title: Protein C depletion early after trauma increases the risk of ventilator-associated pneumonia.
abstract: BACKGROUND
  Mechanically ventilated trauma patients have a high risk for the development of ventilator-associated pneumonia (VAP). We have recently reported that reduced plasma protein C (PC) levels early after trauma/shock are associated with coagulopathy and mortality. Furthermore, trauma patients with tissue injury and shock are at higher risk for the development of VAP.
  
  
  OBJECTIVE
  We hypothesized that low PC levels early after trauma are associated with an increased susceptibility to VAP in trauma patients.
  
  
  METHODS
  Fifty-nine acutely injured, intubated trauma patients were admitted to the critical care unit. Serial blood samples were drawn and coagulation factors were measured. VAP was diagnosed by presence of bacteria on bronchial alveolar lavage specimen, bilateral infiltrates on chest roentgenogram, and fever or elevated white blood cell count.
  
  
  RESULTS
  There were no differences in demographic or injury characteristics between patients who developed VAP and those who did not. As expected, patients who developed VAP had more ventilator days, hospital days, intensive care unit days, and greater mortality (all p < 0.05). Patients in both groups had lower mean PC levels at 6 hours compared with baseline. Noninfected patients' PC subsequently returned to near baseline levels, whereas those patients who eventually acquired VAP had significantly lower PC levels at both 12 and 24 hours (12 hours: 79 vs. 96%, p = 0.05; 24 hours: 75 vs. 97% p = 0.02). Soluble endothelial PC receptor (sEPCR) levels were also lower at 24 hours (82 vs. 99% in the noninfected group, p = 0.04).
  
  
  CONCLUSIONS
  The activation of PC pathway early after trauma may protect the vascular endothelium by both its anticoagulant and cytoprotective effects. However, trauma patients who later developed VAP have significantly lower plasma levels of PC within 24 hours after injury, suggesting a possible consumption of this vitamin K-dependent protein and an inhibition of its activation by inflammatory mediators. EPCR is involved in the activation of PC and is also a mediator of its cytoprotective effects.
  
  
  CONCLUSIONS
  Critically ill trauma patients have an early activation of the PC pathway, associated with a rapid decrease in the plasma levels of this protein and increase in EPCR. Plasma levels of PC return to normal levels within 24 hours in most patients. However, patients who go on to acquire VAP have persistently low plasma levels of PC in the immediate period after trauma. Whether PC could play a mechanistic role in the host response against nosocomial lung infection warrants further study.
authors.affiliation: Department of Surgery, University of California, San Francisco, California, USA. mcohen@sfghsurg.ucsf.edu
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Cohen
authors.forename: Natasha
authors.initials: N
authors.lastname: Bir
authors.forename: Pamela
authors.initials: P
authors.lastname: Rahn
authors.forename: Rachel
authors.initials: R
authors.lastname: Dotson
authors.forename: Karim
authors.initials: K
authors.lastname: Brohi
authors.forename: Brian B
authors.initials: BB
authors.lastname: Chesebro
authors.forename: Robert
authors.initials: R
authors.lastname: Mackersie
authors.forename: Michel
authors.initials: M
authors.lastname: Carles
authors.forename: Jeanine
authors.initials: J
authors.lastname: Wiener-Kronish
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Pittet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D000074283:Endothelial Protein C Receptor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000097:blood*; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000097:blood; D012121:Respiration, Artificial / Q000009:adverse effects*; D012307:Risk Factors; D018180:Thrombomodulin / Q000097:blood; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000097:blood*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface; D018180:Thrombomodulin