Preoperative plasma bilirubin may be associated with postoperative delirium in old patients undergoing knee/hip arthroplasty: the PNDRFAP study and the PNDABLE study
Authors: Hua Shuhui , Wang Yuanlong , Xu Shanling , Kong Jian , Gong Hongyan , Dong Rui , Lin Yanan , Li Chuan , Wang Bin , Lin Xu , Bi Yanlin 
Published: February 2024

Background Along with society'saging, the prevalence rate of postoperative delirium (POD) is increasing. Assessing the risk factors of delirium is essential to diagnose and treatpostoperative delirium (POD). The aim of this study was to examine the correlation between bilirubin levels and postoperative delirium.
Methods This study included 621 patients, of whom were from the Perioperative Neurocognitive Impairment and Biomarker Lifestyle (PNDABLE) database. The remaining 577 patients were from the Perioperative Neurocognitive Impairment Risk Factors and Prognosis (PNDRFAP) study. The Mini-Mental State Examination (MMSE) and Confusion Assessment Method (CAM) were used to assess cognitive function before operation, while Memorial Delirium Assessment Scale (MDAS) was used to measure the severity of postoperative delirium (POD). Cerebrospinal fluid biomarkers, including Aβ42, T-tau, P-tau, Aβ42/T-tau, and Aβ42/P-tau, were measured using enzyme-linked immunosorbent assay (ELISA). We conducted logistic regression using data from patients in the PNDRFAP study and the PNDABLE study，which collectively identified risk factors for postoperative cognitive impairment. Nomograms and ROC curves were used as evaluation indices to assess the predictive effect of bilirubin on postoperative delirium (POD). POD events can be predicted by creating a dynamic nomogram model of the network. Finally, a mediation analysis of 10,000 bootstrap iterations was conducted to assess the mediating role of CSF biomarkers.
Results The logistic regression models of the PNDABLE and PNDRFAP studies showed that total bilirubin, direct bilirubin and indirect bilirubin were higher in the postoperative delirium group than in the non-postoperative delirium group. These results suggest that total bilirubin, direct bilirubin and indirect bilirubin may be risk factors for delirium. [PNDRFAP: Total Bilirubin, OR (95% CI): 1.839 (1.645-2.056), P < 0.001; Direct Bilirubin, OR (95% CI): 1.725 (1.448-2.054), P < 0.001; Indirect Bilirubin, OR (95% CI): 1.558 (1.424-1.705), P < 0.001. PNDABLE: Total Bilirubin, OR (95% CI): 1.203 (1.137-1.274), P < 0.001; Direct Bilirubin, OR (95% CI): 1.724 (1.465-2.030), P < 0.001; Indirect Bilirubin, OR (95% CI): 1.182 (1.109-1.260), P < 0.001]. Adjusted for age, sex, educational level and MMSE, total bilirubin, direct bilirubin and indirect bilirubin remained related to POD. Mediation analysis indicted that T-tau mediated the effect of total bilirubin, direct bilirubin and indirect bilirubin on delirium. The respective proportions are 9.08%, 10.26% and 8.70%.
Conclusions Total bilirubin, direct bilirubin and indirect bilirubin are preoperative risk factors associated with an increased risk of postoperative delirium (POD). The association between bilirubin and postoperative delirium may be partly attributed to T-tau levels in cerebrospinal fluid.
Clinical Trial Registration Clinical Registration No. ChiCTR2000033439.