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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.

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.

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.

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.