Tocilizumab is associated with reduced delirium and coma in critically ill patients with COVID-19.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Antibodies, Monoclonal, Humanized*/therapeutic use ; Delirium*/drug therapy ; COVID-19*/complications ; COVID-19*/mortality ; Coma*/etiology ; Coma*/drug therapy ; Critical Illness*; Humans ; Male ; Female ; Middle Aged ; Aged ; COVID-19 Drug Treatment ; Intensive Care Units ; SARS-CoV-2/isolation & purification ; Interleukin-6

Recent preclinical studies demonstrate a direct pathological role for the interleukin-6 (IL-6) pathway in mediating structural and functional delirium-like phenotypes in animal models of acute lung injury. Tocilizumab, an IL-6 pathway inhibitor, has shown reduced duration of ventilator dependency and mortality in critically ill patients with COVID-19. In this study, we test the hypothesis that tocilizumab is associated with reduced delirium/coma prevalence in critically ill patients with COVID-19. 253 patients were included in the study cohort, 69 in the tocilizumab group and 184 in the historical control group who did not receive tocilizumab. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) with a positive score indicating delirium. Coma was defined as a Richmond Agitation-Sedation Scale score of - 4 or - 5. Tocilizumab was associated with significantly greater number of days alive without delirium/coma (tocilizumab [7 days (IQR: 3-9 days)] vs control [3 days (IQR: 1-8 days)]; p < 0.001). These results remained significant after adjusting for age, sex, sepsis, Charlson Comorbidity Index, Sequential Organ Failure Assessment score, and median daily dose of analgesics/sedatives ( β ^  = 0.671, p = 0.010). There were no significant differences in mortality ( β ^  = - 0.204, p = 0.561), ventilator duration ( β ^  = 0.016, p = 0.956), and ICU or hospital length of stay ( β ^  = - 0.134, p = 0.603; β ^  = 0.003, p = 0.991, respectively). Tocilizumab use was associated with significantly increased number of days without delirium/coma. Confirmation of these findings in randomized prospective studies may inform a novel paradigm of pharmacological amelioration of delirium/coma during critical illness.
(© 2024. The Author(s).)

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R01 AG035117 United States NH NIH HHS; R01 AG058639 United States NH NIH HHS; I01 RX002992 United States RX RRD VA; I01RX002992 United States NH NIH HHS; R01 AG027472 United States NH NIH HHS

Keywords: COVID-19; Delirium; ICU; Interleukin-6; Sars-CoV-2; Tocilizumab

0 (Antibodies, Monoclonal, Humanized)
I031V2H011 (tocilizumab)
0 (Interleukin-6)

Date Created: 20240522 Date Completed: 20240522 Latest Revision: 20240525

20240525

PMC11111809

10.1038/s41598-024-62505-1

38778074