title: The early second hit in trauma management augments the proinflammatory immune response to multiple injuries.
abstract: BACKGROUND
  Today's management of patients with multiple injuries remains controversial with regard to damage control and the appropriate timing of operative treatment ("second hit"). Among the multitude of physiologic parameters critical to the immune defense and clinical course of recovery, recent research has proven the regulation of distinct pro- and anti-inflammatory mediators to be closely associated with posttraumatic outcome and complications, including systemic inflammatory response syndrome (SIRS) and sepsis. This study sought to investigate the significance of multiple injuries and consecutive operative treatment ("second hit") with regard to the early inflammatory profile and its importance within the host's immune function.
  
  
  METHODS
  Peripheral whole blood was obtained from 32 patients with multiple injuries (injury severity score [ISS] >20) and 14 healthy control subjects on the day of injury (day 0) and 24 hours thereafter (day 1). Trauma patients were divided into two groups (trauma versus trauma + immediate operation ["second hit"]). Whole blood was centrifuged at 400 g at room temperature for subsequent plasma collection and analyses of Interleukin-6 (IL-6), IL-10 and soluble triggering receptor expressed on myeloid cells (sTREM)-1 plasma concentrations by enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  IL-6 plasma levels from second hit trauma patients (n = 18, ISS 35.5 +/- 12.2) significantly exceeded values determined in both trauma patients without a second hit (n = 14, ISS 30.5 +/- 5.3) and healthy control subjects (n = 14) by posttrauma day 1 (p < 0.05). IL-10 plasma concentrations on day 1 were equally and significantly elevated in both trauma patient populations, when compared with control samples (p < 0.05). In contrast, sTREM-1 was exclusively increased in trauma patients with a second hit, suggesting a strong proinflammatory response in patients with multiple injuries challenged with immediate surgical care (p < 0.05).
  
  
  CONCLUSIONS
  Immediate surgical treatment of patients with multiple injuries augments the proinflammatory immune response in the early phase of recovery as determined by increased IL-6 and sTREM-1 plasma levels. If not required solely for damage control, the early second hit from additional surgical stress might promote posttraumatic complications by surcharging the innate immune response to injury.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Charité-University Hospitals Berlin, Campus Benjamin Franklin, Berlin, Germany. sven-kevin.tschoeke@charite.de
authors.forename: Sven K
authors.initials: SK
authors.lastname: Tschoeke
authors.forename: Markus
authors.initials: M
authors.lastname: Hellmuth
authors.forename: Arwed
authors.initials: A
authors.lastname: Hostmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ertel
authors.forename: Andreas
authors.initials: A
authors.lastname: Oberholzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood / Q000276:immunology*; D011971:Receptors, Immunologic / Q000097:blood; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D016753:Interleukin-10