Effects of Clonidine on the Cardiovascular, Renal, and Inflammatory Responses to Experimental Bacteremia

INTRODUCTION:Supra-clinical doses of clonidine appear beneficial in experimental sepsis, but there is limited understanding of the effects of clonidine at clinically relevant doses. METHODS:In conscious sheep, with implanted renal and pulmonary artery flow probes, sepsis was induced by infusion of live Escherichia coli. At 24 h, a high clinical dose of clonidine (HCDC) [1.0 μg/kg/h], a low clinical dose of clonidine (LCDC) [0.25 μg/kg/h] or vehicle, was infused for 8 h. RESULTS:Animals developed hyperdynamic, hypotensive sepsis with acute kidney injury. The HCDC decreased heart rate (153 ± 6 to 119 ± 7 bpm) and cardiac output (5.6 ± 0.4 to 5.0 ± 0.4 L/min), with no reduction in mean arterial pressure (MAP). In contrast, LCDC increased cardiac output with peripheral vasodilatation. Both doses induced a large transient increase in urine output, an increase in plasma osmolality and, with the high dose, an increase in plasma arginine vasopressin. Sepsis increased plasma interleukin-6 (IL-6) and IL-10 and clonidine further increased IL-10 (1.6 ± 0.1 to 3.3 ± 0.7 ng/mL), but not IL-6. Clonidine reduced rectal temperature. During recovery from sepsis, MAP returned to baseline values more rapidly in the HCDC group (P