Association of intraoperative dexamethasone administration with postoperative delirium and the role of hyperglycaemia: a retrospective cohort study.

Background: Postoperative delirium is a frequent, serious complication triggered by various factors including systemic inflammation. Dexamethasone, an inexpensive anti-inflammatory steroid frequently administered for prophylaxis of postoperative nausea and vomiting, attenuates inflammation. We hypothesised that intraoperative dexamethasone administration is associated with a lower risk of postoperative delirium and assessed whether this is modified by the occurrence of its key side effect, hyperglycaemia. Methods: This retrospective cohort study analysed electronic health data from adult hospitalised patients undergoing non-cardiac, non-neurosurgical, and non-transplant procedures at Beth Israel Deaconess Medical Center (Boston, MA, USA) between January 1, 2008, and January 15, 2024. Patients with missing data, preoperative delirium or glucocorticoid use, mechanical ventilation for 72 h or more, and those not expected to survive without the procedure, were excluded. The primary exposure was intraoperative administration of intravenous dexamethasone. The primary outcome was 7-day postoperative delirium, identified by keyword-triggered manual discharge note reviews, diagnostic codes, and the Confusion Assessment Method. Hyperglycaemia was defined as peak 24-h postoperative blood glucose of more than 180 mg/dL. All analyses were adjusted for 43 patient-related and procedure-related variables. Findings: 92,832 patients were included (55.8% female, median age 60 years [IQR 48-70]), of which 41,983 (45.2%) received dexamethasone at a median dose of 8 mg (IQR 4-8). 2575 (2.8%) patients developed postoperative delirium. Emergency procedures accounted for 11,970 (12.9%) of cases. Intraoperative administration of dexamethasone was associated with a lower risk of delirium (adjusted odds ratio [aOR] 0.63, 95% CI 0.56-0.70; p < 0.001; adjusted absolute risk difference -1.1%, 95% CI -1.3 to -0.8). The exploratory four-way mediation analysis suggested a 10.4% greater dexamethasone-associated reduction of postoperative delirium risk when hyperglycaemia did not occur (no hyperglycaemia aOR 0.59, 95% CI 0.51-0.67; p < 0.001; hyperglycaemia aOR 0.85, 95% CI 0.68-1.07; p = 0.17). Interpretation: Intraoperative dexamethasone administration is associated with a lower risk of postoperative delirium, although this association was not evident in patients experiencing hyperglycaemia. Prospective studies should investigate the role of dexamethasone and optimised blood glucose control in delirium prevention. Funding: Unrestricted philanthropic grant by Dr. J. and J. Buzen.