title: Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses.
abstract: OBJECTIVE
  To review how biotrauma leads to the development of multiple system organ failure (MSOF).
  
  
  METHODS
  Published articles on experimental and clinical studies and review articles in the English language were collected and analyzed.
  
  
  RESULTS
  The concept that ventilation strategies using "large" tidal volumes and zero PEEP of injured lungs can enhance injury by the release of inflammatory mediators into the lungs and circulation, a mechanism that has been called biotrauma, is supported by evidence from experimental models ranging from mechanically stressed cell systems, to isolated lungs, intact animals, and humans. Biotrauma may lead to MSOF via spillover of lung-borne inflammatory mediators into the systemic circulation. However, spillover of other agents such as bacteria and soluble proapoptotic factors may also contribute to the onset of MSOF. Other less well studied mechanisms such as peripheral immunosuppression and translocation of bacteria and/or products from the gut may play an important role. Finally, genetic variability is a crucial factor.
  
  
  CONCLUSIONS
  The development of MSOF is a multifactorial process. Our proposed mechanisms linking mechanical ventilation and MSOF suggest several novel therapeutic approaches. However, it will first be necessary to study the mechanisms described above to delineate more precisely the contribution of each proposed factor, their interrelationships, and their time course. We suggest that scientific advances in immunology may offer novel approaches for prevention of MSOF secondary to ventilator-induced lung injury.
authors.affiliation: Department of Pediatric Intensive Care, VU Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. fb.plotz@vumc.nl
authors.forename: Frans B
authors.initials: FB
authors.lastname: Plötz
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: van Vught
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
mesh_terms: D000818:Animals; D017209:Apoptosis; D018988:Bacterial Translocation; D006801:Humans; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D009102:Multiple Organ Failure / Q000209:etiology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000628:therapy; D012307:Risk Factors; D013312:Stress, Physiological / Q000378:metabolism; D013990:Tidal Volume
chemical_list: D018836:Inflammation Mediators