Acute perioperative alterations in metabolism: A pilot study using mass spectrometry–based metabolomics

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.