What is the recommended dosage of propranolol (beta blocker) for patients with liver cirrhosis and portal hypertension?

Propranolol Dosing for Portal Hypertension in Cirrhosis

Start propranolol at 20-40 mg twice daily and titrate every 2-3 days to achieve a resting heart rate of 55-60 bpm or a 25% reduction from baseline, with a maximum dose of 160 mg daily in patients with ascites or 320 mg daily in those without ascites. 1, 2, 3

Initial Dosing Strategy

• Begin with 20-40 mg orally twice daily, with the lower end (20 mg) preferred in patients with severe liver disease (serum albumin <30 g/L) due to impaired drug clearance and risk of excessive plasma concentrations 3, 4
• Initiate therapy in hospital for patients with severe decompensation to monitor for hemodynamic instability 4

Titration Protocol

• Increase the dose every 2-3 days based on heart rate response and blood pressure tolerance 2, 3
• The therapeutic target is a resting heart rate of 55-60 beats per minute or a 25% reduction from baseline, while maintaining systolic blood pressure ≥90 mmHg 1, 2, 3
• The ultimate hemodynamic goal is reducing hepatic venous pressure gradient (HVPG) to <12 mmHg or achieving ≥20% reduction from baseline 1, 2, 5

Maximum Dose Based on Disease Severity

Compensated cirrhosis (no ascites):

• Maximum dose: 320 mg daily (160 mg twice daily) 1, 3
• Long-acting formulations can be used at 160 mg daily once stable dosing is established 1

Decompensated cirrhosis (with ascites):

• Maximum dose: 160 mg daily (80 mg twice daily) 1, 2, 3
• This lower ceiling reflects increased risk of hemodynamic compromise in decompensated disease 2, 3

Refractory ascites:

• Consider limiting to 80 mg daily for safety 1, 2
• Recent evidence suggests this lower dose (80 mg/day) in patients with spontaneous bacterial peritonitis is associated with improved survival 2

Monitoring Requirements

At each visit, monitor:

• Heart rate to guide dose adjustments 1, 3
• Blood pressure, maintaining systolic BP ≥90 mmHg 2, 3
• Serum creatinine and sodium, with dose reduction or discontinuation if creatinine exceeds 1.5 mg/dL or sodium falls below 130 mmol/L 2

Contraindications

Absolute contraindications include: 1

• Asthma
• Severe chronic obstructive pulmonary disease (COPD)
• Heart block
• Significant bradycardia
• Hypotension
• Decompensated heart failure

Common Pitfalls and Side Effects

• Approximately 15% of patients require dose adjustment or discontinuation due to side effects 3
• Most common adverse effects include dizziness (24% in one study), fatigue, general weakness, dyspnea, headache, hypotension, bradycardia, and erectile dysfunction 3, 5
• Never abruptly discontinue propranolol, as this increases risk of variceal bleeding and mortality; prefer dose reduction over complete cessation 2, 3

Alternative Therapies When Propranolol Cannot Be Used

First-line alternative:

• Endoscopic variceal ligation (EVL) performed every 2-8 weeks until variceal eradication 1, 2, 3

Second-line alternative:

• Isosorbide mononitrate 20 mg twice daily, though less effective than propranolol or EVL 1, 2

For propranolol-resistant portal hypertension:

• Consider adding spironolactone 100 mg daily, which can achieve adequate HVPG reduction (≥20%) in combination with propranolol in patients who don't respond to propranolol alone 6

Long-term Management

• Continue propranolol therapy indefinitely, as discontinuation increases risk of variceal bleeding and mortality 1
• Long-acting formulations (80-160 mg daily) can improve compliance once stable dosing is established 1, 2
• The mean effective dose in clinical studies was approximately 154 mg daily when titrated to target heart rate 5