitted to the ICU) were included. No statistically significant difference in mortality rate was found between patients receiving n-3 PUFA-enriched lipid emulsions and those receiving standard lipid emulsions (RR = 0.89; 0.59, 1.33), possibly reflecting a relatively low underlying mortality risk. However, n-3 PUFA-enriched emulsions are associated with a statistically and clinically significant reduction in the infection rate (RR = 0.61; 0.45, 0.84) and the lengths of stay, both in the ICU (-1.92; -3.27, -0.58) and in hospital overall (-3.29; -5.13, -1.45). Other beneficial effects included reduced markers of inflammation, improved lung gas exchange, liver function, antioxidant status and fatty acid composition of plasma phospholipids, and a trend towards less impairment of kidney function.ConclusionsThese results confirm and extend previous findings, indicating that n-3 PUFAs-enriched parenteral nutrition regimens are safe and effective in reducing the infection rate and hospital/ICU stay in surgical and ICU patients.

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Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

Publications

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

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