Pathophysiological Pathways of the Adult Respiratory Distress Syndrome

  • W. M. Zapol
  • J. Qvist
  • R. L. Trelstad
  • F. Lemaire


To achieve a better understanding of the pathogenesis of acute lung injuries which can lead to the adult respiratory distress syndrome, the intensive care physician must recognize that most hospitalized patients with acute respiratory failure (ARF) fall into two broad categories:


Right Ventricular Acute Lung Injury Pulmonary Artery Pressure Pulmonary Capillary Wedge Pressure Adult Respiratory Distress Syndrome 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ashbaugh DG, Bigelow DB, Petty TL, Levine BE (1967) Acute respiratory distress in the adult. Lancet 11: 319–323CrossRefGoogle Scholar
  2. 2.
    Bachofen M, Weibel ER (1977) Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116: 561–589Google Scholar
  3. 3.
    Barratt-Boyes BG, Wood EH (1958) Cardiac output and related measurements and pressure values in the right heart and associated vessels, together with an analysis of the hemodynamic response to the inhalation of high oxygen mixtures in healthy subjects. J Lab Clin Med 51: 72–90PubMedGoogle Scholar
  4. 4.
    Bayley T, Clements JA, Osbahr AJ (1967) Pulmonary and circulatory effects of fibrinopeptides. Circ Res 21: 469–485PubMedGoogle Scholar
  5. 5.
    Bell RC, Coalson JJ, Smith JD, Johanson WG (1983) Multiple organ system failure and infection in adult respiratory distress syndrome. Ann Intern Med 99: 293–298PubMedGoogle Scholar
  6. 6.
    Benumof J (1979) Hypoxic vasoconstriction and infusion of sodium nitroprusside. Anesthesiology 50: 481–483PubMedCrossRefGoogle Scholar
  7. 7.
    Bernard GR, Luce JM, Sprung CL et al. (1987) High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 317: 1565–1570PubMedCrossRefGoogle Scholar
  8. 8.
    Blaisdell FW, Lewis FR Jr (1977) Respiratory distress syndrome of shock and trauma, ( Major problems in clinical surgery, vol XXI.) WB Saunders, PhiladelphiaGoogle Scholar
  9. 9.
    Bove AA, Santamore WP (1981) Ventricular interdependence. Prog Cardiovasc Dis 23: 365PubMedCrossRefGoogle Scholar
  10. 10.
    Brigham KL, Woolverton WC, Blake LH, Staub NC (1974) Increased sheep lung vascular permeability caused by pseudomonas bacteremia. J Clin Invest 54: 792–804PubMedCrossRefGoogle Scholar
  11. 11.
    Brigham KL, Snell JD, Harris TR et al. (1979) Indicator dilution lung water and vascular permeability in humans. Circ Res 44: 523–530PubMedGoogle Scholar
  12. 12.
    Calvin JE, Baer RW, Glantz SA (1986) Pulmonary injury depresses cardiac systolic function through Starling mechanism. Am J Physiol 251: H722PubMedGoogle Scholar
  13. 13.
    Carvalho ACA (1985) Blood alterations in ARDS. In: Zapol WM, Falke K (eds) Acute respiratory failure. Marcel Dekker, New York, pp 303–346Google Scholar
  14. 14.
    Carvalho ACA, Bellman SM, Saullo VJ, Quinn D, Zapol WM (1982) Altered factor VIII in acute respiratory failure. N Engl J Med 307: 1113–1119PubMedCrossRefGoogle Scholar
  15. 15.
    Collee G, Lynch K, Hill RD, Zapol WM (1987) Bedside measurement of pulmonary capillary pressure in patients with acute respiratory failure. Anesthesiology 66: 614–620PubMedCrossRefGoogle Scholar
  16. 16.
    Colley PS, Cheney FW, Hlastala MP (1979) Ventilation-perfusion and gas exchange effects of sodium nitroprusside in dogs with normal and edematous lung. Anesthesiology 50: 489–495PubMedCrossRefGoogle Scholar
  17. 17.
    Cook JA, Wise WC, Halushka PV (1980) Elevated thromboxane levels in the rat during endotoxin shock. J Clin Invest 65: 227–230PubMedCrossRefGoogle Scholar
  18. 18.
    Dantzker DR, Brook CJ, Dehart P, Lynch JP, Weg JG (1979) Ventilation perfusion distributions in ARDS. Am Rev Respir Dis 120: 1039–1052PubMedGoogle Scholar
  19. 19.
    Deby-Dupont G, Braun M, Lamy M, Deby C, Pincemail J, Faymonville ME, Damas P, Bodson L, Lecart MP, Goutier R (1987) Thromboxane and prostacyclin release in adult respiratory distress syndrome. Intensive Care Med 13: 167–174PubMedCrossRefGoogle Scholar
  20. 20.
    Deneke SM, Fanburg BL (1980) Normobaric oxygen toxicity of the lung. N Engl J Med 303: 76–86PubMedCrossRefGoogle Scholar
  21. 21.
    Duchateau J, Haas M, Schreyen H et al. (1984) Complement activation in patients at risk of developing the adult respiratory distress syndrome. Am Rev Respir Dis 130:1058-–1064PubMedGoogle Scholar
  22. 22.
    Eeles GH, Sevitt S (1967) Microthrombosis in injured and burned patients. J Pathol Bacteriol 93: 275–293PubMedCrossRefGoogle Scholar
  23. 23.
    Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver MB (1972) Ventilation with end expiratory pressure in acute lung disease. J Clin Invest 51: 2315–2323PubMedCrossRefGoogle Scholar
  24. 24.
    Fallat RJ, Lamy M, Koeninger E, Hill JD (1976) Use of physiologic and pathologic correlations in evaluating adult respiratory distress syndrome. In: Zapol WM, Qvist J (eds) Artificial lungs for acute respiratory failure. Academic Press, New York, pp 391–404Google Scholar
  25. 25.
    Fountain SW, Martin BA, Musclow CE, Cooper JD (1980) Pulmonary leukostasis and its relationship to pulmonary dysfunction in sheep and rabbits. Circ Res 46: 175–180PubMedGoogle Scholar
  26. 26.
    Fowler AA, Hamman RF, Good JT et al. (1983) Adult respiratory distress syndrome: risk with common predispositions. Ann Intern Med 98: 593–597PubMedGoogle Scholar
  27. 27.
    Gattinoni L, Pesenti A, Mascheroni D et al. (1986) Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. JAMA 256: 881–886PubMedCrossRefGoogle Scholar
  28. 28.
    Gattinoni L, Pesenti A, Bambino M et al. (1988) Relationship between lung computed tomographic density, gas exchange and PEEP in acute respiratory failure. Anesthesiology 69: 824–832PubMedCrossRefGoogle Scholar
  29. 29.
    Grant K, Rodvien R, Mielke CH (1978) Altered factor VIII complexes in patients with acute respiratory insufficiency. Thromb Haemost 40: 326–334PubMedGoogle Scholar
  30. 30.
    Greene R, Boggis CRM, Jantsch HS (1985) Radiography and angiography of the pulmonary circulation in ARDS. In: Zapol WM, Falke K (eds) Acute respiratory failure. Marcel Dekker, New York, pp 275–302Google Scholar
  31. 31.
    Greene R, Lind S, Jantsch H et al. (1987) Pulmonary vascular obstruction in severe ARDS: angiographic alterations following intravenous fibrinolytic therapy. Am J Roentgenol 148: 501–508Google Scholar
  32. 32.
    Hemmer M, Suter PM (1979) Treatment of cardiac and renal effects of PEEP with dopamine in patients with acute respiratory failure. Anesthesiology 50: 399–403PubMedCrossRefGoogle Scholar
  33. 33.
    Hill JD, Ratliff JL, Parrott JCW et al. (1976) Pulmonary pathology in acute respiratory insufficiency: lung biopsy as a diagnostic tool. J Thorac Cardiovasc Surg 71: 64–71PubMedGoogle Scholar
  34. 34.
    Hill JD, Rodvien R, Snider MT, Bartlett RH (1978) State of the Art Address: clinical extracorporeal membrane oxygenation for acute respiratory insufficiency. Trans Am Soc Artif Intern Organs 24: 753–763PubMedGoogle Scholar
  35. 35.
    Hjortso E, Qvist J, Bud MI et al. (1988) Progressive fatal ARDS after accidental inhalation of zinc chloride smoke. Intensive Care Med 14: 17–24PubMedCrossRefGoogle Scholar
  36. 36.
    Hopewell PC, Murray JF (1976) Effects of continuous positive-pressure ventilation in experimental pulmonary edema. J Appl Physiol 40: 568–574PubMedGoogle Scholar
  37. 37.
    Jardin F, Eveleigh MC, Gurdjian F, Delille F, Margairaz A (1979) Venous admixture in human septic shock: comparative effects of blood volume expansion, dopamine infusion and isoproterenol infusion on mismatching of ventilation and pulmonary blood flow in peritonitis. Circulation 60: 155–159PubMedGoogle Scholar
  38. 38.
    Jones R, Zapol WM, Tomashefski JF, Kirton OC, Kobayashi K, Reid L (1985) Pulmonary vascular pathology; human and experimental studies. In: Zapol WM, Falke K (eds) Acute respiratory failure. Marcel Dekker, New York, pp 23–160Google Scholar
  39. 39.
    Kadowitz PJ, Capnick BM, Feigen LP, Hyman AL, Nelson PK, Spannhake EW (1978) Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin PGI2. J Appl Physiol 45: 408–413PubMedGoogle Scholar
  40. 40.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) Prognosis in acute organ-system failure. Ann Surg 202: 685–693PubMedCrossRefGoogle Scholar
  41. 41.
    Kreil EA, Greene E, Fitzgibbon C, Robinson DR, Zapol WM (1990) The effects of recombinant human tumor necrosis factor alpha, lymphotoxin, and Escherichia coli lipopolysaccharide on hemodynamics, lung microvascular permeability, and eicosanoid synthesis in anesthetized sheep. Circ Res 65: 502–514Google Scholar
  42. 42.
    Kolobow T, Moretti MP, Fumagalli R et al. (1987) Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation. Am Rev Resp Dis 135: 312–315PubMedGoogle Scholar
  43. 43.
    Lampron N, Lemaire F, Harf A, Palot M, Matamis D, Lorino AM (1985) Mechanical ventilation with 100% oxygen does not increase intrapulmonary shunt in patients with severe bacterial pneumonia. Am Rev Respir Dis 131: 409–413PubMedGoogle Scholar
  44. 44.
    Lamy M, Fallat RJ, Koeniger E et al. (1976) Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis 114: 267–284PubMedGoogle Scholar
  45. 45.
    Lemaire F, Harari A, Rapin M, Jardin F, Teisseire B, Laurent D (1976) Assessment of gas exchange during venoarterial bypass using the membrane lung. In: Zapol WM, Qvist J (eds) Artificial lungs for acute respiratory failure. Academic Press, New York, pp 421–433Google Scholar
  46. 46.
    Lemaire F, Gastinne H, Regnier B, Teisseire B, Rapin M (1978) Perfusion changes modify intrapulmonary shunt QS/QT in patients with ARDS. Am Rev Respir Dis 117: 144Google Scholar
  47. 47.
    Lemaire F, Jardin F, Regnier B et al. (1978) Pulmonary gas exchange during venoarterial bypass with a membrane lung for acute respiratory failure. J Thorac Cardiovasc Surg 75: 839–846PubMedGoogle Scholar
  48. 48.
    Lemaire F, Regnier B, Simoneau G, Harf A (1980) PEEP suppresses the increase of shunting caused by dopamine infusion. Anesthesiology 52: 376–377PubMedCrossRefGoogle Scholar
  49. 49.
    Loyd JE, Newman JH, Brigham KL (1984) Permeability pulmonary edema. Arch Intern Med 144: 143–147CrossRefGoogle Scholar
  50. 50.
    Lynch JP, Mhyre JG, Dantzker DR (1979) The influence of cardiac output on intrapulmonary shunt. J Appl Physiol 46: 315–321PubMedGoogle Scholar
  51. 51.
    Malo J, Ali J, Duke K, Gallagher W, Wood LDH (1980) How does PEEP reduce QS/QT in pulmonary edema. Fed Proc 39: 280Google Scholar
  52. 52.
    Martyn JAJ, Snider MT, Szyfelbein SK, Burke JF, Laver MB (1980) Right ventricular dysfunction following acute thermal injury. Ann Surg 191: 330–335PubMedCrossRefGoogle Scholar
  53. 53.
    Martyn JAJ, Wilson RS, Burke JF (1981) Thermodilution right ventricular volume: a novel and better predictor of volume replacement in acute thermal injury. J Trauma 21: 619PubMedCrossRefGoogle Scholar
  54. 54.
    Matamis D, Lemaire F, Harf A, Brun-Buisson C, Ansquer JC, Atlan G (1984) Total respiratory pressure volume curves in the adult respiratory distress syndrome. Chest 86:54-–57CrossRefGoogle Scholar
  55. 55.
    Matamis D, Lemaire F, Harf A, Teisseire B, Brun-Buisson C (1984) Redistribution of pulmonary blood flow induced by positive end-expiratory pressure and dopamine infusion in acute respiratory failure. Am Rev Respir Dis 129: 39–44PubMedGoogle Scholar
  56. 56.
    Maunder RJ, Hackman RC, Riff E, Albert RK, Sprungmeyer SC (1986) Occurrence of adult respiratory distress syndrome in neutropenic patients. Am Rev Resp Dis 133: 313–316PubMedGoogle Scholar
  57. 57.
    Maunder RJ, Shuman WP, McHugh JW, Margolin SI, Butler J (1986) Preservation of normal lung regions in the adult respiratory distress syndrome: Analysis by computed tomography. JAMA 255: 2463–2465PubMedCrossRefGoogle Scholar
  58. 58.
    Montgomery BA, Stager MA, Carrico CJ, Hudson LD (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132: 485–489PubMedGoogle Scholar
  59. 59.
    Morel DR, Dargent F, Bachmann M, Suter PM, Junod AF (1985) Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome. Am Rev Respir Dis 132: 479–484PubMedGoogle Scholar
  60. 60.
    Murray JF (1986) The normal lung: the basis for diagnosis and treatment of pulmonary disease, 3rd edn. WB Saunders, PhiladelphiaGoogle Scholar
  61. 61.
    Naeije R, Melot C, Mols P, Hallemans R (1982) Effects of vasodilators on hypoxic pulmonary vasoconstriction in normal man. Chest 82: 404–410PubMedCrossRefGoogle Scholar
  62. 62.
    National Heart, Lung, and Blood Institute, Division of Lung Diseases (1979) Extracorporeal support for respiratory insufficiency: a collaborative study. National Institutes of Health, BethesdaGoogle Scholar
  63. 63.
    Neilems JM, Cooper JD, Henderson RD, Peng T, Phillips MJ (1976) Emergency open lung biopsy. Ann Thorac Surg 22: 260–264CrossRefGoogle Scholar
  64. 64.
    Ognibene FP, Martin SE, Parker MM et al. (1986) Adult respiratory distress syndrome in patients with severe neutropenia. Chest 90: 547–551Google Scholar
  65. 65.
    Payen D, Carli P, Brun-Buisson C et al. (1985) Lower body positive pressure vs dopamine during PEEP in humans. J Appl Physiol 58: 77–82PubMedGoogle Scholar
  66. 66.
    Pontoppidan H, Geffin B, Lowenstein E (1973) Acute respiratory failure in the adult. Little Brown, BostonGoogle Scholar
  67. 67.
    Pontoppidan H, Wilson RS, Rie MA, Schneider RC (1977) Respiratory intensive care. Anesthesiology 47: 96–116PubMedCrossRefGoogle Scholar
  68. 68.
    Pontoppidan H, Hüttemeier P, Quinn DA (1985) Acute respiratory failure: etiology, demography, and outcome. In: Zapol WM, Falke K (eds) Acute respiratory failure. Marcel Dekker, New York, pp 1–21Google Scholar
  69. 69.
    Pratt PC, Vollmer RT, Shelburne JD, Crapo JB (1979) Pulmonary morphology in a multihospital collaborative extracorporeal membrane oxygenation project. I. Light microscopy. Am J Pathol 95: 191–214PubMedGoogle Scholar
  70. 70.
    Qvist J, Mygind T, Crottogini A et al. (1988) Cardiovascular adjustments to acute pulmonary vascular injury in dogs. Anesthesiology 68: 341–349PubMedCrossRefGoogle Scholar
  71. 71.
    Radermacher P, Huet Y, Pluskwa F et al. (1988) Comparison of ketanserin and sodium nitroprusside in patients with severe ARDS. Anesthesiology 68: 152–157PubMedCrossRefGoogle Scholar
  72. 72.
    Ralph DD, Robertson HT, Weaver LJ, Hlastala MP, Carrico CJ, Hudson LD (1985) Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome. Am Rev Respir Dis 131: 54–60PubMedGoogle Scholar
  73. 73.
    Regnier B, Rapin M, Gory G, Lemaire F, Teisseire B, Harari A (1977) Hemodynamic effects of dopamine in septic shock. Intensive Care Med 3: 47–53PubMedCrossRefGoogle Scholar
  74. 74.
    Regnier B, Safran D, Carlet J, Teisseire B (1979) Comparative haemodynamic effects of dopamine and dobutamine in septic shock. Intensive Care Med 5: 115–120PubMedCrossRefGoogle Scholar
  75. 75.
    Saldeen T (ed) (1979) The microembolism syndrome, a review. In: The microembolism syndrome. Almqvist Wiksell International, Stockholm, pp 7–44Google Scholar
  76. 76.
    Salvador RA, Fiedler-Nagy C, Coffey JW (1985) Biochemical basis for drug therapy to prevent pulmonary fibrosis in ARDS. In: Zapol WM, Kalke KJ (eds) Acute respiratory failure. Marcel Dekker, New York, pp 407–506Google Scholar
  77. 77.
    Schneider R, Zapol WM, Carvalho ACA (1980) Platelet consumption and sequestration in severe acute respiratory failure. Am Rev Respir Dis 122: 445–451PubMedGoogle Scholar
  78. 78.
    Seidenfeld JJ, Pohl DF, Bell RC, Harris GD, Johanson WG (1986) Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 134: 12–16PubMedGoogle Scholar
  79. 79.
    Sibbald WJ, Driedger AA, Cunningham DG, Cheung H (1986) Right and left ventricular performance in acute hypoxemic respiratory failure. Crit Care Med 14: 852–857PubMedCrossRefGoogle Scholar
  80. 80.
    Snider MT, Zapol WM (1976) Assessment of pulmonary oxygenation during venoarterial bypass with aortic root return. In: Zapol WM, Qvist J (eds) Artificial lungs for acute respiratory failure. Academic Press, New York, pp 251–274Google Scholar
  81. 81.
    Snider MT, Rie MA, Bingham JB, Lauer J, Urbina A, Strauss HW (1980) Right ventricular performance in ARDS: radionuclide scintiscan and thermal dilution studies. Am Rev Respir Dis 121: 192Google Scholar
  82. 82.
    Suter PM, Fairley HB, Schlobohm RM (1975) Shunt, lung volume and perfusion during short periods of ventilation with oxygen. Anesthesiology 43: 617–627PubMedCrossRefGoogle Scholar
  83. 83.
    Teboul J-L, Zapol WM, Brun-Bruisson C, Abrouk F, Rauss A, Lemaire F (1989) A comparison of pulmonary artery occlusion pressure and left ventricular end-diastolic pressure during mechanical ventilation with PEEP in patients with severe ARDS. Anesthesiology 70: 261–266PubMedCrossRefGoogle Scholar
  84. 84.
    Tomashefski JF, Davies P, Boggis C, Greene R, Zapol WM, Reid LM (1983) The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol 112:112-–126PubMedGoogle Scholar
  85. 85.
    West JB (1987) Pulmonary pathophysiology: the essentials, 3rd edn. Williams & Wilkins, BaltimoreGoogle Scholar
  86. 86.
    Zapol WM (1987) Membrane lung perfusion for acute respiratory failure. In: Grillo HC, Eschapasse H (eds) Major challenges in thoracic surgery. (International trends in general thoracic surgery, vol 2.) pp 177–186Google Scholar
  87. 87.
    Zapol WM, Jones R (1987) Vascular components of ARDS: clinical pulmonary hemodynamics and morphology. Am Rev Respir Dis 136: 471–474PubMedCrossRefGoogle Scholar
  88. 88.
    Zapol WM, Snider MT (1977) Pulmonary hypertension in severe acute respiratory failure. N Engl J Med 296: 476–480PubMedCrossRefGoogle Scholar
  89. 89.
    Zapol WM, Snider MT (1980) Membrane lungs for acute respiratory failure: current status. Am Rev Respir Dis 121: 907–909PubMedGoogle Scholar
  90. 90.
    Zapol WM, Snider MT, Schneider RC, Rie MA (1976) Pulmonary hypertension in severe acute respiratory failure. In: Zapol WM, Qvist J (eds) Artificial lungs for acute respiratory failure: theory and practice. Academic Press, New York, pp 435–454Google Scholar
  91. 91.
    Zapol WM, Trelstad RL, Coffey JW, Tsai I, Salvador RA (1979) Pulmonary fibrosis in severe acute respiratory failure. Am Rev Respir Dis 119: 547–554PubMedGoogle Scholar
  92. 92.
    Zapol WM, Snider MT, Rie M, Frikker M, Quinn D (1985) Pulmonary circulation during ARDS. In: Zapol WM, Falke K (eds) Acute respiratory failure. Marcel Dekker, New York, pp 241–273Google Scholar

Copyright information

© Springer-Verlag London Limited 1992

Authors and Affiliations

  • W. M. Zapol
  • J. Qvist
  • R. L. Trelstad
  • F. Lemaire

There are no affiliations available

Personalised recommendations