Long-Term Cognitive Impairment After Critical Illness

Long-term cognitive impairment is a significant public health problem. In the October 3 issue of the New England Journal of Medicine, the BRAIN-ICU Investigators, led by Pratik Pandharipande, MD, conducted a multicenter, prospective cohort study to estimate the prevalence of long-term cognitive impairment after critical illness and to test the hypothesis that patients with a longer duration of delirium and a higher sedative and analgesic requirement have more severe cognitive impairment up to 1 year after hospital discharge.

Adults admitted to a medical or surgical ICU with respiratory failure, cardiogenic shock, or septic shock were included. While hospitalized, they were evaluated for delirium and level of consciousness daily with the use of the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale (RASS). Global cognition and executive functions were assessed three and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test, Part B. Multiple linear regression with adjustment for multiple variables was used to examine independent risk factors for global cognition scores and secondary outcomes.

Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and 74% developed delirium during the hospital stay. At three months, 40% of the patients had global cognition scores that were approximately 1.5 standard deviations below the age-adjusted population mean and worse than scores observed in patients with moderate traumatic brain injury. Twenty-six percent of patients had scores 2 standard deviations below the population mean, which was similar to patients with mild Alzheimer disease. At 12 months, deficits of the same severity were also common. At both three and 12 months, a longer duration of delirium was independently associated with worse global cognition (P = 0.001 and P = 0.04, respectively) and worse executive function (P = 0.004 and P = 0.007, respectively). The use of sedatives or analgesics was not consistently associated with worse outcomes at 3 and 12 months after discharge.

The major findings from this study show that cognitive impairment after critical illness is common and persists for at least one year in some patients. This impairment is not seen only in aged patients or those with coexisting conditions at baseline. Limitations to this work include a diverse set of admission diagnoses, patients lost to follow-up or disenrolled before the 3- and 12-month assessments, and some missing data that required imputation techniques. The majority of study patients (>88%) were white, and the median level of education was 12 years. Hence, the results may not be externally generalizable across populations with higher or lower education levels or different racial or ethnic status. Patients were maintained on mechanical ventilation for a median of two to three days; it is possible that prolonged critical illness and longer duration of mechanical ventilation may cause even worse cognitive outcomes. Nearly three of four patients in the study had delirium. Delirium likely remains underdiagnosed in intensive care units, but when present, the longer the duration, the worse the impaired cognition.

This Concise Critical Appraisal is authored by Guirguiss Tadros, MD, fellow in Surgical Critical Care, University of Maryland R Adams Cowley Shock Trauma Center, Baltimore, Maryland.

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7 thoughts on “Long-Term Cognitive Impairment After Critical Illness

  1. Debra Roberts

    Thank you for addressing the topic– a study worthy of critical acclaim. Wondering whether subgroups by exact sedative used showed any trends for one sedative or class being worse than another or no?

  2. Jonathan Wood, MD

    I am a boarded pediatric intensivist with 17+ year of experience. I am very troubled by the way this article was written. Better put, I am troubled by the HEADLINE and then the FIRST SENTENCE of your article. The headline highlights sedative use and does not mention delerium. The first sentence states: “Long- term cognitive impairment caused by the use of sedatives in critically ill patients is a significant public health problem.” Both are misleading.

    Your article goes on to cite the details of the NEJM study with (1) an independent correlation of delerium being associated with cognitive defects at 3 mo and 1 year and (2) NO correlation between these cognitive changes and sedative use.

    I admit to having not yet pulled the article, but I do not believe I misread Dr Tadros’ summation of it. He clearly states that “the use of sedatives or analgesics was not consistently associated with worse outcomes at 3 and 12 months after discharge,” but it is unfortunately buried withhin the text. Whether Dr Tadros is responsible or your editorial staff, this is misleading. For those of us scanning headlines and first paragraphs, something many busy clinicians are guilty of, we would be left with false conclusions.

    Whether intentional or not, this sort of misinformation does nothing constructive toward our collective efforts to apply Evidence Based Medicine. It feels sensational at best and deliberately misleading at worst. I believe this demands an addendum and clarification.
    Please let me know your thoughts on this.

    Sincerely, Jonathan Wood, MD

    1. Sam Galvagno

      Dr. Wood,

      Thank you for your comments. We have since edited the piece for clarity. However, I respectfully disagree with your assessment of the way this brief summary was written. There is no agenda here, and no intention of making these CCAs “deliberately misleading” or “sensational.” Our CCAs are designed to lead readers to the article, and to stimulate discussion and thought about critical care literature published in high impact journals. There is no possible way every nuance of the article can be summarized in four paragraphs. There is also no question that long-term cognitive impairment after critical illness is a major public health problem. Moreover, the headline for this piece is the actual title of the article , so I am not sure how we could have made that less controversial. Thanks again for your feedback.
      Sam G.

  3. Javier Finkielman

    The title of this note is completely misleading. I would suggest the writer to read the article and change the title.

  4. John Reeves

    How can the title of this article be “Long-Term Cognitive Impairment in Critically Ill Patients Due to Sedative Usage”?
    The last sentence in the fourth paragraph, quoting directly from the NEJM abstract says “The use of sedatives or analgesics was not consistently associated with worse outcomes at 3 and 12 months after discharge”.
    Perhaps another interpretation is that patients with worse delerium require more sedation and then go on to have worse long term cognitive outcomes.

  5. Rosemary Meding

    I find this article very informative although ‘flawed’ for the reasons listed above. However, the importance of this syndrome is critical for patients to be made aware of after supposed ‘recovery’. If they knew this was a reality …it might not be so upsetting as they realize their impairment is not a figment of their imagination. A friend of mine happened to see an article on FOX news..this was the first we had heard of this problem as no one had told us about it. Doctors—Please have a qualified individual on hand to discuss this very upsetting news to your patients in the future and include their ‘loved ones’ as well. It is not fair to keep this hidden when by acknowledging it …it could remove some of the fear of the ‘unknown’ behavior. If anyone wants to study me about this …I am willing to discuss my documented experience with a qualified individual.

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