4.6 Article

Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients

期刊

CRITICAL CARE MEDICINE
卷 35, 期 1, 页码 112-117

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.CCM.0000251925.18961.CA

关键词

delirium; critical care; sepsis; respiratory failure; aging; apolipoprotein E4

资金

  1. NCRR NIH HHS [M01 RR 00095] Funding Source: Medline
  2. NIA NIH HHS [K23 AG 01023-01A1, AG 24080 3] Funding Source: Medline
  3. NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000095] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE ON AGING [K23AG001023] Funding Source: NIH RePORTER

向作者/读者索取更多资源

Objective., To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium. Design: Prospective, observational cohort study. Setting: A 541-bed, community-based teaching hospital. Patients: Fifty-three mechanically ventilated intensive care unit patients. Interventions. None. Measurements and Main Results., All patents were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). DNA was extracted from whole blood samples obtained on enrollment and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4-). APOE4+ patients were younger (53.2 +/- 21.9 vs. 65.4 +/- 13.4, p =.08) and less often admitted for pneumonia (0% vs. 29.3%, p =.05) compared with APOE4- patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p =.05). No other clinical outcomes were significantly different between the APOE4+ and APOE4- patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82-29.51, p =.005). Conclusions. APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.

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