Objective: To characterize early physiologic stresses imposed by surgery by applying metabolomic analyses to deeply phenotype pre- and postoperative plasma and urine of patients undergoing elective surgical procedures.
Background: Patients experience perioperative stress through depletion of metabolic fuels. Bowel stasis or injury might allow more microbiome-derived uremic toxins to enter the blood, while the liver and kidney are simultaneously clearing analgesic and anesthetic drugs. Metabolomics provides a broad-scale snapshot of small-molecule chemicals generated in vital energetic and detoxification pathways, enabling a mechanistic understanding of surgical stressors.
Methods: We performed metabolomic analysis of paired preoperative and early-recovery plasma (n = 34) and urine (n = 35) from patients who underwent elective surgeries, spanning cardiovascular, gastrointestinal, hernia, oncologic, and urologic procedures. Mass spectrometry-based metabolomics analyses were performed together with the analysis of select metabolites and macromolecules via conventional clinical assays.
Results: Fuel stress during elective surgery manifested in changes across all major metabolic pathways, encompassing lipolysis, glycolysis-Krebs cycle, ketogenesis, and glycogenolysis. A common signature of enhanced amino acid oxidation and urea-cycle activity emerged, which was especially pronounced in patients given citrulline boluses before visceral procedures. Excretion of amino acid-derived catabolite toxins increased during surgery, notably those derived from gut microbes, as did an extract of disposable surgical plasticware, bis(2-ethylhexyl)phthalate.
Conclusion: Elective surgery imposes broad-scale early and measurable metabolic changes. The use of citrulline-enriched preoperative carbohydrate drinks needs further study to limit metabolic burden. Attention to perioperative nutrition and intraoperative control of gut-microbial toxins might reduce metabolic derangements and lead to better postoperative outcomes.
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