title: Combination of ketanserin and verapamil or propranolol in patients with alcoholic cirrhosis: search for an additive effect.
abstract: Drugs reported to reduce portal pressure through different mechanisms were combined in the hope of either additive portal hypotensive effects in "responders," or inducing a portal hypotensive effect in "nonresponders" to the initial drug. Seven patients with alcoholic cirrhosis received verapamil, 10 mg i.v., and, 60 min later, ketanserin, 5 mg i.v. Verapamil decreased heart rate and increased free hepatic venous pressure but had no effect on hepatic venous pressure gradient or azygos blood flow. When combined with verapamil, ketanserin significantly diminished wedged hepatic venous pressure and hepatic venous pressure gradient. Ten other patients with alcoholic cirrhosis received propranolol, 15 mg i.v., and 45 min later, ketanserin, 5 mg i.v. In all patients, heart rate, cardiac index and azygos blood flow significantly decreased after propranolol. After propranolol alone, however, wedged hepatic venous pressure decreased in only five patients, responders. In five other patients, defined as nonresponders, propranolol did not decrease this pressure. The addition of ketanserin to propranolol induced further significant reduction in wedged hepatic venous pressure, hepatic venous pressure gradient and azygos blood flow. Among the five nonresponders, three had a reduced wedged hepatic venous pressure after ketanserin was combined. We conclude that verapamil does not reduce portal pressure or collateral blood flow in patients with alcoholic cirrhosis. The splanchnic hemodynamic effects of propranolol and ketanserin appear to be independent and additive, without significant systemic alteration.
authors.affiliation: Unité de Recherches de Physiopathologie Hépatique (INSERM), Hôpital Beaujon, Clichy, France.
authors.forename: A
authors.initials: A
authors.lastname: Hadengue
authors.forename: R
authors.initials: R
authors.lastname: Moreau
authors.forename: R
authors.initials: R
authors.lastname: Cerini
authors.forename: A
authors.initials: A
authors.lastname: Koshy
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
mesh_terms: D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy*; D007650:Ketanserin / Q000008:administration & dosage*; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy*; D011433:Propranolol / Q000008:administration & dosage*; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage*
chemical_list: D007650:Ketanserin; D011433:Propranolol; D014700:Verapamil