Prevention of Recurrent Bleeding: Pharmacological Procedures

  • Wolfgang E. Fleig


Based on the factors which determine the transhepatic pressure gradient and, according to Laplace’s law, wall tension of esophageal varices, the aim of pharmacological agents for the prevention of initial and recurrent variceal bleeding should be to decrease portal flow and increase the diameter of the portal vascular bed and/or decrease transmural pressure of the varices and local bood flow through the gastroesophageal collateral veins. Transmural variceal pressure should be directly related to the transhepatic pressure gradient and, in the same patient, probably is. However, when a series of patients is analyzed, no conclusive correlation between these parameters is detected [1]. The obscured relationship between portal and variceal pressure on a statistical basis is most likely the result of a wide interindividual variation in the contribution of the different portal-systemic collateral channels (i. e., gastroesophageal versus rectal, splenorenal, umbilical etc.) to total collateral flow. Although the number of patients investigated was small and the follow-up short, recurrent variceal bleeding under a regimen of chronic endoscopic sclerotherapy appeared to be related to the pre-sclerotherapy variceal pressure [2]. The intra-individual relationship between portal pressure and the risk of first variceal bleeding and thus, indirectly, between portal and variceal pressure has been convincingly demonstrated in the recent Spanish-American prophylactic β-blocker trial [3]. In this study, no patient bled from varices whose portal pressure—either spontaneously or as a consequence of beta-adrenergic blockade— fell below 12 mmHg. Therefore, reduction of portal pressure and of gastroesophageal collateral flow should be the aim of any pharmacological intervention. Several drugs such as beta-adrenergic blockers, calcium antagonists, nitrates, serotonin antagonists, and others have been evaluated hemodynamically [4]. However, sufficient data on the prevention of variceal rebleeding from prospective controlled clinical trials are available only for beta-blockers. Therefore, this section will focus on beta-adrenergic blockers. The other drug candidates for the treatment of portal hypertension are discussed in Chap. 4.


Portal Hypertension Cirrhotic Patient Esophageal Varix Portal Pressure Hepatic Venous Pressure Gradient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gertsch PH, Bohnet J, Mosimann R (1983) Endoscopic non-aggressive assessment of oesophageal variceal pressure compared with wedged hepatic venous pressure in alcoholic liver cirrhosis. Endoscopy 5: 101–103CrossRefGoogle Scholar
  2. 2.
    Gertsch P, Loup P, Diserens H, Mosimann F, Mosimann R (1982) Endoscopic noninvasive manometry of esophageal varices: Prognostic significance. Am J Surg 144: 528–530PubMedCrossRefGoogle Scholar
  3. 3.
    Groszmann RJ, Bosch J, Grace N, Conn HO, Garcia-Tsao G, Navasa M, Albert J, Bermann M, Patrick M, Ródes J (1988) Hemodynamic events in a prospective randomized trial of propranolol vs. placebo in the prevention of the first variceal hemorrhage (abstract). Hepatology 8: 1242CrossRefGoogle Scholar
  4. 4.
    Fleig WE (1988) Pharmacological methods for the prevention of first and recurrent bleeding from esophagogastric varices. Z Gastroenterol 26: 40–48PubMedGoogle Scholar
  5. 5.
    Price HL, Cooperman LH, Warden JC (1967) Control of splanchnic circulation in man. Role of β-adrenergic receptors. Circ Res 21: 333–340Google Scholar
  6. 6.
    Lebrec D, Nouel O, Corbic M, Benhamou J-P (1980) Propranolol-A medical treatment for portal hypertension?. Lancet II: 180–182CrossRefGoogle Scholar
  7. 7.
    Lebrec C, Hillon P, Munoz C, Jungers J, Goldfarb G, Benhamou J-P (1982) The effect of propranolol on portal hypertension in patients with cirrhosis. A hemodynamic study. Hepatology 2: 523–527CrossRefGoogle Scholar
  8. 8.
    Hillon P, Lebrec D, Munoz C, Jungers J, Goldfarb G, Benhamou J-P (1982) Comparison of the effects of a cardioselective and a nonselective β-blocker on portal hypertension in patients with cirrhosis. Hepatology 2: 528–531PubMedCrossRefGoogle Scholar
  9. 9.
    Kong C-W, Lay C-S, Tsai Y-T, Lee S-D, Lai K-H, Lo K-J, Chiang BN (1986) Hemodynamic effect of propranolol on portal hypertension in patients with HBsAg-positive cirrhosis. Dig Dis Sci 31: 1303–1306PubMedCrossRefGoogle Scholar
  10. 10.
    Buetzow GH, Remmecke J, Braeuer A (1982) Metoprolol in portal hypertension. A controlled study. Klin Wochenschr 60: 1311–1314CrossRefGoogle Scholar
  11. 11.
    Mills PR, Rae AP, Farah DA, Russel RI, Lorimer AR, Carter DC (1984) Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension. Gut 25: 73–78PubMedCrossRefGoogle Scholar
  12. 12.
    Westaby D, Bihari DJ, Gimson AES, Crossley IR, Williams R (1984) Selective and non-selective beta receptor blockade in the reduction of portal pressure in patients with cirrhosis and portal hypertension. Gut 25: 121–124PubMedCrossRefGoogle Scholar
  13. 13.
    Kroeger RJ, Groszmann RJ (1985) Effect of selective blockade of β2-adrenergic receptors on portal and systemic hemodynamics in a portal hypertensive rat model. Gastroenterology 88: 896–900PubMedGoogle Scholar
  14. 14.
    Bihari D, Westaby D, Gimson AES, Crossley IR, Williams R (1984) Reductions in portal pressure by selective beta-2-adrenoreceptor blockade in patients with cirrhosis and portal hypertension. Br J Clin Pharmacol 17: 753–757PubMedCrossRefGoogle Scholar
  15. 15.
    Zoli M, Marchesini G, Brunori A, Cordiani MR, Pisi E (1986) Portal venous flow in response to acute β-blocker and vasodilatory treatment in patients with liver cirrhosis. Hepatology 6: 1248–1251PubMedCrossRefGoogle Scholar
  16. 16.
    Braillon A, Lee SS, Valla D, Geoffroy P, Sauvanet JP, Lebrec D (1988) Comparative haemodynamic effects of betaxolol and propranolol in patients with cirrhosis. Scand J Gastroenterol 23: 691–695PubMedCrossRefGoogle Scholar
  17. 17.
    Bosch J, Mastai R, Kravetz D, Bruix J, Gaya J, Rigau J, Ródes J (1984) Effects of propranolol on azygos venous blood flow and hepatic and systemic hemodynamics in cirrhosis. Hepatology 4: 1200–1205PubMedCrossRefGoogle Scholar
  18. 18.
    Garcia-Tsao G, Grace ND, Groszmann RJ, Conn HO, Bermann MM, Patrick MJC, Morse SS, Alberts JL (1986) Short-term effects of propranolol on portal venous pressure. Hepatology 6: 101–106PubMedCrossRefGoogle Scholar
  19. 19.
    Wensing G, Kamm M, Kratzshmer B, Hahn EG, Fleig WE (1990) Die Wirkung von Propranolol auf Pfortaderhochdruck und Portosystemichen Umgehungskreislauf bei Patienten mit alkoholischer Zirrhose (Abstract). SubmittedGoogle Scholar
  20. 20.
    Bosch J, Groszmann RJ (1984) Measurement of azygos venous blood flow by a continuous thermal dilution technique: An index of flow through gastroesophageal collaterals in cirrhosis. Hepatology 4: 424–429PubMedCrossRefGoogle Scholar
  21. 21.
    Cales P, Braillon A, Jiron MI, Lebrec D (1984) Superior portosystemic collateral circulation estimated by azygos blood flow in patients with cirrhosis. Lack of correlation with oesophageal varices and gastrointestinal bleeding. Effect of propranolol. J Hepatol 1: 37–46CrossRefGoogle Scholar
  22. 22.
    Mastai R, Bosch J, Navasa M, Kravetz D, Bruix J, Viola C, Ródes J (1987) Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis. J Hepatol 4: 71–79PubMedCrossRefGoogle Scholar
  23. 23.
    Ohnishi K, Nakayama T, Saito M, Hatano H, Tsukamoto T, Terabayashi H, Sugita S, Wada K, Nomura F, Koen H, Okuda K (1985) Effects of propranolol on portal hemodynamics in patients with chronic liver disease. Am J Gastroenterol 80: 132–135PubMedGoogle Scholar
  24. 24.
    Valla D, Bercoff E, Menu Y, Bataille C, Lebrec D (1984) Discrepancy between wedged hepatic venous pressure and portal venous pressure after acute propranolol administration in patients with alcoholic cirrhosis. Gastroenterology 86: 1400–1403PubMedGoogle Scholar
  25. 25.
    Rector WG (1985) Propranolol for portal hypertension: Evaluation of therapeutic response by direct measurement of portal vein pressure. Arch Intern Med 145: 648–650PubMedCrossRefGoogle Scholar
  26. 26.
    Hillon P, Blanchet L, Lebrec D (1982) Effect of propranolol on hepatic blood flow in normal and portal hypertensive rats. Clin Sci 63: 29–32PubMedGoogle Scholar
  27. 27.
    Gatta A, Sacerdoti D, Merkel C, Milani L, Battaglia G, Zuin R (1984) Effects of nadolol treatment on renal and hepatic hemodynamics and function in cirrhotic patients with portal hypertension. Am Heart J 108: 1167–1172PubMedCrossRefGoogle Scholar
  28. 28.
    Braillon A, Cales P, Lebrec D (1985) Comparison of the short-term effects of mepindolol and propranolol on splanchnic and systemic hemodynamics in patients with cirrhosis. Int J Clin Pharmacol Res 5: 223–228PubMedGoogle Scholar
  29. 29.
    Wink K (1984) Acute and chronic effects of the beta-receptor blocker mepindolol on hemodynamics and the portal circulation. Int J Pharmacol Ther Toxicol 22: 447–450Google Scholar
  30. 30.
    Spina, GP, Galeotti F, Opocher E, Santambrogio R, Cucchiaro G, Cornalbe G, Rota L, Ferrario M (1986) Effect of levomoprolol on systemic and portal haemodynamics. Ital J Gastroenterol 18: 241–244Google Scholar
  31. 31.
    Colman J, Jennings GL, McLean AJ, Mignot PR, Dudley FJ (1982) Propranolol in decompensated alcoholic cirrhosis (letter). Lancet II: 1040–1041CrossRefGoogle Scholar
  32. 32.
    Braillon A, Cales P, Valla D, Gaudy D, Geoffroy P, Lebrec D (1986) Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis. Gut 27: 1204–1209PubMedCrossRefGoogle Scholar
  33. 33.
    Caujolle B, Ballet F, Poupon R (1988) Relationship among beta-adrenergic blockade, propranolol concentration, and liver function in patients with cirrhosis. Scand J Gastroenterol 23: 925–930PubMedCrossRefGoogle Scholar
  34. 34.
    Gerbes AL, Remien J, Juengst D, Sauerbruch T, Paumgartner G (1986) Evidence for down-regulation of beta-2-adrenoreceptors in cirrhotic patients with severe ascites. Lancet I: 1409–1411CrossRefGoogle Scholar
  35. 35.
    Galant SP, Duriseti L, Underwood S, Insel PA (1978) Decreased beta-adrenergic receptors on polymorphonuclear leukocytes after adrenergic therapy. N Engl J Med 299: 933–936PubMedCrossRefGoogle Scholar
  36. 36.
    Aarons RA, Nies AS, Gal J, Hegstrand LR, Molinoff PB (1980) Elevation of β-adrenergic receptor density in human lymphocytes after propranolol administration. J Clin Invest 65: 949–957PubMedCrossRefGoogle Scholar
  37. 37.
    Henriksen JH, Ring-Larsen H, Christensen NJ (1984) Sympathetic nervous activity in cirrhosis. A survey of plasma catecholamine studies. J Hepatol 1: 55–65CrossRefGoogle Scholar
  38. 38.
    Lebrec D, Nouel O, Bernuau J, Bouygues M, Rueff B, Benhamou J-P (1981) Propranolol in prevention of recurrent gastrointestinal bleeding in cirrhotic patients. Lancet I: 920–921CrossRefGoogle Scholar
  39. 39.
    Lebrec D, Poynard T, Bernuau J, Bercoff E, Nouel O, Capron J-P, Poupon R, Bouvry M, Rueff B, Benhamou J-P (1984) A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: A final report. Hepatololgy 4: 355–358CrossRefGoogle Scholar
  40. 40.
    Lebrec D, Poynard T, Hillon P, Benhamou J-P (1981) Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis. Engl J Med 305: 1371–1374CrossRefGoogle Scholar
  41. 41.
    Conn HO (1984) Propranolol in portal hypertension: Problems in paradise? (editorial). Hepatology 4: 560–564PubMedCrossRefGoogle Scholar
  42. 42.
    Burroughs AK, Jenkins WJ, Sherlock S, Dunk A, Walt RP, Osuafor TOK, Mackie S, Dick R (1983) Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis. N Engl J Med 309: 1539–1542PubMedCrossRefGoogle Scholar
  43. 43.
    Villeneuve J-P, Pomier-Layrargues G, Infante-Rivard C, Willems B, Huet P-M, Marleau D, Viallet A (1986) Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial. Hepatology 6: 1239–1243PubMedCrossRefGoogle Scholar
  44. 44.
    Queuniet AM, Czernichow P, Lerebours E, Ducrotte P, Tranvouez JL, Colin R (1987) Controlled trial of propranolol for the prevention of recurrent gastrointestinal bleeding in patients with cirrhosis. Gastroenterol Clin Biol 11: 41–47PubMedGoogle Scholar
  45. 45.
    Kobe E, Schentke K-U (1987) Unsichere Rezidivprophylaxe von Oesophagusvarizenblutungen durch Propranolol bei Leberzirrhotikern: Eine prospektive kontrollierte Studie. Z Klin Med 42: 507–510Google Scholar
  46. 46.
    Colombo M, DeFranchis R, Tommasini M, Sangiovanni A, Dioguardi N (1989) β-Blockade prevents recurrent gastrointestinal bleeding in well-compensated patients with alcoholic cirrhosis: A multicenter randomized controlled trial. Hepatology 9: 433–438PubMedCrossRefGoogle Scholar
  47. 47.
    Gatta A, Merkel C, Sacerdoti D, Bolognesi M, Caregaro L, Zuin R, Angeli P, Ruol A (1987) Nadolol for prevention of variceal rebleeding in cirrhosis: A controlled clinical trial. Digestion 37: 22–28PubMedCrossRefGoogle Scholar
  48. 48.
    Marbet UA, Straumann A, Gyr KE, Beglinger C, Schaub N, Voegtlin J, Kiowski W, Ritz R, Stalder GA (1988) Reduction in early recurrence of variceal bleeding by propranolol. Scand J Gastroenterol 23: 369–374PubMedCrossRefGoogle Scholar
  49. 49.
    Sheen IS, Chen TY, Liaw YF (1989) Randomized controlled study of propranolol for prevention of recurrent esophageal varices bleeding in patients with cirrhosis. Liver 9: 1–5PubMedCrossRefGoogle Scholar
  50. 50.
    Cerbelaud P, Lavignolle A, Perrin D, Jutel D, Beaujard F, Colomb P, Le Bodic L (1986) Propranolol et prevention des recidives par rupture de varice oesophagienne du cirrhotique (abstract). Gastroenterol Clin Biol 18: A10Google Scholar
  51. 51.
    Mills PR, Garden OJ, Birnie GG, Carter DC (1987) Propranolol in the prevention of further variceal hemorrhage in cirrhosis (abstract). Gastroenterology 92: 1755Google Scholar
  52. 52.
    Kiire CF (1989) Controlled trial of propranolol to prevent recurrent variceal bleeding in patients with non-cirrhotic portal fibrosis. Br Med J 298: 1363–1365CrossRefGoogle Scholar
  53. 53.
    Papazian A, Braillon A, Dupas JL, Sevenet F, Capron JP (1986) Portal hypertensive gastric mucosa: An endoscopic study. Gut 27: 1199–1203PubMedCrossRefGoogle Scholar
  54. 54.
    Sankary H, Sarfeh IJ, Tarnawski A, Maeda R, Ivey KJ, Mason GR (1986) Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats. Dig Dis Sci 31: 162–165PubMedCrossRefGoogle Scholar
  55. 55.
    Hosking SW, Kennedy HJ, Seddon I, Triger DR (1987) The role of propranolol in congestive gastropathy of portal hypertension. Hepatology 7: 437–441PubMedCrossRefGoogle Scholar
  56. 56.
    Korula J, Balart LA, Radvan G, Zweiban BE, Larson W, Kao HW, Yamada S (1985) A prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy. Hepatology 5: 584–589PubMedCrossRefGoogle Scholar
  57. 57.
    Soederlund C, Ihre T (1985) Endoscopic sclerotherapy v. conservative management of bleeding oesophageal varices. Acta Chir Scand 151: 449–456Google Scholar
  58. 58.
    Terblanche J, Bornman PC, Kahn D, Jonker MAT, Campbell JAH, Wright J, Kirsch R (1983) Failure of repeated injection sclerotherapy to improve long-term survival after oesophageal variceal bleeding. A five-year prospective controlled clinical trial. Lancet II: 1328–1332CrossRefGoogle Scholar
  59. 59.
    The Copenhagen esophageal varices sclerotherapy project (1984) Sclerotherapy after first variceal hemorrhage in cirrhosis. A randomized multicenter trial. N Engl J Med 311: 1594–1600CrossRefGoogle Scholar
  60. 60.
    Westaby D, Macdougall BRD, Williams R (1985) Improved survival following injection sclerotherapy of esophageal varices: Final analysis of a controlled trial. Hepatology 5: 827–830PubMedCrossRefGoogle Scholar
  61. 61.
    Alexandrino PT, Alves MM, Pinto Correia J (1988) Propranolol or endoscopie sclerotherapy in the prevention of recurrence of variceal bleeding. A prospective, randomized controlled trial. J Hepatol 7: 175–185PubMedCrossRefGoogle Scholar
  62. 62.
    Dollet JM, Champigneulle B, Patris A, Bigard MA, Gaucher P (1988) Sclérotherapie endoscopique contre propranolol après hémorragie par rupture de varices oesophagiennes chez le cirrhotique. Resultats à 4 ans d’une étude randomisée. Gastroenterol Clin Biol 12: 234–239PubMedGoogle Scholar
  63. 63.
    Fleig WE, Stange EF, Hunecke R, Schoenborn W, Hurler U, Rainer K, Gaus W, Ditschuneit H (1987) Prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage: Prospective, randomized comparison of propranolol and sclerotherapy. Hepatology 7: 355–361PubMedCrossRefGoogle Scholar
  64. 64.
    Fleig WE, Stange EF, Schoenborn W, Woerdehoff D, Preclik G, Nuber R, Rainer K, Ditschuneit H (1988) Final analysis of a randomized trial of propranolol vs. sclerotherapy for the prevention of recurrent variceal hemorrhage in cirrhosis (abstract). Hepatology 8: 1220Google Scholar
  65. 65.
    Teres J, Bosch J, Bordas JM, Navasa M, Mas A, Mastai R, Rodes J (1987) Endoscopic sclerotherapy vs propranolol in the elective treatment of variceal bleeding. Preliminary results of a randomized controlled clinical trial (abstract). J Hepatol 5: S210Google Scholar
  66. 66.
    Westaby D, Melia WM, Macdougall BRD, Hegarty JE, Gimson AE, Williams R (1985) B1-selective adrenoreceptor blockade for the long-term management of variceal bleeding. A prospective randomised trial to compare oral metoprolol with injection sclerotherapy in cirrhosis. Gut 26: 421–425PubMedCrossRefGoogle Scholar
  67. 67.
    Westaby D, Poison RJ, Gimson AES, Hayes PC, Hayllar K, Williams R (1990) A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term management of variceal bleeding. Hepatology 11: 353–359PubMedCrossRefGoogle Scholar
  68. 68.
    Jensen LS, Krarup N (1989) Propranolol in prevention of rebleeding from oesophageal varices during the course of endoscopie sclerotherapy. Scand J Gastroenterol 24: 339–345PubMedCrossRefGoogle Scholar
  69. 69.
    O’Connor KW, Lehman G, Yune H, Brunelle R, Christiansen P, Hast J, Compton M, McHenry R, Klatte E, Cockerill E, Holden R, Becker G, Kopecky K, Hawes R, Pound D, Rex D, Lui A, Snodgrass P, Weddle R, Crabb D, Lumeng L (1989) Comparison of three nonsurgical treatments for bleeding esophageal varices. Gastroenterology 96: 899–906PubMedGoogle Scholar
  70. 70.
    Westaby D, Melia W, Hegarty J, Gimson AES, Stellon AJ, Williams R (1986) Use of propranolol to reduce the rebleeding rate during injection sclerotherapy prior to variceal obliteration. Hepatology 6: 673–675PubMedCrossRefGoogle Scholar
  71. 71.
    Westaby D, Hayes PC, Gimson AES, Vlavianos P, Williams R (1987) The complexity of response of both systemic and portal hemodynamics to propranolol. A study of dose response (abstract). J Hepatol 5: S72Google Scholar
  72. 72.
    Poynard T, Lebrec D, Hillon P, Sayegh R, Bernuau J, Naveau S, Chaput J-C, Klepping C, Rueff B, Benhamou J-P (1987) Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: A prospective study of factors associated with rebleeding. Hepatology 7: 447–451PubMedCrossRefGoogle Scholar
  73. 73.
    Zelen M (1971) The analysis of several 2 × 2 contingency tables. Biometrika 58: 129–137Google Scholar
  74. 74.
    Burroughs AK, McCormick PA (1990) Long-term pharmacologic therapy of portal hypertension. Surg Clin North Am 70: 319–339PubMedGoogle Scholar
  75. 75.
    Bendtsen F, Henriksen JH, Becker U, Soerensen TIA (1987) Effect of oral propranolol on splanchnic oxygen uptake and haemodynamics in patients with cirrhosis. J Hepatol 5: 137–143PubMedCrossRefGoogle Scholar
  76. 76.
    Vinel JP, Caucans JP, Cales P, Suduca JM, Voigt JJ, Pascal JP (1988) Effect of propranolol on metabolic activity of the liver in patients with alcoholic cirrhosis. J Hepatol 7: 186–192PubMedCrossRefGoogle Scholar
  77. 77.
    Snady H, Lieber CS (1988) Venous, arterial, and arterialized-venous blood ammonia levels and their relationship to hepatic encephalopathy after propranolol. Am J Gastroenterol 83: 249–255PubMedGoogle Scholar
  78. 78.
    Van Buuren HR, Van der Velden PC, Koorevaar G, Silberbusch J (1982) Propranolol increases arterial ammonia in liver cirrhosis. Lancet II: 951–952CrossRefGoogle Scholar
  79. 79.
    Reding P (1982) Risk of hepatic encephalopathy in patients taking propranolol for portal hypertension (letter). Lancet II: 550CrossRefGoogle Scholar
  80. 80.
    Tarver D, Walt RP, Dunk AA, Jenkins WJ, Sherlock S (1983) Precipitation of hepatic encephalopathy by propranolol in cirrhosis. Br Med J 287: 585CrossRefGoogle Scholar
  81. 81.
    Arthur MJP, Tanner AR, Patel C, George CF, Wright R (1982) Portal hypertension, propranolol, and hepatic encephalopathy (letter). Lancet II: 879CrossRefGoogle Scholar
  82. 82.
    Watson P, Hayes JR (1983) Cirrhosis, hepatic encephalopathy, and propranolol (letter). Br Med J 287: 1067CrossRefGoogle Scholar
  83. 83.
    De Leeuw PW, Birkenhager WH (1982) Renal response to propranolol treatment in hypertensive humans. Hypertension 4: 125–131PubMedCrossRefGoogle Scholar
  84. 84.
    Bataille C, Bercoff E, Pariente EA, Valla D, Lebrec D (1984) Effects of propranolol on renal blood flow and renal function in patients with cirrhosis. Gastroenterology 86: 129–133PubMedGoogle Scholar
  85. 85.
    Wilkinson SP, Bernardi M, Smith IK, Jowett TP, Slater JDH, Williams R (1977) Effect of β-adrenergic blocking drugs on the renin-aldosterone system, sodium excretion, and renal hemodynamics in cirhosis with ascites. Gastroenterology 73: 659–663PubMedGoogle Scholar
  86. 86.
    Hayes PC, Stewart WW, Bouchier IAD (1984) Influence of propranolol on weight and salt and water homeostasis in chronic liver disease. Lancet II: 1064–1068CrossRefGoogle Scholar
  87. 87.
    Lee S, Braillon A, Girod C, Geoffroy P, Lebrec D (1986) Haemodynamic rebound phenomena after abrupt cessation of propranolol therapy in portal hypertensive rats. J Hepatol 3: 38–41PubMedCrossRefGoogle Scholar
  88. 88.
    Lebrec D, Bernuau J, Rueff B, Benhamou J-P (1982) Gastrointestinal bleeding after abrupt cessation of propranolol administration in cirrhossis (letter). N Engl J Med 307: 560PubMedGoogle Scholar
  89. 89.
    Alabaster SL, Gogel HK, McCarthy DM (1983) Propranolol withdrawal and variceal hemorrhage (letter). JAMA 250: 3047PubMedCrossRefGoogle Scholar
  90. 90.
    Maringhini A, Simonetti RM, Marceno MP, Pagliaro L (1982) Propranolol for gastrointestinal bleeding in cirrhosis (letter). N Engl J, Med 307: 1710Google Scholar
  91. 91.
    Lebrec D, Poynard T, Capron J-P, Hillon P, Geoffroy P, Roulot D, Chaput J-C, Rueff B, Benhamou J-P (1988) Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis. A randomized trial. J Hepatol 7: 118–125PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 1991

Authors and Affiliations

  • Wolfgang E. Fleig
    • 1
  1. 1.Medizinische Klinik I mit PoliklinikFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Personalised recommendations