What is the recommended dose of propranolol (beta-blocker) for esophageal varices?

Propranolol Dosing for Esophageal Varices

For primary prophylaxis of variceal bleeding, 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 and increase the dose every 2-3 days based on heart rate response and blood pressure tolerance 1
• The therapeutic goal is to reduce resting heart rate to 55-60 beats per minute or achieve a 25% reduction from baseline 1, 2
• Systolic blood pressure must be maintained ≥90 mmHg throughout titration 1

Maximum Dose Considerations

Patients Without Ascites

• Maximum daily dose: 320 mg/day (typically given as 160 mg twice daily) 1
• These patients can tolerate higher doses due to better hemodynamic stability 1

Patients With Ascites

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

Patients With Refractory Ascites

• Consider limiting to 80 mg/day total for safety 3, 4
• Recent evidence suggests low-dose propranolol (80 mg/day) in patients with spontaneous bacterial peritonitis is associated with improved survival 3
• Close monitoring of blood pressure and renal function is essential in this population 1, 4

Practical Titration Protocol

1. Start at 20-40 mg twice daily 1
2. Check heart rate and blood pressure after 2-3 days 1
3. Increase by 20 mg/day (10 mg per dose) if heart rate remains >60 bpm and systolic BP >90 mmHg 1, 5
4. Continue titration until target heart rate of 55-60 bpm is achieved or maximum dose is reached 1
5. Monitor for side effects at each dose adjustment, including dizziness, fatigue, dyspnea, and erectile dysfunction 1

Alternative Formulations

• Long-acting propranolol (80-160 mg once daily) can be used once stable dosing is established to improve compliance 3, 6
• The long-acting formulation should only be initiated after determining the appropriate total daily dose with immediate-release propranolol 3

Monitoring Requirements

Essential Parameters

• Heart rate at each visit to guide dose adjustments 1, 6
• Blood pressure at each visit, maintaining systolic BP ≥90 mmHg 1, 3
• Serum creatinine and sodium in decompensated patients, with dose reduction if creatinine exceeds 1.5 mg/dL or sodium falls below 130 mmol/L 3

No Endoscopic Surveillance Required

• Patients on propranolol for primary prophylaxis do not require serial endoscopic monitoring 1
• This is a key advantage over endoscopic variceal ligation, which requires repeated procedures 1

Common Pitfalls and Contraindications

Absolute Contraindications

• Sinus bradycardia, second- or third-degree atrioventricular heart block 1, 6
• Severe chronic obstructive pulmonary disease or asthma 1, 6
• Decompensated heart failure 1, 6
• Peripheral arterial insufficiency 1

Relative Contraindications

• Insulin-dependent diabetes mellitus (increased risk of masking hypoglycemia) 1
• Aortic valve disease 1

Side Effects Requiring Dose Adjustment or Discontinuation

• Approximately 15% of patients experience side effects severe enough to require dose reduction 1
• Another 15% have contraindications to therapy 1
• Common side effects include dizziness, fatigue, general weakness, dyspnea, headache, hypotension, bradycardia, and erectile dysfunction 1

When Propranolol Cannot Be Used

First-Line Alternative

• Endoscopic variceal ligation (EVL) is recommended if propranolol is contraindicated or not tolerated 1, 6
• EVL should be performed every 2-8 weeks until variceal eradication 1

Important Caveat About Discontinuation

• Never abruptly discontinue propranolol as this increases the risk of variceal bleeding and mortality 1, 3, 4
• If propranolol must be stopped, transition to EVL before discontinuation 1, 4
• Dose reduction is strongly preferred over complete discontinuation when possible 3

Evidence Quality Note

The dosing recommendations are consistent across multiple high-quality guidelines, including the 2017 American Association for the Study of Liver Diseases (AASLD) guidelines 1 and the 2020 Korean Association for the Study of the Liver (KASL) guidelines 1. The evidence demonstrates that propranolol effectively prevents first variceal hemorrhage 7, 2, though it does not improve overall survival 2. The dose-dependent effect plateaus around 80-120 mg/day, with higher doses offering no additional hemodynamic benefit but increased intolerance 5.