Bench-to-bedside review: Metabolism and nutrition

Acute kidney injury (AKI) develops mostly in the context of critical illness and multiple organ failure, characterized by alterations in substrate use, insulin resistance, and hypercatabolism. Optimal nutritional support of intensive care unit patients remains a matter of debate, mainly because of a lack of adequately designed clinical trials. Most guidelines are based on expert opinion rather than on solid evidence and are not fundamentally different for critically ill patients with or without AKI. In patients with a functional gastrointestinal tract, enteral nutrition is preferred over parenteral nutrition. The optimal timing of parenteral nutrition in those patients who cannot be fed enterally remains controversial. All nutritional regimens should include tight glycemic control. The recommended energy intake is 20 to 30 kcal/kg per day with a protein intake of 1.2 to 1.5 g/kg per day. Higher protein intakes have been suggested in patients with AKI on continuous renal replacement therapy (CRRT). However, the inadequate design of the trials does not allow firm conclusions. Nutritional support during CRRT should take into account the extracorporeal losses of glucose, amino acids, and micronutrients. Immunonutrients are the subject of intensive investigation but have not been evaluated specifically in patients with AKI. We suggest a protocolized nutritional strategy delivering enteral nutrition whenever possible and providing at least the daily requirements of trace elements and vitamins

Asymétrie d’information et marchés financiers : une synthèse de la littérature récente

Cet article est une synthèse des recherches récentes en matière d’asymétrie d’informations sur les marchés financiers. L’impact de différentes hypothèses sur l’existence et l’efficience informationnelle des équilibres est étudié. Le cas de la concurrence parfaite est d’abord analysé (Grossman et Stiglitz, 1980). Puis la concurrence imparfaite est analysée. On distingue deux cas, selon que le bruit qui empêche le prix d’être parfaitement révélateur provient d’une offre exogène (KyIe, 1985, 1989), ou d’une dotation aléatoire des agents informés (Glosten, 1989; Bhattacharya et Spiegel, 1990; Bossaerts et Hughson, 1991). Dans le premier cas, l’équilibre existe toujours. Dans le second cas, il n’existe que si le bruit est assez élevé ou si le support de sa distribution est borné.The impact of different hypotheses on the existence and informativeness of rational expectations equilibria is analyzed within a simple synthetic model. The case of perfect competition is first analyzed (Grossman and Stiglitz, 1980). Second imperfect competition with exogenous noise trading is studied (KyIe 1985, 1989). Informational efficiency is lower than in the previous case, because of the strategic behaviour of the insider. Third, imperfect competition without noise trader, but with unknown random endowments of the informed agent is analyzed (Glosten, 1989; Bhattacharya and Spiegel, 1990; Bossaerts and Hughson, 1991). In contrast with the previous case, equilibrium exists only if there is enough noise

Gastrointestinal biomarkers and their association with feeding in the first five days of pediatric critical illness

OBJECTIVES: Predicting the patients' tolerance to enteral nutrition (EN) would help clinicians optimize individual nutritional intake. This study investigated the course of several gastrointestinal (GI) biomarkers and their association with EN advancement (ENA) longitudinally during pediatric intensive care unit (PICU) admission.METHODS: This is a secondary analysis of the PEPaNIC RCT. EN was started early and increased gradually. The cholecystokinin (CCK), leptin, glucagon, intestinal fatty acid-binding protein 2 (I-FABP2), and citrulline plasma concentrations were measured upon PICU admission, day three and day five. ENA was defined as kcal EN provided as % of predicted resting energy expenditure (pREE). The course of the biomarkers and ENA was examined in patients with samples on all time points using Friedman and Wilcoxon signed-rank tests. The association of ENA with the biomarkers was examined using a two-part mixed-effects model with data of the complete population, adjusted for possible confounders.RESULTS: For 172 patients, median age 8.6 years (first quartile (Q1); third quartile (Q3): 4.2; 13.4), samples were available, of which 55 had samples on all time points. The median ENA was 0 (0; 0) on admission, 14.5 (0.0; 43.8) on day 3 and 28.0 (7.6; 94.8) on day 5. During PICU stay, CCK and I-FABP2 concentrations decreased significantly, whereas glucagon concentrations increased significantly, and leptin and citrulline remained stable. None of the biomarkers was longitudinally associated with ENA.CONCLUSIONS: Based on the current evidence, CCK, leptin, glucagon, I-FABP2, and citrulline appear to have no added value in predicting ENA in the first five days of pediatric critical illness.</p

When to start Parenteral Micronutrients?

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Commentary by the authors on “Early versus Late Parenteral nutrition in Critically Ill Adults.

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Impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients (EPaNIC trial): a study protocol and statistical analysis plan for a randomized controlled trial

Abstract Background For critically ill patients treated in intensive care units (ICU), two feeding strategies are currently being advocated, one by American/Canadian and the other by European expert guidelines. These guidelines differ particularly in the timing of initiating parenteral nutrition (PN) in patients for whom enteral nutrition (EN) does not reach caloric targets. Methods/Design The EPaNIC trial is an investigator-initiated, non-commercial, multi-center, randomized, controlled, clinical trial with a parallel group design. This study compares early (European guideline) versus late (American/Canadian guideline) initiation of PN when EN fails to reach a caloric target. In the early PN group, PN is initiated within 24-48 hours after ICU admission to complete early enteral nutrition (EN) up to a calculated nutritional target. In the late PN group, PN completing EN is initiated when the target is not reached on day 8. In both groups, the same early EN protocol is applied. The study is designed to compare clinical outcome (morbidity and mortality) in the 2 study arms as well as to address several mechanistical questions. We here describe the EPaNIC study protocol and the statistical analysis plan for the primary report of the clinical results. Discussion The study has been initiated as planned on august 01 2007. One interim analysis advised continuation of the trial. The study will be completed in February 2011. Trial Registration ClinicalTrials (NCT): NCT00512122</p

OR16-4 The Growth Hormone Axis in Relation to Muscle Weakness in the ICU: Effect of Early Macronutrient Deficit.

Abstract The activity of the growth hormone (GH) axis is altered by critical illness. In the acute phase, GH resistance, as reflected by increased GH and decreased insulin-like growth factor-I (IGF-I), mimics fasting-induced changes in health. Although early full feeding in ICU has long been assumed to prevent muscle wasting and weakness, the EPaNIC RCT observed fewer complications and faster recovery with accepting the macronutrient deficit in the first ICU week, as compared with early full feeding, including less acquired muscle weakness [1,2]. We previously observed that accepting the early macronutrient deficit attenuated rather than aggravated the rise in GH as compared with early full feeding [3]. We have now further characterized its impact on the GH axis, in relation to the risk of acquiring muscle weakness in ICU. This was a preplanned sub-analysis of the EPaNIC RCT. For 10 matched patients per group, serum GH was quantified every 10 min between 9 PM and 6 AM, followed by deconvolution analyses to estimate GH secretion. For 564 patients per group, matched for baseline characteristics, and for all patients investigated for muscle weakness (n=600), serum IGF-I, IGF binding protein 3 (IGFBP3) and IGFBP1 were measured upon ICU admission, at day 4 (if still in ICU), and on the last ICU day (LD). Matched healthy subjects (n=65) were included as controls. Groups were compared with Wilcoxon test or repeated-measures ANOVA. Associations between changes in concentrations from baseline to day 4 or LD for patients with shorter ICU stay (d4/LD) and risk of muscle weakness were assessed with nominal logistic regression analysis, adjusted for baseline risk factors, baseline hormone concentrations and randomization. Upon ICU admission, patients revealed low IGF-I and IGFBP3 and high IGFBP1 as compared with controls (p<0.001). Tolerating an early macronutrient deficit in ICU decreased basal (non-pulsatile) GH secretion (p=0.005) without affecting pulsatile GH secretion. From admission to d4/LD IGF-I and IGFBP3 increased, whereas IGFBP1 decreased (all p<0.001) in the fully fed group. Compared to full feeding, tolerating the early macronutrient deficit prevented the rise in IGF-I (p<0.001), did not affect IGFBP3 and attenuated the decrease in IGFBP1 (p<0.001). A stronger rise in GH and IGF-I from admission to d4/LD was independently associated with a lower risk of acquiring muscle weakness (OR (95%CI) per ng/ml change 0.88 (0.81-0.96) for GH, p=0.001; 0.98 (0.97-0.99) for IGF-I, p=0.002). Tolerating the early macronutrient deficit suppresses basal but not pulsatile GH secretion and alters IGF-I bioavailability during critical illness. These effects may counteract the protection of the intervention against the development of muscle weakness. 1. Casaer et al. N Engl J Med 2011;365:506-17 2. Hermans et al. Lancet Respir Med 2013;1:621-9 3. Van Dyck et al. ENDO 2018;SUN601status: publishe

ESPEN guideline on clinical nutrition in the intensive care unit

Following the new ESPEN Standard Operating Procedures, the previous guidelines to provide best medical nutritional therapy to critically ill patients have been updated. These guidelines define who are the patients at risk, how to assess nutritional status of an ICU patient, how to define the amount of energy to provide, the route to choose and how to adapt according to various clinical conditions. When to start and how to progress in the administration of adequate provision of nutrients is also described. The best determination of amount and nature of carbohydrates, fat and protein are suggested. Special attention is given to glutamine and omega-3 fatty acids. Particular conditions frequently observed in intensive care such as patients with dysphagia, frail patients, multiple trauma patients, abdominal surgery, sepsis, and obesity are discussed to guide the practitioner toward the best evidence based therapy. Monitoring of this nutritional therapy is discussed in a separate document.status: Published onlin