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Critical Care
Published in: Critical Care 3/2002

01-06-2002 | Review

Science review: Mechanisms of ventilator-induced injury

Authors: James A Frank, Michael A Matthay

Published in: Critical Care | Issue 3/2002

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Abstract

Acute respiratory distress syndrome (ARDS) and acute lung injury are among the most frequent reasons for intensive care unit admission, accounting for approximately one-third of admissions. Mortality from ARDS has been estimated as high as 70% in some studies. Until recently, however, no targeted therapy had been found to improve patient outcome, including mortality. With the completion of the National Institutes of Health-sponsored Acute Respiratory Distress Syndrome Network low tidal volume study, clinicians now have convincing evidence that ventilation with tidal volumes lower than those conventionally used in this patient population reduces the relative risk of mortality by 21%. These data confirm the long-held suspicion that the role of mechanical ventilation for acute hypoxemic respiratory failure is more than supportive, in that mechanical ventilation can also actively contribute to lung injury. The mechanisms of the protective effects of low tidal volume ventilation in conjunction with positive end expiratory pressure are incompletely understood and are the focus of ongoing studies. The objective of the present article is to review the potential cellular mechanisms of lung injury attributable to mechanical ventilation in patients with ARDS and acute lung injury.

Literature
  1. Ashbaugh D, Bigelow D, Petty T, Levine B: Acute respiratory distress syndrome in adults. Lancet 1967, 2: 319-323. 10.1016/S0140-6736(67)90168-7View ArticlePubMed
  2. Petty T, Ashbaugh D: The adult respiratory distress syndrome: clinical features, factors influencing prognosis, and principles of management. Chest 1971, 60: 233-239.PubMed
  3. Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000, 342: 1334-1349. 10.1056/NEJM200005043421806View ArticlePubMed
  4. ARDS Network Investigators: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801View Article
  5. Frank J, Imai Y, Slutsky A: Pathogenesis of ventilator-induced lung injury. In Acute Respiratory Distress Syndrome (Edited by: Matthay M). Marcel Dekker, New York , in press.
  6. Thomsen GE, Morris AH: Incidence of the adult respiratory distress syndrome in the state of Utah. Am J Respir Crit Care Med 1995, 152: 965-971.View ArticlePubMed
  7. Luhr OR, Antonsen K, Karlsson M, Aardal S, Thorsteinsson A, Frostell CG, Bonde J: Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med 1999, 159: 1849-1861.View ArticlePubMed
  8. Hudson LD, Steinberg KP: Epidemiology of acute lung injury and ARDS. Chest 1999, 116: 74S-82S. 10.1378/chest.116.suppl_1.74S-aView ArticlePubMed
  9. Arroliga AC, Ghamra ZW, Trepichio AP, Trepichio PP, Komara JJ Jr, Smith A, Wiedemann HP: Incidence of ARDS in an Adult Population of Northeast Ohio. Chest 2002, 121: 1972-1976. 10.1378/chest.121.6.1972View ArticlePubMed
  10. Rubenfeld G, Caldwell E, Martin D, Steinberg K, Hudson L: The incidence of acute lung injury in adults in the U.S.: Results of the King County lung injury project [abstract]. Am J Respir Crit Care Med 2002, 165: A219.
  11. Gattinoni L, Caironi P, Pelosi P, Goodman LR: What has computed tomography taught us about the acute respiratory distress syndrome? Am J Respir Crit Care Med 2001, 164: 1701-1711.View ArticlePubMed
  12. Mead J, Takishima T, Leith D: Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol 1970, 28: 596-608.PubMed
  13. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999, 282: 54-61. 10.1001/jama.282.1.54View ArticlePubMed
  14. Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K: Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest 1995, 107: 1062-1073.View ArticlePubMed
  15. Goodman RB, Strieter RM, Martin DP, Steinberg KP, Milberg JA, Maunder RJ, Kunkel SL, Walz A, Hudson LD, Martin TR: Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med 1996, 154: 602-611.View ArticlePubMed
  16. Imanaka H, Shimaoka M, Matsuura N, Nishimura M, Ohta N, Kiyono H: Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs. Anesthesia Analgesia 2001, 92: 428-436.View ArticlePubMed
  17. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS: Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 1997, 99: 944-952.PubMed CentralView ArticlePubMed
  18. Dreyfuss D, Saumon G: Production of inflammatory cytokines in ventilator-induced lung injury: a reappraisal. Am J Respir Crit Care Med 2001, 163: 1176-1180.View ArticlePubMed
  19. Chiumello D, Pristine G, Slutsky AS: Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Crit Care Med 1999, 160: 109-116.View ArticlePubMed
  20. Nakamura T, Malloy J, McCaig L, Yao LJ, Joseph M, Lewis J, Veldhuizen R: Mechanical ventilation of isolated septic rat lungs: effects on surfactant and inflammatory cytokines. J Appl Physiol 2001, 91: 811-820.PubMed
  21. Imai Y, Kawano T, Iwamoto S, Nakagawa S, Takata M, Miyasaka K: Intratracheal anti-tumor necrosis factor-alpha antibody attenuates ventilator-induced lung injury in rabbits. J Appl Physiol 1999, 87: 510-515.PubMed
  22. Narimanbekov IO, Rozycki HJ: Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model. Exp Lung Res 1995, 21: 239-254.View ArticlePubMed
  23. Pugin J, Dunn I, Jolliet P, Tassaux D, Magnenat JL, Nicod LP, Chevrolet JC: Activation of human macrophages by mechanical ventilation in vitro. Am J Physiol 1998, 275: L1040-L1050.PubMed
  24. Dunn I, Pugin J: Mechanical ventilation of various human lung cells in vitro: identification of the macrophage as the main producer of inflammatory mediators. Chest 1999,116(1 suppl):95S-97S. 10.1378/chest.116.suppl_1.95SView ArticlePubMed
  25. Kurdowska A, Miller EJ, Noble JM, Baughman RP, Matthay MA, Brelsford WG, Cohen AB: Anti-IL-8 autoantibodies in alveolar fluid from patients with the adult respiratory distress syndrome. J Immunol 1996, 157: 2699-2706.PubMed
  26. Miller EJ, Cohen AB, Matthay MA: Increased interleukin-8 concentrations in the pulmonary edema fluid of patients with acute respiratory distress syndrome from sepsis. Crit Care Med 1996, 24: 1448-1454. 10.1097/00003246-199609000-00004View ArticlePubMed
  27. Held HD, Boettcher S, Hamann L, Uhlig S: Ventilation-induced chemokine and cytokine release is associated with activation of nuclear factor-KB and is blocked by steroids. Am J Respir Crit Care Med 2001, 163: 711-716.View ArticlePubMed
  28. Webb H, Tierney D: Experimental pulmonary edema due to intermittent positive pressure ventilation. Protection by positive end-expiratory pressure. Am Rev Respir Dis 1974, 110: 556-565.PubMed
  29. Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988, 137: 1159-1164.View ArticlePubMed
  30. West JB, Tsukimoto K, Mathieu-Costello O, Prediletto R: Stress failure in pulmonary capillaries. J Appl Physiol 1991, 70: 1731-1742.PubMed
  31. Parker JC, Ivey CL: Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs. J Appl Physiol 1997, 83: 1962-1967.PubMed
  32. Parker JC, Ivey CL, Tucker JA: Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs. J Appl Physiol 1998, 84: 1113-1118. 10.1063/1.368111View ArticlePubMed
  33. Parker JC, Ivey CL, Tucker A: Phosphotyrosine phosphatase and tyrosine kinase inhibition modulate airway pressure-induced lung injury. J Appl Physiol 1998, 85: 1753-1761.PubMed
  34. Parker JC: Inhibitors of myosin light chain kinase and phosphodiesterase reduce ventilator-induced lung injury. J Appl Physiol 2000, 89: 2241-2248.PubMed
  35. Wysolmerski RB, Lagunoff D: Involvement of myosin light-chain kinase in endothelial cell retraction. Proc Natl Acad Sci USA 1990, 87: 16-20.PubMed CentralView ArticlePubMed
  36. Cooper JA, van der Zee H, Line BR, Malik AB: Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance. J Appl Physiol 1987, 63: 1586-1590.PubMed
  37. Marks JD, Luce JM, Lazar NM, Wu JN, Lipavsky A, Murray JF: Effect of increases in lung volume on clearance of aerosolized solute from human lungs. J Appl Physiol 1985, 59: 1242-1248.PubMed
  38. Egan EA: Lung inflation, lung solute permeability, and alveolar edema. J Appl Physiol 1982, 53: 121-125.PubMed
  39. Egan EA: Responseof alveolar epithelial solute permeability to changes in lung inflation. J Appl Physiol 1980, 49: 1032-1036.PubMed
  40. Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA: Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med 2002, 165: 242-249.View ArticlePubMed
  41. Imai Y, Nakagawa S, Ito Y, Kawano T, Slutsky AS, Miyasaka K: Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation. J Appl Physiol 2001, 91: 1836-1844.PubMed
  42. Simma B, Luz G, Trawoger R, Hormann C, Klima G, Kreczy A, Baum M: Comparison of different modes of high-frequency ventilation in surfactant-deficient rabbits. Pediatr Pulmonol 1996, 22: 263-270. View ArticlePubMed
  43. Tschumperlin DJ, Oswari J, Margulies AS: Deformation-induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude. Am J Respir Crit Care Med 2000, 162: 357-362.View ArticlePubMed
  44. Vlahakis NE, Schroeder MA, Pagano RE, Hubmayr RD: Deformation-induced lipid trafficking in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2001, 280: L938-L946.PubMed
  45. Vlahakis N, Schroeder MA, Pagano RE, Hubmayr RD: The role of the cytoskeleton in deformation induced alveolar epithelial wounding and repair [abstract]. Am J Respir Crit Care Med 2002, 165: A379.
  46. von Bethmann AN, Brasch F, Nusing R, Vogt K, Volk HD, Muller KM, Wendel A, Uhlig S: Hyperventilation induces release of cytokines from perfused mouse lung. Am J Respir Crit Care Med 1998, 157: 263-272.View ArticlePubMed
  47. Douzinas E, Tsidemiadou P, Pitaridis M, Andrianakis I, Bobota-Chloraki A, Katsouyanni K, Sfyras D, Malagari K, Roussos C: The regional production of cytokines and lactate in sepsis-related multiple organ failure. Am J Respir Crit Care Med 1997, 155: 53-59.View ArticlePubMed
  48. Nahum A, Hoyt J, Schmitz L, Moody J, Shapiro R, Marini JJ: Effect of mechanical ventilation strategy on dissemination of intra-tracheally instilled Escherichia coli in dogs. Crit Care Med 1997, 25: 1733-1743. 10.1097/00003246-199710000-00026View ArticlePubMed
  49. Verbrugge SJ, Sorm V, van't Veen A, Mouton JW, Gommers D, Lachmann B: Lung overinflation without positive end-expiratory pressure promotes bacteremia after experimental Kleb-siella pneumoniae inoculation. Intensive Care Med 1998, 24: 172-177. 10.1007/s001340050541View ArticlePubMed
  50. Savel RH, Yao EC, Gropper MA: Protective effects of low tidal volume ventilation in a rabbit model of Pseudomonas aeruginosa -induced acute lung injury. Crit Care Med 2001, 29: 392-398. 10.1097/00003246-200102000-00032View ArticlePubMed
  51. Imai Y, Kajikawa O, Frevert C, de Perrot M, Fischer S, Parodo J, Edwards V, Cutz E, Zhang H, Ranieri M, Liu M, Keshavjee S, Marshall J, Martin T, Slutsky A: Injurious ventilatory strategies enhance organ apoptosis in rabbits [abstract]. Am J Respir Crit Care Med 2001, 163: 667A.View Article
  52. Guery B, Neviere R, Fialdes P, Chidiac C, Rousel-Delvallez M, Marchandise X, Beaucaire G: Mechanical ventilation regimen induces intestinal permeability changes in a rat model [abstract]. Am J Respir Crit Care Med 2002, 165: A505.
  53. Yukitake K, Brown CL, Schlueter MA, Clements JA, Hawgood S: Surfactant apoprotein A modifies the inhibitory effect of plasma proteins on surfactant activity in vivo. Pediatr Res 1995, 37: 21-25.View ArticlePubMed
  54. Wyszogrodski I, Kyei-Aboagye K, Taeusch HW Jr, Avery ME: Surfactant inactivation by hyperventilation: conservation by end-expiratory pressure. J Appl Physiol 1975, 38: 461-466.PubMed
  55. Veldhuizen RA, Welk B, Harbottle R, Hearn S, Nag K, Petersen N, Possmayer F: Mechanical ventilation of isolated rat lungs changes the structure and biophysical properties of surfactant. J Appl Physiol 2002, 92: 1169-1175.View ArticlePubMed
  56. Martynowicz MA, Minor TA, Walters BJ, Hubmayr RD: Regional expansion of oleic acid-injured lungs. Am J Respir Crit Care Med 1999, 160: 250-258.View ArticlePubMed
  57. Dreyfuss D, Martin-Lefevre L, Saumon G: Hyperinflation-induced lung injury during alveolar flooding in rats: effect of perfluoro-carbon instillation. Am J Respir Crit Care Med 1999, 159: 1752-1757.View ArticlePubMed
  58. Lecuona E, Saldias F, Comellas A, Ridge K, Guerrero C, Sznajder JI: Ventilator-associated lung injury decreases lung ability to clear edema in rats. Am J Respir Crit Care Med 1999, 159: 603-609.View ArticlePubMed
  59. Saldias FJ, Lecuona E, Comellas AP, Ridge KM, Rutschman DH, Sznajder JI: Beta-adrenergic stimulation restores rat lung ability to clear edema in ventilator-associated lung injury. Am J Respir Crit Care Med 2000, 162: 282-287.View ArticlePubMed
  60. Matthay MA, Wiener-Kronish JP: Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 1990, 142: 1250-1257.View ArticlePubMed
  61. Ware L, Matthay M: Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001, 163: 1376-1383.View ArticlePubMed
  62. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998, 338: 347-354. 10.1056/NEJM199802053380602View ArticlePubMed
  63. Hickling KG, Walsh J, Henderson S, Jackson R: Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med 1994, 22: 1568-1578.View ArticlePubMed
  64. Brower RG, Shanholtz CB, Fessler HE, Shade DM, White P Jr, Wiener CM, Teeter JG, Dodd-o JM, Almog Y, Piantadosi S: Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999, 27: 1492-1498. 10.1097/00003246-199908000-00015View ArticlePubMed
  65. Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez-Mondejar E, Clementi E, Mancebo J, Factor P, Matamis D, Ranieri M, Blanch L, Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun-Buisson C, Tobin M, Lemaire F: Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med 1998, 158: 1831-1838.View ArticlePubMed
  66. Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten BD, Todd TR, Slutsky AS: Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med 1998, 338: 355-361. 10.1056/NEJM199802053380603View ArticlePubMed
  67. Adams AB, Cakar N, Marini JJ: Static and dynamic pressure-volume curves reflect different aspects of respiratory system mechanics in experimental acute respiratory distress syndrome. Respir Care 2001, 46: 686-693.PubMed
  68. Hickling KG: The pressure–volume curve is greatly modified by recruitment. A mathematical model of ARDS lungs. Am J Respir Crit Care Med 1998, 158: 194-202.View ArticlePubMed
  69. Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F, Brochard L: Pressure–volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med 1999, 159: 1172-1178.View ArticlePubMed
  70. Karason S, Sondergaard S, Lundin S, Wiklund J, Stenqvist O: Evaluation of pressure/volume loops based on intratracheal pressure measurements during dynamic conditions. Acta Anaesthesiol Scand 2000, 44: 571-577. 10.1034/j.1399-6576.2000.00515.xView ArticlePubMed
  71. Brower R, for the ARDS Network investigators: Update on the ALVEOLI Study. American Thoracic Society International Conference, Atlanta, GA Monday, May 20, 2002
  72. Ranieri VM, Zhang H, Mascia L, Aubin M, Lin CY, Mullen JB, Grasso S, Binnie M, Volgyesi GA, Eng P, Slutsky AS: Pressure-time curve predicts minimally injurious ventilatory strategy in an isolated rat lung model. Anesthesiology 2000, 93: 1320-1328. 10.1097/00000542-200011000-00027View ArticlePubMed
  73. Mehta S, Lapinsky SE, Hallett DC, Merker D, Groll RJ, Cooper AB, MacDonald RJ, Stewart TE: Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome. Crit Care Med 2001, 29: 1360-1369. 10.1097/00003246-200107000-00011View ArticlePubMed
  74. Fort P, Farmer C, Westerman J, Johannigman J, Beninati W, Dolan S, Derdak S: High-frequency oscillatory ventilation for adult respiratory distress syndrome – a pilot study. Crit Care Med 1997, 25: 937-947. 10.1097/00003246-199706000-00008View ArticlePubMed
  75. The HIFI Study Group: High-frequency oscillatory ventilation compared with conventional intermittent mechanical ventilation in the treatment of respiratory failure in preterm infants: neurodevelopmental status at 16 to 24 months of postterm age. J Pediatr 1990, 117: 939-946.View Article
  76. Eisner MD, Thompson T, Hudson LD, Luce JM, Hayden D, Schoenfeld D, Matthay MA: Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001, 164: 231-236.View ArticlePubMed
Metadata
Title
Science review: Mechanisms of ventilator-induced injury
Authors
James A Frank
Michael A Matthay
Publication date
01-06-2002
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2002
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc1829

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