Dose-dependent effect of propranolol on the hemodynamic response in cirrhotic patients with gastroesophageal varices

Eur J Gastroenterol Hepatol. 2019 Mar;31(3):368-374. doi: 10.1097/MEG.0000000000001293.

Abstract

Objective: Propranolol is always titrated to the maximum tolerated dose to prevent gastroesophageal variceal bleeding. However, some patients do not achieve a hemodynamic response and experience more intolerance and discontinuation. This study evaluated the dose-dependent effect of propranolol on hemodynamic response and tolerance in cirrhotic patients.

Patients and methods: This retrospective study included 95 consecutive patients recruited from our prospective database. After hepatic venous pressure gradient measurement, patients received propranolol 10 mg, twice daily increased 10 mg daily until to 80 or 120 mg/day. Secondary hepatic venous pressure gradient was also measured. For nonresponders at 80 mg/day, propranolol was titrated to 120 mg/day.

Results: For 58 patients, propranolol was titrated to 80 mg/day, whereas for 37 patients, it was titrated to 120 mg/day. Hemodynamic response was similar in both groups (50 vs. 54.1%, P=0.700). Eighteen of the 29 nonresponders at propranolol 80 mg/day received a dose of 120 mg/day. Two patients achieved a hemodynamic response, but two could not tolerate the dose. Nine (15.5%) patients achieved the target dose of propranolol at 80 mg/day, whereas 16 (43.2%) patients at 120 mg/day achieved this (P=0.003). The difference in patients achieving the target dose between responders and nonresponders was not significant (14 vs. 14, P=0.642). Reduction or discontinuation was required by two (6.9%) patients using 80 mg/day propranolol and six (30%) patients using 120 mg/day propranolol (P=0.032).

Conclusion: There is no dose-dependent effect of 80-120 mg/day of propranolol on the hemodynamic response in cirrhotic patients with gastroesophageal varices. This indicates that low-dose propranolol below the target dose might lead to a considerable hemodynamic response and is much safer and well tolerated.

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / adverse effects
  • Adult
  • Aged
  • Databases, Factual
  • Dose-Response Relationship, Drug
  • Esophageal and Gastric Varices / diagnosis
  • Esophageal and Gastric Varices / drug therapy*
  • Esophageal and Gastric Varices / etiology
  • Esophageal and Gastric Varices / physiopathology
  • Female
  • Gastrointestinal Hemorrhage / diagnosis
  • Gastrointestinal Hemorrhage / drug therapy*
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / physiopathology
  • Hemodynamics / drug effects*
  • Humans
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / diagnosis
  • Male
  • Middle Aged
  • Propranolol / administration & dosage*
  • Propranolol / adverse effects
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Propranolol