Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

Abstract

Background: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae.

Methods: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression.

Findings: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU.

Interpretation: Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.

Funding: None.

Translations: For the French and Spanish translations of the abstract see Supplementary Materials section.

Figure 1

Study flow diagram ICU=intensive care unit. *All patients who were COVID-19 positive and admitted to an ICU from the first reported case in each ICU until April 28th, 2020, were considered for inclusion.

Figure 2

Mental status and respiratory support status in the 21-day study period (n=2088) (A) Mental status over time. Coma was defined as a day when the patients were unresponsive to verbal stimulation (Richmond Agitation-Sedation Scale score of –4 or –5 or Glasgow Coma Scale score of <8). Patients were considered delirious if they had a positive delirium assessment scale assessment (Confusion Assessment Method for the Intensive Care Unit or the Intensive Care Delirium Screening Checklist) documented. All other patients were considered awake without delirium. Discharge represents discharge from the intensive care unit. (B) Respiratory status over time. ICU=intensive care unit.

Figure 3

Forest plot of daily probability of delirium All patients who had at least 90% delirium or coma assessments during their index ICU stay and 2 days of ICU stay were included in this analysis (n=2049). Other states, such as comatose, awake without delirium, deceased, and discharged (from index ICU) were considered as competing risks for this multinomial regression analysis. Risk factors with scores greater than 1 (and not crossing 1) were associated with a statistically higher risk of delirium the following day. ICU=intensive care unit. OR=odds ratio. SAPS II=Simplified Acute Physiology Score II. *For all continuous variables (age, SAPS II, proportion of ABCDE elements performed), comparisons shown in parentheses correspond to the 75th vs 25th percentile values for that variable. †p values shown represent the overall p values for the variable and are not associated with the level to level comparisons within these variables, which are represented by the 95% CIs. ‡Bundle element F was assessed separately since COVID-19 presents a unique circumstance in which in-person visitation was restricted at most of the participating sites.

Figure 4

Forest plot of days alive and free of coma or delirium All patients who had at least 90% delirium or coma assessments during their index intensive care unit stay were included in this analysis (n=2062). Risk factors with an OR of less than 1 indicate a negative patient outcome (fewer days alive and free of brain dysfunction coma or delirium). OR=odds ratio. SAPS II=Simplified Acute Physiology Score II. *For all continuous variables (age, SAPS II, proportion of ABCDE elements performed), comparisons shown in parentheses correspond to the 75th vs 25th percentile values for that variable. †p values shown represent the overall p values for the variable and are not associated with the level to level comparisons within these variables, which are represented by the 95% CIs.