What is the role of Non-Selective Beta Blockers (NSBBs) in the management of gastro issues, particularly in patients with cirrhosis and portal hypertension?

Role of Non-Selective Beta Blockers (NSBBs) in Gastroesophageal Varices Management

Non-selective beta blockers (NSBBs) are the cornerstone of both primary and secondary prophylaxis of variceal bleeding in patients with cirrhosis and portal hypertension, reducing first bleeding risk from 30% to 14% and mortality. 1

Primary Prophylaxis of Variceal Bleeding

For Small Varices

• For small varices with high bleeding risk (Child B/C cirrhosis or red wale marks):
  • NSBBs (propranolol or nadolol) are recommended 1
  • Target heart rate: 55-60 beats per minute 1
  • Treatment should continue indefinitely 1

For Medium/Large Varices

• For medium/large varices that have not bled:
  • NSBBs (propranolol or nadolol), carvedilol, or endoscopic variceal ligation (EVL) are recommended 1
  • NSBBs reduce first bleeding risk from 30% to 14% 1
  • One bleeding episode is avoided for every 10 patients treated with NSBBs 1
  • Combination of NSBBs and EVL can also be considered 1

Medication Selection and Dosing

Propranolol

• Starting dose: 20-40 mg twice daily 2
• Maximum dose: 320 mg daily (160 mg in patients with ascites) 2
• Titrate every 2-3 days until heart rate reaches 55-60 beats/minute 2

Nadolol

• Starting dose: 20-40 mg once daily 2
• Maximum dose: 160 mg daily (80 mg in patients with ascites) 2
• Titrate similarly to propranolol 2

Carvedilol

• Starting dose: 6.25 mg once daily (or 3.125 mg twice daily) 2
• Increase after 3 days to 6.25 mg twice daily 2
• Maximum dose: 12.5 mg daily 3
• More effective than propranolol in reducing portal pressure due to additional anti-α1-adrenergic activity 4, 3

Mechanism of Action

NSBBs work through dual mechanisms:

1. β1-blockade: Reduces cardiac output 5
2. β2-blockade: Produces splanchnic vasoconstriction, reducing portal flow 5

The combined effect reduces portal pressure, which is the primary driver of variceal bleeding 1, 5.

A reduction in hepatic venous pressure gradient (HVPG):

• To less than 12 mmHg essentially eliminates bleeding risk 1, 5
• By ≥20% from baseline significantly reduces first variceal bleeding risk 1, 5

Beyond Bleeding Prevention

NSBBs provide additional benefits:

• Prevent development of ascites in compensated patients 6
• Reduce bacterial translocation 4
• Decrease risk of first decompensation in patients with cirrhosis and enduring clinically significant portal hypertension (CSPH) after etiological treatment 7
• Reduce bacterial infection rates 7

Monitoring and Follow-up

• Monitor heart rate (target: 55-60 beats/minute) 1, 2
• Monitor blood pressure (maintain systolic BP >90 mmHg) 1, 2
• Monitor renal function, especially in patients with ascites 2
• For patients with small varices on NSBBs, follow-up endoscopy is not necessary 1
• For patients not on NSBBs, repeat endoscopy every 2 years, or annually if decompensation occurs 1

Contraindications and Precautions

• Contraindications: Sinus bradycardia, insulin-dependent diabetes mellitus, obstructive pulmonary disease, heart failure, aortic valve disease, second or third-degree AV block, peripheral arterial insufficiency 2
• Special populations:
  • Elderly: Reduced clearance and prolonged half-life of propranolol 8
  • Renal insufficiency: Delayed absorption and reduced half-life 8
  • Hepatic insufficiency: Increased propranolol concentration (2.5-fold) and half-life 8
  • Refractory ascites: Use NSBBs with caution; consider dose reduction or discontinuation if hypotension or renal dysfunction develops 6

Important Caveats

• Abrupt discontinuation of NSBBs increases risk of variceal bleeding 2
• Heart rate reduction does not necessarily correlate with reduction in HVPG 5
• Selective beta-blockers (atenolol, metoprolol) are less effective and suboptimal for prophylaxis 1
• In patients with refractory ascites, NSBBs should be carefully monitored as they may impair cardiac reserve and compromise renal perfusion 6

NSBBs remain the cornerstone of therapy for portal hypertension in cirrhotic patients, with carvedilol emerging as potentially the NSBB of choice due to its superior efficacy in lowering portal pressure 3.