Faculty Collaboration Database

Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One 2014;9(1):e87538

Date

02/06/2014

Pubmed ID

24498130

Pubmed Central ID

PMC3907548

DOI

10.1371/journal.pone.0087538

Scopus ID

2-s2.0-84900401311 (requires institutional sign-in at Scopus site)   110 Citations

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.

Author List

Rogers AJ, McGeachie M, Baron RM, Gazourian L, Haspel JA, Nakahira K, Fredenburgh LE, Hunninghake GM, Raby BA, Matthay MA, Otero RM, Fowler VG, Rivers EP, Woods CW, Kingsmore S, Langley RJ, Choi AM

Author

Ronny M. Otero MD Vice Chair, Professor in the Emergency Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Bayes Theorem
Biomarkers
Community-Acquired Infections
Critical Illness
Female
Hospital Mortality
Humans
Intensive Care Units
Male
Metabolomics
Middle Aged
Prognosis
Sepsis