Pierre Singer

ESPEN Guidelines on Parenteral Nutrition: Intensive care

Nutritional support in the intensive care setting represents a challenge but it is fortunate that its delivery and monitoring can be followed closely. Enteral feeding guidelines have shown the evidence in favor of early delivery and the efficacy of use of the gastrointestinal tract. Parenteral nutrition (PN) represents an alternative or additional approach when other routes are not succeeding (not necessarily having failed completely) or when it is not possible or would be unsafe to use other routes. The main goal of PN is to deliver a nutrient mixture closely related to requirements safely and to avoid complications. This nutritional approach has been a subject of debate over the past decades. PN carries the considerable risk of overfeeding which can be as deleterious as underfeeding. Therefore the authors will present not only the evidence available regarding the indications for PN, its implementation, the energy required, its possible complementary use with enteral nutrition, but also the relative importance of the macro- and micronutrients in the formula proposed for the critically ill patient. Data on long-term survival (expressed as 6 month survival) will also be considered a relevant outcome measure. Since there is a wide range of interpretations regarding the content of PN and great diversity in its practice, our guidance will necessarily reflect these different views. The papers available are very heterogeneous in quality and methodology (amount of calories, nutrients, proportion of nutrients, patients, etc.) and the different meta-analyses have not always taken this into account. Use of exclusive PN or complementary PN can lead to confusion, calorie targets are rarely achieved, and different nutrients continue to be used in different proportions. The present guidelines are the result of the analysis of the available literature, and acknowledging these limitations, our recommendations are intentionally largely expressed as expert opinions.

Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury.

Objective:To explore the effects of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants on the respiratory profile and outcome of patients with acute lung injury. Design:Single-center, prospective, randomized, controlled, unblinded study. Setting:General intensive care department of a tertiary-care, university-affiliated hospital. Patients:A total of 100 patients with acute lung injury, diagnosed according to the American-European Consensus Conference on ARDS. Interventions:Patients were randomized to receive the standard isonitrogenous, isocaloric enteral diet or the standard diet supplemented with EPA and GLA for 14 days. Measurements and Main Results:Patient demographics, Acute Physiology and Chronic Health Evaluation II score, and type of admission were noted at admission. Compared with baseline oxygenation (EPA + GLA group vs. control group), by days 4 and 7, patients receiving the EPA + GLA diet showed significant improvement in oxygenation (Pao2/Fio2, 317.3 ± 99.5 vs. 214.3 ± 56.4 and 296.5 ± 165.3 vs. 236.3 ± 79.8, respectively; p < .05). Compliance was significantly higher in the EPA + GLA group observed at day 7 (55.1 ± 46.5 vs. 35.2 ± 20.0 mL/mbar, p < .05). No significant difference was found in nutritional variables. Resting energy expenditure was significantly higher in patients in the EPA + GLA group, but their body mass index was also higher (p < .05). A significant difference was found in length of ventilation (p < .04) in favor of the EPA + GLA group. There was no between-group difference in survival. Conclusions:In patients with acute lung injury, a diet enriched with EPA + GLA may be beneficial for gas exchange, respiratory dynamics, and requirements for mechanical ventilation.

Decreased food intake is a risk factor for mortality in hospitalised patients: The NutritionDay survey 2006

BACKGROUND & AIMS Malnutrition is a known risk factor for the development of complications in hospitalised patients. We determined whether eating only fractions of the meals served is an independent risk factor for mortality. METHODS The NutritionDay is a multinational one-day cross-sectional survey of nutritional factors and food intake in 16,290 adult hospitalised patients on January 19th 2006. The effect of food intake and nutritional factors on death in hospital within 30 days was assessed in a competing risk analysis. RESULTS More than half of the patients did not eat their full meal provided by the hospital. Decreased food intake on NutritionDay or during the previous week was associated with an increased risk of dying, even after adjustment for various patient and disease related factors. Adjusted hazard ratio for dying when eating about a quarter of the meal on NutritionDay was 2.10 (1.53-2.89); when eating nothing 3.02 (2.11-4.32). More than half of the patients who ate less than a quarter of their meal did not receive artificial nutrition support. Only 25% patients eating nothing at lunch receive artificial nutrition support. CONCLUSION Many hospitalised patients in European hospitals eat less food than provided as regular meal. This decreased food intake represents an independent risk factor for hospital mortality.

Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective

IntroductionFish oil-based nutrition is protective in severe critical care conditions. Regulation of the activity of transcription factor NF-κB is an important therapeutic effect of the major omega-3 fatty acids in fish oil, eicosapentaenoic and docosahexaenoic acid (EPA and DHA).Methods and resultsUsing the articles obtained by a Pubmed research, this article reviews three aspects of NF-κB/inflammatory inhibition by fish oil. (1) Inhibition of the NF-κB pathway at several subsequent steps: extracellular, free omega-3 inhibits the activation of the Toll-like receptor 4 by endotoxin and free saturated fatty acids. In addition, EPA/DHA blocks the signaling cascade between Toll-like/cytokine receptors and the activator of NF-κB, IKK. Oxidized omega-3 also interferes with the initiation of transcription by NF-κB. (2) The altered profile of lipid mediators generated during inflammation, with production of the newly identified, DHA-derived inflammation-resolving mediator classes (in addition to the formation of less pro-inflammatory eicosanoids from EPA). Resolvin D1 and Protectin D1 are potent, endogenous, DHA-derived lipid mediators that attenuate neutrophil migration and tissue injury in peritonitis and ischemia-reperfusion injury. Their production is increased in the later stages of an inflammatory response, at which time they enhance the removal of neutrophils. (3) Modulation of vagal tone with potential anti-inflammatory effects: vagal fibers innervating the viscera down-regulate inflammation by activating nicotinic receptors upon infiltrating and resident macrophages. Stimulation of the efferent vagus is therapeutic in experimental septic shock. Fish oil supplementation increases vagal tone following myocardial infarction and in experimental human endotoxinemia.ConclusionIt remains to be shown whether these pleiotropic actions of EPA/DHA contribute to fish oil’s therapeutic effect in sepsis.

The Use of an Inflammation-Modulating Diet in Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome: A Meta-Analysis of Outcome Data

BACKGROUND This meta-analysis of clinical trials compares an inflammation-modulating diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and elevated antioxidants (EPA + GLA) vs a control diet to determine the effectiveness of this specialized diet on oxygenation and clinical outcomes in mechanically ventilated patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). METHODS MEDLINE, EMBASE, Cochrane Clinical Trials Register, and the U.S. National Institute of Health Clinical Trials databases were searched. The outcome measures assessed were 28-day in-hospital mortality, 28-day ventilator-free and intensive care unit (ICU)-free days, and the development of new organ failures. An evaluation of oxygenation and ventilatory variables was also performed. Outcomes were analyzed using both fixed-effects and random-effects models. RESULTS Three randomized controlled studies (n = 411 patients) were included in this meta-analysis. Among the most important findings of this evaluation is a significant reduction in the risk of mortality (odds ratio [OR] = 0.40; 95% confidence interval [CI] = 0.24-0.68; P = .001), with significant reductions in the risk of developing new organ failures (OR = 0.17; 95% CI = 0.08-0.34; P < .0001), time on mechanical ventilation (standardized mean difference [SMD] = 0.56; 95% CI = 0.32-0.79; P < .0001), and ICU stay (SMD = 0.51; 95% CI = 0.27-0.74; P < .0001) in patients who received EPA + GLA. CONCLUSIONS The meta-analysis showed a significant reduction in the risk of mortality as well as relevant improvements in oxygenation and clinical outcomes of ventilated patients with ALI/ARDS given EPA + GLA.

Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions

BackgroundEnergy deficit is a common and serious problem in intensive care units and is associated with increased rates of complications, length of stay, and mortality. Parenteral nutrition (PN), either alone or in combination with enteral nutrition, can improve nutrient delivery to critically ill patients. Lipids provide a key source of calories within PN formulations, preventing or correcting energy deficits and improving outcomes.DiscussionIn this article, we review the role of parenteral lipid emulsions (LEs) in the management of critically ill patients and highlight important biologic activities associated with lipids. Soybean-oil-based LEs with high contents of polyunsaturated fatty acids (PUFA) were the first widely used formulations in the intensive care setting. However, they may be associated with increased rates of infection and lipid peroxidation, which can exacerbate oxidative stress. More recently developed parenteral LEs employ partial substitution of soybean oil with oils providing medium-chain triglycerides, ω-9 monounsaturated fatty acids or ω-3 PUFA. Many of these LEs have demonstrated reduced effects on oxidative stress, immune responses, and inflammation. However, the effects of these LEs on clinical outcomes have not been extensively evaluated.ConclusionsOngoing research using adequately designed and well-controlled studies that characterize the biologic properties of LEs should assist clinicians in selecting LEs within the critical care setting. Prescription of PN containing LEs should be based on available clinical data, while considering the individual patient’s physiologic profile and therapeutic requirements.

Effectiveness and safety of colistin: prospective comparative cohort study

BACKGROUND Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics. METHODS This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported. RESULTS Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08-2.31). In the adjusted analysis the OR was 1.44 (0.91-2.26) overall and 1.99 (1.06-3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01-1.60) overall and 1.65 (1.18-2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54-7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up. CONCLUSIONS The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than beta-lactam antibiotics.

Metabolic and nutritional support of critically ill patients: consensus and controversies

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients.

ESPEN guideline: Clinical nutrition in surgery

Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include: • integration of nutrition into the overall management of the patient • avoidance of long periods of preoperative fasting • re-establishment of oral feeding as early as possible after surgery • start of nutritional therapy early, as soon as a nutritional risk becomes apparent • metabolic control e.g. of blood glucose • reduction of factors which exacerbate stress-related catabolism or impair gastrointestinal function • minimized time on paralytic agents for ventilator management in the postoperative period • early mobilisation to facilitate protein synthesis and muscle function The guideline presents 37 recommendations for clinical practice.

Polyphenols in the treatment of inflammatory bowel disease and acute pancreatitis

Polyphenols are phytochemicals that are abundant in food and beverages derived from plants. Although no deficiency state has been described for them, increased intake of polyphenols appears to protect against disease in virtue of their anti-inflammatory and vasculoprotective properties. This article focuses on four polyphenols with established anti-inflammatory properties: resveratrol, epigallocatechin gallate, curcumin and quercetin. In rodents, ingestion or systemic administration of these agents inhibits nuclear factor κ B-dependent gene expression and induces phase II antioxidant and detoxifying proteins. Conditions prevented and/or ameliorated by these polyphenols include inflammatory colitis and acute pancreatitis. Polyphenols also attenuate ischaemia-reperfusion injury and endotoxemic sepsis, which has a role in the development of multiple organ dysfunction in severe acute pancreatitis. Enteral nutrition has an important role in the management of inflammatory bowel disease (IBD)—mainly of Crohn’s disease, and of acute pancreatitis. Parenteral nutrition is reserved for refractory cases and disease-associated complications. Artificial nutrition attempts to safely administer the essential and otherwise beneficial constituents of food to patients with an impaired ability to ingest or digest food; yet, polyphenols are not included in the formulas. We suggest that the addition of polyphenols to artificial nutritional formulas would improve the outcome of patients with IBD and acute pancreatitis in need of enteral or parenteral nutrition. Plants, like other unicellular and multicellular organisms, contain ubiquitous organic molecules (eg, amino acids, carbohydrates and fatty acids) termed primary metabolites that are essential to cell structure and basic metabolism. These compounds also serve as substrates for the synthesis of an array of chemicals called secondary plant metabolites, which are accumulated at lower concentrations and are more variably distributed among different species. Once thought to be waste products, these agents are now considered to have a role in ecological interactions with friendly and hostile microorganisms and macroorganisms, and protection from environmental stressors. …