Seyffert, Sarah

OBJECTIVES: 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 (β = 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.

Abstract Background: Delirium is a highly prevalent and morbid syndrome in mechanically ventilated intensive care unit (ICU) patients. Music is a promising non-pharmacological intervention with beneficial effects on anxiety and stress, while its effects on delirium duration and severity are not well understood.Methods/design: Our study is a two-arm, randomized parallel-group, clinical trial to evaluate the efficacy of music intervention compared to a silence-track attention control on delirium/coma duration in mechanically ventilated critically ill older adults. One-hundred-sixty mechanically ventilated adults 50 years of age or older will be randomized to one of two arms within 72 hours of ICU admission: (1) one-hour music listening sessions twice daily through noise-cancelling headphones, or (2) one-hour sessions of a silence track twice daily through noise-cancelling headphones. Our primary aim is to compare delirium/coma free days after randomization during the 7-day study intervention phase using the Confusion Assessment Method for the ICU (CAM ICU) and the Richmond Agitation Sedation Scale (RASS) for delirium and coma. Secondary outcomes include pain and anxiety evaluated twice daily during the intervention phase and throughout the duration of ICU stay using the Critical Care Pain Observation Tool (CPOT) and Visual Analogue Scale-Anxiety (VAS-A). Enrolled participants will be followed after hospital discharge to further measure cognition as well as screening for depression and anxiety using the following telephone-based instruments: Indiana University Telephone-Based Assessment of Neuropsychological Status (IU TBANS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7).Discussion: This randomized clinical trial will measure the efficacy of a music listening intervention for delirium and coma duration early in the intensive care unit among older adults.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04182334