Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients.
ABSTRACT: BACKGROUND:Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS:This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS:Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS:Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.
Project description: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.
Project description:<h4>Background</h4>Nutrients, 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.<h4>Objective</h4>Explore 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.<h4>Methods</h4>Secondary 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.<h4>Results</h4>eHSP70 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.<h4>Conclusion</h4>Our 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:<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:Healthcare-associated infections (HAI) in preterm infants are a challenge to the care of these fragile patients. HAI-incidence rates range from 6 to 27 infections per 1000 patient-days. Most nosocomial infections are bloodstream infections and of these, the majority is associated with the use of central venous catheters. Many studies identified parenteral nutrition as an independent risk factor for HAI, catheter-associated bloodstream infection, and clinical sepsis. This fact and various published outbreaks due to contaminated parenteral nutrition preparations highlight the importance of appropriate standards in the preparation and handling of intravenous solutions and parenteral nutrition. Ready-to-use parenteral nutrition formulations may provide additional safety in this context. However, there is concern that such formulations may result in overfeeding and necrotizing enterocolitis. Given the risk for catheter-associated infection, handling with parenteral nutrition should be minimized and the duration shortened. Further research is required about this topic.
Project description: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.
Project description:Total parenteral nutrition (TPN) results in a number of derangements to the intestinal epithelium, including a loss of epithelial barrier function (EBF). As TPN supplemented with glutamine has been thought to prevent this loss, this article further defined the impact of glutamine on EBF, and investigated potential mechanisms that contributed to the preservation of EBF. C57BL/6J male mice were randomized to enteral nutrition (control), TPN, or TPN supplemented with glutamine (TPN+GLN). Changes in intraepithelial lymphocyte (IEL)-derived cytokine expression were measured, and EBF was assessed with electrophysiologic methods and assessment of junctional protein expression. TPN resulted in a significant decline in EBF, and this loss of EBF was significantly prevented in the TPN+GLN group. Coincident with these changes was a loss of intraepithelial lymphocyte (IEL, mucosal lymphocyte)-derived IL-10 and increase in interferon-gamma (IFN-gamma) expression, and a decline in IEL numbers in the TPN group. A prevention in the increase in IFN-gamma and decline in IL-10 expression was seen in the TPN+GLN group. To determine the mechanism responsible for these glutamine-associated cytokine changes, we tested whether blockade of the IL-7 signaling pathway between epithelial cells (EC) and IEL would prevent these changes; however, blockade failed to influence IEL-derived cytokine changes. Glutamine-supplemented TPN leads to a specific IEL-derived cytokine profile, which may account for the preservation of EBF; and such action may be due to a direct action of glutamine on the IEL.
Project description:The state-of-the-art nutrition used for critically ill children is based essentially on expert opinion and extrapolations from adult studies or on studies in non-critically ill children. In critically ill adults, withholding parenteral nutrition (PN) during the first week in ICU improved outcome, as compared with early supplementation of insufficient enteral nutrition (EN) with PN. We hypothesized that withholding PN in children early during critical illness reduces the incidence of new infections and accelerates recovery.The Pediatric Early versus Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC) study is an investigator-initiated, international, multicenter, randomized controlled trial (RCT) in three tertiary referral pediatric intensive care units (PICUs) in three countries on two continents. This study compares early versus late initiation of PN when EN fails to reach preset caloric targets in critically ill children. In the early-PN (control, standard of care) group, PN comprising glucose, lipids and amino acids is administered within the first days to reach the caloric target. In the late-PN (intervention) group, PN completing EN is only initiated beyond PICU-day 7, when EN fails. For both study groups, an early EN protocol is applied and micronutrients are administered intravenously. The primary assessor-blinded outcome measures are the incidence of new infections during PICU-stay and the duration of intensive care dependency. The sample size (n?=?1,440, 720 per arm) was determined in order to detect a 5% absolute reduction in PICU infections, with at least 80% 1-tailed power (70% 2-tailed) and an alpha error rate of 5%. Based on the actual incidence of new PICU infections in the control group, the required sample size was confirmed at the time of an a priori- planned interim-analysis focusing on the incidence of new infections in the control group only.Clinical evidence in favor of early administration of PN in critically ill children is currently lacking, despite potential benefit but also known side effects. This large international RCT will help physicians to gain more insight in the clinical effects of omitting PN during the first week of critical illness in children.ClinicalTrials.gov: NCT01536275 on 16 February 2012.
Project description:BACKGROUND:Malnutrition is common in inflammatory bowel disease (IBD), requiring timely and sufficient nutritional supplementation. In patients hospitalized for active disease, symptoms and/or altered intestinal function hinder enteral nutrition feasibility. In this scenario, parenteral nutrition (PN) is used. We aimed (1) to assess the frequency of PN use between 1997 and 2012 among hospitalized pediatric patients with IBD, (2) to determine the risk of in-hospital thrombus and infection associated with PN, and (3) to identify predictors of thrombus and infection in pediatric IBD hospitalizations utilizing PN. METHODS:We performed a cross-sectional analysis of pediatric patients hospitalized between 1997 and 2012. We used the Kids' Inpatient Database (KID) to identify pediatric patients (?18 years of age) with Crohn's disease (CD) or ulcerative colitis (UC), PN exposure, and primary outcomes including thrombus and infection. We used multivariable regression to identify risk factors for outcomes of interest. RESULTS:Parenteral nutrition was utilized in 3732 (12%) of 30,914 IBD hospitalizations. Three percent of PN patients experienced a thrombotic complication, and 5.5% experienced an infectious complication. Multivariate analysis showed PN as an independent risk factor for thrombus (odds ratio [OR], 4.3; 95% confidence interval [CI], 3.2-5.6) and infection (OR, 3.8; 95% CI, 3.1-4.6). Surgery was an independent risk factor for thrombus (OR, 2.0; 95% CI, 1.4-2.7) and infection (OR, 2.5; 95% CI, 2.0-3.1) in hospitalizations exposed to PN. CONCLUSIONS:Hospitalized pediatric IBD patients, particularly surgical, receiving PN are at increased risk for thrombosis and infection. Clinicians must balance these risks with the benefits of PN.
Project description:<h4>Objectives</h4>The prognosis of severe acute pancreatitis (SAP) patients is closely related to early nutritional support. It is well-established that changes in glutamine (Gln), an important amino acid and nutritional supplement, can reflect disease severity. However, no consensus has been reached on the role of Gln nutrition therapy for SAP patients. We conducted this systematic review and meta-analysis to summarize and evaluate the advantages of Gln supplementation in SAP.<h4>Methods</h4>PubMed, Web of Science, the Embase, Cochrane Library, and Chinese databases (CNKI, SinoMed, Wanfang, and VIP) were systematically searched for eligible studies that included glutamine supplementation in SAP patients from inception to October 31 2021, excluding non-SAP studies. Primary outcome measures included mortality, APACHE II score, complications, and length of hospital stay. The meta-analysis was registered with PROSPERO (CRD42021288371) and was conducted using Review Manager and Stata softwares.<h4>Results</h4>This meta-analysis included 30 randomized controlled trials (RCTs) with a total of 1,201 patients. Six primary outcomes and six secondary outcomes were analyzed. For the primary outcomes, Gln supplementation was associated with lower mortality (OR = 0.38, 95% CI: 0.21-0.69, <i>P</i> = 0.001), total hospital stay (MD = -3.41, 95% CI: -4.93 to -1.88, <i>P</i> < 0.0001) and complications (OR = 0.45, 95% CI: 0.31-0.66, <i>P</i> < 0.0001) compared with conventional nutrition. Further subgroup analysis found that parenteral glutamine was more effective in reducing mortality. In terms of secondary outcomes, Gln supplementation helped restore liver, kidney and immune function, with significantly increased serum albumin (SMD = 1.02, 95% CI: 0.74-1.31, <i>P</i> < 0.00001) and IgG levels (MD = 1.24, 95% CI: 0.82-1.67, <i>P</i> < 0.00001), and decreased serum creatinine (Scr) (MD = -12.60, 95% CI: -21.97 to -3.24, <i>P</i> = 0.008), and inflammatory indicators such as C-reaction protein (CRP) (SMD = -1.67, 95% CI: -2.43 to -0.90, <i>P</i> < 0.0001).<h4>Conclusion</h4>Although Gln supplementation is not routinely recommended, it is beneficial for SAP patients. Indeed, glutamine nutrition has little effect on some indicator outcomes but contributes to improving the prognosis of this patient population.<b>Systematic Review Registration:</b> PROSPERO (york.ac.uk). Unique Identifier: CRD42021288371.
Project description:<h4>Aim</h4>To give evidence-based recommendations on the application of ketogenic diet parenteral nutrition (KD-PN) in emergency situations.<h4>Method</h4>An international group of experts (n=14) researched the literature and distributed a survey among 150 expert centers. International accepted guidelines (European Society for Clinical Nutrition and Metabolism/European Society for Paediatric Gastroenterology Hepatology and Nutrition and the American Society for Parenteral and Enteral Nutrition) and handbooks for parenteral nutrition were considered general standards of care.<h4>Results</h4>In the literature, we identified 35 reports of patients treated by KD-PN. International guidelines and handbooks provided some conflicting information. Twenty-four expert teams from nine countries responded to the survey, reflecting the limited clinical experience.<h4>Interpretation</h4>This paper highlights 23 consensus-based recommendations for safe and effective KD-PN (e.g. diet initiation, calculation, application, monitoring, and evaluation) based on the best evidence available and expert opinions.<h4>What this paper adds</h4>In acute settings, ketogenic diet therapy (KDT) can be administered parenterally. Parenteral administration of KDT should be started only at the intensive care unit. Initiate ketogenic parenteral nutrition stepwise to the highest ratio possible with the lowest level of complications. Evaluate the risk-benefit ratio of parenteral administration continuously. Restart enteral feeding as soon as appropriate.