Serum Levels of Acylcarnitines and Amino Acids Are Associated with Liberation from Organ Support in Patients with Septic Shock

Abstract

Sepsis-induced metabolic dysfunction is associated with mortality, but the signatures that differentiate variable clinical outcomes among survivors are unknown. Our aim was to determine the relationship between host metabolism and chronic critical illness (CCI) in patients with septic shock. We analyzed metabolomics data from mechanically ventilated patients with vasopressor-dependent septic shock from the placebo arm of a recently completed clinical trial. Baseline serum metabolites were measured by liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance. We conducted a time-to-event analysis censored at 28 days. Specifically, we determined the relationship between metabolites and time to extubation and freedom from vasopressors using a competing risk survival model, with death as a competing risk. We also compared metabolite concentrations between CCI patients, defined as intensive care unit level of care ≥ 14 days, and those with rapid recovery. Elevations in two acylcarnitines and four amino acids were related to the freedom from organ support (subdistributional hazard ratio < 1 and false discovery rate < 0.05). Proline, glycine, glutamine, and methionine were also elevated in patients who developed CCI. Our work highlights the need for further testing of metabolomics to identify patients at risk of CCI and to elucidate potential mechanisms that contribute to its etiology.

Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response

“…In addition, pro-resolving mediators, including RvD2 and RvD3 (on day 3); RvE3 and RvD6 (on days 3 and 7); 17R-RvD1 (on day 7); 10S,17S-diHDHA, an isomer of protectin D1 (on days 1, 3 and 7); 17R-PD1 (on Day 3); 5-HEPE, a metabolite of eicosapentaenoic acid; and 14-HDHA, an intermediate in the synthesis of maresin 1 [ 137 ] (on days 0 and 3) were also significantly increased in septic patients with ARDS compared to those without [ 94 ] ( Figure 1 ). Another study investigating metabolic differences in mechanically ventilated septic patients found that proline, glycine, glutamine, methionine, acetylcarnitine and valerylcarnitine were associated with liberation from mechanical ventilation and vasopressors at 28 days [ 138 ].…”

Predictive value of presepsin and acylcarnitines for severity and biliary drainage in acute cholangitis

“…Metabolic flexibility was shown to be an important characteristic of patients with sepsis for survival[ 27 ]. Plasma C2 Level was shown to be associated with multiple organ dysfunction, extubation, and freedom from vasopressors, or mortality in patients with sepsis[ 10 , 11 ]. In several studies, plasma short chain and medium chain acylcarnitines (C2, C3, C4, C5, C6, C8, C10) were significantly increased in the non-survivors[ 11 , 28 - 30 ] and only C2 was associated with all of these indices and 28-d mortality in sepsis[ 12 ].…”

Ex Vivo Evaluation of Glutamine Treatment in Sepsis and Trauma in a Human Peripheral Blood Mononuclear Cells Model

“…Randomized studies, however, suggested that glutamine decreases gastric colonization, infectious complications, and ICU length of stay [ 25 , 26 , 27 , 28 ]. Further confusing its role, elevations in glutamine along with proline, glycine, methionine, and two acylcarnitines were not only related to organ-support-free days but also chronic critical illness development [ 29 ].…”