CIRCULATING ICAM-1 IS INCREASED IN SEPTIC SHOCK

Adhesion molecules play a critical role in the interaction of circulating neutrophils with vascular endothelium during inflammation. Increased quantities of soluble, circulating intercellular adhesion molecule-1 (cICAM-1) are present in various inflammatory conditions. The purpose of this investigation was to measure cICAM-1 levels in septic adults, as well as to examine the relationship between this potential marker of endothelial-cell activation and the consequences of sepsis (i.e., multiple organ failure and death). Using a sandwich-type enzyme-linked immunosorbent assay (ELISA), we measured cICAM-1 in blood samples obtained within 12 h of admission to an intensive care unit (ICU) for sepsis and other conditions. We found cICAM-1 levels to be increased in 25 septic patients (1,259 +/- 159 ng/ml, mean +/- SEM) as compared with 12 healthy volunteers(355 +/- 41 ng/ml, p < 0.0001) and four ICU patients without systemic inflammatory response syndrome (SIRS) (585 +/- 76 ng/ml, p < 0.001). Twenty-five patients with SIRS but no evidence of causative infection also had elevated levels of cICAM-1 (937 +/- 144 ng/ml, p = 0.12 versus sepsis). Serial measurements over the first week of sepsis demonstrated persistent elevation in most patients. Day 1 cICAM-1 levels were higher(p = 0.017, ANOVA) in 16 patients with septic shock than in seven with severe sepsis and two with sepsis but without hypotension or hypoperfusion. There was a positive correlation (r = 0.50, p = 0.009) between Day-1 cICAM-1 measurements and severity of shock as determined by the presence of hypotension and vasopressor use. There was a positive, although modest, correlation (r = 0.46, p = 0.02) between the Day-1 cICAM-1 level and cumulative organ-system failure over the course of critical illness. Nonsurvivors (n = 12) exhibited significantly higher Day-1 cICAM-1 levels than did survivors (1,697 +/- 258 ng/ml versus 854 +/- 111 ng/ml, p = 0.0096). Using logistic regression, the presence of failure in three or more organ systems on Day 1 of sepsis and Day 1 cICAM-1 > 1,200 ng/ml independently correlated with a high likelihood of nonsurvival. We conclude that cICAM-1 is increased in sepsis in adults, and corresponds with the intensity of sepsis and severity of shock, as well as with subsequent organ failure and eventual outcome.