Frailty increases vulnerability to postoperative cognitive dysfunction following general anesthesia in aged rats

Background:Based on previous studies showing that frailty is associated with postoperative adverse events in older patients undergoing various surgical procedures, older patients with frailty may be more vulnerable to POCD.This study was designed to evaluate the effect of frailty on postoperative cognitive dysfunction (POCD) in aged rats undergoing general anaesthesia.Methods: Male Sprague-Dawley rats aged 18 months were allocated to Control and Frailty groups according to hind limb immobilisation using aluminium splints.Before and after general anaesthesia, Ymaze test for cognitive function and frailty status were evaluated.Frailty, including muscle atrophy, assessed by quadriceps weight, was further evaluated by measuring glutathione peroxidase 4 (GPX4) and threonine.Results: Twenty rats were enrolled and evenly allocated between the two groups, with no dropouts.There was no significant difference in the alternation ratio in the Y maze test between the groups before general anaesthesia; however, a significant difference was observed two days after general anaesthesia (65% ± 37% in the Control group vs 29% ± 28% in the Frailty group, p = 0.01).Body weight was similar between the groups throughout the study.By contrast, quadriceps weight was significantly lower in the Frailty group [2.4 (2.3-2.6)g vs 2.0 (1.7-2.3)g, p = 0.0001].GPX4 and threonine levels in the quadriceps were also significantly lower in the Frailty group.Conclusion: Frailty was significantly associated with POCD.Prevention of frailty may be important for reducing the risk of POCD.