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. Activated neutrophils adherent to inflamed endothelia have been implicated 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 reperfusion, and (2) these elevated selectin levels would correlate with injury severity, shock, major complications, and mortality.


METHODS
Blood samples were drawn from 50 patients with multiple trauma every 2 hours 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 (ISS), 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, sepsis, or organ dysfunction, had minimal increase in circulating E- and P-selectin over admission levels. In patients who subsequently developed infectious complications, organ dysfunction, or both, or subsequently went on to die, elevated levels of E-selectin levels were evident by 36 hours, and in some cases, earlier. Differences between nonsurvivors and survivors was statistically significant. There was also a trend toward increased levels of P-selectin in the same group of patients, although these differences were not significant. There was no differentiation in either of the two selections when patients were stratified according to ISS or presence of shock.


CONCLUSIONS
A subset of major trauma patients manifest increased levels of circulating E-selectin adhesion molecules after resuscitation. These patients seem to be at increased risk of death and possibly at risk for infections complications and organ failure. Selectin blockade is a potential new immunomodulatory strategy in this subgroup of patients.
Simons
R K
RK
Division of Trauma, University of California, San Diego, USA.
Hoyt
D B
DB
Winchell
R J
RJ
Rose
R M
RM
Holbrook
T
T
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000276:immunology; D019007:P-Selectin / Q000097:blood*; D018570:Risk Assessment; D018805:Sepsis / Q000097:blood* / Q000276:immunology; D014947:Wounds and Injuries / Q000097:blood* / Q000276:immunology
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D019040:E-Selectin; D019007:P-Selectin