title: How to ventilate patients with acute lung injury and acute respiratory distress syndrome.
abstract: OBJECTIVE
  The purpose of this paper is to review the mechanisms of ventilator-induced lung injury as a basis for providing the less damaging mechanical ventilation in patients with acute respiratory failure.
  
  
  RESULTS
  In normal lungs, high tidal volume causes an immediate gene upregulation and downregulation. Although the importance of alveolar inflammatory reaction is well known, recent findings suggest the potential role of airway distension in causing ventilator-induced lung injury. The initial activation has been shown to occur in the airways, accounting for the damages induced by high peak flow. The healthier lung regions are more exposed to the injury, since they may be subjected to strain. Challenge with endotoxin enhances in a synergistic manner the pulmonary inflammation induced by mechanical ventilation. However, mechanical strain and endotoxin seem to trigger lung inflammation through two different pathways. Despite convincing experimental and clinical evidences of lung injury, the clinical implementation of low tidal volume ventilation is still limited and has not yet become part of standard clinical practice. Setting positive end-expiratory pressure remains an open problem because the ALVEOLI study did not provide any exhaustive answers, likely because of methodologic problems and, unphysiologic design.
  
  
  CONCLUSIONS
  Gentle lung ventilation must be standard practice. Because stress and strain are the triggers of ventilator-induced lung injury, their clinical equivalents should be measured (transpulmonary pressure and the ratio between tidal volume and end-expiratory lung volume). For a rational application of positive end-expiratory pressure, the potential for recruitment in any single patient should be estimated.
authors.affiliation: Istituto di Anestesia e Rianimazione, Ospedale Maggiore di Milano-IRCCS, Università degli Studi di Milano, Milano, Italy. gattinon@policlinico.mi.it
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Pietro
authors.initials: P
authors.lastname: Caironi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Carlesso
mesh_terms: D000818:Animals; D002985:Clinical Protocols; D004195:Disease Models, Animal; D006801:Humans; D055370:Lung Injury; D008954:Models, Biological; D011175:Positive-Pressure Respiration / Q000379:methods; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D013314:Stress, Mechanical