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 (1)H-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.