Recurrent variceal bleeding despite endoscopic and medical therapy
2004; Elsevier BV; Volume: 127; Issue: 2 Linguagem: Inglês
10.1053/j.gastro.2004.05.060
ISSN1528-0012
AutoresAnastasios A. Mihas, Arun J. Sanyal,
Tópico(s)Gastrointestinal Bleeding Diagnosis and Treatment
ResumoA 50-year-old female with cirrhosis due to hepatitis C was hospitalized 2 months ago with esophageal variceal bleeding and treated with endoscopic variceal band ligation (EVL). After discharge she was scheduled for repeated EVL. However, before this could be performed, she was readmitted with variceal hemorrhage, which was treated with EVL and octreotide. Despite the use of β-blocker therapy and 2 additional sessions of EVL following discharge, she is now readmitted with hematemesis and near syncope. Her physical examination reveals an anxious-appearing lady with a resting heart rate of 110 beats per minute and a blood pressure of 95/55 mm Hg. She has no evidence of ascites or asterixis. The current laboratory tests show hemoglobin = 7 gm/dL, bilirubin = 1.2 mg/dL, albumin = 3.5 gm/dL, INR = 1.2, creatinine = 0.9. Upper endoscopy, performed after resuscitation, reveals esophageal varices to be the source of bleeding and EVL is performed. Variceal hemorrhage remains a major cause of morbidity and mortality in patients with cirrhosis of the liver. While an improvement in the mortality associated with active hemorrhage has been reported in recent years,1Chalasani N. Kahi C. Francois F. Pinto A. Marathe A. Bini E.J. Pandya P. Sitaraman S. Shen J. Improved patient survival after acute variceal bleeding: a multicenter, cohort study.Am J Gastroenterol. 2003; 98: 653-659Crossref PubMed Scopus (329) Google Scholar, 2El Serag H.B. Everhart J.E. Improved survival after variceal hemorrhage over an 11-year period in the Department of Veterans Affairs.Am J Gastroenterol. 2000; 95: 3566-3573Crossref PubMed Google Scholar the long-term natural history of subjects who have survived an index bleed remains poor.3D'amico G. Morabito A. Pagliaro L. Marubini E. Survival and prognostic indicators in compensated and decompensated cirrhosis.Dig Dis Sci. 1986; 31: 468-475Crossref PubMed Scopus (493) Google Scholar, 4Fleischer D. 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Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension.J Hepatol. 2000; 33: 846-852Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar Any bleeding that occurs more than 48 hours after the initial admission for variceal hemorrhage and is separated by at least a 24-hour bleed-free period is considered to represent rebleeding. Rebleeding that occurs within 6 weeks of onset of an acute bleed represents early rebleeding while bleeding episodes that occur at later times are defined as late rebleeding episodes. Failure to prevent rebleeding is defined as a single rebleeding episode that meets the following criteria7de Franchis R. Developing consensus in portal hypertension.J Hepatol. 1996; 25: 390-394Abstract Full Text PDF PubMed Scopus (121) Google Scholar: (1) transfusion requirement of ≥2 units packed red cells within a 24-hour period from the time of hospitalization (time-zero) for that specific episode together with (2) a systolic blood pressure < 100 mm Hg or a postural change > 20 mm Hg and/or pulse rate > 100/min at time zero. It must be remembered that these definitions were primarily designed for standardization of nomenclature in clinical trials and, in routine clinical practice, one must continuously monitor the patient for signs of active bleeding and consider this in the context of the treatments provided. With currently available first-line treatment, i.e., medical and endoscopic treatment, the risk of failure to control acute bleeding is approximately 10%–20%.10D'amico G. Pagliaro L. Bosch J. 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It has recently been recognized that infections, both clinically apparent as well as inapparent, play an important role in the genesis of variceal hemorrhage and are important predictors of failure of first-line treatment in the setting of acute bleeding.18Zhao C. Chen S.B. Zhou J.P. Xiao W. Fan H.G. Wu X.W. Feng G.X. He W.X. Prognosis of hepatic cirrhosis patients with esophageal or gastric variceal hemorrhage: multivariate analysis.Hepatobiliary Pancreat Dis Int. 2002; 1: 416-419PubMed Google Scholar, 19Goulis J. Armonis A. Patch D. Sabin C. Greenslade L. Burroughs A.K. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage.Hepatology. 1998; 27: 1207-1212Crossref PubMed Scopus (340) Google Scholar, 20Bernard B. Cadranel J.F. Valla D. Escolano S. Jarlier V. Opolon P. 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Portal hypertension and variceal bleeding: an AASLD single topic symposium.Hepatology. 1998; 28: 868-880Crossref PubMed Scopus (330) Google Scholar During the first 6 weeks, recurrent variceal hemorrhage following EVL can occur both from varices and EVL-associated ulcers. Banding ulcers, while less frequent than endoscopic sclerotherapy (EST)-associated ulcers, can produce severe and recurrent hemorrhage. As expected, recurrent variceal hemorrhage usually occurs before the varices are obliterated by EVL.28Hou M.C. Lin H.C. Kuo B.I. Lee F.Y. Chang F.Y. Lee S.D. The rebleeding course and long-term outcome of esophageal variceal hemorrhage after ligation: comparison with sclerotherapy.Scand J Gastroenterol. 1999; 34: 1071-1076Crossref PubMed Scopus (33) Google Scholar High variceal pressures are likely to be associated with larger varices and greater difficulty in achieving variceal obliteration by EST.29Hou M.C. Lin H.C. Kuo B.I. Liao T.M. Lee F.Y. Chang F.Y. Lee S.D. 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The influence of endoscopic variceal ligation on the portal pressure gradient in cirrhotics.Hepatogastroenterology. 2003; 50: 102-106PubMed Google Scholar, 40Sarin S.K. Shahi H.M. Jain M. Jain A.K. Issar S.K. Murthy N.S. The natural history of portal hypertensive gastropathy: influence of variceal eradication.Am J Gastroenterol. 2000; 95: 2888-2893Crossref PubMed Google Scholar, 41Sarin S.K. Jain A.K. Lamba G.S. Gupta R. Chowdhary A. Isolated gastric varices: prevalence, clinical relevance and natural history.Dig Surg. 2003; 20: 42-47Crossref PubMed Scopus (27) Google Scholar These are important additional causes of rebleeding after esophageal variceal obliteration by EVL. The objectives of treatment in a person who rebleeds despite endoscopic treatment are clear: immediate achievement of hemostasis, and prevention of further rebleeding, liver failure, and death. Orthotopic liver transplantation (OLT) is the only modality that accomplishes all of these objectives.42Vargas H.E. Rakela J. Liver transplantation for variceal hemorrhage.Gastrointest Endosc Clin North Am. 1999; 9: 347-353PubMed Google Scholar Therefore, all patients who have survived a variceal bleed should be evaluated as potential candidates for OLT. While subjects are being evaluated for transplantation, several options are available for the prevention of recurrent variceal bleeding (Table 2 and Figure 3).Table 2Treatment Modalities Available for Recurrent Variceal HemorrhagePharmacologic Vasopressin and its analogues Somatostatin and its analoguesBalloon tamponadeEndoscopic Sclerotherapy Band ligation Hemoclips Argon plasma coagulation Tissue adhesives Thrombin/fibrin sealant (thrombin/fibrinogen)Radiologic Transjugular intrahepatic portosystemic shunt (TIPS) Transvenous retrograde variceal embolizationSurgery Decompressive procedures (shunts) Nonselective/total (portacaval) Selective (distal splenorenal) Partial (small H-graft) Nondecompressive procedures Esophageal transection Sugiura procedure Splenectomy Liver transplantation Open table in a new tab The normal first-line treatment of acute variceal hemorrhage includes pharmacologic treatment along with either EST or EVL. 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Somatostatin versus Sengstaken balloon tamponade for primary haemostasia of bleeding esophageal varices. A randomized pilot study.J Hepatol. 1991; 12: 100-105Abstract Full Text PDF PubMed Scopus (73) Google Scholar The principles of management of the individual who is readmitted for active bleeding after surviving a hospitalization for acute variceal hemorrhage are similar to those for acute variceal bleeding in general (Table 3). These individuals should be resuscitated hemodynamically and given prophylactic antibiotics.21Hou M.C. Lin H.C. Liu T.T. Kuo B.I. Lee F.Y. Chang F.Y. Lee S.D. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial.Hepatology. 2004; 39: 746-753Crossref PubMed Scopus (326) Google Scholar, 22Pohl J. Pollmann K. Sauer P. Ring A. Stremmel W. Schlenker T. 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Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial.Gastroenterology. 2002; 123: 17-23Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar and aid in the diagnosis of bleeding gastric varices.Table 3General Medical Management of Variceal HemorrhageVolume resuscitation Keep hemoglobin≈9–10 gm/dL Maintain urine output of at least 50 mL/hrCorrect hematologic status Packed red cells to replace blood loss Platelet transfusions if platelet counts < 50,000/mm3 Fresh frozen plasma versus recombinant factor VII for severe coagulopathySepsis Blood cultures and paracentesis Prophylactic intravenous antibiotics (3rd generation cephalosporin) switched to an oral quinolone when feasibleElectrolytes Monitor for hypokalemia, hypomagnesemia, hypophosphatemia in alcoholic subjects Monitor for hypocalcemia if large amounts of EDTA-containing blood products are usedManagement of encephalopathy and mental status changes Thiamine for the alcoholic subjects Monitor for and manage alcohol withdrawal Clear GI tract of blood with lactulose or PEG lavage solution and achieve hemostasisMaintain cardiopulmonary functions Protect airway for severe bleeding or mental status changes Optimize volume statusRenal functions Monitor urine output and serum creatinine Aseptic techniques for catheterization Open table in a new tab An attempt at endoscopic treatment may be attempted if the esophageal varices appear amenable to therapy and no obvious local complications of previous endoscopic treatment are apparent. The decision to perform additional endoscopic therapy must be individualized because there are no controlled trials that provide hard data on the value of these modalities in the setting of early rebleeding. The value of endosopic clips, snares, injection of thrombin, or injection of cyanoacrylate in this setting is not known. If additional endoscopic treatment is performed, one must be vigilant for signs of continued or recurrent bleeding and institute salvage therapy as soon as such signs appear. Transjugular intrahepatic portosystemic shunt (TIPS) represents an artificial communication between the hepatic and portal veins that is created angiographically.51Sanyal A.J. The use and misuse of transjugular intrahepatic portasystemic shunts.Curr Gastroenterol Rep. 2000; 2: 61-71Crossref PubMed Scopus (28) Google Scholar TIPS serves as a side-to-side portasystemic anastamosis and allows portal decompression without the need for major surgery or general anesthesia. The ability to achieve portal decompression without major surgery or risks of general anesthesia have led to numerous studies of its use both for the management of active variceal hemorrhage and prevention of recurrent variceal bleeding. Nine studies, that include 297 subjects, documenting the safety and efficacy of TIPS as a salvage treatment in the setting of acute variceal hemorrhage have been published (Table 4).52Banares R. Casado M. Rodriguez-Laiz J.M. Camunez F. Matilla A. Echenagusia A. Simo G. Piqueras B. Clemente G. Cos E. Urgent transjugular intrahepatic portosystemic shunt for control of acute variceal bleeding.Am J Gastroenterol. 1998; 93: 75-79Crossref PubMed Scopus (105) Google Scholar, 53Sanyal A.J. Freedman A.M. Shiffman M.L. Purdum P.P. Luketic V.A. Tisnado J. Cole P. Cheatham A. 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