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Fasolato, Silvano (2008) Terapia diuretica combinata "Ab Initio" versus terapia diuretica sequenziale nel trattamento dell'ascite moderata in pazienti con cirrosi epatica senza insufficienza renale. [Ph.D. thesis]

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Abstract (english)

Sequential versus "ab initio" combined diuretic treatment of moderate ascites in cirrhotic patients: preliminary results of a randomized controlled multicenter clinical study.
Background: the most rational treatment of cirrhotic patients with moderate ascites is a stepwise sequential therapy with increasing oral doses of an aldosterone antagonist. If no response occurs at the maximum dosage of the aldosterone antagonist (400mg/day), furosemide is added at increasing oral doses in a stewise way up to 160 mg/day (sequential diuretic treatment). Nevetheless, the onset of response following a sequential diuretic trreatment of ascites may requires to much time.
Aim of the study: as a consequence, the aim of the study was to compare sequential diuretic therapy with a schedule combining "ab initio" aldosterone antagonist and furosemide in the treatment of moderate ascites in nonazotemic cirrhotic patients.
Material and method: sixty-eight nonazotemic cirrhotic patients with moderate ascites wererandomly assigned to be treated by sequential diuretic treatment (Group A, n°=37) or by "ab initio" combined diuretic treatment (Group B, n°=31). In patients of Group A, potassium kanrenoate was used at the initial dosage of 200 mg/day (1st step) and if no response was obtained, it was peaked to 400 mg/day (2nd step). In nonresponders to 400 mg/day of potassium kanrenoate, furosemide was added at the initial dosage of 50 mg b.i.d. (3rd step) eventually inceasing to 100 mg/day b.i.d. (4th step) and then up to 150 mg/day b.i.d. (common step). Patients of Group B received 200 mg/day of potassium kanrenoate and 50 mg b.i.d. of furosemide as 1st step. If no response was observed the dosages of potassium kanrenoate and furosemide were increased to 400 mg/day and 100 mg b.i.d. (2nd step) and then up to 400 mg/day and 150 mg b.i.d., respectively (3rd step).No response was defined as a three-day weight loss lower than 600 gr.
Outcome: the response rate was similar in both groups (88 % in Group A vs 96 % in Group B, p= N.S.). The patients's rate that need to change the effective diuretic step for diureticinduced complications was significantly lower in Group B (20%) than in Group A (38%) (p <0,05). The mean time to mobilize ascites was shorter in patients of Group B than in patients of Group A (15.5 ±,9 vs 20.7 ±1.1 days, respectively, p = 0.001). Even excluding the time which was necessary to reach the effective diuretic regimen (5.0 ± 0.3 giorni nel gruppo B vs 6.0 ± 0.4 giorni nel gruppo A, p < 0.05) the mean time for the mobilization of ascites was greater in Group A than in Group B 10.6 ± 0.7 giorni nel Gruppo B vs 14,5 ± 1,0 giorni nel Gruppo A, p < 0.003). The multivariate analysis identified PRA value as predictive factor to develop adverse effects, indipendently from the type of diuretic treatment particularly when this value is > 10.2 ug/ml.
Conclusions. "ab initio" combined diuretic treatment by means of potassium kanrenoate and furosemide makes it possible to shorten the time to mobilize moderate ascites in nonazotemic cirrhotic patients if comared to a sequential diuretic treatment. Thus, it appears the more suitable and cost-effective diuretic treatment schedule in these patients. Moreover, the probability to develop diuretic-induced adverse effects is correlated with basal value of plasma renin activity (PRA).

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EPrint type:Ph.D. thesis
Tutor:Merkel, Carlo
Ph.D. course:Ciclo 20 > Scuole per il 20simo ciclo > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > EPATOLOGIA
Data di deposito della tesi:2008
Anno di Pubblicazione:2008
Key Words:Cirrhosis - Ascites - Diuretic therapyc - Potassium Kanrenoate - Furosemide - Hyponatremia - Plasma renin activity
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/09 Medicina interna
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Medicina Clinica e Sperimentale
Codice ID:774
Depositato il:08 Oct 2008
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