Time-course of cytokines during delirium in elderly patients with hip fractures

OBJECTIVES: To compare the time-course of cytokine levels in patients with and without delirium and investigate differences in cytokine concentrations in delirium subtypes. DESIGN: Prospective cohort study. SETTING: Academic Medical Center, Amsterdam, 2005 through 2007. PARTICIPANTS: Patients aged 65 and older admitted for surgery after hip fracture. MEASUREMENTS: Experienced geriatric physicians used the Confusion Assessment Method to assess delirium and the Delirium Symptom Interview to assess delirium subtype. Tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and IL-12 were assayed in repeated serum samples using a cytometric bead array immunoassay. RESULTS: Of 221 admitted patients, 98 (mean age 84, 50 patients with delirium) were included, resulting in a total of 324 samples. Ninety-six percent of these samples had TNF-alpha, IL-1 beta, and IL-10 levels below the reliable detection level. Differences between patients with and without delirium were observed in IL-6 (median 51 vs 36 pg/mL, P=.01) and IL-8 (median 15 vs 9 pg/mL, P=.03) levels. Changes over time in IL-6 and IL-8 levels in patients with delirium differed significantly from changes in levels in patients without delirium. The highest levels of IL-6 were present during delirium, and the highest levels of IL-8 were present before the development of delirium. Patients with the hyperactive (median 71 pg/mL) or mixed (median 73 pg/mL) subtype of delirium had higher IL-6 levels than patients with hypoactive delirium (median 16 pg/mL) (P=.02). CONCLUSION: IL-6 and IL-8 may contribute to the pathogenesis of postoperative delirium in elderly people. IL-6 may play a role in the hyperactive behavior of delirium.