The relationships of hypocholesterolemia to cytokine concentrations and mortality in critically ill patients with systemic inflammatory response syndrome.
BACKGROUND
Decreased concentrations of total cholesterol, lipoproteins, and lipoprotein cholesterols occur early in the course of critical illness. Low cholesterol concentrations correlate with high concentrations of cytokines such as interleukin (IL)-6 and IL-10, and may be due to decreased synthesis or increased catabolism of cholesterol. Low cholesterol concentrations have been associated clinically with several adverse outcomes, including the development of nosocomial infections. The study was performed to test the hypothesis that a low cholesterol concentration predicts mortality and secondarily predicts the development of organ dysfunction in critical surgical illness.


METHODS
A prospective study was undertaken of 215 patients admitted to a university surgical ICU with systemic inflammatory response syndrome (SIRS). Serial blood samples were collected within 24 h of admission, as well as on the morning of days 2, 4, and 7 of the ICU stay for as long as the patients were in the ICU. Demographic data and predetermined outcomes were noted.


RESULTS
One hundred nine patients had at least two samples drawn and form the population for analysis. Sixty-two of the patients had three samples obtained, whereas 42 patients had four samples obtained. By univariate analysis, non-survivors were more severely ill on admission (APACHE III), more likely to have been admitted to the ICU as an emergency, more likely to develop a nosocomial infection, and more likely to develop severe organ dysfunction (MODS) (all, p < 0.05). Death was associated on day 1 with increased concentrations of sIL2R, IL-6, IL-10, and sTNFR-p75 (all, p < 0.01), but there were initially no differences in serum lipid concentrations. However, by day 2, concentrations of IL-6, IL-10, and cholesterol had decreased significantly (all, p < 0.05) from day 1 in non-survivors but not in survivors; the difference in serum cholesterol concentration persisted to day 7 (p < 0.05). Persistently elevated concentrations of IL-6 and IL-10 were observed in patients who developed severe MODS. By logistic regression, increased APACHE III score, development of a nosocomial infection, and decreased cholesterol concentration were independently associated with mortality.


CONCLUSIONS
Decreased serum cholesterol concentration is an independent predictor of mortality in critically ill surgical patients. Repletion of serum lipids is a feasible therapeutic approach for the management of critical illness.
Bonville
Daniel A
DA
Department of Surgery, Weill Medical College of Cornell University, New York, New York, USA.
Parker
Thomas S
TS
Levine
Daniel M
DM
Gordon
Bruce R
BR
Hydo
Lynn J
LJ
Eachempati
Soumitra R
SR
Barie
Philip S
PS
D018806:APACHE; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D016638:Critical Illness / Q000401:mortality*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy
D015415:Biomarkers; D016207:Cytokines; D002784:Cholesterol