Study finds high prevalence of acute brain dysfunction in critically ill patients with COVID-19

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Study data showed that acute brain dysfunction was highly prevalent and prolonged in critically ill patients with coronavirus disease 2019 (COVID-19) and the overuse of benzodiazepine sedative infusions and lack of family visitation were associated with more delirium.

These findings, published in The Lancet Respiratory Medicine, came from a study which included 2,088 critically ill patients with COVID-19 admitted to 69 intensive care units (ICUs) across 14 countries between January 20 and April 28, 2020. Researchers collected de-identified data from electronic health records for a 21-day period. The primary outcomes of the study were prevalence of delirium and coma, risk factors associated with development of delirium the next day and predictors of number of days alive without delirium or coma.

“The study highlights a high burden of acute brain dysfunction (>80% of patients had coma and >50% developed delirium) that lasted for a median of 2 weeks, which might have implications for survivorship (eg, acquired dementia),” reported Brenda T Pun, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues. “The two strongest modifiable predictors of delirium were benzodiazepine infusion (around 60% higher risk of delirium) and family visitation (around 30% lower risk of delirium).”

The median age of patients was 64 years with a median Charlson comorbidity score of 1.0 (interquartile range [IQR], 0.0-2.0) and a median Simplified Acute Physiology Score (SAPS) II of 40.0 (IQR, 30.0-53.0). Of the patients, 1,397 (66.9%) were invasively mechanically ventilated on the day of ICU admission and 1,827 (87.5%) were invasively mechanically ventilated at some point during hospitalisation. Most patients received continuous sedative infusions while on mechanical ventilation, whereby 1,337 (64.0%) were given benzodiazepines for a median of 7.0 (IQR, 4.0-12.0) days and 1,481 (70.9%) were given propofol for a median of 7.0 (IQR, 4.0-11.0) days. Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3).

Study data revealed that 1,704 (81.6%) patients were comatose for a median of 10.0 days (IQR, 6.0-15.0) while 1,147 (54.9%) were delirious for a median of 3.0 days (IQR, 2.0-6.0). Overall, acute brain dysfunction affected patients for a median of 12.0 days (IQR, 7.0–18.0). During the 21-day study period, patients were alive without delirium or coma for a median of 5.0 days (IQR, 0.0–14.0). Meanwhile, 601 (28.8%) patients died within 28 days of admission, with most of those deaths occurring in the ICU.

Researchers found that older age (odds ratio, [OR], 1.13; 95% confidence interval [CI], 1.03–1.25; P = 0.036), higher SAPS II score (OR, 1.17; 95% CI, 1.07–1.29; P = 0.0013), smoking or alcohol abuse (OR, 1.37; 95% CI, 1.13–1.67; P = 0.0013), invasive mechanical ventilation (OR, 1.48; 95% CI, 1.17–1.87; P = 0.0013), vasopressors (OR, 1.25; 95% CI, 1.10–1.43; P = 0.0009), restraint use (OR, 1.32; 95% CI,1.16–1.50; P <0.0001), antipsychotics (OR, 1.59; 95% CI, 1.36–1.85; P <0.0001), and sedative benzodiazepine infusions (OR, 1.59; 95% CI, 1.33–1.91; P <0.0001), and continuous opioid infusions (OR, 1.39; 95% CI, 1.21–1.60; P<0.0001) were each associated with higher risk of delirium the next day. Family visitation, however, was associated with a 27% lower risk of delirium (OR, 0.73; 95% CI, 0.63–0.84; P <0.0001).

Meanwhile, older age (OR, 0.62; 95% CI, 0.52–0.74; P<0.0001), higher SAPS II scores (OR, 0.51; 95% CI, 0.42–0.62; P<0.0001), smoking or alcohol abuse (OR, 0.65; 95% CI, 0.47–0.88; P = 0.0056), invasive mechanical ventilation on day 1 (OR, 0.17; 95% CI, 0.11–0.26; P<0.0001), and vasopressor use on day 1 (OR, 0.73; 95% CI, 0.59–0.92; P = 0.0070) were independently associated with fewer delirium and coma-free days, whereas female sex (OR, 1.34; 95% CI, 1.08–1.67; P = 0.0087) was associated with more delirium-free and coma-free days during the 21-day study period.

“To our knowledge, this study is the only multisite study to assess critically ill patients with COVID-19 for delirium and coma using validated assessments and is the largest cohort of mechanically ventilated patients with COVID-19 published to date,” the authors wrote. “We found that risk of delirium among patients with severe COVID-19 was lower when benzodiazepine sedative infusions were avoided and family was present, whereas greater severity of illness and greater respiratory support was associated with a higher risk of delirium.”

“Our results support avoidance of benzodiazepine sedative infusions which were associated with a 59% higher risk of developing delirium,” the authors noted. “When possible, health-care providers should adhere to current sedation guidelines for mechanically ventilated patients, even those with COVID-19, which recommend limiting neuromuscular blockade, avoidance of continuous infusions of benzodiazepines, light levels of sedation, frequent awakening and breathing trials, and mobilisation; these practices improve short-term outcomes and might also reduce the risk of post-intensive care syndrome, which affects a high proportion of acute respiratory failure survivors.”

“This study provides evidence that clinicians should aim to use supportive and proven therapies that avoid deep sedation with benzodiazepine infusions, and facilitate safe in-person or virtual visitation for patients with COVID-19,” the authors added.