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Objectives: The evidence suggests that L-carnitine may reduce mortality in critically ill patients with sepsis. However, the conclusions of different studies are inconsistent. A meta-analysis was conducted to evaluate the effect of L-carnitine compliance on mortality in patients with sepsis., Methods: A search of the PubMed, Embase, and Cochrane Library databases was conducted on 1 June 2024. The risk ratio (RR) was pooled with a 95% confidence interval (CI) for dichotomous data. The publications were subjected to a review in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This study has been registered with INPLASY (number INPLASY202460086)., Results: A total of 356 patients were included in four randomized controlled trials. The results indicated that L-carnitine supplementation was not associated with 28-day mortality in sepsis patients (RR: 0.65; 95% CI 0.33-1.28; I 2  = 70%; P = 0.21). And there was no significant effect on 12-month mortality (RR: 0.72; 95% CI 0.47-1.11; I 2  = 0%; P = 0.14) compared to placebo., Conclusions: The use of L-carnitine was not found to be significantly correlated with 28-day or 12-month mortality in patients with sepsis., (© 2024. The Author(s).)

Patients with sepsis experience metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutrition. A ketogenic diet (KD) may offer an immunologically advantageous alternative, although clinical evidence is limited. We conducted a single-center, open-label, randomized controlled trial to assess whether a KD could induce stable ketosis in critically ill patients with sepsis. Secondary outcomes included assessment of feasibility and safety of KD, as well as explorative analysis of clinical and immunological characteristics. Forty critically ill adults were randomized to either a ketogenic or standard high-carbohydrate diet. Stable ketosis was achieved in all KD patients, with significant increases in β-hydroxybutyrate levels compared with controls [mean difference 1.4 milimoles per liter; 95% confidence interval (CI): 1.0 to 1.8; P < 0.001). No major adverse events or harmful metabolic side effects (acidosis, dysglycemia, or dyslipidemia) were observed. After day 4, none of the patients in the KD group required insulin treatment, whereas in the control group, insulin dependency ranged between 35% and 60% ( P = 0.009). There were no differences in 30-day survival, but ventilation-free [incidence rate ratio (IRR) 1.7; 95% CI: 1.5 to 2.1; P < 0.001], vasopressor-free (IRR 1.7; 95% CI: 1.5 to 2.0; P < 0.001), dialysis-free (IRR 1.5; 95% CI: 1.3 to 1.8; P < 0.001), and intensive care unit-free days (IRR 1.7; 95% CI: 1.4 to 2.1; P < 0.001) were higher in the ketogenic group. Next-generation sequencing of CD4 + /CD8 + T cells and protein analyses showed reduced immune dysregulation, with decreased gene expression of T-cell activation and signaling markers and lower pro-inflammatory cytokine secretion. This trial demonstrated the safe induction of a stable ketogenic state in sepsis, warranting larger trials to investigate potential benefits in sepsis-related organ dysfunction.

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22 nd , 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention., Competing Interests: Declaration of competing interest Ping-Tao Tseng, Bing-Yan Zeng, Pin-Yang Yeh, Bing-Syuan Zeng, Brendon Stubbs, John S. Kuo, Cheuk-Kwan Sun, Yu-Shian Cheng, Yen-Wen Chen, Tien-Yu Chen, Yi-Cheng Wu, Yu-Kang Tu, Pao-Yen Lin, Dian-Jeng Li, Chih-Sung Liang, Mein-Woei Suen, Yi-Che Lee, Wei-Chieh Yang, Chih-Wei Hsu, Yow-Ling Shiue, and Kuan-Pin Su declared that there were no any competing interests existed., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150-160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.

Background: Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and meta-analysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients., Methods: A systematic search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to the random effects model., Results: Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, L-carnitine supplementation may not have clinically a significant effect on mortality rate., Conclusion: L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using a dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The study investigated the effect of soluble dietary fiber supplementation on gut microbiota, mucosal barrier function, inflammatory markers, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). The expression of muc2 was down-regulated in septic mice. However, muc2 expression was significantly increased in the septic mice that received soluble dietary fiber. Survival was also improved in the septic mice treated with dietary fiber. The survival benefit was associated with decreased serum concentrations of pro-inflammatory cytokines and reduced neutrophil infiltration in the gut. Furthermore, the mucus thickness, inflammatory response, and degree of gut injury were remarkably alleviated in septic mice treated with soluble dietary fiber, while it was aggravated in septic mice treated with antibiotics in addition to the soluble fiber. Bacterial 16S ribosomal RNA gene sequencing also showed that fiber supplementation caused an increase in the relative abundance of probiotics, commonly associated with metabolic health. Administration of antibiotics to mice fed fiber diet negated the enrichment of probiotics as well as the survival benefit, following cecal ligation and puncture. Dietary supplementation with cellulose offers a microbe-mediated survival advantage in a murine model of sepsis. Improved understanding of the connection between diet, microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Much of the world's prominent and burdensome chronic diseases, such as diabetes, Alzheimer's, and heart disease, are caused by impaired metabolism. By acting as both an efficient fuel and a powerful signalling molecule, the natural ketone body, d-β-hydroxybutyrate (βHB), may help circumvent the metabolic malfunctions that aggravate some diseases. Historically, dietary interventions that elevate βHB production by the liver, such as high-fat diets and partial starvation, have been used to treat chronic disease with varying degrees of success, owing to the potential downsides of such diets. The recent development of an ingestible βHB monoester provides a new tool to quickly and accurately raise blood ketone concentration, opening a myriad of potential health applications. The βHB monoester is a salt-free βHB precursor that yields only the biologically active d-isoform of the metabolite, the pharmacokinetics of which have been studied, as has safety for human consumption in athletes and healthy volunteers. This review describes fundamental concepts of endogenous and exogenous ketone body metabolism, the differences between the βHB monoester and other exogenous ketones and summarises the disease-specific biochemical and physiological rationales behind its clinical use in diabetes, neurodegenerative diseases, heart failure, sepsis related muscle atrophy, migraine, and epilepsy. We also address the limitations of using the βHB monoester as an adjunctive nutritional therapy and areas of uncertainty that could guide future research., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Early enteral feeding is a potentially modifiable risk factor for necrotising enterocolitis (NEC) and late onset sepsis (LOS), however enteral feeding practices for preterm infants are highly variable. High-quality evidence is increasingly available to guide early feeding in preterm infants. Meta-analyses of randomised trials indicate that early trophic feeding within 48 h after birth and introduction of progressive enteral feeding before 4 days of life at an advancement rate above 24 ml/kg/day can be achieved in clinically stable very preterm and very low birthweight (VLBW) infants, without higher mortality or incidence of NEC. This finding may not be generalisable to high risk infants such as those born small for gestational age (SGA) or following absent/reversed end diastolic flow velocity (AREDFV) detected antenatally on placental Doppler studies, due to the small number of such infants in existing trials. Trials targeting such high-risk preterm infants have demonstrated that progressive enteral feeding started in the first 4 days is safe and does not lead to higher NEC or mortality; however, there is a paucity of data to guide feeding advancement in such infants. There is little trial evidence to support bolus or continuous gavage feeding as being superior in clinically stable preterm infants. Trials that examine enteral feeding are commonly unblinded for technical and practical reasons, which increases the risk of bias in such trials, specifically when considering potentially subjective outcome such as NEC and LOS; future clinical trials should focus on objective, primary outcome measures such as all-cause mortality, long term growth and neurodevelopment. Alternatively, important short-term outcomes such as NEC could be used with blinded assessment., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Septic shock is one of the main causes of mortality in intensive care units worldwide. Nutritional support can affect the survival of patients with sepsis., Objective: To evaluate whether resting energy expenditure, respiratory quotient, and oxygen consumption and carbon dioxide production (measured by indirect calorimetry) differ between critically ill patients with vs without sepsis., Methods: A total of 205 patients receiving mechanical ventilation were evaluated consecutively within the first 48 hours of admission. Demographic and clinical data were collected, including age, body mass index, oxygen consumption, carbon dioxide production, respiratory quotient, and resting energy expenditure, with the clinical data measured or estimated via indirect calorimetry., Results: Of the 205 patients, 114 (56%) had no sepsis and 91 (44%) had sepsis. The median values of the studied variables in the no sepsis and sepsis groups, respectively, were as follows: age, 53 vs 58 years ( P = .07); body mass index, 25 vs 26 ( P = .14); Acute Physiology and Chronic Health Evaluation II score, 24 vs 25 ( P = .04); death risk, 47% vs 63% ( P = .04); oxygen consumption, 211 vs 202 mL/min ( P = .72); and resting energy expenditure, 1434 vs 1430 kcal/d ( P = .73). Analysis of receiver operating characteristic curves showed no significant differences between patients with and without sepsis for any of the indirect calorimetry variables., Conclusion: In clinical practice, patients with sepsis do not seem to require an increased energy supply. Additional studies are needed to confirm this conclusion.

Purpose: The purpose of this study was to determine the opinions and reported nutrition practices of Canadian Registered Dietitians (RDs) with regard to feeding patients with severe sepsis., Methods: In 2017, surveys were sent to 112 eligible Canadian RDs in 10 provinces who were practicing in an intensive care environment. The survey included embedded branching logic questions developed to address major facets of sepsis, critical illness, and nutrition. The survey instrument assimilated all data in an anonymous manner, so respondents could not be linked to their answers., Results: Of the 64 RDs who responded (57% response rate), the majority practiced in adult intensive care (81%), within an academic center (59%), and in a mixed unit (73%). A wide variability of Canadian RDs' opinions and practice was reported in determining energy requirements, enteral nutrition (EN) practice, EN with vasoactive agents, parenteral nutrition (PN), and supplemental micronutrients., Conclusions: Practice variability of Canadian RDs likely reflects gaps in both evidence and guidelines for severe sepsis. Further research efforts are needed to customize nutritional requirements in the patient with evolving sepsis, EN with patients at high risk for gastrointestinal dysfunction, optimizing PN, and the role of micronutrients.

Sepsis is a deleterious immune response to infection that leads to organ failure and is the 11th most common cause of death worldwide. Despite plaguing humanity for thousands of years, the host factors that regulate this immunological response and subsequent sepsis severity and outcome are not fully understood. Here we describe how the Western diet (WD), a diet high in fat and sucrose and low in fiber, found rampant in industrialized countries, leads to worse disease and poorer outcomes in an LPS-driven sepsis model in WD-fed mice compared with mice fed standard fiber-rich chow (SC). We find that WD-fed mice have higher baseline inflammation (metaflammation) and signs of sepsis-associated immunoparalysis compared with SC-fed mice. WD mice also have an increased frequency of neutrophils, some with an "aged" phenotype, in the blood during sepsis compared with SC mice. Importantly, we found that the WD-dependent increase in sepsis severity and higher mortality is independent of the microbiome, suggesting that the diet may be directly regulating the innate immune system through an unknown mechanism. Strikingly, we could predict LPS-driven sepsis outcome by tracking specific WD-dependent disease factors (e.g., hypothermia and frequency of neutrophils in the blood) during disease progression and recovery. We conclude that the WD is reprogramming the basal immune status and acute response to LPS-driven sepsis and that this correlates with alternative disease paths that lead to more severe disease and poorer outcomes., Competing Interests: The authors declare no conflict of interest.

Intestinal dysbiosis precedes and is a likely causative factor in necrotizing enterocolitis (NEC) and many cases of late-onset sepsis. Randomized controlled trials and observational cohort studies demonstrate decreased risk of NEC, sepsis, and death with the administration of probiotic microbes and decreased risk of NEC and sepsis with feeding of human milk. Animal studies suggest promising mechanisms by which probiotic microbes and human milk oligosaccharides alter the composition of the intestinal microbiota and may prevent disease in premature infants. Inclusion of parents in discussions of the risks and benefits of human milk and probiotics for premature infants is essential., (Copyright © 2019 by the American Academy of Pediatrics.)

Introduction: Intensive care unit-acquired weakness (ICU-AW) is often observed in critically ill patients with prolonged intensive care unit (ICU) stay. We hypothesized that evolving metabolic abnormalities during prolonged ICU stay are reflected by changing nutrient patterns in blood, urine and skeletal muscle, and that these patterns differ in patients with/without ICU-AW and between patients with/without sepsis., Methods: In a prospective single-center observational trial, we aim to recruit 100 critically ill patients (ICU length of stay ≥ 5 days) with severe sepsis/septic shock ("sepsis group", n = 50) or severe head trauma/intracerebral hemorrhage ("CNS group", n = 50). Patients will be sub-grouped for presence or absence of ICU-AW as determined by the Medical Research Council sum score. Blood and urine samples will be collected and subjected to comprehensive nutrient analysis at different time points by targeted quantitative mass spectrometric methods. In addition, changes in muscular tissue (biopsy, when available), muscular architecture (ultrasound), electrophysiology, body composition analyses (bioimpedance, cerebral magnetic resonance imaging), along with clinical status will be assessed. Patients will be followed-up for 180 and 360 days including assessment of quality of life., Discussion: Key objective of this trial is to assess changes in nutrient pattern in blood and urine over time in critically ill patients with/without ICU-AW by using quantitative nutrient analysis techniques. Peer-reviewed published NAChO data will allow for a better understanding of metabolic changes in critically ill patients on standard liquid enteral nutrition and will likely open up new avenues for future therapeutic and nutritional interventions.

Purpose: To determine whether the association of early enteral nutrition (EEN) with mortality from sepsis differs between patients with and without sarcopenia., Materials and Methods: We retrospectively reviewed septic patients treated at our centre between January 2010 and August 2017. The skeletal muscle area (SMA) at the level of the third lumbar vertebra was measured with CT on admission, and sarcopenia was defined as SMA < 80% of the predicted value. Patients were divided into two subgroups (sarcopenic and non-sarcopenic patients), and in-hospital mortality was compared in patients treated with and without EEN within each subgroup. We used logistic regression to examine factors associated with in-hospital mortality in each subgroup., Results: EEN was administered to 35/91 sarcopenic patients and 43/100 non-sarcopenic patients. In-hospital mortality did not differ between non-sarcopenic patients with EEN and those without EEN (16% vs 16%, P = 0.947), but was significantly lower in sarcopenic patients with EEN than in those without EEN (9% vs 34%, P = 0.005). Logistic regression showed that EEN was independently associated with reduced in-hospital mortality in sarcopenic patients (OR 0.18, 95% CI 0.05-0.71, P = 0.014), but not in non-sarcopenic patients., Conclusions: EEN may be more beneficial in sarcopenic patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Nutritional management is crucial during the acute phase of severe illnesses. However, the appropriate nutritional requirements for patients with sepsis are poorly understood. We investigated alterations in carbohydrate, fat, and protein metabolism in mice with different degrees of sepsis., Materials and Methods: C57BL/6 mice were divided into three groups: control mice group, administered with saline, and low- and high-dose lipopolysaccharide (LPS) groups, intraperitoneally administered with 1 and 5 mg of LPS/kg, respectively. Rectal temperature, food intake, body weight, and spontaneous motor activity were measured. Indirect calorimetry was performed using a respiratory gas analysis for 120 h, after which carbohydrate oxidation and fatty acid oxidation were calculated. Urinary nitrogen excretion was measured to evaluate protein metabolism. The substrate utilization ratio was recalculated. Plasma and liver carbohydrate and lipid levels were evaluated at 24, 72, and 120 h after LPS administration., Results: Biological reactions decreased significantly in the low- and high-LPS groups. Fatty acid oxidation and protein oxidation increased significantly 24 h after LPS administration, whereas carbohydrate oxidation decreased significantly. Energy substrate metabolism changed from glucose to predominantly lipid metabolism depending on the degree of sepsis, and protein metabolism was low. Plasma lipid levels decreased, whereas liver lipid levels increased at 24 h, suggesting that lipids were transported to the liver as the energy source., Conclusions: Our findings revealed that energy substrate metabolism changed depending on the degree of sepsis. Therefore, in nutritional management, such metabolic alterations must be considered, and further studies on the optimum nutritional intervention during severe sepsis are necessary., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction Intensivist involvement for patients with sepsis is associated with decreased complications and mortality, and lower hospital resource utilization, but few studies have evaluated outcomes for patients exposed to electronic intensive care unit (eICU) telemedicine sepsis management in the emergency department (ED). In this study, we assess whether eICU cart exposure in the ED improved compliance with components of the 2010 Surviving Sepsis Campaign bundles, length of stay (LOS), disposition and hospital costs. Methods An institutional review board-approved, retrospective cohort study was completed on patients with confirmed sepsis who presented to our ED from July 2010 through February 2013. Results Of 711 patient ED encounters, 314 cases met criteria for analysis (95 exposed and 219 non-exposed). Patient cohorts had similar demographics and comorbid International Classification of Diseases, Ninth Edition (ICD-9) diagnoses. The exposed cohort received antibiotics more quickly (122.3 minutes ±83.3 versus 163.4 minutes ±204.4, p = 0.043) and were more likely to have lactic acid levels drawn within six hours (98.9% vs. 90%, p = 0.019). The exposed cohort had a shortened ED LOS (in days) 0.08 ± 0.28 versus 0.16 ± 0.37, p = 0.036. Hospital LOS, disposition and death were similar in both cohorts. Total hospital costs for the exposed cohort were lower and less variable (US$19,713 ± 16,550 vs. US$24,364 ± 25068), but this was not significant ( p = 0.274). Discussion Our findings suggest that in individuals with confirmed sepsis, ED exposure to a telemedicine-based eICU cart impacted adherence to aspects of the Surviving Sepsis Campaign recommended bundle, but did not impact overall survival and medical costs.

Purpose: A specific therapeutic strategy in sepsis-induced myocardial dysfunction remains to be determined. Nitrite may have cardioprotective effects against sepsis-induced myocardial dysfunction. This study investigated the cardioprotective effects of nitrite on myocardial function, mitochondrial bioenergetics, and its underlying molecular mechanisms in severe septic rats., Methods: Sepsis was induced in male Wistar rats by cecal ligation and puncture (CLP). After CLP, we administered normal saline (NS group) or nitrite (nitrite group) subcutaneously. We administered nitrite at different doses (0.1-10 mg/kg) to ascertain the most effective dose and examined cardiac function in an isolated heart experiment 8 h after CLP. We investigated mitochondrial bioenergetics and molecular mechanisms underlying the administration of nitrite in vitro., Results: In isolated heart experiments, the left ventricular developed pressure (96 ± 5 mmHg) at a moderate nitrite dose (1.0 mg/kg) was significantly higher than that in the NS group (75 ± 4 mmHg, P < 0.05). Mitochondrial oxidative phosphorylation in the nitrite group was significantly higher than that in the NS group (P < 0.01). Immunoblotting revealed that nitrite significantly increased the phosphorylation of Akt (P < 0.05) and reduced the nuclear translocation of NF-κB (P < 0.05) compared with the NS group. Nitrite was also shown to improve the rate of survival in severe septic rats (P < 0.001)., Conclusions: Our results showed that a moderate nitrite dose improved septic myocardial dysfunction at organ, cellular, and molecular levels via modulation of stress signal responses, which resulted in an improvement in survival.

Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48-0.74), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed for culture-positive and culture-negative sepsis and lower respiratory tract infections. These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195.

Objective: The objective was to investigate the benefits of supplementing enteral feeding with omega-3 fatty acids in children with mild to moderate sepsis and its effects on acute-phase reactants and interleukin 6 (IL-6) level., Methods: The study was a prospective randomized, double-blind, placebo-controlled study from January 2012 to June 2014, which included 2 groups of children with mild to moderate sepsis tolerating enteral feeding. Group A included 60 children supplemented with omega-3 fatty acids, whereas group B included 60 children who received enteral feeding without omega-3 supplementation. Both groups had complete blood pictures, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum albumin, and IL-6 before and after 7 days from supplementation., Results: There was a significant improvement in hemoglobin percentage ( P < .0001), total white blood cell (WBC) count ( P < .0001), and platelet count ( P < .0001) and significant decrease in CRP ( P < .0001), ESR ( P < .0001), IL-6 ( P < .0001), and albumin level ( P < .001) in the supplemented group than the nonsupplemented group. The supplemented group also had a significantly shorter duration of stay in pediatric intensive care unit (PICU; P < .01) and decreased death rate than the nonsupplemented group., Conclusion: Children with mild to moderate sepsis showed significant improvement in inflammatory markers and had shorter PICU admission when enteral feeding was supplemented with omega-3 essential fatty acids.

Background: A previous systematic review and meta-analysis reported that omega-3 fatty acids nutrition may reduce mortality in septic patients. As new randomized controlled trials began to accumulate, we conducted an update., Methods: A PubMed database was searched through Feb 2016, and randomized controlled trials comparing omega-3 fatty acids with control were selected by two reviewers independently., Results: Eleven trials randomly assigning 808 patients were included in the present study. Using a fixed effects model, we found no significant effect of omega-3 fatty acids on overall mortality (risk ratio 0.84; 95 % confidence interval (CI): 0.67 to 1.05, P = 0.12), or infectious complications (risk ratio 0.95; 95 % CI: 0.72 to 1.25, P = 0.70). However, the duration of mechanical ventilation was markedly reduced by omega-3 fatty acids (weighted mean differences (WMD) = -3.82; 95 % CI: -4.61 to -3.04; P < 0.00001). A significant heterogeneity was found when the duration of hospital (I (2) = 93 %; WMD = -2.82; 95 % CI: -9.88 to 4.23, P = 0.43), or intensive care stay (I (2) = 87 %; WMD = -2.70; 95 % CI: -6.40 to 1.00, P = 0.15) were investigated., Conclusions: Omega-3 fatty acids confer no mortality benefit but are associated with a reduction in mechanical ventilation duration in septic patients. However, low sample size and heterogeneity of the cohorts included in this analysis limits the generalizability of our findings.

Objectives: Visceral adipose tissue is a major site for expression of proinflammatory and procoagulant genes during acute systemic inflammation. In this study, we tested whether the loss of fat mass by dietary restriction would remove the major source of these factors resulting in improved tolerance to sepsis and endotoxemia., Design: Prospective, laboratory controlled experiments., Setting: Aging and critical care research laboratory in a university hospital., Subjects: Middle-aged (12-month old) male C57BL/6 mice., Interventions: Mice were subjected to 40% dietary restriction for 3 weeks followed by induction of abdominal sepsis or endotoxemia by intraperitoneal injection with cecal slurry or lipopolysaccharide, respectively., Measurements and Main Results: Compared with freely fed mice, dietary restricted mice exhibited dramatically improved survival (80% vs 0% after sepsis; p < 0.001 and 86% vs 12% after endotoxemia; p = 0.013) and significantly reduced visceral fat-derived messenger RNA expression of interleukin-6, thrombospondin-1, plasminogen activator inhibitor-1, and tissue factor, which positively correlated with fat mass. Plasma levels of interleukin-6 were significantly reduced by dietary restriction and correlated with adipose interleukin-6 messenger RNA levels and fat mass (p < 0.001; R = 0.64 and 0.89). In vitro culture of visceral fat explants from naive dietary restricted mice showed significantly reduced interleukin-6 secretion compared with that from freely fed mice in response to lipopolysaccharide. Analysis of major adipose immune cell populations by flow cytometry demonstrated that macrophages were the only cell population reduced by dietary restriction and that CD11c/CD206 (M2-type) and CD11c/CD206 (double negative) macrophages, in addition to T cells, are the major immune cell populations that produce interleukin-6 in middle-aged mice during systemic inflammation., Conclusions: Short-term dietary restriction drastically improved the survival outcome of middle-aged mice during both polymicrobial sepsis and sterile endotoxemia. Improved survival was accompanied by a significantly attenuated inflammatory response in adipose tissue, which is likely due to alterations of both fat mass quantity and qualitative changes, including a reduction in macrophage populations.

Purpose of Review: Few areas in neonatal medicine have generated as much discussion and controversy as the use of prophylactic probiotics for the prevention of necrotizing enterocolitis. We summarize recent studies from the last 1-2 years., Recent Findings: Systematic reviews show that probiotics reduce the risk of necrotizing enterocolitis but there are methodological limitations to all the published trials, and the largest trial to date is at odds with the conclusions of the meta-analyses. Trials have used a range of commercially available products with differing species, and administered these at different times to heterogeneous populations of preterm babies. Although there is strong evidence to show that 'probiotics' are likely to represent a major advance for neonatal care, it is increasingly clear that not all species have beneficial effects in preterm infants. This makes interpretation of meta-analyses complex, and the determination of a single 'risk reduction' potentially flawed., Summary: Despite current uncertainties, it is difficult for clinicians to ignore the current data, and increasing numbers now use commercially available products. It remains a matter of concern that many products lack the robust quality control most clinicians and parents would consider important for use in vulnerable populations. Head-to-head trials are needed.

Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: Sepsis is a severe inflammatory disorder with a high mortality in intensive care units mostly due to multiorgan failure. Mitochondrial dysfunction is regarded as a key factor involved in the pathogenesis of septic disorders, leading to a decline in energy supply. The aim of the present study was to evaluate whether application of short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) could improve mitochondrial function and thus might serve as a potential energy source under inflammatory conditions., Materials and Methods: As an experimental approach, starved human endothelial cells and monocytes were incubated with hexanoic acid, heptanoic acid, octanoic acid, or glucose and subsequently subjected to high-resolution respirometry to assess mitochondrial function under baseline conditions. In a second set of experiments, cells were pretreated with tumor necrosis factor-α to mimic inflammation and sepsis., Results: We demonstrated that addition of SCFAs and MCFAs increases mitochondrial respiratory capacity at baseline and inflammatory conditions in both cell types. None of the fatty acids induced changes in mitochondrial DNA content or the generation of proinflammatory cytokines, indicating a beneficial safety profile., Conclusion: We deduce that SCFAs and MCFAs are suitable and safe sources of energy under inflammatory conditions with the capability to partly restore mitochondrial respiration., (© 2013 American Society for Parenteral and Enteral Nutrition.)

Background & Aims: High supply of protein and energy has been introduced to very-low-birth-weight infants to improve growth and cognitive development. The aim of this study was to compare two different feeding strategies on postnatal growth and clinical outcome during neonatal hospitalization., Methods: Fifty very-low-birth-weight infants were randomized to either an enhanced or a standard feeding protocol within 24 h after birth. Chi-square and T-tests were applied., Results: First week protein, fat and energy supply was significantly higher in the intervention group compared to the control group (all P < 0.001). After inclusion of 50 patients we observed a higher occurrence of septicemia in the intervention group, 63% vs. 29% (P = 0.02), and no more patients were included. The infants in the intervention group demonstrated improved postnatal growth, but they also disclosed significant electrolyte deviations during the first week of life with hypophosphatemia, hypokalemia and hypercalcemia. First week phosphate nadir was lower in the infants experiencing septicemia (1.23 (0.50) mmol/L) as compared to the infants without (1.61 (0.61) mmol/L) (P = 0.03)., Conclusion: Our study implies that enhanced feeding may induce electrolyte imbalances in VLBW infants, and that deleterious side effects similar to those seen in refeeding syndrome may occur. ClinicalTrials.gov, number NCT01103219 and the EudraCT number is 2010-020464-38., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Arginine is an important amino acid during disease and healing because of functions in the immune system and as precursor of nitric oxide (NO). In critically ill adults and children, plasma arginine and citrulline concentrations are substantially decreased, indicating an arginine-deficient state. Arginine availability is reduced because of increased arginine disposal in combination with reduced de novo arginine synthesis. The latter is most likely caused by reduced citrulline availability. As a result, NO synthesis may be impaired, which might compromise microcirculation. These metabolic changes seem to be dependent on the severity of inflammation. Arginine or citrulline supplementation in severe inflammation might therefore be beneficial. Possibly, the use of protein-energy-enriched formulas may be a first step to improve arginine availability and NO synthesis. In critically ill children, arginine metabolism and supplementation is however a virtually unexplored field. Since pediatric sepsis is a significant health problem, which differs in epidemiology and pathophysiology from sepsis in adults, and because of the scarcity of data in this population, studies focused on pathophysiological mechanisms and possible interventions in arginine metabolism in pediatric critical illness are warranted., (Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Background: It is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to assess the efficacy of parenteral selenium supplementation on clinical outcomes., Methods/principal Findings: Randomized trials investigating parenteral selenium supplementation administered in addition to standard of care to critically ill patients were included. CENTRAL, Medline, EMBASE, the Science Citation Index, and CINAHL were searched with complementary manual searches. The primary outcome was all-cause mortality. Trials published in any language were included. Two authors independently extracted data and assessed trial quality. A third author was consulted to resolve disagreements and for quality assurance. Twelve trials were included and meta-analysis was performed on nine trials that recruited critically ill septic patients. These comprised 965 participants in total. Of these, 148 patients (30.7%) in the treatment groups, and 180 patients (37.3%) in control groups died. Parenteral selenium treatment significantly reduced all-cause mortality in critically ill patients with sepsis (relative risk [RR] 0.83, 95% CI 0.70-0.99, p = 0.04, I(2) = 0%). Subgroup analyses demonstrated that the administration schedule employing longer duration (RR 0.77, 95% CI 0.63-0.94, p = 0.01, I(2) = 0%), loading boluses (RR 0.73, 95% CI 0.58-0.94, p = 0.01, I(2) = 0%) or high-dose selenium treatment (RR 0.77, 95% CI 0.61-0.99, p = 0.04, I(2) = 0%) might be associated with a lower mortality risk. There was no evidence of adverse events., Conclusions/significance: Parenteral selenium supplementation reduces risk of mortality among critically ill patients with sepsis. Owing to the varied methodological quality of the studies, future high-quality randomized trials that directly focus on the effect of adequate-duration of parenteral selenium supplementation for severe septic patients are needed to confirm our results. Clinicians should consider these findings when treating this high-risk population., Systematic Review Registration: PROSPERO 2011; CRD42011001768.

Probiotics are live microbial feed supplements that beneficially affect the recipient by improving intestinal balance. In an updated systematic review, nineteen trials randomizing more than 2800 infants were included. In a meta-analysis of trial data, enteral probiotic supplementation significantly reduced the incidence of severe necrotizing enterocolitis (typical RR 0.35, 95% CI 0.24 to 0.52) and mortality (typical RR 0.55, 95% CI 0.40 to 0.74). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.89, 95% CI 0.77 to 1.03). The included trials reported no systemic infection with - supplemented probiotics. Recent data in addition to a report by the European Society for Pediatric Gastroenterology (ESPGAN) concluded probiotics could be generally considered safe.

Females with sepsis have a better prognosis than males, while those of both genders with cirrhosis have a high mortality. Impaired immunity accompanies liver cirrhosis. The potential association between sex and immunologic response of cirrhotic rats in sepsis following immunonutrition was investigated. One hundred and forty-three rats were randomly divided into groups. Liver cirrhosis was produced by weekly feeding of CCl(4) for 8 weeks. Among them, 24 male and 19 female underwent castration one month before studying. The rats were fed with either immune enhancing diet or control diet for five days, then sepsis was induced with cecal ligation and two holes puncture. Main outcomes included mortality and serum cytokines (IL-1β, 6, and 10). Comparisons were made both within and between genders. Cirrhotic non-castrated male rats showed a significant decrease in mortality (64.1% vs. 32.1%, p = 0.032) with better survival than control diet following immune enhancing diet. Lower mortality of cirrhotic non-castrated female rats was found after immune enhancing diet (69.6% vs. 52.1%, p = 0.365). Cirrhotic castrated male rats showed a lower mortality (44.4%) following immune enhancing diet, and cirrhotic castrated female rats also showed significantly lower mortality and better survival than control diet after immune enhancing diet (87.5% vs. 33.3%, p = 0.004). Plasma concentrations of IL-1β were higher in non-oophorectomized female rats fed with control diet compared to immune enhancing diet. Non-orchidectomized males and non-oophorectomized females exhibited similar increases in IL-10 after immune enhancing diet. Our results demonstrated that immunonutrition was more beneficial for male than female cirrhotic rats following sepsis. Though orchidectomy was not found to be more advantageous for the normal male rats in sepsis, immunonutrition seemed to be as important as sex hormone for female rats in sepsis.

Lipid emulsions based on soybean oil have been an integral part of parenteral nutrition supplying n-6 fatty acids, with possible negative effects in critically ill patients. Newer lipid emulsions supply less n-6 fatty acids. In addition, fish oil-based lipids may be included in the lipid component of parenteral nutrition. While clinical benefits of lipid emulsions with a reduced fraction in n-6 lipids and the addition of fish oil have been described in postoperative patients, data are less clear in critically ill or septic patients. Recent data suggest that beneficial effects may be achieved when used early but clearly more data are needed to come to a definitive conclusion. The present commentary will highlight current data in critically ill and septic patients and the use of fish oil as a part of parenteral nutrition.

Soyabean oil-based emulsions high in linoleic acid used in parenteral nutrition (PN) could interfere with immune function and may increase the risk of septic complications. Olive oil-based emulsions, high in oleic acid, could have fewer immune effects. We compared the effects of a soyabean oil-based emulsion v. an olive oil-based emulsion on infection rate, appearance of new infection episodes, leucocyte count (peak and evolution), acute-phase proteins, and major health outcomes in intensive care unit (ICU) adult patients receiving PN. The study was designed as an observational, retrospective, single-centre, cohort study in a general ICU. Patients in the SOYA cohort (n 16) received a soyabean oil-based emulsion and patients in the OLIVE cohort (n 23), an olive oil-based emulsion. Both cohorts had similar basal characteristics and received a similar energy load. The SOYA cohort received an oleic acid:linoleic acid ratio of 0.43 and the OLIVE cohort 2.99 (P < 0.001). No differences were observed in infection rate and appearance, acute-phase proteins, and major health outcomes. At the end of PN, blood leucocyte count decreased by 3.25 x 109 cells/l in the SOYA cohort and increased by 4.51 x 109 cells/l in the OLIVE cohort from baseline values (P = 0.036). Peak leucocyte count presented a trend for a higher value in the OLIVE cohort v. the SOYA cohort (18.86 v. 15.28 x 109 cells/l; P = 0.078). The use of an olive oil-based emulsion in PN had no effect on infection, acute-phase proteins, major health outcomes, and presented higher leucocyte count at the end of PN and a trend to higher peak leucocyte count when compared with soyabean oil-based emulsion in ICU patients.

Background: The purpose of the present study was to determine whether total enteral nutrition (TEN) or total parenteral nutrition (TPN) differ in their modulation of ghrelin production and cardiac dysfunction induced by lipopolysaccharide (LPS)., Materials and Methods: Vascular catheters or gastrostomy tubes were surgically placed into rats who received isocaloric parenteral or enteral nutrition postoperatively. After 7 d, the rats were injected intravenously with LPS (2.5 mg/kg). Serum ghrelin levels were determined by enzyme-linked immunosorbent assay and myocardiac function was assessed via the Langendorff isolated heart technique., Results: Before and after the administration of LPS, TEN was found to be more effective at increasing the plasma ghrelin levels than TPN. After LPS administration, left-ventricular developed pressure decreased in animals receiving TPN when compared with animals receiving TEN. Animals receiving TPN also had significant reductions in their maximal rates of increase (+dp/dt max) and decrease (-dp/dt max) in left ventricular pressure when compared with animals receiving TEN (unpaired t-test, P < 0.05). Upon reperfusion after 30 min of ischemia, the left ventricular resting tension decreased in animals receiving TPN compared with animals receiving TEN. Thereafter, left-ventricular developed pressure, +dp/dt max, and -dp/dt max decreased in the TEN recipients in comparison to the TPN-receiving animals., Conclusions: We conclude that TEN more effectively increases plasma ghrelin levels than TPN. The maintenance of higher ghrelin levels in TEN-fed rats is associated with maintaining cardiac function during LPS-induced septic shock.

Introduction: Early nutrition is recommended for patients with sepsis, but data are conflicting regarding the optimum route of delivery. Enteral nutrition (EN), compared with parenteral nutrition (PN), results in poorer achievement of nutritional goals but may be associated with fewer infections. Mechanisms underlying differential effects of the feeding route on patient outcomes are not understood, but probably involve the immune system and the anabolic response to nutrients. We studied the effect of nutrition and the route of delivery of nutrition on cytokine profiles, the growth hormone-insulin-like growth factor-1 (IGF-I) axis and a potential mechanism for immune and anabolic system interaction, the suppressors of cytokine signaling (SOCS), in rodents with and without sepsis., Methods: Male Sprague-Dawley rats were randomized to laparotomy (Sham) or to cecal ligation and puncture (CLP), with postoperative saline infusion (Starve), with EN or with PN for 72 hours. Serum levels of IL-6 and IL-10 were measured by immunoassay, and hepatic expressions of cytokine-inducible SH2-containing protein, SOCS-2, SOCS-3, IGF-I and the growth hormone receptor (GHR) were measured by real-time quantitative PCR., Results: IL-6 was detectable in all groups, but was only present in all animals receiving CLP-PN. IL-10 was detectable in all but one CLP-PN rat, one CLP-EN rat, approximately 50% of the CLP-Starve rats and no sham-operated rats. Cytokine-inducible SH2-containing protein mRNA was increased in the CLP-EN group compared with the Sham-EN group and the other CLP groups (P < 0.05). SOCS-2 mRNA was decreased in CLP-PN rats compared with Sham-PN rats (P = 0.07). SOCS-3 mRNA was increased with CLP compared with sham operation (P < 0.03). IGF-I mRNA (P < 0.05) and GHR mRNA (P < 0.03) were greater in the fed CLP animals and in the Sham-PN group compared with the starved rats., Conclusion: In established sepsis, nutrition and the route of administration of nutrition influences the circulating cytokine patterns and expression of mRNA of SOCS proteins, GHR and IGF-I. The choice of the administration route of nutrition may influence cellular mechanisms that govern the response to hormones and mediators, which further influence the response to nutrients. These findings may be important in the design and analysis of clinical trials of nutritional interventions in sepsis in man.

Nutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.

Despite recent advances in antibiotic therapy and intensive care, sepsis remains a widespread problem in critically ill patients. The high mortality from sepsis is in part mediated by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., tumor necrosis factor, interleukin-1, and interferon-gamma) and late [e.g., high mobility group box 1 protein (HMGB1)] proinflammatory cytokines. Our discovery of HMGB1 as a late mediator of lethal systemic inflammation has initiated a new field of investigation for the development of experimental therapeutics. A popular Chinese herb, Angelica sinensis (also known as Dang Gui or Dong Quai) has been used traditionally for treating women with gynecological disorders (such as dysmenorrheal and hot flashes). Here we examined the effect of Angelica sinensis extract on endotoxin-induced HMGB1 release in vitro, and explored its therapeutic potential in animal models of lethal endotoxemia and sepsis [induced by cecal ligation and puncture (CLP)] in vivo. We demonstrated that a low-molecular-weight (<10 kDa) fraction of A. sinensis extract significantly attenuated endotoxin-induced HMGB1 release in part through interfering with its cytoplasmic translocation in macrophage cultures. Prophylactic administration of an aqueous extract of A. sinensis significantly attenuated systemic HMGB1 accumulation in vivo, and conferred a dose-dependent protection against lethal endotoxemia. Furthermore, delayed administration of A. sinensis extract beginning 24 h after CLP attenuated systemic HMGB1 accumulation, and significantly rescued mice from lethal sepsis. Taken together, these data suggest that A. sinensis contains water-soluble components that exert protective effects against lethal endotoxemia and experimental sepsis in part by attenuating systemic accumulation of a late proinflammatory cytokine, HMGB1.

Chronic feeding with enteral immune-enhancing diets (IEDs) provides benefits based on composition of the diet, route of feeding, and timing of feeding in relation to timing of trauma or surgery. Our prior studies of acute feeding in naïve rats demonstrated that IED promotes blood flow and proinflammatory cytokines in the ileum. We hypothesized that chronic feeding with IED would shift gut immune status to an anti-inflammatory state during chronic sepsis, resulting in an altered state of cytokine expression in the gut. Five days prior to feeding, gauze was implanted subcutaneously in the backs of male Sprague-Dawley rats, which were fed for 3 days with either control diet (CD, Boost; Mead-Johnson, Evansville, IL) or IED (Impact; Novartis) and randomly assigned to one of four groups: saline control (NS) + control diet (CD), sepsis (EC) + CD, NS + IED, or EC + IED. EC rats were inoculated with 10(9) CFU Escherichia coli and 10(9) CFU Bacteroides fragilis in 2 ml normal saline into the back sponge while NS rats received 2 mL normal saline alone. After 3 days, animals were anesthetized and gut tissue samples were harvested and frozen at -80 degrees C. Tissue protein was extracted and ELISA was performed for interleukin (IL-1beta, IL-5, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. In saline controls, IED feeding decreased IL-1beta, IL-5, IL-6, TNF-alpha, and IFN-gamma and increased IL-10 compared with CD-fed animals. In septic animals, IED feeding increased IL-5 and IL-6, while decreasing IFN-gamma and IL-10 in the distal third of the small intestine compared with CD-fed septic rats, whereas IL-1beta and TNF-alpha levels were unchanged. Chronic IED feeding produced a anti-inflammatory state via decreased IFN-gamma and increased IL-5 and IL-6, which both promote gut IgA class switching, suggesting that the gut is shifted toward humoral immunity during chronic IED feeding in septic rats.

Aim: To investigate the effects of arginine (Arg)-enriched diets before sepsis and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis., Methods: Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels., Results: Plasma interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN-gamma) were not detectable 3 d after CLP. There were no differences in the distributions of CD45Ra(+), CD3(+), CD4(+), and CD8(+) cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-gamma was significantly higher in group 4 than in the other three groups. There was no difference in TNF-alpha mRNA expression among the four groups., Conclusion: The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut-derived sepsis.

Newer immunosuppressive agents have dramatically reduced the rates of acute graft rejection over the last decade but may have exacerbated the problem of post-transplant infections. Causes of early mortality include graft dysfunction and sepsis. Late mortality occurs mainly due to sepsis. An excessive inflammatory response followed with a dramatic paralysis of cell-mediated immunity has been documented in septic patients. In transplanted individuals the pathophysiological changes of the immune response are further complicated by immunosuppressive agents. This article will focus on the effect of immunosuppressive agents and sepsis on cell-mediated immune responses. Moreover, potentially promising immunomodulatory approaches, i.e. human activated protein C, immunomodulatory diets containing L-arginine and fish oil, selective cytokine blockade, platelet-activating factor receptor antagonist, LPS receptor CD14 blockade and G-CSF, for the treatment of immunodysfunction in septic patients will be outlined in this review article. Most of them, however, have not been tested in the clinical arena in transplanted patients. Thus, the main part of the article, immunomodulation during sepsis in organ transplanted children is quite speculative and based on immunomodulatory strategies in other non-transplanted septic patients.

Sepsis, with its associated complications, is a leading cause of death in intensive care units. It is a major public health problem world-wide. The altered metabolism, severe condition and specific organ failure in sepsis patients get entangled in a vicious circle. Their treatment should invariably include nutritional support. The present survey summarizes the sepsis-induced metabolic changes so that they can be adequately compensated by nutritional support using specialized enteral formulas. We argue the necessity of introducing new efficient formulas as part of the so called immunonutrition. The basic requirements these formulas should meet are: 1. to provide sufficient amount of protein and energy substrate that can preserve the muscle function; 2. to be a source of substances that stimulate and protect enterocytes with restriction of bacterial translocation; 3. to help keep the liver function normal; 4. by including various substances with immunomodulating features to prevent and compensate the disturbances in the immune response.

Optimal nutritional status contributes to health maintenance and the prevention of infection. The function of healthy cells is maintained by the provision of adequate nutrition. When nutrient availability is disrupted, primary and secondary malnutrition develop. Malnutrition contributes to a cascade of adverse metabolic events that compromise the immune system and impair the body's ability to adapt, recover, and survive. Malnutrition is treated by the early delivery of essential nutrients in an effective and comprehensive manner. Nurses are challenged to understand the importance of adequate nutritional support in the prevention of infection, multiple organ failure, and sepsis.

Objective: To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using a formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), improves clinical outcomes, when compared with a common use, high protein enteral feed without these nutrients., Design: A prospective, randomized, multicentered trial., Setting: ICUs of six hospitals in Spain., Patients: One hundred eighty-one septic patients (122 males, 59 females) presenting for enteral nutrition in an ICU., Interventions: Septic ICU patients with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of > or =10 received either an enteral feed enriched with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), or a common use, high protein control feed (Precitene Hiperproteico)., Measurements and Main Results: One hundred seventy-six (89 Impact patients, 87 control subjects) were eligible for intention-to-treat analysis. The mortality rate was reduced for the treatment group compared with the control group (17 of 89 vs. 28 of 87; p < .05). Bacteremias were reduced in the treatment group (7 of 89 vs. 19 of 87; p = .01) as well as the number of patients with more than one nosocomial infection (5 of 89 vs. 17 of 87; p = .01). The benefit in mortality rate for the treatment group was more pronounced for patients with APACHE II scores between 10 and 15 (1 of 26 vs. 8 of 29; p = .02)., Conclusions: Immune-enhancing enteral nutrition resulted in a significant reduction in the mortality rate and infection rate in septic patients admitted to the ICU. These reductions were greater for patients with less severe illness.

Sepsis is a common surgical problem which can induce profound changes in the plasma concentrations of cytokines and hormones, leading to a catabolic state. Hypertriglyceridaemia and increased fat oxidation are the main features of altered fat metabolism encountered in this state. The endogenous catabolism of sepsis can be reduced by administering exogenous lipid emulsions as a source of metabolic fuel, although the changes in lipid metabolism associated with sepsis may affect the handling of these exogenous lipids. An exciting area for future research is an examination of the ability of lipid emulsions to reduce the morbidity and mortality associated with sepsis by altering immune responses, in addition to limiting catabolism.

The effects of dietary treatment for 3 weeks with soybean oil, linseed- and safflower oil (high alpha-linolenic acid, ALA), or borage oil (high gamma-linolenic acid, GLA) on the liver fatty acid profile and lipid metabolism in fed rats, in normal fasted rats, and septic fasted rats, and on survival from sepsis, were studied. The results were the following: 1) Dietary ALA increased incorporation of alpha-linolenic (18:3w3), eicosapentaenoic (20:5w3), and docosapentaenoic (22:5w3) acids in neutral lipids and phospholipids, and docosahexaenoic (22:6w3), dihomo-gamma-linolenic (20:3w6), arachidonic (20:4w6), stearic (18:0), oleic (18:1w9), and linoleic (18:2w6) acids in phospholipids in the livers of fed, fasted, and septic fasted rats. Dietary GLA increased all w6 fatty acids except 18:2w6, and reduced all w3 fatty acids in neutral lipids and phospholipids. 2) Dietary ALA increased liver phospholipid content in fasted as well as in septic fasted rats and was more potent than GLA in lowering serum cholesterol and liver neutral lipids. 3) Dietary ALA counteracted sepsis-related changes in liver weight, platelet count, body temperature, prekallikrein, serum glucose, beta-hydroxybutyrate, and free fatty acids. 4) Dietary GLA reduced survival from sepsis. The results suggest a role for w3 fatty acids to balance w6 fatty acids in the septic state.

Since an omega 3 fatty acid (FA) diet may have beneficial effects in inflammatory processes, we tested the hypothesis that the physiologic response to sepsis could be modified by altering the eicosanoid precursor pool via an omega 3 FA diet. Two groups (n = 8) of pigs were prefed for 8 days either an omega 3 FA or an omega 6 FA diet (Weaner Pig Feed with either menhaden or corn oil to produce a eucaloric feed with 15% fat) and then injected with live Escherichia coli. The omega 3 FA diet increased the concentration of eicosapentainoic acid (EPA, 20:5 omega 3) in plasma lipids, and increased the ratio of EPA to arachidonic acid (AA, 20:4 omega 6) in platelets from 1:20 to 1:1 over the 8 days. Following the injection of bacteria, there was a fall in PaO2 and blood pressure that was attenuated (p less than 0.05) by the omega 3 FA diet. The omega 3 FA diet, compared to the omega 6 FA diet, also attenuated the rise in thromboxane B2 (3.0 +/- 1.1 vs 12.9 +/- 5.7 ng/mL) and 6 keto-PGF1 alpha (0.8 +/- 0.5 vs 1.7 +/- 1.1 ng/mL) associated with bacteremia. We conclude that dietary omega 3 FA attenuated the physiologic response to sepsis, possibly by modifying arachidonic acid metabolism.