What medications provide long-term control of the source of bleeding in a patient with hematemesis, melena, and liver cirrhosis?

From the Guidelines

For long-term control of bleeding in patients with hematemesis, melena, and liver cirrhosis, the combination of non-selective beta-blockers (NSBBs) and endoscopic variceal ligation (EVL) is the most effective medication recommendation. This approach is supported by the most recent and highest quality study [ 1 ], which suggests that combination therapy is significantly more effective than EVL alone in preventing all-source GI hemorrhage. Non-selective beta-blockers such as propranolol (starting at 20-40mg twice daily and titrating based on heart rate) or nadolol (starting at 20-40mg once daily) are the most commonly used options and should be continued indefinitely to reduce portal pressure by decreasing cardiac output and causing splanchnic vasoconstriction, thereby preventing rebleeding episodes [ 1 ].

Key Considerations

• Carvedilol (starting at 6.25mg daily, increasing to 12.5mg daily if tolerated) is an alternative that may be more effective due to its additional alpha-blocking properties, but its use in secondary prophylaxis of variceal hemorrhage is not well established [ 1 ].
• For patients who cannot tolerate or have contraindications to beta-blockers, isosorbide mononitrate (starting at 10mg twice daily, increasing to 20mg twice daily) can be considered, though it's less effective when used alone [ 1 ].
• In patients with recurrent bleeding despite beta-blocker therapy, combination therapy with beta-blockers and endoscopic band ligation provides superior protection [ 1 ].
• Proton pump inhibitors like pantoprazole or omeprazole may be used short-term after acute bleeding episodes, but they don't address the underlying portal hypertension that causes varices in cirrhotic patients [ 1 ].

Management Approach

• The management approach should be individualized based on the patient's risk of death and the presence of other complications of cirrhosis [ 1 ].
• Patients who recover from the first episode of variceal hemorrhage have a high rebleeding risk and should receive therapy to prevent rebleeding, which should be instituted before discharge from the hospital [ 1 ].
• Transjugular intrahepatic portosystemic shunt (TIPS) should be considered in patients who experience recurrent variceal hemorrhage despite combination pharmacological and endoscopic therapy [ 1 ].

From the FDA Drug Label

In a study conducted in 6 patients with cirrhosis and 7 healthy subjects receiving 160 mg of a long-acting preparation of propranolol once a day for 7 days, the steady-state propranolol concentration in patients with cirrhosis was increased 2.5-fold in comparison to controls. Single doses of octreotide have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers.

The medications that provide long-term control of the source of bleeding in a patient with hematemesis, melena, and liver cirrhosis are:

• Propranolol: a beta-blocker that can reduce the risk of bleeding in patients with cirrhosis by decreasing portal pressure.
• Octreotide: a somatostatin analogue that can decrease bile secretion and inhibit gallbladder contractility, which may help control bleeding in patients with cirrhosis.

Key points:

• Propranolol may be used to reduce portal pressure and prevent bleeding in patients with cirrhosis 2.
• Octreotide may be used to control acute bleeding in patients with cirrhosis, but its long-term use is not well established 3.

From the Research

Medications for Long-Term Control of Bleeding in Liver Cirrhosis

• Non-selective beta-blockers (NSBB) are recommended for primary and secondary prophylaxis of variceal bleeding in patients with liver cirrhosis 4.
• Carvedilol, a NSBB with intrinsic anti-α(1)-adrenergic activity, may be more effective than propranolol in lowering portal hypertension 4.
• Octreotide may reduce the risk of early rebleeding in cirrhotic patients treated with beta-blockers and/or sclerotherapy after control of acute upper digestive bleeding 5.

Combination Therapy for Secondary Prevention of Variceal Bleeding

• Combination therapy with pharmacotherapy and endoscopic variceal ligation (EVL) is effective in reducing rebleeding and mortality in cirrhotic patients 6, 7.
• EVL plus nadolol may be the preferred choice for preventing rebleeding in cirrhotic patients with one previous episode of variceal hemorrhage 7.
• Beta-blockers with isosorbide mononitrate (ISMN) may be a potential alternative to improve mortality 7.

Management of Non-Variceal Upper Gastrointestinal Bleeding

• Intravenous proton pump inhibitors are the mainstay in the initial management of upper GI bleeding from a non-variceal etiology 8.
• Endoscopic therapy should ideally be performed within 24 hours of presentation after initial stabilization with crystalloids and blood products 8.
• Pro-kinetic agents can be given 30 minutes to an hour before endoscopy and may aid in the diagnosis of UGIB 8.