Effects of Combination Dobutamine and Vasopressin Therapy on Microcirculatory Blood Flow in a Porcine Model of Severe Endotoxic Shock

Abstract

Dobutamine (DB) has been recommended in combination with vasopressor therapy in septic shock, given its reported ability to improve mesenteric and microcirculatory perfusion. Vasopressin (VP) is typically reserved as a second-line agent due to the concern of ischemia. The purpose of our study was to determine whether combination DB and VP therapy improved microcirculatory blood flow in severe endotoxic shock. Septic shock was induced in 20 anesthetized piglets with injection of E. coli endotoxin. DB (10 μg/kg/min, n = 5) and VP (0.04 units/min, n = 10) were administered alone and in combination (n = 15). Measurements were compared at baseline, following endotoxin administration, and following treatment. Microcirculatory blood flow was determined via the injection of colored microspheres. VP completely reversed endotoxin-mediated hypotension with a mean arterial pressure (MAP) of 85 ± 4.5 mm Hg, which was not significantly altered with the addition of DB (77 ± 4.9 mm Hg). Endotoxin uniformly depressed cardiac output (CO) from baseline (227 ± 10.7 versus 174 ± 12.4 mL/min/kg) despite treatment with VP alone or in combination with DB. The addition of DB did not improve the CO in this severe septic shock model. VP was found to shunt microcirculatory flow from the skin and GI tract to vital organs such as the brain, liver, and kidneys, which was not altered with the addition of DB. Results indicate that DB is ineffective in increasing CO or improving mesenteric blood flow when used with physiologic replacement doses of VP. In combination, DB is unable to overcome the blood flow distribution achieved with VP administration alone in severe endotoxic shock.