Role of Terlipressin in Managing Refractory Ascites in Cirrhosis
Terlipressin is not currently recommended as a primary treatment for refractory ascites in cirrhosis, but may have a beneficial role as adjunctive therapy in selected patients, particularly those with concurrent hepatorenal syndrome. 1
Current Evidence for Terlipressin in Refractory Ascites
Primary Treatment Approaches
Refractory ascites in cirrhosis is primarily managed through:
- Maximum diuretic therapy
- Albumin administration
- Large volume paracentesis
- TIPS (transjugular intrahepatic portosystemic shunt) in selected cases
Terlipressin's Mechanism in Ascites
Terlipressin works by:
- Causing vasoconstriction of the splanchnic vascular bed
- Increasing mean arterial pressure
- Improving renal perfusion and glomerular filtration rate
- Potentially enhancing sodium excretion
Specific Clinical Scenarios Where Terlipressin May Be Beneficial
1. Refractory Ascites with Hepatorenal Syndrome (HRS)
When refractory ascites is complicated by HRS-AKI (acute kidney injury):
- Terlipressin combined with albumin is the most effective pharmacological treatment 1
- Dosing: 1 mg every 4-6 hours, increased to maximum 2 mg/4-6 hours if no reduction in serum creatinine by 25% after 3 days 1
- Treatment duration: Until serum creatinine decreases below 1.5 mg/dl 1
- Response rate: 40-50% of patients 1
2. Prevention of Paracentesis-Induced Circulatory Dysfunction
- Terlipressin may help prevent circulatory dysfunction after large volume paracentesis 2
- This is achieved by increasing mean arterial pressure and systemic vascular resistance 2
3. Refractory Ascites Without HRS
Limited evidence suggests potential benefit:
- One study showed synergistic effect when terlipressin was added to albumin plus diuretics in refractory ascites 3
- Complete response was observed in 16/26 patients with refractory ascites 3
- May improve hemodynamics by decreasing heart rate and cardiac output while increasing mean arterial pressure 2
Important Monitoring and Safety Considerations
Adverse Effects to Monitor
Cardiovascular complications (12% of patients) 1:
- Angina
- Arrhythmias
- Digital ischemia
Respiratory complications (8-30% of patients) 1:
- Pulmonary edema
- Respiratory failure, especially in patients with:
- ACLF-3 (acute-on-chronic liver failure grade 3)
- Baseline hypoxemia
- Higher mean arterial pressure at baseline
Gastrointestinal effects 1:
- Abdominal pain
- Diarrhea (due to increased intestinal motility)
Contraindications
- Known ischemic conditions
- Severe cardiovascular disease
- Caution in patients with cardiac failure or underlying respiratory conditions 1
Predictors of Response to Terlipressin
Better outcomes are associated with:
- Serum bilirubin ≤10 mg/dL 1
- Serum creatinine ≤5 mg/dL 1
- Increase in mean arterial pressure ≥5 mmHg with treatment 1
- Lower grades of acute-on-chronic liver failure 1
Administration Considerations
- Standard regimen: 1 mg IV every 4-6 hours for up to 14 days 1
- Alternative: Continuous infusion (starting at 2 mg/day, increased to maximum 12 mg/day) may achieve similar efficacy with lower total daily dose and fewer side effects 1
- Albumin co-administration: 1 g/kg on day 1, followed by 40 g/day 1
- Monitoring: Close observation for pulmonary edema, especially in patients with cirrhotic cardiomyopathy 1
Conclusion for Clinical Practice
While terlipressin is well-established for HRS treatment, its routine use for refractory ascites without HRS remains investigational. The strongest evidence supports its use in patients with refractory ascites complicated by HRS, where it significantly improves renal function and may enhance survival in responders. For patients with refractory ascites without HRS, terlipressin may be considered as an adjunctive therapy when standard treatments have failed, but more robust evidence is needed before it can be recommended as standard care.