Clinical management of the cardiovascular failure in sepsis

Current Vascular Pharmacology

Volumn 11, Issue 2, 2013, Pages 222-242

  De Backer, Daniel ^a   Scolletta, Sabino ^a  

^a ERASME HOSPITAL   (Belgium)

Author keywords

Cardiac dysfunction; Fluids; Hypotension; Inotropic agents; Microcirculation; Sepsis; Septic shock; Vasopressor; Vasoreactivity

Indexed keywords

ADRENALIN; ALBUMIN; ALPHA ADRENERGIC RECEPTOR; ANTICOAGULANT AGENT; BETA 1 ADRENERGIC RECEPTOR; CALCIUM; CATECHOLAMINE; CYCLIC AMP; CYTOKINE; DOPAMINE; DOPAMINE RECEPTOR; ENDOTHELIN; ENDOTOXIN; G PROTEIN COUPLED RECEPTOR; HETASTARCH; HYPERTENSIVE AGENT; INDUCIBLE NITRIC OXIDE SYNTHASE; INOTROPIC AGENT; MITOGEN ACTIVATED PROTEIN KINASE; MYOSIN LIGHT CHAIN KINASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NITRIC OXIDE; NORADRENALIN; PEROXYNITRITE; PHENYLEPHRINE; PROTEIN KINASE C; STEROID; UNINDEXED DRUG; VASCULOTROPIN; VASOPRESSIN; CARDIOTONIC AGENT; VASOCONSTRICTOR AGENT;

ARTICLE; BLOOD PRESSURE; BLOOD VESSEL TONE; CARDIOMYOPATHY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HEART FAILURE; HEART LEFT VENTRICLE FUNCTION; HEART MUSCLE CONTRACTILITY; HEART MUSCLE PERFUSION; HEART OUTPUT; HEART RIGHT VENTRICLE FUNCTION; HEMODYNAMICS; HUMAN; HYPOTENSION; HYPOVOLEMIA; INFLAMMATION; META ANALYSIS (TOPIC); MICROCIRCULATION; MULTICENTER STUDY (TOPIC); MYOCARDIAL DISEASE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK; SEPSIS; SHOCK; SIGNAL TRANSDUCTION; SPLANCHNIC BLOOD FLOW; ANIMAL; CARDIOMYOPATHIES; COMPLICATION; DISEASE MANAGEMENT; OXYGEN CONSUMPTION; PATHOPHYSIOLOGY; PHYSIOLOGY; PROCEDURES;

ANIMALS; CARDIOMYOPATHIES; CARDIOTONIC AGENTS; DISEASE MANAGEMENT; HEART FAILURE; HUMANS; OXYGEN CONSUMPTION; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEPSIS; VASOCONSTRICTOR AGENTS;

EID: 84875281977     PISSN: 15701611     EISSN: 18756212     Source Type: Journal    
DOI: 10.2174/157016113805290209     Document Type: Article

References (259)

1. 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.
2. Antonelli M, Levy M, Andrews PJ, et al. Hemodynamic monitoring in shock and implications for management: International Consensus Conference, Paris, France, 27-28 April 2006. Intensive Care Med 2007; 33:575-90.
3. 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; 29:1303-10.
4. Brun-Buisson C, Meshaka P, Pinton P, Vallet B. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med 2004; 30:580-8.
5. Blanco J, Muriel-Bombin A, Sagredo V, et al. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care 2008; 12:R158.
6. Rivers EP, Kruse JA, Jacobsen G, et al. The influence of early hemodynamic optimization strategies on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007; 35:2016-24.
7. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296-327.
8. Court O, Kumar A, Parrillo JE, Kumar A. Clinical review: Myocardial depression in sepsis and septic shock. Crit Care 2002; 6:500-8.
9. O'Dwyer ST, Michie HR, Ziegler TR, Revhaug A, Smith RJ, Wilmore DW. A single dose of endotoxin increases intestinal permeability in healthy humans. Arch Surg 1988; 123:1459-64.
10. Fink MP, Antonsson JB, Wang H, Rothschild HR. Increased intestinal permeability in endotoxic pigs. Arch Surg 1991; 126:211-8.
11. Veliz LP, Gonzalez FG, Duling BR, Saez JC, Boric MP. Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo. Am J Physiol Heart Circ Physiol 2008; 295:H1056-H1066.
12. Ramirez R, Chong T, Victorino GP. Angiotensin II Effect on Hydraulic Permeability: Interaction with Endothelin-1, Nitric Oxide, and Platelet Activating Factor. J Surg Res 2006; 134:259-64.
13. Porter LP, McNamee JE, Wolf MB. Endothelin-1 induces endothelial barrier failure in the cat hindlimb. Shock 1999; 11:111-4.
14. Chavez AM, Menconi MJ, Hodin RA, Fink MP. Cytokine-induced intestinal epithelial hyperpermeability: role of nitric oxide. Crit Care Med 1999; 27:2246-51.
15. Chappell D, Jacob M, Hofmann-Kiefer K, et al. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology 2007; 107:776-84.
16. Liaudet L, Szabo A, Soriano FG, Zingarelli B, Szabo C, Salzman AL. Poly (ADP-ribose) synthetase mediates intestinal mucosal barrier dysfunction after mesenteric ischemia. Shock 2000; 14:134-41.
17. Shen Q, Rigor RR, Pivetti CD, Wu MH, Yuan SY. Myosin light chain kinase in microvascular endothelial barrier function. Cardiovasc Res 2010; 87:272-80.
18. Kumar P, Shen Q, Pivetti CD, Lee ES, Wu MH, Yuan SY. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Rev Mol Med 2009; 11:e19.
19. Pinsky MR, Matuschak GM. Cardiovascular determinants of the hemodynamic response to acute endotoxemia in the dog. J Crit Care 1986; 1:18-31.
20. Ayuse T, Brienza N, Revelly JP, O'Donnell CP, Boitnott JK, Robotham JL. Alterations in liver hemodynamics in an intact porcine model of endotoxin shock. Am J Physiol 1995; 268:H1106-H1114.
21. Stephan F, Novara A, Tournier B, et al. Determination of total effective vascular compliance in patients with sepsis syndrome. Am J Respir Crit Care Med 1998; 157:50-6.
22. Levy B, Collin S, Sennoun N, et al. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med 2010; 36:2019-29.
23. Annane D, Bellissant E, Sebille V, et al. Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve. Br J Clin Pharmacol 1998; 46:589-97.
24. Umans JG, Wylam ME, Samsel RW, Edwards J, Schumacker PT. Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta. Am Rev Respir Dis 1993; 148:1638-45.
25. Farmer MR, Roberts RE, Gardiner SM, Ralevic V. Effects of in vivo lipopolysaccharide infusion on vasoconstrictor function of rat isolated mesentery, kidney, and aorta. J Pharmacol Exp Ther 2003; 306:538-45.
26. Dorman T, Breslow MJ, Lipsett PA, et al. Radial artery pressure monitoring underestimates central arterial pressure during vasopressor therapy in critically ill surgical patients. Crit Care Med 1998; 26:1646-9.
27. Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997; 95:1122-5.
28. Jochberger S, Morgenthaler NG, Mayr VD, et al. Copeptin and arginine vasopressin concentrations in critically ill patients. J Clin Endocrinol Metab 2006; 91:4381-6.
29. Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D. Circulating vasopressin levels in septic shock. Crit Care Med 2003; 31:1752-8.
30. Jochberger S, Mayr VD, Luckner G, et al. Serum vasopressin concentrations in critically ill patients. Crit Care Med 2006; 34:293-9.
31. Sonneville R, Guidoux C, Barrett L, Viltart O, Mattot V, Polito A, et al. Vasopressin synthesis by the magnocellular neurons is different in the supraoptic nucleus and in the paraventricular nucleus in human and experimental septic shock. Brain Pathol 2010; 20:613-22.
32. Bucher M, Hobbhahn J, Taeger K, Kurtz A. Cytokine-mediated downregulation of vasopressin V(1A) receptors during acute endotoxemia in rats. Am J Physiol Regul Integr Comp Physiol 2002; 282:R979-R984.
33. Hamu Y, Kanmura Y, Tsuneyoshi I, Yoshimura N. The effects of vasopressin on endotoxin-induced attenuation of contractile responses in human gastroepiploic arteries in vitro. Anesth Analg 1999; 88:542-8.
34. Carnio EC, Stabile AM, Batalhao ME, et al. Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase. Pflugers Arch 2005; 450:390-4.
35. Dunser MW, Werner ER, Wenzel V, et al. Arginine vasopressin and serum nitrite/nitrate concentrations in advanced vasodilatory shock. Acta Anaesthesiol Scand 2004; 48:814-9.
36. Schirmer JM, Fry DE. Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia. Arch Surg 1989; 124:445-8.
37. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC. Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 1990; 259:H1038-H1043.
38. Boyle WA, III, Parvathaneni LS, Bourlier V, Sauter C, Laubach VE, Cobb JP. iNOS gene expression modulates microvascular responsiveness in endotoxin-challenged mice. Circ Res 2000; 87:E18-E24.
39. Gunnett CA, Chu Y, Heistad DD, Loihl A, Faraci FM. Vascular effects of LPS in mice deficient in expression of the gene for inducible nitric oxide synthase. Am J Physiol 1998; 275:H416-H421.
40. Hollenberg SM, Broussard M, Osman J, Parrillo JE. Increased microvascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase. Circ Res 2000; 86:774-8.
41. Kooy NW, Royall JA. Agonist-induced peroxynitrite production from endothelial cells. Arch Biochem Biophys 1994; 310:352-9.
42. Salvemini D, Wang ZQ, Zweier JL, et al. A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science 1999; 286:304-6.
43. Hocherl K, Schmidt C, Kurt B, Bucher M. Activation of the PGI(2)/IP system contributes to the development of circulatory failure in a rat model of endotoxic shock. Hypertension 2008; 52:330-5.
44. Suzuki Y, Lu Q, Xu DZ, Szabo C, Hasko G, Deitch EA. Na+, K+-ATPase activity is inhibited in cultured intestinal epithelial cells by endotoxin or nitric oxide. Int J Mol Med 2005; 15:871-7.
45. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001; 345:588-95.
46. Kuo JH, Chen SJ, Shih CC, Lue WM, Wu CC. Abnormal activation of potassium channels in aortic smooth muscle of rats with peritonitis-induced septic shock. Shock 2009; 32:74-9.
47. Collin S, Sennoun N, Dron AG, et al. Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock. Intensive Care Med 2011; 37:861-9.
48. Landry DW, Oliver JA. The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. J Clin Invest 1992; 89:2071-4.
49. Lange M, Williams W, Bone HG, et al. Continuously infused glipizide reverses the hyperdynamic circulation in ovine endotoxemia. Shock 2007; 27:701-6.
50. Warrillow S, Egi M, Bellomo R. Randomized, double-blind, placebo-controlled crossover pilot study of a potassium channel blocker in patients with septic shock. Crit Care Med 2006; 34:980-5.
51. Morelli A, Lange M, Ertmer C, et al. Glibenclamide dose response in patients with septic shock: Effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport. Shock 2007; 28(5):530-5.
52. Preiser JC, Zhang H, Debelle F, et al. Hemodynamic effects of glibenclamide during endotoxemia: contrasting findings in vitro versus in vivo. Shock 2003; 19:223-8.
53. O'Brien A, Stidwill RP, Clapp LH, Singer M. Variable effects of inhibiting iNOS and closing the vascular ATP-sensitive potassium channel (via its pore-forming and sulfonylurea receptor subunits) in endotoxic shock. Shock 2009; 31:535-41.
54. Rothwell PM, Udwadia ZF, Lawler PG. Cortisol response to corticotropin and survival in septic shock. Lancet 1991; 337:582-3.
55. Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000; 283:1038-45.
56. Bollaert PE, Fieux F, Charpentier C, Levy B. Baseline cortisol levels, cortisol response to corticotropin, and prognosis in late septic shock. Shock 2003; 19:13-5.
57. Siraux V, De Backer D, Yalavatti G, et al. Relative adrenal insufficiency in patients with septic shock: comparison of low-dose and conventional corticotropin tests. Crit Care Med 2005; 33:2479-86.
58. Wan MX, Zhang XW, Torkvist L, Thorlacius H. Low molecular weight heparin inhibits tumor necrosis factor alpha-induced leukocyte rolling. Inflamm Res 2001; 50:581-4.
59. Ertmer C, Bone HG, Morelli A, et al. Methylprednisolone reverses vasopressin hyporesponsiveness in ovine endotoxemia. Shock 2007; 27:281-8.
60. Maeder M, Fehr T, Rickli H, Ammann P. Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest 2006; 129:1349-66.
61. Rabuel C, Mebazaa A. Septic shock: a heart story since the 1960s. Intensive Care Med 2006; 32:799-807.
62. Maeder M, Ammann P, Kiowski W, Rickli H. B-type natriuretic peptide in patients with sepsis and preserved left ventricular ejection fraction. Eur J Heart Fail 2005; 7:1164-7.
63. Hoesel LM, Niederbichler AD, Ward PA. Complement-related molecular events in sepsis leading to heart failure. Mol Immunol 2007; 44:95-102.
64. Parker MM, Shelhamer JH, Bacharach SL, et al. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 1984; 100:483-90.
65. Ognibene FP, Parker MM, Natanson C, Shelhamer JH, Parrillo JE. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock. Chest 1988; 93:903-10.
66. Levy RJ, Piel DA, Acton PD, et al. Evidence of myocardial hibernation in the septic heart. Crit Care Med 2005; 33:2752-6.
67. Levy RJ, Deutschman CS. Evaluating myocardial depression in sepsis. Shock 2004; 22:1-10.
68. Jardin F, Brun-Ney D, Auvert B, Beauchet A, Bourdarias JP. Sepsis-related cardiogenic shock. Crit Care Med 1990; 18:1055-60.
69. Jardin F, Fourme T, Page B, et al. Persistent preload defect in severe sepsis despite fluid loading: A longitudinal echocardiographic study in patients with septic shock. Chest 1999; 116:1354-9.
70. Poelaert J, Declerck C, Vogelaers D, Colardyn F, Visser CA. Left ventricular systolic and diastolic function in septic shock. Intensive Care Med 1997; 23:553-60.
71. Vieillard-Baron A, Prin S, Chergui K, Dubourg O, Jardin F. Hemodynamic instability in sepsis: bedside assessment by Doppler echocardiography. Am J Respir Crit Care Med 2003; 168:1270-6.
72. Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F. Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med 2008; 36:1701-6.
73. Zanotti-Cavazzoni SL, Guglielmi M, Parrillo JE, Walker T, Dellinger RP, Hollenberg SM. Fluid resuscitation influences cardiovascular performance and mortality in a murine model of sepsis. Intensive Care Med 2009; 35:748-54.
74. Zanotti Cavazzoni SL, Guglielmi M, Parrillo JE, Walker T, Dellinger RP, Hollenberg SM. Ventricular dilation is associated with improved cardiovascular performance and survival in sepsis. Chest 2010; 138:848-55.
75. Bouhemad B, Nicolas-Robin A, Arbelot C, Arthaud M, Feger F, Rouby JJ. Isolated and reversible impairment of ventricular relaxation in patients with septic shock. Crit Care Med 2008; 36:766-74.
76. Etchecopar-Chevreuil C, Francois B, Clavel M, Pichon N, Gastinne H, Vignon P. Cardiac morphological and functional changes during early septic shock: a transesophageal echocardiographic study. Intensive Care Med 2008; 34:250-6.
77. Parker MM, McCarthy KE, Ognibene FP, Parrillo JE. Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterize the cardiac depression of septic shock in humans. Chest 1990; 97:126-31.
78. Vieillard-Baron A, Schmitt JM, Beauchet A, et al. Early preload adaptation in septic shock? A transesophageal echocardiographic study. Anesthesiology 2001; 94:400-6.
79. Dhainaut JF, Pinsky MR, Nouria S, Slomka F, Brunet F. Right ventricular function in human sepsis: a thermodilution study. Chest 1997; 112:1043-9.
80. Furian T, Aguiar C, Prado K, et al. Ventricular dysfunction and dilation in severe sepsis and septic shock: Relation to endothelial function and mortality. J Crit Care 2011.
81. Kimchi A, Ellrodt AG, Berman DS, Riedinger MS, Swan HJ, Murata GH. Right ventricular performance in septic shock: a combined radionuclide and hemodynamic study. J Am Coll Cardiol 1984; 4:945-51.
82. Cohen RI, Shapir Y, Chen L, Scharf SM. Right ventricular overload causes the decrease in cardiac output after nitric oxide synthesis inhibition in endotoxemia. Crit Care Med 1998; 26:738-47.
83. Lefer AM. Role of a myocardial depressant factor in the pathogenesis of circulatory shock. Fed Proc 1970; 29:1836-47.
84. Parrillo JE, Burch C, Shelhamer JH. A circulating myocardial depressant substance in humans with septic shock. J Clin Invest 1985; 76:1539-53.
85. Reilly JM, Cunnion RE, Burch-Whitman C, Parker MM, Shelhamer JH, Parrillo JE. A circulating myocardial depressant substance is associated with cardiac dysfunction and peripheral hypoperfusion (lactic acidemia) in patients with septic shock. Chest 1989; 95:1072-80.
86. Natanson C, Eichenholz PW, Danner RL, et al. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 1989; 169:823-32.
87. Vincent JL, Bakker J, Marécaux G, Schandene L, Kahn RJ, Dupont E. Anti-TNF antibodies administration increases myocardial contractility in septic shock patients. Chest 1992; 101:810-5.
88. Goldhaber JI, Kim KH, Natterson PD, Lawrence T, Yang P, Weiss JN. Effects of TNF-alpha on [Ca2+]i and contractility in isolated adult rabbit ventricular myocytes. Am J Physiol 1996; 271:H1449-H1455.
89. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992; 257:387-9.
90. Markel TA, Crisostomo PR, Wang M, Herrmann JL, Abarbanell AM, Meldrum DR. Right ventricular TNF resistance during endotoxemia: the differential effects on ventricular function. Am J Physiol Regul Integr Comp Physiol 2007; 293:R1893-R1897.
91. Finkel MS, Oddis CV, Mayer OH, Hattler BG, Simmons RL. Nitric oxide synthase inhibitor alters papillary muscle force-frequency relationship. J Pharmacol Exp Ther 1995; 272:945-52.
92. Massion PB, Feron O, Dessy C, Balligand JL. Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 2003; 93:388-98.
93. Ullrich R, Scherrer-Crosbie M, Bloch KD, et al. Congenital deficiency of nitric oxide synthase 2 protects against endotoxininduced myocardial dysfunction in mice. Circulation 2000; 102:1440-6.
94. Ichinose F, Buys ES, Neilan TG, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 prevents myocardial dysfunction in murine models of septic shock. Circ Res 2007; 100:130-9.
95. Cunnion RE, Schaer GL, Parker MM, Natanson C, Parrillo JE. The coronary circulation in human septic shock. Circulation 1986; 73:637-44.
96. Dhainaut JF, Huyghebaert MF, Monsallier JF, et al. Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 1987; 75:533-41.
97. Bateman RM, Tokunaga C, Kareco T, Dorscheid DR, Walley KR. Myocardial hypoxia-inducible HIF-1{alpha}, VEGF and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol 2007; 293:H448-H456.
98. Sharshar T, Gray F, Lorin dlG, et al. Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 2003; 362:1799-805.
99. Silverman HJ, Penaranda R, Orens JB, Lee NH. Impaired betaadrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: association with myocardial hyporesponsiveness to catecholamines. Crit Care Med 1993; 21:31-9.
100. Tang C, Liu MS. Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis. Am J Physiol 1996; 270:R254-R263.
101. Levy RJ, Vijayasarathy C, Raj NR, Avadhani NG, Deutschman CS. Competitive and noncompetitive inhibition of myocardial cytochrome C oxidase in sepsis. Shock 2004; 21:110-4.
102. Gellerich FN, Trumbeckaite S, Hertel K, et al. Impaired energy metabolism in hearts of septic baboons: diminished activities of Complex I and Complex II of the mitochondrial respiratory chain. Shock 1999; 11:336-41.
103. Tavernier B, Mebazaa A, Mateo P, Sys S, Ventura-Clapier R, Veksler V. Phosphorylation-dependent alteration in myofilament ca2+ sensitivity but normal mitochondrial function in septic heart. Am J Respir Crit Care Med 2001; 163:362-7.
104. Chen HW, Hsu C, Lu TS, Wang SJ, Yang RC. Heat shock pretreatment prevents cardiac mitochondrial dysfunction during sepsis. Shock 2003; 20:274-9.
105. Oddis CV, Finkel MS. Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. Biochem Biophys Res Commun 1995; 213:1002-9.
106. Brealey D, Brand M, Hargreaves I, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 2002; 360:219-23.
107. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 2007; 35:1599-608.
108. Rossi MA, Celes MR, Prado CM, Saggioro FP. Myocardial structural changes in long-term human severe sepsis/septic shock may be responsible for cardiac dysfunction. Shock 2007; 27:10-8.
109. Lancel S, Joulin O, Favory R, et al. Ventricular myocyte caspases are directly responsible for endotoxin-induced cardiac dysfunction. Circulation 2005; 111:2596-604.
110. Favory R, Lancel S, Marchetti P, et al. Endotoxin-induced myocardial dysfunction: evidence for a role of sphingosine production. Crit Care Med 2004; 32:495-501.
111. Larche J, Lancel S, Hassoun SM, et al. Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality. J Am Coll Cardiol 2006; 48:377-85.
112. Hassoun SM, Lancel S, Petillot P, et al. Sphingosine impairs mitochondrial function by opening permeability transition pore. Mitochondrion 2006; 6:149-54.
113. Tavernier B, Li JM, El Omar MM, et al. Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats. FASEB J 2001; 15:294-6.
114. Nelson DP, Beyer C, Samsel RW, Wood LDH, Schumacker PT. Pathological supply dependence of O2 uptake during bacteremia in dogs. J Appl Physiol 1987; 63:1487-92.
115. Zhang H, Smail N, Cabral A, Cherkaoui S, Peny MO, Vincent JL. Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin. J Surg Res 1999; 81:129-38.
116. Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R. Effect of a maldistribution of microvascular blood flow on capillary O(2) extraction in sepsis. Am J Physiol 2002; 282:H156-H164.
117. Vincent JL, De Backer D. Oxygen transport-the oxygen delivery controversy. Intensive Care Med 2004; 30:1990-6.
118. Budinger GRS, Chandel N, Shao ZH, et al. Cellular energy utilization and supply during hypoxia in embryonic cardiac myocytes. Am J Physiol 1996; 270:L44-L53.
119. Sautner T, Wessely C, Riegler M, et al. Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock. Ann Surg 1998; 228:239-48.
120. Nakajima Y, Baudry N, Duranteau J, Vicaut E. Microcirculation in Intestinal Villi. A comparison between hemorrhagic and endotoxin shock. Am J Respir Crit Care Med 2001; 164:1526-30.
121. Tugtekin I, Radermacher P, Theisen M, et al. Increased ilealmucosal-arterial PCO2 gap is associated with impaired villus microcirculation in endotoxic pigs. Intensive Care Med 2001; 27:757-66.
122. Marik PE. Gastric intramucosal pH: a better predictor of multiorgan dysfunction syndrome and death than oxygen-derived variables in patients with sepsis. Chest 1993; 104:225-9.
123. Levy B, Gawalkiewicz P, Vallet B, Briancon S, Nace L, Bollaert PE. Gastric capnometry with air-automated tonometry predicts outcome in critically ill patients. Crit Care Med 2003; 31:474-80.
124. Gomersall CD, Joynt GM, Freebairn RC, Hung V, Buckley TA, Oh TE. Resuscitation of critically ill patients based on the results of gastric tonometry: a prospective, randomized, controlled trial. Crit Care Med 2000; 28:607-14.
125. Due V, Bonde J, Espersen K, Jensen TH, Perner A. Lactic acidosis in the rectal lumen of patients with septic shock measured by luminal equilibrium dialysis. Br J Anaesth 2002; 89:919-22.
126. Jorgensen VL, Nielsen SL, Espersen K, Perner A. Increased colorectal permeability in patients with severe sepsis and septic shock. Intensive Care Med 2006; 32:1790-6.
127. Yu P, Martin CM. Increased gut permeability and bacterial translocation in Pseudomonas pneumonia-induced sepsis. Crit Care Med 2000; 28:2573-7.
128. Sapin V, Nicolet L, Aublet-Cuvelier B, et al. Rapid decrease in plasma D-lactate as an early potential predictor of diminished 28-day mortality in critically ill septic shock patients. Clin Chem Lab Med 2006; 44:492-6.
129. Poeze M, Solberg BC, Greve JW, Ramsay G. Gastric PgCO2 and Pg-aCO2 gap are related to D-lactate and not to L-lactate levels in patients with septic shock. Intensive Care Med 2003; 29:2081-5.
130. Meier-Hellmann A, Specht M, Hannemann L, Hassel H, Bredle DL, Reinhart K. Splanchnic blood flow is greater in septic shock treated with norepinephrine than in severe sepsis. Intensive Care Med 1996; 22:1354-9.
131. Dahn MS, Lange P, Lobdell K, Hans B, Jacobs LA, Mitchell RA. Splanchnic and total body oxygen consumption differences in septic and injured patients. Surgery 1987; 101:69-80.
132. Dahn MS, Mitchell RA, Lange MP, Smith S, Jacobs LA. Hepatic metabolic response to injury and sepsis. Surgery 1995; 117:520-30.
133. Dahn MS, Lange MP, McCurdy B, Mahaffey S. Metabolic function of the isolated perfused rat liver in chronic sepsis. J Surg Res 1995; 59:287-91.
134. Ruokonen E, Takala J, Uusaro A. Effect of vasoactive treatment on the relationship between mixed venous and regional oxygen saturation. Crit Care Med 1991; 19:1365-9.
135. De Backer D, Creteur J, Noordally O, Smail N, Gulbis B, Vincent JL. Does hepato-splanchnic VO2/DO2 dependency exist in critically ill septic patients? Am J Respir Crit Care Med 1998; 157:1219-25.
136. Madorin WS, Martin CM, Sibbald WJ. Dopexamine attenuates flow motion in ileal mucosal arterioles in normotensive sepsis. Crit Care Med 1999; 27:394-400.
137. Temmesfeld-Wollbrück B, Szalay A, Mayer K, Olschewski H, Seeger W, Grimminger F. Abnormalities of gastric mucosal oxygenation in septic shock. Am J Respir Crit Care Med 1998; 157:1586-92.
138. Lobo SM, De Backer D, Sun Q, et al. Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia. J Appl Physiol 2003; 95:2047-54.
139. Pannen BHJ, Bauer M, Zhang JX, Robotham JL, Clemens MG. A time-dependent balance between endothelins and nitric oxide regulating protal resistance after endotoxin. Am J Physiol 1996; 271:H1953-H1961.
140. Baveja R, Yokoyama Y, Korneszczuk K, Zhang JX, Clemens MG. Endothelin 1 impairs oxygen delivery in livers from LPS-primed animals. Shock JID-9421564 2002; 17:383-8.
141. Nishida J, McCuskey RS, McDonnell D, Fox ES. Protective role of NO in hepatic microcirculatory dysfunction during endotoxemia. Am J Physiol 1994; 267:G1135-G1141.
142. Corso CO, Gundersen Y, Dörger M, Lilleaasen P, Aasen AO, Messmer K. Effects of nitric oxide synthase inhibitors NG-nitro-Larginine methyl eshter and aminoethyl-isothiourea on the liver microcirculation in rat endotoxemia. J Hepatol 1998; 28:61-9.
143. Gundersen Y, Corso CO, Leiderer R, et al. The nitric oxide donor sodium nitroprusside protects against hepatic microcirculatory dysfunction in early endotoxaemia. Intensive Care Med 1998; 24:1257-63.
144. Croner RS, Hoerer E, Kulu Y, et al. Hepatic platelet and leukocyte adherence during endotoxemia. Crit Care 2006; 10:R15.
145. Secor D, Li F, Ellis CG, et al. Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries. Intensive Care Med 2010; 36:1928-34.
146. Verdant CL, De Backer D, Bruhn A, et al. Evaluation of sublingual and gut mucosal microcirculation in sepsis: a quantitative analysis. Crit Care Med 2009; 37:2875-81.
147. Farquhar I, Martin CM, Lam C, Potter R, Ellis CG, Sibbald WJ. Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis. J Surg Res 1996; 61:190-6.
148. Taccone FS, Su F, Pierrakos C, et al. Cerebral microcirculation is impaired during sepsis: an experimental study. Crit Care 2010; 14:R140.
149. De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002; 166:98-104.
150. Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistant microvasculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 2004; 32:1825-31.
151. Top AP, Ince C, de Meij N, van Dijk M, Tibboel D. Persistent low microcirculatory vessel density in nonsurvivors of sepsis in pediatric intensive care. Crit Care Med 2011; 39:8-13.
152. Kao R, Xenocostas A, Rui T, Yu P, Huang W, Rose J, et al. Erythropoietin improves skeletal muscle microcirculation and tissue bioenergetics in a mouse sepsis model. Crit Care 2007; 11:R58.
153. Creteur J, De Backer D, Sakr Y, Koch M, Vincent JL. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med 2006; 32:516-23.
154. Trzeciak S, McCoy JV, Phillip DR, et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med 2008; 34:2210-7.
155. De Backer D, Creteur J, Dubois MJ, et al. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 2006; 34:403-8.
156. Doerschug KC, Delsing AS, Schmidt GA, Haynes WG. Impairments in microvascular reactivity are related to organ failure in human sepsis. Am J Physiol Heart Circ Physiol 2007; 293: H1065-H1071.
157. Creteur J, Carollo T, Soldati G, Buchele G, De Backer D, Vincent JL. The prognostic value of muscle StO(2) in septic patients. Intensive Care Med 2007; 33:1549-56.
158. Tyml K, Wang X, Lidington D, Ouellette Y. Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo. Am J Physiol Heart Circ Physiol 2001; 281: H1397-H1406.
159. Marechal X, Favory R, Joulin O, et al. Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock 2008; 29:572-6.
160. Cabrales P, Vazquez BY, Tsai AG, Intaglietta M. Microvascular and capillary perfusion following glycocalyx degradation. J Appl Physiol 2007; 102:2251-9.
161. De Backer D, Donadello K, Favory R. Link between coagulations abnormalities and microcirculatory dysfunction in critically ill patients. Curr Opin Anaesthesiol 2010; 22:150-4.
162. Piagnerelli M, Boudjeltia KZ, Vanhaeverbeek M, Vincent JL. Red blood cell rheology in sepsis. Intensive Care Med 2003; 29:1052-61.
163. Eichelbronner O, Sielenkamper A, Cepinskas G, Sibbald WJ, Chin-Yee IH. Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow. Crit Care Med 2000; 28:1865-70.
164. Poeze M, Solberg BC, Greve JW, Ramsay G. Monitoring global volume-related hemodynamic or regional variables after initial resuscitation: What is a better predictor of outcome in critically ill septic patients? Crit Care Med 2005; 33:2494-500.
165. Regueira T, Banziger B, Djafarzadeh S, et al. Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration. Crit Care 2008; 12:R88.
166. Nakajima Y, Baudry N, Duranteau J, Vicaut E. Effects of vasopressin, norepinephrine and L-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 2006; 1752-7.
167. Sennoun N, Montemont C, Gibot S, Lacolley P, Levy B. Comparative effects of early versus delayed use of norepinephrine in resuscitated endotoxic shock. Crit Care Med 2007; 35:1736-40.
168. Sun Q, Tu Z, Lobo S, et al. Optimal Adrenergic Support in Septic Shock Due to Peritonitis. Anesthesiology 2003; 98:888-96.
169. Albanese J, Leone M, Garnier F, Bourgoin A, Antonini F, Martin C. Renal effects of norepinephrine in septic and nonseptic patients. Chest 2004; 126:534-9.
170. Varpula M, Tallgren M, Saukkonen K, Voipio-Pulkki LM, Pettila V. Hemodynamic variables related to outcome in septic shock. Intensive Care Med 2005; 31:1066-71.
171. Dunser MW, Ruokonen E, Pettila V, et al. Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care 2009; 13:R181.
172. LeDoux D, Astiz ME, Carpati CM, Rackow EC. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000; 28:2729-32.
173. Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C. Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 2005; 33:780-6.
174. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008; 34:17-60.
175. Thooft A, Favory R, Salgado DR, et al. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care 2011; 15:R222.
176. Cholley BP, Lang RM, Berger DS, Korcarz C, Payen D, Shroff SG. Alterations in systemic arterial mechanical properties during septic shock: role of fluid resuscitation. Am J Physiol 1995; 269:H375-H384.
177. De Backer D, Zhang H, Cherkhaoui S, Borgers M, Vincent JL. Effects of dobutamine on hepato-splanchnic hemodynamics in an experimental model of hyperdynamic endotoxic shock. Shock 2001; 15:208-14.
178. Shoemaker WC, Appel PL, Kram HB, Bishop MH, Abraham E. Sequence of physiologic patterns in surgical septic shock. Crit Care Med 1993; 21:1876-89.
179. Shoemaker WC, Appel PL, Kram HB, Bishop MH, Abraham E. Temporal hemodynamic and oxygen transport patterns in medical patients: septic shock. Chest 1993; 104:1529-36.
180. Tuchschmidt J, Fried J, Astiz M, Rackow E. Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest 1992; 102:216-20.
181. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med 1995; 333:1025-32.
182. Rivers E, Nguyen B, Havstadt S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-77.
183. Hollenberg SM, Dumasius A, Easington C, Colilla SA, Neumann A, Parrillo JE. Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography. Am J Respir Crit Care Med 2001; 164:891-5.
184. van der Heijden M, Verheij J, Nieuw Amerongen GP, Groeneveld AB. Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and nonseptic critically ill patients with hypovolemia*. Crit Care Med 2009; 37:1275-82.
185. Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh J, Norton R. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 2011; 37:86-96.
186. Delaney AP, Dan A, McCaffrey J, Finfer S. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis. Crit Care Med 2011; 39:386-91.
187. Schortgen F, Lacherade JC, Bruneel F, et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357:911-6.
188. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125-39.
189. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34:344-53.
190. Boyd JH, Forbes J, Nakada TA, 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; 39:259-65.
191. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354:2564-75.
192. Axler O, Tousignant C, Thompson CR, et al. Small hemodynamic effect of typical rapid volume infusions in critically ill patients. Crit Care Med 1997; 25:965-70.
193. Ospina-Tascon G, Neves AP, Occhipinti G, et al. Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med 2010; 36:949-55.
194. Osman D, Ridel C, Ray P, et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007; 35:64-8.
195. Feissel M, Michard F, Mangin I, Ruyer O, Faller JP, Teboul JL. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest 2001; 119:867-73.
196. Michard F, Boussat S, Chemla D, et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med 2000; 162:134-8.
197. Heenen S, De Backer D, Vincent JL. How can the response to volume expansion in patients with spontaneous respiratory movements be predicted? Crit Care 2006; 10:R102.
198. De Backer D, Heenen S, Piagnerelli M, Koch M, Vincent JL. Pulse pressure variations to predict fluid responsiveness: influence of tidal volume. Intensive Care Med 2005; 31:517-23.
199. Monnet X, Osman D, Ridel C, Lamia B, Richard C, Teboul JL. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients. Crit Care Med 2009; 37:951-6.
200. Monnet X, Rienzo M, Osman D, et al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med 2006; 34:1402-7.
201. Vincent JL, Weil MH. Fluid challenge revisisted. Crit Care Med 2006; 34:1337.
202. Levy B, Dusang B, Annane D, Gibot S, Bollaert PE. Cardiovascular response to dopamine and early prediction of outcome. A prospective multicenter study. Crit Care Med 2005; 33:2172-7.
203. Asfar P, De Backer D, Meier-Hellmann A, Radermacher P, Sakka SG. Clinical review: influence of vasoactive and other therapies on intestinal and hepatic circulations in patients with septic shock. Crit Care 2004; 8:170-9.
204. Zhang H, De Jongh R, De Backer D, Cherkaoui S, Vray B, Vincent JL. Effects of alpha-and beta-adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock. Crit Care Med 2001; 29:581-8.
205. De Backer D, Zhang H, Manikis P, Vincent JL. Regional effects of dobutamine in endotoxic shock. J Surg Res 1996; 65:93-100.
206. van den Berghe G, de Zegher F. Anterior pituitary function during critical illness and dopamine treatment. Crit Care Med 1996; 24:1580-90.
207. De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: Which is best? Crit Care Med 2003; 31:1659-67.
208. Levy B, Bollaert PE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Intensive Care Med 1997; 23:282-7.
209. Annane D, Vignon P, Renault A, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 2007; 370:676-84.
210. Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008; 34:2226-34.
211. Levy B, Perez P, Perny J, Thivilier C, Gerard A. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med 2011; 39:450-5.
212. Loeb HS, Winslow EB, Rahimtoola SH, Rosen KM, Gunnar RM. Acute hemodynamic effects of dopamine in patients with shock. Circulation 1971; 44:163-73.
213. Schreuder WO, Schneider AJ, Groeneveld ABJ, Thijs LG. Effect of dopamine vs norepinephrine on hemodynamics in septic shock. Chest 1989; 95:1282-8.
214. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362:779-89.
215. Meier-Hellmann A, Bredle DL, Specht M, Spies C, Hannemann L, Reinhart K. The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock. Intensive Care Med 1997; 23:31-7.
216. Patel GP, Grahe JS, Sperry M, et al. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock 2010; 33:375-80.
217. Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med 2000; 28:2758-65.
218. Boulain T, Runge I, Bercault N, Benzekri-Lefevre D, Wolf M, Fleury C. Dopamine therapy in septic shock: Detrimental effect on survival? J Crit Care 2009; 24:575-82.
219. Sakr Y, Reinhart K, Vincent JL, et al. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study. Crit Care Med 2006; 34:589-97.
220. Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE. Norepinephrine or dopamine for septic shock: a systematic review of randomized clinical trials. J Intensive Care Med 2012; 27:172-178.
221. De Backer D, Aldecoa C, Njimi H, Vincent J-L. Dopamine versus norepinephrine in the treatment of septic shock:: a metaanalysis. Crit Care Med 2012; 40:725-730.
222. Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 2002; 96:576-82.
223. Klinzing S, Simon M, Reinhart K, Bredle DL, Meier-Hellmann A. High-dose vasopressin is not superior to norepinephrine in septic shock. Crit Care Med 2003; 31:2646-50.
224. Dunser MW, Mayr AJ, Ulmer H, et al. The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: a retrospective analysis. Anesth Analg 2001; 93:7-13.
225. Lopez A, Lorente JA, Steingrub J, et al. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 2004; 32:21-30.
226. Saetre T, Hoiby EA, Aspelin T, Lermark G, Egeland T, Lyberg T. Aminoethyl-isothiourea, a nitric oxide synthase inhibitor and oxygen radical scavenger, improves survival and counteracts hemodynamic deterioration in a porcine model of streptococcal shock. Crit Care Med 2000; 28:2697-706.
227. Johannes T, Mik EG, Klingel K, et al. Effects of 1400W and/or nitroglycerin on renal oxygenation and kidney function during endotoxaemia in anaesthetised rats. Clin Exp Pharmacol Physiol 2009; 36(9):870-9.
228. Mitaka C, Hirata Y, Yokoyama K, Imai T. L-canavanine, a selective inhibitor of inducible NO synthase, increases plasma endothelin-1 concentrations in dogs with endotoxic shock. J Crit Care 2001; 16:17-23.
229. Bellissant E, Annane D. Effect of hydrocortisone on phenylephrine--mean arterial pressure dose-response relationship in septic shock. Clin Pharmacol Ther 2000; 68:293-303.
230. Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 1998; 26:645-50.
231. 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; 288:862-71.
232. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358:111-24.
233. Annane D, Cariou A, Maxime V, et al. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 2010; 303:341-8.
234. Vincent JL, Roman A, De Backer D, Kahn RJ. Oxygen Uptake/ Supply dependency: Effects of short-term dobutamine infusion. Am Rev Respir Dis 1990; 142:2-8.
235. Hayes MA, Timmins AC, Yau EHS, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994; 330:1717-22.
236. Jansen TC, van Bommel J, Schoonderbeek J, et al. Early Lactate-Guided Therapy in ICU Patients: A Multicenter, Open-Label, Randomized, Controlled Trial. Am J Respir Crit Care Med 2010; 182:752-61.
237. Ait-Oufella H, Lemoinne S, Boelle PY, et al. Mottling score predicts survival in septic shock. Intensive Care Med 2011; 37:801-7.
238. Vallee F, Vallet B, Mathe O, et al. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med 2008; 34:2218-25.
239. Vallee F, Mateo J, Dubreuil G, et al. Cutaneous ear lobe PCO2 at 37{degrees}C to evaluate micro perfusion in septic patients. Chest 2010; 138:1062-70.
240. Pottecher J, Deruddre S, Teboul JL, et al. Both passive leg raising and intravascular volume expansion improve sublingual microcirculatory perfusion in severe sepsis and septic shock patients. Intensive Care Med 2010; 36:1867-74.
241. Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Schildberg FW, Menger MD. Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia. Anesthesiology 2002; 97:460-70.
242. Sakr Y, Chierego M, Piagnerelli M, et al. Microvascular response to red blood cell transfusion in patients with severe sepsis. Crit Care Med 2007; 35:1639-44.
243. Secchi A, Wellmann R, Martin E, Schmidt H. Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat. J Crit Care 1997; 12:137-41.
244. Georger JF, Hamzaoui O, Chaari A, Maizel J, Richard C, Teboul JL. Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients. Intensive Care Med 2010; 36:1882-9.
245. Deruddre S, Cheisson G, Mazoit JX, Vicaut E, Benhamou D, Duranteau J. Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Med 2007; 33:1557-62.
246. Dubin A, Pozo MO, Casabella CA, et al. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 2009; 13:R92.
247. Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 2002; 360:1395-6.
248. Boerma EC, Koopmans M, Konijn A, et al. Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: A doubleblind randomized placebo controlled trial. Crit Care Med 2010; 38:93-100.
249. den Uil CA, Caliskan K, Lagrand WK, et al. Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure. Intensive Care Med 2009; 35:1893-9.
250. Salgado DR, He X, Su F, et al. Sublingual Microcirculatory Effects of Enalaprilat in an Ovine Model of Septic Shock. Shock 2011.
251. Gierer P, Hoffmann JN, Mahr F, et al. Activated protein C reduces tissue hypoxia, inflammation, and apoptosis in traumatized skeletal muscle during endotoxemia. Crit Care Med 2007; 35:1966-71.
252. Gupta A, Berg DT, Gerlitz B, et al. Role of protein C in renal dysfunction after polymicrobial sepsis. J Am Soc Nephrol 2007; 18:860-7.
253. De Backer D, Verdant C, Chierego M, Koch M, Gullo A, Vincent JL. Effects of Drotecogin Alfa Activated on microcirculatory alterations in patients with severe sepsis. Crit Care Med 2006; 34:1918-24.
254. Hoffmann JN, Vollmar B, Romisch J, Inthorn D, Schildberg FW, Menger MD. Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium. Crit Care Med 2002; 30:218-25.
255. Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD. The thrombin antagonist hirudin fails to inhibit endotoxin-induced leukocyte/endothelial cell interaction and microvascular perfusion failure. Shock 2000; 14:528-34.
256. Donati A, Romanelli M, Botticelli L, et al. Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy. Crit Care 2009; 13 (Suppl 5):S12.
257. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:699-709.
258. Ranieri-VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock NEJM 2012; 366: 2055-2064.
259. Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286:1869-78.