Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients

Abstract

BackgroundAging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery.MethodsPatients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann–Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses.ResultsSixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively.ConclusionsOur findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process.Trial registrationThe Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.Registration number: NCT00497978. Local ethical protocol number: NL16222.094.07.

C-reactive protein is an independent predictor for 1-year mortality in elderly patients undergoing hip fracture surgery

“…Postoperative CRP is a sensitive marker for detecting postoperative complications, especially delirium, in elderly patients undergoing hip fracture surgery. [ 20 21–25 ] In agreement with previous studies, our results showed that patients with postoperative delirium had higher pre- and postoperative CRP levels than did those without. Delirium per se is associated with an increased risk of death in elderly patients with hip fractures.…”

The interface between delirium and dementia in elderly adults

“…These findings suggest that the underlying mechanisms governing the development of delirium in patients with inflammation may differ from those without inflammation. 68 Others have found cytokines such as insulin-like growth factor (IGF)-1, IL-1β and IL-1 receptor antagonist (RA) to be associated with delirium, 69-71 and high levels of interferon (IFN-γ) with low levels of IGF-1 were associated with delirium severity. 72 S100B, a marker of astrocyte damage, has been shown to be elevated in delirium, both in plasma and in CSF.…”

Sleep Disruption at Home As an Independent Risk Factor for Postoperative Delirium

“…Delayed or impaired sleep can cause disruption of the circadian rhythm, which has been associated with delirium . Rodent studies demonstrate that sleep disruption impairs innate immune defense, which may lead to the inflammatory dysregulation associated with postoperative delirium . Sleep, then, may contribute over the long term to the integrity of brain homeostatic mechanisms that enable resilience in the face of stressors such as surgery.…”