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

Dunja Westhoff, Joost Witlox, Leo Koenderman, Kees J Kalisvaart, Jos F M de Jonghe, Mireille F M van Stijn, Alexander P J Houdijk, Inge C M Hoogland, Alasdair M J Maclullich, David J van Westerloo, Diederik van de Beek, Piet Eikelenboom, Willem A van Gool, Dunja Westhoff, Joost Witlox, Leo Koenderman, Kees J Kalisvaart, Jos F M de Jonghe, Mireille F M van Stijn, Alexander P J Houdijk, Inge C M Hoogland, Alasdair M J Maclullich, David J van Westerloo, Diederik van de Beek, Piet Eikelenboom, Willem A van Gool

Abstract

Background: Aging 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.

Methods: Patients 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.

Results: Sixty-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.

Conclusions: Our 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 registration: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.

Registration number: NCT00497978. Local ethical protocol number: NL16222.094.07.

Figures

Figure 1
Figure 1
Flowchart of study inclusion.

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