Body composition and muscle strength at the end of ICU stay are associated with 1-year mortality, a prospective multicenter observational study.

BACKGROUND & AIMS: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay. METHODS: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality. RESULTS: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%. CONCLUSION: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied.

A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial.

BACKGROUND: Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). METHODS: In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery. RESULTS: In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed. CONCLUSIONS: Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated-potentially focusing on the more poorly EN-fed surgical ICU setting. TRIAL REGISTRATION: NCT01206166.

"Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents.

BACKGROUND: Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats. DESIGN: Rats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed. RESULTS: Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats. CONCLUSIONS: Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L-arginine supplementation.

Lipid emulsions for parenteral nutrition in critical illness.

Critical illness is a life-threatening multisystem process that can result in significant morbidity and mortality. In most patients, critical illness is preceded by a physiological deterioration, characterized by a catabolic state and intense metabolic changes, resulting in malnutrition and impaired immune functions. In this context, parenteral lipid emulsions may modulate inflammatory and immune reactions, depending on their fatty acid composition. These effects appear to be based on complex modifications in the composition and structure of cell membranes, through eicosanoid and cytokine synthesis and by modulation of gene expression. The pathophysiological mechanisms underlying these fatty acid-induced immune function alterations in critical ill patients are however complex and partially understood. Indeed, despite a very abundant literature, experimental and clinical data remain contradictory. The optimization of lipid emulsion composition thus represents a major challenge for clinical medicine, to adequately modulate the inflammatory pathways. In the present review, we first address the metabolic response to aggression, the effects of parenteral lipid emulsions on inflammation and immunity, and finally the controversial place of these lipid emulsions during critical illness. The analysis furthermore highlights the pathophysiological mechanisms underlying the differential effects of lipid emulsions and their potential for improving the handling of critically ill patients.

Medium-chain triglyceride supplementation exacerbates peritonitis-induced septic shock in rats: role on cell membrane remodeling.

BACKGROUND AND AIMS: Lipid emulsions for parenteral nutrition interfere with immunity and may alter the cell plasma membrane and microparticle release, thus modulating their biological effects. Our aim was to evaluate the effect of two lipid emulsions for parenteral nutrition containing either a mixture of long- and medium-chain triglycerides (LCTs and MCTs) or LCTs only, to assess their role on microparticle release and acute inflammation during septic shock in rats. METHODS AND RESULTS: Septic rats (cecal ligation and puncture) and sham rats were infused with 5% dextrose or a lipid emulsion during 22 h. After 18 h, rats were resuscitated during 4 h and hemodynamic parameters monitored. Circulating microparticles and their phenotype were measured by prothrombinase assay; heart and aorta were collected for Western blotting and electron paramagnetic resonance measurements. No significant effect of lipid emulsions was observed in sham rats. In septic rats, norepinephrine requirements were increased in MCT/LCT-infused rats compared with 5% dextrose- or LCT-infused rats (2.7 ± 0.2 vs. 1.9 ± 0.8 and 1.2 ± 0.3 µg/kg per minute, respectively; P < 0.05) with increased procoagulant microparticle generation (38.6 ± 5.8 vs. 18.8 ± 3.1 and 19.2 ± 3.0 nM equivalent phosphatidylserine [Eq PhtdSer]; P < 0.05), leukocyte- (17.4 ± 3.5 vs. 7.7 ± 1.8 and 6.0 ± 1.1 nM Eq PhtdSer; P < 0.05), platelet- (13.9 ± 2.5 vs. 4.4 ± 0.7 and 5.4 ± 1.3 nM Eq PhtdSer; P < 0.05), and endothelial-derived microparticles (16.9 ± 3.6 vs. 6.4 ± 1.4 and 5.6 ± 0.8 nM Eq PhtdSer; P < 0.05). The mixture of MCTs/LCTs significantly increased cardiac and vascular nitric oxide and superoxide anion production, phosphorylated IκB, and cyclooxygenase 2 expression compared with the lipid emulsion containing only LCTs. CONCLUSIONS: Compared with 5% dextrose, MCT/LCT supplementation during septic shock in rats induced deleterious effects with increased inflammation and cell activation, associated to vascular hyporeactivity. During septic shock, LCT supplementation seemed to be neutral compared with 5% dextrose infusion.

Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability.

The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)-induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell-growth medium was supplemented with three different industrial lipid emulsions: Intralipid(®), containing long-chain triglycerides (LCT--soybean oil); Medialipid(®), containing LCT (soybean oil) and medium-chain triglycerides (MCT--coconut oil); and SMOFlipid(®), containing LCT, MCT, omega-9 and -3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid(®) compared to Intralipid(®), SMOFlipid(®) and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid-treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n-3 and n-9 fatty acids have no effect on endotoxin-induced cell death and inflammation.

Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study.

INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ± 886 ml in the HES group and 1,709 ± 1,164 ml in the NaCl group (mean difference = -331 ± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ± 11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups. CLINICALTRIALSGOV: NCT00464204.

Arginine reduces bacterial invasion in rats with head injury: an in vivo evaluation by bioluminescence.

OBJECTIVES: The benefit of arginine in intensive care unit patients with severe sepsis is still controversial. An excessive supply of arginine could lead to an overproduction of nitric oxide and could be responsible for septic shock and multiorgan failure. However, this claim is not supported by any experimental or clinical data. We set out to determine whether an enteral supply of arginine would modulate bacterial invasion in rats with head injury. METHODS: Male Sprague-Dawley rats with head injury were randomized into two groups. Group 1 included rats with head injury fed a standard enteral nutrition (Sondalis HP, n = 10) and group 2 included rats with head injury fed the standard enteral nutrition plus arginine (4 g/kg/d, n = 11). Two days after head injury, the rats received a single enteral bolus of luminescent Escherichia coli Xen 14. Bacterial proliferation was evaluated in vivo at time + 2 hrs and time + 6 hrs after E. coli challenge. Four days after head injury, blood was sampled for arginine and fibrinogen assay. Muscles, intestine, spleen, and thymus were removed and weighed. RESULTS: There was no mortality in either group. The luminescence signal was similar in the two groups at time +2 hrs (group 1: 414 [5-823] vs. group 2: 496 [0.1-993] (median value[min-max]; not significant) and was significantly lower at time +6 hrs in group 2 (group 1: 71 [0-142] vs. group 2: 8.5 [0-17]; p = .026). Arginine treatment did not improve any nutritional parameters. CONCLUSIONS: Arginine was not responsible for mortality in rats with head injury with infectious complications and reduced the intensity of bacterial invasion.

L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study.

OBJECTIVE: Glutamine (Gln)-supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated. DESIGN: Prospective, double-blind, controlled, randomized trial. SETTING: ICUs in 16 hospitals in France. PATIENTS: One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11). INTERVENTIONS: Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids.kg-1.day-1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g.kg-1.day-1; Ala-Gln group, n=58) or L-alanine+L-proline (control group, n=56) over at least 5 days. MEASUREMENTS AND MAIN RESULTS: Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p<.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p<.05) and incidence of pneumonia (10 vs. 19; p<.05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p<.05) and there were fewer insulin-requiring patients (14 vs. 22; p<.05) in the Ala-Gln group. CONCLUSIONS: TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.

Lipids in the nutritional support of the critically ill patients.

PURPOSE OF REVIEW: This review reports recent findings on lipid use in artificial nutrition in patients with acute respiratory failure or severe sepsis or undergoing major surgery. It examines current knowledge of fatty acid safety, biologic effects, and the impact on patients' morbidity and mortality. The newly emerging area of genotypic influence and timing of immunonutrition is also discussed. RECENT FINDINGS: In acute respiratory distress syndrome, the debate concerning the use of long-chain fatty acids as opposed to physical mixtures of medium- and long-chain fatty acids, specifically regarding their effects on gas exchange and pulmonary hemodynamics, still remains unresolved. By contrast, providing fish oil fatty acids (mainly eicosapentaenoic and docosahexaenoic acids) and/or gamma-linolenic acid, seems to decrease harmful excessive inflammatory/immune activation and to improve clinical outcome. Similar effects, although not conclusively demonstrated, have been reported for n-3 fatty acid-enriched lipid emulsions in patients with sepsis. Few recent studies examined the impact of n-3 fatty acid-enriched enteral formulas on patients undergoing major surgery. Most studies focused on intravenous fish oil and suggest beneficial effects both on inflammatory/immune parameters and patient outcome. Studies suggest that lipid use in critically ill patients may be improved by increased knowledge of genetic determinants of severity of injury and response to therapeutic agents as well as by the development of tools that allow better timing of immunonutritional intervention. SUMMARY: Overall, lipids, in particular n-3 fatty acids, emerge as powerful nutrients with pharmacologic properties potentially improving prognosis in critically ill patients. However, heterogeneity in study design makes the interpretation of available studies difficult. Consequently, larger prospective, randomized, double-blind trials with comparable methodologies are necessary for detailed evaluation of the pharmacologic impact of lipids. In addition, a better knowledge of the influence of genotypic variation and postinjury inflammatory/immune temporal patterns may improve our current therapeutic use of various fatty acids.

[Treatment of malnutrition: parenteral nutrition]. / Traitement de la dénutrition: nutrition parentérale.

Malnutrition affects a high number of hospitalized patients and worsen their outcome. Nutritional support is then essential and the appropriate way is in the most cases represented by dietary supplementation or enteral feeding. Parenteral nutrition may be required in some cases of particularly severe malnutrition. Its efficiency is widely proved and parenteral nutrition provides an adequate nutritional support when oral or enteral nutrition is impossible or insufficient. The energy supply by a mixture of nutrients in multicompartiment bags is now routinely accepted and all-in-one mixtures facilitate home parenteral nutrition. The strict respect for indications and for procedures during use should reduce the parenteral nutrition-induced complications. The benefits of this therapy are obtained with a carefully trained team but the most undernourished patients should not be deprived of its advantages.

The prognostic value of nutritional and inflammatory indices in critically ill patients with acute respiratory failure.

In critically ill patients suffering from acute respiratory failure, weaning from ventilatory assistance is a key survival factor in intensive care units (ICU). The aim of this study was to provide deeper insight into laboratory methods allowing improved monitoring of that critical period. Eighty-three ICU patients (mean age 63.9 years), classified according to the Second Acute Physiology and Chronic Health Evaluation criteria, were submitted to mechanical ventilation, antibiotherapy and nutritional support. Weaning attempts required degressive pressure support ventilation. The biological status of the patients was assessed by the serial measurement of inflammatory (C-reactive protein and alpha1-acid glycoprotein) and of nutritional (albumin and transthyretin) indicators whose aggregation yields a prognostic inflammatory and nutritional index (PINI). Statistical analyses compared ventilatory and biological data recorded on admission and at the time of extubation. Results showed that vital capacity and plasma concentrations of albumin and transthyretin rose, whereas rapid shallow breathing index, C-reactive protein and PINI values declined during the tested period. Persistent low transthyretin concentrations were predictive of lethality while increased values were associated with improved ventilatory performances. The PINI scoring formula worked as an independent predictor of the weaning trial outcome. The study underlined the value of the PINI system for the successful management of the weaning procedure.