Ascites in liver cirrhosis is explained by increased production of vasoactive substances,
such as nitric oxide, carbon monoxide, and endocannabinoids, which cause splanchnic
vasodilatation, increased blood flow through this area, and a decrease in peripheral vascular
resistance and the effective arterial volume with resulting reduction in renal blood flow
with subsequent activation of rennin-angiotensin-aldosterone system which in turn leads to
renal vasoconstriction and salt and water retention. The retained water then accumulates in
the peritoneal cavity under the effect of portal hypertension and low albumin.
The International Ascites Club defines refractory ascites as ascites that cannot be mobilized
or prevented from early recurrence after large-volume paracentesis despite medical therapy
and dietary sodium restriction.
There are two varieties of refractory ascites: diuretic-resistant ascites that is
unresponsive to the maximal tolerable dose of diuretic therapy and diuretic-intractable
ascites when complications such as hepatic encephalopathy, renal dysfunction, or electrolyte
abnormalities limit the use of diuretics in the effective therapeutic dose (Cárdenas and
Arroyo, 2005)
The therapeutic options for refractory ascites are serial therapeutic paracentesis,
transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, and liver
transplantation.
Midodrine is transformed into the active metabolite desglymidodrine, which is an α1 receptor
agonist causing an increase in vascular tone and increase in blood pressure without
β-adrenergic receptors stimulation so, it can improve systemic and renal hemodynamics in
non-azotemic cirrhotic patients by counteracting mesenteric vasodilatation, which is
accentuated in cirrhosis. It diffuses poorly across the blood-brain barrier with no central
effects.
In a study included 600 adult patients with refractory ascites, midodrine was added to
diuretic therapy and lead to enhancement of diuresis with the improvement of systemic, renal
hemodynamics and short-term survival. Approximately, the only use of midodrine hydrochloride
in children was in postural orthostatic tachycardia syndrome (POTS) which showed a good
efficacy and safety profile.