Sepsis: Current definition, pathophysiology, diagnosis, and management

Nutrition in Clinical Practice

Volumn 32, Issue 3, 2017, Pages 296-308

  Taeb, Abdalsamih M ^a   Hooper, Michael H ^a   Marik, Paul E ^a  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

Author keywords

Critically ill; Intensive care unit; Nutritional support; Sepsis; Systemic inflammatory response syndrome

Indexed keywords

ANTIINFECTIVE AGENT; CORTICOSTEROID; DOPAMINE; HYDROCORTISONE; HYPERTENSIVE AGENT; INOTROPIC AGENT; NORADRENALIN; VASOCONSTRICTOR AGENT;

ANTIMICROBIAL THERAPY; CANDIDA; CLINICAL TRIAL (TOPIC); FLUID THERAPY; HEART STROKE VOLUME; HUMAN; IMMUNE RESPONSE; MEDICAL TERMINOLOGY; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); NONHUMAN; PATHOPHYSIOLOGY; PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESUSCITATION; REVIEW; SEPSIS; SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE; SYSTEMATIC REVIEW (TOPIC); VASOPLEGIA; DISEASE MANAGEMENT;

ADRENAL CORTEX HORMONES; ANTI-INFECTIVE AGENTS; DISEASE MANAGEMENT; HUMANS; META-ANALYSIS AS TOPIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEPSIS; VASOCONSTRICTOR AGENTS;

EID: 85021773264     PISSN: 08845336     EISSN: 19412452     Source Type: Journal    
DOI: 10.1177/0884533617695243     Document Type: Review

References (155)

1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-810
2. 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
3. Cohen J, Vincent J-L, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis. 2015;15(5):581-614
4. 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
5. Liu V, Escobar GJ, Greene JD, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312(1):90-92
6. Torio CM, Andrews RM. National inpatient hospital costs: the most expensive conditions by payer, 2011: statistical brief #160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville, MD: Agency for Healthcare Research and Quality; 2013
7. 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
8. Marik PE. Early management of severe sepsis: concepts and controversies. Chest. 2014;145(6):1407-1418
9. Vincent J-L, 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
10. 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. Chest. 1992;101(6):1644-1655
11. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29(4):530-538
12. 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;315:775-787
13. 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(8):762-774
14. Kaukonen K-M, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015;372(17):1629-1638
15. Whippy A, Skeath M, Crawford B, et al. Kaiser Permanente's performance improvement system, part 3: multisite improvements in care for patients with sepsis. Jt Comm J Qual Patient Saf. 2011;37(11):483-493
16. Churpek MM, Zadravecz FJ, Winslow C, Howell MD, Edelson DP. Incidence and prognostic value of the systemic inflammatory response syndrome and organ dysfunctions in ward patients. Am J Respir Crit Care Med. 2015;192(8):958-964
17. Williams JM, Greenslade JH, McKenzie JV, Chu K, Brown AF, Lipman J. SIRS, qSOFA and organ dysfunction: insights from a prospective database of emergency department patients with infection [published online November 19, 2016]. Chest
18. Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10(12):826-837
19. Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature. 2001;410(6832):1103-1107
20. Nau GJ, Richmond JFL, Schlesinger A, Jennings EG, Lander ES, Young RA. Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci USA. 2002;99(3):1503-1508
21. van der Poll T, Lowry SF. Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense? Shock. 1995;3(1):1-12
22. Pruitt JH, Copeland EM, Moldawer LL. Interleukin-1 and interleukin-1 antagonism in sepsis, systemic inflammatory response syndrome, and septic shock. Shock. 1995;3(4):235-251
23. Barriere SL, Lowry SF. An overview of mortality risk prediction in sepsis. Crit Care Med. 1995;23(2):376-393
24. Bone RC. Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intern Med. 1996;125(8):680-687
25. Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets-an updated view. Mediators Inflamm. 2013;2013(6):165974
26. Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8(10):776-787
27. Parrish WR, Gallowitsch-Puerta M, Czura CJ, Tracey KJ. Experimental therapeutic strategies for severe sepsis: mediators and mechanisms. Ann N Y Acad Sci. 2008;1144(1):210-236
28. Osler SW. The Evolution of Modern Medicine. New Haven, CT: Yale University Press; 1921
29. Skrupky LP, Kerby PW, Hotchkiss RS. Advances in the management of sepsis and the understanding of key immunologic defects. Anesthesiology. 2011;115(6):1349-1362
30. Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594-2605
31. Leentjens J, Kox M, van der Hoeven JG, Netea MG, Pickkers P. Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? Am J Respir Crit Care Med. 2013;187(12):1287-1293
32. Marik PE, Flemmer M. The immune response to surgery and trauma: implications for treatment. J Trauma Acute Care Surg. 2012;73(4): 801-808
33. McGown CC, Brown NJ, Hellewell PG, Brookes ZLS. ROCK induced inflammation of the microcirculation during endotoxemia mediated by nitric oxide synthase. Microvasc Res. 2011;81(3):281-288
34. Piagnerelli M, Boudjeltia KZ, Brohee D, Vincent J-L, Vanhaeverbeek M. Modifications of red blood cell shape and glycoproteins membrane content in septic patients. Adv Exp Med Biol. 2003;510:109-114
35. Piagnerelli M, Boudjeltia KZ, Vanhaeverbeek M, Vincent J-L. Red blood cell rheology in sepsis. Intensive Care Med. 2003;29(7): 1052-1061
36. Kirschenbaum LA, Aziz M, Astiz ME, Saha DC, Rackow EC. Influence of rheologic changes and platelet-neutrophil interactions on cell filtration in sepsis. Am J Respir Crit Care Med. 2000;161(5):1602-1607
37. Brealey D, Brand M, Hargreaves I, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002;360(9328):219-223
38. Crouser ED, Julian MW, Blaho DV, Pfeiffer DR. Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity. Crit Care Med. 2002;30(2):276-284
39. Marshall JC, Watson RW. Programmed cell death (apoptosis) and the resolution of systemic inflammation. Can J Surg. 1997;40(3):169-174
40. Coopersmith CM, Stromberg PE, Dunne WM, et al. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumoniainduced sepsis. JAMA. 2002;287(13):1716-1721
41. Goldenberg NM, Steinberg BE, Slutsky AS, Lee WL. Broken barriers: a new take on sepsis pathogenesis. Sci Transl Med. 2011;3(88):88ps25
42. Hernandez G, Bruhn A, Ince C. Microcirculation in sepsis: new perspectives. Curr Vasc Pharmacol. 2013;11(2):161-169
43. De Backer D, Creteur J, Preiser J-C, Dubois M-J, Vincent J-L. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98-104
44. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med. 2006;34(1):15-21
45. Prescott HC, Dickson RP, Rogers MAM, Langa KM, Iwashyna TJ. Hospitalization type and subsequent severe sepsis. Am J Respir Crit Care Med. 2015;192(5):581-588
46. Kempker JA, Martin GS. The changing epidemiology and definitions of sepsis. Clin Chest Med. 2016;37(2):165-179
47. Kirn TJ, Weinstein MP. Update on blood cultures: how to obtain, process, report, and interpret. Clin Microbiol Infect. 2013;19(6):513-520
48. Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366(22): 2055-2064
49. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(5):426-435
50. Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322-1331
51. Leli C, Ferranti M, Moretti A, Dhahab Al ZS, Cenci E, Mencacci A. Procalcitonin levels in gram-positive, gram-negative, and fungal bloodstream infections. Dis Markers. 2015;2015(31-32):701480-701488
52. Brodska H, Maličkova K, Adamkova V, Benakova H, Štastna MM, Zima T. Significantly higher procalcitonin levels could differentiate Gram-negative sepsis from Gram-positive and fungal sepsis. Clin Exp Med. 2013;13(3):165-170
53. Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med. 2010;38(11):2229-2241
54. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228
55. Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med. 2015;43(9):1907-1915
56. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-1596
57. Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis. 2001;32(9):1249-1272
58. Kollef MH, Napolitano LM, Solomkin JS, et al. Health care-associated infection (HAI): a critical appraisal of the emerging threat-proceedings of the HAI Summit. Clin Infect Dis. 2008;47(suppl 2):S55-S101
59. Johnson MT, Reichley R, Hoppe-Bauer J, Dunne WM, Micek S, Kollef M. Impact of previous antibiotic therapy on outcome of Gram-negative severe sepsis. Crit Care Med. 2011;39(8):1859-1865
60. Shindo Y, Ito R, Kobayashi D, et al. Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2013;188(8):985-995
61. Sibbald WJ, Vincent J-L. Round table conference on clinical trials for the treatment of sepsis. Chest. 1995;23:394-399
62. Verhoef J, Hustinx WM, Frasa H, Hoepelman AI. Issues in the adjunct therapy of severe sepsis. J Antimicrob Chemother. 1996;38(2):167-182
63. Cortegiani A, Russotto V, Maggiore A, et al. Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev. 2016;(1):CD004920
64. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50
65. Timsit J-F, Azoulay E, Schwebel C, et al. Empirical micafungin treatment and survival without invasive fungal infection in adults with ICU-acquired sepsis, Candida colonization, and multiple organ failure: the EMPIRICUS randomized clinical trial. JAMA. 2016;316(15): 1555-1564
66. Schuster MG, Edwards JE, Sobel JD, et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. 2008;149(2):83-90
67. Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40
68. Aliberti S, Blasi F, Zanaboni AM, et al. Duration of antibiotic therapy in hospitalised patients with community-acquired pneumonia. Eur Respir J. 2010;36(1):128-134
69. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93
70. Pugh R, Grant C, Cooke RPD, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015;(8):CD007577
71. Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015;372(21):1996-2005
72. Marshall JC, Maier RV, Jimenez M, Dellinger EP. Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med. 2004;32(11)(suppl):S513-S526
73. Sudarsky LA, Laschinger JC, Coppa GF, Spencer FC. Improved results from a standardized approach in treating patients with necrotizing fasciitis. Ann Surg. 1987;206(5):661-665
74. Kox M, Pickkers P. "Less is more" in critically ill patients: not too intensive. JAMA Intern Med. 2013;173(14):1369-1372
75. Hilton AK, Bellomo R. A critique of fluid bolus resuscitation in severe sepsis. Crit Care. 2012;16(1):302
76. Marik PE. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Ann Intensive Care. 2014;4(1):21
77. Marik PE, Monnet X, Teboul J-L. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care. 2011;1(1):1
78. Marik PE. Fluid responsiveness and the six guiding principles of fluid resuscitation. Crit Care Med. 2016;44(10):1920-1922
79. Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med. 2013;41(7):1774-1781
80. Wetterslev M, Haase N, Johansen RR, Perner A. Predicting fluid responsiveness with transthoracic echocardiography is not yet evidence based. Acta Anaesthesiol Scand. 2013;57(6):692-697
81. Muller L, Bobbia X, Toumi M, et al. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use. Crit Care. 2012;16(5):R188
82. Corl K, Napoli AM, Gardiner F. Bedside sonographic measurement of the inferior vena cava caval index is a poor predictor of fluid responsiveness in emergency department patients. Emerg Med Australas. 2012;24(5):534-539
83. Monnet X, Marik P, Teboul J-L. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensive Care Med. 2016;42(12):1935-1947
84. Cherpanath TGV, Hirsch A, Geerts BF, et al. Predicting fluid responsiveness by passive leg raising: a systematic review and meta-analysis of 23 clinical trials. Crit Care Med. 2016;44(5):981-991
85. Marik P, Bellomo R. A rational approach to fluid therapy in sepsis. Br J Anaesth. 2016;116(3):339-349
86. Lammi MR, Aiello B, Burg GT, et al. Response to fluid boluses in the fluid and catheter treatment trial. Chest. 2015;148(4):919-926
87. Nunes TSO, Ladeira RT, Bafi AT, Azevedo LCP, Machado FR, Freitas FGR. Duration of hemodynamic effects of crystalloids in patients with circulatory shock after initial resuscitation. Ann Intensive Care. 2014;4(1):25
88. Glassford NJ, Eastwood GM, Bellomo R. Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data. Crit Care. 2014;18(6):696
89. Monge Garcia MI, Guijo Gonzalez P, Gracia Romero M, et al. Effects of fluid administration on arterial load in septic shock patients. Intensive Care Med. 2015;41(7):1247-1255
90. Pierrakos C, Velissaris D, Scolletta S, Heenen S, De Backer D, Vincent J-L. Can changes in arterial pressure be used to detect changes in cardiac index during fluid challenge in patients with septic shock? Intensive Care Med. 2012;38(3):422-428
91. Brandt S, Regueira T, Bracht H, et al. Effect of fluid resuscitation on mortality and organ function in experimental sepsis models. Crit Care. 2009;13(6):R186
92. Rosenberg AL, Dechert RE, Park PK, Bartlett RH; NIH NHLBI ARDS Network. 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
93. Alsous F, Khamiees M, DeGirolamo A, Amoateng-Adjepong Y, Manthous CA. Negative fluid balance predicts survival in patients with septic shock: a retrospective pilot study. Chest. 2000;117(6):1749-1754
94. Murphy CV, Schramm GE, Doherty JA, et al. The importance of fluid management in acute lung injury secondary to septic shock. Chest. 2009;136(1):102-109
95. Chung F-T, Lin S-M, Lin S-Y, Lin H-C. Impact of extravascular lung water index on outcomes of severe sepsis patients in a medical intensive care unit. Respir Med. 2008;102(7):956-961
96. Bouchard J, Soroko SB, Chertow GM, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009;76(4):422-427
97. Micek ST, McEvoy C, McKenzie M, Hampton N, Doherty JA, Kollef MH. Fluid balance and cardiac function in septic shock as predictors of hospital mortality. Crit Care. 2013;17(5):R246
98. Boyd JH, Forbes J, Nakada T-A, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011;39(2):259-265
99. Kelm DJ, Perrin JT, Cartin-Ceba R, Gajic O, Schenck L, Kennedy CC. Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock. 2015;43(1):68-73
100. Kirkpatrick AW, Roberts DJ, De Waele J, et al. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med. 2013;39(7):1190-1206
101. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364(26):2483-2495
102. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology. 1999;90(5):1265-1270
103. Kellum JA, Bellomo R, Kramer DJ, Pinsky MR. Etiology of metabolic acidosis during saline resuscitation in endotoxemia. Shock. 1998;9(5):364-368
104. Reid F, Lobo DN, Williams RN, Rowlands BJ, Allison SP. Abnormal saline and physiological Hartmann's solution: a randomized doubleblind crossover study. Clin Sci. 2003;104(1):17-24
105. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyteR 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256(1):18-24
106. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012;308(15):1566-1572
107. Raghunathan K, Shaw A, Nathanson B, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med. 2014;42(7):1585-1591
108. Young P, Bailey M, Beasley R, et al. Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial. JAMA. 2015;314(16):1701-1710
109. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012;367(2):124-134
110. Patel A, Laffan MA, Waheed U, Brett SJ. Randomised trials of human albumin for adults with sepsis: systematic review and metaanalysis with trial sequential analysis of all-cause mortality. BMJ. 2014;349(10):g4561-g4561
111. SAFE Study Investigators,Finfer S, McEvoy S, et al. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 2011;37(1):86-96
112. Xu J-Y, Chen Q-H, Xie J-F, et al. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials. Crit Care. 2014;18(6):702
113. Kremer H, Baron-Menguy C, Tesse A, et al. Human serum albumin improves endothelial dysfunction and survival during experimental endotoxemia: concentration-dependent properties. Crit Care Med. 2011;39(6):1414-1422
114. Bellomo R, Giantomasso DD. Noradrenaline and the kidney: friends or foes? Crit Care. 2001;5(6):294-298
115. Lehman L-W, Saeed M, Talmor D, Mark R, Malhotra A. Methods of blood pressure measurement in the ICU. Crit Care Med. 2013;41(1): 34-40
116. Varpula M, Tallgren M, Saukkonen K, Voipio-Pulkki LM, Pettila V. Hemodynamic variables related to outcome in septic shock. Intensive Care Med. 2005;31(8):1066-1071
117. Asfar P, Meziani F, Hamel J-F, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17): 1583-1593
118. De Backer D, Aldecoa C, Njimi H, Vincent J-L. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012;40(3):725-730
119. Malay M-B, Ashton JL, Dahl K, et al. Heterogeneity of the vasoconstrictor effect of vasopressin in septic shock. Crit Care Med. 2004;32(6):1327-1331
120. Persichini R, Silva S, Teboul J-L, et al. Effects of norepinephrine on mean systemic pressure and venous return in human septic shock. Crit Care Med. 2012;40(12):3146-3153
121. Monnet X, Jabot J, Maizel J, Richard C, Teboul J-L. Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients. Crit Care Med. 2011;39(4):689-694
122. Hamzaoui O, Georger J-F, Monnet X, et al. Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. Crit Care. 2010;14(4):R142
123. Abid O, Akca S, Haji-Michael P, Vincent J-L. Strong vasopressor support may be futile in the intensive care unit patient with multiple organ failure. Crit Care Med. 2000;28(4):947-949
124. Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95(5):1122-1125
125. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877-887
126. Smith B, Phillips R, Madigan V, West M. Decreased mortality, morbidity and emergency transport in septic shock: a new protocol based on advanced noninvasive haemodynamics and early antibiotics. Crit Care Med. 2012;40(12):1-328
127. Rissmiller R. Patients are not airplanes and doctors are not pilots. Crit Care Med. 2006;34(11):2869
128. Silva Ramos FJ, Azevedo L. Hemodynamic and perfusion end points for volemic resuscitation in sepsis. Shock. 2010;34(suppl 1):34-39
129. 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(18):1683-1693
130. 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(16):1496-1506
131. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-1311
132. Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood flow and function during recovery from experimental septic acute kidney injury. Intensive Care Med. 2007;33(9):1614-1618
133. Langenberg C, Wan L, Egi M, May CN. Renal blood flow in experimental septic acute renal failure. Kidney Int. 2006;69(11):1996-2002
134. Wan L, Bagshaw SM, Langenberg C. Pathophysiology of septic acute kidney injury: what do we really know? Critical Care. 2008;36(4) (suppl):S198-S203
135. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):840-851
136. Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactateguided therapy in intensive care unit patients. Am J Respir Crit Care Med. 2010;182(6):752-761
137. Jones AE, Shapiro NI, Trzeciak S, Arnold RC. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739-746
138. Marik PE, Bellomo R. Lactate clearance as a target of therapy in sepsis: a flawed paradigm. OA Crit Care. 2013;1(1):3
139. James JH, Luchette FA, McCarter FD, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet. 1999;354(9177):505-508
140. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care. 2014;18(5):207
141. Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+ K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet. 2005;365(9462):871-875
142. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-1308
143. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO 2 Collaborative Group. N Engl J Med. 1995;333(16):1025-1032
144. Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330(24):1717-1722
145. 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: a randomized clinical trial. JAMA. 2013;310(16):1683-1691
146. Saugel B, Ringmaier S, Holzapfel K, et al. Physical examination, central venous pressure, and chest radiography for the prediction of transpulmonary thermodilution-derived hemodynamic parameters in critically ill patients: a prospective trial. J Crit Care. 2011;26(4):402-410
147. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288(7):862-871
148. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-124
149. Minneci PC, Deans KJ, Eichacker PQ, Natanson C. The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis. Clin Microbiol Infect. 2009;15(4):308-318
150. Annane D, Bellissant E, Bollaert P-E, Briegel J, Keh D, Kupfer Y. Corticosteroids for treating sepsis. Cochrane Database Syst Rev. 2015;(12):CD002243
151. Venkatesh B, Myburgh J, Finfer S, et al. The ADRENAL study protocol: adjunctive corticosteroid treatment in critically ill patients with septic shock. Crit Care Resusc. 2013;15(2):83-88
152. McCulloh R, Opal SM. Human recombinant lactoferrin for sepsis: too good to be true? Crit Care Med. 2013;41(3):908-909
153. Opal SM, Laterre P-F, Francois B, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 2013;309(11):1154-1162
154. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study [published online December 6, 2016]. Chest
155. 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