Extended delirium raises cognitive risk in critically ill



Critical illness survivors who experienced a long period of delirium during an intensive care unit stay can have long-term global cognition and executive function scores similar to those seen in traumatic brain injury and Alzheimer’s patients, according to a multicenter prospective cohort study.

The finding of an association between longer duration of delirium and worse long-term global cognition and executive function was independent of sedative or analgesic medication use, age, preexisting cognitive impairment, the burden of coexisting conditions, and ongoing organ failure during ICU care, Dr. P.P. Pandharipande of Vanderbilt University, Nashville, Tenn., and his colleagues reported. The findings were published Oct. 2 in The New England Journal of Medicine.

Courtesy Vanderbilt University

Dr Pratik P. Pandharipande (right, lead author) and Dr. Wes Ely (left, senior author).

Of 821 patients with respiratory failure, cardiogenic shock, or septic shock who were treated in a medical or surgical ICU, 6% had cognitive impairment at baseline and 74% experienced delirium during their hospital stay. Median global cognition scores at 3 and 12 months as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were 79 and 80, respectively.

"These scores were approximately 1.5 [standard deviations] below the age-adjusted population mean of 100 plus or minus 15 and were similar to scores for patients with mild cognitive impairment. At 3-months, 40% of the patients had global cognition scores that were worse than those typically seen in patients with moderate traumatic brain injury, and 26% had scores 2 SD below the population means, which were similar to scores for patients with mild Alzheimer’s disease," the investigators reported.

The deficits occurred regardless of patient age and persisted to 12 months, with 34% and 24% of patients demonstrating scores similar to those for patients with moderate traumatic brain injury and for patients with mild Alzheimer’s disease, respectively, they said (N. Engl. J. Med. 2013;369:1306-16).

Duration of delirium was significantly associated with worse global cognition and significantly worse executive function at both 3- and 12-month follow-up. For example, patients with a 5-day mean duration of delirium had mean RBANS scores that were 6.3 points lower at 3 months and 5.6 points lower at 12 months than those with no delirium. They had Trails B executive-function scores that were 5.1 points lower at 3 months and 6.0 points lower at 12 months.

"A longer duration of delirium was also a risk factor for worse function in several individual RBANS domains," Dr. Pandharipande and his associates noted.

Although the investigators hypothesized that higher doses of sedative and analgesic use also would be independently associated with more severe cognitive impairment at 12 months, this did not prove to be the case. The use of higher benzodiazepine doses during hospitalization, however, was associated with worse executive function scores at 3 months.

The patients, who had a median age of 61 years and high severity of illness, were enrolled in the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study between March, 2007 and May, 2010. Delirium was assessed by the Confusion Assessment Method for the ICU, and level of consciousness was assessed using the Richmond Agitation-Sedation Scale.

It remains unclear whether any preventive or treatment strategies can reduce the risk of long-term cognitive impairment after critical illness, they said, noting that this is of concern, as "long-term cognitive impairment after critical illness may be a growing public health problem, given the large number of acutely ill patients being treated in intensive care units globally."

Though limited by an inability to test patients’ cognition before their emergent illness (although the investigators took several precautions to address this limitation), and by the fact that some patients were unable to complete all cognitive tests, the findings nevertheless demonstrate that cognitive impairment after critical illness is very common – even more so among those with longer duration of delirium – and can persist for at least 1 year, they said.

It is "possible that patients who are vulnerable to delirium owing to severe critical illness are also vulnerable to long-term cognitive impairment and that delirium does not play a causal role in the development of persistent cognitive impairment," investigators noted.

This study was supported by grants from the National Institutes of Health and the Veteran’s Affairs Clinical Science Research and Development Service, as well as by a Mentored Research Training Grant from the Foundation for Anesthesia Education and Research and the VA Tennessee Valley Geriatric Research Education and Clinical Center. Multiple study authors reported disclosures; details are available with the full text of the article at

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