ELEVATED SELECTIN LEVELS AFTER SEVERE TRAUMA - A MARKER FOR SEPSIS AND ORGAN FAILURE AND A POTENTIAL TARGET FOR IMMUNOMODULATORY THERAPY

Severe injury is frequently complicated by sepsis and organ failure, A ctivated neutrophils adherent to inflamed endothelia have been implica ted in the pathogenesis of these complications, Identification of high -risk patients to target immunomodulatory therapy, however, remains an elusive goal, We postulated that (1) patients at risk for sepsis and organ failure could be identified by measuring shed selectin adhesions molecules as a marker of endothelial activation after injury and repe rfusion, and (2) these elevated selectin levels would correlate with i njury severity, shock, major complications, and mortality. Methods: Bl ood samples were drawn from 50 patients with multiple trauma every 2 h ours after admission for the first 24 hours, and every 6 hours for the subsequent 24 hours, and assayed for levels of shed E- and P-selectin , Patients were then stratified according to Injury Severity Score (IS S), presence or absence of shock, presence or absence of organ failure and/or infectious complications, and finally, death versus survival. Results: Trauma patients who had ISS < 30,who did not develop shock, s epsis, or organ dysfunction, had minimal increase in circulating E- an d P-selectin over admission levels, In patients who subsequently devel oped infectious complications, organ dysfunction, or both, or subseque ntly went on to die, elevated levels of E-selectin levels were evident by 36 hours, and in some cases, earlier, Differences between nonsurvi vors and survivors was statistically significant, There was also a tre nd toward increased levels of P-selectin in the same group of patients , although these differences were not significant, There was no differ entiation in either of the two selectins when patients were stratified according to ISS or presence of shock. Conclusion: A subset of major trauma patients manifest increased levels of circulating E-selectin ad hesion molecules after resuscitation, These patients seem to be at inc reased risk of death and possibly at risk for infectious complications and organ failure. Selectin blockade is a potential new immunomodulat ory strategy in this subgroup of patients.