Intensive Care Medicine

, Volume 36, Issue 12, pp 2019–2029 | Cite as

Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside

  • B. Levy
  • S. Collin
  • N. Sennoun
  • N. Ducrocq
  • A. Kimmoun
  • P. Asfar
  • P. Perez
  • F. Meziani



To delineate some of the characteristics of septic vascular hypotension, to assess the most commonly cited and reported underlying mechanisms of vascular hyporesponsiveness to vasoconstrictors in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.


Source data were obtained from a PubMed search of the medical literature with the following MeSH terms: Muscle, smooth, vascular/physiopathology; hypotension/etiology; shock/physiopathology; vasodilation/physiology; shock/therapy; vasoconstrictor agents.


Nitric oxide (NO) and peroxynitrite are crucial components implicated in vasoplegia and vascular hyporeactivity. Vascular ATP-sensitive and calcium-activated potassium channels are activated during shock and participate in hypotension. In addition, shock state is characterized by inappropriately low plasma glucocorticoid and vasopressin concentrations, a dysfunction and desensitization of alpha-receptors, and an inactivation of catecholamines by oxidation. Numerous other mechanisms have been individualized in animal models, the great majority of which involve NO: MEK1/2–ERK1/2 pathway, H2S, hyperglycemia, and cytoskeleton dysregulation associated with decreased actin expression.


Many therapeutic approaches have proven their efficiency in animal models, especially therapies directed against one particular compound, but have otherwise failed when used in human shock. Nevertheless, high doses of catecholamines, vasopressin and terlipressin, hydrocortisone, activated protein C, and non-specific shock treatment have demonstrated a partial efficiency in reversing sepsis-induced hypotension.


Septic shock Vasopressor Nitric oxide Potassium channels Catecholamine 


  1. 1.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310CrossRefPubMedGoogle Scholar
  2. 2.
    Merx MW, Weber C (2007) Sepsis and the heart. Circulation 116:793–802CrossRefPubMedGoogle Scholar
  3. 3.
    Matsuda N, Hattori Y (2007) Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction. J Smooth Muscle Res 43:117–137CrossRefPubMedGoogle Scholar
  4. 4.
    Umans JG, Wylam ME, Samsel RW, Edwards J, Schumacker PT (1993) Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit and rat aorta. Am Rev Respir Dis 148:1638–1645PubMedGoogle Scholar
  5. 5.
    Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78CrossRefPubMedGoogle Scholar
  6. 6.
    Bernardin G, Pradier C, Tiger F, Deloffre P, Mattei M (1996) Blood pressure and arterial lactate level are early indicators of short-term survival in human septic shock. Intensive Care Med 22:17–25CrossRefPubMedGoogle Scholar
  7. 7.
    Abid O, Akca S, Haji-Michael P, Vincent JL (2000) Strong vasopressor support may be futile in the intensive care unit patient with multiple organ failure. Crit Care Med 28:947–949CrossRefPubMedGoogle Scholar
  8. 8.
    Lamia B, Chemla D, Richard C, Teboul JL (2005) Clinical review: interpretation of arterial pressure wave in shock states. Crit Care 9:601–606CrossRefPubMedGoogle Scholar
  9. 9.
    Benchekroune S, Karpati PC, Berton C, Nathan C, Mateo J, Chaara M, Riche F, Laisne MJ, Payen D, Mebazaa A (2008) Diastolic arterial blood pressure: a reliable early predictor of survival in human septic shock. J Trauma 64:1188–1195CrossRefPubMedGoogle Scholar
  10. 10.
    Benedict CR, Rose JA (1992) Arterial norepinephrine changes in patients with septic shock. Circ Shock 38:165–172PubMedGoogle Scholar
  11. 11.
    Landry DW, Oliver JA (2001) The pathogenesis of vasodilatory shock. N Engl J Med 345:588–595CrossRefPubMedGoogle Scholar
  12. 12.
    Alvarez S, Boveris A (2004) Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia. Free Radic Biol Med 37:1472–1478CrossRefPubMedGoogle Scholar
  13. 13.
    Lundberg JO, Weitzberg E (2005) NO generation from nitrite and its role in vascular control. Arterioscler Thromb Vasc Biol 25:915–922CrossRefPubMedGoogle Scholar
  14. 14.
    Rees DD, Monkhouse JE, Cambridge D, Moncada S (1998) Nitric oxide and the haemodynamic profile of endotoxin shock in the conscious mouse. Br J Pharmacol 124:540–546CrossRefPubMedGoogle Scholar
  15. 15.
    Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC (1990) Loss of vascular responsiveness induced by endotoxin involves l-arginine pathway. Am J Physiol 259:H1038–H1043PubMedGoogle Scholar
  16. 16.
    Boyle WA 3rd, Parvathaneni LS, Bourlier V, Sauter C, Laubach VE, Cobb JP (2000) iNOS gene expression modulates microvascular responsiveness in endotoxin-challenged mice. Circ Res 87:E18–E24PubMedGoogle Scholar
  17. 17.
    Walker TA, Curtis SE, King-VanVlack CE, Chapler CK, Vallet B, Cain SM (1995) Effects of nitric oxide synthase inhibition on regional hemodynamics and oxygen transport in endotoxic dogs. Shock 4:415–420PubMedGoogle Scholar
  18. 18.
    Vincent JL, Zhang H, Szabo C, Preiser JC (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161:1781–1785PubMedGoogle Scholar
  19. 19.
    Lopez A, Lorente JA, Steingrub J, Bakker J, McLuckie A, Willatts S, Brockway M, Anzueto A, Holzapfel L, Breen D, Silverman MS, Takala J, Donaldson J, Arneson C, Grove G, Grossman S, Grover R (2004) 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 32:21–30CrossRefPubMedGoogle Scholar
  20. 20.
    Levy B, Valtier M, de Chillou C, Bollaert PE, Cane D, Mallie JP (1999) Beneficial effects of l-canavanine, a selective inhibitor of inducible nitric oxide synthase, on lactate metabolism and muscle high energy phosphates during endotoxic shock in rats. Shock 11:98–103CrossRefPubMedGoogle Scholar
  21. 21.
    Cauwels A (2007) Nitric oxide in shock. Kidney Int 72:557–565CrossRefPubMedGoogle Scholar
  22. 22.
    Cauwels A, Buys ES, Thoonen R, Geary L, Delanghe J, Shiva S, Brouckaert P (2009) Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase-dependent manner. J Exp Med 206:2915–2924CrossRefPubMedGoogle Scholar
  23. 23.
    Wang P, Zhou M, Cioffi WG, Bland KI, Ba ZF, Chaudry IH (2000) Is prostacyclin responsible for producing the hyperdynamic response during early sepsis? Crit Care Med 28:1534–1539CrossRefPubMedGoogle Scholar
  24. 24.
    Schildknecht S, Bachschmid M, Baumann A, Ullrich V (2004) COX-2 inhibitors selectively block prostacyclin synthesis in endotoxin-exposed vascular smooth muscle cells. FASEB J 18:757–759PubMedGoogle Scholar
  25. 25.
    Höcherl K, Schmidt C, Kurt B, Bucher M (2008) Activation of the PGI(2)/IP system contributes to the development of circulatory failure in a rat model of endotoxic shock. Hypertension 52:330–335CrossRefPubMedGoogle Scholar
  26. 26.
    Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 336:912–918CrossRefPubMedGoogle Scholar
  27. 27.
    Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424CrossRefPubMedGoogle Scholar
  28. 28.
    Szabo C, Salzman AL, Ischiropoulos H (1995) Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo. FEBS Lett 363:235–238CrossRefPubMedGoogle Scholar
  29. 29.
    Macarthur H, Westfall TC, Riley DP, Misko TP, Salvemini D (2000) Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock. Proc Natl Acad Sci U S A 97:9753–9758CrossRefPubMedGoogle Scholar
  30. 30.
    Salvemini D, Wang ZQ, Zweier JL, Samouilov A, Macarthur H, Misko TP, Currie MG, Cuzzocrea S, Sikorski JA, Riley DP (1999) A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science 286:304–306CrossRefPubMedGoogle Scholar
  31. 31.
    Landry DW, Oliver JA (1992) The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. J Clin Invest 89:2071–2074CrossRefPubMedGoogle Scholar
  32. 32.
    Buckley JF, Singer M, Clapp LH (2006) Role of KATP channels in sepsis. Cardiovasc Res 72:220–230CrossRefPubMedGoogle Scholar
  33. 33.
    Warrillow S, Egi M, Bellomo R (2006) Randomized, double-blind, placebo-controlled crossover pilot study of a potassium channel blocker in patients with septic shock. Crit Care Med 34:980–985CrossRefPubMedGoogle Scholar
  34. 34.
    Morelli A, Lange M, Ertmer C, Broeking K, Van Aken H, Orecchioni A, Rocco M, Bachetoni A, Traber DL, Landoni G, Pietropaoli P, Westphal M (2007) Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport. Shock 28:530–535PubMedGoogle Scholar
  35. 35.
    Cauwels A, Brouckaert P (2008) Critical role for small and large conductance calcium-dependent potassium channels in endotoxemia and TNF toxicity. Shock 29:577–582PubMedGoogle Scholar
  36. 36.
    Pickkers P, Dorresteijn MJ, Bouw MP, van der Hoeven JG, Smits P (2006) In vivo evidence for nitric oxide-mediated calcium-activated potassium-channel activation during human endotoxemia. Circulation 114:414–421CrossRefPubMedGoogle Scholar
  37. 37.
    Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M (2008) Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 36:1937–1949CrossRefPubMedGoogle Scholar
  38. 38.
    Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P (2006) Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med 174:1319–1326CrossRefPubMedGoogle Scholar
  39. 39.
    Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124CrossRefPubMedGoogle Scholar
  40. 40.
    Briegel J, Sprung CL, Annane D, Singer M, Keh D, Moreno R, Mohnle P, Weiss Y, Avidan A, Brunkhorst FM, Fiedler F, Vogeser M (2009) Multicenter comparison of cortisol as measured by different methods in samples of patients with septic shock. Intensive Care Med 35:2151–2156CrossRefPubMedGoogle Scholar
  41. 41.
    Wu LL, Tang C, Liu MS (1997) Hyper- and hypocardiodynamic states are associated with externalization and internalization, respectively, of alpha-adrenergic receptors in rat heart during sepsis. Shock 7:318–323CrossRefPubMedGoogle Scholar
  42. 42.
    McMillan M, Chernow B, Roth BL (1986) Hepatic alpha 1-adrenergic receptor alteration in a rat model of chronic sepsis. Circ Shock 19:185–193PubMedGoogle Scholar
  43. 43.
    Hwang TL, Lau YT, Huang SF, Chen MF, Liu MS (1994) Changes of alpha 1-adrenergic receptors in human liver during intraabdominal sepsis. Hepatology 20:638–642CrossRefPubMedGoogle Scholar
  44. 44.
    de Montmollin E, Aboab J, Mansart A, Annane D (2009) Bench-to-bedside review: β-adrenergic modulation in sepsis. Crit Care 13:230CrossRefPubMedGoogle Scholar
  45. 45.
    Pacheco ME, Beltran A, Redondo J, Manso AM, Alonso MJ, Salaices M (2006) High glucose enhances inducible nitric oxide synthase expression. Role of protein kinase C-betaII. Eur J Pharmacol 538:115–123CrossRefPubMedGoogle Scholar
  46. 46.
    Ellger B, Richir MC, van Leeuwen PA, Debaveye Y, Langouche L, Vanhorebeek I, Teerlink T, Van den Berghe G (2008) Glycemic control modulates arginine and asymmetrical-dimethylarginine levels during critical illness by preserving dimethylarginine-dimethylaminohydrolase activity. Endocrinology 149:3148–3157CrossRefPubMedGoogle Scholar
  47. 47.
    Holger JS, Dries DJ, Barringer KW, Peake BJ, Flottemesch TJ, Marini JJ (2010) Cardiovascular and metabolic effects of high-dose insulin in a porcine septic shock model. Acad Emerg Med 17:429–435CrossRefPubMedGoogle Scholar
  48. 48.
    Annane D, Cariou A, Maxime V, Azoulay E, D’Honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santre C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec’h C, Mayaux J, Lejeune J, Chevret S (2010) Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 303:341–348CrossRefPubMedGoogle Scholar
  49. 49.
    Mitchell JA, Kohlhaas KL, Sorrentino R, Warner TD, Murad F, Vane JR (1993) Induction by endotoxin of nitric oxide synthase in the rat mesentery: lack of effect on action of vasoconstrictors. Br J Pharmacol 109:265–270PubMedGoogle Scholar
  50. 50.
    Stoclet JC, Martinez MC, Ohlmann P, Chasserot S, Schott C, Kleschyov AL, Schneider F, Andriantsitohaina R (1999) Induction of nitric oxide synthase and dual effects of nitric oxide and cyclooxygenase products in regulation of arterial contraction in human septic shock. Circulation 100:107–112PubMedGoogle Scholar
  51. 51.
    Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF (2002) Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 360:1395–1396CrossRefPubMedGoogle Scholar
  52. 52.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60CrossRefPubMedGoogle Scholar
  53. 53.
    De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL (2010) Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362:779–789CrossRefPubMedGoogle Scholar
  54. 54.
    LeDoux D, Astiz ME, Carpati CM, Rackow EC (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28:2729–2732CrossRefPubMedGoogle Scholar
  55. 55.
    Breslow MJ, Ligier B (1991) Hyperadrenergic states. Crit Care Med 19:1566–1579CrossRefPubMedGoogle Scholar
  56. 56.
    Insel PA (1996) Seminars in medicine of the Beth Israel Hospital, Boston. Adrenergic receptors—evolving concepts and clinical implications. N Engl J Med 334:580–585CrossRefPubMedGoogle Scholar
  57. 57.
    Katsaragakis S, Kapralou A, Theodorou D, Markogiannakis H, Larentzakis A, Stamou KM, Drimousis P, Bramis I (2006) Refractory septic shock: efficacy and safety of very high doses of norepinephrine. Methods Find Exp Clin Pharmacol 28:307–313CrossRefPubMedGoogle Scholar
  58. 58.
    Lange M, Ertmer C, Westphal M (2008) Vasopressin vs. terlipressin in the treatment of cardiovascular failure in sepsis. Intensive Care Med 34:821–832CrossRefPubMedGoogle Scholar
  59. 59.
    Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjornsson B, Nedashkovsky EV, Bjertnaes LJ (2001) Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med 29:1860–1867CrossRefPubMedGoogle Scholar
  60. 60.
    Honore PM, Matson JR (2002) Short-term high-volume hemofiltration in sepsis: perhaps the right way is to start with. Crit Care Med 30:1673–1674CrossRefPubMedGoogle Scholar
  61. 61.
    Ataman K, Jehmlich M, Kock S, Neumann S, Leischik M, Filipovic Z, Hopf HB (2002) Short-term cardiovascular effects of plasmapheresis in norepinephrine-refractory septic shock. Intensive Care Med 28:1164–1167CrossRefPubMedGoogle Scholar
  62. 62.
    Landry DW, Levin HR, Gallant EM, Ashton RC Jr, Seo S, D’Alessandro D, Oz MC, Oliver JA (1997) Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 95:1122–1125PubMedGoogle Scholar
  63. 63.
    Sharshar T, Carlier R, Blanchard A, Feydy A, Gray F, Paillard M, Raphael JC, Gajdos P, Annane D (2002) Depletion of neurohypophyseal content of vasopressin in septic shock. Crit Care Med 30:497–500CrossRefPubMedGoogle Scholar
  64. 64.
    Leone M, Boyle WA (2006) Decreased vasopressin responsiveness in vasodilatory septic shock-like conditions. Crit Care Med 34:1126–1130CrossRefPubMedGoogle Scholar
  65. 65.
    Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358:877–887CrossRefPubMedGoogle Scholar
  66. 66.
    Westphal M, Traber DL (2005) Low-dose terlipressin for hemodynamic support in sepsis and systemic inflammatory response syndrome: art for (he)art’s sake or state of the art? Crit Care Med 33:455–457CrossRefPubMedGoogle Scholar
  67. 67.
    Broking K, Lange M, Morelli A, Ertmer C, Aken HV, Luecke M, Rehberg S, Bowering N, Bone HG, Traber DL, Westphal M (2008) Employing dobutamine as a useful agent to reverse the terlipressin-linked impairments in cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. Shock 29:71–77PubMedGoogle Scholar
  68. 68.
    Lange M, Morelli A, Ertmer C, Broking K, Rehberg S, Van Aken H, Traber DL, Westphal M (2007) Role of adenosine triphosphate-sensitive potassium channel inhibition in shock states: physiology and clinical implications. Shock 28:394–400CrossRefPubMedGoogle Scholar
  69. 69.
    Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709CrossRefPubMedGoogle Scholar
  70. 70.
    Mosnier LO, Zlokovic BV, Griffin JH (2007) The cytoprotective protein C pathway. Blood 109:3161–3172CrossRefPubMedGoogle Scholar
  71. 71.
    Esmon CT (2006) The endothelial protein C receptor. Curr Opin Hematol 13:382–385CrossRefPubMedGoogle Scholar
  72. 72.
    Joyce DE, Gelbert L, Ciaccia A, DeHoff B, Grinnell BW (2001) Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 276:11199–11203CrossRefPubMedGoogle Scholar
  73. 73.
    Bilbault P, Lavaux T, Launoy A, Gaub MP, Meyer N, Oudet P, Pottecher T, Jaeger A, Schneider F (2007) Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mononuclear cells: a cohort study in septic shock patients. Crit Care Med 35:69–75Google Scholar
  74. 74.
    Nacira S, Meziani F, Dessebe O, Cattan V, Collin S, Montemont C, Gibot S, Asfar P, Ramaroson A, Regnault V, Slama M, Lecompte T, Lacolley P, Levy B (2009) Activated protein C improves lipopolysaccharide-induced cardiovascular dysfunction by decreasing tissular inflammation and oxidative stress. Crit Care Med 37:246–255CrossRefPubMedGoogle Scholar
  75. 75.
    Favory R, Lancel S, Marechal X, Tissier S, Neviere R (2006) Cardiovascular protective role for activated protein C during endotoxemia in rats. Intensive Care Med 32:899–905CrossRefPubMedGoogle Scholar
  76. 76.
    Monnet X, Lamia B, Anguel N, Richard C, Bonmarchand G, Teboul JL (2005) Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients. Intensive Care Med 31:1573–1576CrossRefPubMedGoogle Scholar
  77. 77.
    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871CrossRefPubMedGoogle Scholar
  78. 78.
    Prigent H, Maxime V, Annane D (2004) Clinical review: corticotherapy in sepsis. Crit Care 8:122–129CrossRefPubMedGoogle Scholar
  79. 79.
    Kilger E, Weis F, Briegel J, Frey L, Goetz AE, Reuter D, Nagy A, Schuetz A, Lamm P, Knoll A, Peter K (2003) Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Crit Care Med 31:1068–1074CrossRefPubMedGoogle Scholar
  80. 80.
    Gibot S, Massin F, Alauzet C, Montemont C, Lozniewski A, Bollaert PE, Levy B (2008) Effects of the TREM-1 pathway modulation during mesenteric ischemia-reperfusion in rats. Crit Care Med 36:504–510CrossRefPubMedGoogle Scholar
  81. 81.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377CrossRefPubMedGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • B. Levy
    • 1
    • 2
  • S. Collin
    • 1
  • N. Sennoun
    • 1
  • N. Ducrocq
    • 1
    • 2
  • A. Kimmoun
    • 1
    • 2
  • P. Asfar
    • 3
  • P. Perez
    • 1
  • F. Meziani
    • 4
  1. 1.Groupe Choc, Contrat Avenir INSERM 2006, Faculté de MédecineNancy UniversitéVandœuvre-lès-Nancy CedexFrance
  2. 2.Service de Réanimation Médicale, Institut du Coeur et des VaisseauxHôpitaux de Brabois, CHU de NancyVandœuvre-lès-NancyFrance
  3. 3.Laboratoire HIFIH UPRES EA 3859Université d’AngersAngersFrance
  4. 4.Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS, Faculté de PharmacieUniversité de StrasbourgIllkirch, StrasbourgFrance

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