Developing a newdefinition and assessing newclinical criteria for Septic shock: For the third international consensus definitions for sepsis and septic shock (sepsis-3)

JAMA - Journal of the American Medical Association

Volumn 315, Issue 8, 2016, Pages 775-787

  Shankar Hari, Manu ^a,b   Phillips, Gary S ^c   Levy, Mitchell L ^d   Seymour, Christopher W ^e   Liu, Vincent X ^f   Deutschman, Clifford S ^g,h   Angus, Derek C ^e,i   Rubenfeld, Gordon D ^j,k   Singer, Mervyn ^l  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^c THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^d BROWN UNIVERSITY   (United States)

^e UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^f DIVISION OF RESEARCH   (United States)

^g DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

^h FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

ⁱ JAMA   (United States)

^j UNIVERSITY OF TORONTO   (Canada)

^k SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^l UNIVERSITY COLLEGE LONDON   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

HYPERTENSIVE FACTOR; LACTIC ACID; BIOLOGICAL MARKER; LACTIC ACID DERIVATIVE; VASOCONSTRICTOR AGENT;

ADULT; ARTICLE; BLOOD PRESSURE; CLINICAL CRITERIA; COHORT ANALYSIS; DELPHI STUDY; DISEASE ASSOCIATION; DISEASE CLASSIFICATION; ELECTROLYTE DISTURBANCE; ELECTRONIC MEDICAL RECORD; FLUID RESUSCITATION; HUMAN; LACTATE BLOOD LEVEL; MEDICAL SOCIETY; MORTALITY; PRIORITY JOURNAL; SEPSIS; SEPTIC SHOCK; SYSTEMATIC REVIEW; ADVISORY COMMITTEE; BLOOD; BLOOD PRESSURE MEASUREMENT; CONSENSUS; CONSENSUS DEVELOPMENT; FLUID THERAPY; HYPOTENSION; LITERATURE; META ANALYSIS; OBSERVATIONAL STUDY; PROCEDURES; RESUSCITATION; SHOCK, SEPTIC;

ADULT; ADVISORY COMMITTEES; BIOMARKERS; BLOOD PRESSURE DETERMINATION; COHORT STUDIES; CONSENSUS; DELPHI TECHNIQUE; FLUID THERAPY; HUMANS; HYPOTENSION; LACTATES; OBSERVATIONAL STUDIES AS TOPIC; RESUSCITATION; REVIEW LITERATURE AS TOPIC; SHOCK, SEPTIC; VASOCONSTRICTOR AGENTS;

EID: 84959308793     PISSN: 00987484     EISSN: 15383598     Source Type: Journal    
DOI: 10.1001/jama.2016.0289     Document Type: Article

References (120)

1. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101(6):1644-1655.
2. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250-1256.
3. Rhee C, Gohil S, Klompas M. Regulatory mandates for sepsis care-reasons for caution. N Engl J Med. 2014;370(18):1673-1676.
4. Iwashyna TJ, Angus DC. Declining case fatality rates for severe sepsis. JAMA. 2014;311(13):1295-1297.
5. 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(10):1204-1213.
6. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36(2):222-231.
7. Klein Klouwenberg PM, Ong DS, Bonten MJ, Cremer OL. Classification of sepsis, severe sepsis and septic shock: the impact ofminor variations in data capture and definition of SIRS criteria. Intensive Care Med. 2012;38(5):811-819.
8. Shankar-Hari M, Bertolini G, Brunkhorst FM, et al. Judging quality of current septic shock definitions and criteria. Crit Care. 2015;19(1):445.
9. Iwashyna TJ, Govindan S. Did they just prove that a diagnosis of "septic shock" is meaningless? Am J Respir Crit Care Med. 2014;189(10):1156-1157.
10. Singer M. The role ofmitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence. 2014;5(1):66-72.
11. Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression. Nat Rev Immunol. 2013;13(12):862-874.
12. 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(5):509-517.
13. Rudiger A, Dyson A, Felsmann K, et al. Early functional and transcriptomic changes in the myocardium predict outcome in a long-term rat model of sepsis. Clin Sci (Lond). 2013;124(6):391-401.
14. Singer M, Deutschman C, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. doi:10.1001/jama.2016.0287.
15. US Department of Health and Human Services (DHHS). Frequently Asked Questions About Human Research. DHHS website. http://www.hhs.gov/ohrp/policy/faq/index.html. May 10, 2010. Accessed Feburary 1, 2016.
16. Seymour CW, Liu V, Iwashyna TJ et al. Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. doi:10.1001/jama.2016.0288.
17. Casserly B, Phillips GS, Schorr C, et al. Lactate measurements in sepsis-induced tissue hypoperfusion. Crit Care Med. 2015;43(3):567-573.
18. World Health Organisation (WHO). Health Statistics and Information Systems: Definition of Region Groupings. WHO website. http://www.who.int/healthinfo/global-burden-disease/definition-regions/en/. July 5, 2015.
19. Ortiz G, Duenas C, Rodriguez F, et al. Epidemiology of sepsis in Colombian intensive care units. Biomedica. 2014;34(1):40-47.
20. Ogura H, Gando S, Saitoh D, et al. Epidemiology of severe sepsis in Japanese intensive care units. J Infect Chemother. 2014;20(3):157-162.
21. Liu V, Escobar GJ, Greene JD, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312(1):90-92.
22. Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311(13):1308-1316.
23. Goncalves-Pereira J, Pereira JM, Ribeiro O, et al. Impact of infection on admission and of the process of care on mortality of patients admitted to the intensive care unit: the INFAUCI study. Clin Microbiol Infect. 2014;20(12):1308-1315.
24. Whittaker SA, Mikkelsen ME, Gaieski DF, Koshy S, Kean C, Fuchs BD. Severe sepsis cohorts derived from claims-based strategies appear to be biased toward a more severely ill patient population. Crit Care Med. 2013;41(4):945-953.
25. Sakr Y, Elia C, Mascia L, et al. Epidemiology and outcome of sepsis syndromes in Italian ICUs. Minerva Anestesiol. 2013;79(9):993-1002.
26. Quenot JP, Binquet C, Kara F, et al. The epidemiology of septic shock in French intensive care units. Crit Care. 2013;17(2):R65.
27. Nesseler N, Defontaine A, Launey Y, Morcet J, Malledant Y, Seguin P. Long-term mortality and quality of life after septic shock. Intensive Care Med. 2013;39(5):881-888.
28. Park DW, Chun BC, Kim JM, et al. Epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock. J Korean Med Sci. 2012;27(11):1308-1314.
29. Levy MM, Artigas A, Phillips GS, et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe. Lancet Infect Dis. 2012;12(12):919-924.
30. Zahar JR, Timsit JF, Garrouste-Orgeas M, et al. Outcomes in severe sepsis and patients with septic shock [published correction appears in Crit Care Med. 2011;39(10):2392]. Crit Care Med. 2011;39(8):1886-1895.
31. Rodriguez F, Barrera L, De La Rosa G, et al. The epidemiology of sepsis in Colombia: a prospective multicenter cohort study in ten university hospitals. Crit Care Med. 2011;39(7):1675-1682.
32. Phua J, Koh Y, Du B, et al. Management of severe sepsis in patients admitted to Asian intensive care units. BMJ. 2011;342:d3245.
33. Moore LJ, McKinley BA, Turner KL, et al. The epidemiology of sepsis in general surgery patients. J Trauma. 2011;70(3):672-680.
34. Kauss IA, Grion CM, Cardoso LT, et al. The epidemiology of sepsis in a Brazilian teaching hospital. Braz J Infect Dis. 2010;14(3):264-270.
35. Povoa PR, Carneiro AH, Ribeiro OS, Pereira AC; Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Crit Care Med. 2009;37(2):410-416.
36. Peake SL, Bailey M, Bellomo R, et al. Australasian resuscitation of sepsis evaluation (ARISE). Resuscitation. 2009;80(7):811-818.
37. Khwannimit B, Bhurayanontachai R. The epidemiology of, and risk factors for, mortality from severe sepsis and septic shock in a tertiary-care university hospital setting. Epidemiol Infect. 2009;137(9):1333-1341.
38. Angkasekwinai N, Rattanaumpawan P, Thamlikitkul V. Epidemiology of sepsis in Siriraj Hospital 2007. J Med Assoc Thai. 2009;92(suppl 2):S68-S78.
39. Sakr Y, Vincent JL, Schuerholz T, et al. Early-versus late-onset shock in European intensive care units. Shock. 2007;28(6):636-643.
40. Karlsson S, Varpula M, Ruokonen E, et al. Incidence, treatment, and outcome of severe sepsis in ICU-treated adults in Finland: the Finnsepsis study. Intensive Care Med. 2007;33(3):435-443.
41. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward. Crit Care Med. 2007;35(5):1284-1289.
42. Engel C, Brunkhorst FM, Bone HG, et al. Epidemiology of sepsis in Germany. Intensive Care Med. 2007;33(4):606-618.
43. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34(2):344-353.
44. Shapiro N, Howell MD, Bates DW, Angus DC, Ngo L, Talmor D. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Ann Emerg Med. 2006;48(5):583-590.
45. Gasparoví V, Gornik I, Ivanoví D. Sepsis syndrome in Croatian intensive care units: piloting a national comparative clinical database. Croat Med J. 2006;47(3):404-409.
46. Degoricija V, Sharma M, Legac A, et al. Survival analysis of 314 episodes of sepsis in medical intensive care unit in university hospital. Croat Med J. 2006;47(3):385-397.
47. Laupland KB, Zygun DA, Doig CJ, et al. One-year mortality of bloodstream infection-associated sepsis and septic shock among patients presenting to a regional critical care system. Intensive Care Med. 2005;31(2):213-219.
48. Silva E, Pedro Mde A, Sogayar AC, et al. Brazilian Sepsis Epidemiological Study (BASES study). Crit Care. 2004;8(4):R251-R260.
49. Laupland KB, Davies HD, Church DL, et al. Bloodstream infection-associated sepsis and septic shock in critically ill adults. Infection. 2004;32(2):59-64.
50. Flaatten H. Epidemiology of sepsis in Norway in 1999. Crit Care. 2004;8(4):R180-R184.
51. Annane D, Aegerter P, Jars-Guincestre MC, Guidet B; CUB-Rea Network. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med. 2003;168(2):165-172.
52. Alberti C, Brun-Buisson C, Burchardi H, et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002;28(2):108-121.
53. Schoenberg MH, Weiss M, Radermacher P. Outcome of patients with sepsis and septic shock after ICU treatment. Langenbecks Arch Surg. 1998;383(1):44-48.
54. Lundberg JS, Perl TM, Wiblin T, et al. Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units. Crit Care Med. 1998;26(6):1020-1024.
55. Salvo I, De Cian W, Musicco M, et al. The Italian SEPSIS study: preliminary results on the incidence and evolution of SIRS, sepsis, severe sepsis and septic shock. Intensive Care Med. 1995;21(suppl 2):S244-S249.
56. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). JAMA. 1995;273(2):117-123.
57. Pittet D, Rangel-Frausto S, Li N, et al. Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock. Intensive Care Med. 1995;21(4):302-309.
58. McLauchlan GJ, Anderson ID, Grant IS, Fearon KC. Outcome of patients with abdominal sepsis treated in an intensive care unit. Br J Surg. 1995;82(4):524-529.
59. Dahmash NS, Chowdhury NH, Fayed DF. Septic shock in critically ill patients. J Infect. 1993;26(2):159-170.
60. Whittaker SA, Fuchs BD, Gaieski DF, et al. Epidemiology and outcomes in patients with severe sepsis admitted to the hospital wards. J Crit Care. 2015;30(1):78-84.
61. Cross G, Bilgrami I, Eastwood G, et al. The epidemiology of sepsis during rapid response team reviews in a teaching hospital. Anaesth Intensive Care. 2015;43(2):193-198.
62. Vincent JL, Marshall JC, Namendys-Silva SA, et al; ICON Investigators. Assessment of the worldwide burden of critical illness. Lancet Respir Med. 2014;2(5):380-386.
63. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis. Crit Care Med. 2014;42(3):625-631.
64. Koupetori M, Retsas T, Antonakos N, et al; Hellenic Sepsis Study Group. Bloodstream infections and sepsis in Greece. BMC Infect Dis. 2014;14:272.
65. Bouza C, Lopez-Cuadrado T, Saz-Parkinson Z, Amate-Blanco JM. Epidemiology and recent trends of severe sepsis in Spain. BMC Infect Dis. 2014;14:3863.
66. Storgaard M, Hallas J, Gahrn-Hansen B, et al. Short- and long-term mortality in patients with community-acquired severe sepsis and septic shock. Scand J Infect Dis. 2013;45(8):577-583.
67. Stiermaier T, Herkner H, Tobudic S, et al. Incidence and long-term outcome of sepsis on general wards and in an ICU at the General Hospital of Vienna: an observational cohort study. Wien Klin Wochenschr. 2013;125(11-12):302-308.
68. Rohde JM, Odden AJ, Bonham C, et al. The epidemiology of acute organ system dysfunction from severe sepsis outside of the intensive care unit. J HospMed. 2013;8(5):243-247.
69. Gray A, Ward K, Lees F, et al. The epidemiology of adults with severe sepsis and septic shock in Scottish emergency departments. Emerg Med J. 2013;30(5):397-401.
70. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41(5):1167-1174.
71. Czupryna P, Garkowski A, Moniuszko A, et al. Patients with sepsis in infectious diseases department in years 1997-2010-epidemiology and clinical features. Przegl Epidemiol. 2013;67(3):429-434.
72. Seymour CW, Rea TD, Kahn JM, Walkey AJ, Yealy DM, Angus DC. Severe sepsis in pre-hospital emergency care. Am J Respir Crit Care Med. 2012;186(12):1264-1271.
73. Sancho S, Artero A, Zaragoza R, et al. Impact of nosocomial polymicrobial bloodstream infections on the outcome in critically ill patients. Eur J Clin Microbiol Infect Dis. 2012;31(8):1791-1796.
74. 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(3):754-761.
75. Bastani A, Galens S, Rocchini A, et al. ED identification of patients with severe sepsis/septic shock decreases mortality in a community hospital. Am J Emerg Med. 2012;30(8):1561-1566.
76. Vesteinsdottir E, Karason S, Sigurdsson SE, et al. Severe sepsis and septic shock: a prospective population-based study in Icelandic intensive care units. Acta Anaesthesiol Scand. 2011;55(6):722-731.
77. Rosado V, Pérez L, Guerra H, et al. Outcomes associated with conventional management of severe sepsis at Damas Hospital. Bol Asoc Med P R. 2011;103(2):35-38.
78. Davis JS, Cheng AC, McMillan M, Humphrey AB, Stephens DP, Anstey NM. Sepsis in the tropical Top End of Australia's Northern Territory. Med J Aust. 2011;194(10):519-524.
79. Wilhelms SB, Huss FR, Granath G, Sjöberg F. Assessment of incidence of severe sepsis in Sweden using different ways of abstracting International Classification of Diseases codes. Crit Care Med. 2010;38(6):1442-1449.
80. Shen HN, Lu CL, Yang HH. Epidemiologic trend of severe sepsis in Taiwan from 1997 through 2006. Chest. 2010;138(2):298-304.
81. Husak L, Marcuzzi A, Herring J, et al. National analysis of sepsis hospitalizations and factors contributing to sepsis in-hospital mortality in Canada. Healthc Q. 2010;13(Spec No):35-41.
82. Bateman BT, Schmidt U, Berman MF, Bittner EA. Temporal trends in the epidemiology of severe postoperative sepsis after elective surgery. Anesthesiology. 2010;112(4):917-925.
83. Vogel TR, Dombrovskiy VY, Lowry SF. Trends in postoperative sepsis: are we improving outcomes? Surg Infect (Larchmt). 2009;10(1):71-78.
84. Beale R, Reinhart K, Brunkhorst FM, et al. Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry. Infection. 2009;37(3):222-232.
85. Baharoon S, Al-Jahdali H, Al Hashmi J, Memish ZA, Ahmed QA. Severe sepsis and septic shock at the Hajj. Travel Med Infect Dis. 2009;7(4):247-252.
86. Rezende E, Silva JM Jr, Isola AM, et al. Epidemiology of severe sepsis in the emergency department and difficulties in the initial assistance. Clinics (Sao Paulo). 2008;63(4):457-464.
87. Blanco J, Muriel-Bombín A, Sagredo V, et al; Grupo de Estudios y Análisis en Cuidados Intensivos. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care. 2008;12(6):R158.
88. Beovic B, Hladnik Z, Pozenel P, Siuka D; Slovenian Severe Sepsis Study Group. Epidemiology of severe sepsis in Slovenian intensive care units for adults. J Chemother. 2008;20(1):134-136.
89. Andreu Ballester JC, Ballester F, González Sánchez A, et al. Epidemiology of sepsis in the Valencian Community (Spain), 1995-2004. Infect Control Hosp Epidemiol. 2008;29(7):630-634.
90. Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med. 2007;35(8):1928-1936.
91. Cheng B, Xie G, Yao S, et al. Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Crit Care Med. 2007;35(11):2538-2546.
92. Tanriover MD, Guven GS, Sen D, Unal S, Uzun O. Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country. Epidemiol Infect. 2006;134(2):315-322.
93. Strehlow MC, Emond SD, Shapiro NI, Pelletier AJ, Camargo CA Jr. National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med. 2006;48(3):326-331.
94. Harrison DA, Welch CA, Eddleston JM. The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004. Crit Care. 2006;10(2):R42.
95. Záhorec R, Firment J, Straková J, et al. Epidemiology of severe sepsis in intensive care units in the Slovak Republic. Infection. 2005;33(3):122-128.
96. Sundararajan V, Macisaac CM, Presneill JJ, Cade JF, Visvanathan K. Epidemiology of sepsis in Victoria, Australia. Crit Care Med. 2005;33(1):71-80.
97. Adrie C, Alberti C, Chaix-Couturier C, et al. Epidemiology and economic evaluation of severe sepsis in France. J Crit Care. 2005;20(1):46-58.
98. Van Gestel A, Bakker J, Veraart CP, Van Hout BA. Prevalence and incidence of severe sepsis in Dutch intensive care units. Crit Care. 2004;8(4):R153-R162.
99. Finfer S, Bellomo R, Lipman J, French C, Dobb G, Myburgh J. Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units. Intensive Care Med. 2004;30(4):589-596.
100. Brun-Buisson C, Meshaka P, Pinton P, Vallet B; EPISEPSIS Study Group. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004;30(4):580-588.
101. Padkin A, Goldfrad C, Brady AR, Young D, Black N, Rowan K. 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(9):2332-2338.
102. 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(16):1546-1554.
103. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-1310.
104. Wichmann MW, Inthorn D, Andress HJ, Schildberg FW. Incidence and mortality of severe sepsis in surgical intensive care patients. Intensive Care Med. 2000;26(2):167-172.
105. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997;278(3):234-240.
106. Sasse KC, Nauenberg E, Long A, Anton B, Tucker HJ, Hu TW. Long-term survival after intensive care unit admission with sepsis. Crit Care Med. 1995;23(6):1040-1047.
107. Brun-Buisson C, Doyon F, Carlet J, et al; French ICU Group for Severe Sepsis. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. JAMA. 1995;274(12):968-974.
108. Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014;5(1):4-11.
109. Moss M, Martin GS. A global perspective on the epidemiology of sepsis. Intensive Care Med. 2004;30(4):527-529.
110. Linde-Zwirble WT, Angus DC. Severe sepsis epidemiology: sampling, selection, and society. Crit Care. 2004;8(4):222-226.
111. 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(2):580-637.
112. Bernard GR, Vincent JL, Laterre PF, et al; Recombinant human protein CWorldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699-709.
113. Vincent JL, Moreno R, Takala J, et al; Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22(7):707-710.
114. Li P, Stuart EA, Allison DB. Multiple imputation: a flexible tool for handlingmissing data. JAMA. 2015;314(18):1966-1967.
115. Mikkelsen ME, Miltiades AN, Gaieski DF, et al. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med. 2009;37(5):1670-1677.
116. Vincent JL, Ince C, Bakker J. Clinical review: Circulatory shock-an update: a tribute to Professor Max HarryWeil. Crit Care. 2012;16(6):239.
117. Nichol AD, Egi M, Pettila V, et al. Relative hyperlactatemia and hospital mortality in critically ill patients. Crit Care. 2010;14(1):R25.
118. Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock. Lancet. 2005;365(9462):871-875.
119. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care. 2014;18(5):503.
120. Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet. 2002;359(9302):248-252.