Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness.

Purpose of reviewLoss of 'health-promoting' microbes and overgrowth of pathogenic bacteria (dysbiosis) in ICU is believed to contribute to nosocomial infections, sepsis, and organ failure (multiple organ dysfunction syndrome). This review discusses new understanding of ICU dysbiosis, new data for probiotics and fecal transplantation in ICU, and new data characterizing the ICU microbiome.Recent findingsICU dysbiosis results from many factors, including ubiquitous antibiotic use and overuse. Despite advances in antibiotic therapy, infections and mortality from often multidrug-resistant organisms (i.e., Clostridium difficile) are increasing. This raises the question of whether restoration of a healthy microbiome via probiotics or other 'dysbiosis therapies' would be an optimal alternative, or parallel treatment option, to antibiotics. Recent clinical data demonstrate probiotics can reduce ICU infections and probiotics or fecal microbial transplant (FMT) can treat Clostridium difficile. This contributes to recommendations that probiotics should be considered to prevent infection in ICU. Unfortunately, significant clinical variability limits the strength of current recommendations and further large clinical trials of probiotics and FMT are needed. Before larger trials of 'dysbiosis therapy' can be thoughtfully undertaken, further characterization of ICU dysbiosis is needed. To addressing this, we conducted an initial analysis demonstrating a rapid and marked change from a 'healthy' microbiome to an often pathogen-dominant microbiota (dysbiosis) in a broad ICU population.SummaryA growing body of evidence suggests critical illness and ubiquitous antibiotic use leads to ICU dysbiosis that is associated with increased ICU infection, sepsis, and multiple organ dysfunction syndrome. Probiotics and FMT show promise as ICU therapies for infection. We hope future-targeted therapies using microbiome signatures can be developed to correct 'illness-promoting' dysbiosis to restore a healthy microbiome post-ICU to improve patient outcomes

Editorial: Glutamine, heat shock protein, and inflammation — opportunity from the midst of difficulty

No Abstract Available South African Journal of Clinical Nutrition Vol.17(3) 2004: 84-8

Extreme Dysbiosis of the Microbiome in Critical Illness.

Critical illness is hypothesized to associate with loss of "health-promoting" commensal microbes and overgrowth of pathogenic bacteria (dysbiosis). This dysbiosis is believed to increase susceptibility to nosocomial infections, sepsis, and organ failure. A trial with prospective monitoring of the intensive care unit (ICU) patient microbiome using culture-independent techniques to confirm and characterize this dysbiosis is thus urgently needed. Characterizing ICU patient microbiome changes may provide first steps toward the development of diagnostic and therapeutic interventions using microbiome signatures. To characterize the ICU patient microbiome, we collected fecal, oral, and skin samples from 115 mixed ICU patients across four centers in the United States and Canada. Samples were collected at two time points: within 48 h of ICU admission, and at ICU discharge or on ICU day 10. Sample collection and processing were performed according to Earth Microbiome Project protocols. We applied SourceTracker to assess the source composition of ICU patient samples by using Qiita, including samples from the American Gut Project (AGP), mammalian corpse decomposition samples, childhood (Global Gut study), and house surfaces. Our results demonstrate that critical illness leads to significant and rapid dysbiosis. Many taxons significantly depleted from ICU patients versus AGP healthy controls are key "health-promoting" organisms, and overgrowth of known pathogens was frequent. Source compositions of ICU patient samples are largely uncharacteristic of the expected community type. Between time points and within a patient, the source composition changed dramatically. Our initial results show great promise for microbiome signatures as diagnostic markers and guides to therapeutic interventions in the ICU to repopulate the normal, "health-promoting" microbiome and thereby improve patient outcomes. IMPORTANCE Critical illness may be associated with the loss of normal, "health promoting" bacteria, allowing overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure. This has significant world health implications, because sepsis is becoming a leading cause of death worldwide, and hospital-acquired infections contribute to significant illness and increased costs. Thus, a trial that monitors the ICU patient microbiome to confirm and characterize this hypothesis is urgently needed. Our study analyzed the microbiomes of 115 critically ill subjects and demonstrated rapid dysbiosis from unexpected environmental sources after ICU admission. These data may provide the first steps toward defining targeted therapies that correct potentially "illness-promoting" dysbiosis with probiotics or with targeted, multimicrobe synthetic "stool pills" that restore a healthy microbiome in the ICU setting to improve patient outcomes

Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis

INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection

Nutritional Optimization of the Surgical Patient: A Narrative Review.

An increasing body of literature supports the clinical benefit of nutritional assessment and optimization in surgical patients; however, this&nbsp;data has yet to be consolidated in a practical fashion for use by surgeons. In this narrative review, we concisely aggregate emerging&nbsp;data&nbsp;to highlight the role of nutritional optimization as a promising, practical perioperative intervention to reduce complications and improve outcomes in surgical patients. This review of the surgical nutrition literature was conducted via large database review. There were no distinct inclusion/exclusion criteria for this review; however, we focused on adult populations using up-to-date literature from high-quality systematic reviews or randomized controlled trials when available. Current perioperative management focuses on the mitigation of intraoperative and immediate postoperative complications. Well-defined risk calculators attempt to stratify patient surgical risk preoperatively to reduce adverse events directly related to surgical procedures, such as hemorrhage, cardiopulmonary&nbsp;compromise, or infection. However, there is a lack of standardization of prognostic tools, nutritional protocols, and guidelines governing the assessment, composition, and administration of nutritional supplementation. Substantial data exist demonstrating&nbsp;the clinical benefit in the operative setting. In this work, we provide a fundamental primer for surgeons to understand the clinical importance of nutritional optimization along with practical prognostic tools and recommendations for use in their practice. While the extent to which nutritional optimization improves patient outcomes is debatable, the evidence clearly demonstrates a clinically meaningful benefit. Evaluating nutritional status differs based on disease severity and etiology of presentation, thus surgeons must select the appropriate prognostic tools to assess their patients during the perioperative period. This information will catalyze subsequent work&nbsp;with a multidisciplinary team to provide personalized dietary plans for patients and spark research to establish protocols for specific&nbsp;presentations

Hospital Change to Mixed Lipid Emulsion From Soybean Oil-Based Lipid Emulsion for Parenteral Nutrition in Hospitalized and Critically Ill Adults Improves Outcomes: A Pre-Post-Comparative Study

INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. METHODS: We conducted a single-center retrospective cohort study among adult patients (\u3e 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. RESULTS: We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95-0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87-0.93, p \u3c 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82-0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (- 1.6, 95% CI - 2.8 to - 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26-0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. CONCLUSION: 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients

Predicting critical illness mortality and personalizing therapy: moving to multi-dimensional data

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A novel ultrasound approach in assessing IMAT in critically ill patients

BACKGROUND: Muscle wasting is a common finding in critically ill patients associated with increased days of mechanical ventilation in the ICU. Muscle wasting and associated morphological changes are hallmarks of ICU-acquired weakness. Muscle wasting can be diagnosed and quantified by muscle biopsy, but biopsies can cause multiple adverse effects. MuscleSound® has developed a non-invasive, real-time novel MusculoSkeletal (MSK) ultrasound approach to measure the ratio between percentage intramuscular adipose tissue (%IMAT) with muscle cross-section area (MCSA) (termed IMAT-Index). The present study aimed to assess the IMAT-Index in ICU patients longitudinally and compare it to age-matched healthy controls. METHODS: Transverse (short-axis) ultrasound images of the rectus femoris muscle were obtained upon admission and discharge in 35 ICU patients and compared to age-matched healthy controls (n = 975). The echo intensity of the image taken from the muscle is used to automatically calculate the ratio between intramuscular adipose tissue by cm2 (IMAT-Index), the cross-sectional area of the muscle (MCSA), and muscle thickness (MT). RESULTS: IMAT-Index was successfully measured in all subjects. The mean IMAT-index (%IMAT/cm2) upon admission was significantly higher in critically ill patients compared to healthy controls (7.4 ± 4.3 vs. 3.1 ± 0.9, p &amp;lt; 0.001). At ICU discharge, the IMAT-index increased in the ICU group compared to admission (8.1 ± 3.5 vs. 7.4 ± 4.3, p &amp;lt; 0.05). CONCLUSION: Real-time noninvasive MSK ultrasound IMAT-Index was higher in ICU patients than in healthy controls and increased during the ICU stay, both in male and female patients

Parenteral glutamine supplementation in critical illness: a systematic review

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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