Cerebrospinal fluid cortisol and cytokines in delirium after hip fracture.

Introduction: Delirium is a serious and common condition affecting older people. The pathophysiology is incompletely understood and there are no specific treatments. Current hypotheses suggest involvement of exaggerated cortisol release in response to stressors, and amagnified central nervous system (CNS) inflammatory response to peripheral insults. The aim of this collaborative research project was to test the hypotheses that delirium is associated with increased cortisol, increased pro-inflammatory and reduced anti-inflammatory cytokines in cerebrospinal fluid (CSF). Methods: Participants with acute hip fracture were recruited at the Royal Infirmary of Edinburgh and Oslo University Hospital. Theywere assessed for delirium pre-operatively, and at regular intervals for two weeks post-operatively. CSF was collected at the spinal anaesthetic performed for their fracture repair. Cortisol was measured by Enzyme-linked immunosorbent assay, and a highsensitivity panel of cytokines by Luminex assay (Interleukin(IL)-1 , IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IFN, GM-CSF and TNF). Group comparisonswerewith Kruskal–Wallis or Student’s t-test, and logistic regression analysis was used to adjust for potential confounders. Results: Delirium was diagnosed in 68/148 participants (46%) in the cortisol assay and 38/76 (50%) in the cytokine assay. CSF cortisol was higher in those with prevalent delirium (median 36.5nmol/L, IQR26.3–53.1) than incident (30.0nmol/L (16.8–39.2)) or never delirium (27.2nmol/L (18.8–39.3)), p=0.023. CSF cortisol level above the median was still associated with delirium after adjusting for confounders. There were no differences observed in the levels of most cytokines between groups, but IL-5 was low in those with pre-operative delirium. Conclusions: These findings support the hypothesis that delirium is associated with exaggerated cortisol release, but provide little evidence of an exaggerated CNS inflammatory response. Prolonged high cortisol increases neuronal vulnerability to damage or death from various insults. Whether high cortisol is a cause or consequence of delirium merits further detailed investigation.