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1.
Nutrition in Sepsis: A Bench-to-Bedside Review.
De Waele, E, Malbrain, MLNG, Spapen, H
Nutrients. 2020;(2)
Abstract
Nutrition therapy in sepsis is challenging and differs from the standard feeding approach in critically ill patients. The dysregulated host response caused by infection induces progressive physiologic alterations, which may limit metabolic capacity by impairing mitochondrial function. Hence, early artificial nutrition should be ramped-up and emphasis laid on the post-acute phase of critical illness. Caloric dosing is ideally guided by indirect calorimetry, and endogenous energy production should be considered. Proteins should initially be delivered at low volume and progressively increased to 1.3 g/kg/day following shock symptoms wane. Both the enteral and parenteral route can be (simultaneously) used to cover caloric and protein targets. Regarding pharmaconutrition, a low dose glutamine seems appropriate in patients receiving parenteral nutrition. Supplementing arginine or selenium is not recommended. High-dose vitamin C administration may offer substantial benefit, but actual evidence is too limited for advocating its routine use in sepsis. Omega-3 polyunsaturated fatty acids to modulate metabolic processes can be safely used, but non-inferiority to other intravenous lipid emulsions remains unproven in septic patients. Nutrition stewardship, defined as the whole of interventions to optimize nutritional approach and treatment, should be pursued in all septic patients but may be difficult to accomplish within a context of profoundly altered cellular metabolic processes and organ dysfunction caused by time-bound excessive inflammation and/or immune suppression. This review aims to provide an overview and practical recommendations of all aspects of nutritional therapy in the setting of sepsis.
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2.
Altering Routine Intensive Care Unit Practices to Support Commensalism.
Hamilton, LA, Behal, ML
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(3):433-441
Abstract
The gastrointestinal (GI) tract consists of trillions of organisms that support multiple functions in the body, from immunity, digestion, and absorption to drug metabolism. These microbes form an overall collection of microorganisms that form the body's microbiome. In critical illness, many of these functions are aberrant, and the microbiome is altered, leading to untoward effects. Some of the most common medications received by patients include antibiotics and proton pump inhibitors, which affect particular changes in the microbiome. In addition, patients receiving prolonged enteral and parenteral nutrition experience changes in the microbiological composition and diversity of their GI tracts. Research is ongoing to characterize the crosstalk between the microbiome and immune function as targets for drug and nutrition therapy.
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3.
Supplemental parenteral nutrition improves immunity with unchanged carbohydrate and protein metabolism in critically ill patients: The SPN2 randomized tracer study.
Berger, MM, Pantet, O, Jacquelin-Ravel, N, Charrière, M, Schmidt, S, Becce, F, Audran, R, Spertini, F, Tappy, L, Pichard, C
Clinical nutrition (Edinburgh, Scotland). 2019;(5):2408-2416
Abstract
BACKGROUND & AIMS Individualized supplemental parenteral nutrition (SPN) providing measured energy expenditure from day 4 reduced infectious complications in a previous study including 305 intensive care (ICU) patients. The study aimed at investigating the metabolic, and immune responses underlying the clinical response of the previous trial. METHODS Randomized controlled trial enrolling 23 critically ill patients on day 3 (D3) of admission to the ICU who were fed less than 60% of their energy target by the enteral nutrition (EN) alone: allocation to either continued EN or to SPN to a target validated by indirect calorimetry. Protein and glucose metabolism (primary endpoint) were investigated with tracer isotopes on D4 and D9. Secondary endpoints: 1) immune response, investigated in serum and in stimulated peripheral blood mononuclear cells (PMBC), by dosing a panel of cytokines (infectious complications were recorded), and 2) Muscle mass was assessed by ultrasound of the thigh. RESULTS Comparable at baseline, the SPN group (n = 11) received more energy (median 24.3 versus 17.8 kcal/kg/day: p < 0.001) and proteins (1.11 versus 0.69 g/kg/day: p < 0.001) than the control group during the five days' intervention, resulting in a less negative energy balance by D9 (p = 0.0027). Net protein breakdown and Glucose kinetics on D9 did not differ, within or between groups. In agreement with a decrease in infection rate, immune response in the SPN group showed decreased serum IL-6 (p = 0.024), IL-1β, IL-10 levels and TNF-α secretion by PBMC (p = 0.018) at D9. Muscle mass loss from D4 to D15 tended to be less in the SPN group (-16% versus -23%: p = 0.06). Clinical course by D28 did not differ. CONCLUSIONS Feeding patients to cover an individualised measured energy target with SPN from D4 to cover needs, was associated with improved immunity, less systemic inflammation and a trend to less muscle mass loss. CLINICAL TRIAL REGISTRY NCT02022813 at https://clinicaltrials.gov/.
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4.
Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM).
Elke, G, Hartl, WH, Kreymann, KG, Adolph, M, Felbinger, TW, Graf, T, de Heer, G, Heller, AR, Kampa, U, Mayer, K, et al
Clinical nutrition ESPEN. 2019;:220-275
Abstract
PURPOSE Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).
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Chinese guidelines for the assessment and provision of nutrition support therapy in critically ill children.
Zhu, XM, Qian, SY, Lu, GP, Xu, F, Wang, Y, Liu, CF, Ren, XX, Zhang, YC, Gao, HM, Zhou, T, et al
World journal of pediatrics : WJP. 2018;(5):419-428
Abstract
BACKGROUND This document represents the first evidence-based guidelines to describe best practices in nutrition therapy in critically ill children (> 1 month and < 18 years), who are expected to require a length of stay more than 2 or 3 days in a Pediatric Intensive Care Unit admitting medical patients domain. METHODS A total of 25,673 articles were scanned for relevance. After careful review, 88 studies appeared to answer the pre-identified questions for the guidelines. We used the grading of recommendations, assessment, development and evaluation criteria to adjust the evidence grade based on the quality of design and execution of each study. RESULTS The guidelines emphasise the importance of nutritional assessment, particularly the detection of malnourished patients. Indirect calorimetry (IC) is recommended to estimate energy expenditure and there is a creative value in energy expenditure, 50 kcal/kg/day for children aged 1-8 years during acute phase if IC is unfeasible. Enteral nutrition (EN) and early enteral nutrition remain the preferred routes for nutrient delivery. A minimum protein intake of 1.5 g/kg/day is suggested for this patient population. The role of supplemental parenteral nutrition (PN) has been highlighted in patients with low nutritional risk, and a delayed approach appears to be beneficial in this group of patients. Immune-enhancing cannot be currently recommended neither in EN nor PN. CONCLUSION Overall, the pediatric critically ill population is heterogeneous, and an individualized nutrition support with the aim of improving clinical outcomes is necessary and important.
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6.
Should fecal microbial transplantation be used in the ICU?
McClave, SA, Patel, J, Bhutiani, N
Current opinion in critical care. 2018;(2):105-111
Abstract
PURPOSE OF REVIEW Maintaining gut barrier defenses, modulating immune responses, and supporting the role of commensal microbiota are major factors influencing outcome in critical illness. Of these, maintaining a commensal 'lifestyle' and preventing the emergence of a virulent pathobiome may be most important in reducing risk of infection and multiple organ failure. RECENT FINDINGS The polymeric formulas utilized for enteral nutrition in the ICU are absorbed high in the gastrointestinal tract and may not reach the microbial burden in the cecum where their effect is most needed. The provision of a few select probiotic organisms may be insufficient to refaunate the gut and establish a 'recovery pattern,' propelling the patient toward health and homeostasis. Use of fecal microbial transplantation (FMT) appears to be a more successful strategy for replenishing the intestinal microbiome and maintaining its commensal phenotypic expression. SUMMARY FMT has become an attractive option to mitigate multiple organ dysfunction in the ICU. This article discusses the physiology, rationale, early experience, and expectations for such therapy in the critically ill patient.
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Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes.
Carr, AC, Rosengrave, PC, Bayer, S, Chambers, S, Mehrtens, J, Shaw, GM
Critical care (London, England). 2017;(1):300
Abstract
BACKGROUND Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients. METHODS Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients' daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model. RESULTS Overall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients (P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d). CONCLUSIONS Critically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.
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8.
Intestinal T lymphocyte homing is associated with gastric emptying and epithelial barrier function in critically ill: a prospective observational study.
Greis, C, Rasuly, Z, Janosi, RA, Kordelas, L, Beelen, DW, Liebregts, T
Critical care (London, England). 2017;(1):70
Abstract
BACKGROUND Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS We conducted a prospective observational study at two tertiary care medical ICUs. Fifty consecutive patients needing invasive mechanical ventilation were recruited within 24 h of ICU admission, prior to any nutritional support. The acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score and the multiple organ dysfunction score (MODS) were used to assess illness severity and multiple organ dysfunction. Gastric emptying was assessed by paracetamol absorption test. Peripheral blood mononuclear cells were freshly isolated and cultured for 24 h, and TNF-α, IL-1β and IL-10 measured in cell culture supernatants and in serum by ELISA. The intestinal epithelial barrier was assessed, quantifying serum concentrations of intestinal fatty acid binding protein (I-FABP), ileal bile-acid binding protein (I-BABP) and zonulin-1 by ELISA. Small bowel homing T lymphocytes (CD4+ α4β7 + CCR9+) were analyzed by flow cytometry. The Mann-Whitney test and Spearman correlation were used in statistical evaluation. RESULTS CD4 + α4β7 + CCR9+ T lymphocytes were inversely correlated with gastric emptying. Patients with delayed gastric emptying at ICU admission (n = 35) had significantly higher serum and PBMC-induced TNF-α and IL-1β and increased intestinal barrier disruption reflected by higher I-FABP, I-BABP and zonulin-1. Patients who died in the ICU had significantly impaired gastric empting at admission compared to ICU survivors. No differences were observed in APACHE II, SOFA or MODS in patients with delayed gastric emptying compared to patients with normal gastric emptying. CONCLUSIONS Exaggerated CD4 + α4β7 + CCR9+ T lymphocyte homing with increased pro-inflammatory cytokine release and intestinal epithelial barrier disruption are associated with delayed gastric emptying. This is not simply due to differences in overall severity of illness at ICU admission and may represent a pathophysiological mechanism of gut-directed immune activation leading to impaired barrier function in the critically ill.
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9.
Interaction Between 2 Nutraceutical Treatments and Host Immune Status in the Pediatric Critical Illness Stress-Induced Immune Suppression Comparative Effectiveness Trial.
Carcillo, JA, Dean, JM, Holubkov, R, Berger, J, Meert, KL, Anand, KJS, Zimmerman, JJ, Newth, CJL, Harrison, R, Burr, J, et al
JPEN. Journal of parenteral and enteral nutrition. 2017;(8):1325-1335
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Abstract
BACKGROUND AND AIMS The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis. METHODS Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category. RESULTS There were 134 immune-competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P < .05) and on the rate of nosocomial infection and sepsis per 100 patient days ( P < .05). Whey protein treatment protected immune-competent patients without lymphopenia from infection and sepsis, both nutraceutical strategies were equivalent in immune-competent patients with lymphopenia, and zinc, selenium, glutamine, and metoclopramide treatment protected immunocompromised patients from infection and sepsis. CONCLUSIONS The science of immune nutrition is more complex than previously thought. Future trial design should consider immune status at the time of trial entry because differential effects of nutraceuticals may be related to this patient characteristic.
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Influence of nutrition therapy on the intestinal microbiome.
Krezalek, MA, Yeh, A, Alverdy, JC, Morowitz, M
Current opinion in clinical nutrition and metabolic care. 2017;(2):131-137
Abstract
PURPOSE OF REVIEW This review describes the relationship between nutritional therapies and the intestinal microbiome of critically ill patients. RECENT FINDINGS The intestinal microbiome of the critically ill displays a near complete loss of health-promoting microbiota with overgrowth of virulent healthcare-associated pathogens. Early enteral nutrition within 24 h of admission to the ICU has been advocated in medical and surgical patients to avoid derangements of the intestinal epithelium and the microbiome associated with starvation. Contrary to previous dogma, permissive enteral underfeeding has recently been shown to have similar outcomes to full feeding in the critically ill, whereas overfeeding has been shown to be deleterious in those patients who are not malnourished at baseline. Randomized clinical trials suggest that peripheral nutrition can be used safely either as the sole or supplemental source of nutrition even during the early phases of critical care. The use of probiotics has been associated with a significant reduction in infectious complications in the critically ill without a notable mortality benefit. SUMMARY Focus of research is shifting toward strategies that augment the intestinal environment to facilitate growth of beneficial microorganisms, strengthen colonization resistance, and maintain immune homeostasis.