Is continuous infusion of terlipressin (vasopressin analogue) preferred over bolus administration in managing acute variceal bleeding?

Continuous Infusion of Terlipressin is Preferred Over Bolus Administration for Acute Variceal Bleeding

Continuous infusion of terlipressin is more effective than intermittent bolus injections in reducing portal pressure and controlling acute variceal bleeding, with fewer adverse events and at lower total daily doses. 1

Evidence for Continuous Infusion vs. Bolus Administration

Efficacy

• Continuous infusion of terlipressin demonstrates superior hepatic venous pressure gradient (HVPG) response compared to bolus administration:

  • 85.4% vs. 58.2% HVPG response at 24 hours (p=0.002) 1
  • 71.5% vs. 49.1% early HVPG response at 12 hours (p<0.01) 1

• Significantly lower rebleeding rates with continuous infusion:

  • 1.8% vs. 14.5% very early rebleeding (p=0.03) 1
  • 4.7% vs. 20.7% treatment failure rate (p=0.02) 2

Safety Profile

• Continuous infusion requires lower total daily doses:

  • 4.25 ± 1.26 mg vs. 7.42 ± 1.42 mg/24h with bolus administration (p<0.001) 1
  • Fewer adverse events: 36.3% vs. 56.4% (p=0.03) 1

• Common adverse events with terlipressin include:

  • Abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea 3
  • Hyponatremia, myocardial ischemia, and hypoxemia 4

Dosing Recommendations

Continuous Infusion Protocol

• Initial 1 mg IV bolus followed by continuous infusion of 4 mg/24h 2
• HVPG-tailored dosing may further optimize outcomes 1

Traditional Bolus Protocol

• Initial 2 mg IV every 4 hours for the first 48 hours
• Followed by 1 mg IV every 4 hours for an additional 3-5 days 4

Important Considerations and Caveats

Contraindications

• Terlipressin is contraindicated in patients with:
  • Hypoxemia (SpO₂ <90%)
  • Worsening respiratory symptoms
  • Ongoing coronary, peripheral, or mesenteric ischemia 3, 4

Monitoring Requirements

• Continuous pulse oximetry to monitor for hypoxia
• Regular monitoring of serum sodium levels
• Vigilance for signs of cardiac ischemia 4

Treatment Duration

• Standard duration is 5 days
• Shorter course (24-72 hours) may be considered in selected patients with:
  • Child-Pugh A or B cirrhosis
  • No active bleeding during endoscopy 4

Predictors of Treatment Response

• Baseline HVPG (OR 1.90,95% CI=1.25-2.89, p=0.002)
• MELD score (OR 1.18,95% CI=0.99-1.41, p=0.05) 1
• Continuous infusion of terlipressin (OR=0.18,95% CI=0.037-0.91, p=0.04) 2

Alternative Vasoactive Agents

• Octreotide is recommended as the vasoactive drug of choice by the American Gastroenterological Association based on its safety profile 3
• Terlipressin has been shown to reduce mortality compared to placebo (RR 0.66,95% CI 0.49-0.88) 5
• No significant difference in mortality has been demonstrated between terlipressin and somatostatin 5

While octreotide is recommended as the first-line agent in the US due to its safety profile, when terlipressin is used for acute variceal bleeding, the evidence strongly supports continuous infusion over bolus administration for improved efficacy and safety.