Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

Low-dose continuous infusion of terlipressin will be administered to six cirrhotic patients with refractory ascites.

Terlipressin continuous infusion will be adminstered via an ambulatory pump initially for 7 days in a clinical pharmacology unit. Serial blood draws for pharmacokinetic analysis will be performed to determine steady state concentration of both terlipressin and 8-lysine-vasopressin during infusion. After establishing safety and tolerance of infusion for 7 days, patients will be transitioned to an outpatient setting where they will be treated with terlipressin continuous infusion for an additional 21 days, monitored daily by home care nurses.

A total of 6 patients will be treated. Monitoring will include successful management of ascites, with reduction in paracentesis procedures and decreased ascites fluid volume, further supported by improvement in renal function.

Eligibility Criteria:
Inclusion Criteria:

* Patients with cirrhosis and refractory ascites who required 3 or more large volume (4 liters and more) paracenteses in the previous 60 days

Exclusion Criteria:

* Ascites with causes other than cirrhosis such as nephrogenic ascites or malignant ascites due to peritoneal carcinomatosis
* Total bilirubin \> 5 mg/dL
* Blood clotting International normalized ratio (INR) \> 2.5
* Serum creatinine \> 2.0 mg/dL
* Current or recent (within 3 months of consent) renal dialysis
* Hepatic encephalopathy grade 3 or 4
* Superimposed acute liver failure/injury due to factors other than alcoholic hepatitis, including acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom \[Amanita\] poisoning)
* Current or recent treatment (within 7 days) with octreotide, midodrine, vasopressin, dopamine or other vasopressors
* Respiratory failure requiring positive airway pressure devices or intubation
* SIRS/sepsis episode in the previous 28 days from consent
* Episode of spontaneous bacterial peritonitis or gastrointestinal hemorrhage within 28 days of consent
* Ongoing documented or suspected infection
* Severe cardiovascular disease that are contraindication to terlipressin therapy such as advanced arteriosclerosis, arrhythmia, coronary insufficiency or uncontrolled hypertension
* Findings suggestive of organic renal disease (severe proteinuria/hematuria, or abnormal renal ultrasound suggestive of obstructive or other renal pathology)
* Severe comorbidity that in the opinion of the Investigator would affect short-term prognosis and/or disallow safe participation in the trial (such as for example, severe anemia or pancytopenia, advanced neoplasia, hepatocellular carcinoma \[confirmed with serum alpha1-fetoprotein testing\], severe chronic obstructive pulmonary disease or asthma)
* Alcoholics who have not been abstinent for the past 6 months
* Transjugular intrahepatic portosystemic shunt or other surgical shunt
* For female patients: Confirmed pregnancy
* Known allergy or hypersensitivity to terlipressin
* Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of consent.