Clinical Relevance of Preoperative Lymphocyte-to-Monocyte Ratio in Predicting Postoperative Delirium Across Frailty Status in Older Surgical Patients

Background: Postoperative delirium (POD) is a common and severe complication in older surgical patients. Although systemic inflammation and frailty are established risk factors, the predictive value of the lymphocyte-to-monocyte ratio (LMR) across different frailty strata remains unclear. This study aimed to evaluate the association between preoperative LMR and POD and to determine whether this relationship varies according to frailty status. Methods: We performed a retrospective analysis of prospectively collected data from a multicenter cohort of 6,475 patients aged ≥ 65 years undergoing elective non-cardiac, non-neurosurgical surgery in China. Preoperative LMR was calculated from preoperative blood tests. Logistic regression and restricted cubic spline (RCS) analyses were used to assess the association between preoperative LMR and POD, with further stratified analyses performed across different frailty groups. Results: Among 6,475 patients, 789 (12.2%) developed POD. After adjustment for potential confounders, higher LMR was independently associated with a lower risk of POD (per 1-unit increase: OR 0.94, 95% CI 0.90– 0.98, P = 0.009). A significant inverse dose-response relationship was observed. Compared with the lowest quartile (Q1), the adjusted ORs (95% CIs) for Q2–Q4 were 0.73 (0.59– 0.90), 0.69 (0.56– 0.86), and 0.68 (0.54– 0.85), respectively. Stratified analyses revealed distinct patterns across frailty status: a significant nonlinear association was observed only in pre-frail patients (Q4 vs. Q1: adjusted OR 0.69, 95% CI 0.50– 0.95; P for nonlinearity = 0.003). In contrast, the association in frail individuals was weaker and primarily linear, while no significant association was observed in robust patients. Conclusion: Preoperative LMR is independently associated with POD in older surgical patients. Its predictive value varies across frailty strata, with the association most evident among pre-frail individuals. Keywords: lymphocyte-to-monocyte ratio, inflammation, frailty, postoperative delirium, elderly