Metabolomic derangements are associated with mortality in critically ill adult patients.

Abstract

OBJECTIVE: To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults. RATIONALE: Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible. METHODS: We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study. RESULTS: We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations). CONCLUSION: Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.

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Published Version (Please cite this version)

10.1371/journal.pone.0087538

Publication Info

Rogers, Angela J, Michael McGeachie, Rebecca M Baron, Lee Gazourian, Jeffrey A Haspel, Kiichi Nakahira, Laura E Fredenburgh, Gary M Hunninghake, et al. (2014). Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One, 9(1). p. e87538. 10.1371/journal.pone.0087538 Retrieved from https://hdl.handle.net/10161/13313.

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Scholars@Duke

Fowler

Vance Garrison Fowler

Florence McAlister Distinguished Professor of Medicine

Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia
Antibacterial Resistance
Pathogenesis of Bacterial Infections
Tropical medicine/International Health

Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health

1. Emerging Infections
2. Global Health
3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics
5. Bioterrorism Preparedness
6. Surveillance for communicable diseases
7. Antimicrobial resistance


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