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      Liver Cirrhosis with Ascites: Pathogenesis of Resistance to Diuretics and Long-Term Efficacy and Safety of Torasemide

      a , b

      Cardiology

      S. Karger AG

      Liver cirrhosis, Ascites, Xipamide, Spironolactone, Furosemide, Torasemide, Diuretic resistance

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          Abstract

          In a prospective randomized short-term study, the efficacy and safety of xipamide and a combination of spironolactone and furosemide were compared in the treatment of hepatic cirrhotic ascites. Twenty-two patients were randomized to either xipamide, 20 mg/day (group I), or spironolactone, 200 mg/day, combined with furosemide, 40 mg on alternate days (group II). During the first 4 days of treatment, adequate diuresis, measured as loss of body weight greater than 1.6 kg, occurred in 7 patients in group I and in 3 in group II. In the latter group, another 4 patients responded satisfactorily after a further 4 days of treatment. Four patients in group I who failed to respond to xipamide with an adequate loss of body weight were subsequently treated with the spironolactone-furosemide combination, but only one responded. Two patients in group II who failed to respond to the combination of spironolactone and furosemide also failed to respond to xipamide. In both groups, a positive diuretic response occurred only when the pretreatment fractional sodium excretion exceeded 0.2%. Diuretic resistance was overcome only by additional treatments which reduced proximal tubular sodium reabsorption. Xipamide commonly induced hypokalaemia; in contrast hyperkalaemia was seen following treatment with the spironolactone-furosemide combination. Renal function remained stable in all patients during both diuretic treatments. An open ongoing 6-month trial of torasemide, 10-40 mg/day, in combination with spironolactone, 50-400 mg/day, has also been undertaken in 117 patients with cirrhotic ascites who showed inadequate responses to salt and water restriction and spironolactone alone. Twenty-seven patients have been withdrawn from the study, 9 for the complications of hepatic coma, bleeding oesophageal varices, or hyponatraemia. Twenty-two patients are still being treated and 68 have completed the trial on a mean dose of torasemide, 15 mg/day. Body weight was reduced by a mean of 2.3 kg at 6 weeks, 2.6 kg at 14 weeks and 3.2 kg after 6 months. Loss of body weight was primarily associated with reduction of ascites and secondarily with reduction of peripheral oedema. There were no untoward adverse reactions with torasemide, and no significant changes in serum electrolytes, liver, renal, or haematological variables.

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          Author and article information

          Journal
          CRD
          Cardiology
          10.1159/issn.0008-6312
          Cardiology
          S. Karger AG
          978-3-8055-6001-6
          978-3-318-01948-3
          0008-6312
          1421-9751
          1994
          1994
          18 November 2008
          : 84
          : Suppl 2
          : 87-98
          Affiliations
          aMedizinische Klinik I, St.-Bernward-Krankenhaus, Hildesheim, bJohann Wolfgang Goethe University,, Department of Pharmacology, Frankfurt/Main, Germany
          Article
          176461 Cardiology 1994;84:87–98
          10.1159/000176461
          7954550
          © 1994 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 12
          Categories
          Liver Cirrhosis and Ascites: Session IIIA

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