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What Is Sepsis?

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Handbook of Sepsis

Abstract

Sepsis is a perplexing infection-related syndrome documented for thousands of years. It remains a leading cause of mortality and morbidity worldwide. The concepts and understanding of sepsis have evolved in recent decades from a systemic inflammatory response syndrome to infection to, more recently, a life-threatening organ dysfunction due to a dysregulated host response. Clinical recognition of sepsis is often difficult, especially in the early stages of presentation. The disease course of sepsis is also highly variable. Heterogeneity related to age, comorbidity and iatrogenic intervention add further layers of complexity. Specific and sensitive diagnostics to aid identification and guide treatment are still lacking, though novel technologies hold considerable promise. It is now recognized that the biological phenotype of sepsis varies markedly, both between patients and over time. Thus, a one-size-fits-all therapeutic approach is increasingly viewed as over-simplistic, explaining the failure of various strategies in multiple randomized controlled trials.

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References

  1. Singer M, Deutschmann CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–10.

    Article  CAS  Google Scholar 

  2. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369:840–51.

    Article  CAS  Google Scholar 

  3. Fleischmann C, Scherag A, Adhikari NKJ, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72.

    Article  CAS  Google Scholar 

  4. World Health Organization. The top 10 causes of death (Fact sheet updated January 2017). http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed 9 Feb 2018.

  5. Kaukonen K-M, Bailey M, Suzuki S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311:1308–16.

    Article  CAS  Google Scholar 

  6. Rhee C, Gohil S, Klompas M. Regulatory mandates for sepsis care--reasons for caution. N Engl J Med. 2014;370:1673–6.

    Article  CAS  Google Scholar 

  7. Osler W. Principles and practice of medicine designed for the use of practitioners and students of medicine. 3rd ed. Edinburgh: Pentland; 1898.

    Google Scholar 

  8. Majno G. The ancient riddle of sigma eta psi iota sigma (sepsis). J Infect Dis. 1991;163:937–45.

    Article  CAS  Google Scholar 

  9. Haensch S, Bianucci R, Signoli M, et al. Distinct clones of Yersinia pestis caused the black death. PLoS Pathog. 2010;6:e1001134.

    Article  Google Scholar 

  10. Benedictow OJ. The black death 1346–1353: the complete history. Woodbridge: Boydell Press; 2004.

    Google Scholar 

  11. Davaine MC. Recherches sur quelques questions relatives a la septicemie. Paris: G. Masson; 1872.

    Google Scholar 

  12. Lister J. On the antiseptic principle in the practice of surgery. Lancet. 1867;90:353–6.

    Article  Google Scholar 

  13. Fleming A. On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzæ. Br J Exp Pathol. 1929;10:226–36.

    CAS  PubMed Central  Google Scholar 

  14. Kelly FE, Fong K, Hirsch N, et al. Intensive care medicine is 60 years old: the history and future of the intensive care unit. Clin Med. 2014;14:376–9.

    Article  Google Scholar 

  15. Thomas L. Germs. N Engl J Med. 1972;287:553–5.

    Article  CAS  Google Scholar 

  16. Cerra FB. The systemic septic response: multiple systems organ failure. Crit Care Clin. 1985;1:591–607.

    CAS  PubMed  Google Scholar 

  17. Fink MP, Heard SO. Laboratory models of sepsis and septic shock. J Surg Res. 1990;49:186–96.

    Article  CAS  Google Scholar 

  18. Bone RC, Balk RA, Cerra FB, 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;101:1644–55.

    Article  CAS  Google Scholar 

  19. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–6.

    Article  Google Scholar 

  20. Hotchkiss R, Karl I. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138–50.

    Article  CAS  Google Scholar 

  21. Mira JC, Gentile LF, Mathias BJ, et al. Sepsis pathophysiology, chronic critical illness, and persistent inflammation-immunosuppression and catabolism syndrome. Crit Care Med. 2017;XX:1–10.

    Google Scholar 

  22. van Vught LA, Klein Klouwenberg PMC, Spitoni C, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA. 2016;315:1469.

    Article  Google Scholar 

  23. Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997;25:1095–100.

    Article  CAS  Google Scholar 

  24. Angus DC. The search for effective therapy for sepsis: back to the drawing board? JAMA. 2011;306:2614–5.

    Article  CAS  Google Scholar 

  25. Sprung CL, Schein RMH, Balk RA. The new sepsis consensus definitions: the good, the bad and the ugly. Intensive Care Med. 2016;42:2024–6.

    Article  Google Scholar 

  26. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.

    Article  CAS  Google Scholar 

  27. de Grooth H-J, Geenen IL, Girbes AR, et al. SOFA and mortality endpoints in randomized controlled trials: a systematic review and meta-regression analysis. Crit Care. 2017;21:38.

    Article  Google Scholar 

  28. Hotchkiss RS, Moldawer LL, Opal SM, et al. Sepsis and septic shock. Nat Rev Dis Prim. 2016;2:16045.

    Article  Google Scholar 

  29. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med. 2007;35:1599–608.

    Article  Google Scholar 

  30. Haak BW, Wiersinga WJ. The role of the gut microbiota in sepsis. Lancet Gastroenterol Hepatol. 2017;2:135–43.

    Article  Google Scholar 

  31. Hotchkiss RS, Swanson PE, Freeman BD, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27:1230–51.

    Article  CAS  Google Scholar 

  32. Takasu O, Gaut JP, Watanabe E, et al. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med. 2013;187:509–17.

    Article  CAS  Google Scholar 

  33. Singer M, De Santis V, Vitale D, et al. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet (London, England). 2004;364:545–8.

    Article  Google Scholar 

  34. Langley RJ, Tsalik EL, van Velkinburgh JC, et al. An integrated clinico-metabolomic model improves prediction of death in sepsis. Sci Transl Med. 2013;5:195ra95.

    Article  Google Scholar 

  35. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007;369:2196–210.

    Article  Google Scholar 

  36. Heffner AC, Horton JM, Marchick MR, et al. Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department. Clin Infect Dis. 2010;50:814–20.

    Article  Google Scholar 

  37. Pierrakos C, Vincent J-L. Sepsis biomarkers: a review. Crit Care. 2010;14:R15.

    Article  Google Scholar 

  38. Davenport EE, Burnham KL, Radhakrishnan J, et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4:259–71.

    Article  Google Scholar 

  39. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.

    Article  CAS  Google Scholar 

  40. van Vught LA, Holman R, de Jonge E, et al. Diabetes is not associated with increased 90-day mortality risk in critically ill patients with sepsis. Crit Care Med. 2017;45(10):e1026–35. https://doi.org/10.1097/CCM.0000000000002590.

    Article  PubMed  Google Scholar 

  41. Wan Y-D, Sun T-W, Kan Q-C, et al. Effect of statin therapy on mortality from infection and sepsis: a meta-analysis of randomized and observational studies. Crit Care. 2014;18:R71.

    Article  Google Scholar 

  42. Morelli A, Ertmer C, Westphal M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock. JAMA. 2013;310:1683.

    Article  Google Scholar 

  43. Wiewel MA, van Vught LA, Scicluna BP, et al. Prior use of calcium channel blockers is associated with decreased mortality in critically ill patients with sepsis: a prospective observational study. Crit Care Med. 2017;45:454–63.

    Article  CAS  Google Scholar 

  44. Arabi YM, Dara SI, Tamim HM, et al. Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study. Crit Care. 2013;17:R72.

    Article  Google Scholar 

  45. Gentile LF, Cuenca AG, Efron PA, et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012;72:1491–501.

    Article  CAS  Google Scholar 

  46. Angus DC, Carlet J. Surviving intensive care: a report from the 2002 Brussels Roundtable. Intensive Care Med. 2003;29:368–77.

    Article  Google Scholar 

  47. Mehlhorn J, Freytag A, Schmidt K, et al. Rehabilitation interventions for postintensive care syndrome: a systematic review. Crit Care Med. 2014;42:1263–71.

    Article  Google Scholar 

  48. Hutchins NA, Unsinger J, Hotchkiss RS, et al. The new normal: immunomodulatory agents against sepsis immune suppression. Trends Mol Med. 2014;20:224–33.

    Article  CAS  Google Scholar 

  49. Daviaud F, Grimaldi D, Dechartres A, et al. Timing and causes of death in septic shock. Ann Intensive Care. 2015;5:16.

    Article  Google Scholar 

  50. Zolfaghari PS, Pinto BB, Dyson A, et al. The metabolic phenotype of rodent sepsis: cause for concern? Intensive Care Med Exp. 2013;1:6.

    Article  Google Scholar 

  51. Lockhart PB, Brennan MT, Sasser HC, et al. Bacteremia associated with tooth brushing and dental extraction. Circulation. 2008;117:3118–25.

    Article  CAS  Google Scholar 

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Correspondence to Mervyn Singer M.D., F.R.C.P.(Lon) .

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Giesen, L., Singer, M. (2018). What Is Sepsis?. In: Wiersinga, W., Seymour, C. (eds) Handbook of Sepsis. Springer, Cham. https://doi.org/10.1007/978-3-319-73506-1_1

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  • DOI: https://doi.org/10.1007/978-3-319-73506-1_1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-73505-4

  • Online ISBN: 978-3-319-73506-1

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