▪ Objective: To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of Clonidine on such disturbances.
▪ Design: Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous Clonidine in the cirrhotic patients.
▪ Patients: Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls.
▪ Interventions: Intravenous clonidine.
▪ Main Outcome Measures: Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function.
▪ Main Results: In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% Cl, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; Cl, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; Cl, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 µg/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation.
▪ Conclusions: The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.