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

ArticleinLiver international: official journal of the International Association for the Study of the Liver 29(2):169-74 · June 2008with13 Reads
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.
    • "This small volume resuscitation is advantageous in type 1 HRS patients because they already carry a large fluid load and substantial fluid infusion could potentially lead to worsening of ascites, pleural effusion or heart failure [52, 53] . In addition, albumin administration to cirrhotic patients with ascites has been shown to result in markedly reduced plasma renin activity, aldosterone levels and muscle sympathetic nerve activity in a number of patient types with ascites545556. Since the endogenous albumin of patients with decompensated cirrhosis is not only present at reduced levels, but also is functionally impaired [57], the many functions key to homeostasis that albumin performs are likely to be compromised. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes. Methods: Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose. Results: Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5 % (95 % confidence interval, 40.0-59.1 %). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95 % confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95 % confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2 % (95 % confidence interval, 36.4-51.3 %), 51.4 % (95 % confidence interval, 46.3-57.1 %) and 59.0 % (95 % confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period. Conclusions: This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.
    Full-text · Article · Nov 2015
    • "Analogues act on the abundant V1 receptors in the splanchnic vasculature, causing greater vasoconstrictive effects in the mesenteric circulation than in renal or other vascular systems. In retrospective studies, as well as in small prospective pilot studies, it has been demonstrated that prolonged use of an ornipressin [33,34] , terlipressin3536373839404142434445464748 or α-agonist vasoconstrictor (midodrine plus octreotide, noradrenaline alone)4950515253545556 in association with human albumin is capable of recovering renal function in 40%-60% of patients with type 1 HRS. The use of ornipressin was, however, abandoned because of its high rate of ischemic side effects. "
    [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.
    Article · Sep 2012
    • "Titrate to achieve a 10 mm Hg increase in MAP from baseline or MAP > 70 mmHg Noradrenaline [69,77,80] 0.5 to 3.0 mg/hour (continuous infusion). Titrate to achieve a 10 mmHg increase in MAP Midodrine + Octreotide828384858687 Midodrine: 7.5 to 12.5 mg orally three times. Titrate to achieve a 15 mm Hg increase in MAP from baseline Octreotide:100 to 200 μg subcutaneously three times daily or 25 μg bolus, followed by intravenous infusion of 25 μg/ hour MAP: mean arterial pressure Nadim et al. "
    [Show abstract] [Hide abstract] ABSTRACT: Renal dysfunction is a common complication in patients with end-stage cirrhosis. Since the original publication of the definition and diagnostic criteria for the hepatorenal syndrome (HRS), there have been major advances in our understanding of its pathogenesis. The prognosis of patients with cirrhosis who develop HRS remains poor, with a median survival without liver transplantation of less than six months. However, a number of pharmacological and other therapeutic strategies have now become available which offer the ability to prevent or treat renal dysfunction more effectively in this setting. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. We undertook a systematic review of the literature using Medline, PubMed and Web of Science, data provided by the Scientific Registry of Transplant Recipients and the bibliographies of key reviews. We determined a list of key questions and convened a two-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. Of the 30 questions considered, we found inadequate evidence for the majority of questions and our recommendations were mainly based on expert opinion. There was insufficient evidence to grade three questions, but we were able to develop a consensus definition for acute kidney injury in patients with cirrhosis and provide consensus recommendations for future investigations to address key areas of uncertainty. Despite a paucity of sufficiently powered prospectively randomized trials, we were able to establish an evidence-based appraisal of this field and develop a set of consensus recommendations to standardize care and direct further research for patients with cirrhosis and renal dysfunction.
    Full-text · Article · Feb 2012
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