Organ dysfunction as a new standard for defining sepsis

Seitaro Fujishima, Seitaro Fujishima

Abstract

Despite advances in intensive care and the widespread use of standardized care included in the Surviving Sepsis Campaign Guidelines, sepsis remains a leading cause of death, and the prevalence of sepsis increases concurrent with the aging process. The diagnosis of sepsis was originally based on the evidence of persistent bacteremia (septicemia) but was modified in 1992 to incorporate systemic inflammatory response syndrome (SIRS). Since then, SIRS has become the gold standard for the diagnosis of sepsis. In 2016, the Society of Critical Care Medicine and the European Society of Intensive Care Medicine published a new clinical definition of sepsis that is called Sepsis-3. In contrast to previous definitions, Sepsis-3 is based on organ dysfunctions and uses a sequential organ failure (SOFA) score as an index. Thus, patients diagnosed with respect to Sepsis-3 will inevitably represent a different population than those previously diagnosed. We assume that this drastic change in clinical definition will affect not only clinical practice but also the viewpoint and focus of basic research. This review intends to summarize the pathophysiology of sepsis and organ dysfunction and discusses potential directions for future research.

Keywords: Acute kidney injury; Acute respiratory distress syndrome; Disseminated intravascular coagulation; Sepsis-3; Sequential organ failure assessment score.

Figures

Fig. 1
Fig. 1
Schematic diagram showing the previous and new definitions of sepsis. Asterisk indicates a small fraction of infected patients develop organ dysfunction without fulfilling the established SIRS criteria. SIRS systemic inflammatory response syndrome

References

    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315(8):801–10. doi: 10.1001/jama.2016.0287.
    1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55. doi: 10.1378/chest.101.6.1644.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31(4):1250–6. doi: 10.1097/01.CCM.0000050454.01978.3B.
    1. Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015;372(17):1629–38. doi: 10.1056/NEJMoa1415236.
    1. Hayashi T, Nakamura T, Takaoka A. Pattern recognition receptors. Jpn J Clin Immunol. 2011;34:329–45. doi: 10.2177/jsci.34.329.
    1. Schaefer L. Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem. 2014;289(51):35237–45. doi: 10.1074/jbc.R114.619304.
    1. Opitz B, van Laak V, Eitel J, Suttorp N. Innate immune recognition in infectious and noninfectious diseases of the lung. Am J Respir Crit Care Med. 2010;181(12):1294–309. doi: 10.1164/rccm.200909-1427SO.
    1. Okusawa S, Gelfand JA, Ikejima T, Connolly RJ, Dinarello CA. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest. 1988;81(4):1162–72. doi: 10.1172/JCI113431.
    1. Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, et al. Shock and tissue injury induced by recombinant human cachectin. Science. 1986;234(4775):470–4. doi: 10.1126/science.3764421.
    1. Fujishima S, Gando S, Daizoh S, Kushimoto S, Ogura H, Mayumi T, et al. Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock. Respirology. 2016;21(5):898–904. doi: 10.1111/resp.12769.
    1. Sheu CC, Gong MN, Zhai R, Chen F, Bajwa EK, Clardy PF, et al. Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS. Chest. 2010;138(3):559–67. doi: 10.1378/chest.09-2933.
    1. Mallick AA, Ishizaka A, Stephens KE, Hatherill JR, Tazelaar HD, Raffin TA. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion. Chest. 1989;95(5):1114–20. doi: 10.1378/chest.95.5.1114.
    1. Stephens KE, Ishizaka A, Wu ZH, Larrick JW, Raffin TA. Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs. Am Rev Respir Dis. 1988;138(5):1300–7. doi: 10.1164/ajrccm/138.5.1300.
    1. Fujishima S, Aikawa N. Neutrophil-mediated tissue injury and its modulation. Intensive Care Med. 1995;21(3):277–85. doi: 10.1007/BF01701489.
    1. Luo L, Zhang S, Wang Y, Rahman M, Syk I, Zhang E, et al. Proinflammatory role of neutrophil extracellular traps in abdominal sepsis. Am J Physiol Lung Cell Mol Physiol. 2014;307(7):L586–96. doi: 10.1152/ajplung.00365.2013.
    1. Fujishima S. A prominent role of IL-8 in various inflammatory lung diseases and multiple organ dysfunction syndrome. Jpn J Inflamm. 1998;18(6):433–7.
    1. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285(5425):248–51. doi: 10.1126/science.285.5425.248.
    1. Ueno H, Matsuda T, Hashimoto S, Amaya F, Kitamura Y, Tanaka M, et al. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med. 2004;170(12):1310–6. doi: 10.1164/rccm.200402-188OC.
    1. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104–7. doi: 10.1038/nature08780.
    1. Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, et al. Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity. 2013;39(5):874–84. doi: 10.1016/j.immuni.2013.08.039.
    1. Hashimoto S, Kobayashi A, Kooguchi K, Kitamura Y, Onodera H, Nakajima H. Upregulation of two death pathways of perforin/granzyme and FasL/Fas in septic acute respiratory distress syndrome. Am J Respir Crit Care Med. 2000;161(1):237–43. doi: 10.1164/ajrccm.161.1.9810007.
    1. Fujishima S, Gando S, Saitoh D, Mayumi T, Kushimoto S, Shiraishi S, et al. A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines. J Infect Chemother. 2014;20(2):115–20. doi: 10.1016/j.jiac.2013.09.003.
    1. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367–74. doi: 10.1097/CCM.0b013e3181cb0cdc.
    1. 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.
    1. Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, et al. The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med. 2007;35(9):2016–24. doi: 10.1097/01.CCM.0000281637.08984.6E.
    1. Nesseler N, Launey Y, Aninat C, Morel F, Malledant Y, Seguin P. Clinical review: the liver in sepsis. Crit Care. 2012;16(5):235. doi: 10.1186/cc11381.
    1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340(6):448–54. doi: 10.1056/NEJM199902113400607.
    1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34(2):344–53. doi: 10.1097/01.CCM.0000194725.48928.3A.
    1. Zarbock A, Gomez H, Kellum JA. Sepsis-induced acute kidney injury revisited: pathophysiology, prevention and future therapies. Curr Opin Crit Care. 2014;20(6):588–95. doi: 10.1097/MCC.0000000000000153.
    1. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers. 2016;2:16037. doi: 10.1038/nrdp.2016.37.
    1. Gando S, Saitoh D, Ogura H, Fujishima S, Mayumi T, Araki T, et al. A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis. Crit Care. 2013;17(3):R111. doi: 10.1186/cc12783.
    1. Kienast J, Juers M, Wiedermann CJ, Hoffmann JN, Ostermann H, Strauss R, et al. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation. J Thromb Haemost. 2006;4(1):90–7. doi: 10.1111/j.1538-7836.2005.01697.x.
    1. Dhainaut JF, Yan SB, Joyce DE, Pettila V, Basson B, Brandt JT, et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. 2004;2(11):1924–33. doi: 10.1111/j.1538-7836.2004.00955.x.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera