Midodrine and Albumin in Patients With Refractory Ascites

Refractory ascites is seen in 5-10% of patients with cirrhosis.Decompensated cirrhosis with refractory ascites has a mortality rate of around 40% in a year and a median survival of 6 months.Portal hypertension and splanchnic vasodilation are major factors in the development of ascites.The treatment of refractory ascites involves salt restriction, diuretics, large volume paracentesis (LVP), transjugular Intrahepatic Portosystemic shunt (TIPS) and Liver Transplantation (LT). Currently the only curative treatment is LT. However, LT is limited due to organ shortage and high cost. Long-term human albumin (HA) administration in patients with uncomplicated and refractory ascites, has shown to improve survival or delay the complications of cirrhosis. Midodrine, an oral α1- adrenergic agonist has been used in refractory ascites with variable results. However, there is no study on the use of long term Midodrine and HA in patients with refractory ascites. Therefore, we plan to study the effect of long term midodrine and HA in patients with refractory ascites.

Human albumin will be administered by intravenous infusion at a dose of 1.5 gm/kg/week for 2 weeks followed by HA 40 grams every 7days

SMT will include nutritional support, rifaximin, lactulose or lactitol, diuretics, SBP prophylaxis with norfloxacin, restriction of sodium, multivitamins, and other supportive measures as deemed necessary. LVP will be done as needed. Patients on non-selective beta blockers will continue to do so with dose modifications/withdrawal as per Baveno VI guidelines.

Control of ascites will be defined as- Complete response will be total absence of ascites. Partial response as presence of ascites not requiring paracentesis Non response will be defined as persistence of severe ascites requiring paracentesis.

Change in estimated glomerular filtration rate (eGFR) measured by modified diet in renal disease 6 (MDRD6) formula at 3 months intervals

Change in MELD score. The MELD score incorporates the variables of serum bilirubin, creatinine and Internation Normalised Ratio (INR). Higher MELD score indicates worse prognosis

The diagnosis of SBP will be based on neutrophil count in ascitic fluid of >250/mm3 as determined by microscopy and positive ascitic fluid culture or >250 /mm3 with negative culture called as culture negative neutrocytic ascites.20 Other infections will be diagnosed as per CDC criteria.

PICD will be defined as an increase in plasma renin activity (PRA) of >50% of the pre-treatment value to a level > 4ng/ml/hr on 6th day after paracentesis

Change in CTP score. The CTP score incorporates the variables of serum bilirubin, albumin, prothrombin time-INR, grade of ascites and hepatic encephalopathy. The score ranges from 5-15 and a higher score portends a worse prognosis

Inclusion Criteria: Age between 18 and 80 years Refractory ascites in cirrhosis of any etiology Exclusion Criteria: Mixed ascites: cirrhosis plus another cause of ascites Gastrointestinal bleed within 7 days of enrolment. Presence of hepatorenal syndrome Hepatic encephalopathy grade 2 or higher Infection within 1 month preceding the study Cardiovascular disease (ejection fraction < 35% or abnormal ECG) or arterial hypertension (BP > 140/90 mm of Hg) Abnormal urine analysis with proteinuria > 500 mg/24 hour or 50 red blood cells/high power field, or granular casts or ultrasonographic evidence of intrinsic renal disease Presence of hepatocellular carcinoma or portal vein thrombosis Treatment with drug with known effects on systemic and renal hemodynamics within 7 days of inclusion excepting beta-blockers Patient not willing for study. Patient opting for liver transplantation/ transjugular intrahepatic portosystemic shunt