When should beta blockers (beta-adrenergic blocking agents) be initiated in patients with portal hypertension?

When to Start Beta Blockers in Portal Hypertension

Beta blockers should be initiated in patients with medium to large esophageal varices for primary prevention of variceal bleeding, and in all patients who have survived an episode of variceal bleeding for secondary prevention. 1, 2

Primary Prevention (Before First Bleed)

Screening and Risk Stratification

• All patients with newly diagnosed cirrhosis require screening endoscopy to identify varices and assess bleeding risk 1
• Varices are classified as small (F1) or large (F2/F3), with assessment of red color signs indicating high bleeding risk 1
• Endoscopic surveillance should occur every 2-3 years in compensated cirrhosis and every 1-2 years in decompensated cirrhosis 1

When to Start Beta Blockers for Primary Prevention

Start non-selective beta blockers (NSBBs) in:

• All patients with medium to large varices 3
• Patients with small varices who have high-risk features: red wale marks or advanced cirrhosis (Child-Pugh B/C) 3

Do NOT start NSBBs in:

• Patients with cirrhosis but no varices—this is explicitly not recommended as NSBBs do not prevent varix formation 1
• A placebo-controlled trial showed no benefit (39% vs 40% varix incidence, P=0.89) and significantly more serious adverse events (18% vs 6%, P=0.006) with timolol versus placebo 1

Controversial Area: Small Varices Without High-Risk Features

The evidence is mixed regarding NSBBs for small varices without red signs 1:

• One study showed nadolol reduced progression to large varices (7% vs 31% at 2 years) 1
• Another study showed propranolol offered no benefit (23% vs 19% progression, P=0.786) 1, 4
• A meta-analysis suggests NSBBs are not effective for preventing small-to-large varix progression 1
• Recommendation: NSBBs (propranolol/nadolol) are not routinely recommended for small varices without high-risk features 1

Exception—Carvedilol may be different:

• Carvedilol reduced progression from small to large varices (20.6% vs 38.6%, P=0.04) due to its additional anti-α1 activity that decreases intrahepatic resistance 1
• This may be particularly relevant in early-stage cirrhosis where intrahepatic vasoconstriction predominates 1

Secondary Prevention (After Variceal Bleeding)

All patients surviving variceal bleeding must receive NSBBs combined with endoscopic variceal ligation (EVL) for secondary prevention 3

Acute Management Timeline

• Start vasoactive drugs (terlipressin, somatostatin, or octreotide) immediately when variceal bleeding is suspected 2
• Perform endoscopy within 12 hours once hemodynamically stable 2
• Continue vasoactive drugs for 2-5 days post-endoscopy 2
• Transition to oral NSBBs once vasoactive drugs are discontinued 2
• Combine NSBBs with EVL for optimal secondary prevention 3

Special Populations

Non-Cirrhotic Portal Hypertension (NCPH)

• NSBBs should be initiated for prevention of rebleeding in NCPH using the same approach as cirrhotic portal hypertension 5
• Target HVPG reduction of 10-12% or to <12 mmHg 5
• TIPS has lower encephalopathy risk in NCPH due to preserved liver function 5

Children with Extrahepatic Portal Vein Obstruction (EHPVO)

• Insufficient evidence exists to recommend for or against NSBBs for primary prophylaxis in children 6
• Beta blockers decrease bleeding risk in large varices and improve survival in chronic portomesenteric venous obstruction per multivariate analysis 6
• Endoscopic variceal ligation is superior to sclerotherapy in children 6

Critical Contraindications and Monitoring

Absolute Contraindications

• Hypotension: systolic BP <90 mmHg or mean arterial pressure <65 mmHg 1, 6
• In acute bleeding with hypotension, beta blockers should be temporarily suspended 1

Target Dosing and Hemodynamic Goals

• Propranolol or carvedilol achieve the desired 20% portal pressure gradient reduction in 50-75% of patients, respectively 1, 6
• Target HVPG reduction to <12 mmHg or decrease by >10-12% from baseline 5, 2
• Carvedilol 12.5 mg/day is more effective than traditional NSBBs at reducing portal pressure 2

Caution in Advanced Disease

• Use NSBBs carefully in patients with severe or refractory ascites, as they may cause detrimental hemodynamic effects 7
• High NSBB doses should be scrutinized in hemodynamically vulnerable patients 7

Common Pitfalls to Avoid

• Do not use NSBBs to prevent varix formation—this increases adverse events without benefit 1
• Do not withhold NSBBs in patients with medium/large varices—this is the strongest indication 3
• Do not forget to combine NSBBs with EVL for secondary prevention—combination therapy is superior to either alone 3
• Do not continue beta blockers during acute hypotensive bleeding—temporarily suspend until hemodynamically stable 1
• Do not administer large volumes of blood products—this paradoxically increases portal pressure and worsens bleeding 2