Characterization of a metabolomic profile associated with responsiveness to therapy in the acute phase of septic shock

Abstract

The early metabolic signatures associated with the progression of septic shock and with responsiveness to therapy can be useful for developing target therapy. The Sequential Organ Failure Assessment (SOFA) score is used for stratifying risk and predicting mortality. This study aimed to verify whether different responses to therapy, assessed as changes in SOFA score at admission (T1, acute phase) and 48 h later (T2, post-resuscitation), are associated with different metabolite patterns. We examined the plasma metabolome of 21 septic shock patients (pts) enrolled in the Shockomics clinical trial (NCT02141607). Patients for which SOFAT2 was >8 and Δ = SOFAT1 − SOFAT2 < 5, were classified as not responsive to therapy (NR, 7 pts), the remaining 14 as responsive (R). We combined untargeted and targeted mass spectrometry-based metabolomics strategies to cover the plasma metabolites repertoire as far as possible. Metabolite concentration changes from T1 to T2 (Δ = T2 − T1) were used to build classification models. Our results support the emerging evidence that lipidome alterations play an important role in individual patients’ responses to infection. Furthermore, alanine indicates a possible alteration in the glucose-alanine cycle in the liver, providing a different picture of liver functionality from bilirubin. Understanding these metabolic disturbances is important for developing any effective tailored therapy for these patients.

Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy

“…We used SOFA score changes between time point 1 (T1), which was within 16 h of ICU admission, and time point 2 (T2), which was 48 h after study enrolment as an index of response to early supportive treatment to stratify subjects as responders (Rs) or non-responders (NRs) as previously reported [ 13 ]. A subject was classified as NR if the difference in SOFA score between T1 and T2 was less than 5 and the SOFA score at T2 was greater than 8.…”

Blood pressure variability, heart functionality, and left ventricular tissue alterations in a protocol of severe hemorrhagic shock and resuscitation

“…Samples were analyzed with an LC/MS (Triple quad 5500; AB Sciex) method (for analysis of amino acids and biogenic amines) followed by flow injection analysis-MS (analysis of lipids, acylcarnitines, and hexose). Methodological details and data preprocessing have been extensively reported in our previous articles ( 13 , 29 ).…”

Immunometabolic approaches to prevent, detect, and treat neonatal sepsis

“…Changes is the levels of metabolites can also predict sepsis outcome and provide information on responsiveness to therapy. Mass spectrometry-based metabolomics strategies on the plasma metabolome of 21 adult septic shock patients suggest that lipidome alterations play an important role in an individual's response to infection [64]. In a plasma metabolomics and proteomics study involving 1000 adult sepsis patients, FAO was severely impaired in sepsis non-survivors, highlighting fatty acid metabolism as a promising metabolic predictor for survival in sepsis [65].…”