Factors Associated With Severity of Delirium Complicating COVID-19 in Intensive Care Units

Abstract

The clinical outcome of the disease provoked by the SARS-CoV-2 infection, COVID-19, is largely due to the development of interstitial pneumonia accompanied by an Acute Respiratory Distress Syndrome (ARDS), often requiring ventilatory support therapy in Intensive Care Units (ICUs). Current epidemiologic evidence is demonstrating that the COVID-19 prognosis is significantly influenced by its acute complications. Among these, delirium figures as one of the most frequent and severe, especially in the emergency setting, where it shows a significantly negative prognostic impact. In this regard, the aim of our study is to identify clinical severity factors of delirium complicating COVID-19 related-ARDS. We performed a comparative and correlation analysis using demographics, comorbidities, multisystemic and delirium severity scores and anti-delirium therapy in two cohorts of ARDS patients with delirium, respectively, due to COVID-19 (n = 40) or other medical conditions (n = 39). Our results indicate that delirium in COVID-19-related ARDS is more severe since its onset despite a relatively less severe systemic condition at the point of ICU admission and required higher dosages of antipsychotic and non-benzodiazepinic sedative therapy respect to non-COVID patients. Finally, the correlation analysis showed a direct association between the male gender and maximum dosage of anti-delirium medications needed within the COVID-19 group, which was taken as a surrogate of delirium severity. Overall, our results seem to indicate that pathogenetic factors specifically associated to severe COVID-19 are responsible for the high severity of delirium, paving the way for future research focused on the mechanisms of the cognitive alterations associated with COVID-19.

Keywords: ARDS; COVID-19; ICUs; cognition; delirium; prognosis; psychiatric symptoms.

Figure 1

Flowchart depicting the selection process of the patients.

Figure 2

Box plots showing the distribution of the variables resulted significantly different in the comparative analysis between the COV+/DEL+ and COV–/DEL+ groups. BIL, Bilirubin; CAM-S, Confusion Assessment Method—Short Version; HYD, hydroxyzine; PLT, platelets count; QUE, quetiapine; SOFA, Sepsis-related Organ Failure Assessment.

Figure 3

Visualization of the significant results from the correlations in the COV+/DEL+ group. Box plots represent the distribution of haloperidol (Figure 2A), quetiapine (Figure 2E) and hydroxyzine (Figure 2B) maximum dosages for each sex, SOFA scores in subjects assuming LOR vs. subjects not assuming LOR (Figure 2C). The scatter plot with regression line (Figure 2D) represents the distribution of P/F values vs. the maximum dose of alprazolam used. HAL, Haloperidol; HYD, Hydroxyzine; SOFA, Sepsis-related Organ Failure Assessment; P/F, PaO2/FIO2; QUE, Quetiapine; LOR, Lorazepam; ALP Alprazolam.

Figure 4

Visualization of the significant results from the correlations in the COV–/DEL+ group. Box plots represent the bilirubin levels distributions in subjects assuming LOR vs. subjects not assuming LOR (Figure 3A) and the distribution of different CAM-S scores at the onset of delirium in subjects assuming MID and in subjects not assuming MID (Figure 3B). The scatter plot with regression line (Figure 2D) represent age vs. maximum dose of quetiapine used.