Branched-Chain Amino Acids Can Predict Mortality in ICU Sepsis Patients

Sepsis biomarkers and potential therapeutic targets are urgently needed. With proton nuclear magnetic resonance (H-1 NMR) spectroscopy, several metabolites can be assessed simultaneously. Fifty-three adult medical ICU sepsis patients and 25 ICU controls without sepsis were prospectively enrolled. H-1 NMR differences between groups and associations with 28-day and ICU mortality were investigated. In multivariate metabolomic analyses, we found separate clustering of ICU controls and sepsis patients, as well as septic shock survivors and non-survivors. Lipoproteins were significantly different between sepsis and control patients. Levels of the branched-chain amino acids (BCAA) valine (median 43.3 [29.0-53.7] vs. 64.3 [47.7-72.3] normalized signal intensity units; p = 0.005), leucine (57.0 [38.4-71.0] vs. 73.0 [54.3-86.3]; p = 0.034) and isoleucine (15.2 [10.9-21.6] vs. 17.9 [16.1-24.4]; p = 0.048) were lower in patients with septic shock compared to those without. Similarly, BCAA were lower in ICU non-survivors compared to survivors, and BCAA were good discriminators for ICU and 28-day mortality. In uni- and multivariable logistic regression analyses, higher BCAA levels were associated with decreased ICU- and 28-day mortality. In conclusion, metabolomics using H-1 NMR spectroscopy showed encouraging potential for personalized medicine in sepsis. BCAA was significantly lower in sepsis non-survivors and may be used as early biomarkers for outcome prediction.

Automated summary

Metabolomics using H-1 NMR spectroscopy shows promise for personalized medicine in sepsis, with distinct differences in metabolites between sepsis patients and controls, as well as between septic shock survivors and non-survivors. Branched-chain amino acids (BCAA), including valine, leucine, and isoleucine, were significantly lower in sepsis non-survivors and serve as potential early biomarkers for predicting outcomes in ICU and 28-day mortality.