title: Female sex protects from organ failure and sepsis after major trauma haemorrhage.
abstract: BACKGROUND
  Biological sex is considered a risk factor for adverse outcome after major trauma. We hypothesized that female sex is protective against organ failure, sepsis and mortality in patients with traumatic haemorrhage.
  
  
  METHODS
  We selected patients from TraumaRegister DGU(®) (TR-DGU) with primary admission for blunt trauma with an injury severity score ≥ 16 and an ICU stay ≥ 3 days that presented with relevant bleeding in the years 2007-2012. Relevant bleeding was defined as Abbreviated Injury Scale (AIS) ≥ 3 with an estimated blood loss exceeding 20%, any femoral shaft fracture, any pelvic clamp as surrogate for unstable pelvic fracture or the presence of at least one criteria of haemorrhagic shock: shock index of 0.8-1.4; base excess of -2.0 to -10.0 mmol/L; body temperature ≤ 34°C; transfusion of ≥ 4 units of packed red blood cells; application of recombinant activated factor VII; any embolization during trauma room phase and pre-hospital resuscitation volume ≥ 3000 ml or any catecholamine use during pre-hospital care in the absence of cardiopulmonary resuscitation. A total of 7560 males and 2774 females were selected and analyzed for sex differences.
  
  
  RESULTS
  Higher rates of multiple organ failure (24.4 vs. 21.3%, Odds ratio [OR] 1.19 (95% confidence interval [95%CI] 1.07-1.33), p=0.001*) and sepsis (16.5 vs. 11.3%, OR 1.55 (95%CI 1.35-1.77), p<0.001*) were observed in males. Organ function of lung, cardio-circulatory system, liver and kidney were better in females, however, there was no difference in mortality. Stratification by age group revealed that in particular age-group 16-44 years was related to improved organ function which may indicate effects of sex hormones in females at reproductive age. Increased rates of sepsis in males were observed throughout virtually all age groups starting at 16 years of age, except in age group 54-64 years. This may suggest suppressive effect of testosterone on immune function.
  
  
  CONCLUSIONS
  Our study supports the hypothesis that female sex is associated with improved organ function following traumatic injury and haemorrhagic shock, in particular in age groups that are at reproductive age. However, further studies are warranted before sex steroids can be deployed as therapeutic intervention in critically ill trauma patients.
authors.affiliation: Institute for Emergency Medicine and Management in Medicine (INM), University Hospital of Munich, Campus Innenstadt, Munich, Germany. Electronic address: heiko.trentzsch@med.uni-muenchen.de.
authors.forename: H
authors.initials: H
authors.lastname: Trentzsch
authors.affiliation: Academy for Trauma Surgery (AUC), Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Nienaber
authors.affiliation: Department of Surgery, University Hospital of Munich, Campus Großhadern, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Behnke
authors.affiliation: Institute for Research in Operative Medicine (IFOM), University Witten/Herdecke, Campus Cologne-Merhein, Cologne, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lefering
authors.affiliation: Department of Surgery, University Hospital of Munich, Campus Großhadern, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Piltz
mesh_terms: D015998:Abbreviated Injury Scale; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D004967:Estrogens / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D009104:Multiple Trauma / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D011446:Prospective Studies; D020011:Protective Agents / Q000627:therapeutic use; D012151:Resuscitation; D012307:Risk Factors; D018805:Sepsis / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D012737:Sex Factors; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D016019:Survival Analysis; D014193:Trauma Centers / Q000706:statistics & numerical data*; D014949:Wounds, Nonpenetrating / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology
chemical_list: D004967:Estrogens; D020011:Protective Agents
keywords: Age factors; Blunt trauma; Haemorrhagic shock; Mortality; Multiple trauma; Risk factors; Sex; Sex hormones; Trauma registry