ObjectiveExaggerated central nervous system (CNS) inflammatory responses to peripheral stressors may be implicated in delirium. This study hypothesised that the IL-1β family is involved in delirium, predicting increased levels of interleukin-1β (IL-1β) and decreased IL-1 receptor antagonist (IL-1ra) in the cerebrospinal fluid (CSF) of elderly patients with acute hip fracture. We also hypothesised that Glial Fibrillary Acidic Protein (GFAP) and interferon-γ (IFN-γ) would be increased, and insulin-like growth factor 1 (IGF-1) would be decreased.MethodsParticipants with acute hip fracture aged > 60 (N = 43) were assessed for delirium before and 3–4 days after surgery. CSF samples were taken at induction of spinal anaesthesia. Enzyme-linked immunosorbent assays (ELISA) were used for protein concentrations.ResultsPrevalent delirium was diagnosed in eight patients and incident delirium in 17 patients. CSF IL-1β was higher in patients with incident delirium compared to never delirium (incident delirium 1.74 pg/ml (1.02–1.74) vs. prevalent 0.84 pg/ml (0.49–1.57) vs. never 0.66 pg/ml (0–1.02), Kruskal–Wallis p = 0.03). CSF:serum IL-1β ratios were higher in delirious than non-delirious patients. CSF IL-1ra was higher in prevalent delirium compared to incident delirium (prevalent delirium 70.75 pg/ml (65.63–73.01) vs. incident 31.06 pg/ml (28.12–35.15) vs. never 33.98 pg/ml (28.71–43.28), Kruskal–Wallis p = 0.04). GFAP was not increased in delirium. IFN-γ and IGF-1 were below the detection limit in CSF.ConclusionThis study provides novel evidence of CNS inflammation involving the IL-1β family in delirium and suggests a rise in CSF IL-1β early in delirium pathogenesis. Future larger CSF studies should examine the role of CNS inflammation in delirium and its sequelae.

Delirium is often precipitated by peripheral infection or injury, but the causal pathways remain unclear. One hypothesis is that the central nervous system (CNS) changes resulting in delirium are triggered by peripheral inflammation induced by such insults. 1;2 Indeed, several studies have linked altered serum inflammatory markers with delirium. Higher serum levels of interleukin (IL)-6 and IL-8 were reported in hip fracture patients with delirium compared to controls, 3;4 and other studies have reported elevated inflammatory markers such as C-reactive protein and interferon gamma, and reduced anti-inflammatory markers such as insulin-like growth factor 1 and IL-1ra in delirium. 5;6 With ageing, particularly where there is neurodegeneration, CNS immune cells show exaggerated production of pro-inflammatory cytokines in response to peripheral stimulation, providing a possible causal pathway from the periphery to CNS dysfunction and consequent delirium. 2 This has been demonstrated in several animal studies 1;2 but whether there are elevations in CNS pro-inflammatory cytokines in patients with delirium not caused by primary CNS disorders is unknown. Here we compared levels of interleukin (IL)1β, IL-6, IL-8, IL-10 and IL-12p70, and tumor necrosis factor alpha (TNF-α) in the cerebrospinal fluid (CSF) and serum of older hip fracture patients with and without peri-operative delirium. We hypothesized that cases would have higher levels of pro-inflammatory cytokines.Thirty-six patients (28 female) in two university-affiliated hospitals (Edinburgh, Scotland and Amsterdam, the Netherlands) aged 62-93 years with hip fracture and awaiting surgery were assessed for delirium before and 3-4 days after surgery. Delirium was assessed with the Confusion Assessment Method; patients with delirium at any stage were considered cases. CSF in all patients, and serum in the 16 Edinburgh patients, were obtained at the onset of spinal anesthesia as previously described. 7 CSF and serum samples were spun at 1000g for 10 minutes at 4°C; supernatants were stored at −80°C. Cytokine levels were measured with a cytometric bead array immunoassay (Human Inflammatory Cytokine Kit, BD Biosciences) with a detection limit of 20.0 pg/mL; levels below this limit were considered to be zero. Case versus control comparisons were analyzed using the Mann-Whitney U-test. The study was approved by the local ethics committees.Delirium was diagnosed in 15 patients. Nine had delirium pre-operatively, and seven further patients developed delirium post-operatively; one patient who had pre-operative delirium recovered after surgery. Mean ages and Charlson Comorbidity Index scores did not differ between the cases and controls. A history of dementia (N=7) was associated with a higher incidence of delirium (p=0.008).Only IL-8 and IL-6 were detected in CSF with levels above the assay detection limit: IL-8 in 33/36 samples, and IL-6 in 3/36 samples (IL-6 levels were not further analyzed). Delirium cases (N=15) had higher CSF IL-8, with median (IQR) of 69.8 pg/mL (47.9...

(Anesth Analg. 2020;130:1296–1302) Over the last 2 decades, rates of women entering medical school have risen to near parity with men. However, despite gender equivalence in medical school enrollment, rates of female anesthesiologists lag severely behind. Though data are lacking in anesthesiology, causes of the leadership and specialty gaps for surgical residencies have been reviewed in recent publications, finding potential deterrents such as changing career plans due to motherhood, lack of formally institutionalized maternity leave policies, gender discrimination, perceived stigma associated with pregnancy, and perceived incompatibility of surgery with rewarding family life. In congruence with these findings for surgery, a study of major medical specialties determined anesthesiology to have the highest rate of maternal discrimination. The aim of this study was to survey women members of the American Society of Anesthesiologists (ASA) to better understand motherhood-related factors associated with women’s likelihood to recommend against a career in anesthesiology.

BackgroundHigh plasma cortisol levels can cause acute cognitive and neuropsychiatric dysfunction, and have been linked with delirium. CSF cortisol levels more closely reflect brain exposure to cortisol, but there are no studies of CSF cortisol levels in delirium. In this pilot study we acquired CSF specimens at the onset of spinal anaesthesia in patients undergoing hip fracture surgery, and compared CSF and plasma cortisol levels in delirium cases versus controls.FindingsDelirium assessments were performed the evening before or on the morning of operation with a standard battery comprising cognitive tests, mental status assessments and the Confusion Assessment Method. CSF and plasma samples were obtained at the onset of the operation and cortisol levels measured. Twenty patients (15 female, 5 male) aged 62 - 93 years were studied. Seven patients were diagnosed with delirium. The mean ages of cases (81.4 (SD 7.2)) and controls (80.5 (SD 8.7)) were not significantly different (p = 0.88). The median (interquartile range) CSF cortisol levels were significantly higher in cases (63.9 (40.4-102.1) nmol/L) than controls (31.4 (21.7-43.3) nmol/L; Mann-Whitney U, p = 0.029). The median (interquartile range) of plasma cortisol was also significantly higher in cases (968.8 (886.2-1394.4) nmol/L, than controls (809.4 (544.0-986.4) nmol/L; Mann Whitney U, p = 0.036).ConclusionsThese findings support an association between higher CSF cortisol levels and delirium. This extends previous findings linking higher plasma cortisol and delirium, and suggests that more definitive studies of the relationship between cortisol levels and delirium are now required.