Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit

Abstract

IntroductionSeptic shock is a major life-threatening condition in critically ill patients and it is well known that early recognition of septic shock and expedient initiation of appropriate treatment improves patient outcome. Unfortunately, to date no single compound has shown sufficient sensitivity and specificity to be used as a routine biomarker for early diagnosis and prognosis of septic shock in the intensive care unit (ICU). Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients. In this study, we have evaluated whether a combined nuclear magnetic resonance spectroscopy-based metabolomics and a multiplex cytokine/chemokine profiling approach could be used for diagnosis and prognostic evaluation of septic shock patients in the ICU.MethodsSerum and plasma samples were collected from septic shock patients and ICU controls (ICU patients with the systemic inflammatory response syndrome but not suspected of having an infection). 1H Nuclear magnetic resonance spectra were analyzed and quantified using the targeted profiling methodology. The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits.ResultsBy using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality. These metabolites and cytokines/chemokines represent candidate biomarkers of the human response to septic shock and have the potential to improve early diagnosis and prognosis of septic shock.ConclusionsOur findings show that integration of quantitative metabolic and inflammatory mediator data can be utilized for the diagnosis and prognosis of septic shock in the ICU.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0729-0) contains supplementary material, which is available to authorized users.

AME evidence series 001—The Society for Translational Medicine: clinical practice guidelines for diagnosis and early identification of sepsis in the hospital

“…The reference standard used in these studies was defined in the ACCP/SCCM, 2001 SCCM/ESICM/ACCP/ATS/SIS and 2012 SSC guidelines. The index test (i.e., potential diagnostic biomarkers) included, among others, presepsin (sCD14-ST) (24), PCT, Neutrophil CD64 (25), sTREM-1 (26), lipopolysaccharidebinding protein, pro-adrenomedullin, pro-vasopressin and a variety of inflammatory cytokines (27)(28)(29). Furthermore, the efficacy of many scoring systems and screening tools for detecting early sepsis has been evaluated (30,31).…”

Whole Blood Reveals More Metabolic Detail of the Human Metabolome than Serum as Measured by 1H-NMR Spectroscopy

“…The application of untargeted metabolomics to critical care is a rapidly emerging field that holds great promise for lending insight to the mechanistic underpinnings of complex critical illnesses such as sepsis (25, 26). Studying the metabolome in this group is complicated by a number of pathophysiological and logistical hurdles.…”

“…For example, the concentration of glutamate ( Figure 3B ) was more than 3X higher in WB than in serum (Table 2) and is known to be 10X higher in RBC than in plasma (28). Glutamate is integral in glucose metabolism and amino acid transport and utilization, particularly in skeletal muscle, and has also been identified as a potential differentiating metabolite of sepsis (26) as have phenylalanine ( Figure 3C ) and alanine ( Figure 3F ), both of which are transported by RBC (10). Also, creatine phosphate has been reported to decline in sepsis (26).…”

“…Glutamate is integral in glucose metabolism and amino acid transport and utilization, particularly in skeletal muscle, and has also been identified as a potential differentiating metabolite of sepsis (26) as have phenylalanine ( Figure 3C ) and alanine ( Figure 3F ), both of which are transported by RBC (10). Also, creatine phosphate has been reported to decline in sepsis (26). The association between creatine phosphate, a low abundant serum metabolite, and free Hgb ( Figure 3E ) warrants further investigation because even though RBC are known to contain creatine (29), it is generally accepted that RBC lack creatine kinase (30) (EC 2.7.3.2), the enzyme responsible for phosphorylating creatine to creatine phosphate.…”

Laboratory in Diagnosis and Monitoring of Systemic Inflammatory Response Syndrome or Sepsis

“…Nükleer Magnetik Rezonans Spektrometrisi (NMRS) ile hasta kan örneklerinin metabolik ve inflamatuvar profilinin moleküler tanı yöntemi kullanılarak incelenmesi, ileri teknoloji gerektirmektedir (71)(72)(73)(74). Sağlık hizmeti sunumu ve hastayla ilgili çok ve çeşitli verinin (predispoze durumlar, bulgular, tedaviye verdiği cevap vb.)…”