The effect of delirium on the association between frailty and postoperative major complications in elderly patients: a mediation analysis

Purpose: Both preoperative frailty and postoperative delirium (POD) are associated with higher risk of postoperative complications. But it is unclear if the effect of preoperative frailty on postoperative complications was mediated by POD. Methods: This study was a mediation analysis of a pooled database. Patients aged >= 60 years who underwent elective non-cardiac surgery were enrolled. Preoperative frailty was defined as the modified frailty index (mFI) >= 0.27. POD was assessed twice daily within the first 3 days using the Confusion Assessment Method (CAM) for patients without intubation and the CAM for intensive care unit (CAM-ICU) for intubated patients. Major complications within postoperative 30 days were screened. Mediation analysis was employed to explore the relationships between frailty, POD, and postoperative complications. Results: A total of 4684 patients were included. The prevalence of frailty was 10.4% (489/4684). In comparison with non-frail patients, frail patients had a higher incidence of POD (12.7% [62/489] vs 6.5% [271/4195], RR = 2.102, 95% CI 1.568-2.819, P < 0.001) and more postoperative complications (21.5% [105/489] vs 16.7% [701/4195], RR = 1.363, 95% CI 1.082-1.716, P = 0.008). The adjusted total and direct associations between frailty and postoperative complications were 5.8% (adjusted beta, 95% CI, 1.8-9.5%; P < 0.001) and 5.0% (adjusted beta, 95% CI, 1.1-8.7%; P = 0.004), respectively. A significant indirect association via POD was observed (adjusted beta = 0.8%; 95% CI, 0.3-1.4%; P < 0.001), accounting for 13.8% of the total effect. Conclusion: Preoperative frailty is associated with an increased risk of postoperative complications, mediated in part by early POD, in elderly patients following non-cardiac surgery. Given the modest effect size, further research is warranted to confirm these findings.