1.
Changes in lipid metabolism in pediatric patients with severe sepsis and septic shock.
Bermudes, ACG, de Carvalho, WB, Zamberlan, P, Muramoto, G, Maranhão, RC, Delgado, AF
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:104-109
Abstract
OBJECTIVES Limited knowledge exists regarding the lipid profiles of critically ill pediatric patients with systemic inflammatory response syndrome. The aim of this study was to evaluate the relationship between the intensity of the inflammatory response and changes in the lipid profiles of critically ill pediatric patients admitted to a pediatric intensive care unit (PICU) with severe sepsis/septic shock. METHODS This was a prospective and observational study at a 15-bed PICU at a public university hospital. We analyzed the lipid profiles of 40 patients with severe sepsis/septic shock admitted to the PICU on the first and seventh days of hospitalization. C-reactive protein was used as a marker for systemic inflammation. Forty-two pediatric patients seen in the emergency department and without systemic inflammatory response syndrome were used to provide control values. RESULTS On day 1 of admission to the PICU, the patients had significantly lower levels of total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) as well as higher concentrations of triacylglycerols compared with the control group. There was a significant increase in the TC, HDL, LDL, and apolipoprotein levels from day 1 to day 7 of the study. CONCLUSIONS During severe sepsis/septic shock, we found lower serum levels of lipoproteins and apolipoproteins, and these were negatively correlated with C-reactive protein. As the inflammatory response improved, the levels of TC, HDL, LDL, and apolipoproteins increased, suggesting a direct relationship between changes in the lipid profiles and inflammation.
2.
Human metabolic response to systemic inflammation: assessment of the concordance between experimental endotoxemia and clinical cases of sepsis/SIRS.
Kamisoglu, K, Haimovich, B, Calvano, SE, Coyle, SM, Corbett, SA, Langley, RJ, Kingsmore, SF, Androulakis, IP
Critical care (London, England). 2015;(1):71
Abstract
INTRODUCTION Two recent, independent, studies conducted novel metabolomics analyses relevant to human sepsis progression; one was a human model of endotoxin (lipopolysaccharide (LPS)) challenge (experimental endotoxemia) and the other was community acquired pneumonia and sepsis outcome diagnostic study (CAPSOD). The purpose of the present study was to assess the concordance of metabolic responses to LPS and community-acquired sepsis. METHODS We tested the hypothesis that the patterns of metabolic response elicited by endotoxin would agree with those in clinical sepsis. Alterations in the plasma metabolome of the subjects challenged with LPS were compared with those of sepsis patients who had been stratified into two groups: sepsis patients with confirmed infection and non-infected patients who exhibited systemic inflammatory response syndrome (SIRS) criteria. Common metabolites between endotoxemia and both these groups were individually identified, together with their direction of change and functional classifications. RESULTS Response to endotoxemia at the metabolome level elicited characteristics that agree well with those observed in sepsis patients despite the high degree of variability in the response of these patients. Moreover, some distinct features of SIRS have been identified. Upon stratification of sepsis patients based on 28-day survival, the direction of change in 21 of 23 metabolites was the same in endotoxemia and sepsis survival groups. CONCLUSIONS The observed concordance in plasma metabolomes of LPS-treated subjects and sepsis survivors strengthens the relevance of endotoxemia to clinical research as a physiological model of community-acquired sepsis, and gives valuable insights into the metabolic changes that constitute a homeostatic response. Furthermore, recapitulation of metabolic differences between sepsis non-survivors and survivors in LPS-treated subjects can enable further research on the development and assessment of rational clinical therapies to prevent sepsis mortality. Compared with earlier studies which focused exclusively on comparing transcriptional dynamics, the distinct metabolomic responses to systemic inflammation with or without confirmed infection, suggest that the metabolome is much better at differentiating these pathophysiologies. Finally, the metabolic changes in the recovering patients shift towards the LPS-induced response pattern strengthening the notion that the metabolic, as well as transcriptional responses, characteristic to the endotoxemia model represent necessary and "healthy" responses to infectious stimuli.