Comparative study of spironolactone and eplerenone in management of ascites in patients of cirrhosis of liver.

INTRODUCTION: The present study was conducted to compare the efficacy and side effects of Spironolactone and Eplerenone in management of ascites due to liver cirrhosis. MATERIALS AND METHODS: 105 patients of ascites with liver cirrhosis were randomized into three groups of 35 patients each. Group I was given Spironolactone 100 mg, group II was given Eplerenone 100 mg and group III was given Eplerenone 50 mg. All patients were put on salt-restricted diet (less than or equal to 2 g of sodium) and no loop diuretics were used. Patients were followed after 7 days from the baseline and then biweekly for the period of three months and serial measurements of weight, abdominal girth and incidence of side effects especially gynecomastia, mastalgia, hyperkalemia were recorded. Results were compared. Patients having Child-Turcotte-Pugh score-C, massive ascites, hepatic encephalopathy, Hepatorenal syndrome and ascites due to cardiac, renal, malignant causes were excluded. OBSERVATIONS: Difference in mean weight reduction was non significant (P = 0.964) in group I and group II whereas the difference was significant when comparison was made between Group I and III; and Group II and III (P = <0.001, <0.001, respectively). In group I, the incidence of gynecomastia was 14.28% whereas in group II and group III no case of gynecomastia was observed (P <0.001, <0.001). Hyperkalemia was present in one patient (2.8%) in group I whereas no patient developed hyperkalemia in group II and group III (P = >0.05, >0.05). CONCLUSION: Eplerenone and spironolactone are equally effective in management of ascites due to liver cirrhosis but side effect profile of eplerenone scores over Spironolactone.

Sodium restriction in patients with cirrhotic ascites: a protocol for a systematic review.

BACKGROUND: Avid renal sodium and water retention among other mechanisms produce ascites in patients with cirrhosis. The main guidelines recommend sodium intake reduction in order to counteract this complication. However, some randomized controlled trials have suggested a lack of benefit with a sodium-restricted over an unrestricted diet, and even an increase in ascites and renal complications has been reported. There are no systematic reviews addressing this question. METHODS: A systematic review protocol has been designed and will be reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for randomized controlled trials evaluating a salt-restricted versus unrestricted regime in patients with cirrhosis and ascites in EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. We will also try to identify literature by reviewing reference list of included studies and relevant reviews, screening main conference proceedings, and searching for unpublished and ongoing trials in the World Health Organization (WHO) International Clinical Trials Registry Platform. Two researchers will independently undertake selection of studies, data extraction, and assessment of the quality of included studies. We will estimate pooled risk ratios for dichotomous data and the mean difference or standardized mean difference for continuous outcomes. A random effect model will be used for meta-analyses. Data synthesis and other analyses will be conducted using RevMan software. ETHICS AND DISSEMINATION: no ethics approval is considered necessary. Results of this study will be disseminated via peer-reviewed publications and social networks DISCUSSION: Sodium restriction is a widely accepted coadjuvant therapy for ascites; however, this indication is based primarily on expert recommendations. As far as we know, this will be the first systematic review assessing the effects of a sodium-restricted diet for ascites in cirrhotic patients. Our systematic review will aim to provide a high-quality synthesis of current evidence for patients and clinicians about this question. The main limitation might result from the reduced number and quality of primary studies available. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015022161.

Adherence to a moderate sodium restriction diet in outpatients with cirrhosis and ascites: a real-life cross-sectional study.

BACKGROUND & AIMS: A moderate sodium restriction diet should be indicated in patients with cirrhosis and ascites. Nevertheless, there is a lack of specific investigation on its correct application. To evaluate the adherence of patients with cirrhosis and ascites to a moderately low-salt diet and the impact on intake of total calories and serum sodium concentration. METHODS: A total of 120 outpatients with cirrhosis and ascites were interviewed with a pre-established questionnaire. A quantitative assessment of nutrient and salt intake was performed. RESULT: A moderately low-salt diet was followed by 37 patients (Group A). Of the 83 patients who did not follow the diet (Group B), 54 thought that they were following it. The mean daily sodium intake was 79.5 ± 5.5 mmol/day (Group A) and 205.9 ± 14.1 mmol/day (Group B), P < 0.0001. The adherence to diet was related to the severity of cirrhosis, and was higher among candidates for liver transplantation and in patients followed through the Care Management Program. Patients of Group A had reduced the mean daily calorie intake by 20% compared with Group B patients (P < 0.0005), while there was no difference on the occurrence of hyponatraemia. CONCLUSIONS: This study shows a poor adherence of patients with cirrhosis and ascites to a moderate dietary sodium restriction. Adherence to a diet seems to increase with the worsening of liver disease, probably because of the reduction of alternative therapeutic options. In addition, a deficiency in the educational process can lead the patient to follow a sodium-reduced diet by means of dangerous tools, such as reducing the overall daily food intake.

[Influence of non-sodium restricted diet with diuretics on plasma rennin, renal blood flow and in patients with cirrhotic ascites].

OBJECTIVE: To explore influence of sodium restricted diet and non-sodium restricted diet on plasma rennin (PRA), angiotensin II (All), ALD, renal blood flow (RBF) and subside of ascites in patients with cirrhotic ascites. METHODS: Eighty cases of hepatitis B with cirrhotic ascites were randomly divided into sodium restricted diet group and non-sodium restricted diet group. 39 cases were in non-sodium restricted diet group, taking sodium chloride 6500-8000 mg daily; 41 cases were in sodium restricted diet group, taking sodium chloride 5000 mg daily. Both groups received diuretics furosemide and spironolactone. Blood sodium, urine sodium, PRA, AII, ALD, RBF ascites subsiding were compared after treatment. RESULTS: In non-sodium restricted diet group, blood sodium and urine sodium increased 10 days after treatment compared with those before treatment, and compared with those of sodium restricted diet group 10 days after treatment, P <0. 01. RBF increased compared with that before treatment, and compared with that of sodium restricted diet group 10 days after treatment, P < 0. 01. Renal damage induced by low blood sodium after treatment was less in non-sodium restricted diet group than that in sodium restricted diet group, P <0. 05. Ascites disappearance upon discharge was more in sodium restricted diet group than that in non-sodium restricted diet group, P <0. 01. Time of ascites disappearance was shorter in non-sodium restricted diet group than that in sodium restricted diet group, P < 0. 01. CONCLUSION: Compared with sodium restricted diet, while using diuretics of both groups, non-sodium restricted diet can increase level of blood sodium, thus increasing excretion of urine sodium and diuretic effect. It can also decrease levels of PRA, AII and ALD, increase renal blood flow and prevent renal damage induced by low blood sodium and facilitate subsiding of ascites.

Spot urinary sodium for assessing dietary sodium restriction in cirrhotic ascites.

AIM: To evaluate the accuracy of spot urinary Na/K and Na/creatinine (Cr) ratios as an alternative to 24-h urinary sodium in monitoring dietary compliance in patients with liver cirrhosis and ascites treated with diuretics. METHODS: The study was carried on 40 patients with liver cirrhosis and ascites treated with diuretic therapy. Patients were divided into two groups according to 24-h urinary sodium. We measured spot urine Na/K ratio, Na/Cr ratio and 24-h urinary sodium. Student's t test was used to compare the interval variables and chi(2) test to compare the nominal variables between the two groups. Receiver operator characteristic curve was used to identify the best cutoff point for Na/K and Na/Cr ratio. RESULTS: The best cutoff point for Na/K ratio was 2.5 (P < 0.001) and area under the curve (AUC) was 0.9, and for Na/Cr ratio, the best cutoff point was 35 (P < 0.001) and AUC was 0.885. Na/K ratio showed higher sensitivity and accuracy compared to Na/Cr ratio (87.5% and 87% for Na/K ratio; 81% and 85% for Na/Cr ratio, respectively). CONCLUSION: Spot urine Na/K ratio has adequate accuracy for assessment of dietary sodium restriction compared with 24-h urinary sodium in patients with liver cirrhosis and ascites.

Microprocessor-controlled iontophoretic drug delivery of 5-fluorouracil: pharmacodynamic and pharmacokinetic study.

PURPOSE: The purpose of this study was to fabricate monolithic 5-fluorouracil (5-FU) transdermal patch with microprocessor- controlled iontophoretic delivery, to evaluate the pharmacodynamic effects on Dalton's lymphoma ascites (DLA) induced in Balb/c mice, and to study pharmacokinetics in rabbits. MATERIALS AND METHODS: The transdermal patches were prepared by solvent casting method; a reprogrammable microprocessor was developed and connected to the patches. DLA cells were injected to the hind limb of Balb/c mice (10 animals/group). In the first group of mice 5-FU was administered i.v. (12 mg/kg). In the second group of mice, transdermal patches (20 mg/patch/animal) were installed and kept for 10 consecutive days, while the third (control) group was kept without any treatment. The tumor diameter was measured every 5th day for 30 days, and the animal survival time and death pattern were studied. The electric current density protocol of 0.5 mA/cm(2) for 30 min was used in the pharmacokinetic study in rabbits. RESULTS: There was a significant reduction in tumor volume in the animals treated with monolithic matrix 5-FU transdermal patch compared to untreated controls and i.v. therapy. Tumor volume of the control animals was 5.8 cm(3) on the 30th day, while in 5-FU with transdermal patch delivery animals it was only 0.23 cm(3) (p <0.05). DLA cells tumor-bearing mice treated with 5-FU with transdermal patch had significantly increased lifespan (ILS). Control animals survived only 21+/-1 days after the tumor inoculation, while i.v. 5-FU and 5-FU patches animals survived 24+/-2.7 days and 39.5+/-1.87 days with ILS of 25.58% and 88.09%, respectively (p <0.01). There was significant sustained release of 5-FU through microprocessor-controlled patches and half-life was significantly higher (p <0.05) compared to the i.v. route. CONCLUSION: Cytotoxic concentration of 5-FU can be achieved through the transdermal drug delivery and effective therapeutic drug concentration can be maintained up to 24 h, with less toxicity. A new generation of transdermal drug delivery systems based on microprocessor-controlled iontophoresis is in the late stages of development and promises to enhance the treatment of local and systemic medical conditions. The incorporation of microprocessor into these systems has been an important advancement to ensure safe and efficient administration of a wide variety of drugs.

La restricción de sal a los cirróticos españoles es demasiado rigurosa / Sodium restriction for Spanish cirrhotics is too severe

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Ascites: medical therapy and paracentesis.

An overview is given of diagnostic determinations to be carried out on ascites fluid, and on the medical therapy as based on our knowledge of the pathophysiology. Paracentesis has become more frequently used. It is slightly more effective than therapy with high doses of diuretics and carries less side effects. Longterm studies are needed to investigate whether albumin can be safely substituted by dextran-70 or haemaccel.

[Diet therapy in acute and chronic liver diseases]. / Ernährungstherapie bei akuten und chronischen Lebererkrankungen.

Nutrition is an essential part of the therapy of patients with acute and chronic liver diseases. Special recommendations are given for patients with ascites, hepatorenal syndrome, encephalopathy, liver failure and secondary diabetes. Nutrition is an essential treatment in patients with hepatic encephalopathy. In acute liver failure, parenteral nutrition is basic for the restoration of homeostasis. This article provides detailed recommendations for nutrient supply for patients with acute and chronic liver diseases.

Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content.

In order to clarify debated issues of the medical treatment of ascites in cirrhosis--the usefulness of a low sodium diet and washout period preceding diuretic administration, maximal dosage of antimineralocorticoid to be reached before the addition of a loop diuretic, identifications of factors influencing treatment efficacy--115 hospitalized patients with non-azotemic cirrhosis and ascites were recruited and randomized to receive a diet providing either 40 or 120 mmol of sodium daily. After a washout period from the outpatient diuretic regimen for 7 days (Step 1), increasing dosages of K-canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing spontaneous diuresis (Step 2). Upon the failure of Step 2, K-canrenoate (400 mg/day) and furosemide at increasing dosage (25-50-100 mg every other day) were given (Step 3). Nine percent of patients underwent spontaneous diuresis, and 77% developed a negative sodium balance by the end of Step 2 (69% with a dosage of K-canrenoate < or = 400 mg/day) and 93% by the end of Step 3. Two patients were withdrawn from the protocol due to diuretic side-effects. Univariate analysis showed that the type of diet did not influence the response to treatment. The washout period led to a significant increase in endogenous creatinine clearance; natremia significantly rose in hyponatremic patients. Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascitis. Fisiopatología y tratamiento

Cirrhosis of the liver is the main cause of ascitis. Recent studies have shown in compensated cirrhotics a 40 percent chance to develop ascitis after five years of follow up. The presence of ascitis is usually associated with advanced liver disease, and higher mortality than patients with compensated cirrhosis. Many theories have been proposed to explain ascitis formation being the most important the presence of portal hypertension and sodium retention. Extravascular fluid accumulation depends directly of a balance between hydrostatic and colloid-osmotic pressure (Starling law). Hepatic sinusoids differ from splanchnic ones in regard to the presence of fenestrae, that allows albumin and other substances to flow freely from the sinusoid to the extravascular space. For these reasons the sinusoids lacks colloid-osmotic pressure, and the hydrostatic pressure regulates the flow of fluids passing through them. In cirrhosis, diffuse fibrosis and nodule formation cause functional obstruction to the hepatic blood flow, and a secondary increase in the sinusoidal pressure, that leads to exit of fluids from the sinusoids to the hepatic lymphatics and the thoracic duct. When the amount of fluid that leaves the sinusoids exceeds the capacity of the thoracic duct, fluids accumulate in the abdominal cvity (ascitis). A new theory about ascitis formation states that the first event is a diffuse peripheral arterial vasodilation that cause ineffective plasma volume that triggers the production of humoral factors directed to retain sodium in the kidney...

Prophylactic and therapeutic treatment of ascites in broiler chickens.

1. This work examined the effect of using three different feeding regimens in the prophylaxis and treatment of ascites in fastgrowing broilers stressed by exposure to cold (less than 10 degrees C), itself a potent inducer of ascites. 2. Broilers were exposed to cold in tiered cages in a semi-open poultry shed from the age of 24, 29 or 34 d and from day 35 they were given one of three types of food (pellets, pellets with high energy content, mash). Total mortality and mortality with ascites were recorded and erythrocyte packed cell volume (PCV) and relative weight of the right ventricle were measured (both reliable indices of ascites development). 3. Despite relatively low ambient temperatures and consequent high mortality from ascites, the mash diet was effective both in preventing ascites (prophylaxis) and in treating existing ascites.

[Use of diuretics in the treatment of ascites in patients with cirrhosis]. / Emploi des diurétiques dans le traitement de l'ascite chez les cirrhotiques.

The cirrhotic patient with ascites has an increased tubular reabsorption of sodium. Diuretic therapy allows an urinary loss of sodium. The strongest diuretics which inhibit sodium reabsorption in the ascending limb of the loop of Henle (like furosemide) are not the most effective in cirrhotic patients; indeed the increased load of sodium arriving in the distal part of the tubule is reabsorbed because of hyperaldosteronism. Potassium-sparing diuretics, like spironolactone, which act beyond the sites of reabsorption of most of the filtered sodium, are mostly effective when combined with other diuretics which impair sodium reabsorption more proximally. We propose to treat ascites by: 1. Sodium restriction (maximum: 60 mmol per day); 2. Spironolactone 100 to 500 mg per day, combined with furosemide 40 to 200 mg per day if spironolactone does not induce a natriuretic effect.