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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 and prolonged cortisol and pro-inflammatory cytokine release in response to stressors.
This study aimed to test the hypotheses that delirium is associated with increased cortisol levels and loss of cortisol diurnal rhythm, and with increased pro-inflammatory cytokines.
Methods Participants with acute hip fracture were recruited at the Royal Infirmary of Edinburgh. They were assessed for delirium pre-operatively, and regularly for two weeks post-operatively. Morning serum and diurnal saliva samples were collected pre-operatively and on post-operative days 4 and 10-14, with additional saliva samples on day 7. Cortisol was measured by Enzyme-linked immunosorbent assay, and a panel of cytokines by Luminex assay (Interleukin(IL)-1β, IL-1ra, IL-5, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, and TNF-α). Group comparisons were with Mann-Whitney U test. Logistic regression modelling was used to examine the relationship between delirium and longitudinal log-transformed cortisol level and cortisol AM:PM ratio, adjusting for confounders.
Results Delirium was diagnosed in 42/104 participants (40.4%). Serum cortisol was higher in the delirium group, and this was significant for those with active delirium on day 4. PM salivary cortisol was significantly higher in the delirium group on days 4 and 7. Morning cortisol was associated with delirium after adjusting for age, gender, illness severity, co-morbidity and dementia. The delirium group had higher levels of serum IL-1ra, IL-6, IL-8 and TNF-α, and a higher pro:anti-inflammatory ratio.
Conclusions These findings support the hypothesis that delirium is associated with increased cortisol and attenuation of the normal nadir of cortisol diurnal rhythm, and that there is a shift towards a pro-inflammatory state. Future studies could investigate ways to attenuate this, such as the use of 11-β hydroxysteroid dehydrogenase inhibitors.