Serum Metabolomic Profiles in Critically Ill Patients with Shock on Admission to the Intensive Care Unit

Abstract

Inflammatory processes are common in intensive care (ICU) patients and can induce multiple changes in metabolism, leading to increased risks of morbidity and mortality. Metabolomics enables these modifications to be studied and identifies a patient's metabolic profile. The objective is to precise if the use of metabolomics at ICU admission can help in prognostication. This is a prospective ex-vivo study, realized in a university laboratory and a medico-surgical ICU. Metabolic profiles were analyzed by proton nuclear magnetic resonance. Using multivariable analysis, we compared metabolic profiles of volunteers and ICU patients divided into predefined subgroups: sepsis, septic shock, other shock and ICU controls. We also assessed possible correlations between metabolites and mortality. One hundred and eleven patients were included within 24 h of ICU admission, and 19 healthy volunteers. The ICU mortality rate was 15%. Metabolic profiles were different in ICU patients compared to healthy volunteers (p < 0.001). Among the ICU patients, only the subgroup of patients with septic shock had significant differences compared to the ICU control patients in several metabolites: pyruvate, lactate, carnitine, phenylalanine, urea, creatine, creatinine and myo-inositol. However, there was no correlation between these metabolite profiles and mortality. On the first day of ICU admission, we observed changes in some metabolic products in patients with septic shock, suggesting increased anaerobic glycolysis, proteolysis, lipolysis and gluconeogenesis. These changes were not correlated with prognosis.

Keywords: gluconeogenesis; lipolysis; prognosis; proteolysis; septic shock.

Figure 1

Scores plot (healthy volunteers versus ICU patients). The abbreviations HV represent healthy volunteers; the abbreviation I represent ICU patients. PLS-DA shows a separation between healthy volunteers and ICU patients (R²X = 0.27; R²Y = 0.62; Q² = 0.44).

Figure 2

Scores plot (septic shock versus ICU control group). Septic shock patients (in blue) versus ICU control patients (in green). The supervised OPLS-DA method shows a significant difference between septic shock patients and ICU control patients (CV-ANOVA, p = 0.006).

Figure 3

Loadings plot (septic shock versus ICU control group). Different expressions of metabolites between septic shock and ICU control group (R²X = 0.53; R²Y = 0.58; Q² = 0.29).

Figure 4

VIP plot (septic shock vs. ICU control group). Identified metabolites considered as relevant when VIP > 1: creatine, creatinine, urea, myo-inositol, phenylalanine, mannitol, alanine, valine, glutamine, glutamate, leucine.