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Morandi A.,Rehabilitation and Aged Care Unit | Morandi A.,Geriatric Research Group | Morandi A.,Vanderbilt University | Hughes C.G.,Vanderbilt University | And 14 more authors.
Critical Care Medicine | Year: 2014

Objective: Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium. Design: Multicenter, prospective cohort study. Setting: Medical and surgical ICUs in two large tertiary care hospitals in the United States. Patients: Patients with acute respiratory failure or shock. Interventions: None. Measurements and main results: We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51-70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19-31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10-0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46-1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35-1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44-1.66; p = 0.18), yet the longer a prehospital statin user's statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions). Conclusions: In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Pandharipande P.P.,Vanderbilt University | Girard T.D.,Vanderbilt University | Girard T.D.,Geriatric Research Education and Clinical Center | Jackson J.C.,United Allergy Services | And 22 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. Copyright © 2013 Massachusetts Medical Society.


Cummings J.,Cleveland Clinic | Froelich L.,University of Heidelberg | Black S.E.,University of Toronto | Bakchine S.,Reims University Hospital Center | And 7 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2012

Aim: Determine whether patients with Alzheimer's disease demonstrating functional and cognitive decline, following 24-48 weeks of open-label treatment with 9.5 mg/24 h (10 cm2) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm2) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-IADL) scale and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAS-cog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated. Copyright © 2012 S. Karger AG, Basel.


Brummel N.E.,Vanderbilt University | Balas M.C.,Ohio State University | Morandi A.,Vanderbilt University | Morandi A.,Geriatric Research Group | And 4 more authors.
Critical Care Medicine | Year: 2015

Objective: To review how disability can develop in older adults with critical illness and to explore ways to reduce long-term disability following critical illness. Data Sources: We searched PubMed, CINAHL, Web of Science and Google Scholar for studies reporting disability outcomes (i.e., activities of daily living, instrumental activities of daily living, and mobility activities) and/or cognitive outcomes among patients treated in an ICU who were 65 years or older. We also reviewed the bibliographies of relevant citations to identify additional citations. Study Selection: We identified 19 studies evaluating disability outcomes in critically ill patients who were 65 years and older. Data Extraction: Descriptive epidemiologic data on disability after critical illness. Data Synthesis: Newly acquired disability in activities of daily living, instrumental activities of daily living, and mobility activities was commonplace among older adults who survived a critical illness. Incident dementia and less severe cognitive impairment were also highly prevalent. Factors related to the acute critical illness, ICU practices, such as heavy sedation, physical restraints, and immobility, as well as aging physiology, and coexisting geriatric conditions can combine to result in these poor outcomes. Conclusions: Older adults who survive critical illness have physical and cognitive declines resulting in disability at greater rates than hospitalized, noncritically ill and community dwelling older adults. Interventions derived from widely available geriatric care models in use outside of the ICU, which address modifiable risk factors including immobility and delirium, are associated with improved functional and cognitive outcomes and can be used to complement ICU-focused models such as the ABCDEs. © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.


Morandi A.,Center for Health Services Research | Morandi A.,Geriatric Research Group | Jackson J.C.,Center for Health Services Research | Jackson J.C.,Vanderbilt Medical Center | Jackson J.C.,VA Tennessee Valley Geriatric Research
Neurologic Clinics | Year: 2011

Delirium occurs commonly in both general medical and intensive care unit (ICU) patients, with prevalence rates of up to 80% reported. A common expression of acute brain dysfunction, it is related to wide-ranging untoward outcomes such as prolonged hospitalization, increased costs, higher mortality, and, potentially long-term cognitive impairment. Different risk factors are associated with delirium, including sedation, which has implications for patient management. Multicomponent interventions to prevent delirium, developed in the non-ICU setting, can be adapted to critically ill patients with the purpose of reducing its incidence. Future studies should evaluate target interventions to prevent delirium in the ICU. © 2011 Elsevier Inc.

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