Perioperative metabolic phenotyping: emerging evidence and translational potential for risk stratification and anesthetic dosing

Metabolic phenotyping during the perioperative period, defined as the patient-specific characterization of metabolic activities across the pre-, intra-, and postoperative phases, is increasingly recognized as a promising component of emerging precision perioperative medicine, although it has not yet become an established pillar. It differs from conventional approaches based on static baseline assessments by capturing dynamic metabolic responses to surgical stress and anesthesia, which may enable more informative risk stratification than conventional assessment tools. Advances in metabolomics, pharmacometabolomics, and multiomics methodologies have enabled the identification of metabolic signatures associated with perioperative risk, medication responses, organ dysfunction, and recovery. This narrative review uses a structured search strategy in major databases (2015–2026) to synthesize current evidence regarding the utility, methodologies, and future potential of perioperative metabolic phenotyping in adults undergoing surgery. The review describes how studies were selected and critically evaluates the available evidence, emphasizing that most primary research consists of single-center observational cohort studies that require external validation. The review summarizes historical developments, mass spectrometry and nuclear magnetic resonance (NMR)-based techniques, and how these technologies are combined with artificial intelligence and pharmacogenomics to study anesthesia and intensive care outcomes. In addition, it collates clinical studies examining the associations between metabolic phenotypes and delirium, emergence agitation (EA), acute kidney injury, stress hyperglycemia, and organ dysfunction, and discusses pharmacometabolomic approaches to anesthetic drug selection and dosing. Finally, the review outlines key challenges to clinical adoption, including methodological heterogeneity, lack of external and interventional validation, economic and point-of-care barriers, and ethical and regulatory considerations, and highlights research priorities that must be addressed before perioperative metabolic phenotyping can evolve from exploratory research into a clinically robust decision support tool.

Perioperative metabolic phenotyping; Pharmacometabolomics; Precision anesthesia; Multi-omics integration; Predictive metabolic biomarkers

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