Bioenergetic Crisis in ICU-Acquired Weakness Gene Signatures Was Associated With Sepsis-Related Mortality: A Brief Report

Abstract

OBJECTIVES: To investigate the relationship between ICU-acquired weakness (ICUAW) signatures and sepsis-related mortality using gene expression from the blood within 24 hours of sepsis onset. DESIGN: Observational study using differential gene expression analysis. SETTING: Publicly available gene expression profile GSE54514, single-center medical and surgical ICU. PATIENTS: Patients with primary bacteremia- and respiratory-triggered sepsis including 8 nonsurvivors and 13 survivors who were 18 years old and older and admitted to ICU. MEASUREMENTS AND MAIN RESULTS: Among validated 526 ICUAW gene signatures, differential gene expression analysis controlling for age identified 38 significantly expressed genes between nonsurvivors and survivors. Functional enrichment analysis of differentially expressed ICUAW genes identified impaired cadherin binding, sarcomere formation, and energy metabolism among nonsurvivors. CONCLUSIONS: Our findings demonstrated a biological association between sepsis-related mortality and ICUAW signatures in the early phase of sepsis. Defects in energy metabolism and muscle fiber formation were associated with sepsis-related mortality.