title: Associations Between Delirium and Preoperative Cerebrospinal Fluid C-Reactive Protein, Interleukin-6, and Interleukin-6 Receptor in Individuals with Acute Hip Fracture.
abstract: 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).
  
  
  
  Prospective cohort study.
  
  
  
  Two university hospitals in Oslo, Norway, and Edinburgh, United Kingdom.
  
  
  
  Individuals admitted with acute hip fracture (N = 151).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Bjørn Erik
authors.initials: BE
authors.lastname: Neerland
authors.affiliation: Edinburgh Delirium Research Group, University of Edinburgh, Edinburgh, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Roanna J
authors.initials: RJ
authors.lastname: Hall
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
authors.affiliation: Department of Orthopedic Surgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Frede
authors.initials: F
authors.lastname: Frihagen
authors.affiliation: Edinburgh Delirium Research Group, University of Edinburgh, Edinburgh, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Alasdair M J
authors.initials: AM
authors.lastname: MacLullich
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Anesthesiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Raeder
authors.affiliation: Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Torgeir Bruun
authors.initials: TB
authors.lastname: Wyller
authors.affiliation: Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.|Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Leiv Otto
authors.initials: LO
authors.lastname: Watne
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid*; D003693:Delirium / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015577:Geriatric Assessment; D006620:Hip Fractures / Q000150:complications* / Q000601:surgery; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid*; D008297:Male; D009664:Norway; D011446:Prospective Studies; D019947:Receptors, Interleukin-6 / Q000032:analysis*; D011795:Surveys and Questionnaires; D006113:United Kingdom
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D002097:C-Reactive Protein
keywords: C-reactive protein; cerebrospinal fluid; delirium; hip fracture; interleukin-6; soluble IL-6 receptor