Advances in Therapy

, 25:1105 | Cite as

Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome

  • Aleksander KragEmail author
  • Tine Borup
  • Søren Møller
  • Flemming Bendtsen


Terlipressin is an analog of the natural hormone arginine-vasopressin. It is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS): two of the most dramatic and feared complications of cirrhosis. Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors. These receptors are located in vascular smooth muscle and mediate vasoconstriction. In patients with cirrhosis and portal hypertension, treatment with terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration. Furthermore, in patients with ascites terlipressin improves glomerular filtration and excretion of sodium. Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available. Terlipressin in combination with albumin reverses type 1 HRS in 33%–60% of cases and is the only treatment with proven efficacy in randomized trials. The safety profile is favorable when considering the clinical efficacy and the high mortality of these clinical entities. Adverse events are mostly cardiovascular and related to vasoconstriction. Mortality and withdrawal of terlipressin due to adverse events occurs in less than 1% of cases. Mild adverse events related to terlipressin treatment occur in 10%–20% of patients. The benefit, however, of terlipressin on long-term survival in HRS remains to be determined. At present, treatment with terlipressin and albumin is considered the most efficient therapy and should therefore be recommended for the treatment of type 1 HRS-1.


cirrhosis hepatorenal syndrome portal hypertension terlipressin variceal bleeding 


  1. 1.
    Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7: 122–128.PubMedCrossRefGoogle Scholar
  2. 2.
    Colle I, Durand F, Pessione F, et al. Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with terlipressin: a retrospective analysis. J Gastroenterol Hepatol. 2002;17:882–888.PubMedCrossRefGoogle Scholar
  3. 3.
    Carbonell N, Pauwels A, Serfaty L, Fourdan O, Levy VG, Poupon R. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology. 2004;40:652–659.PubMedCrossRefGoogle Scholar
  4. 4.
    McCormick PA, O’Keefe C. Improving prognosis following a first variceal haemorrhage over four decades. Gut. 2001;49:682–685.PubMedCrossRefGoogle Scholar
  5. 5.
    Freeman JG, Cobden I, Lishman AH, Record CO. Controlled trial of terlipressin (’Glypressin’) versus vasopressin in the early treatment of oesophageal varices. Lancet. 1982;2:66–68.PubMedCrossRefGoogle Scholar
  6. 6.
    Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet. 2003;362:1819–1827.PubMedCrossRefGoogle Scholar
  7. 7.
    Martín-Llahí M, Pepin MN, Guevara M, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134:1352–1359.PubMedCrossRefGoogle Scholar
  8. 8.
    Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci. 2008;53:830–835.PubMedCrossRefGoogle Scholar
  9. 9.
    Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360–1368.PubMedCrossRefGoogle Scholar
  10. 10.
    D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–231.PubMedCrossRefGoogle Scholar
  11. 11.
    Bosch J, Garcia-Pagan JC, Berzigotti A, Abraldes JG. Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liver Dis. 2006;26:348–362.PubMedCrossRefGoogle Scholar
  12. 12.
    Abraldes JG, Villanueva C, Banares R, et al. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48: 229–236.PubMedCrossRefGoogle Scholar
  13. 13.
    Ripoll C, Groszmann R, Garcia-Tsao G, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133:481–488.PubMedCrossRefGoogle Scholar
  14. 14.
    Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960–974.PubMedCrossRefGoogle Scholar
  15. 15.
    Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838–851.PubMedCrossRefGoogle Scholar
  16. 16.
    Pinzani M, Gentilini P. Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis. Semin Liver Dis. 1999;19:397–410.PubMedCrossRefGoogle Scholar
  17. 17.
    Groszmann RJ, Abraldes JG. Portal hypertension: from bedside to bench. J Clin Gastroenterol. 2005;39:S125–S130.PubMedCrossRefGoogle Scholar
  18. 18.
    D’Amico G, de Franchis R. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology. 2003;38:599–612.PubMedCrossRefGoogle Scholar
  19. 19.
    The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med. 1988;319:983–989.Google Scholar
  20. 20.
    Bambha K, Kim WR, Pedersen RA, Bida JP, Kremers WK, Kamath PS. Predictors of rebleeding and mortality following acute variceal hemorrhage in patients with cirrhosis. Gut. 2008;57:814–820.PubMedCrossRefGoogle Scholar
  21. 21.
    Bendtsen F, Krag A, Møller S. Treatment of acute variceal bleeding. Dig Liver Dis. 2008;40:328–336.PubMedCrossRefGoogle Scholar
  22. 22.
    de Franchis R, Primignani M. Endoscopic treatments for portal hypertension. Semin Liver Dis. 1999;19:439–455.PubMedCrossRefGoogle Scholar
  23. 23.
    Bernard B, Grange JD, Khac EN, Amiot X, Opolon P, Poynard T. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology. 1999;29:1655–1661.PubMedCrossRefGoogle Scholar
  24. 24.
    D’Amico G, Luca A. TIPS is a cost effective alternative to surgical shunt as a rescue therapy for prevention of recurrent bleeding from esophageal varices. J Hepatol. 2008;48:387–390.PubMedCrossRefGoogle Scholar
  25. 25.
    Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology. 1981;80:800–809.PubMedGoogle Scholar
  26. 26.
    Stokkeland K, Brandt L, Ekbom A, Hultcrantz R. Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969-2002. Hepatology. 2006;43:500–505.PubMedCrossRefGoogle Scholar
  27. 27.
    Garcia-Pagan JC, Escorsell A, Moitinho E, Bosch J. Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension. Semin Liver Dis. 1999;19:427–438.PubMedCrossRefGoogle Scholar
  28. 28.
    D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis: a Cochrane meta-analysis. Gastroenterology. 2003;124:1277–1291.PubMedCrossRefGoogle Scholar
  29. 29.
    Kowalski HJ, Abelmann WH. The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest. 1953;32:1025–1033.PubMedCrossRefGoogle Scholar
  30. 30.
    Hecker R, Sherlock S. Electrolyte and circulatory changes in terminal liver failure. Lancet. 1956;271:1121–1125.PubMedCrossRefGoogle Scholar
  31. 31.
    Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–1157.PubMedCrossRefGoogle Scholar
  32. 32.
    Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology. 2006;43:S121–S131.PubMedCrossRefGoogle Scholar
  33. 33.
    Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med. 2004;350:1646–1654.PubMedCrossRefGoogle Scholar
  34. 34.
    Schrier RW. Decreased effective blood volume in edematous disorders: what does this mean? J Am Soc Nephrol. 2007;18: 2028–2031.PubMedCrossRefGoogle Scholar
  35. 35.
    Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. J Hepatol. 2003;38(suppl. 1):S69–S89.PubMedCrossRefGoogle Scholar
  36. 36.
    Ruiz-del-Arbol L, Urman J, Fernandez J, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38:1210–1218.PubMedCrossRefGoogle Scholar
  37. 37.
    Ruiz-del-Arbol L, Monescillo A, Arocena C, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005;42:439–447.PubMedCrossRefGoogle Scholar
  38. 38.
    Epstein M, Berk DP, Hollenberg NK, et al. Renal failure in the patient with cirrhosis. The role of active vasoconstriction. Am J Med. 1970;49:175–185.PubMedCrossRefGoogle Scholar
  39. 39.
    Arroyo V, Terra C, Gines P. Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome. J Hepatol. 2007;46:935–946.PubMedCrossRefGoogle Scholar
  40. 40.
    Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310–1318.PubMedCrossRefGoogle Scholar
  41. 41.
    Alessandria C, Ottobrelli A, Bernardi-Venon W, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007;47:499–505.PubMedCrossRefGoogle Scholar
  42. 42.
    Halimi C, Bonnard P, Bernard B, et al. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol. 2002;14:153–158.PubMedCrossRefGoogle Scholar
  43. 43.
    Moreau R, Durand F, Poynard T, et al. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology. 2002;122:923–930.PubMedCrossRefGoogle Scholar
  44. 44.
    Mulkay JP, Louis H, Donckier V, et al. Longterm terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study. Acta Gastroenterol Belg. 2001;64:15–19.PubMedGoogle Scholar
  45. 45.
    Ortega R, Gines P, Uriz J, et al. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology. 2002;36:941–948.PubMedGoogle Scholar
  46. 46.
    Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103:1689–1697.PubMedCrossRefGoogle Scholar
  47. 47.
    Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol. 2003;18:152–156.PubMedCrossRefGoogle Scholar
  48. 48.
    Testro AG, Wongseelashote S, Angus PW, Gow PJ. Long-term outcome of patients treated with terlipressin for types 1 and 2 hepatorenal syndrome. J Gastroenterol Hepatol. 2007;23:1535–1540.CrossRefGoogle Scholar
  49. 49.
    Forsling ML, Aziz LA, Miller M, Davies R, Donovan B. Conversion of triglycylvasopressin to lysine-vasopressin in man. J Endocrinol. 1980;85:237–244.PubMedGoogle Scholar
  50. 50.
    Nilsson G, Lindblom P, Ohlin M, Berling R, Vernersson E. Pharmacokinetics of terlipressin after single i.v. doses to healthy volunteers. Drugs Exp Clin Res. 1990;16:307–314.PubMedGoogle Scholar
  51. 51.
    Holmes CL, Landry DW, Granton JT. Science review: vasopressin and the cardiovascular system part 1-receptor physiology. Crit Care. 2003;7:427–434.PubMedCrossRefGoogle Scholar
  52. 52.
    Krag A, Møller S, Henriksen JH, Holstein-Rathlou NH, Larsen FS, Bendtsen F. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology. 2007;46:1863–1871.PubMedCrossRefGoogle Scholar
  53. 53.
    Hirasawa A, Shibata K, Kotosai K, Tsujimoto G. Cloning, functional expression and tissue distribution of human cDNA for the vascular-type vasopressin receptor. Biochem Biophys Res Commun. 1994;203:72–79.PubMedCrossRefGoogle Scholar
  54. 54.
    Walker BR, Childs ME, Adams EM. Direct cardiac effects of vasopressin: role of V1-and V2-vasopressinergic receptors. Am J Physiol. 1988;255:H261–H265.PubMedGoogle Scholar
  55. 55.
    Boyle WA 3rd, Segel LD. Direct cardiac effects of vasopressin and their reversal by a vascular antagonist. Am J Physiol. 1986;251:H734–H741.PubMedGoogle Scholar
  56. 56.
    Barrett LK, Singer M, Clapp LH. Vasopressin: mechanisms of action on the vasculature in health and in septic shock. Crit Care Med. 2007;35:33–40.PubMedCrossRefGoogle Scholar
  57. 57.
    Treschan TA, Peters J. The vasopressin system: physiology and clinical strategies. Anesthesiology. 2006;105:599–612.PubMedCrossRefGoogle Scholar
  58. 58.
    Fenton RA, Knepper MA. Mouse models and the urinary concentrating mechanism in the new millennium. Physiol Rev. 2007;87:1083–1112.PubMedCrossRefGoogle Scholar
  59. 59.
    Nielsen S, Frøkiær J, Marples D, Kwon TH, Agre P, Knepper MA. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002;82:205–244.PubMedGoogle Scholar
  60. 60.
    Møller S, Hansen EF, Becker U, Brinch K, Henriksen JH, Bendtsen F. Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients. Liver. 2000;20:51–59.PubMedCrossRefGoogle Scholar
  61. 61.
    Romero G, Kravetz D, Argonz J, Bildozola M, Suarez A, Terg R. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. J Hepatol. 2000;32:419–425.PubMedCrossRefGoogle Scholar
  62. 62.
    Kiszka-Kanowitz M, Henriksen JH, Hansen EF, Møller S, Bendtsen F. Effect of terlipressin on blood volume distribution in patients with cirrhosis. Scand J Gastroenterol. 2004;39:486–492.PubMedCrossRefGoogle Scholar
  63. 63.
    Merkel C, Gatta A, Bolognesi M, et al. Hemodynamic changes of systemic, hepatic, and splenic circulation following triglycyllysin-vasopressin administration in alcoholic cirrhosis. Dig Dis Sci. 1988;33:1103–1109.PubMedCrossRefGoogle Scholar
  64. 64.
    Hansen EF, Bendtsen F, Brinch K, Møller S, Henriksen JH, Becker U. Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension. Scand J Gastroenterol. 2001;36:318–325.PubMedCrossRefGoogle Scholar
  65. 65.
    Baik SK, Jeong PH, Ji SW, et al. Acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis: a randomized comparison. Am J Gastroenterol. 2005;100:631–635.PubMedCrossRefGoogle Scholar
  66. 66.
    Escorsell A, Bandi JC, Moitinho E, et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. J Hepatol. 1997;26:621–627.PubMedCrossRefGoogle Scholar
  67. 67.
    Lin HC, Yang YY, Hou MC, et al. Hemodynamic effects of a combination of octreotide and terlipressin in patients with viral hepatitis related cirrhosis. Scand J Gastroenterol. 2002;37:482–487.PubMedCrossRefGoogle Scholar
  68. 68.
    Escorsell A, Bandi JC, Andreu V, et al. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology. 2001;120:161–169.PubMedCrossRefGoogle Scholar
  69. 69.
    Villanueva C, Planella M, Aracil C, et al. Hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. Am J Gastroenterol. 2005;100:624–630.PubMedCrossRefGoogle Scholar
  70. 70.
    Nevens F, Van SW, Yap SH, Fevery J. Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide. Gut. 1996;38:129–134.PubMedCrossRefGoogle Scholar
  71. 71.
    Cestari R, Braga M, Missale G, Ravelli P, Burroughs AK. Haemodynamic effect of triglycyl-lysine-vasopressin (glypressin) on intravascular oesophageal variceal pressure in patients with cirrhosis. A randomized placebo controlled trial. J Hepatol. 1990;10:205–210.PubMedCrossRefGoogle Scholar
  72. 72.
    Lote CJ, McVicar AJ, Thewles A. Renal haemodynamic actions of pressor doses of lysine vasopressin in the rat. J Physiol. 1987;391:407–418.PubMedGoogle Scholar
  73. 73.
    Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG. Association of beta-arrestin with G protein-coupled receptors during clathrinmediated endocytosis dictates the profile of receptor resensitization. J Biol Chem. 1999;274:32248–32257.PubMedCrossRefGoogle Scholar
  74. 74.
    Krag A, Bendtsen F, Pedersen EB, Holstein-Rathlou NH, Moller S. Effects of terlipressin on the aquaretic system-evidence of antidiuretic effects. Am J Physiol Renal Physiol. 2008 [Epub ahead of print]Google Scholar
  75. 75.
    Nadvornikova H, Schuck O. The influence of a single dose of vasopressin analogs on human renal potassium excretion. Int J Clin Pharmacol Ther Toxicol. 1982;20:155–158.PubMedGoogle Scholar
  76. 76.
    Stephan F, Paillard F. Terlipressinexacerbated hypokalaemia. Lancet. 1998;351:1249–1250.PubMedCrossRefGoogle Scholar
  77. 77.
    de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005;43:167–176.PubMedCrossRefGoogle Scholar
  78. 78.
    Ioannou GN, Doust J, Rockey DC. Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther. 2003;17:53–64.PubMedCrossRefGoogle Scholar
  79. 79.
    Hu RH, Lee PH. Open, randomized, comparative study of efficacy and safety between Haemopressin and Glypressin in treating acute esophageal varices hemorrhage. Hepatogastroenterology. 2008;55:448–452.PubMedGoogle Scholar
  80. 80.
    Bruha R, Marecek Z, Spicak J, et al. Doubleblind randomized, comparative multicenter study of the effect of terlipressin in the treatment of acute esophageal variceal and/or hypertensive gastropathy bleeding. Hepatogastroenterology. 2002;49:1161–1166.PubMedGoogle Scholar
  81. 81.
    Levacher S, Letoumelin P, Pateron D, Blaise M, Lapandry C, Pourriat JL. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. Lancet. 1995;346:865–868.PubMedCrossRefGoogle Scholar
  82. 82.
    Söderlund C, Magnusson I, Torngren S, Lundell L. Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. A double-blind, randomized, placebo-controlled trial. Scand J Gastroenterol. 1990;25:622–630.PubMedCrossRefGoogle Scholar
  83. 83.
    Walker S, Stiehl A, Raedsch R, Kommerell B. Terlipressin in bleeding esophageal varices: a placebo-controlled, double-blind study. Hepatology. 1986;6:112–115.PubMedCrossRefGoogle Scholar
  84. 84.
    Pauwels A, Florent C, Desaint B, Van Guivarch PH, Levy VG. Terlipressin and somatostatin in the treatment of hemorrhages from rupture of esophageal varices (letter) [French]. Gastroenterologie Clinique Biologique. 1994;18:388–389.Google Scholar
  85. 85.
    Brunati X, Ceriani R, Curioni R, Brunelli L, Repaci G, Morini L. Sclerotherapy alone vs scherotherapy plus terlipressin vs sclerotherapy plus octreotide in the treatment of acute variceal hemorrhage. Hepatology. 1996;24:207A.Google Scholar
  86. 86.
    Patch D, Caplin M, Greenslade L, Burroughs A. Randomized double blind controlled trial of 5 day terlipressin vs placebo in acute variceal hemorrhage. J Hepatol. 1999;30(suppl. 1):55.Google Scholar
  87. 87.
    Garcia-Tsao G, Groszmann RJ. Portal hemodynamics during nitroglycerin administration in cirrhotic patients. Hepatology. 1987;7:805–809.PubMedCrossRefGoogle Scholar
  88. 88.
    Moitinho E, Planas R, Banares R, et al. Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding. J Hepatol. 2001;35:712–718.PubMedCrossRefGoogle Scholar
  89. 89.
    Ottesen LH, Flyvbjerg A, Møller S, Bendtsen F. The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients. Aliment Pharmacol Ther. 1998;12:657–665.PubMedCrossRefGoogle Scholar
  90. 90.
    Møller S, Brinch K, Henriksen JH, Becker U. Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis. J Hepatol. 1997;26:1026–1033.PubMedCrossRefGoogle Scholar
  91. 91.
    Gotzsche PC, Hrobjartsson A. Somatostatin analogues for acute bleeding oesophageal varices. Cochrane Database Syst Rev. 2008;(3):CD000193.PubMedGoogle Scholar
  92. 92.
    Banares R, Albillos A, Rincon D, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology. 2002;35:609–615.PubMedCrossRefGoogle Scholar
  93. 93.
    Fort E, Sautereau D, Silvain C, Ingrand P, Pillegand B, Beauchant M. A randomized trial of terlipressin plus nitroglycerin vs. balloon tamponade in the control of acute variceal hemorrhage. Hepatology. 1990;11:678–681.PubMedCrossRefGoogle Scholar
  94. 94.
    Garcia-Compean D, Blanc P, Bories JM, et al. Treatment of active gastroesophageal variceal bleeding with terlipressin or hemostatic balloon in patients with cirrhosis. A randomized controlled trial. Arch Med Res. 1997;28:241–245.PubMedGoogle Scholar
  95. 95.
    Colin R, Giuli N, Czernichow P, et al. Prospective comparison of glypressin, tamponade and their association in the treatment of bleeding esophageal varices. In: Lebrec, D, Blei, AT, eds. Vasopressin Analogs and Portal Hypertension. Paris: John Libbey Eurotext; 1987:149–153.Google Scholar
  96. 96.
    Pedretti G, Elia G, Calzetti C, Magnani G, Fiaccadori F. Octreotide versus terlypressin in acute variceal hemorrhage in liver cirrhosis. Emergency control and prevention of early rebleeding. Clin Investig. 1994;72:653–659.PubMedCrossRefGoogle Scholar
  97. 97.
    Silvain C, Carpentier S, Sautereau D, et al. Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multicenter randomized trial. Hepatology. 1993;18:61–65.PubMedGoogle Scholar
  98. 98.
    Walker S, Kreichgauer HP, Bode JC. Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices-final report of a placebo-controlled, double-blind study. Gastroenterol. 1996;34:692–698.Google Scholar
  99. 99.
    Feu F, Ruiz del Arbol L, Banares R, Planas R, Bosch J. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Variceal Bleeding Study Group. Gastroenterology. 1996;111:1291–1299.PubMedCrossRefGoogle Scholar
  100. 100.
    Escorsell A, Ruiz del Arbol L, Planas R, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology. 2000;32:471–476.PubMedCrossRefGoogle Scholar
  101. 101.
    Wechowski J, Connolly M, Woehl A, et al. An economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with liver cirrhosis. Curr Med Res Opin. 2007;23:1481–1491.PubMedCrossRefGoogle Scholar
  102. 102.
    Connolly M, Bhatt A, Wechowski J, Colle I. An economic evaluation of vasoactive agents used to treat acute bleeding oesophageal varices in Belgium. Acta Gastroenterol Belg. 2008;71:230–236.PubMedGoogle Scholar
  103. 103.
    Angeli P, Merkel C. Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis. J Hepatol. 2008;48(suppl. 1):S93–S103.PubMedCrossRefGoogle Scholar
  104. 104.
    Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996;23:164–176.PubMedCrossRefGoogle Scholar
  105. 105.
    Duvoux C, Zanditenas D, Hezode C, et al. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study. Hepatology. 2002;36:374–380.PubMedCrossRefGoogle Scholar
  106. 106.
    Restuccia T, Ortega R, Guevara M, et al. Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study. J Hepatol. 2004;40:140–146.PubMedCrossRefGoogle Scholar
  107. 107.
    Barcroft H, Konzett H. On the actions of noradrenaline, adrenaline and isopropyl noradrenaline on the arterial blood pressure, heart rate and muscle blood flow in man. J Physiol. 1949;110:194–204.PubMedGoogle Scholar
  108. 108.
    Swan HJ. Noradrenaline, adrenaline, and the human circulation. BMJ. 1952;1:1003–1006.PubMedGoogle Scholar
  109. 109.
    Bellomo R, Giantomasso DD. Noradrenaline and the kidney: friends or foes? Crit Care. 2001;5:294–298.PubMedCrossRefGoogle Scholar
  110. 110.
    Pittner H, Turnheim K. Pulmonary and systemic circulatory effects of midodrine, a new sympathomimetic, and its metabolite, ST 1059. Arch Int Pharmacodyn Ther. 1974;207:180–192.PubMedGoogle Scholar
  111. 111.
    Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology. 1998;28:937–943.PubMedCrossRefGoogle Scholar
  112. 112.
    Kalambokis G, Economou M, Fotopoulos A, et al. The effects of chronic treatment with octreotide versus octreotide plus midodrine on systemic hemodynamics and renal hemodynamics and function in nonazotemic cirrhotic patients with ascites. Am J Gastroenterol. 2005;100:879–885.PubMedCrossRefGoogle Scholar
  113. 113.
    Kalambokis G, Fotopoulos A, Economou M, Pappas K, Tsianos EV. Effects of a 7-day treatment with midodrine in non-azotemic cirrhotic patients with and without ascites. J Hepatol. 2007;46:213–221.PubMedCrossRefGoogle Scholar
  114. 114.
    Angeli P, Volpin R, Gerunda G, et al. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology. 1999;29:1690–1697.PubMedCrossRefGoogle Scholar
  115. 115.
    Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004;40:55–64.PubMedCrossRefGoogle Scholar
  116. 116.
    Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci. 2007;52:742–748.PubMedCrossRefGoogle Scholar
  117. 117.
    Pomier-Layrargues G, Paquin SC, Hassoun Z, Lafortune M, Tran A. Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. Hepatology. 2003;38:238–243.PubMedCrossRefGoogle Scholar
  118. 118.
    Ottesen LH, Aagaard NK, Kiszka-Kanowitz M, et al. Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial. Hepatology. 2001;34:471–477.PubMedCrossRefGoogle Scholar
  119. 119.
    Kiser TH, Fish DN, Obritsch MD, Jung R, MacLaren R, Parikh CR. Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal syndrome: a retrospective study. Nephrol Dial Transplant. 2005;20:1813–1820.PubMedCrossRefGoogle Scholar
  120. 120.
    Gines P, Tito L, Arroyo V, et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology. 1988;94:1493–1502.PubMedGoogle Scholar
  121. 121.
    Moreau R, Asselah T, Condat B, et al. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study. Gut. 2002;50:90–94.PubMedCrossRefGoogle Scholar
  122. 122.
    Lata J, Marecek Z, Fejfar T, et al. The efficacy of terlipressin in comparison with albumin in the prevention of circulatory changes after the paracentesis of tense ascites-a randomized multicentric study. Hepatogastroenterology. 2007;54:1930–1933.PubMedGoogle Scholar
  123. 123.
    Singh V, Dheerendra PC, Singh B, et al. Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study. Am J Gastroenterol. 2008;103:1399–1405.PubMedCrossRefGoogle Scholar
  124. 124.
    Eefsen M, Dethloff T, Frederiksen HJ, Hauerberg J, Hansen BA, Larsen FS. Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support. J Hepatol. 2007;47:381–386.PubMedCrossRefGoogle Scholar
  125. 125.
    Shawcross DL, Davies NA, Mookerjee RP, et al. Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy. Hepatology. 2004;39:471–475.PubMedCrossRefGoogle Scholar
  126. 126.
    Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev. 2003;(1):CD002147.PubMedGoogle Scholar
  127. 127.
    D’Amico G, Traina M, Vizzini G et al. Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital. J Hepatol. 1994;20:206–212.PubMedCrossRefGoogle Scholar
  128. 128.
    Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterology. 2008;134:1715–1728.PubMedCrossRefGoogle Scholar
  129. 129.
    Gulberg V, Bilzer M, Gerbes AL. Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine. Hepatology. 1999;30:870–875.PubMedCrossRefGoogle Scholar
  130. 130.
    Guevara M, Gines P, Fernandez-Esparrach G, et al. Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology. 1998;27:35–41.PubMedCrossRefGoogle Scholar
  131. 131.
    Lee MY, Chu CS, Lee KT, et al. Terlipressinrelated acute myocardial infarction: a case report and literature review. Kaohsiung J Med Sci. 2004;20:604–608.PubMedGoogle Scholar
  132. 132.
    Rosario R, Lalanne B, Lebre P, et al. Myocardial infarction after injection of terlipressin for digestive hemorrhage. Gastroenterol Clin Biol. 1996;20:712–713.PubMedGoogle Scholar
  133. 133.
    Urge J, Sincl F, Prochazka V, Urbanek K. Terlipressin-induced ventricular arrhythmia. Scand J Gastroenterol. 2008;43:1145–1148.PubMedCrossRefGoogle Scholar
  134. 134.
    Kelly KJ, Stang JM, Mekhjian HS. Vasopressin provocation of ventricular dysrhythmia. Ann Intern Med. 1980;92:205–206.PubMedGoogle Scholar
  135. 135.
    Eden E, Teirstein A, Wiener I. Ventricular arrhythmia induced by vasopressin: torsade de pointes related to vasopressin-induced bradycardia. Mt Sinai J Med. 1983;50:49–51.PubMedGoogle Scholar
  136. 136.
    Mauro VF, Bingle JF, Ginn SM, Jafri FM. Torsade de pointes in a patient receiving intravenous vasopressin. Crit Care Med. 1988;16:200–201.PubMedCrossRefGoogle Scholar
  137. 137.
    Kupferschmidt H, Meier CH, Sulzer M, Meier PJ, Buhler H. Clinicopharmacological case. Bradycardia and ventricular tachycardia of the torsades de pointes type as a side effect of vasopressin: 3 case reports. Praxis. 1996;85:340–343.PubMedGoogle Scholar
  138. 138.
    Faigel DO, Metz DC, Kochman ML. Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. Am J Gastroenterol. 1995;90:822–824.PubMedGoogle Scholar
  139. 139.
    Stein LB, Dabezies MA, Silverman M, Brozena SC. Fatal torsade de pointes occurring in a patient receiving intravenous vasopressin and nitroglycerin. J Clin Gastroenterol. 1992;15:171–174.PubMedCrossRefGoogle Scholar
  140. 140.
    Klein GJ. Vasopressin, “torsades de pointes”, and QT syndrome. Ann Intern Med. 1980;93:511–512.PubMedGoogle Scholar
  141. 141.
    Ouattara A, Landi M, Le MY, et al. Comparative cardiac effects of terlipressin, vasopressin, and norepinephrine on an isolated perfused rabbit heart. Anesthesiology. 2005;102:85–92.PubMedCrossRefGoogle Scholar
  142. 142.
    Wu IC, Yu FJ, Chou JJ, et al. Predictive risk factors for upper gastrointestinal bleeding with simultaneous myocardial injury. Kaohsiung J Med Sci. 2007;23:8–16.PubMedCrossRefGoogle Scholar
  143. 143.
    Di Micoli A, Bracci E, Cappa FM, et al. Terlipressin infusion induces ischemia of breast skin in a cirrothic patient with hepatorenal syndrome. Dig Liver Dis. 2008;40:304–305.PubMedCrossRefGoogle Scholar
  144. 144.
    Donnellan F, Cullen G, Hegarty JE, McCormick PA. Ischaemic complications of Glypressin in liver disease: a case series. Br J Clin Pharmacol. 2007;64:550–552.PubMedCrossRefGoogle Scholar
  145. 145.
    Lee JS, Lee HS, Jung SW, et al. A case of peripheral ischemic complication after terlipressin therapy. Korean J Gastroenterol. 2006;47:454–457.PubMedGoogle Scholar
  146. 146.
    Vaccaro F, Giorgi A, Riggio O, De SA, Laviano A, Rossi-Fanelli F. Is spontaneous bacterial peritonitis an inducer of vasopressin analogue side-effects? A case report. Dig Liver Dis. 2003;35:503–506.PubMedCrossRefGoogle Scholar
  147. 147.
    Oh JE, Ha JS, Cho DH, Yu GJ, Shim SG. A case of ischemic skin necrosis after glypressin therapy in liver cirrhosis. Korean J Gastroenterol. 2008;51:381–384.PubMedGoogle Scholar
  148. 148.
    Willems MG, Schoenemann J, Rey C, Schafer H, Lindecken KD. Ischemia of the cecum caused by glycylpressin [in German]. Leber Magen Darm. 1985;15:165–168.PubMedGoogle Scholar
  149. 149.
    Hansen M, Bjerg J, Gilsaa T. Terlipressin and reversible intestinal ischaemia [in Danish]. Ugeskr Laeger. 2007;169:1802–1803.PubMedGoogle Scholar
  150. 150.
    Schmitt W, Wagner-Thiessen E, Lux G. Ischaemic colitis in a patient treated with glypressin for bleeding oesophageal varices. Hepatogastroenterology. 1987;34:134–136.PubMedGoogle Scholar
  151. 151.
    Machova A. Antidiuretic activity of terlipressin (triglycyl-lysine vasopressin)-role of pressure natriuresis. Physiol Res. 1992;41:121–127.PubMedGoogle Scholar
  152. 152.
    Douriez E, Mollard P, Laval C, Albengres E, Laporte JP, Tillement JP. Severe hyponatremia after repeated administration of terlipressin [in French]. Therapie. 1993;48:518–519.PubMedGoogle Scholar
  153. 153.
    Dunwoodie E, Jowett S. Terlipressin causing a hyponatraemic seizure. Scand J Gastroenterol. 2007;42:665.PubMedCrossRefGoogle Scholar
  154. 154.
    Chalasani N, Kahi C, Francois F, et al. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol. 2003;98:653–659.PubMedCrossRefGoogle Scholar
  155. 155.
    Alessandria C, Ozdogan O, Guevara M, et al. MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology. 2005;41:1282–1289.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare Communications 2008

Authors and Affiliations

  • Aleksander Krag
    • 1
    • 4
  • Tine Borup
    • 2
  • Søren Møller
    • 3
  • Flemming Bendtsen
    • 2
  1. 1.Departments of Gastroenterology and Clinical PhysiologyHvidovre University Hospital, Faculty of Health Sciences, University of CopenhagenCopenhagenDenmark
  2. 2.Department of GastroenterologyHvidovre University Hospital, Faculty of Health Sciences, University of CopenhagenCopenhagenDenmark
  3. 3.Department of Clinical PhysiologyHvidovre University Hospital, Faculty of Health Sciences, University of CopenhagenCopenhagenDenmark
  4. 4.Department of Medical GastroenterologyHvidovreDenmark

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