What is the role of beta blockers in the management of esophageal varices bleeding?

Role of Beta Blockers in the Management of Esophageal Varices Bleeding

Non-selective beta blockers are a cornerstone therapy for prevention of variceal rebleeding but should not be used during acute bleeding episodes due to their potential to worsen hemodynamic status.

Mechanism of Action of Beta Blockers in Portal Hypertension

• Non-selective beta blockers (NSBBs) reduce portal pressure through two primary mechanisms:
  • β1-receptor blockade decreases cardiac output
  • β2-receptor blockade causes splanchnic vasoconstriction through unopposed alpha-adrenergic activity 1
• These effects lead to decreased portal venous inflow and lower portal pressure, with a desired reduction of 20% in portal pressure gradient achievable in 50-75% of patients with propranolol or carvedilol 1
• Beyond reducing hepatic venous pressure gradient, beta blockers also reduce azygos blood flow, which contributes to their effectiveness in preventing variceal bleeding 1

Acute Variceal Bleeding Management

• Beta blockers should NOT be used during acute variceal bleeding episodes as they decrease blood pressure and blunt the physiologic increase in heart rate associated with bleeding 1
• In hypotensive patients (systolic BP <90 mmHg or MAP <65 mmHg) with active bleeding, beta blockers should be temporarily suspended 1
• First-line pharmacological therapy for acute bleeding should instead include:
  • Vasoactive drugs (terlipressin, somatostatin, or octreotide) started as soon as variceal bleeding is suspected, even before endoscopy 1
  • Short-course prophylactic antibiotics to reduce infection risk and improve survival 1

Secondary Prevention of Variceal Bleeding

• Beta blockers play a critical role in preventing rebleeding after the acute episode has resolved 1
• The combination of non-selective beta blockers plus endoscopic variceal ligation (EVL) is the best option for secondary prophylaxis of variceal hemorrhage 1
• This combination approach is superior to EVL alone, with rebleeding rates of 14-23% for combination therapy versus 38-47% for EVL alone 1
• The non-selective beta blocker should be titrated to the maximal tolerated dose 1
• Patients who are "HVPG responders" (reduction in hepatic venous pressure gradient to ≤12 mmHg or by >20% from baseline) have the lowest rebleeding rate of approximately 10% 1

Primary Prevention of Variceal Bleeding

• Non-selective beta blockers are the gold standard for prevention of first variceal hemorrhage in patients with medium/large varices 1
• They significantly reduce the risk of first hemorrhage in patients with large varices and improve survival 2
• Endoscopic variceal ligation is an alternative for patients who have contraindications or intolerance to beta blockers 2, 3

Important Considerations and Pitfalls

• Contraindications to beta blockers must be recognized:

  • Hypotension (systolic BP <90 mmHg or MAP <65 mmHg) 1
  • Acute bleeding episodes 1
  • Other standard contraindications (severe bradycardia, high-degree heart block, asthma, etc.)

• Timing considerations:

  • Do not start beta blockers during acute bleeding
  • Begin beta blockers for secondary prophylaxis once patient has recovered from acute episode (no evidence of hemorrhage for at least 24 hours) and before discharge from hospital 1
  • Continue indefinitely unless contraindications develop

• Monitoring response:

  • Ideally, hepatic venous pressure gradient (HVPG) measurement would guide therapy, but this requires specialized expertise 1, 2
  • In clinical practice, titrate to maximum tolerated dose based on heart rate and blood pressure 1

Specific Beta Blockers and Dosing

• Propranolol and carvedilol are the most commonly used non-selective beta blockers 1, 4
• Carvedilol may have advantages due to additional anti-alpha1-adrenergic activity, potentially providing better reduction in portal pressure 4
• The combination of beta blockers with isosorbide mononitrate may be more effective than beta blockers alone for secondary prophylaxis, but has more side effects and is often poorly tolerated 1, 5