What is the recommended terlipressin (glypressin) infusion dose for an adult patient with liver cirrhosis and acute variceal bleeding?

Terlipressin Infusion Dose for Acute Variceal Bleeding

For adults with cirrhosis and acute variceal bleeding, administer terlipressin 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled, then reduce to 1 mg IV every 4 hours for a total treatment duration of 2-5 days. 1, 2, 3

Initial Phase Dosing (First 48 Hours)

• Start with 2 mg IV every 4 hours immediately when variceal bleeding is suspected, even before endoscopic confirmation 1, 2, 3
• This higher initial dose is critical for achieving rapid hemodynamic response and portal pressure reduction 3
• A single 2 mg dose acutely decreases hepatic venous pressure gradient from 22.2 to 19.1 mmHg 1
• Continue this dose until bleeding is controlled, typically within the first 48 hours 1, 2

Maintenance Phase Dosing

• Reduce to 1 mg IV every 4 hours once hemorrhage is controlled 1, 2, 3
• Continue maintenance dosing for a total treatment duration of 2-5 days 1, 2, 3

Treatment Duration Considerations

• For Child-Pugh class A or B patients with no active bleeding during endoscopy: Consider shortening treatment to 2 days 1, 2
• For Child-Pugh class C patients, active bleeding during endoscopy, or high MELD score (>19): Continue treatment for up to 5 days 2
• The incidence of adverse effects increases with longer duration (24.32% with 5 days vs 10.8% with 2 days) 2

Alternative: Continuous Infusion Approach

While the standard bolus regimen above is guideline-recommended, emerging evidence supports continuous infusion as a potentially superior alternative:

• Continuous infusion at 4 mg/24 hours is more effective than bolus administration in reducing hepatic venous pressure gradient (85.4% vs 58.2% response rate at 24 hours) 4
• This approach uses significantly lower total doses (4.25 mg vs 7.42 mg per 24 hours) with fewer adverse events (36.3% vs 56.4%) 4
• However, data for continuous infusion in variceal bleeding remain limited, and bolus administration remains the standard guideline-recommended approach 1

Mandatory Combination Therapy

Terlipressin should never be used as monotherapy 2, 3. The standard approach requires three simultaneous components:

• Vasoactive therapy (terlipressin) started immediately 2, 3
• Endoscopic band ligation performed within 12 hours 2, 3
• Prophylactic antibiotics (ceftriaxone 1 g IV daily for up to 7 days) 2, 3

This combination achieves 77% five-day hemostasis versus only 58% with endoscopy alone 2

Absolute Contraindications

Do not administer terlipressin in patients with:

• Hypoxia or worsening respiratory symptoms 2, 3
• Ongoing coronary, peripheral, or mesenteric ischemia 2, 3
• Oxygen saturation <90% 2

Common Adverse Effects

• Terlipressin increases adverse events 2.39-fold compared to octreotide 1, 2, 3
• Common side effects include abdominal pain, chest pain, diarrhea, hyponatremia, nausea, and respiratory failure 1, 2, 3
• Monitor closely for cardiovascular complications, particularly in patients with underlying cardiac disease 1

Clinical Pearls

• Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality (RR 0.66,95% CI 0.49-0.88) 2, 3
• Stop terlipressin if endoscopy reveals non-variceal upper gastrointestinal bleeding, as vasoactive drugs are not expected to work in other causes 1
• For high-risk patients (Child-Pugh C score 10-13 or Child-Pugh B with active bleeding despite therapy), consider early TIPS placement 2, 3
• Use a restrictive transfusion strategy with hemoglobin threshold of 7 g/dL and target of 7-9 g/dL 2