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.

Objectives: 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.

Figure 1. Outcome measures by delirium

Discharge disposition by Acute Brain Dysfunction. A. Percent of subjects in each discharge disposition group. Individuals without Acute Brain Dysfunction were more likely to be discharged to home. B. Percent of subjects who lived/died in each Acute Brain Dysfunction group. Note that significantly more subjects with Acute Brain Dysfunction died compared to those without dysfunction. Acute Brain Dysfunction had a negative effect on recovery such that those with Acute Brain Dysfunction were more likely to die and, for those survivors, were more likely to be discharged to a high care need facility after controlling for age, sex, 24 hour medication doses, APACHE III, and Charlson comorbidity index.

Figure 2. Mean IL-6 (±SE) over time

Mean IL-6 (±SE) over time. A. Daily mean IL-6 in different delirium groups (CAM-ICU Negative, CAM-ICU Positive, Coma). B. Daily mean IL-6 concentrations over time by Acute Brain Dysfunction presence. IL-6 was higher in patients with delirium (CAM-ICU positive) and those with Acute Brain Dysfunction compared to those without dysfunction.

Figure 3. Mean IL-6 (±SE) over time by APOE genotype

Mean IL-6 (±SE) over time by APOE genotype. Daily mean IL-6 in groups based on APOE genotypes by hospital day. Subjects with IL-6 was greatest in APOE 3/3 genotype > APOE 2/3 genotype > APOE 2/4 genotype > APOE 3/4 genotype.