SCK-3: TARGET METABOLOMICS FOR IMPROVING EARLY PREDICTION OF DEATH IN PATIENTS WITH SEPTIC SHOCK.

INTRODUCTION: Elucidation of early metabolic signatures that predict survival in septic shock might help clinicians in prioritizing individual patient treatment. In this preliminary investigation, we examined plasma metabolome and clinical features in a subset of 20 patients with septic shock, enrolled in the multicenter Albumin Italian Outcome Sepsis (ALBIOS, NCT00707122).

METHODS: Patients were divided into two groups according to their 28-days and 90-days survival. A mass spectrometry-based metabolomic approach was used to quantify acylcarnitines, aminoacids, biogenic amines, glycerophospolipids, sphingolipids, sugars. Metabolites were measured one day (d1) and one week (d7) after ICU admission.

RESULTS: Profiles of specific metabolites differed markedly between survivors and non-survivors. An overall decrease from d1 to d7 in levels of different species of lysophosphatidylcholines (LPC) and phosphatidylcholines (PC) was observed together with a significant increase in kynurenine (KYN), in non-survivors compared to survivors both at 28- and 90-days (Wilcoxon test p < 0.05, FDR < 0.05). Data-mining techniques were then used to highlight metabolite levels associated with mortality. Twenty-eight days mortality was associated at d1 with increased levels of diacyl-PC-C38:1, butyrylacylcarnitine, but decreased diacyl-PC-C40:6 and diacyl-alkyl-PC-38:0; whereas at d7 with increased diacyl-PC-C42:4, KYN and decreased diacyl-alkyl-PC40:1, LPC-C24:0. Ninety-days mortality was associated only at d7 with elevation of KYN, diacyl-PC-C44:3 and reduction of diacyl- alkyl-PC40:1, LPC-C24:0.

CONCLUSION: Our preliminary results suggest that increased KYN, that may contribute to hypotension in sepsis, as well as alterations of different LPC and PC species, able to modulate immune and inflammatory responses, might represent not only a risk factor for septic shock patients but important pathophysiologic mechanisms deserving further investigation.