Abstract
Objective
To compare the effects of arginine-vasopressin (AVP) and norepinephrine (NE) on hemodynamic variables, organ dysfunction, and adverse events in early hyperdynamic septic shock.
Design and setting
Randomized, controlled, open-label trial.
Patients and participants
Twenty-three patients with early (12 h) hyperdynamic septic shock in two teaching hospitals.
Interventions
AVP (0.04–0.20 U min–1, n = 13) as a single agent or NE (0.1–2.8 μg kg–1 min–1, n = 10) infusion for 48 h to achieve mean arterial pressure at or above 70 mmHg.
Measurements and results
Hemodynamic parameters and Sequential Organ Failure Assessment (SOFA) score were measured. AVP and NE equally increased mean arterial pressure over 48 h, but NE was required in 36% of AVP patients at 48 h. Compared to baseline, AVP increased systemic vascular resistance, decreased exposure to NE, decreased cardiac output by decreasing heart rate, increased creatinine clearance, and improved SOFA score. The PrCO2 – PaCO2 difference remained stable throughout the study. One AVP patient developed acute coronary syndrome with dose-dependent ECG changes. Three patients in both groups died during their ICU stay.
Conclusion
In early hyperdynamic septic shock, the administration of high-dose AVP as a single agent fails to increase mean arterial pressure in the first hour but maintains it above 70 mmHg in two-thirds of patients at 48 h. AVP decreases NE exposure, has no effect on the PrCO2 – PaCO2 difference, and improves renal function and SOFA score.
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References
Hoyert DL, Kung HC, Smith BL (2005) Deaths: preliminary data for 2003. Natl Vital Stat Rep 53:1–48
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 29:1303–1310
Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D (2006) Sepsis Occurrence in Acutely Ill Patients Investigators. Crit Care Med 34:344–353
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, for the Early Goal-Directed Therapy Collaborative Group (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377
Müllner M, Urbanek B, Havel C, Losert H, Waechter F, Gamper G (2004) Vasopressors for shock. Cochrane Database of Systematic Reviews, issue 3: CD003709
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 95:1122–1125
Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D (2003) Circulating vasopressin levels in septic shock. Crit Care Med 31:1752–1758
Luckner G, Dunser MW, Jochberger S, Mayr VD, Wenzel V, Ulmer H, Schmid S, Knotzer H, Pajk W, Hasibeder W, Mayr AJ, Friesenecker B (2005) Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med 33:2659–2666
Hall LG, Oyen LJ, Taner CB, Cullinane DC, Baird TK, Cha SS, Sawyer MD (2004) Fixed-dose vasopressin compared with titrated dopamine and norepinephrine as initial vasopressor therapy for septic shock. Pharmacotherapy 24:1002–1012
Obritsch MD, Jung R, Fish DN, MacLaren R (2004) Effects of continuous vasopressin infusion in patients with septic shock. Ann Pharmacother 38:1117–1122
Klinzing S, Simon M, Reinhart K, Bredle DL, Meier-Hellmann A (2003) High-dose vasopressin is not superior to norepinephrine in septic shock. Crit Care Med 31:2646–2650
Haren FMP van, Rozendaal FW, van der Hoeven JG (2003) The effect of vasopressin on gastric perfusion in catecholamine-dependent patients in septic shock. Chest 124:2256–2260
Dunser MW, Mayr AJ, Ulmer H, Ritsch N, Knotzer H, Pajk W, Luckner G, Mutz NJ, Hasibeder WR (2001) The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: a retrospective analysis. Anesth Analg 93:7–13
Tsuneyoshi I, Yamada H, Kakihana Y, Nakamura M, Nakano Y, Boyle WA (2001) Hemodynamic and metabolic effects of low dose vasopressin infusions in vasodilatory septic shock. Crit Care Med 29:487–493
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 27:1416–1421
Landry DW, Levin HR, Gallant EM, Seo S, D'Alessandro D, Oz MC, Oliver JA (1997) Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 25:1279–1282
Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, Friesenecker B, Hasibeder WR (2003) Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 107:2313–2319
Patel BM, Chittock DR, Russell JA, Walley KR (2002) Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 96:576–582
Malay MB, Ashton RC Jr, Landry DW, Townsend RN (1999) Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma 47:699–703
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874
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 288:862–871
Jochberger S, Mayr VD, Luckner G, Wenzel V, Ulmer H, Schmid S, Knotzer H, Pajk W, Hasibeder W, Friesenecker B, Mayr AJ, Dünser MW (2006) Serum vasopressin concentrations in critically ill patients. Crit Care Med 34:293–299
Bucher M, Hobbhahn J, Taeger K, Kurtz A (2002) Cytokine-mediated down-regulation of vasopressin V1A receptors during acute endotoxemia in rats. Am J Physiol Regul Integr Comp Physiol 282:R979–R984
Leone M, Boyle WA (2006) Decreased vasopressin responsiveness in vasodilatory septic shock-like conditions. Crit Care Med 34:1126–1130
Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, Williams MD (2005) Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med 33:2194–2201
Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286:1754–1758
Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S (1999) The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Intensive Care Med 25:686–696
Lévy B, Vallée C, Lauzier F, Plante GE, Mansart A, Mallie JP, Lesur O (2004) Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock. Am J Physiol Heart Circ Physiol 287:H209–H215
Albert M, Losser MR, Hayon D, Faivre V, Payen D (2004) Systemic and renal macro- and microcirculatory responses to arginine vasopressin in endotoxic rabbits. Crit Care Med 32:1891–1898
Edwards RM, Trizna W, Kinter LB (1989) Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol 256:F274–F278
Rudichenko VM, Beierwaltes WH (1995) Arginine vasopressin-induced renal vasodilation mediated by nitric oxide. J Vasc Res 32:100–105
McVicar AJ (1988) Dose-response effects of pressor doses of arginine vasopressin on renal haemodynamics in the rat. J Physiol (Lond) 404:535–546
Albanese J, Leone M, Delmas A, Martin C (2005) Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med 33:1897–1902
Boyle WA III, Segel LD (1986) Direct cardiac effects of vasopressin and their reversal by a vascular antagonist. Am J Physiol 251:H734–H741
Walker BR, Childs ME, Adams EM (1988) Direct cardiac effects of vasopressin: role of V1- and V2-vasopressinergic receptors. Am J Physiol 255:H261–H265
Imperiale TF, Teran JC, McCullough AJ (1995) A meta-analysis of somatostatin versus vasopressin in the management of acute esophageal variceal hemorrhage. Gastroenterology 109:1289–1294
Asfar P, Pierrot M, Veal N, Moal F, Oberti F, Croquet V, Douay O, Gallois Y, Saumet JL, Alquier P, Cales P (2003) Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats. Crit Care Med 31:215–220
Thibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik RA, Erzurum SC (1999) Human vascular endothelial cells express oxytocin receptors. Endocrinology 140:1301–1309
Okamura T, Toda M, Ayajiki K, Toda N (1997) Receptor subtypes involved in relaxation and contraction by arginine vasopressin in canine isolated short posterior ciliary arteries. J Vasc Res 34:464–472
Wallace AW, Tunin CM, Shoukas AA (1989) Effects of vasopressin on pulmonary and systemic vascular mechanics. Am J Physiol 257:H1228–H1234
Acknowledgements
The authors thank Dr. Deborah Cook for reviewing the manuscript and Drs. Julie Abel, Dominique Bérard, Claude Cyr, Eric Deland, Sophie Laflamme, Marcel Martin, and Catherine St-Pierre for their help in recruiting patients.
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This work was supported by the Cardiovascular Critical Care research Network FRSQ and departmental funding.
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Lauzier, F., Lévy, B., Lamarre, P. et al. Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med 32, 1782–1789 (2006). https://doi.org/10.1007/s00134-006-0378-0
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DOI: https://doi.org/10.1007/s00134-006-0378-0