Inflammatory Indices and Their Associations with Postoperative Delirium

Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (eg, mortality); however, inflammatory indices have not yet been examined in delirium. Four inflammatory markers, C-reactive protein, interleukin-6, soluble tumor necrosis factor alpha receptor-1, and chitinase-3 like protein-1, were measured preoperatively and on postoperative day 2 in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, 4 inflammatory indices were considered: (i) quartile summary score, (ii) weighted summary score, (iii) principal component score, and (iv) a well-established inflammatory (least absolute shrinkage and selection operator-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method, supplemented by chart review. Generalized linear models with a log-link term were used to determine the association between each inflammatory index and delirium incidence. Among the inflammatory indices, the weighted summary score demonstrated the strongest association with delirium: participants in the weighted summary score quartile (Q)4 had a higher risk of delirium versus participants in Q1, after clinical variable adjustment (relative risk, 95% confidence interval for preoperatively: 3.07, 1.80-5.22; and postoperative day 2: 2.65, 1.63-4.30). The weighted summary score was more strongly associated with delirium than the strongest associated individual inflammatory marker (preoperatively chitinase-3 like protein-1 [relative risk 2.45, 95% confidence interval 1.53-3.92]; postoperative day 2 interleukin-6 [relative risk 2.39, 95% confidence interval 1.50-3.82]). A multi-protein inflammatory index using a weighted summary score provides a slight advantage over individual inflammatory markers in their association with delirium.