Acute Variceal Bleeding

Juan Carlos García-Pagán; Enric Reverter; Juan G. Abraldes; Jaime Bosch

doi:10.1055/s-0032-1301734

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2012; 33(01): 46-54
DOI: 10.1055/s-0032-1301734

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acute Variceal Bleeding

Juan Carlos García-Pagán

¹Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

²Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

,

Enric Reverter

¹Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

²Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

,

Juan G. Abraldes

¹Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

²Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

,

Jaime Bosch

¹Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

²Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

› Author Affiliations

Abstract

Bleeding from gastroesophageal varices is a frequent complication of cirrhosis. Mortality from a variceal bleeding episode has decreased in the last 2 decades from 40% to 15 to 20% due to the implementation of effective treatments and improvement in the general medical care. Initial treatment should include adequate fluid resuscitation and transfusion to maintain hemoglobin around 7 to 8 g/dL, and prophylactic antibiotics (norfloxacin or ceftriaxone). It is currently recommended that a vasoactive drug be started as soon as variceal bleeding is suspected. Vasoactive therapy should be maintained for up to 5 days to prevent early rebleeding. Where available, terlipressin, a vasopressin derivative, is the preferred agent because of its safety profile; it represents the only drug with proven efficacy in improving survival. Somatostatin and octreotide are used and are as effective as terlipressin in control of bleeding but have not been shown to reduce mortality. Endoscopic therapy must be performed within the first 12 hours after admission when the patient is stable. Variceal band ligation is the recommended endoscopic treatment, but injection sclerotherapy is an alternative if band ligation is technically difficult. Despite this standard of care, 10 to 20% of patients may still exhibit initial failure to control bleeding or early rebleeding within the first 5 days. In failures to control bleeding the use of rescue transjugular intrahepatic portosystemic shunt (TIPS) using covered stents is the best alternative. In mild early rebleeding a second course of endoscopic therapy may be attempted. If rebleeding is severe, placement of TIPS using covered stents is the first-choice rescue treatment. In refractory variceal bleeding episodes, balloon tamponade may be used as a temporary bridge to TIPS. Identification of patients that are at high risk of treatment failure may guide new strategies to improve outcomes. Indeed, a recent trial has shown that placement of TIPS, using covered stents, within 72 hours of admission in patients at high risk of treatment failure (i.e., those Child B with active bleeding or Child C less than 14 points) markedly decreased rebleeding and improved survival.

Keywords

cirrhosis - portal hypertension - variceal bleeding - endoscopic band ligation - sclerotherapy - terlipressin - somatostatin - tips

Full Text

References

References
1 D’Amico G. Esophageal varices: from appearance to rupture; natural history and prognostic indicators. In: Groszmann RJ, Bosch J, , eds. Portal Hypertension in the 21st Century. Dordrecht: Kluwer Academic; 2004: 147-154
2 Christensen E, Fauerholdt L, Schlichting P, Juhl E, Poulsen H, Tygstrup N. Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone. Gastroenterology 1981; 81 (5) 944-952
3 D’Amico G, Luca A. Natural history: clinical-haemodynamic correlations. Prediction of the risk of bleeding. Baillieres Clin Gastroenterol 1997; 11 (2) 243-256
4 de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis 2001; 5 (3) 645-663
5 Merli M, Nicolini G, Angeloni S , et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol 2003; 38 (3) 266-272
6 Groszmann RJ, Garcia-Tsao G, Bosch J , et al; Portal Hypertension Collaborative Group. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005; 353 (21) 2254-2261
7 D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999; 19 (4) 475-505
8 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 (15) 983-989
9 D’Amico G, De Franchis R ; Cooperative Study Group. Upper digestive bleeding in cirrhosis: post-therapeutic outcome and prognostic indicators. Hepatology 2003; 38 (3) 599-612
10 de Franchis R ; Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53 (4) 762-768
11 Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology 1981; 80 (4) 800-809
12 Chalasani N, Kahi C, Francois F , et al. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol 2003; 98 (3) 653-659
13 Bernard B, Cadranel JF, Valla D, Escolano S, Jarlier V, Opolon P. Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study. Gastroenterology 1995; 108 (6) 1828-1834
14 Goulis J, Armonis A, Patch D, Sabin C, Greenslade L, Burroughs AK. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage. Hepatology 1998; 27 (5) 1207-1212
15 Abraldes JG, Villanueva C, Bañares R , et al; Spanish Cooperative Group for Portal Hypertension and Variceal Bleeding. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol 2008; 48 (2) 229-236
16 Moitinho E, Escorsell A, Bandi JC , et al. Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology 1999; 117 (3) 626-631
17 Monescillo A, Martínez-Lagares F, Ruiz-del-Arbol L , et al. Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding. Hepatology 2004; 40 (4) 793-801
18 Carbonell N, Pauwels A, Serfaty L, Fourdan O, Lévy VG, Poupon R. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology 2004; 40 (3) 652-659
19 Augustin S, Muntaner L, Altamirano JT , et al. Predicting early mortality after acute variceal hemorrhage based on classification and regression tree analysis. Clin Gastroenterol Hepatol 2009; 7 (12) 1347-1354
20 Augustin S, Altamirano J, González A , et al. Effectiveness of combined pharmacologic and ligation therapy in high-risk patients with acute esophageal variceal bleeding. Am J Gastroenterol 2011; 106 (10) 1787-1795
21 Nidegger D, Ragot S, Berthelémy P , et al. Cirrhosis and bleeding: the need for very early management. J Hepatol 2003; 39 (4) 509-514
22 Cárdenas A, Ginès P, Uriz J , et al. Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis. Hepatology 2001; 34 (4 Pt 1) 671-676
23 Blei AT, Córdoba J ; Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. Am J Gastroenterol 2001; 96 (7) 1968-1976
24 Katon RM. Complications of upper gastrointestinal endoscopy in the gastrointestinal bleeder. Dig Dis Sci 1981; 26 (7, Suppl) 47S-54S
25 Kravetz D, Sikuler E, Groszmann RJ. Splanchnic and systemic hemodynamics in portal hypertensive rats during hemorrhage and blood volume restitution. Gastroenterology 1986; 90 (5 Pt 1) 1232-1240
26 Castañeda B, Morales J, Lionetti R , et al. Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats. Hepatology 2001; 33 (4) 821-825
27 Villanueva C, Ortiz J, Miñana J , et al. Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding. Gastroenterology 2001; 121 (1) 110-117
28 Morales J, Moitinho E, Abraldes JG, Fernández M, Bosch J. Effects of the V1a vasopressin agonist F-180 on portal hypertension-related bleeding in portal hypertensive rats. Hepatology 2003; 38 (6) 1378-1383
29 Tripodi A, Primignani M, Chantarangkul V , et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137 (6) 2105-2111
30 Ejlersen E, Melsen T, Ingerslev J, Andreasen RB, Vilstrup H. Recombinant activated factor VII (rFVIIa) acutely normalizes prothrombin time in patients with cirrhosis during bleeding from oesophageal varices. Scand J Gastroenterol 2001; 36 (10) 1081-1085
31 Bosch J, Thabut D, Bendtsen F , et al; European Study Group on rFVIIa in UGI Haemorrhage. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004; 127 (4) 1123-1130
32 Bosch J, Thabut D, Albillos A , et al; International Study Group on rFVIIa in UGI Hemorrhage. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: a randomized, controlled trial. Hepatology 2008; 47 (5) 1604-1614
33 Hou MC, Lin HC, Liu TT , et al. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Hepatology 2004; 39 (3) 746-753
34 Bernard B, Grangé 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 (6) 1655-1661
35 Rimola A, García-Tsao G, Navasa M , et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club. J Hepatol 2000; 32 (1) 142-153
36 Fernández J, Ruiz del Arbol L, Gómez C , et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology 2006; 131 (4) 1049-1056, quiz 1285
37 Villanueva C, Ortiz J, Sàbat M , et al. Somatostatin alone or combined with emergency sclerotherapy in the treatment of acute esophageal variceal bleeding: a prospective randomized trial. Hepatology 1999; 30 (2) 384-389
38 Bañares R, Albillos A, Rincón D , et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology 2002; 35 (3) 609-615
39 Escorsell A, Bandi JC, Moitinho E , et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. J Hepatol 1997; 26 (3) 621-627
40 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 (3) 471-476
41 Ioannou GN, Doust J, Rockey DC. Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther 2003; 17 (1) 53-64
42 Uriz J, Ginès P, Cárdenas A , et al. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol 2000; 33 (1) 43-48
43 Solà E, Lens S, Guevara M , et al. Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension. Hepatology 2010; 52 (5) 1783-1790
44 Tydén G, Sammegård H, Thulin L, Friman L, Efendić S. Treatment of bleeding esophageal varices with somatostatin. N Engl J Med 1978; 299 (26) 1466-1467
45 Bosch J, Kravetz D, Rodes J. Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin. Gastroenterology 1981; 80 (3) 518-525
46 Moitinho E, Planas R, Bañares R , et al; Variceal Bleeding Study Group. Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding. J Hepatol 2001; 35 (6) 712-718
47 Chen L, Groszmann RJ. Blood in the gastric lumen increases splanchnic blood flow and portal pressure in portal-hypertensive rats. Gastroenterology 1996; 111 (4) 1103-1110
48 McCormick PA, Jenkins SA, McIntyre N, Burroughs AK. Why portal hypertensive varices bleed and bleed: a hypothesis. Gut 1995; 36 (1) 100-103
49 Abraldes JG, Bosch J. Somatostatin and analogues in portal hypertension. Hepatology 2002; 35 (6) 1305-1312
50 Escorsell A, Bordas JM, del Arbol LR , et al; Variceal Bleeding Study Group. Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following acute variceal hemorrhage in patients with cirrhosis. J Hepatol 1998; 29 (5) 779-788
51 Escorsell A, Bandi JC, Andreu V , et al. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology 2001; 120 (1) 161-169
52 Burroughs AK ; International Octreotide Varices Study Group. Double blind RCT of 5 day octreotide versus placebo, associated with sclerotherapy for trial failures. Hepatology 1996; 24: 352A
53 Corley DA, Cello JP, Adkisson W, Ko WF, Kerlikowske K. Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology 2001; 120 (4) 946-954
54 Hsu YC, Chung CS, Tseng CH , et al. Delayed endoscopy as a risk factor for in-hospital mortality in cirrhotic patients with acute variceal hemorrhage. J Gastroenterol Hepatol 2009; 24 (7) 1294-1299
55 Cheung J, Soo I, Bastiampillai R, Zhu Q, Ma M. Urgent vs. non-urgent endoscopy in stable acute variceal bleeding. Am J Gastroenterol 2009; 104 (5) 1125-1129
56 Villanueva C, Piqueras M, Aracil C , et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol 2006; 45 (4) 560-567
57 Lo GH, Lai KH, Cheng JS , et al. A prospective, randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices. Hepatology 1995; 22 (2) 466-471
58 Abraldes JG, Angermayr B, Bosch J. The management of portal hypertension. Clin Liver Dis 2005; 9 (4) 685-713, vii
59 Avgerinos A, Armonis A, Stefanidis G , et al. Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis. Hepatology 2004; 39 (6) 1623-1630
60 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 (8979) 865-868
61 Avgerinos A, Nevens F, Raptis S, Fevery J. Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Lancet 1997; 350 (9090) 1495-1499
62 Calès P, Masliah C, Bernard B , et al; French Club for the Study of Portal Hypertension. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med 2001; 344 (1) 23-28
63 D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995; 22 (1) 332-354
64 Panés J, Terés J, Bosch J, Rodés J. Efficacy of balloon tamponade in treatment of bleeding gastric and esophageal varices: results in 151 consecutive episodes. Dig Dis Sci 1988; 33 (4) 454-459
65 Avgerinos A, Armonis A. Balloon tamponade technique and efficacy in variceal haemorrhage. Scand J Gastroenterol Suppl 1994; 207: 11-16
66 Terés J, Cecilia A, Bordas JM, Rimola A, Bru C, Rodés J. Esophageal tamponade for bleeding varices: controlled trial between the Sengstaken-Blakemore tube and the Linton-Nachlas tube. Gastroenterology 1978; 75 (4) 566-569
67 Hubmann R, Bodlaj G, Czompo M , et al. The use of self-expanding metal stents to treat acute esophageal variceal bleeding. Endoscopy 2006; 38 (9) 896-901
68 Zehetner J, Shamiyeh A, Wayand W, Hubmann R. Results of a new method to stop acute bleeding from esophageal varices: implantation of a self-expanding stent. Surg Endosc 2008; 22 (10) 2149-2152
69 Wright G, Lewis H, Hogan B, Burroughs A, Patch D, O’Beirne J. A self-expanding metal stent for complicated variceal hemorrhage: experience at a single center. Gastrointest Endosc 2010; 71 (1) 71-78
70 Boyer TD, Henderson JM, Heerey AM , et al; DIVERT Study Group. Cost of preventing variceal rebleeding with transjugular intrahepatic portal systemic shunt and distal splenorenal shunt. J Hepatol 2008; 48 (3) 407-414
71 Bosch J. Salvage transjugular intrahepatic portosystemic shunt: is it really life-saving?. J Hepatol 2001; 35 (5) 658-660
72 Escorsell A, Bañares R, García-Pagán JC , et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial. Hepatology 2002; 35 (2) 385-392
73 Patch D, Nikolopoulou V, McCormick A , et al. Factors related to early mortality after transjugular intrahepatic portosystemic shunt for failed endoscopic therapy in acute variceal bleeding. J Hepatol 1998; 28 (3) 454-460
74 García-Pagán JC, Caca K, Bureau C , et al; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362 (25) 2370-2379
75 Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 1992; 16 (6) 1343-1349
76 Sarin SK, Agarwal SR. Gastric varices and portal hypertensive gastropathy. Clin Liver Dis 2001; 5 (3) 727-767, x
77 Huang YH, Yeh HZ, Chen GH , et al. Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl) injection: long-term efficacy and safety. Gastrointest Endosc 2000; 52 (2) 160-167
78 Lo GH, Lai KH, Cheng JS, Chen MH, Chiang HT. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology 2001; 33 (5) 1060-1064
79 Tan PC, Hou MC, Lin HC , et al. A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation. Hepatology 2006; 43 (4) 690-697
80 Sarin SK, Jain AK, Jain M, Gupta R. A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices. Am J Gastroenterol 2002; 97 (4) 1010-1015
81 Chau TN, Patch D, Chan YW, Nagral A, Dick R, Burroughs AK. “Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding. Gastroenterology 1998; 114 (5) 981-987
82 Barange K, Péron JM, Imani K , et al. Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices. Hepatology 1999; 30 (5) 1139-1143
83 Mahadeva S, Bellamy MC, Kessel D, Davies MH, Millson CE. Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding. Am J Gastroenterol 2003; 98 (12) 2688-2693
84 Lo GH, Liang HL, Chen WC , et al. A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding. Endoscopy 2007; 39 (8) 679-685
85 Procaccini NJ, Al-Osaimi AM, Northup P, Argo C, Caldwell SH. Endoscopic cyanoacrylate versus transjugular intrahepatic portosystemic shunt for gastric variceal bleeding: a single-center U.S. analysis. Gastrointest Endosc 2009; 70 (5) 881-887
86 Matsumoto A, Hamamoto N, Nomura T , et al. Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices. Am J Gastroenterol 1999; 94 (3) 643-649