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Midodrine and Clonidine in Patients With Cirrhosis and Refractory or Recurrent Ascites: A Randomized Pilot Study

Singh, Virendra MD, DM, FASGE1; Singh, Ajay MD2; Singh, Baljinder MSc, PhD3; Vijayvergiya, Rajesh MD, DM4; Sharma, Navneet MD2; Ghai, Anchal MSc3; Bhalla, Ashish MD2

American Journal of Gastroenterology: April 2013 - Volume 108 - Issue 4 - p 560–567
doi: 10.1038/ajg.2013.9
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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.

1 Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

2 Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

3 Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

4 Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence: Virendra Singh, MD, DM, FASGE, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India. E-mail: virendrasingh100@hotmail.com

Received 6 August 2012; accepted 1 January 2013

published online 19 February 2013

© The American College of Gastroenterology 2013. All Rights Reserved.
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