What is the role of Propranolol (beta-blocker) in managing cirrhosis patients with esophageal varices?

From the Guidelines

Propranolol is a crucial medication in managing cirrhosis patients with esophageal varices, and its use should be prioritized to reduce portal pressure and prevent variceal bleeding, with a recommended starting dose of 20-40mg orally twice daily and titration up to the maximum tolerated dose, with a target heart rate reduction of 25% from baseline or to 55-60 beats per minute 1.

Key Considerations

• Propranolol works through two mechanisms: blocking beta-1 receptors to reduce cardiac output and blocking beta-2 receptors to cause splanchnic vasoconstriction, both of which decrease portal venous pressure.
• The medication is indicated for primary prevention in high-risk varices (medium to large varices or small varices with red signs) and for secondary prevention after a bleeding episode, typically in combination with endoscopic band ligation.
• Common side effects include fatigue, dizziness, and hypotension, and the medication should be used cautiously in patients with asthma, severe bradycardia, heart block, or decompensated heart failure.

Important Guidelines

• The maximum dose of propranolol is 320 mg daily in patients without ascites and 160 mg daily in patients with ascites, and systolic blood pressure should not decrease <90 mmHg 1.
• In patients with end-stage liver disease, such as refractory ascites or spontaneous bacterial peritonitis, the administration of propranolol has not yet been established, and its use should be carefully considered, with thorough monitoring of blood pressure and renal function, and dose reduction or discontinuation considered in patients who develop low blood pressure or impaired renal function 1.
• The recent BAVENO VI consensus proposed that in patients with refractory ascites and certain conditions, such as systolic blood pressure <90 mmHg, or SCr >1.5 mg/dl, or hyponatraemia <130 mmol/L, the propranolol dose should be reduced or even temporarily discontinued 1.

Clinical Decision-Making

• The use of propranolol should be based on a critical risk/benefit evaluation in patients with refractory ascites and signs of systemic circulatory dysfunction, and parameters such as severe hyponatraemia, low mean arterial pressure or cardiac output, and increasing SCr should be considered to identify more vulnerable patients 1.
• In the setting of secondary prophylaxis of variceal hemorrhage, combination therapy with propranolol and endoscopic band ligation is recommended, and if propranolol is not tolerated, TIPS should be considered, particularly if the patient has another complication that could benefit from TIPS 1.

From the Research

Role of Propranolol in Managing Cirrhosis Patients with Esophageal Varices

• Propranolol, a beta-blocker, is used to prevent the first gastrointestinal bleeding in patients with cirrhosis and esophageal varices 2, 3, 4, 5.
• The medication works by reducing the heart rate and the hepatic venous pressure gradient, which in turn decreases the risk of bleeding from esophageal varices 3, 4.
• Studies have shown that propranolol is effective in preventing the first variceal hemorrhage in patients with cirrhosis and large esophageal varices 2, 3, 4.
• The optimal dose of propranolol for this indication is still a matter of debate, with some studies suggesting that a dose-dependent effect may not be present 6.
• Propranolol has been shown to be effective in patients with alcoholic cirrhosis and large esophageal varices, but its effect on survival is still unclear 3, 4.

Patient Selection and Dosing

• Patients with cirrhosis and esophageal varices who are at risk of bleeding should be considered for propranolol therapy 2, 3, 4, 5.
• The dose of propranolol should be titrated to reduce the heart rate by 25% or to achieve a hepatic venous pressure gradient of less than 12 mmHg 3, 4.
• The dose of propranolol can be increased gradually to a maximum tolerated dose, but some patients may not achieve a hemodynamic response and may experience more intolerance and discontinuation 6.

Efficacy and Safety

• Propranolol has been shown to be effective in preventing the first variceal hemorrhage in patients with cirrhosis and large esophageal varices, with a significant reduction in the risk of bleeding compared to placebo 2, 3, 4.
• The safety profile of propranolol in this patient population is generally good, but side effects such as hypotension, bradycardia, and fatigue can occur 3, 4, 5.
• The use of propranolol in patients with cirrhosis and esophageal varices should be carefully monitored, with regular follow-up and adjustment of the dose as needed to minimize the risk of side effects and maximize the benefits of therapy 2, 3, 4, 5.