Sympatho‐inhibition in an Ovine Model of Septic Shock: Cardiovascular and Renal Effects

Abstract

There is evidence that inhibition of the increased sympathetic outflow in sepsis is beneficial, but the mechanisms are unclear. In conscious sheep, at 24 hours of septic shock induced by intravenous infusion of live E. coli, the effect of intravenous infusion of clonidine for 8 hours on cardiovascular and renal function was examined. Administration of E. coli caused hyperdynamic septic shock: hypotension, tachycardia, increased cardiac output, increased renal blood flow, oliguria and decreased glomerular filtration rate. During sepsis, clonidine (1.0 μg/kg/h) reduced cardiac index (from 7.5±0.8 to 5.9±0.5 L/min), heart rate (from 146±9 to 124±8 b/min), but mean arterial pressure did not significantly fall (79±4 vs. 73±5 mmHg). Clonidine reduced renal blood flow (363±9 to 312±30 mL/min) and increased urine output (22±5 to 46±19 mL/h), but did not improve creatinine clearance (42±4 to 29±9 mL/min). In hyperdynamic sepsis, clonidine treatment did not increase the degree of hypotension despite a fall in cardiac output, it increased urine output but did not improve glomerular filtration rate.This research was supported by the NHMRC, Australia.