Management of actively bleeding esophageal varices

Abstract

Patients with variceal hemorrhage have more clinically severe bleeding with significantly more complications, blood transfusions, interventions, and deaths than patients with other causes of upper gastrointestinal bleeding. Most patients who present with acute bleeding due to esophageal varices do not have evidence of active bleeding at the time of endoscopy. For example, a recent overview of seven prospective, randomized trials comparing ligation and sclerotherapy for the treatment of variceal hemorrhage found that only 27% of patients had active bleeding at the time of initial endoscopy.1Laine L Cook D Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: A meta-analysis.Ann Intern Med. 1995; 123: 280-287Crossref PubMed Scopus (606) Google Scholar Furthermore, some investigators may overestimate the proportion of patients with active bleeding because in a patient with a recent major bleeding episode, large amounts of red blood may be moving back and forth in the proximal stomach and esophagus, leading to an erroneous diagnosis of “active bleeding.” I only label varices as actively bleeding if I can clearly identify blood emanating from a varix. In our unit, we find that about one fifth of patients with esophageal varices as a source of bleeding who undergo endoscopy within 24 hours of presentation have active bleeding.2Laine L El-Newihi HM Migicovsky B Sloane R Garcia F Endoscopic ligation compared with sclerotherapy for treatment of bleeding esophageal varices.Ann Intern Med. 1993; 119: 1-7Crossref PubMed Scopus (322) Google Scholar, 3Laine L Stein C Sharma V Randomized comparison of ligation vs. ligation plus sclerotherapy in patients with bleeding esophageal varices.Gastroenterology. 1996; 110: 529-533Abstract Full Text PDF PubMed Scopus (108) Google ScholarBecause a significant proportion of patients with cirrhosis (and even with documented varices) bleed from a nonvariceal source, I believe it is important to perform endoscopy early in patients with known or suspected portal hypertension to determine if varices are the source of bleeding or if a nonvariceal site is present. Bleeding from a nonvariceal source predicts a better prognosis for the patient and therefore provides important information. During this diagnostic endoscopy, if varices are identified as the source of bleeding (i.e., active bleeding, overlying clot or white nipple sign, or documented upper gastrointestinal bleeding with no other potential bleeding sites on upper endoscopy), then endoscopic therapy should be applied.Endoscopic sclerotherapy has been reported to stop active variceal bleeding in 62% to 100% of patients and generally appears to be more effective than standard therapy, such as vasopressin or balloon tamponade.4Larson AW Cohen H Zweiban B Chapman D Gourdji M Korula J et al.Acute esophageal variceal sclerotherapy: results of a prospective randomized controlled trial.JAMA. 1986; 255: 497-500Crossref PubMed Scopus (157) Google Scholar, 5Westaby D Hayes PC Gimson AES Polson RJ Williams R Controlled clinical trial of injection sclerotherapy for active variceal bleeding.Hepatology. 1989; 9: 274-277Crossref PubMed Scopus (189) Google Scholar, 6Paquet KJ Feussner H Endoscopic sclerosis and esophageal balloon tamponade in acute hemorrhage from esophagogastric varices: a prospective controlled randomized trial.Hepatology. 1985; 5: 580-583Crossref PubMed Scopus (251) Google Scholar, 7Moreto M Zaballa M Bernal A Ibanez W Ojembarrena E Rodriguez A A randomized trial of tamponade or sclerotherapy as immediate treatment for bleeding esophageal varices.Surg Gyn Obstet. 1988; 167: 331-334PubMed Google Scholar, 8Hartigan PM Gebhard RL Gregory PB Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis.Gastrointest Endosc. 1997; 46: 1-7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar The study in this issue of Gastrointestinal Endoscopy from Hartigan et al.8Hartigan PM Gebhard RL Gregory PB Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis.Gastrointest Endosc. 1997; 46: 1-7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar specifically examines the subset of patients in the large VA Cooperative Variceal Sclerotherapy Group Study who had episodes of active bleeding. The VA Cooperative study9The Veterans Affairs Cooperative Variceal Sclerotherapy Group Sclerotherapy for male alcoholic cirrhotic patients who have bled from esophageal varices: results of a randomized, multicenter clinical trial.Hepatology. 1994; 20: 618-625PubMed Google Scholar did not have any specific clinical entry criteria regarding episodes of bleeding; they included anyone with alcoholic liver disease and a history of bleeding from esophageal varices. Thus 49 (19%) of 253 enrolled patients were “actively bleeding,” 176 (70%) had bleeding within the previous 2 weeks, and the remainder bled more than 2 weeks earlier (including 8 patients with bleeding episodes more than 1 year earlier). Interestingly, active bleeding is not defined in this and many other studies, so we do not know for certain if active bleeding means blood emanating from the varix or just the presence of red blood in the upper gastrointestinal tract at endoscopy.Hartigan et al.8Hartigan PM Gebhard RL Gregory PB Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis.Gastrointest Endosc. 1997; 46: 1-7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar report that sclerotherapy was clearly beneficial in the group of patients with active bleeding: endoscopic therapy was efficacious in halting bleeding and in decreasing recurrent bleeding, transfusion requirements, the rate of shunt surgery, and mortality. In the group presenting with active bleeding at the index endoscopy, the survival rates at 6 months still favored sclerotherapy (60% vs 38% survival), but by 2 years the rates had narrowed so that both treated and untreated patients fared poorly (38% vs 27% survival).9The Veterans Affairs Cooperative Variceal Sclerotherapy Group Sclerotherapy for male alcoholic cirrhotic patients who have bled from esophageal varices: results of a randomized, multicenter clinical trial.Hepatology. 1994; 20: 618-625PubMed Google ScholarThe VA Cooperative Esophageal Variceal Study was initiated in February 1985—more than a decade ago.9The Veterans Affairs Cooperative Variceal Sclerotherapy Group Sclerotherapy for male alcoholic cirrhotic patients who have bled from esophageal varices: results of a randomized, multicenter clinical trial.Hepatology. 1994; 20: 618-625PubMed Google Scholar A variety of changes have occurred since 1985 in medical, endoscopic, and radiologic options for the treatment of patients with bleeding esophageal varices. The VA Cooperative Study and other studies do demonstrate a benefit with the use of sclerotherapy as compared to no sclerotherapy and to “conservative” medical therapy for patients with active bleeding. But what about other newer therapies?Endoscopic ligation appears to have a number of advantages over sclerotherapy for the treatment of esophageal varices, including lower rates of recurrent bleeding, lower mortality, fewer local complications (e.g., esophageal strictures), and fewer treatment sessions required to achieve variceal obliteration.1Laine L Cook D Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: A meta-analysis.Ann Intern Med. 1995; 123: 280-287Crossref PubMed Scopus (606) Google Scholar Endoscopic ligation therapy also is effective in stopping active esophageal variceal bleeding, with rates of hemostasis around 80% to 100%.10Laine L Ligation: endoscopic treatment of choice for patients with bleeding esophageal varices?.Hepatology. 1995; 22: 663-665Crossref PubMed Google Scholar However, evaluation of randomized trials comparing ligation and sclerotherapy indicate that the two endoscopic therapies have similar efficacies in the control of active bleeding.1Laine L Cook D Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: A meta-analysis.Ann Intern Med. 1995; 123: 280-287Crossref PubMed Scopus (606) Google Scholar, 10Laine L Ligation: endoscopic treatment of choice for patients with bleeding esophageal varices?.Hepatology. 1995; 22: 663-665Crossref PubMed Google ScholarAt present, I believe that ligation therapy should generally be considered the endoscopic treatment of choice for esophageal variceal bleeding. However, results from the trials mentioned above do suggest that either sclerotherapy or ligation may be considered effective in the subset of patients with active bleeding. Furthermore, ligation sometimes may be technically difficult to perform in patients with a large amount of blood in the esophagus. The cylinder attached to the tip of the endoscope markedly decreases the field of view, and blood filling the interior of the cylinder also may obscure the endoscopist's view. Therefore, treatment of active bleeding at the initial endoscopy may be more easily accomplished with sclerotherapy than with ligation in some cases. Nevertheless, I would employ ligation therapy for the subsequent elective endoscopic treatment sessions. In addition, ligation also occasionally may be difficult to perform at the end of a course of treatment when only small varices remain and fibrosis from endoscopic treatment prevents the proper degree of aspiration of the varices into the ligation cylinder. In this case as well, sclerotherapy may be employed, using small amounts of sclerosant to treat the remaining variceal channels.Although sclerotherapy appears to be more effective than medical therapies such as vasopressin, trials comparing sclerotherapy with octreotide or somatostatin have failed to document a significantly better rate of hemostasis with sclerotherapy in the first days of hospitalization for acute variceal bleeding.11Burroughs AK Octreotide in variceal bleeding.Gut. 1994; 35: S23-S27Crossref PubMed Scopus (32) Google Scholar However, even if octreotide is an effective agent, because it is delivered by constant infusion, it can be viewed only as initial therapy and a temporizing measure. Endoscopy is still necessary to document the source of bleeding and endoscopic therapy is still indicated at the time of this initial endoscopy to hopefully prevent recurrent bleeding after the octreotide infusion is discontinued.Transjugular intrahepatic portosystemic shunt has also come into widespread clinical use since the VA Cooperative Sclerotherapy Study was performed. Although certainly an effective therapy to decrease rebleeding from varices, it generally is not employed in the setting of acute bleeding before medical and endoscopic therapy are attempted.In summary, endoscopic therapy for actively bleeding esophageal varices is clinically effective. Although ligation should generally be the endoscopic treatment of choice for esophageal variceal bleeding, sclerotherapy may still be useful in some situations: in the setting of a large amount of blood in the esophagus and near the end of a course of treatment when varices are small and difficult to aspirate into the ligation cylinder. A shift in variceal treatment from sclerotherapy to ligation may decrease the experience of fellows in training with sclerotherapy and result in a decreased level of skill among future gastroenterologists. Because sclerotherapy will still have a place in the treatment of varices, we should try to maintain competence by continuing to perform sclerotherapy in some patients with variceal bleeding. In addition, fellows should be able to develop expertise in injection sclerotherapy techniques because injection is used commonly for nonvariceal indications such as treatment of bleeding ulcers and saline-assisted polypectomies. Patients with variceal hemorrhage have more clinically severe bleeding with significantly more complications, blood transfusions, interventions, and deaths than patients with other causes of upper gastrointestinal bleeding. Most patients who present with acute bleeding due to esophageal varices do not have evidence of active bleeding at the time of endoscopy. For example, a recent overview of seven prospective, randomized trials comparing ligation and sclerotherapy for the treatment of variceal hemorrhage found that only 27% of patients had active bleeding at the time of initial endoscopy.1Laine L Cook D Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: A meta-analysis.Ann Intern Med. 1995; 123: 280-287Crossref PubMed Scopus (606) Google Scholar Furthermore, some investigators may overestimate the proportion of patients with active bleeding because in a patient with a recent major bleeding episode, large amounts of red blood may be moving back and forth in the proximal stomach and esophagus, leading to an erroneous diagnosis of “active bleeding.” I only label varices as actively bleeding if I can clearly identify blood emanating from a varix. In our unit, we find that about one fifth of patients with esophageal varices as a source of bleeding who undergo endoscopy within 24 hours of presentation have active bleeding.2Laine L El-Newihi HM Migicovsky B Sloane R Garcia F Endoscopic ligation compared with sclerotherapy for treatment of bleeding esophageal varices.Ann Intern Med. 1993; 119: 1-7Crossref PubMed Scopus (322) Google Scholar, 3Laine L Stein C Sharma V Randomized comparison of ligation vs. ligation plus sclerotherapy in patients with bleeding esophageal varices.Gastroenterology. 1996; 110: 529-533Abstract Full Text PDF PubMed Scopus (108) Google Scholar Because a significant proportion of patients with cirrhosis (and even with documented varices) bleed from a nonvariceal source, I believe it is important to perform endoscopy early in patients with known or suspected portal hypertension to determine if varices are the source of bleeding or if a nonvariceal site is present. Bleeding from a nonvariceal source predicts a better prognosis for the patient and therefore provides important information. During this diagnostic endoscopy, if varices are identified as the source of bleeding (i.e., active bleeding, overlying clot or white nipple sign, or documented upper gastrointestinal bleeding with no other potential bleeding sites on upper endoscopy), then endoscopic therapy should be applied. Endoscopic sclerotherapy has been reported to stop active variceal bleeding in 62% to 100% of patients and generally appears to be more effective than standard therapy, such as vasopressin or balloon tamponade.4Larson AW Cohen H Zweiban B Chapman D Gourdji M Korula J et al.Acute esophageal variceal sclerotherapy: results of a prospective randomized controlled trial.JAMA. 1986; 255: 497-500Crossref PubMed Scopus (157) Google Scholar, 5Westaby D Hayes PC Gimson AES Polson RJ Williams R Controlled clinical trial of injection sclerotherapy for active variceal bleeding.Hepatology. 1989; 9: 274-277Crossref PubMed Scopus (189) Google Scholar, 6Paquet KJ Feussner H Endoscopic sclerosis and esophageal balloon tamponade in acute hemorrhage from esophagogastric varices: a prospective controlled randomized trial.Hepatology. 1985; 5: 580-583Crossref PubMed Scopus (251) Google Scholar, 7Moreto M Zaballa M Bernal A Ibanez W Ojembarrena E Rodriguez A A randomized trial of tamponade or sclerotherapy as immediate treatment for bleeding esophageal varices.Surg Gyn Obstet. 1988; 167: 331-334PubMed Google Scholar, 8Hartigan PM Gebhard RL Gregory PB Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis.Gastrointest Endosc. 1997; 46: 1-7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar The study in this issue of Gastrointestinal Endoscopy from Hartigan et al.8Hartigan PM Gebhard RL Gregory PB Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis.Gastrointest Endosc. 1997; 46: 1-7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar specifically examines the subset of patients in the large VA Cooperative Variceal Sclerotherapy Group Study who had episodes of active bleeding. The VA Cooperative study9The Veterans Affairs Cooperative Variceal Sclerotherapy Group Sclerotherapy for male alcoholic cirrhotic patients who have bled from esophageal varices: results of a randomized, multicenter clinical trial.Hepatology. 1994; 20: 618-625PubMed Google Scholar did not have any specific clinical entry criteria regarding episodes of bleeding; they included anyone with alcoholic liver disease and a history of bleeding from esophageal varices. Thus 49 (19%) of 253 enrolled patients were “actively bleeding,” 176 (70%) had bleeding within the previous 2 weeks, and the remainder bled more than 2 weeks earlier (including 8 patients with bleeding episodes more than 1 year earlier). Interestingly, active bleeding is not defined in this and many other studies, so we do not know for certain if active bleeding means blood emanating from the varix or just the presence of red blood in the upper gastrointestinal tract at endoscopy. Hartigan et al.8Hartigan PM Gebhard RL Gregory PB Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis.Gastrointest Endosc. 1997; 46: 1-7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar report that sclerotherapy was clearly beneficial in the group of patients with active bleeding: endoscopic therapy was efficacious in halting bleeding and in decreasing recurrent bleeding, transfusion requirements, the rate of shunt surgery, and mortality. In the group presenting with active bleeding at the index endoscopy, the survival rates at 6 months still favored sclerotherapy (60% vs 38% survival), but by 2 years the rates had narrowed so that both treated and untreated patients fared poorly (38% vs 27% survival).9The Veterans Affairs Cooperative Variceal Sclerotherapy Group Sclerotherapy for male alcoholic cirrhotic patients who have bled from esophageal varices: results of a randomized, multicenter clinical trial.Hepatology. 1994; 20: 618-625PubMed Google Scholar The VA Cooperative Esophageal Variceal Study was initiated in February 1985—more than a decade ago.9The Veterans Affairs Cooperative Variceal Sclerotherapy Group Sclerotherapy for male alcoholic cirrhotic patients who have bled from esophageal varices: results of a randomized, multicenter clinical trial.Hepatology. 1994; 20: 618-625PubMed Google Scholar A variety of changes have occurred since 1985 in medical, endoscopic, and radiologic options for the treatment of patients with bleeding esophageal varices. The VA Cooperative Study and other studies do demonstrate a benefit with the use of sclerotherapy as compared to no sclerotherapy and to “conservative” medical therapy for patients with active bleeding. But what about other newer therapies? Endoscopic ligation appears to have a number of advantages over sclerotherapy for the treatment of esophageal varices, including lower rates of recurrent bleeding, lower mortality, fewer local complications (e.g., esophageal strictures), and fewer treatment sessions required to achieve variceal obliteration.1Laine L Cook D Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: A meta-analysis.Ann Intern Med. 1995; 123: 280-287Crossref PubMed Scopus (606) Google Scholar Endoscopic ligation therapy also is effective in stopping active esophageal variceal bleeding, with rates of hemostasis around 80% to 100%.10Laine L Ligation: endoscopic treatment of choice for patients with bleeding esophageal varices?.Hepatology. 1995; 22: 663-665Crossref PubMed Google Scholar However, evaluation of randomized trials comparing ligation and sclerotherapy indicate that the two endoscopic therapies have similar efficacies in the control of active bleeding.1Laine L Cook D Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: A meta-analysis.Ann Intern Med. 1995; 123: 280-287Crossref PubMed Scopus (606) Google Scholar, 10Laine L Ligation: endoscopic treatment of choice for patients with bleeding esophageal varices?.Hepatology. 1995; 22: 663-665Crossref PubMed Google Scholar At present, I believe that ligation therapy should generally be considered the endoscopic treatment of choice for esophageal variceal bleeding. However, results from the trials mentioned above do suggest that either sclerotherapy or ligation may be considered effective in the subset of patients with active bleeding. Furthermore, ligation sometimes may be technically difficult to perform in patients with a large amount of blood in the esophagus. The cylinder attached to the tip of the endoscope markedly decreases the field of view, and blood filling the interior of the cylinder also may obscure the endoscopist's view. Therefore, treatment of active bleeding at the initial endoscopy may be more easily accomplished with sclerotherapy than with ligation in some cases. Nevertheless, I would employ ligation therapy for the subsequent elective endoscopic treatment sessions. In addition, ligation also occasionally may be difficult to perform at the end of a course of treatment when only small varices remain and fibrosis from endoscopic treatment prevents the proper degree of aspiration of the varices into the ligation cylinder. In this case as well, sclerotherapy may be employed, using small amounts of sclerosant to treat the remaining variceal channels. Although sclerotherapy appears to be more effective than medical therapies such as vasopressin, trials comparing sclerotherapy with octreotide or somatostatin have failed to document a significantly better rate of hemostasis with sclerotherapy in the first days of hospitalization for acute variceal bleeding.11Burroughs AK Octreotide in variceal bleeding.Gut. 1994; 35: S23-S27Crossref PubMed Scopus (32) Google Scholar However, even if octreotide is an effective agent, because it is delivered by constant infusion, it can be viewed only as initial therapy and a temporizing measure. Endoscopy is still necessary to document the source of bleeding and endoscopic therapy is still indicated at the time of this initial endoscopy to hopefully prevent recurrent bleeding after the octreotide infusion is discontinued. Transjugular intrahepatic portosystemic shunt has also come into widespread clinical use since the VA Cooperative Sclerotherapy Study was performed. Although certainly an effective therapy to decrease rebleeding from varices, it generally is not employed in the setting of acute bleeding before medical and endoscopic therapy are attempted. In summary, endoscopic therapy for actively bleeding esophageal varices is clinically effective. Although ligation should generally be the endoscopic treatment of choice for esophageal variceal bleeding, sclerotherapy may still be useful in some situations: in the setting of a large amount of blood in the esophagus and near the end of a course of treatment when varices are small and difficult to aspirate into the ligation cylinder. A shift in variceal treatment from sclerotherapy to ligation may decrease the experience of fellows in training with sclerotherapy and result in a decreased level of skill among future gastroenterologists. Because sclerotherapy will still have a place in the treatment of varices, we should try to maintain competence by continuing to perform sclerotherapy in some patients with variceal bleeding. In addition, fellows should be able to develop expertise in injection sclerotherapy techniques because injection is used commonly for nonvariceal indications such as treatment of bleeding ulcers and saline-assisted polypectomies.