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09/10/13 www.medscape.com/viewarticle/812041_print

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www.medscape.com

Dr. Pratik P.

Pandharipande

Oct 03, 2013

Profound cognitive impairment, even in young patients, is gaining recognition as a significant risk following a stay

in an intensive care unit (ICU).

A new study found that 1 in 4 patients had cognitive impairment a year after release from an ICU that was similar

in severity to having mild Alzheimer's disease (AD), and 1 in 3 had cognitive impairment similar to that seen with

moderate traumatic brain injury (TBI).

"With improvements in medical care, there has been increased survival after a critical illness, but even though we

are getting these patients out of the ICU alive, they are left with cognitive impairments that prevent them from

getting back their quality of life," said lead author Pratik P. Pandharipande, MD, professor, anesthesiology and

critical care medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.

This new study should remind medical professionals that post-ICU cognitive impairment is a very real

phenomenon, Dr. Pandharipande told Medscape Medical News. "When these patients come into your office

complaining about having a difficult time with their finances, having a difficult time planning certain events, or

having memory problems, pay attention to it and don't completely ignore it."

The study is publishedOctober 3 in the New England Journal of Medicine.

BRAIN-ICU

The multicenter, prospective study, Bringing to Light the Risk Factors and Incidence of

Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU), included 821 adults with a

median age of 61 yearswho were admitted to a medical or surgical ICU with respiratory

failure, cardiogenic shock, or septic shock.

Certified evaluators who assessed patients using the Clinical Dementia Rating found that

only 6% of the patients had evidence of pre-existing cognitive impairment.

Between enrollment and the 3-month follow-up, 31% of patients died; 7% of the remaining

cohort died before the12-month follow-up. Researchers assessed global cognition using the Repeatable Battery

for the Assessment of Neuropsychological Status (RBANS) in 467 patients at 3 months, 12 months, or both.

They also assessed executive function using the Trail Making Test Part B.

The median RBANS score for global cognition was 79 at 3 months and 80 at 12 months, which is about 1.5

standard deviations (SDs) below the age-adjusted population mean and similar to scores for patients with mildcognitive impairment.

At 3 months, 40% of the patients had scores that were worse than those typically seen in patients with moderate

TBI, and 26% had scores 2 SDs below the population mean, which is similar to scores for patients with mild AD.

At 12 months, 34% and 24% of patients had scores similar to those for patientswith moderate TBI and those with

mild AD, respectively.

Cognitive impairment was not limited to older patients. Those aged 49 years of age or younger had median global

cognition scores of 78 and 80 at 3 months and 12 months, respectively.

Cognitive Problems "Striking"

"We found that even vigorously healthy people who became acutely ill left the ICU with acquired cognitive

problems, and those problems were often quite striking," said another study author, James C. Jackson, PsyD,

assistant professor, medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, and the Center for

Critical Illness Linked to Cognitive ImpairmentPauline Anderson
http://www.nejm.org/doi/full/10.1056/NEJMoa1301372http://www.medscape.com/http://www.nejm.org/doi/full/10.1056/NEJMoa1301372http://www.medscape.com/


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Dr. James C.

Jackson

Health Services Research, Vanderbilt University School of Medicine. "Being young clearly does not protect one

against developing meaningful cognitive problems after the ICU."

The emotional impact of these cognitive problems is often much greater for younger

patients, added Dr. Jackson, a licensed clinical psychologist who studies psychological

and cognitive functioning in survivors of critical illness and the effects of cognitive

rehabilitation in ICU survivors with brain injuries.

"If you leave the ICU and you're 80 and you have a bad outcome, your family expects thaton some level; if you leave the ICU and you're 29 and you find out you are so limited you

can't return to work, it's much more disruptive on a lot of levels, and emotionally it's much

more jarring."

Cognitive deficits were seen "across the board," commented Dr. Pandharipande. "Even

many of the youngest of our patients who had no prior coexisting illness had the same

significant cognitive impairment that we saw in our oldest and sickest patients."

Because only 6% of patients showed evidence of mild to moderate cognitive impairment before ICU admission,

these cognitive deficits were new in most cases.

Duration of coma was not associated with cognition scores at 3 or 12 months, but this was not the case for

delirium, a form of acute brain dysfunction diagnosed on the basis of change in mental status, inattention,

disorganized thinking, and altered level of consciousness. Delirium affected 74% of study patients during their

hospital stay, with a median delirium duration of 4 days.

Longer duration of delirium was an independent risk factor for worse executive function and for lower RBANS

global cognition scores at both 3 and 12 months (P= .001 and P= .04, respectively). This association was

independent of sedative or analgesic use, pre-existing cognitive impairment, coexisting conditions, and ongoing

organ failures during ICU care.

Delirium is associated with inflammation and neuronal apoptosis, which may lead to brain atrophy and has also

been associated with cerebral atrophy and reduced white matter integrity, both of which are associated with

cognitive impairment, said the authors.

It's probably too early to start routinely assessing cognition of all ICU patients, said Dr. Pandharipande. But he

does think that it 's "reasonable" that patients get some sort of testing after leaving the ICU. Vanderbilt has set up

an ICU survivor clinic where patients who have been severely septic or on mechanical ventilation can come back

to the hospital and get assessed for cognitive impairment.

To reduce the risk while in the ICU, Dr. Pandharipande suggests more monitoring for delirium. "The first step is to

diagnose delirium and recognize which patients have it and which do not," he said. "Important strategies could bekeeping patients relatively lightly sedated, trying to get them awake as early as possible even on mechanical

ventilation, and trying to get them mobilized because early exercise has been shown to improve outcomes and

reduce delirium duration."

Cognitive rehabilitation, an approach often used in traditional TBI, might be effective after release from the ICU,

added Dr. Jackson. "You modify risk factors in the ICU in an attempt to reduce the problem, but when people

leave withthe problem, you attempt to impact that and one way is through cognitive rehabilitation."

Such rehabilitation, he said, can involve "trying to leverage the strengths of patients and minimizing the

weaknesses, teaching them strategies for living more effectively, teaching how to use adaptive devices of various

kinds, and basically assisting them to be more effective in their daily lives."

While the study didn't find an independent association between higher doses of benzodiazepines and worse long-

term cognitive scores, "we still feel that sedation management and attention to sedation is important," said Dr.

Pandharipande. "Sedatives have been associated with delirium, and now we have shown that delirium is


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associated with long-term cognitive impairment, so it's possible that some of the effect of sedation on long-term

impairment is through delirium."

Data "Impressive"

Unlike earlier studies, the current analysis enrolled a large sample of patients with a diverse set of diagnoses and

a broad age range. That, according to Edward R. Marcantonio, MD, professor of medicine, Harvard Medical

School, and director, Aging Research Program, Division of General Medicine and Primary Care, Beth Israel

Deaconess Medical Center, Boston, Massachusetts, made the study that much more impressive.

Dr. Marcantonio was also impressed by the study's descriptive data showing the degree of cognitive impairment

that the ICU survivors experienced. Although other research has had similar findings, he said, "this was a broader

population, a larger population, and using these instruments the RBANS and Trail B enabled the authors to

correlate the deficits with other populations," such as those with TBI and mild AD.

"This study certainly points out the magnitude of the problem and the fact that we need to do more to try to figure

out what's going on and see if we can intervene," Dr. Marcantonio added.

And although the paper doesn't spell out what those interventions should be, "certainly this is a clarion call, if

nothing else, to the importance of the problem," he added.

Postdischarge cognitive rehabilitation, said Dr. Marcantonio, is an area of growing interest. "One of the principles

of geriatrics, which I think would pertain here even though it's more a mixed age population, is that it's always

easier to prevent something than to rehabilitate someone. If we could figure out what's causing cognitive

impairment, if any of it is potentially modifiable, that would probably be a better way to go than rehabilitation, but

certainly rehab is worthwhile looking into as well."

Dr. Marcantonio, whose focus most of his career has been on delirium, agreed that reducing the amount of

sedating medications administered in the ICU may be important in preventing delirium or reducing its duration.

"The old view was that the ICU was a horrible experience and the best thing you could do for patients was to just

sedate them the entire time and then wake them up when they were better and hopefully that would spare them

some trauma," he said."Now there's increasing evidence showing that that is not such a good idea, that lightening

the sedation and waking patients up every day to see how they're doing, and even potentially getting them out of

bed and ambulating them, may reduce delirium and other complications in the ICU."

Funding information is available with the original article. Dr. Pandharipande reports he has received honorarium

and research grants from Hospira Inc.

N Engl J Med. 2013;369:1306-1316.Abstract

Medscape Medical News 2013 WebMD, LLC

Send comments and news tips to [email protected] .

Cite this article: Critical Illness Linked to Cognitive Impairment. Medscape. Oct 03, 2013.
mailto:[email protected]://www.nejm.org/doi/full/10.1056/NEJMoa1301372

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