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.