The effect of 1 month of therapy with midodrine, octreotide-LAR and albumin in refractory ascites: A pilot study

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Liver international: official journal of the International Association for the Study of the Liver (Impact Factor: 4.85). 06/2008; 29(2):169-74. DOI: 10.1111/j.1478-3231.2008.01778.x
Source: PubMed


The pathogenesis of refractory ascites (RA) is linked to splanchnic vasodilation. We hypothesized that a combination of midodrine, octreotide long-acting release (LAR) and albumin would result in increased natriuresis, better control of ascites and an improvement in renal function in patients with RA+/-Type 2 hepatorenal syndrome.
A prospective pilot study in patients with RA as defined by the International Ascites Club. Consecutive patients received an intramuscular injection of octreotide-LAR, 50 g of albumin three times per week and midodrine titrated to increase the systolic blood pressure for 1 month.
Ten patients with RA were enrolled and eight with complete data to 1 month post-treatment were included in the analysis. There was no change in renal function but there was a trend towards a reduction in the volume of ascites removed by paracentesis (P=0.08) and a significant reduction in the plasma renin (P=0.01) and aldosterone concentrations (P=0.01). Interestingly, there was a transient worsening in the model for end-stage liver disease (MELD) score (P=0.01). The deterioration in MELD was completely reversible after discontinuation of therapy.
To our knowledge, this is the first study of prolonged midodrine, octreotide and albumin therapy in RA. We observed a significant reduction in the plasma renin and aldosterone concentrations and a trend towards a reduction in the volume of ascites removed by paracentesis without an effect on renal function. The beneficial effects are at the expense of a reversible deterioration in the MELD score. Large controlled trials are needed before this therapy can be routinely recommended.

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    • "Earlier studies evaluating midodrine [20] or midodrine plus octreotide [19] in nonazotemic cirrhotics did not show a significant change in hepatic function. However, in a recent pilot study, there was a significant deterioration in the MELD score during treatment with midodrine [22]. "
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    ABSTRACT: Splanchnic arterial vasodilatation plays an important role in cirrhotic ascites. The aim of this study was to evaluate the effects of long term administration of midodrine on systemic hemodynamics, renal function, and control of ascites in patients with cirrhosis and refractory or recurrent ascites. Forty cirrhotic patients with refractory or recurrent ascites were prospectively studied after long term administration of midodrine plus standard medical therapy (n=20) or standard medical therapy alone (n=20) in a randomized controlled trial at a tertiary centre. A significant increase in urinary volume, urinary sodium excretion, mean arterial pressure, and decrease in plasma renin activity (p<0.05) was noted after 1 month of midodrine administration. There was also a significant decrease in cardiac output and an increase in systemic vascular resistance after midodrine therapy at 3 months (p<0.05). There was no change in glomerular filtration rate and model for end-stage liver disease (MELD) score. Midodrine plus standard medical therapy was significantly superior to standard medical therapy alone in the control of ascites (p=0.013) at 3 months. The mortality rate in the standard medical therapy group was significantly higher than the midodrine group (p<0.046). There was no significant difference in the frequency of various complications at the end of follow-up. The results of this randomized pilot study suggest that midodrine plus standard medical therapy improves the systemic hemodynamics without any renal or hepatic dysfunction in these patients and is superior to standard medical therapy alone for the control of ascites.
    Full-text · Article · Jul 2011 · Journal of Hepatology
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    ABSTRACT: Some patients with ascites due to liver cirrhosis become no longer responsive to diuretics. Once other causes of ascites such as portal vein thrombosis, malignancy or infection and non-compliance with medications and low sodium diet have been excluded, the diagnosis of refractory ascites can be made based on strict criteria. Patients with refractory ascites have very poor prognosis and therefore referral for consideration for liver transplantation should be initiated. Search for reversible components of the underlying liver pathology should be undertaken and targeted therapy, when available, should be considered. Currently, serial large volume paracentesis (LVP) and transjugular intrahepatic portasystemic stent-shunt (TIPS) are the two mainstay treatment options for refractory ascites. Other treatment options are available but not widely used either because they carry high morbidity and mortality (most surgical options) rates, or are new interventions that have shown promise but still need further evaluation. In this comprehensive review, we describe the evaluation and management of patients with refractory ascites from the prospective of the practicing physician.
    Preview · Article · Feb 2009 · World Journal of Gastroenterology
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    ABSTRACT: The development of ascites indicates a pathological imbalance between the production and resorption of intraperitoneal fluid. The appearance and composition of ascites are variable, based on the underlying pathophysiology. Most commonly, ascites develops in the setting of decompensated cirrhosis, peritoneal infection, carcinomatosis, congestive heart failure or a combination (mixed ascites). The diagnosis can be difficult in some patients. Management options for ascites from decompensated liver disease focus on low-sodium diets and diuretics supplemented by large-volume paracentesis, transvenous intrahepatic portosystemic shunts and liver transplantation. The development of refractory ascites, hepatic hydrothorax, hyponatraemia or hepatorenal syndrome presents unique challenges to the provider and the patient. In some of these patients, therapy with liver transplantation will be the only viable therapeutic option. The diagnosis of infectious ascites, such as tuberculosis, and carcinomatous ascites remain diagnostic and therapeutic challenges for the clinician.
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