What drugs are used to treat variceal bleeding?

Pharmacological Management of Variceal Bleeding

For acute variceal bleeding, initiate terlipressin (2 mg IV every 4 hours) or octreotide/somatostatin immediately upon suspicion—even before endoscopy—and continue for 2-5 days in combination with endoscopic therapy and prophylactic antibiotics. 1, 2

Acute Bleeding: First-Line Vasoactive Drugs

Terlipressin is the preferred vasoactive agent because it is the only drug proven to reduce bleeding-related mortality (relative risk 0.66), with superior efficacy compared to other splanchnic vasoconstrictors 2. The dosing regimen is:

• Initial phase: 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled 2
• Maintenance phase: 1 mg IV every 4 hours after initial control 2
• Total duration: 2-5 days, with shorter courses (2 days) acceptable in Child-Pugh A/B patients without active bleeding at endoscopy 2

Alternative vasoactive agents with comparable hemostatic efficacy but without proven mortality benefit include 1, 3:

• Octreotide: 50 μg IV bolus, then 50 μg/hr continuous infusion 2
• Somatostatin: 250 μg IV bolus, then 250 μg/hr continuous infusion 2

A large multicenter trial of 780 patients demonstrated no significant difference in 5-day treatment success between terlipressin (86.2%), somatostatin (83.4%), and octreotide (83.8%), with similar rates of bleeding control, rebleeding, and mortality 3. However, terlipressin remains preferred due to its mortality benefit and longer half-life 2, 4.

Essential Combination Therapy

Vasoactive drugs should never be used as monotherapy. The standard approach requires three simultaneous components 2, 5:

• Vasoactive therapy (terlipressin/octreotide/somatostatin) started immediately
• Endoscopic variceal ligation performed within 12 hours of presentation 1, 2
• Prophylactic antibiotics (ceftriaxone 1 g IV every 24 hours for up to 7 days) 1, 2

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

Drugs to Avoid in Acute Bleeding

Vasopressin alone is not recommended due to significant systemic side effects including mesenteric and myocardial ischemia, reduced cardiac output, and increased peripheral resistance 1. While vasopressin combined with nitroglycerin reduces failure to control bleeding compared to vasopressin alone, it offers no survival benefit and has been superseded by safer alternatives 1.

Beta-blockers must be temporarily suspended during acute bleeding if the patient is hypotensive (systolic BP <90 mmHg or mean arterial pressure <65 mmHg), despite their role in prophylaxis 1, 5.

Prophylaxis: Non-Selective Beta-Blockers

For primary and secondary prophylaxis (not acute bleeding), non-selective beta-blockers are first-line therapy 5:

• Propranolol: Start 20-40 mg orally twice daily, titrate every 2-3 days to target heart rate 55-60 bpm (max 320 mg/day without ascites, 160 mg/day with ascites) 5
• Nadolol: Start 20-40 mg orally once daily, titrate to target heart rate 55-60 bpm (max 160 mg/day without ascites, 80 mg/day with ascites) 5

Beta-blockers reduce portal pressure through decreased cardiac output and splanchnic vasoconstriction, reducing first variceal bleeding risk from 30% to 14% in patients with medium/large varices 5.

Critical Clinical Pearls

• Start vasoactive drugs immediately when variceal bleeding is suspected clinically, before diagnostic endoscopy 1, 2, 6
• Restrictive transfusion strategy: Maintain hemoglobin 7-9 g/dl with transfusion threshold of 7 g/dl 1
• Pre-endoscopy erythromycin (250 mg IV, 30-120 minutes before) improves endoscopic visualization in the absence of QT prolongation 1
• High-risk patients (Child-Pugh C <14 points or Child-Pugh B with active bleeding) should be considered for early pre-emptive TIPS within 24-72 hours 1

Common Pitfalls

Terlipressin has important contraindications including hypoxia, worsening respiratory symptoms, ongoing coronary/peripheral/mesenteric ischemia, and oxygen saturation <90% 2. Common adverse effects include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea, with a 2.39-fold increase in adverse events compared to octreotide 2. The incidence of adverse effects increases with longer treatment duration (24.32% at 5 days vs 10.8% at 2 days) 2.