Risk factors for dementia in older intensive care unit (ICU) survivors.

INTRODUCTION: As the number of older intensive care unit (ICU) survivors grows, there is an urgent need to identify modifiable risk factors for post-ICU dementia. METHODS: We performed a secondary data analysis of 3144 ICU patients ≥ 50 years of age without a history of dementia or severe mental illness who were screened as part of the Pharmacological Management of Delirium (PMD) study. Delirium was assessed using the Confusion Assessment Method for the ICU. Dementia was identified using International Classification of Diseases Ninth and Tenth revision codes for dementia or prescription of anti-dementia medication. RESULTS: Average age (standard deviation) was 65.2 ± 9.5 years; 50.4% were female; and 37.3% were Black. Analyses identified stroke (adjusted hazard ratio [HR] 2.49; 95% confidence interval [CI: 1.52, 4.07], P < 0.001), and depression (adjusted HR 3.03; 95% CI [1.80, 5.10], P < 0.001) as post-ICU risk factors for dementia. DISCUSSION: Future studies will need to examine whether interventions targeting post-ICU stroke and depression can lower dementia incidence in ICU survivors. HIGHLIGHTS: Risk factors for post-intensive care unit (ICU) dementia were distinct from those of Alzheimer's disease. Cardiovascular risk factors were not associated with dementia in older ICU survivors. Post-ICU stroke was associated with a higher risk of dementia in older ICU survivors. Post-ICU depression was associated with a higher risk of dementia in older ICU survivors.

Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study.

OBJECTIVE: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU). PATIENTS: 178 ICU patients with delirium, alive and remaining in ICU at one week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. CONCLUSION: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.

Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19.

Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. DESIGN: Retrospective, observational cohort study. SETTING: ICUs at two large, urban, academic referral hospitals. PATIENTS: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17-2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02-1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14-1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08-2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04-1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14-2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03-1.79; p = 0.030) and delirium severity the next day (ß = 0.30; se, 0.07; p ≤ 0.01). CONCLUSIONS: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.