Elsevier

Journal of Hepatology

Volume 56, Issue 2, February 2012, Pages 348-354
Journal of Hepatology

Research Article
Midodrine in patients with cirrhosis and refractory or recurrent ascites: A randomized pilot study

https://doi.org/10.1016/j.jhep.2011.04.027Get rights and content

Background & Aims

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.

Methods

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.

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 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.

Conclusions

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.

Introduction

Ascites is the most common complication of cirrhosis. Refractory ascites develops in approximately 5–10% of all cases of ascites and 50% of such patients die within 6 months of its development [1]. Portal hypertension and splanchnic vasodilatation are major factors in the development of ascites [2], [3]. Splanchnic arterial vasodilatation causes more marked arterial underfilling and the sodium retaining mechanisms become permanently activated [4]. The therapeutic options available for patients with refractory ascites are serial therapeutic paracentesis, liver transplantation, transjugular intrahepatic portosystemic shunt (TIPS), and peritoneovenous shunt [5], [6], [7], [8], [9]. Several studies have evaluated the efficacy of various vasopressors in patients with hepatorenal syndrome (HRS) [10], [11], [12], [13]. Vasopressors have also been used for the prevention of post-paracentesis circulatory dysfunction with variable results [14], [15], [16], [17], [18]. Recently, various vasoconstrictors have been used in nonazotemic cirrhotic patients with ascites and showed an improvement in circulatory and renal function and sodium excretion [19], [20], [21]. Midodrine, an oral α1-adrenergic agonist along with octreotide and albumin, has been shown to better control ascites in a short term pilot study in patients with refractory ascites [22]. There are no reports of long term use of midodrine in patients with cirrhosis and ascites. Therefore, we plan to study the role of long term administration of midodrine in patients with cirrhosis with refractory or recurrent ascites in a pilot study.

Section snippets

Materials and methods

A total of 59 patients with cirrhosis and refractory or recurrent ascites were evaluated for inclusion in the study between December 2007 and June 2009. Nineteen of 59 screened patients were excluded during the screening period for various reasons (spontaneous bacterial peritonitis in 6, encephalopathy in 6, acute renal failure in 3, hepatorenal syndrome in 1, and gastrointestinal bleeding in 3 patients). Therefore, 40 patients with cirrhosis and refractory or recurrent ascites [23] with stable

Results

The demographic profile, clinical and laboratory parameters were similar between standard medical therapy and midodrine groups (Table 1). Twenty-eight patients had recurrent and 12 refractory ascites. Four patients did not respond to sodium-restricted diet and high-dose diuretic treatment. Eight patients stopped these medications due to side-effects. Baseline body weight did not differ significantly between two groups (p = 0.658). In both treatment groups, no significant difference in weight was

Discussion

Splanchnic vasodilation plays a major role in the development of ascites and hepatorenal syndrome. The therapeutic options available for patients with refractory ascites are serial therapeutic paracentesis, TIPS, peritoneovenous shunts, and liver transplantation. Currently, the first line approach to refractory ascites is serial LVP up to every 2 weeks. Vasopressors have been used in patients with HRS [10], [11], [12], [13] as well as for the prevention of post-paracentesis circulatory

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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