Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia.

INTRODUCTION: Arginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO2I) in an established model of ovine endotoxemia. METHODS: Twenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 +/- 1.5 kg (mean +/- SEM)) were randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 microg kg-1min-1 and was increased to 5 and 10 microg kg-1 min-1 after 30 and 60 minutes, respectively. RESULTS: AVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 +/- 0.5 versus 8.2 +/- 0.3 l min-1 m-2), DO2I (577 +/- 68 versus 1,150 +/- 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5 +/- 1.8% versus 69.4 +/- 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 +/- 0.7 l min-1 m-2 versus 4.4 +/- 0.5 l min-1 m-2), DO2I (1323 +/- 102 versus 633 +/- 61 ml min-1 m-2) and SvO2 (72.2 +/- 1.7% versus 56.5 +/- 2.0%, all p < 0.001 at dobutamine 10 microg kg-1 min-1 versus AVP group) and further increased MAP. CONCLUSION: This study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.

Dopexamine reverses the vasopressin-associated impairment in tissue oxygen supply but decreases systemic blood pressure in ovine endotoxemia.

Since arginine vasopressin (AVP) may reduce cardiac output and, in proportion, oxygen delivery, we studied the efficacy of dopexamine (DPX) as an adjunct to AVP infusion. After 1 h of continuous AVP infusion (0.04 U/min) in healthy sheep (n = 7), DPX was additionally administered in incremental doses (1, 5, and 10 microg. kg(-1). min(-1); each dose for 30 min). After a 24-h period of recovery, endotoxin was continuously infused in the same sheep to induce and maintain a hypotensive/hyperdynamic circulation. After 16 h of endotoxemia, AVP and DPX were given as described previously. AVP infusion increased systemic vascular resistance index and decreased cardiac index in both healthy and endotoxemic conditions (P < 0.001 each). This was accompanied by an augmented pulmonary vascular resistance index in endotoxemia (159 +/- 13 dynes. cm(-5). m(-2) versus 202 +/- 16 dynes. cm(-5). m(-2)) and a decrease in oxygen delivery index (health: 842 +/- 66 mL. min(-2). m(-2) versus 475 +/- 38 mL. min(-2). m(-2); endotoxemia: 1073 +/- 49 mL. min(-2). m(-2) versus 613 +/- 44 mL. min(-2). m(-2)) and mixed venous oxygen content (health: 63% +/- 2% versus 47% +/- 2%; endotoxemia: 68% +/- 2% versus 51% +/- 3%; P < 0.001 each). Small doses of DPX (1 and 5 microg. kg(-1). min(-1)) improved not only the AVP-associated depressions in cardiac index, oxygen delivery index, and mixed venous oxygen content, but also the pulmonary vasopressive effect in both groups. While large-dose DPX (10 microg. kg(-1). min(-1)) also reduced mean pulmonary arterial pressure in endotoxemia (27 +/- 1 mm Hg versus 23 +/- 1 mm Hg; P < 0.05 versus baseline), mean arterial blood pressure decreased (105 +/- 4 mm Hg versus 80 +/- 3 mm Hg) and heart rate increased (84 +/- 4 bpm versus 136 +/- 9 bpm; P < 0.001 versus AVP alone), thereby limiting its therapeutic use.