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|Title:||Effects of Clonidine on the Cardiovascular, Renal and Inflammatory Responses to Experimental Bacteremia.|
|Authors:||Calzavacca, Paolo;Booth, Lindsea C;Lankadeva, Yugeesh R;Bailey, Simon R;Burrell, Louise M;Bailey, Michael;Bellomo, Rinaldo;May, Clive N|
|Affiliation:||Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia|
School of Medicine, University of Melbourne, Parkville, Victoria, Australia
Department of Anaesthesia and Intensive Care, ASST Melegnano e della Martesana, PO Uboldo, Cernusco sul Naviglio, Italy
Faculty of Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
|Citation:||Shock (Augusta, Ga.) 2018; online first: 27 February|
|Abstract:||Supra-clinical doses of clonidine appear beneficial in experimental sepsis, but there is limited understanding of the effects of clonidine at clinically relevant doses. In conscious sheep, with implanted renal and pulmonary artery flow probes, sepsis was induced by infusion of live Escherichia coli. At 24 hours, 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 hours. 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). 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.|
|Appears in Collections:||Journal articles|
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