Assessment of βrenergic Blockade with Propranolol in Patients with Cirrhosis

Abstract

Fourteen patients with cirrhosis and bleeding esophageal varices were treated with propranolol. The dose of propranolol was determined by decreasing the resting heart rate by 25% 12 hr after an oral dose of propranolol which was given twice a day. Significant decreases in the hepatic venous pressure gradient and cardiac output after 1 month of propranolol administration was observed. To assess beta-adrenergic blockade, the isoproterenol test and plasma propranolol levels were evaluated. Increasing doses of isoproterenol were injected to increase the resting heart rate 25 beats per minute (chronotropic dose 25 or CD25 ). Plasma propranolol concentrations were measured in blood samples drawn 4 hr after the last oral dose. The mean CD25 was 5 +/- 2 micrograms before and 146 +/- 84 micrograms after 1 month of propranolol administration. The plasma propranolol level after 1 month of drug administration was 0.69 +/- 0.47 microM per liter i.e. 2.33 +/- 1.59 micrograms per ml. A significant correlation was found between the CD25 measured after continuous propranolol administration and plasma propranolol level. In conclusion, the efficacy of beta-adrenergic blockade was estimated by the isoproterenol test which correlates with the plasma propranolol level in patients with cirrhosis. This study suggests that the isoproterenol test is useful in assessing beta-adrenergic blockade with propranolol in patients with cirrhosis.

Propranolol in the Primary Prevention of Upper Gastrointestinal Tract Haemorrhage in Patients with Cirrhosis of the Liver and Oesophageal Varices1

“…This was 53 titrated until a 20 to 25% reduction in resting heart rate (Bercoff et al 1984) occurred 6 hours after administration, or until the maximum permitted dose was reached (320mg of long-acting propranolol once daily) [Leahey et al 1980]. Patients were evaluated every 2 months and the end-points were death or haemorrhage.…”

The use of beta‐blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis

“…In patients with cirrhosis, nonselective beta-blockers (NSBB) prevent primary and secondary gastrointestinal haemorrhage and reduce the mortality rate associated with bleeding (1)(2)(3)(4). However, the beneficial effect of NSBB in advanced cirrhosis has recently been questioned giving rise to a heated debate (5)(6)(7)(8)(9)(10).…”

Effect of propranolol on hepatic blood flow in patients with cirrhosis

“…The dose and the route of propranolol administration were different in patients with cirrhosis with and without surgical portacaval shunts, but the changes in heart rate and cardiac output in the three groups provide some assurance that the assessment of p-adrenergic blockade was comparable. 1 This finding demonstrated that hepatic arterial blood flow is modulated independently of the fall in cardiac output. The effect might be interpreted as an expression of hepatic arterial autoregulation to preserve liver perfusion, but a direct effect of propranolol on intrahepatic circulation cannot be excluded.…”