From the Guidelines
The initial dosing for propranolol for esophageal varices due to cirrhosis is typically 20-40 mg orally twice daily, as recommended by the most recent and highest quality study 1. This dose should be titrated gradually based on heart rate response, with the goal of reducing the resting heart rate by 25% from baseline or to 55-60 beats per minute, whichever is higher. The maximum recommended dose is usually 160-320 mg per day, divided into two or three doses, in patients without ascites, and 160 mg daily in patients with ascites, as stated in the study 1. Some key points to consider when initiating propranolol therapy include:
- Monitoring for potential side effects such as hypotension, bradycardia, and worsening of ascites
- Regularly checking blood pressure and heart rate during dose adjustments
- Using propranolol cautiously in patients with severe liver dysfunction, as its metabolism may be impaired, potentially leading to increased drug levels and side effects
- Continuing the medication indefinitely as long as it is tolerated, as discontinuation can lead to rebound portal hypertension and increased bleeding risk, as noted in the study 1. It's also worth noting that propranolol works by reducing portal pressure through decreasing cardiac output and causing splanchnic vasoconstriction, thereby reducing the risk of variceal bleeding, as explained in the study 1. Overall, the use of propranolol for esophageal varices due to cirrhosis is supported by the most recent and highest quality evidence, and its benefits in reducing the risk of variceal bleeding and improving patient outcomes are well-established, as seen in the studies 1.
From the Research
Initial Dosing for Propranolol
The initial dosing for propranolol in the treatment of esophageal varices due to cirrhosis can vary.
- According to a study published in 1991 2, the daily dosage of propranolol was determined by the administration of progressively increasing doses to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg, or a decrease in resting heart rate to less than 55 beats/min. The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day.
- A 2019 study 3 found that propranolol was titrated to 80 mg/day in 58 patients and to 120 mg/day in 37 patients, with no significant difference in hemodynamic response between the two groups.
- Another study from 1993 4 used propranolol up to the maximum tolerated dose, with a median follow-up of 29 months.
- A 2000 study 5 used nadolol (40-160 mg/d) with or without isosorbide mononitrate (10-20 mg 3 times per day) for primary prophylaxis of variceal bleeding in cirrhosis.
- A 1999 study 6 used long-acting propranolol (160 mg/day) to evaluate its effect in preventing the development of large oesophageal varices in patients with cirrhosis.
Key Findings
- The optimal initial dosing for propranolol in the treatment of esophageal varices due to cirrhosis is not clearly established, but doses ranging from 80 mg/day to 160 mg/day have been used in various studies 2, 3, 4, 5, 6.
- The dose of propranolol should be titrated to achieve a decrease in hepatic venous pressure gradient or a decrease in resting heart rate 2.
- Low-dose propranolol may be effective in achieving a hemodynamic response and is generally well tolerated 3.