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

Sikandar H Khan; Anthony J Perkins; Rosalyn Chi; Sarah Seyffert; Peter Conrad; Heidi Lindroth; Sophia Wang; Malissa Mulkey; Sujuan Gao; Babar Khan

doi:10.1097/CCE.0000000000000851

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

Crit Care Explor. 2023 Jan 18;5(1):e0851. doi: 10.1097/CCE.0000000000000851. eCollection 2023 Jan.

Authors

Sikandar H Khan^{1

2}, Anthony J Perkins³, Rosalyn Chi¹, Sarah Seyffert¹, Peter Conrad⁴, Heidi Lindroth⁵, Sophia Wang⁶, Malissa Mulkey⁷, Sujuan Gao³, Babar Khan^{1

2}

Affiliations

¹ Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
² Indiana University Center for Aging Research, Regenstrief Institute, Indianapolis, IN.
³ Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN.
⁴ Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN.
⁵ Department of Nursing, Mayo Clinic, Rochester, MN.
⁶ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN.
⁷ Indiana University School of Nursing, Indianapolis, IN.

Abstract

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.

Keywords: COVID-19; biomarkers; coma; critical care; delirium; delirium severity.

Abstract

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