What is the recommended dose of propranolol (beta blocker) for managing oesophageal varices?

Propranolol Dosing for Oesophageal Varices

Start propranolol at 20-40 mg orally twice daily and titrate every 2-3 days to achieve a resting heart rate of 55-60 beats per minute, with a maximum dose of 320 mg/day in patients without ascites or 160 mg/day in patients with ascites. 1

Initial Dosing Strategy

• Begin with 20-40 mg twice daily (or 40 mg once daily as an alternative starting point) and increase progressively based on heart rate response 1, 2
• The therapeutic goal is to achieve a resting heart rate of 55-60 beats per minute or a 25% reduction from baseline 1, 3
• Maintain systolic blood pressure ≥90 mm Hg throughout titration 1, 4

Titration Protocol

• Adjust dose every 2-3 days until the treatment goal is achieved 1, 4
• The median effective dose in clinical trials was 80-100 mg/day, though individual requirements vary 5, 6
• Long-acting formulations at 80 or 160 mg daily can be used once stable dosing is established to improve compliance 2, 4

Maximum Dose Considerations

Patients WITHOUT Ascites

• Maximum daily dose: 320 mg/day (typically 160 mg twice daily) 1, 3
• This higher dose is permitted due to better hemodynamic stability in compensated cirrhosis 3

Patients WITH Ascites

• Maximum daily dose: 160 mg/day (typically 80 mg twice daily) 1, 3
• The reduced maximum reflects increased risk of hemodynamic compromise in decompensated cirrhosis 2, 3

Patients with Refractory Ascites

• Consider limiting to 80 mg/day for safety 2, 4
• Close monitoring of blood pressure and renal function is essential in this population 2

Monitoring Requirements

• Heart rate and blood pressure should be checked at each visit to guide dose adjustments 3
• In decompensated disease, monitor serum creatinine and sodium: reduce or discontinue if creatinine exceeds 1.5 mg/dL or sodium falls below 130 mmol/L 4
• Patients on propranolol for primary prophylaxis do not require serial endoscopic surveillance 1

Therapeutic Goals and Mechanism

• The ideal hemodynamic target is reducing hepatic venous pressure gradient (HVPG) to <12 mm Hg or achieving a ≥20% reduction from baseline 1, 4
• Since HVPG measurement is not widely available, heart rate reduction serves as a practical surrogate endpoint 1
• Propranolol works through β1-mediated reduction in cardiac output and β2-mediated splanchnic vasoconstriction, thereby reducing portal blood flow 1

Common Pitfalls and Side Effects

• Approximately 15% of patients require dose adjustment or discontinuation due to side effects including dizziness, fatigue, dyspnea, bradycardia, and hypotension 3
• Never abruptly discontinue propranolol, as this increases risk of variceal bleeding and mortality 4, 3
• If discontinuation is necessary, transition to endoscopic variceal ligation (EVL) first, or prefer dose reduction over complete cessation 4, 3

Alternative Therapies

• Endoscopic variceal ligation (EVL) is the first-line alternative if propranolol is contraindicated or not tolerated, performed every 2-8 weeks until variceal eradication 1, 3
• Carvedilol (starting at 6.25 mg once daily, increasing to 6.25 mg twice daily after 3 days, maximum 12.5 mg/day) is an alternative that may be more effective in propranolol non-responders 1, 7
• Isosorbide mononitrate (20 mg twice daily) is a second-line option when neither propranolol nor EVL can be used, though it is less effective 2, 4

Contraindications

• Absolute contraindications include asthma, severe COPD, heart block, significant bradycardia, hypotension, and decompensated heart failure 2

Duration of Therapy

• Prophylactic therapy should be continued indefinitely, as discontinuation leads to recurrence of bleeding risk 1