Energy Demand and Cholesterol Catabolism Intensify Prior to the Onset of ARDS in Surgical ICU Patients

Post-operative acute respiratory distress syndrome (ARDS) is associated with high rates of morbidity and mortality. Despite the substantial need to discover strategies to prevent post-operative ARDS, no studies have explored metabolic biomarkers that indicate the impending development of post-operative ARDS. We investigated early metabolic biomarker signs of the development of post-operative ARDS.MethodsWe investigated a total of 49 surgical critical care patients and 32 of those who developed post-operative ARDS admitted to a surgical ICU at an urban, level I trauma center in North America. ARDS was identified using the Berlin criteria, and we defined post-operative ARDS if it was diagnosed within seven days of ICU admission after operation. To investigate the prognostic biomarkers of ARDS, we used liquid chromatography-mass spectrometry-based targeted metabolomics for the blood during ICU stay. We separated blood specimens according to intervals bracketing ARDS onset: -7 to -3 days, -3 to -1 days, -1 to 0 day, 0 to +2 days, +2 to +5 days, and +5 to +7.4 days meeting ARDS criteria. Control samples from surgical critical care patients who did not develop ARDS were matched based on the same time post-ICU admission for each group, and a moderated T-test was used to analyze the mean level of each metabolite (unadjusted p value <0.05). ResultsThe median time to ARDS onset was 3.0 days [IQR: 2.0 days, 5.0 days]. Among 86 available metabolites, 27 metabolites were significantly distinct when comparing post-operative ARDS and control groups. The concentration of 3- hydroxybutyric acid was lower in post-operative ARDS more than 3 days prior to ARDS onset compared with control, and it persisted during the pre-ARDS phase. Moreover, cholic acid concentration was greater than control within 1 day prior to ARDS onset, and it remained higher after ARDS. In the post ARDS phase, metabolites associated with the citric cycle, such as citric acid and nicotinamide, were lower concentration in patients who developed ARDS.ConclusionsWe observed dysregulation in metabolites associated with the citric cycle and bile acid, both preceding at least one day prior and following the development of ARDS. These signatures suggested an increase in energy demand and cholesterol catabolism in patients with post-operative ARDS. Furthermore, dysregulation of 3-hydroxybutyric acid and cholic acid may be used to predict ARDS development in surgical critical care patients.

DOI: Kobara S, Yang C, Fensore C, Gaur H, Natarajan K, Davis CM, Ghneim K, Caten FT, Pelletier AN, Sharma AA, Enriquez AB. Energy Demand and Cholesterol Catabolism Intensify Prior to the Onset of ARDS in Surgical ICU Patients. InC40. ARDS AND ACUTE RESPIRATORY FAILURE: MECHANISM, RISK, AND OUTCOMES 2024 May (pp. A5497-A5497). American Thoracic Society.