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Risk Factors for Persistent Cognitive Impairment After Critical Illness, Nested Case-Control Study

Sakusic, Amra, MD1–,3; Gajic, Ognjen, MD, MSc3,4; Singh, Tarun D., MBBS3,5; O’Horo, John C., MD, MPH3,6; Jenkins, Gregory, MS7; Wilson, Gregory A., RRT3; Petersen, Ronald, MD, PhD5; Fryer, John D., MD, PhD8; Kashyap, Rahul, MBBS3,9; Rabinstein, Alejandro A., MD5

doi: 10.1097/CCM.0000000000003395
Neurologic Critical Care

Objectives: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment.

Design: An observational case-control study.

Settings: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015.

Patients: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge.

Interventions: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization.

Measurements and Main Results: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment.

Conclusions: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

1Departments of Internal Medicine and Pulmonary Medicine, Tuzla University Medical Center, Tuzla, Bosnia and Herzegovina.

2Medical Faculty, University of Tuzla, Tuzla, Bosnia and Herzegovina.

3Multidisciplinary Epidemiology and Translational Research in Intensive Care, Emergency and Perioperative Medicine (METRIC), Mayo Clinic, Rochester, MN.

4Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.

5Department of Neurology, Mayo Clinic, Rochester, MN.

6Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN.

7Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

8Department of Neuroscience, Mayo Clinic, FL.

9Department of Anesthesiology, Mayo Clinic, Rochester, MN.

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This publication was made possible, supported, in part, by funding from The Mayo Critical Care Research Committee and grants from the National Institute on Aging (U01 AG006786, P50 AG016574, and R01 AG034676).

Drs. Sakusic, Gajic, O`Horo, and Singh, Mr. Jenkins, Mr. Wilson, and Drs. Petersen and Fryer have made substantial contribution to conception and design, acquisition of data, analysis and interpretation. Dr. O’Horo received support for article research from the National Institutes of Health. Drs. O’Horo and Jenkins disclosed work for hire. Dr. Rabinstein takes full responsibility for the data, the analysis and interpretation, and the conduct of research. All the authors have provided the final approval of the version to be published. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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