Effects of Clonidine on the Cardiovascular, Renal, and Inflammatory Responses to Experimental Bacteremia. Issue 3 (March 2019)

• Record Type: Journal Article
• Authors: Calzavacca, Paolo; Booth, Lindsea C.; Lankadeva, Yugeesh R.; Bailey, Simon R.; Burrell, Louise M.; Bailey, Michael; Bellomo, Rinaldo; May, Clive N.
• Is Part Of: Shock. Volume 51:Issue 3(2019)
• Publication Date: 2019-03
• Subjects: Acute kidney injury -- alpha2-adrenoceptor agonist -- cardiac output -- cytokine -- renal blood flow -- renal function; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000001134
• Languages: English
• ISSNs: 1073-2322

Abstract

ABSTRACT: 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 < 0.001). Conclusions: In hyperdynamic, hypotensive sepsis, the effects of clonidine at clinically relevant doses are complex and dose dependent. HCDC attenuated sepsis-related increases in heart rate and cardiac output, with little effect on arterial pressure. It also induced a water diuresis, increased AVP, reduced body temperature, and had an anti-inflammatory action. Low-dose clonidine had similar but less pronounced effects, except that it induced moderate vasodilatation and increased cardiac output.