Metabolic Flexibility as a Candidate Mechanism for the Development of Postoperative Morbidity

BACKGROUND: This study investigates the role of metabolic flexibility in determining perioperative outcomes. Metabolic flexibility, a key feature of metabolic health, is the ability to efficiently switch between different fuel sources (predominantly carbohydrates and fats) depending on energy demands and availability. Given the rapidly changing physiological conditions in the perioperative period, we hypothesized that good metabolic adaptability could mitigate postoperative complications. METHODS: We conducted a retrospective observational study utilizing a prospectively collected, single-center preoperative cardiopulmonary exercise testing (CPET) database of patients undergoing a range of major surgeries between 2012 and 2022. On day 3, patients were categorized into 3 groups based on their Postoperative Morbidity Survey (POMS) scores: 0 to 1, 2, and 3 to 6. Metabolic flexibility was evaluated through measurements of fat and carbohydrate oxidation during exercise testing (CPET). Associations were explored between metabolic flexibility, cardiorespiratory fitness, and postoperative outcomes. RESULTS: Of 585 patients, those with no or low postoperative day 3 morbidity (POMS 0-1; n = 204) demonstrated significantly higher fat oxidation early in exercise before anaerobic threshold (fatty acid oxidation [FATox] area under the curve [AUC] 826 [578-1147]) compared to both POMS 2 (658 [448-922; n = 268]) and POMS 3 to 6 (608 [414-845; n = 113]); both P <.001. POMS 0 to 1 patients also had more effective carbohydrate utilization at peak exercise intensity. Higher postoperative morbidity (POMS) categories were associated with diminished metabolic flexibility characterized by a reduced ability to switch between metabolic substrates - carbohydrate oxidation (CHOox) POMS 0 to 1 group AUC 10277 (interquartile range [IQR] 7773-13358) compared to POMS 2 AUC 8356 (IQR 6548-10377) and POMS 3 to 6 AUC 6696 (IQR 473-9392); both P <.001. Reduced metabolic flexibility correlated with increased postoperative complications and an extended hospital stay. CONCLUSIONS: Metabolic flexibility may be a pivotal factor in determining postoperative outcomes. Patients with greater metabolic adaptability had fewer complications and shorter hospitalization by 4 days on average. This suggests that preoperative metabolic conditioning - something potentially achieved by targeted prehabilitation - could be linked to surgical recovery. Future research should focus on prospective studies to confirm these relationships and explore underlying mechanisms. If confirmed, metabolic flexibility assessments could be integrated into routine preoperative evaluation to better predict and improve patient outcomes.