Assessment of beta-adrenergic blockade with propranolol in patients with cirrhosis

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.