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

Beata Mickiewicz, Patrick Tam, Craig N Jenne, Caroline Leger, Josee Wong, Brent W Winston, Christopher Doig, Paul Kubes, Hans J Vogel

Septic 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. Serum 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). (1)H 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. By 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. Our 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.