Immuno-metabolic Reprogramming in Perioperative Medicine: A New Determinant of Surgical Outcomes

Abstract

Chronic surgical stress represents a critical window during which surgical stress, anesthesia, and host immune responses interact to shape short- and long-term patient outcomes. Traditionally, perioperative physiology has been interpreted through isolated frameworks of inflammation, hemodynamics, and organ-specific injury. However, emerging evidence highlights a unifying paradigm—immunometabolic reprogramming—whereby immune cell function is tightly coupled to metabolic pathways. This dynamic interplay influences the magnitude and persistence of inflammation, tissue repair, and susceptibility to complications.

Immunometabolism refers to the metabolic processes that govern immune cell activation, differentiation, and function. In the perioperative setting, surgical trauma induces a shift toward glycolysis-dominant metabolism in innate immune cells, supporting rapid cytokine production and inflammatory signaling. While this acute response is adaptive, persistent metabolic dysregulation can promote organ dysfunction, impaired healing, and adverse outcomes such as postoperative cognitive dysfunction, acute kidney injury, and sepsis.

Recent advances have demonstrated that key metabolic pathways—including glycolysis, oxidative phosphorylation, fatty acid oxidation, and mitochondrial signaling—play central roles in modulating perioperative immune responses. Metabolites such as succinate and lactate act not merely as energy intermediates but as signaling molecules that amplify inflammatory cascades. Furthermore, mitochondrial dysfunction and reactive oxygen species generation contribute to inflammasome activation and cellular injury.

Understanding these mechanisms opens new therapeutic avenues. Targeting immunometabolic pathways through pharmacological modulation, nutritional interventions, and anesthetic strategies may allow clinicians to recalibrate the perioperative immune response rather than simply suppress it. This approach represents a shift toward precision perioperative medicine, where interventions are tailored to the metabolic and immunological state of the patient.

This narrative review synthesizes current evidence on immunometabolic reprogramming in perioperative medicine, highlights its role in surgical outcomes, and discusses emerging therapeutic strategies. Recognizing immunometabolism as a central determinant of perioperative physiology may transform how anesthesiologists approach inflammation, organ protection, and recovery in surgical patients.