Specific antagonist of receptor for advanced glycation end­products attenuates delirium­like behaviours induced by sevoflurane anaesthesia with surgery in aged mice partially by improving damage to the blood­brain barrier.

Postoperative delirium (POD), which occurs in hospital up to 1-week post-procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood-brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end-products (RAGE) expression and ß-amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD-like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD-like behaviour. FPS-ZM1, a specific RAGE antagonist, ameliorated POD-like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS-ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD.

Incidence and risk factors of delirium in critically ill patients after non-cardiac surgery.

BACKGROUND: Delirium is a common and deleterious complication in critically ill patients after surgery. The purpose of this study was to determine the incidence and risk factors of delirium in critically ill patients after non-cardiac surgery, and to investigate the relationship between the serum cortisol level and the occurrence of postoperative delirium. METHODS: In a prospective cohort study, 164 consecutive patients who were admitted to the surgical intensive care unit after non-cardiac surgery were enrolled. Baseline characteristics and perioperative variables were collected. Blood samples were obtained on the first postoperative day and serum cortisol concentrations were measured. Delirium was assessed using the Nursing Delirium Screening Scale until the seventh postoperative day or the disappearance of delirious symptoms. RESULTS: Postoperative delirium occurred in 44.5% of patients (73 of 164). The median time to first onset of delirium is 0 (range 0 to 5 days) and the median duration of delirium is 3 (1 to 13) days. Independent risk factors of postoperative delirium included increasing age (odds ratio (OR) 2.646, 95% confidence interval (CI) 1.431 to 4.890, P = 0.002), a history of previous stroke (OR 4.499, 95%CI 1.228 to 16.481, P = 0.023), high Acute Physiology and Chronic Health Evaluation II score on surgical intensive care unite admission (OR 1.391, 95%CI 1.201 to 1.612, P < 0.001), and high serum cortisol level on the 1st postoperative day (OR 3.381, 95%CI 1.690 to 6.765, P = 0.001). The development of delirium was linked to higher incidence of postoperative complications (28.8% vs. 7.7%, P < 0.001), and longer duration of hospitalization (18 (7 to 74) days vs. 13 (3 to 48) days, P < 0.001). CONCLUSIONS: Delirium was a frequent complication in critically ill patients after non-cardiac surgery. High serum cortisol level was associated with increased incidence of postoperative delirium.