Interest of the association clonidine-spironolactone in cirrhotic patients with ascites and activation of sympathetic nervous system

Background : The aim of this study was to examine the effects of spironolactone, clonidine and the association of clonidine-spirono- lactone on renin-aldosterone and sympathetic systems, renal func- tion, systemic hemodynamics and mobilization of ascites in 32 alcoholic cirrhotic patients with marked increase in sympa- thetic system. Methods : Measurements were taken before and after an 8-day treatment with spironolactone (200 mg/day), after an 8-day treat- ment with clonidine (0.150 mg/day) and 10 days after adjunction of spironolactone (200 mg/day) to clonidine. Results: Three patients abandoned the treatment or were excluded because lack of compliance. Spironolactone alone induced an increase in renin-aldosterone and sympathetic systems without any remarkable increase of natriuresis and body weight loss. Given for 8 days, clonidine alone induced a significant decrea- se in plasma norepinephrine associated with a significant increase in glomerular filtration rate without effect on natriuresis. In con- trast, 10 days after adjunction of spironolactone to clonidine, plas- ma renin and aldosterone significantly decreased, natriuresis increased (from 7.4 ± 0.7 to 41.6 ± 3.2 mEq/24h) and body weight decreased (from 66.03 ± 2.3 to 63.5 ± 2.3 kg) without adverse effects. Conclusion : In cirrhotic patients with ascites and marked acti- vation of sympathetic nervous system, spironolactone (200 mg/day) is unable to mobilize ascites. In these patients, after 8 days, clonidine decreases sympathetic activity, increases glome- rular filtration rate and after 18 days, decreases plasma renin and aldosterone concentrations allowing a better action of spironolac- tone. The association clonidine-spironolactone enhances natriure- sis and body weight loss. (Acta gastroenterol. belg., 2002, 65, 1-5).