What is the recommended dose of terlipressin (vasopressin analogue) for upper gastrointestinal (UGI) bleeding?

Terlipressin Dosing for Upper Gastrointestinal Bleeding

For acute variceal hemorrhage, start terlipressin at 2 mg IV every 4 hours for the first 48 hours, then reduce to 1 mg IV every 4 hours, continuing for a total duration of 2-5 days. 1, 2

Initial Dosing Phase (First 48 Hours)

• Administer 2 mg IV every 4 hours until bleeding is controlled 1, 2, 3
• Start terlipressin immediately when variceal bleeding is suspected, even before diagnostic endoscopy is performed 1, 3
• This higher initial dose is critical for achieving rapid portal pressure reduction—a single 2 mg dose acutely decreases hepatic venous pressure gradient from 22.2 to 19.1 mmHg 2

Maintenance Dosing Phase

• 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 from initiation 1, 2
• For patients with poor response, the maintenance dose can be increased back to 2 mg IV every 4 hours 3

Duration Considerations

The optimal duration remains somewhat flexible based on clinical context:

• Standard duration is 2-5 days to prevent early rebleeding 1
• Shorter 2-day courses may be reasonable in selected Child-Pugh class A and B patients with no active bleeding identified during endoscopy 1
• Research supports that 24-hour courses can be as effective as 72-hour courses when used as adjunct to successful endoscopic variceal ligation, though this shorter duration is not yet guideline-endorsed 4, 5

Critical Adjunctive Therapy Requirements

Terlipressin is never used alone:

• Combine with prophylactic antibiotics: ceftriaxone 1 g IV daily for up to 7 days (preferred in advanced cirrhosis or quinolone-resistant settings) 1, 3
• Perform endoscopic variceal ligation within 12 hours of presentation 1, 3
• Administer IV albumin: 1 g/kg on day 1 (maximum 100 g), then 20-40 g/day thereafter 1
• Maintain restrictive transfusion strategy: hemoglobin threshold of 7 g/dL with target range 7-9 g/dL 1

Safety Profile and Contraindications

While terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality (RR 0.66,95% CI 0.49-0.88) 2, it carries significant adverse event risk:

• Adverse events increase 2.39-fold compared to octreotide, including abdominal pain, chest pain, diarrhea, and hyponatremia 1, 2
• Absolute contraindications: hypoxia, worsening respiratory symptoms, ongoing coronary/peripheral/mesenteric ischemia, oxygen saturation <90% 2, 3
• Recent evidence suggests octreotide may be preferred based on safety profile, with similar efficacy but fewer complications 1

High-Risk Patient Considerations

For patients at highest risk of treatment failure:

• Consider early TIPS placement (within 72 hours) for Child-Pugh C score 10-13 or Child-Pugh B with active bleeding despite vasoactive therapy 1, 2, 3
• Patients with MELD-Na score elevation have higher treatment failure rates and may benefit from continuous infusion rather than intermittent boluses 6

Alternative Administration Route

Emerging evidence suggests continuous infusion (1 mg IV bolus followed by 4 mg over 24 hours) may reduce treatment failure rates compared to intermittent boluses (4.7% vs 20.7%, p=0.02), though this is not yet guideline-endorsed 6