What is the role of beta blockers (e.g. propranolol) in managing variceal bleeding in children?

Role of Beta Blockers in Managing Variceal Bleeding in Children

Non-selective beta blockers play a crucial role in both primary and secondary prevention of variceal bleeding in children with portal hypertension, with propranolol being the most studied agent in pediatric populations. 1, 2

Mechanism of Action

• Non-selective beta blockers (NSBBs) reduce portal pressure through two mechanisms: decreasing cardiac output via β1-receptor blockade and producing splanchnic vasoconstriction through β2-receptor blockade 3
• These hemodynamic effects lead to decreased portal venous inflow and lower portal pressure, with a target reduction of 20% in portal pressure gradient 1, 3
• Selective beta blockers (e.g., atenolol, metoprolol) are less effective and suboptimal for variceal hemorrhage prophylaxis 4

Primary Prevention of Variceal Bleeding

• NSBBs are recommended for children with small varices who have high bleeding risk (Child B/C or presence of red wale marks on varices) 4
• In children with cirrhosis, propranolol (1-2 mg/kg/day) is effective for preventing first variceal bleeding, particularly in Child-Pugh Class A patients 2
• The risk of first variceal bleeding is significantly reduced with beta blockers (from 30% to 14% in patients with medium/large varices) 4
• One bleeding episode is avoided for every 10 patients treated with beta blockers 4

Secondary Prevention of Variceal Bleeding

• Combination therapy with NSBBs plus endoscopic variceal ligation (EVL) is superior to EVL alone for preventing rebleeding 3
• Propranolol appears more effective for secondary prevention in Child-Pugh Class A patients than in Class B or C patients 2
• In children who have undergone endoscopic sclerotherapy, adding propranolol (1-2 mg/kg/day) may shorten the time required for variceal obliteration 5

Dosing and Administration

• Propranolol is typically started at 1-2 mg/kg/day in children 5, 2
• The dose should be titrated to the maximum tolerated dose rather than targeting heart rate reduction, as heart rate reduction does not correlate with HVPG reduction 4
• Once started, beta blocker therapy should be continued indefinitely unless contraindications develop 4, 3

Important Considerations and Contraindications

• 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 3
• Contraindications include hypotension, severe bradycardia, high-degree heart block, and asthma 3
• Adverse events are more common with beta blockers compared to placebo (11% vs 1% withdrawal rate in studies) 4
• Beta blockers should be started for secondary prophylaxis once the patient has recovered from the acute bleeding episode and before discharge from hospital 3

Monitoring and Follow-up

• In patients with small varices receiving beta blockers, follow-up endoscopy may not be necessary 4
• For those not receiving beta blockers, endoscopy should be repeated every 2 years, or annually if there is evidence of hepatic decompensation 4
• The lowest rebleeding rate (approximately 10%) is observed in patients who are "HVPG responders" (those achieving HVPG reduction to ≤12 mmHg or ≥20% reduction from baseline) 4, 3

Beta blockers remain a cornerstone in the management of variceal bleeding in children, particularly for primary prevention in those with high-risk varices and for secondary prevention in combination with endoscopic therapy. The choice of therapy should consider the child's liver function, size of varices, and previous bleeding history.