Sepsis pp 143-157 | Cite as

Sepsis and the Lung

  • MaryEllen Antkowiak
  • Lucas Mikulic
  • Benjamin T. SurattEmail author
Part of the Respiratory Medicine book series (RM)


Infections of the lung and pleural space are frequently associated with the development of sepsis syndromes. Additionally, sepsis from any source, pulmonary or extrapulmonary, may result in additional injury to the lung, known as the acute respiratory distress syndrome (ARDS), a syndrome characterized by an over-exuberant inflammatory response in the lung leading to increased alveolar-capillary permeability and predominantly non-hydrostatic pulmonary edema and hypoxemia. This syndrome and its complications contribute heavily to the morbidity and mortality associated with sepsis, and although no specific therapy exists to treat ARDS, supportive therapy including the use of low tidal volume ventilation can significantly improve outcomes.


Acute respiratory distress syndrome Sepsis Ventilator-induced lung injury Pulmonary fibrosis Pulmonary edema Surfactant Inflammatory cytokines Neutrophils 


  1. 1.
    Dremsizov T, Clermont G, Kellum JA, Kalassian KG, Fine MJ, Angus DC. Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course? Chest. 2006;129(4):968–78. doi: 10.1378/chest.129.4.968.CrossRefPubMedGoogle Scholar
  2. 2.
    Ashbaugh DG, Petty TL. Sepsis complicating the acute respiratory distress syndrome. Surg Gynecol Obstet. 1972;135(6):865–9.PubMedGoogle Scholar
  3. 3.
    Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818–24. doi: 10.1164/ajrccm.149.3.7509706.CrossRefPubMedGoogle Scholar
  4. 4.
    Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38(10):1573–82. doi: 10.1007/s00134-012-2682-1.CrossRefPubMedGoogle Scholar
  5. 5.
    Thille AW, Esteban A, Fernandez-Segoviano P, Rodriguez JM, Aramburu JA, Penuelas O, et al. Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med. 2013;187(7):761–7. doi: 10.1164/rccm.201211-1981OC.CrossRefPubMedGoogle Scholar
  6. 6.
    Fein AM, Lippmann M, Holtzman H, Eliraz A, Goldberg SK. The risk factors, incidence, and prognosis of ARDS following septicemia. Chest. 1983;83(1):40–2.CrossRefPubMedGoogle Scholar
  7. 7.
    Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995;151(2 Pt 1):293–301. doi: 10.1164/ajrccm.151.2.7842182.CrossRefPubMedGoogle Scholar
  8. 8.
    Li G, Malinchoc M, Cartin-Ceba R, Venkata CV, Kor DJ, Peters SG, et al. Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota. Am J Respir Crit Care Med. 2011;183(1):59–66. doi: 10.1164/rccm.201003-0436OC.CrossRefPubMedGoogle Scholar
  9. 9.
    Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685–93. doi: 10.1056/NEJMoa050333.CrossRefPubMedGoogle Scholar
  10. 10.
    Rubenfeld GD, Herridge MS. Epidemiology and outcomes of acute lung injury. Chest. 2007;131(2):554–62. doi: 10.1378/chest.06-1976.CrossRefPubMedGoogle Scholar
  11. 11.
    Villar J, Blanco J, Anon JM, Santos-Bouza A, Blanch L, Ambros A, et al. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011;37(12):1932–41. doi: 10.1007/s00134-011-2380-4.CrossRefPubMedGoogle Scholar
  12. 12.
    Moss M, Guidot DM, Steinberg KP, Duhon GF, Treece P, Wolken R, et al. Diabetic patients have a decreased incidence of acute respiratory distress syndrome. Crit Care Med. 2000;28(7):2187–92.CrossRefPubMedGoogle Scholar
  13. 13.
    Moss M, Bucher B, Moore FA, Moore EE, Parsons PE. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. JAMA. 1996;275(1):50–4.CrossRefPubMedGoogle Scholar
  14. 14.
    Moss M, Burnham EL. Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction. Crit Care Med. 2003;31(4 Suppl):S207–12. doi: 10.1097/01.CCM.0000057845.77458.25.CrossRefPubMedGoogle Scholar
  15. 15.
    Marshall RP, Webb S, Hill MR, Humphries SE, Laurent GJ. Genetic polymorphisms associated with susceptibility and outcome in ARDS. Chest. 2002;121(3 Suppl):68S–9S.CrossRefPubMedGoogle Scholar
  16. 16.
    Sun X, Ma SF, Wade MS, Acosta-Herrera M, Villar J, Pino-Yanes M, et al. Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2013;305(7):L467–77. doi: 10.1152/ajplung.00010.2013.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bajwa EK, Cremer PC, Gong MN, Zhai R, Su L, Thompson BT, et al. An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among Caucasians. PLoS One. 2011;6(5):e19469. doi: 10.1371/journal.pone.0019469.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tejera P, Meyer NJ, Chen F, Feng R, Zhao Y, O'Mahony DS, et al. Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin. J Med Genet. 2012;49(11):671–80. doi: 10.1136/jmedgenet-2012-100972.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    American Thoracic Society, The European Society of Intensive Care Medicine, and The Societe de Reanimation de Langue Francaise, and was approved by the ATS Board of Directors, July 1999, International consensus conferences in intensive care medicine: ventilator-associated Lung Injury in ARDS. Am J Respir Crit Care Med. 1999;160(6):2118–24. doi: 10.1164/ajrccm.160.6.ats16060.CrossRefGoogle Scholar
  20. 20.
    Rocco PR, Pelosi P. Pulmonary and extrapulmonary acute respiratory distress syndrome: myth or reality? Curr Opin Crit Care. 2008;14(1):50–5. doi: 10.1097/MCC.0b013e3282f2405b.CrossRefPubMedGoogle Scholar
  21. 21.
    Menezes SL, Bozza PT, Neto HC, Laranjeira AP, Negri EM, Capelozzi VL, et al. Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses. J Appl Physiol (1985). 2005;98(5):1777–83. doi: 10.1152/japplphysiol.01182.2004.CrossRefGoogle Scholar
  22. 22.
    Albaiceta GM, Taboada F, Parra D, Blanco A, Escudero D, Otero J. Differences in the deflation limb of the pressure-volume curves in acute respiratory distress syndrome from pulmonary and extrapulmonary origin. Intensive Care Med. 2003;29(11):1943–9. doi: 10.1007/s00134-003-1965-y.CrossRefPubMedGoogle Scholar
  23. 23.
    Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercesi P, Lissoni A. Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease. Different syndromes? Am J Respir Crit Care Med. 1998;158(1):3–11. doi: 10.1164/ajrccm.158.1.9708031.CrossRefPubMedGoogle Scholar
  24. 24.
    Negri EM, Hoelz C, Barbas CS, Montes GS, Saldiva PH, Capelozzi VL. Acute remodeling of parenchyma in pulmonary and extrapulmonary ARDS. An autopsy study of collagen-elastic system fibers. Pathol Res Pract. 2002;198(5):355–61. doi: 10.1078/0344-0338-00266.CrossRefPubMedGoogle Scholar
  25. 25.
    The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–8. doi: 10.1056/NEJM200005043421801.CrossRefGoogle Scholar
  26. 26.
    Doyle RL, Szaflarski N, Modin GW, Wiener-Kronish JP, Matthay MA. Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1818–24. doi: 10.1164/ajrccm.152.6.8520742.CrossRefPubMedGoogle Scholar
  27. 27.
    TenHoor T, Mannino DM, Moss M. Risk factors for ARDS in the United States: analysis of the 1993 National Mortality Followback Study. Chest. 2001;119(4):1179–84.CrossRefPubMedGoogle Scholar
  28. 28.
    Divertie MB, Brown Jr AL. The fine structure of the normal human alveolocapillary membrane. JAMA. 1964;187:938–41.CrossRefPubMedGoogle Scholar
  29. 29.
    Adeniji K, Steel AC. The pathophysiology of perioperative lung injury. Anesthesiol Clin. 2012;30(4):573–90. doi: 10.1016/j.anclin.2012.08.011.CrossRefPubMedGoogle Scholar
  30. 30.
    Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1334–49. doi: 10.1056/NEJM200005043421806.CrossRefPubMedGoogle Scholar
  31. 31.
    Suratt BT, Parsons PE. Mechanisms of acute lung injury/acute respiratory distress syndrome. Clin Chest Med. 2006;27(4):579–89. abstract viii doi: 10.1016/j.ccm.2006.06.005.CrossRefPubMedGoogle Scholar
  32. 32.
    Matthay MA, Zimmerman GA. Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol. 2005;33(4):319–27. doi: 10.1165/rcmb.F305.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Pierrakos C, Karanikolas M, Scolletta S, Karamouzos V, Velissaris D. Acute respiratory distress syndrome: pathophysiology and therapeutic options. J Clin Med Res. 2012;4(1):7–16. doi: 10.4021/jocmr761w.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Strieter RM, Belperio JA, Keane MP. Cytokines in innate host defense in the lung. J Clin Invest. 2002;109(6):699–705. doi: 10.1172/JCI15277.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Skoutelis AT, Kaleridis V, Athanassiou GM, Kokkinis KI, Missirlis YF, Bassaris HP. Neutrophil deformability in patients with sepsis, septic shock, and adult respiratory distress syndrome. Crit Care Med. 2000;28(7):2355–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Bellingan GJ. The pulmonary physician in critical care * 6: the pathogenesis of ALI/ARDS. Thorax. 2002;57(6):540–6.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ware LB, Eisner MD, Thompson BT, Parsons PE, Matthay MA. Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med. 2004;170(7):766–72. doi: 10.1164/rccm.200310-1434OC.CrossRefPubMedGoogle Scholar
  38. 38.
    Idell S. Endothelium and disordered fibrin turnover in the injured lung: newly recognized pathways. Crit Care Med. 2002;30(5 Suppl):S274–80.CrossRefPubMedGoogle Scholar
  39. 39.
    Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5(1):58–68. doi: 10.1038/nri1528.CrossRefPubMedGoogle Scholar
  40. 40.
    Michaud G, Cardinal P. Mechanisms of ventilator-induced lung injury: the clinician’s perspective. Crit Care. 2003;7(3):209–10. doi: 10.1186/cc1874.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Galani V, Tatsaki E, Bai M, Kitsoulis P, Lekka M, Nakos G, et al. The role of apoptosis in the pathophysiology of acute respiratory distress syndrome (ARDS): an up-to-date cell-specific review. Pathol Res Pract. 2010;206(3):145–50. doi: 10.1016/j.prp.2009.12.002.CrossRefPubMedGoogle Scholar
  42. 42.
    Korns D, Frasch SC, Fernandez-Boyanapalli R, Henson PM, Bratton DL. Modulation of macrophage efferocytosis in inflammation. Front Immunol. 2011;2:57. doi: 10.3389/fimmu.2011.00057.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Papazian L, Doddoli C, Chetaille B, Gernez Y, Thirion X, Roch A, et al. A contributive result of open-lung biopsy improves survival in acute respiratory distress syndrome patients. Crit Care Med. 2007;35(3):755–62. doi: 10.1097/01.CCM.0000257325.88144.30.CrossRefPubMedGoogle Scholar
  44. 44.
    Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014;43(1):276–85. doi: 10.1183/09031936.00196412.CrossRefPubMedGoogle Scholar
  45. 45.
    Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, et al. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013;368(9):795–805. doi: 10.1056/NEJMoa1215554.CrossRefPubMedGoogle Scholar
  46. 46.
    Young D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, et al. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med. 2013;368(9):806–13. doi: 10.1056/NEJMoa1215716.CrossRefPubMedGoogle Scholar
  47. 47.
    Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698):1351–63. doi: 10.1016/S0140-6736(09)61069-2.CrossRefPubMedGoogle Scholar
  48. 48.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–77. doi: 10.1056/NEJMoa010307.CrossRefPubMedGoogle Scholar
  49. 49.
    Rosenberg AL, Dechert RE, Park PK, Bartlett RH, Network NNA. Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort. J Intensive Care Med. 2009;24(1):35–46. doi: 10.1177/0885066608329850.CrossRefPubMedGoogle Scholar
  50. 50.
    National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564–75. doi: 10.1056/NEJMoa062200.CrossRefGoogle Scholar
  51. 51.
    National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, et al. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011;184(5):561–8. doi: 10.1164/rccm.201012-2090OC.CrossRefGoogle Scholar
  52. 52.
    Alhazzani W, Alshahrani M, Jaeschke R, Forel JM, Papazian L, Sevransky J, et al. Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials. Crit Care. 2013;17(2):R43. doi: 10.1186/cc12557.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Beitler JR, Shaefi S, Montesi SB, Devlin A, Loring SH, Talmor D, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40(3):332–41. doi: 10.1007/s00134-013-3194-3.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159–68. doi: 10.1056/NEJMoa1214103.CrossRefPubMedGoogle Scholar
  55. 55.
    Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107–16. doi: 10.1056/NEJMoa1005372.CrossRefPubMedGoogle Scholar
  56. 56.
    Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354(16):1671–84. doi: 10.1056/NEJMoa051693.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • MaryEllen Antkowiak
    • 1
  • Lucas Mikulic
    • 1
  • Benjamin T. Suratt
    • 1
    Email author
  1. 1.Division of Pulmonary and Critical Care MedicineUniversity of Vermont College of MedicineBurlingtonUSA

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