Delirium and Apolipoprotein Delirium, a disturbance is consciousness with inattention accompanied by a change in cognition or perceptual disturbances, is a common occurrence in hospitalized patients in and out of the ICU. Factors increasing risk for the development of delirium include increasing age, metabolic disturbances, electrolyte imbalances, drug (alcohol withdrawal, infection, seizures, dehydration, hyperthermia, head trauma, vascular disorders, intracranial space occupying lesions and others. Delirium in the ICU has been associated with prolonged ICU stay, prolonged hospital stay, and poorer outcome. Currently, there are no biomarkers available to predict delirium onset or duration in ICU patients. Recent research has identified a potential association between presence of the apolipoprotein E (APOE) 4 allele, a gene with known influence on neurologic recovery and disease, and delirium in ICU patients. The proposed study will explore the relationship between APOE 4 allele presence and development and duration of delirium in ICU patients. A secondary goal of the proposed study is to explore the potential relationship between APOE 4 allele presence, serum apolipoprotein E protein levels, serum cytokine levels (IL-1, IL-6, IL-8 and IL-10) and development and duration of delirium in ICU patients. Subjects will be identified upon admission to the ICU and consent obtained by a clinical nurse collaborating with the research team. Blood will be drawn upon enrollment and daily for the first 5 days of admission. DNA will be extracted from the first blood sample drawn. Serum will be extracted from each sample for apoE protein and cytokine quantification. Delirium will be assessed daily by the clinical nurse using the confusion assessment method-ICU (CAM-ICU). Chi-square analysis and repeat measures analysis of variance will be used to explore associations between APOE 4 allele presence and development/duration of delirium. Hierarchical linear and nonlinear modeling will be used to explore the relationship between APOE 4 allele presence, apolipoprotein E protein level, and cytokine level and delirium development/duration. Identification of a genetic and/or proteomic biomarker for individuals at risk for delirium would aid in focusing nursing care on individuals at risk and formation of individualized care to improve outcome. The results of the proposed study will inform future studies aimed at 1) development of screening protocols for patients at increased risk of delirium, 2) defining pathophysiologic mechanisms driving delirium development and ultimately 3) individualized interventions to limit delirium development thereby improving outcomes. Long Term Outcomes in ICU Patients: Delirium and Apolipoprotein E Delirium is a disturbance is consciousness with inattention accompanied by a change in cognition or perceptual disturbances and is a common occurrence in hospitalized patients. Older patients with multiple medical conditions are at increased risk for delirium, along with patients with metabolic disturbances, electrolyte imbalances, drug or alcohol withdrawal, infection, seizures, dehydration, fever or brain disorders. Patients experiencing delirium in the ICU spend more time in the ICU and the hospital and have worse recovery. Currently, there are no biomarkers available to predict who will develop delirium or how long it will last. Recent research has identified a potential association between presence of one version of the apolipoprotein E (APOE) gene, known as the APOE 4 allele, and delirium in ICU patients. The current study will explore the relationship between APOE 4 allele presence, the protein product made by that gene and markers of inflammation in patients who do and do not develop delirium in the ICU. Subjects will be identified upon admission to the ICU and consent obtained by a clinical nurse collaborating with the research team. Blood will be drawn upon enrollment and daily for the first 5 days of admission. DNA will be extracted from the first blood sample drawn. Serum will be extracted from each sample for apoE protein and cytokine quantification. Delirium will be assessed daily using a well established tool, the confusion assessment method- ICU (CAM-ICU). Statistical tests (Chi-square analysis and repeat measures analysis of variance) will describe APOE 4 allele presence and delirium in these patients. Additional statistical tests (Hierarchical linear and nonlinear modeling) will be used to describe the relationship between the gene, protein, and inflammatory markers and delirium.
Identification of a genetic biomarker for individuals at risk for delirium would aid in focusing nursing care on individuals at risk and formation of individualized care to improve outcome of ICU patients. This would likely lead to decreased time in the ICU and hospital.
| Alexander, Sheila A; Ren, Dianxu; Gunn, Scott R et al. (2014) Interleukin 6 and apolipoprotein E as predictors of acute brain dysfunction and survival in critical care patients. Am J Crit Care 23:49-57 |
