When are beta blockers (beta-adrenergic blocking agents) inappropriate in patients with cirrhosis and grade 2 esophageal varices?

From the Guidelines

Beta blockers are inappropriate in patients with cirrhosis and grade 2 esophageal varices when they have refractory ascites, spontaneous bacterial peritonitis, severe or refractory hepatic encephalopathy, or when the patient is in a state of decompensated cirrhosis with low blood pressure (systolic blood pressure <90 mmHg). These medications should also be avoided in patients with significant bradycardia (heart rate <55 beats per minute), hypotension, severe bronchospastic disease, or peripheral arterial disease. According to the EASL clinical practice guidelines for the management of patients with decompensated cirrhosis 1, the use of non-selective beta blockers (NSBBs) in patients with refractory ascites and signs of systemic circulatory dysfunction should be based on a critical risk/benefit evaluation. Parameters such as severe hyponatraemia, low mean arterial pressure or cardiac output, and increasing SCr identify more vulnerable patients among those with decompensated cirrhosis, in whom a dose reduction or temporal discontinuation of NSBB treatment should be considered. The recent BAVENO VI consensus proposed that in patients with refractory ascites and (i) systolic blood pressure <90 mmHg, or (ii) SCr >1.5 mg/dl, or (iii) hyponatraemia <130 mmol/L, the NSBB dose should be reduced or even temporarily discontinued 1.

Key Considerations

• Refractory ascites is a critical condition where the protective effects of NSBBs may cease and a detrimental impact may begin 1
• Patients with advanced cirrhosis often have a hyperdynamic circulation that compensates for their reduced effective blood volume, and beta blockers can interfere with this compensatory mechanism 1
• The use of NSBBs should be based on a critical risk/benefit evaluation in patients with refractory ascites and signs of systemic circulatory dysfunction 1
• Common beta blockers used for varices include non-selective agents like propranolol and nadolol, which are typically titrated to achieve a 25% reduction in heart rate or a target heart rate of 55-60 beats per minute 1

Recommendations

• In patients with cirrhosis and grade 2 esophageal varices, the use of NSBBs should be considered to prevent first variceal bleeding, but with caution in patients with refractory ascites or decompensated cirrhosis 1
• A combination of NSBBs and endoscopic variceal ligation (EVL) can also be considered in patients with large esophageal varices 1
• In patients with refractory ascites and signs of systemic circulatory dysfunction, the NSBB dose should be reduced or even temporarily discontinued 1

From the Research

Inappropriateness of Beta Blockers in Cirrhosis

• Beta blockers are generally used to reduce the risk of variceal bleeding in patients with cirrhosis and portal hypertension 2.
• However, their use may be inappropriate in certain situations, such as in patients with decompensated cirrhosis accompanying significant ascites 3.
• A study found that the use of non-selective beta blockers (NSBB) in patients with significant ascites (≥grade 2) may worsen their prognosis, with a higher all-cause mortality rate compared to those receiving endoscopic variceal ligation (EVL) only 3.
• In contrast, another study suggested that beta blockers may be beneficial in patients with cirrhosis and ascites, with a lower mortality rate compared to those not taking beta blockers 4.

Specific Situations

• Patients with grade 2 varices, good blood pressure, and normal sodium may still benefit from beta blockers, as they can reduce the risk of variceal bleeding 2, 5.
• However, patients with significant ascites (≥grade 2) may not benefit from beta blockers and may even experience a worsening of their prognosis 3.
• The use of beta blockers in patients with cirrhosis and portal hypertension should be individualized, taking into account the patient's specific clinical characteristics and the presence of any contraindications 2, 4.

Clinical Considerations

• The decision to use beta blockers in patients with cirrhosis and portal hypertension should be based on a careful evaluation of the patient's clinical status and the potential benefits and risks of therapy 2, 3, 4.
• Patients with significant ascites (≥grade 2) should be closely monitored and alternative treatments, such as EVL, should be considered 3.
• Further studies are needed to clarify the role of beta blockers in patients with cirrhosis and portal hypertension, particularly in those with significant ascites 3, 4.