Associations Between Delirium and Preoperative Cerebrospinal Fluid C-Reactive Protein, Interleukin-6, and Interleukin-6 Receptor in Individuals with Acute Hip Fracture

J Am Geriatr Soc. 2016 Jul;64(7):1456-63. doi: 10.1111/jgs.14238. Epub 2016 Jun 24.


Objectives: To examine whether delirium in individuals with hip fracture is associated with high C-reactive protein (CRP), interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R) levels in the cerebrospinal fluid (CSF).

Design: Prospective cohort study.

Setting: Two university hospitals in Oslo, Norway, and Edinburgh, United Kingdom.

Participants: Individuals admitted with acute hip fracture (N = 151).

Measurements: Participants were assessed for delirium pre- and postoperatively using the Confusion Assessment Method. Prefracture cognitive impairment was detected using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Serum was collected preoperatively and CSF just before the onset of spinal anesthesia. Cytokine levels in serum and CSF samples were determined using an enzyme-linked immunosorbent assay. Student t-tests or Mann-Whitney U-tests were used for between-group comparisons. Spearman rho was used for correlations.

Results: Sixty participants had prior cognitive impairment (IQCODE score ≥3.44). Delirium was diagnosed in 46 participants (77%) with prior cognitive impairment and 25 (29%) without. In participants without prior cognitive impairment, CSF CRP levels were higher in participants with delirium (median 0.05 μg/mL, interquartile range (IQR) 0.02-0.12 μg/mL) than in those without delirium (median 0.01 μg/mL, IQR 0.00-0.06 μg/mL) (P = .01); there were no differences in participants with prior cognitive impairment. In secondary analyses, in participants with prior cognitive impairment, the concentration of CSF sIL-6R was higher in those participants who developed delirium than in the other subgroups, but this difference was not statistically significant. Serum levels of CRP, IL-6, and sIL-6R were not different according to delirium in participants with or without prefracture cognitive impairment.

Conclusion: High CSF levels of CRP and sIL-6R may be associated with delirium. Different pathophysiological mechanisms may operate in different subgroups, notably in relation to the presence of prior cognitive impairment.

Keywords: C-reactive protein; cerebrospinal fluid; delirium; hip fracture; interleukin-6; soluble IL-6 receptor.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / cerebrospinal fluid*
  • Delirium / cerebrospinal fluid*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Geriatric Assessment
  • Hip Fractures / complications*
  • Hip Fractures / surgery
  • Humans
  • Interleukin-6 / cerebrospinal fluid*
  • Male
  • Norway
  • Prospective Studies
  • Receptors, Interleukin-6 / analysis*
  • Surveys and Questionnaires
  • United Kingdom


  • Interleukin-6
  • Receptors, Interleukin-6
  • C-Reactive Protein