OBJECTIVES:Terlipressin reduces portal pressure in cirrhotic patients mainly through intense splanchnic vasoconstriction that decrease portal venous inflow. Hepatic blood flow may also be reduced by terlipressin. Prazosin (an alpha1-adrenoceptor antagonist) has also been proposed to decrease portal pressure in cirrhotic patients possibly through a decrease in the intrahepatic vascular resistance. The current study was aimed to evaluate whether a combination of prazosin and terlipressin exerts more beneficial effects than terlipressin alone. METHODS: Patients were randomly assigned to receive either a placebo (n = 12) or an oral administration of prazosin 2 mg (n = 12). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after prazosin or placebo, and 30 min after terlipressin. RESULTS:Placebo administration did not affect any hemodynamic values. Terlipressin administration, on the other hand, resulted in expected changes on the hepatic venous pressure gradient, hepatic blood flow, and systemic hemodynamics. In contrast, prazosin significantly decreased hepatic venous pressure gradient with an increased hepatic blood flow and intrinsic hepatic clearance. After terlipressin administration, a further decrease in hepatic venous pressure gradient was observed with preservation of hepatic blood flow and intrinsic hepatic clearance. The magnitude of decrease in hepatic venous pressure gradient was more profound in patients receiving prazosin plus terlipressin than in those receiving terlipressin alone. However, the magnitude of changes in systemic hemodynamics was no different between the two groups of patients. CONCLUSIONS: The current study showed that a combination of prazosin and terlipressin resulted in a more profound reduction of hepatic venous pressure gradient with a preservation of hepatic blood flow and intrinsic hepatic clearance than did terlipressin alone. However, the combined therapy did not modify the systemic hemodynamic effects exerted by terlipressin.
RCT Entities:
OBJECTIVES: Terlipressin reduces portal pressure in cirrhotic patients mainly through intense splanchnic vasoconstriction that decrease portal venous inflow. Hepatic blood flow may also be reduced by terlipressin. Prazosin (an alpha1-adrenoceptor antagonist) has also been proposed to decrease portal pressure in cirrhotic patients possibly through a decrease in the intrahepatic vascular resistance. The current study was aimed to evaluate whether a combination of prazosin and terlipressin exerts more beneficial effects than terlipressin alone. METHODS:Patients were randomly assigned to receive either a placebo (n = 12) or an oral administration of prazosin 2 mg (n = 12). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after prazosin or placebo, and 30 min after terlipressin. RESULTS: Placebo administration did not affect any hemodynamic values. Terlipressin administration, on the other hand, resulted in expected changes on the hepatic venous pressure gradient, hepatic blood flow, and systemic hemodynamics. In contrast, prazosin significantly decreased hepatic venous pressure gradient with an increased hepatic blood flow and intrinsic hepatic clearance. After terlipressin administration, a further decrease in hepatic venous pressure gradient was observed with preservation of hepatic blood flow and intrinsic hepatic clearance. The magnitude of decrease in hepatic venous pressure gradient was more profound in patients receiving prazosin plus terlipressin than in those receiving terlipressin alone. However, the magnitude of changes in systemic hemodynamics was no different between the two groups of patients. CONCLUSIONS: The current study showed that a combination of prazosin and terlipressin resulted in a more profound reduction of hepatic venous pressure gradient with a preservation of hepatic blood flow and intrinsic hepatic clearance than did terlipressin alone. However, the combined therapy did not modify the systemic hemodynamic effects exerted by terlipressin.
Authors: Davide Roccarina; Lawrence Mj Best; Suzanne C Freeman; Danielle Roberts; Nicola J Cooper; Alex J Sutton; Amine Benmassaoud; Maria Corina Plaz Torres; Laura Iogna Prat; Mario Csenar; Sivapatham Arunan; Tanjia Begum; Elisabeth Jane Milne; Maxine Tapp; Chavdar S Pavlov; Brian R Davidson; Emmanuel Tsochatzis; Norman R Williams; Kurinchi Selvan Gurusamy Journal: Cochrane Database Syst Rev Date: 2021-04-06
Authors: Maria Corina Plaz Torres; Lawrence Mj Best; Suzanne C Freeman; Danielle Roberts; Nicola J Cooper; Alex J Sutton; Davide Roccarina; Amine Benmassaoud; Laura Iogna Prat; Norman R Williams; Mario Csenar; Dominic Fritche; Tanjia Begum; Sivapatham Arunan; Maxine Tapp; Elisabeth Jane Milne; Chavdar S Pavlov; Brian R Davidson; Emmanuel Tsochatzis; Kurinchi Selvan Gurusamy Journal: Cochrane Database Syst Rev Date: 2021-03-30