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Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock

¹Critical Care Medicine Department and ²Department of Laboratory Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; and ³Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts 02114

Submitted 14 May 2004 ; accepted in final form 16 August 2004

During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 µg·kg^–1·min^–1), norepinephrine (0.2, 1.0, or 2.0 µg·kg^–1·min^–1), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P < 0.06), mean arterial pressure (MAP) (P < 0.05), cardiac index (CI) (P < 0.02), and ejection fraction (EF) (P = 0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P = 0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P = 0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis.

vasopressors and systemic perfusion; low cardiac output septic shock; vasopressors and acidosis; vasopressors and cardiac function

This article has been cited by other articles:

				P. Farand, M. Hamel, F. Lauzier, G. E. Plante, and O. Lesur Review article: Organ perfusion/permeability-related effects of norepinephrine and vasopressin in sepsis: [Expose de synthese : Les effets relies a la perfusion et a la permeabilite organique de la norepinephrine et de la vasopressine durant le "sepsis"]. Can J Anesth, September 1, 2006; 53(9): 934 - 946. [Abstract] [Full Text] [PDF]