Oxidative stress and soluble receptor for advanced glycation end-products play a role in the pathophysiology of delirium after cardiac surgery

Abstract

Coronary-artery bypass graft (CABG) surgery is known to improve cardiac function and decrease mortality, albeit, this method of treatment is also associated with a neuropsychiatric complications including postoperative delirium. The pathophysiology of delirium after cardiac surgery remains poorly understood. Thus, the purpose of this study was to investigate whether oxidative stress reflected by decreased preoperative and postoperative plasma antioxidant activity is independently associated with delirium after cardiac surgery. The second aim was to assess whether decreased antioxidant activity is stress-related or mediated by other pathologies such as major depressive disorder (MDD), anxiety disorders, and cognitive impairment. Furthermore, the putative relationship between pre- and postoperative soluble receptor for advanced glycation end-products (sRAGE) overexpression and plasma antioxidant capacity was evaluated. The patients cognitive status was assessed 1 day preoperatively with the use of the Mini-Mental State Examination Test and the Clock Drawing Test. A diagnosis of MDD and anxiety disorders was established on the basis of DSM-5 criteria. Blood samples for antioxidant capacity and sRAGE levels were collected both preoperatively and postoperatively. The Confusion Assessment Method for the Intensive Care Unit was used within the first 5 days postoperatively to screen for a diagnosis of delirium. Postoperative delirium was diagnosed in 34% (61 of 177) of individuals. Multivariate logistic regression analysis revealed that low baseline antioxidant capacity was independently associated with postoperative delirium development. Moreover, increased risk of delirium was observed among patients with a preoperative diagnosis of MDD associated with antioxidant capacity decreased postoperatively. According to receiver operating characteristic analysis, the most optimal cutoff values of the preoperative and postoperative antioxidant capacity that predict the development of delirium were 1.72 mM and 1.89 mM, respectively. Pre- and postoperative antioxidant capacity levels were negatively correlated with postoperative sRAGE concentration (Spearman's Rank Correlation − 0.198 and − 0.158, p < 0.05, respectively). Patients with decreased preoperative antioxidant activity and those with depressive episodes complicated with lower postoperative antioxidant activity are at significantly higher risk of delirium after cardiac surgery development. sRAGE overexpression may be considered as protective mechanism against increased oxidative stress and subsequent cell damage.

Reactive oxygen species contribute to delirium-like behavior by activating CypA/MMP9 signaling and inducing blood-brain barrier impairment in aged mice following anesthesia and surgery

“…ROS produced excessively would mediate detrimental effects, which are known as oxidative stress ( Rosenfeldt et al, 2013 ). It has been demonstrated that perioperative oxidative stress is associated with the increased risk of postoperative delirium ( Karlidag et al, 2006 ; Lopez et al, 2017 , 2020 ; Kazmierski et al, 2021 ). Similarly, in the present study, we found that anesthesia/surgery induced ROS accumulation and delirium-like behavior, while the ROS scavenger NAC attenuated these changes.…”

Anxiety as a Risk Factor for Postoperative Delirium in Elective Spine Deformity Surgeries: A National Database Study

“…In a study by Kazmerski et al examining the relationship between oxidative stressors and the development of postoperative delirium, it was found that pre- and postoperative soluble receptors for advanced glycation end-product (sRAGE) levels were significantly higher in the delirium group compared to the non-delirium subjects. It was also found that preoperative sRAGE levels were significantly increased in patients with anxiety disorders [ 13 ]. Kazmerski et al further elicited a significant relationship between decreased oxidative stress capacity and the development of postoperative delirium; however, there were no significant findings of differences between pre- and post-operative antioxidant activity in patients with and without anxiety disorders [ 13 ].…”

“…It was also found that preoperative sRAGE levels were significantly increased in patients with anxiety disorders [ 13 ]. Kazmerski et al further elicited a significant relationship between decreased oxidative stress capacity and the development of postoperative delirium; however, there were no significant findings of differences between pre- and post-operative antioxidant activity in patients with and without anxiety disorders [ 13 ]. The limited data available suggests there may be a link between the development of postoperative delirium and patients who are suffering from anxiety due to increased advanced glycosylation end products.…”

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

“…The relationship between pre-and post-operative sRAGE and delirium was examined following cardiac surgery [134]. Delirium is accompanied by symptoms such as psychosis, confusion, and depression.…”