Reuters Health Information (2013-03-06): Midodrine and clonidine helpful in cirrhotic ascites
Midodrine and clonidine helpful in cirrhotic ascites
Last Updated: 2013-03-06 15:10:05 -0400 (Reuters Health)
NEW YORK (Reuters Health) - A pilot study suggests that either midodrine or clonidine along with standard medical therapy will improve hemodynamics in patients with cirrhosis and refractory ascites.
The Indian researchers who studied the two drugs reported their findings online February 19 in The American Journal of Gastroenterology.
Dr. Virendra Singh of the Postgraduate Institute of Medical Education and Research, Chandigarh told Reuters Health by email that splanchnic arterial vasodilatation -- and the subsequent activation of antinatriuretic and vasoconstrictive mechanisms -- have an important role in cirrhotic ascites.
Vasopressors, including midodrine, "have been used for control of ascites in patients with refractory or recurrent ascites," Dr. Singh said. "Clonidine, a centrally acting sympatholytic, with diuretics also showed better control of ascites."
Dr. Singh also pointed out that by acting at different sites, vasoconstrictors and sympatholytics "in combination may reverse some of the pathogenic events that result in increased renal sodium retention and refractoriness to diuretic therapy."
To investigate further, the team randomized 15 patients to clonidine, 15 to midodrine and 15 to the agents in combination. All received standard medical therapy and a further 15 patients who received standard medical therapy alone acted as controls.
At one month, cardiac output decreased significantly in all groups compared to controls. Systemic vascular resistance increased significantly in the midodrine and combination group. It did not change in the clonidine group and there was a significant drop in the controls.
Urinary sodium excretion, and urinary output, were significantly increased in the midodrine, clonidine, and combination groups after treatment, but not in controls.
Plasma renin activity significantly decreased at one month, as did plasma aldosterone concentrations, in all of the drug treatment groups but not in controls.
Compared to standard therapy alone, midodrine monotherapy and midodrine plus clonidine showed superior control over ascites. There was only a trend toward a significant effect with clonidine alone.
There was no change in glomerular filtration rate and model for end-stage liver disease score. There were four deaths at one month. One patient in the control group died of gastrointestinal bleeding; one patient in each treatment group died of sepsis.
The researchers conclude that the two agents alone or in combination along with standard therapy are superior to standard therapy alone. However, "combination therapy was not superior to midodrine or clonidine alone."
Dr. Singh says "a larger randomized trial is warranted."
Commenting on the findings, Dr. Andres Cardenas of the University of Barcelona told Reuters Health by email, "Although provocative and interesting, the study is small, was not a double-blind placebo controlled trial, and the medication was administered for only one month."
"More studies from other centers confirming the efficacy and safety of clonidine/midodrine need to be carried out before considering these drugs as standard therapeutic agents for patients with refractory ascites," he said.
Am J Gastroenterol 2013.