Intensive Care Medicine

, Volume 44, Issue 6, pp 833–846 | Cite as

A global perspective on vasoactive agents in shock

  • Djillali AnnaneEmail author
  • Lamia Ouanes-Besbes
  • Daniel de Backer
  • Bin DU
  • Anthony C. Gordon
  • Glenn Hernández
  • Keith M. Olsen
  • Tiffany M. Osborn
  • Sandra Peake
  • James A. Russell
  • Sergio Zanotti Cavazzoni



We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians’ practices.


This is a narrative review by a multidisciplinary, multinational—from six continents—panel of experts including physicians, a pharmacist, trialists, and scientists.

Results and conclusions

Vasoactive drugs are an essential part of shock management. Catecholamines are the most commonly used vasoactive agents in the intensive care unit, and among them norepinephrine is the first-line therapy in most clinical conditions. Inotropes are indicated when myocardial function is depressed and dobutamine remains the first-line therapy. Vasoactive drugs have a narrow therapeutic spectrum and expose the patients to potentially lethal complications. Thus, these agents require precise therapeutic targets, close monitoring with titration to the minimal efficacious dose and should be weaned as promptly as possible. Moreover, the use of vasoactive drugs in shock requires an individualized approach. Vasopressin and possibly angiotensin II may be useful owing to their norepinephrine-sparing effects.


Shock Cardiovascular system Adrenergic agonists Clinical trials Practice guidelines 



ACG is funded by an NIHR Research Professorship award (RP-2015-06-018).

Compliance with ethical standards

Conflicts of interest

DA reports having received a grant from the French Ministry of Health to conduct a trial comparing epinephrine to norepinephrine plus dobutamine for septic shock (CATS). DDB reports that he acts as a consultant to and material for studies by Edwards Lifesciences. ACG reports that outside of this work he has received speaker fees from Orion Corporation Orion Pharma and Amomed Pharma. He has consulted for Ferring Pharmaceuticals, Tenax Therapeutics, Baxter Healthcare, Bristol-Myers Squibb and GSK, and received grant support from Orion Corporation Orion Pharma, Tenax Therapeutics and HCA International with funds paid to his institution. GH reports no financial conflict of interest. JR reports patents owned by the University of British Columbia (UBC) that are related to PCSK9 inhibitor(s) and sepsis and related to the use of vasopressin in septic shock. JR is an inventor on these patents. JR is a founder, Director and shareholder in Cyon Therapeutics Inc. (developing a sepsis therapy (PCSK9 inhibitor)). JR has share options in Leading Biosciences Inc. JR is a shareholder in Molecular You Corp. JR reports receiving consulting fees in the last 3 years from: (1) Asahi Kesai Pharmaceuticals of America (AKPA)(developing recombinant thrombomodulin in sepsis). (2) La Jolla Pharmaceuticals (developing angiotensin II; JR chaired the DSMB of a trial of angiotensin II from 2015 to 2017)—no longer actively consulting. (3) Ferring Pharmaceuticals (manufactures vasopressin and was developing selepressin)—no longer actively consulting. (4) Cubist Pharmaceuticals (now owned by Merck; formerly Trius Pharmaceuticals; developing antibiotics)—no longer 3 actively consulting. (5) Leading Biosciences (was developing a sepsis therapeutic that is no longer in development)—no longer actively consulting. (6) Grifols (sells albumin)—no longer actively consulting. (7) CytoVale Inc. (developing a sepsis diagnostic)—no longer actively consulting. JR reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that is provided to and administered by UBC.


  1. 1.
    Goodman and Gilman’s (2011) Pharmacological Basis of Therapeutics Twelfth (ed). New YorkGoogle Scholar
  2. 2.
    Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving sepsis campaign: international guidelines for the management of sepsis and septic shock: 2016. Intensive Care Med 43:304–377PubMedCrossRefGoogle Scholar
  3. 3.
    Aguilera G, Rabadan-Diehl C (2000) Vasopressinergic regulation of the hypothalamic-pituitary-adrenal axis: implications for stress adaptation. Regul Pept 96(1–2):23–29PubMedCrossRefGoogle Scholar
  4. 4.
    Yamamoto K, Ikeda U, Okada K et al (1997) Arginine vasopressin increases nitric oxide synthesis in cytokine-stimulated rat cardiac myocytes. Hypertension 30(5):1112–1120PubMedCrossRefGoogle Scholar
  5. 5.
    Rudichenko VM, Beierwaltes WH (1995) Arginine vasopressin-induced renal vasodilation mediated by nitric oxide. J Vasc Res 32(2):100–105PubMedCrossRefGoogle Scholar
  6. 6.
    Landry DW, Levin HR, Gallant EM et al (1997) Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 95(5):1122–1125PubMedCrossRefGoogle Scholar
  7. 7.
    Landry DW, Levin HR, Gallant EM et al (1997) Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 25(8):1279–1282PubMedCrossRefGoogle Scholar
  8. 8.
    Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA (2001) The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 27(8):1416–1421PubMedCrossRefGoogle Scholar
  9. 9.
    Malay MB, Ashton RC Jr, Landry DW, Townsend RN (1999) Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma 47(4):699–703PubMedCrossRefGoogle Scholar
  10. 10.
    Patel BM, Chittock DR, Russell JA, Walley KR (2002) Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 96(3):576–582PubMedCrossRefGoogle Scholar
  11. 11.
    Siami S, Polito A, Porcher R et al (2013) Thirst perception and osmoregulation of vasopressin secretion are altered during recovery from septic shock. PLoS One 8(11):e80190PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Boucheix OB, Milano SP, Henriksson M, Reinheimer TM (2013) Selepressin, a new V1A receptor agonist: hemodynamic comparison to vasopressin in dogs. Shock 39(6):533–538PubMedCrossRefGoogle Scholar
  13. 13.
    Asfar P, Russell JA, Tuckermann J, Radermacher P (2016) Selepressin in septic shock: a step toward decatecholaminization? Crit Care Med 44(1):234–236PubMedCrossRefGoogle Scholar
  14. 14.
    Russell JA, Vincent JL, Kjolbye AL et al (2017) Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care 21(1):213PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    He X, Su F, Taccone FS, Laporte R et al (2016) A selective V(1A) receptor agonist, selepressin, is superior to arginine vasopressin and to norepinephrine in ovine septic shock. Crit Care Med 44(1):23–31PubMedCrossRefGoogle Scholar
  16. 16.
    Maybauer MO, Maybauer DM, Enkhbaatar P et al (2014) The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*. Crit Care Med 42(7):e525–e533PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Farmakis D, Alvarez J, Gal TB et al (2016) Levosimendan beyond inotropy and acute heart failure: evidence of pleiotropic effects on the heart and other organs: an expert panel position paper. Int J Cardiol 222:303–312PubMedCrossRefGoogle Scholar
  18. 18.
    Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365(9453):63–78PubMedCrossRefGoogle Scholar
  19. 19.
    Boldt J, Menges T, Kuhn D, Diridis C, Hempelmann G (1995) Alterations in circulating vasoactive substances in the critically ill–a comparison between survivors and non-survivors. Intensive Care Med 21(3):218–225PubMedCrossRefGoogle Scholar
  20. 20.
    de Montmollin E, Aboab J, Mansart A, Annane D (2009) Bench-to-bedside review: beta-adrenergic modulation in sepsis. Crit Care 13(5):230PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Reynolds RD, Gorczynski RJ, Quon CY (1986) Pharmacology and pharmacokinetics of esmolol. J Clin Pharmacol 26(suppl A):A3–A14PubMedCrossRefGoogle Scholar
  22. 22.
    Atarashi H, Kuruma A, Yashima M et al (2000) Pharmacokinetics of landiolol hydrochloride, a new ultra-short-acting beta-blocker, in patients with cardiac arrhythmias. Clin Pharmacol Ther 68(2):143–150PubMedCrossRefGoogle Scholar
  23. 23.
    Page IH, Helmer OM (1940) A crystalline pressor substance (Angiotonin) resulting form the reaction between renin and renin-activator. J Exp Med 71(1):29–42PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Rajagopalan S, Kurz S, Münzel T et al (1996) Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97(8):1916–1923PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Khanna A, English SW, Wang XS et al (2017) Angiotensin II for the treatment of vasodilatory shock. N Engl J Med 377:419–430PubMedCrossRefGoogle Scholar
  26. 26.
    Vincent JL, De Backer D (2013) Circulatory shock. N Engl J Med 369(18):1726–1734PubMedCrossRefGoogle Scholar
  27. 27.
    Perez P, Kimmoun A, Blime V, Levy B (2014) Increasing mean arterial pressure in cardiogenic shock secondary to myocardial infarction: effects on hemodynamics and tissue oxygenation. Shock 41(4):269–274PubMedCrossRefGoogle Scholar
  28. 28.
    Maas JJ, Pinsky MR, de Wilde RB, de Jonge E, Jansen JR (2013) Cardiac output response to norepinephrine in postoperative cardiac surgery patients: interpretation with venous return and cardiac function curves. Crit Care Med 41(1):143–150PubMedCrossRefGoogle Scholar
  29. 29.
    Levy B, Perez P, Perny J, Thivilier C, Gerard A (2011) 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 39(3):450–455PubMedCrossRefGoogle Scholar
  30. 30.
    Guinot PG, Longrois D, Kamel S, Lorne E, Dupont H (2018) Ventriculo-arterial coupling analysis predicts the hemodynamic response to norepinephrine in hypotensive postoperative patients: a prospective observational study. Crit Care Med 46(1):e17–e25PubMedCrossRefGoogle Scholar
  31. 31.
    Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F (2008) Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med. 36(6):1701–1706PubMedCrossRefGoogle Scholar
  32. 32.
    Sun D, Huang A, Mital S et al (2002) Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles. Circulation 106(5):550–555PubMedCrossRefGoogle Scholar
  33. 33.
    Annane D, Vignon P, Renault A et al (2007) Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370(9588):676–684PubMedCrossRefGoogle Scholar
  34. 34.
    Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J, CAT Study investigators (2008) A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 34(12):2226–2234PubMedCrossRefGoogle Scholar
  35. 35.
    Marik PE, Mohedin M (1994) The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 272(17):1354–1357PubMedCrossRefGoogle Scholar
  36. 36.
    van Diepen S, Katz JN, Albert NM et al (2017) Contemporary management of cardiogenic shock: a scientific statement from the American heart association. Circulation 136(16):e232–e268PubMedCrossRefGoogle Scholar
  37. 37.
    Mon W, Stewart A, Fernando R et al (2017) Cardiac output changes with phenylephrine and ephedrine infusions during spinal anesthesia for cesarean section: a randomized, double-blind trial. J Clin Anesth 37:43–48PubMedCrossRefGoogle Scholar
  38. 38.
    Wasilewski MA, Grisanti LA, Song J et al (2016) Vasopressin type 1A receptor deletion enhances cardiac contractility, β-adrenergic receptor sensitivity and acute cardiac injury-induced dysfunction. Clin Sci 130(22):2017–2027. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Bouferrache K, Amiel JB, Chimot L et al (2012) Initial resuscitation guided by the surviving sepsis campaign recommendations and early echocardiographic assessment of hemodynamics in intensive care unit septic patients: a pilot study. Crit Care Med 40(10):2821–2827PubMedCrossRefGoogle Scholar
  40. 40.
    Schumann J, Henrich EC, Strobl H et al. (2018) Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database of Systematic Reviews. Issue 1, Art. No.: CD009669Google Scholar
  41. 41.
    Morelli A, Ertmer C, Westphal M et al (2013) Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 310(16):1683–1691PubMedCrossRefGoogle Scholar
  42. 42.
    Aviado DM Jr, Schmidt CF (1957) Effects of sympathomimetic drugs on pulmonary circulation: with special reference to a new pulmonary vasodilator. J Pharmacol Exp Ther 120(4):512–527PubMedGoogle Scholar
  43. 43.
    Monnet X, Jabot J, Maizel J, Richard C, Teboul JL (2011) Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients. Crit Care Med 39(4):689–694PubMedCrossRefGoogle Scholar
  44. 44.
    Persichini R, Silva S, Teboul JL et al (2012) Effects of norepinephrine on mean systemic pressure and venous return in human septic shock. Crit Care Med 40(12):3146–3153PubMedCrossRefGoogle Scholar
  45. 45.
    Hajjar LA, Vincent JL, Barbosa Gomes Galas FR et al (2017) Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: the vancs randomized controlled trial. Anesthesiology 126(1):85–93PubMedCrossRefGoogle Scholar
  46. 46.
    James A, Amour J (2018) Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: a discussion of the level of evidence. Anesthesiology 128(1):228PubMedCrossRefGoogle Scholar
  47. 47.
    Cheng Y, Pan T, Ge M, et al. (2018) Evaluation of vasopressin for vasoplegic shock in patients with preoperative left ventricular dysfunction after cardiac surgery: a propensity-score analysis. Shock. Feb 7. 10.1097/shk.0000000000001114Google Scholar
  48. 48.
    Lewis RJ, Angus DC, Laterre PF et al (2018) Rationale and design of an adaptive phase 2b/3 clinical trial of selepressin for adults in septic shock, Selepressin evaluation program for sepsis-induced shock-adaptive clinical trial. Ann Am Thorac Soc 15(2):250–257PubMedCrossRefGoogle Scholar
  49. 49.
    Gordon AC, Perkins GD, Singer M et al (2016) Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med 375(17):1638–1648PubMedCrossRefGoogle Scholar
  50. 50.
    De Backer D, Creteur J, Noordally O, Smail N, Gulbis B, Vincent JL (1998) Does hepato-splanchnic V O2/D O2 dependency exist in critically ill septic patients? Am J Respir Crit Care Med 157:1219–1225PubMedCrossRefGoogle Scholar
  51. 51.
    Hernandez G, Bruhn A, Luengo C et al (2013) Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study. Intensive Care Med 39:1435–1443PubMedCrossRefGoogle Scholar
  52. 52.
    De Backer D, Creteur J, Silva E, Vincent JL (2003) Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med 31:1659–1667PubMedCrossRefGoogle Scholar
  53. 53.
    van Haren FM, Rozendaal FW, van der Hoeven JG (2003) The effect of vasopressin on gastric perfusion in catecholamine-dependent patients in septic shock. Chest 124:2256–2260PubMedCrossRefGoogle Scholar
  54. 54.
    Georger JF, Hamzaoui O, Chaari A, Maizel J, Richard C, Teboul JL (2010) Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients. Intensive Care Med 36:1882–1889PubMedCrossRefGoogle Scholar
  55. 55.
    Boerma EC, Ince C (2010) The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients. Intensive Care Med 36:2004–2018PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Jhanji S, Stirling S, Patel N, Hinds CJ, Pearse RM (2009) The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock. Crit Care Med 37:1961–1966PubMedCrossRefGoogle Scholar
  57. 57.
    Dubin A, Pozo MO, Casabella CA et al (2009) Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 13:R92PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Thooft A, Favory R, Salgado DR et al (2011) Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care 15:R222PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Morelli A, Ertmer C, Rehberg S et al (2008) Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care 12:R143PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Morelli A, Lange M, Ertmer C et al (2008) Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock 29:446–451PubMedCrossRefGoogle Scholar
  61. 61.
    Dubois MJ, De Backer D, Creteur J, Anane S, Vincent JL (2003) Effect of vasopressin on sublingual microcirculation in a patient with distributive shock. Intensive Care Med 29:1020–1023PubMedCrossRefGoogle Scholar
  62. 62.
    Nygren A, Thoren A, Ricksten SE (2009) Vasopressin decreases intestinal mucosal perfusion: a clinical study on cardiac surgery patients in vasodilatory shock. Acta Anaesthesiol Scand 53:581–588PubMedCrossRefGoogle Scholar
  63. 63.
    Boerma EC, van der Voort PHJ, Ince C (2005) Sublingual microcirculatory flow is impaired by the vasopressin- analogue terlipressin in a patient with catecholamine-resistant septic shock. Acta Anaesthesiol Scand 49:1387–1390PubMedCrossRefGoogle Scholar
  64. 64.
    Asfar P, Bracht H, Radermacher P (2008) Impact of vasopressin analogues on the gut mucosal microcirculation. Best Pract Res Clin Anaesthesiol 22:351–358PubMedCrossRefGoogle Scholar
  65. 65.
    Morelli A, Donati A, Ertmer C et al (2011) Short-term effects of terlipressin bolus infusion on sublingual microcirculatory blood flow during septic shock. Intensive Care Med 37:963–969PubMedCrossRefGoogle Scholar
  66. 66.
    Morelli A, Donati A, Ertmer C et al (2011) Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock. Crit Care 15:R217PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Qiu X, Huang Y, Xu J, Qiu H, Yang Y (2014) Effects of terlipressin on microcirculation of small bowel mesentery in rats with endotoxic shock. J Surg Res 188:503–509PubMedCrossRefGoogle Scholar
  68. 68.
    De Backer D, Creteur J, Dubois MJ et al (2006) The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 34:403–408PubMedCrossRefGoogle Scholar
  69. 69.
    Enrico C, Kanoore Edul VS et al (2012) Systemic and microcirculatory effects of dobutamine in patients with septic shock. J Crit Care 27:630–638PubMedCrossRefGoogle Scholar
  70. 70.
    Ospina-Tascón GA, García Marin AF, Echeverri GJ et al (1985) Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O2 extraction during septic shock. J Appl Physiol 122:1406–1417CrossRefGoogle Scholar
  71. 71.
    Dubin A, Murias G, Sottile JP et al (2007) Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study. Intensive Care Med 33:485–494PubMedCrossRefGoogle Scholar
  72. 72.
    Morelli A, Donati A, Ertmer C et al (2010) Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care 14:R232PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Fuchs C, Ertmer C, Rehberg S (2016) Effects of vasodilators on haemodynamic coherence. Best Pract Res Clin Anaesthesiol 30:479–489PubMedCrossRefGoogle Scholar
  74. 74.
    Webber J, MacDonald A (1993) Metabolic actions of catecholamines in man. Baillière’s Clin Endocrinol Metab 7:393–413CrossRefGoogle Scholar
  75. 75.
    Van den Berghe G, de Zegher F (1996) Anterior pituitary function during critical illness and dopamine treatment. Crit Care Med 24(9):1580–1590PubMedCrossRefGoogle Scholar
  76. 76.
    Sharshar T, Annane D (2008) Endocrine effects of vasopressin in critically ill patients. Best Pract Res Clin Anesthesiol 22:265–273CrossRefGoogle Scholar
  77. 77.
    Bermejo-Martin JF, Andaluz-Ojeda D, Almansa R et al (2016) Defining immunological dysfunction in sepsis: a requisite tool for precision medicine. J Infect 72(5):525–536PubMedCrossRefGoogle Scholar
  78. 78.
    Parissis JT, Adamopoulos S, Antoniades C et al (2004) Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure. Am J Cardiol 93(10):1309–1312PubMedCrossRefGoogle Scholar
  79. 79.
    Russell JA, Fjell C, Hsu JL et al (2013) Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock. Am J Resp Crit Care Med 188(3):356–364PubMedCrossRefGoogle Scholar
  80. 80.
    Russell JA, Walley KR (2010) Vasopressin and its immune effects in septic shock. J Innate Immun 2(5):446–460PubMedCrossRefGoogle Scholar
  81. 81.
    Gamper G, Havel C, Arrich J et al (2016) Vasopressors for hypotensive shock. Cochrane Database Syst Rev 2:CD003709PubMedGoogle Scholar
  82. 82.
    Gordon AC, Mason AJ, Thirunavukkarusu N et al (2016) Effect of early vasopressin vs norephinephrine on kidney failure patients with septic shock. The Vanish randomised clinical trial. JAMA 316(5):509–518PubMedCrossRefGoogle Scholar
  83. 83.
    Russell JA, Walley KR, Singer J et al (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358:877–887PubMedCrossRefGoogle Scholar
  84. 84.
    Russell JA, Walley KR, Gordon AC et al (2009) Interaction of vasopressin infusion, corticosteroid treatment and mortality of septic shock. Crit Care Med 37(3):811–818PubMedCrossRefGoogle Scholar
  85. 85.
    De Backer D, Biston P, Devriendt J et al (2010) Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362:779–789PubMedCrossRefGoogle Scholar
  86. 86.
    Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H (2017) Association Between US norepinephrine shortage and mortality among patients with septic shock. JAMA 317(14):1433–1442PubMedCrossRefGoogle Scholar
  87. 87.
    Belletti A, Benedetto U, Biondi-Zoccai G et al (2017) The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials. J Crit Care 37:91–98PubMedCrossRefGoogle Scholar
  88. 88.
    Mehaffey JH, Johnston LE, Hawkins RB et al (2017) Methylene blue for vasoplegic syndrome after cardiac operation: early administration improves survival. Ann Thorac Surg 104:36–41PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Elkayam U, Tasissa G, Binanay C et al (2007) Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure. Am Heart J 153(1):98–104PubMedCrossRefGoogle Scholar
  90. 90.
    Shah P, Cowger JA (2014) Cardiogenic shock. Crit Care Clin 30(3):391–412PubMedCrossRefGoogle Scholar
  91. 91.
    Aranda JM Jr, Schofield RB, Pauly DF et al (2003) Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial. Am Heart J 145(2):324–329PubMedCrossRefGoogle Scholar
  92. 92.
    Harris T, Davenport R, Mak M, Brohi K (2018) The evolving science of trauma resuscitation. Emerg Med Clin North Am 36(1):85–106PubMedCrossRefGoogle Scholar
  93. 93.
    Cannon JW (2018) Hemorrhagic Shock. N Engl J Med 378(4):370–379PubMedCrossRefGoogle Scholar
  94. 94.
    Rossaint R, Bouillon B, Cerny V et al (2016) The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care 20:100PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Bayram B, Hocaoglu N, Atilla R, Kalkan S et al (2012) Effects of terlipressin in a rat model of severe uncontrolled hemorrhage via liver injury. Am J Emerg Med 30(7):1176–1182PubMedCrossRefGoogle Scholar
  96. 96.
    Cohn SM, McCarthy J, Stewart RM et al (2011) Impact of low-dose vasopressin on trauma outcome: prospective randomized study. World J Surg 35(2):430–439PubMedCrossRefGoogle Scholar
  97. 97.
    Westermann I, Dunser MW, Haas T et al (2007) Endogenous vasopressin and copeptin response in multiple trauma patients. Shock 28(6):644–649PubMedGoogle Scholar
  98. 98.
    Hylands M, Toma A, Beaudoin N et al (2017) Early vasopressor use following traumatic injury: a systematic review. BMJ Open 7(11):e017559PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Plurad DS, Talving P, Lam L et al (2011) Early vasopressor use in critical injury is associated with mortality independent from volume status. J Trauma 71(3):565–570 [discussion 570–572] PubMedCrossRefGoogle Scholar
  100. 100.
    Sperry JL, Minei JP, Frankel HL (2008) Early use of vasopressors after injury: caution before constriction. J Trauma 64(1):9–14PubMedCrossRefGoogle Scholar
  101. 101.
    Ponikowski P, Voors AA, Anker SD et al (2016) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC) Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J 37(27):2129–2200PubMedCrossRefGoogle Scholar
  102. 102.
    Excellence NIfHaC (2016) Sepsis : recognition, assessment and early management. In: sepsis: recognition, Assessment and early management. London.Google Scholar
  103. 103.
    Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F (2008) Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med 36(6):1701–1706PubMedCrossRefGoogle Scholar
  104. 104.
    Hollenberg SM (2009) Inotrope and vasopressor therapy of septic shock. Crit Care Clin 25(4):781–802 [ix] PubMedCrossRefGoogle Scholar
  105. 105.
    LeDoux D, Astiz ME, Carpati CM, Rackow EC (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28:2729–2732PubMedCrossRefGoogle Scholar
  106. 106.
    Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C (2005) Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 33:780–786PubMedCrossRefGoogle Scholar
  107. 107.
    Asfar P, Meziani F, Hamel JF et al (2014) High versus low blood-pressure targets in patients with septic shock. N Engl J Med 370:1583–1593PubMedCrossRefGoogle Scholar
  108. 108.
    Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D (1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 330(24):1717–1722PubMedCrossRefGoogle Scholar
  109. 109.
    Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA, Emergency Medicine Shock Research Network (EMShockNet) Investigators (2010) Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 303(8):739–746PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Jansen TC, van Bommel J, Schoonderbeek FJ et al (2010) LACTATE study group: early lactate-guided therapy in intensive care unit patients: A multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 182:752–761PubMedCrossRefGoogle Scholar
  111. 111.
    Teboul JL, Saugel B, Cecconi M et al (2016) Less invasive hemodynamic monitoring in critically ill patients. Intensive Care Med 42:1350–1359PubMedCrossRefGoogle Scholar
  112. 112.
    Cecconi M, De Backer D, Antonelli M et al (2014) Consensus on circulatory shock and hemodynamic monitoring. task force of the European society of intensive care medicine. Intensive Care Med 40:1795–1815PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Merouani M, Guignard B, Vincent F et al (2008) Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic. Crit Care 12:R155PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Hammond DA, McCain K, Painter JT et al (2017) Discontinuation of vasopressin before norepinephrine in the recovery phase of septic shock. J Intensive Care Med 2017:885066617714209Google Scholar
  115. 115.
    Bissell BD, Magee C, Moran P, Bastin MLT, Flannery AH (2017) Hemodynamic instability secondary to vasopressin withdrawal in septic shock. J Intensive Care Med 2017:885066617716396Google Scholar
  116. 116.
    Annane D, Sébille V, Duboc D et al (1998) Incidence and prognosis of sustained arrhythmias in critically ill patients. Am J Respir Crit Care Med 178(1):20–25CrossRefGoogle Scholar
  117. 117.
    Kido K, Guglin M (2017) Drug-induced takotsubo cardiomyopathy. J Cardiovasc Pharmacol Ther 22(6):552–563PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature and ESICM 2018

Authors and Affiliations

  • Djillali Annane
    • 1
    Email author
  • Lamia Ouanes-Besbes
    • 2
  • Daniel de Backer
    • 3
  • Bin DU
    • 4
  • Anthony C. Gordon
    • 5
  • Glenn Hernández
    • 6
  • Keith M. Olsen
    • 7
  • Tiffany M. Osborn
    • 8
  • Sandra Peake
    • 9
    • 10
  • James A. Russell
    • 11
  • Sergio Zanotti Cavazzoni
    • 12
  1. 1.General ICURaymond Poincaré Hospital (APHP), School of Medicine Simone Veil U1173 Laboratory of Infection and Inflammation (University of Versailles SQY, University Paris Saclay/INSERM), CRICS-TRIGERSEP Network (F-CRIN)GarchesFrance
  2. 2.Intensive Care Unit, CHU F. BourguibaMonastirTunisia
  3. 3.Department of Intensive Care, CHIREC HospitalsUniversité Libre de BruxellesBrusselsBelgium
  4. 4.Medical ICUPeking Union Medical College HospitalBeijingChina
  5. 5.Section of Anaesthetics, Pain Medicine and Intensive CareImperial College LondonLondonUK
  6. 6.Departamento de Medicina Intensiva, Facultad de MedicinaPontificia Universidad Católica de ChileSantiagoChile
  7. 7.UAMS College of PharmacyLittle RockUSA
  8. 8.Section of Acute Care Surgical Services, Surgical/Trauma Critical CareBarnes Jewish HospitalSt. LouisUSA
  9. 9.Department of Intensive Care, The Queen Elizabeth Hospital School of MedicineUniversity of AdelaideAdelaideAustralia
  10. 10.School of Epidemiology and Preventive MedicineMonash UniversityVictoriaAustralia
  11. 11.Centre for Heart Lung Innovation, St. Paul’s HospitalUniversity of British ColumbiaVancouverCanada
  12. 12.Sound Critical Care, Sound PhysiciansHoustonUSA

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