Is propranolol (a non-selective beta-blocker) used in patients with cirrhosis and ascites?

Propranolol Use in Cirrhosis with Ascites

Yes, propranolol can be used in patients with cirrhosis and ascites, but the dose must be carefully limited to ≤160 mg/day, and it should be temporarily discontinued or dose-reduced if severe circulatory dysfunction develops (systolic BP <90 mmHg, serum sodium <130 mEq/L, or hepatorenal syndrome). 1

Key Principle: Ascites is NOT an Absolute Contraindication

• Refractory ascites and spontaneous bacterial peritonitis (SBP) are not absolute contraindications for non-selective beta-blockers (NSBBs). 1
• Current evidence from observational studies does not support a harmful effect of NSBBs in most patients with decompensated cirrhosis, including those with ascites. 1
• Three large cohort studies have shown either no differences or even improved survival in patients with ascites treated with NSBBs, including those with refractory ascites. 1

Critical Dose Limitations

The maximum dose of propranolol in patients with ascites is 160 mg/day (compared to 320 mg/day in patients without ascites). 1, 2

• Doses of propranolol above 160 mg/day in decompensated cirrhosis are associated with worse survival. 1
• Doses up to 160 mg/day are associated with improved survival in patients with decompensated cirrhosis. 1
• In patients with SBP specifically, doses <160 mg/day of propranolol were associated with improved survival after adjustment for confounders, whereas doses ≥160 mg/day were not. 1
• For patients with SBP, consider limiting propranolol to 80 mg/day for optimal safety. 3, 2

When to Reduce or Discontinue Propranolol

Dose reduction or temporary discontinuation is required when patients develop signs of severe circulatory dysfunction: 1

• Systolic blood pressure <90 mmHg
• Serum sodium <130 mEq/L
• Hepatorenal syndrome (HRS)
• Unexplained deterioration in renal function

NSBBs may be reintroduced after correction of renal function/circulatory state, particularly when used to prevent recurrent variceal hemorrhage. 1

Titration Protocol in Patients with Ascites

• Start propranolol at 20-40 mg twice daily. 3, 2
• Increase dose every 2-3 days based on heart rate response and tolerability. 3
• Target heart rate of 55-60 beats per minute or 25% reduction from baseline. 3
• Maintain systolic blood pressure ≥90 mmHg at all times. 1, 3
• Maximum dose: 160 mg/day in patients with ascites. 1, 2

Monitoring Requirements

Close monitoring of blood pressure and renal function is essential: 1

• Check blood pressure at each visit, maintaining systolic BP ≥90 mmHg. 3
• Monitor serum creatinine and serum sodium regularly. 3
• Reduce dose or discontinue if creatinine exceeds 1.5 mg/dL or sodium falls below 130 mmol/L. 3
• Mean arterial pressure should remain above 65 mmHg. 4

Evidence on Hemodynamic Effects

The relationship between propranolol and renal function in ascites is complex and depends on baseline sympathoadrenergic tone:

• Propranolol lowers plasma renin activity and aldosterone in cirrhotic patients with ascites. 5
• In patients with normal baseline norepinephrine levels, propranolol may have antinatriuretic effects. 5, 6
• However, in patients with elevated baseline sympathoadrenergic tone, propranolol can actually improve glomerular filtration rate and sodium excretion. 5
• The FDA label notes that steady-state propranolol concentrations in patients with cirrhosis are increased 2.5-fold compared to controls, with half-life prolonged from 2.9 to 7.2 hours. 7

Alternative Considerations

• Carvedilol may be preferred over propranolol in patients with ascites (6.25-12.5 mg daily), as it has demonstrated superior portal pressure reduction and improved survival in decompensated cirrhosis. 4, 8
• Carvedilol showed significantly reduced risk of further decompensation/death in decompensated patients compared to classical NSBBs (propranolol/nadolol). 8
• However, carvedilol should be avoided in patients with refractory ascites and severe circulatory dysfunction due to its additional alpha-1 blocking effects. 2

Common Pitfalls to Avoid

• Do not automatically discontinue propranolol when ascites develops – this is a common error that may worsen outcomes. 1
• Avoid high doses (>160 mg/day) in patients with ascites, as this is associated with worse survival. 1
• Do not abruptly stop propranolol – this increases risk of variceal bleeding and mortality; dose reduction is preferred over complete discontinuation. 3, 2
• Monitor for circulatory dysfunction rather than focusing solely on heart rate targets in advanced cirrhosis. 1, 2
• If propranolol must be discontinued, initiate endoscopic variceal ligation as an alternative. 3, 2

Adjunctive Therapy

• Adding midodrine (an alpha-1 adrenergic agonist) to propranolol in patients with severe/refractory ascites facilitates higher maximum tolerated doses of propranolol, greater HVPG reduction, and reduced incidence of first variceal bleed. 9
• The combination resulted in better ascites control, fewer paracentesis requirements, and fewer ascites-related complications. 9