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 (DO(2)I) 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 μg kg(-1)min(-1 )and was increased to 5 and 10 μg 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)), DO(2)I (577 ± 68 versus 1,150 ± 50 ml min(-1 )m(-2)) and mixed-venous oxygen saturation (S(v)O(2); 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)), DO(2)I (1323 ± 102 versus 633 ± 61 ml min(-1 )m(-2)) and S(v)O(2 )(72.2 ± 1.7% versus 56.5 ± 2.0%, all p < 0.001 at dobutamine 10 μg 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.