When do you start beta blockers (beta-adrenergic blocking agents) for varices in a patient with liver disease, such as cirrhosis, and portal hypertension?

When to Start Beta-Blockers for Varices in Cirrhosis

Beta-blockers should be started when patients with cirrhosis have medium or large esophageal varices (primary prophylaxis), or small varices with high-risk features (Child-Pugh B/C or red wale marks on endoscopy). 1

Primary Prophylaxis Based on Variceal Size and Risk

Medium/Large Varices (No Prior Bleeding)

• All patients with medium or large varices should receive either non-selective beta-blockers (propranolol, nadolol, or carvedilol) or endoscopic variceal ligation (EVL) to prevent first variceal hemorrhage. 1
• Carvedilol is preferred over traditional NSBBs due to its dual mechanism (beta-blockade plus alpha-1 blockade), which reduces both splanchnic blood flow and intrahepatic resistance, resulting in superior portal pressure reduction. 2, 3
• The choice between beta-blockers and EVL depends on patient characteristics: those with Child-Pugh B/C or red wale marks on varices are at highest risk and should definitely receive treatment. 1

Small Varices With High-Risk Features

• Start beta-blockers in patients with small varices who have Child-Pugh B/C cirrhosis OR red wale marks on endoscopy. 1
• These high-risk features significantly increase bleeding risk and warrant prophylactic treatment. 1
• Carvedilol specifically reduces progression from small to large varices (20.6% vs. 38.6% with placebo, p=0.04). 1, 2

Small Varices Without High-Risk Features

• Beta-blockers can be considered but are not mandatory, as long-term benefit is not well established. 1
• If beta-blockers are not used, perform surveillance endoscopy every 2 years (annually if decompensated). 1

When NOT to Start Beta-Blockers

Patients Without Varices

• Do not start beta-blockers to prevent variceal formation in cirrhotic patients without varices. 1, 2
• A large RCT showed no benefit in preventing varices (39% vs. 40% with placebo, p=0.89) and significantly more serious adverse events (18% vs. 6%, p=0.006). 1, 4

Acute Variceal Bleeding

• Temporarily suspend beta-blockers during acute bleeding episodes if systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg. 2, 3
• Beta-blockers play no role in acute management; acute treatment relies on vasoactive drugs (octreotide, terlipressin) and endoscopic therapy. 2
• Restart beta-blockers once hemodynamic stability is restored for secondary prophylaxis. 2, 3

Dosing Protocols

Carvedilol (Preferred Agent)

• Start 6.25 mg once daily 1, 2
• Increase to 6.25 mg twice daily after 3 days 1, 2
• Maximum dose: 12.5 mg/day (except in persistent hypertension) 1, 2
• Goal: Maintain systolic blood pressure ≥90 mmHg 1, 3

Propranolol

• Start 20-40 mg twice daily 1
• Adjust every 2-3 days to target heart rate 55-60 bpm 1
• Maximum: 320 mg/day without ascites; 160 mg/day with ascites 1
• Goal: Systolic blood pressure should not decrease <90 mmHg 1

Nadolol

• Start 20-40 mg once daily 1
• Adjust every 2-3 days to target heart rate 55-60 bpm 1
• Maximum: 160 mg/day without ascites; 80 mg/day with ascites 1

Critical Contraindications and Dose Adjustments

Decompensated Cirrhosis Considerations

• Refractory ascites and spontaneous bacterial peritonitis are NOT absolute contraindications, but require careful dose management. 1
• Avoid high doses (>160 mg/day propranolol or >80 mg/day nadolol) in patients with refractory ascites or SBP, as higher doses are associated with worse outcomes. 1

Severe Circulatory Dysfunction

• Reduce dose or temporarily hold beta-blockers if: 1
  • Systolic blood pressure <90 mmHg 1
  • Serum sodium <130 mEq/L 1
  • Hepatorenal syndrome or unexplained renal deterioration 1
• Beta-blockers may be reintroduced after correction of circulatory dysfunction. 1

Monitoring and Follow-Up

Patients on Beta-Blockers

• No surveillance endoscopy required once on beta-blocker therapy for primary prophylaxis. 1
• Continue beta-blockers indefinitely, as bleeding risk recurs when stopped. 1

Patients on EVL

• Repeat EVL every 1-2 weeks until variceal obliteration 1
• First surveillance endoscopy 1-3 months after obliteration 1
• Subsequent endoscopy every 6-12 months to check for recurrence 1

Common Pitfalls to Avoid

• Do not combine beta-blockers with EVL for primary prophylaxis - one RCT showed no benefit over EVL alone with more side effects. 1
• Do not use nitrates alone - ISMN monotherapy increased bleeding risk compared to placebo. 1
• Do not use sclerotherapy or TIPS for primary prophylaxis - both associated with worse outcomes. 1
• Do not withhold beta-blockers solely due to presence of ascites - only severe circulatory dysfunction warrants dose reduction or temporary discontinuation. 1