Regional Effects of Dobutamine in Endotoxic Shock

Abstract

β-2-Adrenergic agents can increase mesenteric blood flow under normal conditions. However, the effects of dobutamine on regional blood flow in sepsis are less well defined since diverging results had been obtained in some studies due to the differences in animal models. In this fluid-resuscitated hyperdynamic endotoxic dog model, we studied the effects of dobutamine on mesenteric, renal, and femoral perfusion. Twenty-one dogs were anesthetized with pentobarbital and paralyzed. Cardiac output was determined by thermodilution, whole body oxygen consumption (VO2) by indirect calorimetry, and regional blood flow by electromagnetic flow probes. Gut tonometry was also assessed. After 2 mg/kg endotoxin administration, the dogs were randomized to receive fluids (to achieve a pulmonary artery balloon-occluded pressure around 10 mm Hg) either alone (n= 7) or combined with a dobutamine infusion at a rate of 5 μg/kg·min (n= 7) or 10 μg/kg·min (n= 7). After fluid resuscitation, cardiac index increased (from 57 ± 28 to 258 ± 112 ml/kg·min,P< 0.001) but then slightly decreased with time in the control group, but further increased (to 436 ± 85 ml/kg·min,P< 0.001) and remained elevated in the dobutamine-treated animals. Whole body oxygen delivery (DO2) followed a similar course. Whole bodyVO2increased after endotoxin and fluid resuscitation (from 4.9 ± 1.3 to 6.3 ± 1.1 ml/kg·min,P< 0.01), especially in the dobutamine-treated animals (to 6.7 ± 2.1 ml/kg·min,P< 0.01). MesentericDO2increased after fluid administration (from 11.6 ± 6.7 to 56.3 ± 31.9 ml/min,P< 0.01) and further increased with dobutamine (to 91.7 ± 42.5 ml/min,P< 0.01). It decreased with time in all groups. MesentericVO2remained unchanged but gastric intramucosal pH (pHi) continuously decreased with time in the control group (from 7.41 ± 0.24 to 6.80 ± 0.17,P< 0.01) while dobutamine prevented the decrease in pHi(7.08 ± 0.29). RenalDO2and renalVO2decreased with time slightly and similarly in the three groups (from 34.8 ± 13.8 to 22.9 ± 10 ml/min and 4.0 ± 1.6 to 2.8 ± 1.0 ml/min, respectively) but urine output increased only in the dobutamine-treated animals (from 2.0 ± 1.5 to 6.9 ± 7.0 ml/min,P< 0.01). FemoralDO2decreased with time in the control groups but increased in the dobutamine-treated animals. FemoralVO2remained stable. No statistical differences were found between 5 and 10 μg/kg·min dobutamine. In this hyperdynamic endotoxic shock model, administration of a limited dose of dobutamine could be useful to increase mesenteric blood flow and urine output.