Vasopressin and septic shock

  • Sarah Mousavi Mail Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Arginine vasopressin, Septic Shock, Antidiuretic hormone, Norepinephrine


Septic shock continues to be one of the leading causes of death in the Intensive Care Units. When the shock state persists after adequate fluid resuscitation,  vasopressor therapy is required to improve and maintain adequate tissue/organ  perfusion in an attempt to improve survival and prevent the development of multiple organ dysfunction and failure. Various studies have suggested that exogenous administration of arginine vasopressin  may  be  an  effective  adjunctive  therapy  to  traditional  catecholamines for the management of hypotension during septic shock. Vasopressin is both a vasopressor  and  an  antidiuretic  hormone.  It  also  has  hemostatic,  gastrointestinal and thermoregulatory  effects, and is an adrenocorticotropic  hormone secretagogue. Vasopressin  is released from the axonal terminals of magnocellular  neurons in the hypothalamus. Vasopressin mediates vasoconstriction  via V1-receptor activation on vascular smooth muscle and mediates its antidiuretic effect via V2-receptor activation in the renal collecting duct system. Vasopressin  infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels. Current guidelines from the Surviving Sepsis Campaign recommend arginine vasopressin 0.03 unit/minute may be added to norepinephrine with the anticipation of an effect equal to higher doses of norepinephrine alone. Clinicians must be knowledgeable about the use of vasopressin in septic shock, including controversial areas where guidelines do not always provide solid recommendations.


Beale RJ, Hollenberg SM, Vincent JL, Parrillo JE.Vasopressor and inotropic support in septic shock: an evidence-based review. Crit Care Med 2004; 32(11): S455-S465.

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29(7):1303-10.

Epstein FH, Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993; 328(20): 1471-77.

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(10): 699-709.

Guzman JA, Rosado AE, Kruse JA.Vasopressin vs. norepinephrine in endotoxic shock: systemic, renal, and splanchnic hemodynamic and oxygen transport effects. J Appl Physiol 2003; 95(2): 803-9.

Buijs R. Intra-and extrahypothalamic vasopressin and oxytocin pathways in the rat. Cell Tissue Res 1978; 192(3): 423-35.

Robertson G. The regulation of vasopressin function in health and disease. Recent Prog Horm Res 1976; 33: 333-85.

Forrest P. Vasopressin and shock. Anaesth Intensive Care 2001; 29(5): 463- 73.

Robertson GL, Shelton RL, Athar S. The osmoregulation of vasopressin. Kidney Int 1976; 10(1): 25-37.

Schrier R, Berl T, Anderson R. Osmotic and nonosmotic control of vasopressin release. Am J Physiol Renal Physiol 1979; 236(4): F321-F332.

Sklar AH, Schrier RW.Central nervous system mediators of vasopressin release. Physiol Rev 1983; 63(4): 1243-80.

Dunn FL, Brennan TJ, Nelson AE, Robertson GL. The role of blood osmolality and volume in regulating vasopressin secretion in the rat. J Clin Invest 1973; 52(12): 3212- 9.

Pittman QJ, Lawrence D, Mclean L. Central effects of arginine vasopressin on blood pressure in rats. Endocrinology 1982; 110(3): 1058-60.

Reid IA. Role of nitric oxide in the regulation of renin and vasopressin secretion. Front Neuroendocrinol 1994; 15(4): 351-83.

Kimura T, Share L, Wang BC, Crofton JT. The role of central adrenoreceptors in the control of vasopressin release and blood pressure. Endocrinology 1981;108(5):1829-36.

Wilson KC, Weitzman RE, Fisher DA. Arginine vasopressin metabolism in dogs. II. Modeling and system analysis. Am J Physiol 1978; 235(6): E598- 605.

Robertson GL, Athar S. The interaction of blood osmolality and blood volume in regulating plasma vasopressin in man. J Clin Endocrinol Metab 1976; 42(4): 613-20.

Dünser MW, Westphal M.Arginine vasopressin in vasodilatory shock: effects on metabolism and beyond. Curr Opin Anaesthesiol 2008; 21(2): 122-27.

Sutherland AM, Gordon AC, Russell JA. Are vasopressin levels increased or decreased in septic shock? Crit Care Med 2006; 34(2): 542-3.

Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D.Circulating vasopressin levels in septic shock. Crit Care Med 2003; 31(6): 1752-8.

Robin JK, Oliver JA, Landry DW.Vasopressin deficiency in the syndrome of irreversible shock. J Trauma Acute Care Surg 2003;54(5): S149-S154.

Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 2003; 107(18): 2313-9.

Giusti-Paiva A, De Castro M, Antunes-Rodrigues J, Carnio EC. Inducible nitric oxide synthase pathway in the central nervous system and vasopressin release during experimental septic shock. Crit Care Med 2002; 30(6): 1306- 10.

Birnbaumer M. Vasopressin receptors. Trends Endocrinol Metab 2000; 11(10): 406-10.

Barberis C, Mouillac B, Durroux T. Structural bases of vasopressin/oxytocin receptor function. J Endocrinol 1998;156(2): 223-9.

Barberis C, Tribollet E. Vasopressin and oxytocin receptors in the central nervous system. Crit Rev Neurobiol 1996; 10(1): 119- 54.

Cowley Jr, Quillen Jr E, Skelton M. Role of vasopressin in cardiovascular regulation. Fed Proc. 1983; 42(15):3170-6.

Cowley AW, Monos E, Guyton AC. Interaction of vasopressin and the baroreceptor reflex system in the regulation of arterial blood pressure in the dog. Circ Res 1974; 34(4): 505-14.

McNeill JR. Role of vasopressin in the control of arterial pressure. Can J Physiol Pharmacol 1983;61(11): 1226-35.

Mutlu GM, Factor P. Role of vasopressin in the management of septic shock. Intensive Care Med 2004; 30(7): 1276-91.

Farand P, Hamel M, Lauzier F, Plante GE, Lesur O. Organ perfusion/ permeability related effects of norepinephrine and vasopressin in sepsis. Cann J Anaesth 2006; 53(9): 934-46.

Barrett LK, Orie NN, Taylor V, Stidwill RP, Clapp LH, Singer M. Differential effects of vasopressin and norepinephrine on vascular reactivity in a long-term rodent model of sepsis. Crit Care Med 2007;35(10): 2337-43.

Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock. Chest 2001;120(3): 989-1002.

Tavernier B, Makhotine O, Lebuffe G, Dupont J, Scherpereel P. Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology 1998; 89(6): 1313-21.

Holmes CL, Landry DW, Granton JT.Vasopressin and the cardiovascular system part 1- receptor physiology. Crit Care 2003; 7(6): 427-34.

Treschan TA, Peters J. The vasopressin system: physiology and clinical strategies. Anesthesiology 2006;105(3): 599-612.

Fernández N, García JL, García-Villalón AL, Monge L, Gómez B, Diéguez G. Coronary vasoconstriction produced by vasopressin in anesthetized goats. Role of vasopressin V1 and V2 receptors and nitric oxide. Eur J pharmacol 1998; 342(2-3): 225-33.

Kozniewska E, Romaniuk K. Vasopressin in vascular regulation and water homeostasis in the brain. J Physiol Pharmacol 2008; 59(Suppl 8): 109-16.

Evora P, Pearson P, Schaff H. Arginine vasopressin induces endothelium-dependent vasodilatation of the pulmonary artery. V1-receptor-mediated production of nitric oxide. Chest 1993; 103(4): 1241- 5.

Deen PM, Verdijk MA, Knoers NV, et al. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994; 264(5155): 92-5.

Chatterjee K. Neurohormonal activation in congestive heart failure and the role of vasopressin. Am J Cardiol 2005; 95(9): 8-13.

Malay MB, Ashton JL, Dahl K, et al. Heterogeneity of the vasoconstrictor effect of vasopressin in septic shock. Crit Care Med 2004; 32(6): 1327-31.

Knepper MA, Nielsen S, Chou CL, DiGiovanni SR. Mechanism of vasopressin action in the renal collecting duct. Semin nephrol 1994; 14(4):302-21.

Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA. The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 2001; 27(8): 1416-21.

Krejci V, Hiltebrand LB, Jakob SM, Takala J, Sigurdsson GH. Vasopressin in septic shock: effects on pancreatic, renal, and hepatic blood flow. Crit Care 2007;11(6): R129.

de Goeij DC, Jezova D, Tilders FJ. Repeated stress enhances vasopressin synthesis in corticotropin releasing factor neurons in the paraventricular nucleus. Brain Res 1992; 577(1):165- 8.

Haslam R, Rosson G. Aggregation of human blood platelets by vasopressin. Am J Physiol 1972; 223(4): 958- 67.

Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008; 34(1): 17-60.

Redl-Wenzl EM, Armbruster C, Edelmann G, et al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med 1993; 19(3):151- 4.

Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med 2000; 28(8): 2758- 65.

Landry DW, Levin HR, Gallant EM, et al.Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997; 95(5): 1122- 5.

Gold JA HB, Landry DL.Vasopressin for the treatment of septic shock (abstract). Am J Resp Crit Care Med 1998; 157: A116.

Malay MB, Ashton RC Jr, Landry DW, Townsend RN. Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma 1999; 47(4):699-703.

Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 2002; 96(3): 576-82.

Lauzier F, Lévy B, Lamarre P, Lesur O.Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med 2006; 32(11): 1782- 9.

Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358(9): 877- 87.

Torgersen C, Dünser MW, Wenzel V, et al. Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial. Intensive Care Med 2010; 36(1): 57-65.

van Haren FM, Rozendaal FW, van der Hoeven JG. The effect of vasopressin on gastric perfusion in catecholamine-dependent patients in septic shock. Chest 2003; 124(6): 2256- 60.

Hiltebrand LB, Krejci V, Jakob SM, Takala J, Sigurdsson GH. Effects of vasopressin on microcirculatory blood flow in the gastrointestinal tract in anesthetized pigs in septic shock. Anesthesiology 2007; 106(6): 1156- 67.

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(11): 2646- 50.

Westphal M, Freise H, Kehrel BE, Bone HG, Van Aken H, Sielenkämper AW. Arginine vasopressin compromises gut mucosal microcirculation in septic rats. Crit Care Med 2004; 32(1): 194-200.

Luckner G, Dünser MW, Jochberger S, et al. Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med 2005; 33(11): 2659- 66.

Luckner G, Mayr VD, Jochberger S, et al. Comparison of two dose regimens of arginine vasopressin in advanced vasodilatory shock. Crit Care Med 2007; 35(10): 2280- 5.

Torgersen C, Luckner G, Schröder DC, et al. Concomitant arginine-vasopressin and hydrocortisone therapy in severe septic shock: association with mortality. Intensive Care Med 2011. 37(9): 1432- 37.

Bauer SR, Lam SW, Cha SS, Oyen LJ. Effect of corticosteroids on arginine vasopressin–containing vasopressor therapy for septic shock: a case control study. J Crit Care 2008; 23(4): 500-6.

Russell JA, Walley KR, Gordon AC, et al. Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock. Crit Care Med 2009; 37(3): 811- 8.

How to Cite
Mousavi S. Vasopressin and septic shock. J Pharm Care. 1(2):65-73.
Review Article(s)