Sunday, August 7, 2011

Midodrine Controls Ascites, Improves Survival in Cirrhotic Patients

NEW YORK (Reuters Health) Aug 04 - The alpha1-adrenergic agonist midodrine improves ascites control and may also reduce mortality, a new pilot study suggests.

Current options for treating ascites include serial paracentesis, liver transplantation, transjugular intrahepatic portosystemic shunting, and peritoneovenous shunting.

In their report of the new study, Dr. Virendra Singh and colleagues from the Postgraduate Institute of Medical Education & Research in Chandigarh, India, say "it is possible that vasoconstrictors may reverse some of the pathogenic events that result in increased renal sodium retention and refractoriness to diuretic therapy" in cirrhotic patients with ascites.

As reported in the Journal of Hepatology online July 11th, they randomly assigned 40 patients to standard medical therapy or standard medical therapy plus midodrine for six months. Twenty-eight had tense ascites that recurred at least three times in the course of 12 months despite standard treatment, and the other 12 had ascites that could not be mobilized or would return early despite a sodium-restricted diet and diuretic treatment.

All patients had stable renal function.

Standard therapy consisted of a sodium-restricted diet, furosemide, spironolactone, and large-volume paracentesis with intravenous albumin as required. Patients in the midodrine group received 7.5 mg of the drug every eight hours.

At one month, patients in the midodrine group showed an increase in mean arterial pressure, while the standard medical therapy group did not. Urinary volume and urine sodium excretion also increased significantly in patients on midodrine, but not in the control group.

Patients in the midodrine group also showed significant reductions in plasma renin activity and plasma aldosterone concentrations after one month on the drug, while patients on medical therapy alone did not.

Model for end-stage liver disease (MELD) score increased at one, three and six months for patients in the standard medical therapy group but did not change from baseline in the midodrine group.

Patients in the midodrine group survived for a median of one year, while median survival was 90 days for the control group. During follow-up, eight patients in the midodrine group and 15 in the control group died; a Kaplan-Meier survival curve showed that mortality was significantly higher in the standard medical therapy group.

"The results...suggest that long-term midodrine plus standard medical therapy improves systemic hemodynamics and better controls ascites without any renal or hepatic dysfunction in nonazotemic patients with refractory or recurrent ascites with cirrhosis as compared to standard medical therapy alone," the researchers conclude.


J Hepatol 2011.

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