title: Interleukin 6 and apolipoprotein E as predictors of acute brain dysfunction and survival in critical care patients.
abstract: BACKGROUND
  Delirium occurs in up to 80% of intensive care patients and is associated with poor outcomes. The biological cause of delirium remains elusive.
  
  
  OBJECTIVE
  To determine if delirium and recovery are associated with serum levels of interleukins and apolipoprotein E over time and with apolipoprotein E genotype.
  
  
  METHODS
  The sample consisted of 77 patients with no previous cognitive deficits who required mechanical ventilation for 24 to 96 hours. Daily serum samples were obtained for enzyme-linked immunosorbent assay measurements of interleukins 6, 8, and 10 and apolipoprotein E. DNA extracted from blood was analyzed for apolipoprotein E genotyping. The Confusion Assessment Method for the Intensive Care Unit was administered daily on days 2 through 9.
  
  
  RESULTS
  Among the 77 patients, 23% had no delirium, 46% experienced delirium, and 31% experienced coma. Additionally, 77% had delirium or coma (acute brain dysfunction), and compared with other patients, had fewer ventilator-free days (P = .03), longer stay (P = .04), higher care needs at discharge (P = .001), higher mortality (P = .02), and higher levels of interleukin 6 (P = .03), and the APOE*3/*3 apolipoprotein E genotype (P = .05). Serum levels of apolipoprotein E correlated with levels of interleukins 8 and 10. Patients with the E4 allele of apolipoprotein E had shorter duration of delirium (P = .02) and lower mortality (P = .03) than did patients without this allele.
  
  
  CONCLUSIONS
  Apolipoprotein E plays a complex role in illness response and recovery in critically ill patients. The relationship between apolipoprotein E genotype and brain dysfunction and survival is unclear.
authors.affiliation: All authors are at the University of Pittsburgh, Pittsburgh, Pennsylvania. Sheila A. Alexander and Dianxu Ren are assistant professors and Yvette P. Conley is an associate professor in the School of Nursing. Scott R. Gunn is an associate professor and Patrick M. Kochanek is a professor in the School of Medicine. Judith Tate is a postdoctoral fellow, Department of Psychology, and Milos Ikonomovic is a research assistant professor, Department of Neurology.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Alexander
authors.forename: Dianxu
authors.initials: D
authors.lastname: Ren
authors.forename: Scott R
authors.initials: SR
authors.lastname: Gunn
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Judith
authors.initials: J
authors.lastname: Tate
authors.forename: Milos
authors.initials: M
authors.lastname: Ikonomovic
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
mesh_terms: D018806:APACHE; D000208:Acute Disease; D000328:Adult; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001927:Brain Diseases / Q000097:blood / Q000235:genetics* / Q000401:mortality; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003128:Coma / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000097:blood; D003693:Delirium / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D010414:Pennsylvania; D011379:Prognosis; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000706:statistics & numerical data
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D015850:Interleukin-6; D004247:DNA