GOAL-DIRECTED THERAPY WITH DOPEXAMINE, DOBUTAMINE, AND VOLUME EXPANSION - EFFECTS OF SYSTEMIC OXYGEN-TRANSPORT ON HEPATIC ULTRASTRUCTURE INPORCINE SEPSIS

Objectives: Can the hepatic structural deterioration that occurs durin g peritonitis be attenuated by increasing cardiac output and oxygen co nsumption (V over dot O-2)? Do the agents used to achieve these increa ses have any characteristic affects on these hepatic structural change s? Design: Randomized, prospective, observational animal study. Settin g: Research laboratory of a university medical school. Subjects: Twent y-five Middle White adolescent pigs, weighing 25 to 30 kg, divided int o five groups. Interventions: A thermodilution flotation catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular, portal, and hepatic veins, and into the femoral art ery. Ultrasound flow probes were placed around the portal vein and the hepatic artery. A metabolic cart was attached to the ventilator. Base line measurements were made and cardiac output was increased by >25% b y administering either dobutamine (10 mu g/min), dopexamine (10 mu g/k g/min), or colloid. A control group had its cardiac output maintained at its baseline value. Peritonitis was induced in the four groups by c ontamination with cecal content and maintained for 6 hrs. Hepatic tiss ue was then removed for ultrastructural analysis and the animals were killed. Measurements and Main Results: Before infection, cardiac outpu t, V over dot O2, and hepatic blood flow were increased in the three t reatment groups. In the dobutamine and dopexamine groups, oxygen deliv ery increased, but decreased in the volume group. Mean arterial pressu re increased in the dobutamine and dopexamine groups, but in the volum e group, mean arterial pressure was maintained. Six hours after infect ion, cardiac output and V over dot O-2 had further increased in the do butamine and volume groups, but both variables had decreased in the do pexamine group. After infection in the control group, cardiac output h ad decreased, although oxygen delivery and V over dot O-2 increased. T here were no significant differences between hepatic hemodynamic or ox ygen transport variables in any of the groups during the infection per iod. Hepatic ultrastructure was well maintained in the dopexamine grou p, while considerable deterioration was seen in the volume and control groups. In the dobutamine group, hepatic deterioration was greater th an in the other three groups. Conclusions: Increasing cardiac output a nd V over dot O-2 before and during infection was only protective when dopexamine was administered. Dobutamine infusion was associated with greater hepatic deterioration than that effect seen iii either the con trol or volume groups.