Background: Postoperative delirium (POD) might be associated with anesthetic management, but research has focused on choice or dosage of anesthetic drugs. We examined potential contributions of intraoperative ventilatory and hemodynamic management to POD. Methods: This was a sub-study of the ENGAGES-Canada trial (NCT02692300) involving non-cardiac surgery patients enrolled in Winnipeg, Canada. Patients received preoperative psychiatric and cognitive assessments, and intraoperatively underwent high-fidelity data collection of blood pressure, end-tidal respiratory gases and anesthetic agent concentration. POD was assessed by peak and mean POD scores using the Confusion Assessment Method-Severity (CAM-S) tool. Bivariate and multiple linear regression models were constructed controlling for age, psychiatric illness, and cognitive dysfunction in the examination of deviations in intraoperative end-tidal carbon dioxide (areas over (AOC) and under the curve (AUC)) on POD severity scores. Results: A total of 101 subjects [69 (6) years of age] were studied; 89 had comprehensive intraoperative hemodynamic and end-tidal gas measurements (data recorded at 1 Hz). The incidence of POD was 11.9% (12/101). Age, cognitive dysfunction, anxiety, depression, and intraoperative end-tidal CO₂ (AUC) were significant correlates of POD severity. In the multiple regression model, cognitive dysfunction and AUC end-tidal CO₂ (0.67 kPa below median intra-operative value) were the only independent significant predictors across both POD severity (mean and peak) scores. There was no association between cumulative anesthetic agent exposure and POD. Conclusions: POD was associated with intraoperative ventilatory management, reflected by low end-tidal CO₂ concentrations, but not with cumulative anesthetic drug exposure. These findings suggest that maintenance of intraoperative normocapnia might benefit patients at risk of POD.

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