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

Alexander Christian Reisinger,Gunther Marsche,Harald Sourij,Philipp Eller,Kathrin Eller,Gerald Hackl,Tobias Madl,Florian Posch,Benjamin Bourgeois

doi:10.3390/nu13093106

Alexander Christian Reisinger, Gunther Marsche + Show 7 more

Open Access

https://doi.org/10.3390/nu13093106

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Journal: Nutrients	Publication Date: Sep 3, 2021
Citations: 19	License type: CC BY 4.0

Affiliation: Medical University of Graz, BioTechMed-Graz

Abstract

Sepsis biomarkers and potential therapeutic targets are urgently needed. With proton nuclear magnetic resonance (1H NMR) spectroscopy, several metabolites can be assessed simultaneously. Fifty-three adult medical ICU sepsis patients and 25 ICU controls without sepsis were prospectively enrolled. 1H 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 1H 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.

Highlights

Sepsis-3-criteria were applied to define sepsis patients [3], and the control group consisted of consecutive intensive care unit (ICU) patients without sepsis or bacteremia at the time of sampling
We assessed the metabolomic profiles of patients with sepsis and septic shock who were admitted to the ICU and ICU patients without sepsis or bacteremia
Sepsis and septic shock are common in intensive care medicine and have high mortality rates [15,16]

Summary

Introduction

Sepsis is a common global life-threatening medical condition, and more than 31 million patients each year suffer from sepsis or septic shock [1]. The absolute number of sepsis patients is continuously increasing over the last years because of a more widespread use of immunosuppressive therapies, increasing age and the emerge of multi-resistant bacteria [2]. Sepsis is not the presence of bacteremia, and triggered by the host’s response to the infection causing organ dysfunction. This concept is reflected in the current sepsis-3 definition [3]. The diagnosis of sepsis includes a suspected infection and the presence of a new organ dysfunction measured by the sequential organ failure assessment (SOFA)

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