The effect of 1 month of therapy with midodrine, octreotide-LAR and albumin in refractory ascites: a pilot study.
ABSTRACT 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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ABSTRACT: OBJECTIVES:Splanchnic arterial vasodilatation and subsequent activation of anti-natriuretic and vasoconstrictive mechanisms have an important role in cirrhotic ascites. The aim of this study was to evaluate the effects of midodrine, clonidine, and their combination on systemic hemodynamics, renal function, and control of ascites in patients with cirrhosis and refractory or recurrent ascites.METHODS:Sixty cirrhotic patients with refractory or recurrent ascites were prospectively studied after long-term administration of clonidine (n=15) or midodrine (n=15), or both (n=15) plus standard medical therapy (SMT), or SMT alone (n=15), in a randomized controlled trial at a tertiary center.RESULTS: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. There was also a significant decrease in cardiac output (P<0.05) and increase in systemic vascular resistance (P<0.05) in all groups, except clonidine. There was no change in glomerular filtration rate and model for end-stage liver disease score. Midodrine and a combination of midodrine and clonidine plus SMT were superior to SMT alone in the control of ascites (P=0.05), and there was a trend towards better control of ascites in the clonidine group (P=0.1). The mortality and frequency of various complications were similar in all groups.CONCLUSIONS:These results suggest that midodrine, clonidine, and their combination plus SMT improves the systemic hemodynamics without any renal or hepatic dysfunction, and is superior to SMT alone for the control of ascites. However, the combination therapy was not superior to midodrine or clonidine alone.Am J Gastroenterol advance online publication, 19 February 2013; doi:10.1038/ajg.2013.9.The American Journal of Gastroenterology 02/2013; · 9.21 Impact Factor
Article: Hepatorenal syndrome.[Show abstract] [Hide abstract]
ABSTRACT: Hepatorenal syndrome (HRS) is defined as a functional renal failure in patients with liver disease with portal hypertension and it constitutes the climax of systemic circulatory changes associated with portal hypertension. This term refers to a precisely specified syndrome featuring in particular morphologically intact kidneys, where regulatory mechanisms have minimised glomerular filtration and maximised tubular resorption and urine concentration, which ultimately results in uraemia. The syndrome occurs almost exclusively in patients with ascites. Type 1 HRS develops as a consequence of a severe reduction of effective circulating volume due to both an extreme splanchnic arterial vasodilatation and a reduction of cardiac output. Type 2 HRS is characterised by a stable or slowly progressive renal failure so that its main clinical consequence is not acute renal failure, but refractory ascites, and its impact on prognosis is less negative. Liver transplantation is the most appropriate therapeutic method, nevertheless, only a few patients can receive it. The most suitable "bridge treatments" or treatment for patients ineligible for a liver transplant include terlipressin plus albumin. Terlipressin is at an initial dose of 0.5-1 mg every 4 h by intravenous bolus to 3 mg every 4 h in cases when there is no response. Renal function recovery can be achieved in less than 50% of patients and a considerable decrease in renal function may reoccur even in patients who have been responding to therapy over the short term. Transjugular intrahepatic portosystemic shunt plays only a marginal role in the treatment of HRS.World Journal of Gastroenterology 09/2012; 18(36):4978-84. · 2.43 Impact Factor
Article: Le syndrome hépatorénal[Show abstract] [Hide abstract]
ABSTRACT: There has been a real progress of knowledge about the physiopathology of hepatorenal syndrome (HRS). HRS is closely related to haemodynamic disturbances due to severe hepatic failure. HSR may be prevented and treated based on the correction of physiopathological disturbances. Avoiding nephrotoxic agents and early treatment of hepatic disease complications are critical for HRS prevention. Type-1 HRS are treated by vasopressors, fluid expansion with albumin, and in selected patients by the use of tranjugular intrahepatic portosystemic stent shunt (TIPSS) or extracorporeal renal or hepatic dialysis. In type-2 HRS, the gold standard is ascitis withdrawal associated with albumin infusion. Since HRS is the landmark of a severe and lifetreatening hepatic disease, patients are scheduled for hepatic transplantation when eligible, whatever the type of HRS. Palliative treatment aims to maintain patient status until hepatic transplant is available.Le Praticien en Anesthésie Réanimation 09/2009; 13(4).