Pupillometry and Predicted Propofol Effect-Site Concentrations During TIVA-TCI: A Prospective Observational Study

Background Frailty, particularly its cognitive dimension, is increasingly recognized as a major determinant of anaesthetic sensitivity and postoperative vulnerability in older patients. Reliable, rapid, and non-invasive tools to identify brain frailty in the perioperative setting are still lacking. Pupillometry reflects autonomic and central cholinergic function and may provide insights into individual susceptibility to anaesthetic agents. This study investigated the relationship between perioperative pupillometric variables, effect-site propofol concentration (CeP) at different anaesthetic phases, and postoperative delirium (POD) occurrence. Methods In this prospective observational study, 213 female patients undergoing breast oncologic surgery under propofol-remifentanil Total Intravenous Anaesthesia - Target-controlled Infusion (TIVA-TCI) were analysed. Preoperative, intraoperative, and postoperative pupillometric parameters (pupillary diameter (PD), pupillary light reflex latency (PL), and maximum constriction velocity (MCV)) were recorded. CeP values were collected at loss of responsiveness (LoR), maintenance of anaesthesia (MA), burst suppression (BSupp), and return of responsiveness (RoR). POD was assessed using the Confusion Assessment Method (CAM) in the post-anaesthesia care unit. Correlation analyses and multivariable logistic regression models with stepwise AIC selection were performed. Results CeP during MA was inversely correlated with age (p < 0.05) and preoperative left pupillary latency (PL-L) (p < 0.005). CeP LoR was directly correlated with postoperative right pupillary diameter (PD-R) (p < 0.05). CeP at BSupp was inversely correlated with PL-L at BSupp and PL-L during MA (p < 0.05). CeP RoR) was inversely correlated with preoperative PL-L (p < 0.05). CeR during MA was inversely correlated with PD-R measured during MA and BMI (p < 0.05). POD occurred in 7.5% of patients and was associated with lower MCV-L (0.79mm/s vs 0.86mm/s; p<0.05) and MCV-R during MA (0.96mm/s vs 0.95mm/s; p<0.05), prolonged PD-R (1.93mm vs 1.88mm; p <0.01) during MA and prolonged postoperative PL-L (0.33s vs 0.23s; p<0.05) and PL-R (0.30s vs 0.23s; p<0.05), indicating perioperative autonomic and neurophysiological vulnerability. No independent predictors of POD were identified in multivariable analysis. Conclusions Our findings suggest that pupillometry is a promising, non-invasive tool for characterizing individual anaesthetic sensitivity and predicting anaesthetic concentration requirements and susceptibility to postoperative delirium. Preoperative PL may reflect central nervous system responsiveness and help anticipate hypnotic requirements, while intraoperative and postoperative pupillometric parameters could support early identification of patients at risk for delirium and guide tailored anaesthetic dosing and preventive strategies, although further validation in larger and more diverse populations is required.