UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis

Author
Remi Neviere, MD
Section Editor
Polly E Parsons, MD
Deputy Editor
Geraldine Finlay, MD

INTRODUCTION

Sepsis is a clinical syndrome that has physiologic, biologic, and biochemical abnormalities caused by a dysregulated inflammatory response to infection. Sepsis and the inflammatory response that ensues can lead to multiple organ dysfunction syndrome and death.

The epidemiology, definitions, risk factors, clinical presentation, diagnosis, and outcomes of sepsis are reviewed here. The pathophysiology and treatment of sepsis are discussed separately. (See "Pathophysiology of sepsis" and "Evaluation and management of suspected sepsis and septic shock in adults".)

EPIDEMIOLOGY

Incidence — In the late 1970s, it was estimated that 164,000 cases of sepsis occurred in the United States (US) each year [1]. Since then, rates of sepsis in the US and elsewhere have dramatically increased as supported by the following studies [2-5]:

One national database analysis of discharge records from hospitals in the US estimated an annual rate of more than 1,665,000 cases of sepsis between 1979 and 2000 [2].

Another retrospective population-based analysis reported increased rates of sepsis and septic shock from 13 to 78 cases per 100,000 between 1998 and 2009 [3].

                             

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jun 2016. | This topic last updated: Jun 24, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348:1546.
  2. Elixhauser A, Friedman B, Stranges E. Septicemia in U.S. Hospitals, 2009. Agency for Healthcare Research and Quality, Rockville, MD http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf (Accessed on February 15, 2013).
  3. Walkey AJ, Wiener RS, Lindenauer PK. Utilization patterns and outcomes associated with central venous catheter in septic shock: a population-based study. Crit Care Med 2013; 41:1450.
  4. Kaukonen KM, 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.
  5. McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open 2013; 3.
  6. Fleischmann C, Scherag A, Adhikari NK, 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.
  7. Esper AM, Martin GS. Extending international sepsis epidemiology: the impact of organ dysfunction. Crit Care 2009; 13:120.
  8. Blanco J, Muriel-Bombín A, Sagredo V, et al. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care 2008; 12:R158.
  9. Harrison DA, Welch CA, Eddleston JM. The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Crit Care 2006; 10:R42.
  10. Danai P, Martin GS. Epidemiology of sepsis: recent advances. Curr Infect Dis Rep 2005; 7:329.
  11. Danai PA, Sinha S, Moss M, et al. Seasonal variation in the epidemiology of sepsis. Crit Care Med 2007; 35:410.
  12. 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.
  13. Angus DC, Kelley MA, Schmitz RJ, et al. Caring for the critically ill patient. Current and projected workforce requirements for care of the critically ill and patients with pulmonary disease: can we meet the requirements of an aging population? JAMA 2000; 284:2762.
  14. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41:580.
  15. Uslan DZ, Crane SJ, Steckelberg JM, et al. Age- and sex-associated trends in bloodstream infection: a population-based study in Olmsted County, Minnesota. Arch Intern Med 2007; 167:834.
  16. Pop-Vicas A, Tacconelli E, Gravenstein S, et al. Influx of multidrug-resistant, gram-negative bacteria in the hospital setting and the role of elderly patients with bacterial bloodstream infection. Infect Control Hosp Epidemiol 2009; 30:325.
  17. Klotz SA, Chasin BS, Powell B, et al. Polymicrobial bloodstream infections involving Candida species: analysis of patients and review of the literature. Diagn Microbiol Infect Dis 2007; 59:401.
  18. Whittaker SA, Mikkelsen ME, Gaieski DF, et al. Severe sepsis cohorts derived from claims-based strategies appear to be biased toward a more severely ill patient population. Crit Care Med 2013; 41:945.
  19. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med 2007; 35:1244.
  20. Esper A, Martin GS. Is severe sepsis increasing in incidence AND severity? Crit Care Med 2007; 35:1414.
  21. Rangel-Frausto MS, Pittet D, Costigan M, et al. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 1995; 273:117.
  22. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20:864.
  23. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31:1250.
  24. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005; 365:63.
  25. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:801.
  26. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:775.
  27. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:762.
  28. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med 1995; 23:1638.
  29. Le Gall JR, Klar J, Lemeshow S, et al. The Logistic Organ Dysfunction system. A new way to assess organ dysfunction in the intensive care unit. ICU Scoring Group. JAMA 1996; 276:802.
  30. 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.
  31. Kaukonen KM, Bailey M, Pilcher D, et al. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med 2015; 372:1629.
  32. Churpek MM, Zadravecz FJ, Winslow C, et al. Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients. Am J Respir Crit Care Med 2015; 192:958.
  33. Murray CJ, Atkinson C, Bhalla K, et al. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA 2013; 310:591.
  34. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA 1997; 278:234.
  35. Bone RC, Fisher CJ Jr, Clemmer TP, et al. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987; 317:653.
  36. Ziegler EJ, Fisher CJ Jr, Sprung CL, et al. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med 1991; 324:429.
  37. Abraham E, Wunderink R, Silverman H, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA 1995; 273:934.
  38. Dhainaut JF, Vincent JL, Richard C, et al. CDP571, a humanized antibody to human tumor necrosis factor-alpha: safety, pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in patients with septic shock. CPD571 Sepsis Study Group. Crit Care Med 1995; 23:1461.
  39. Jones GR, Lowes JA. The systemic inflammatory response syndrome as a predictor of bacteraemia and outcome from sepsis. QJM 1996; 89:515.
  40. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med 2006; 34:15.
  41. Dremsizov T, Clermont G, Kellum JA, et al. Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course? Chest 2006; 129:968.
  42. Prescott HC, Dickson RP, Rogers MA, et al. Hospitalization Type and Subsequent Severe Sepsis. Am J Respir Crit Care Med 2015; 192:581.
  43. Netea MG, van der Meer JW. Immunodeficiency and genetic defects of pattern-recognition receptors. N Engl J Med 2011; 364:60.
  44. Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA 1995; 274:639.
  45. Cohen J, Vincent JL, Adhikari NK, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 15:581.
  46. Padkin A, Goldfrad C, Brady AR, et al. Epidemiology of severe sepsis occurring in the first 24 hrs in intensive care units in England, Wales, and Northern Ireland. Crit Care Med 2003; 31:2332.
  47. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34:344.
  48. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Facing the challenge: decreasing case fatality rates in severe sepsis despite increasing hospitalizations. Crit Care Med 2005; 33:2555.
  49. Winters BD, Eberlein M, Leung J, et al. Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 2010; 38:1276.
  50. Miller RR 3rd, Dong L, Nelson NC, et al. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med 2013; 188:77.
  51. Pavon A, Binquet C, Kara F, et al. Profile of the risk of death after septic shock in the present era: an epidemiologic study. Crit Care Med 2013; 41:2600.
  52. ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370:1683.
  53. Liu V, Escobar GJ, Greene JD, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA 2014; 312:90.
  54. Leligdowicz A, Dodek PM, Norena M, et al. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med 2014; 189:1204.
  55. Epstein L, Dantes R, Magill S, Fiore A. Varying Estimates of Sepsis Mortality Using Death Certificates and Administrative Codes - United States, 1999-2014. MMWR Morb Mortal Wkly Rep 2016; 65:342.
  56. Lagu T, Rothberg MB, Shieh MS, et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med 2012; 40:754.
  57. Stevenson EK, Rubenstein AR, Radin GT, et al. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*. Crit Care Med 2014; 42:625.
  58. Cannon CM, Holthaus CV, Zubrow MT, et al. The GENESIS project (GENeralized Early Sepsis Intervention Strategies): a multicenter quality improvement collaborative. J Intensive Care Med 2013; 28:355.
  59. ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:1496.
  60. Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med 2014; 40:1623.
  61. Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med 2015; 43:3.
  62. Rhodes A, Phillips G, Beale R, et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med 2015; 41:1620.
  63. van Vught LA, Klein Klouwenberg PM, 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.
  64. Perl TM, Dvorak L, Hwang T, Wenzel RP. Long-term survival and function after suspected gram-negative sepsis. JAMA 1995; 274:338.
  65. Sasse KC, Nauenberg E, Long A, et al. Long-term survival after intensive care unit admission with sepsis. Crit Care Med 1995; 23:1040.
  66. Nesseler N, Defontaine A, Launey Y, et al. Long-term mortality and quality of life after septic shock: a follow-up observational study. Intensive Care Med 2013; 39:881.
  67. Wang T, Derhovanessian A, De Cruz S, et al. Subsequent infections in survivors of sepsis: epidemiology and outcomes. J Intensive Care Med 2014; 29:87.
  68. Prescott HC, Langa KM, Liu V, et al. Increased 1-year healthcare use in survivors of severe sepsis. Am J Respir Crit Care Med 2014; 190:62.
  69. Prescott HC, Langa KM, Iwashyna TJ. Readmission diagnoses after hospitalization for severe sepsis and other acute medical conditions. JAMA 2015; 313:1055.
  70. Jones TK, Fuchs BD, Small DS, et al. Post-Acute Care Use and Hospital Readmission after Sepsis. Ann Am Thorac Soc 2015; 12:904.
  71. Prescott HC, Osterholzer JJ, Langa KM, et al. Late mortality after sepsis: propensity matched cohort study. BMJ 2016; 353:i2375.
  72. Sun A, Netzer G, Small DS, et al. Association Between Index Hospitalization and Hospital Readmission in Sepsis Survivors. Crit Care Med 2016; 44:478.
  73. Knaus WA, Sun X, Nystrom O, Wagner DP. Evaluation of definitions for sepsis. Chest 1992; 101:1656.
  74. Peres Bota D, Lopes Ferreira F, Mélot C, Vincent JL. Body temperature alterations in the critically ill. Intensive Care Med 2004; 30:811.
  75. Kreger BE, Craven DE, McCabe WR. Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. Am J Med 1980; 68:344.
  76. Haase N, Ostrowski SR, Wetterslev J, et al. Thromboelastography in patients with severe sepsis: a prospective cohort study. Intensive Care Med 2015; 41:77.
  77. Neyra JA, Canepa-Escaro F, Li X, et al. Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. Crit Care Med 2015; 43:1938.
  78. Thiery-Antier N, Binquet C, Vinault S, et al. Is Thrombocytopenia an Early Prognostic Marker in Septic Shock? Crit Care Med 2016; 44:764.
  79. van Vught LA, Wiewel MA, Klein Klouwenberg PM, et al. Admission Hyperglycemia in Critically Ill Sepsis Patients: Association With Outcome and Host Response. Crit Care Med 2016; 44:1338.
  80. Walkey AJ, Wiener RS, Ghobrial JM, et al. Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA 2011; 306:2248.
  81. Poutsiaka DD, Davidson LE, Kahn KL, et al. Risk factors for death after sepsis in patients immunosuppressed before the onset of sepsis. Scand J Infect Dis 2009; 41:469.
  82. O'Brien JM Jr, Lu B, Ali NA, et al. Alcohol dependence is independently associated with sepsis, septic shock, and hospital mortality among adult intensive care unit patients. Crit Care Med 2007; 35:345.
  83. Danai PA, Moss M, Mannino DM, Martin GS. The epidemiology of sepsis in patients with malignancy. Chest 2006; 129:1432.
  84. Tolsma V, Schwebel C, Azoulay E, et al. Sepsis severe or septic shock: outcome according to immune status and immunodeficiency profile. Chest 2014; 146:1205.
  85. Girard TD, Opal SM, Ely EW. Insights into severe sepsis in older patients: from epidemiology to evidence-based management. Clin Infect Dis 2005; 40:719.
  86. Krieger JN, Kaiser DL, Wenzel RP. Urinary tract etiology of bloodstream infections in hospitalized patients. J Infect Dis 1983; 148:57.
  87. Bone RC, Fisher CJ Jr, Clemmer TP, et al. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med 1989; 17:389.
  88. Brun-Buisson C, Doyon F, Carlet J. Bacteremia and severe sepsis in adults: a multicenter prospective survey in ICUs and wards of 24 hospitals. French Bacteremia-Sepsis Study Group. Am J Respir Crit Care Med 1996; 154:617.
  89. Zahar JR, Timsit JF, Garrouste-Orgeas M, et al. Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality. Crit Care Med 2011; 39:1886.
  90. Shorr AF, Tabak YP, Killian AD, et al. Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database. Crit Care Med 2006; 34:2588.
  91. Labelle A, Juang P, Reichley R, et al. The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment*. Crit Care Med 2012; 40:2016.
  92. Bassetti M, Righi E, Ansaldi F, et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 2014; 40:839.
  93. Veterans Administration Systemic Sepsis Cooperative Study Group. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 1987; 317:659.
  94. Johnson MT, Reichley R, Hoppe-Bauer J, et al. Impact of previous antibiotic therapy on outcome of Gram-negative severe sepsis. Crit Care Med 2011; 39:1859.
  95. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368.
  96. Haas SA, Lange T, Saugel B, et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med 2016; 42:202.