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Midodrine, clonidine improve ascites control in patients with cirrhosis

Patients with cirrhosis and ascites treated with standard care and midodrine, clonidine or both therapies experienced improvement to hemodynamics and ascites control compared with standard care alone in a recent pilot study.

Researchers prospectively evaluated 60 patients with cirrhosis and refractory or recurrent ascites randomly assigned to 1 month of standard medical therapy (SMT) or 0.1 mg oral clonidine every 12 hours, 7.5 mg oral midodrine every 8 hours, or both treatments, in addition to SMT (n=15 patients each). Blood pressure, heart rate, systemic vascular resistance and cardiac output were measured, liver and renal function tests were performed, and blood samples were collected at baseline and after 1 month.

Following treatment, patients in the midodrine and midodrine/clonidine combination groups experienced better ascites control than patients who only received SMT (P=.05). The clonidine group also trended toward better control compared with SMT (P=.1). Complications and mortality occurred at similar rates across groups.

Mean arterial pressure increased significantly in the midodrine and midodrine/clonidine combination groups, but decreased significantly in the clonidine and SMT groups. All groups, excluding SMT alone, experienced significant decreases in plasma renin activity and cardiac output. Systemic vascular resistance increased significantly in the midodrine and combination groups, but not the clonidine group, and a decrease was observed among those who received SMT alone. Urine output and sodium excretion increased across all groups, but the difference was not statistically significant in the SMT alone group. Serum sodium values increased significantly among the combination group.

No significant changes from baseline were observed for MELD score, serum creatinine levels or glomerular filtration rate in any of the groups.

“The results of this randomized pilot study 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 in patients with refractory or recurrent ascites with cirrhosis,” the researchers concluded. “However, the combination therapy was not superior to midodrine or clonidine alone. A larger randomized trial is warranted.”