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Sclerotherapy in acute variceal bleeding
Letters to the Editor
Sclerotherapy in acute variceal bleeding To the Editor: We have read with interest the article by Hartigan et aLl regarding the value of emergency injection sclerotherapy in actively bleeding esophageal varices. We agree with the authors that endoscopic sclerotherapy is an effective tool to control overt bleeding from esophageal varices. This assertion is based not only on the results of the present study, but also on those of metaanalysis of randomized trials on the same topic. 2,3 Several issues can be raised from the reading of this sham-controlled study. The study population consists of 49 patients whose varices were actively bleeding at the time of endoscopy and who belong to a group of 253 cirrhotic patients who were dealt with in previous articles by the authors. A more thorough description of the term "active bleeding" would have been advisable. In addition to spurting or oozing of blood from the varix, does this expression encompass the presence of fresh blood within the gastric cavity? Other endpoints of the study are also not clearly defined. The authors do not fix the limits of the time frame to make a distinction between the acute episode of bleeding and early recurrence of bleeding. According to the guidelines set at a consensus meeting held in Baveno in 1994, the acute bleeding episode was represented by an interval of 48 hours from time zero with no evidence of clinically significant bleeding between 24 and 48 hours.4 Recurrent bleeding was defined as any further manifestation of hemorrhage after achieving a 24-hour period ofhemostasis. 4 The distinction is not meaningful because some episodes of recurrent bleeding could in fact represent a lack of control of the index episode. This consideration is particularly important when evaluating a hemostatic method s~ch ~ injection sclerosis, which is considered to be effectIve 10 arresting acute bleeding and in avoiding early recurrence of bleeding. Another point that should be taken into account is the specific design of the study, which compares sclerosis with non-active treatment as the control arm. We agree with Dr. Laine that the study was designed and started a decade ago,5 and since then endoscopic and nonendoscopic treatment of portal hypertension has rapidly evolved. Meta-analysis of randomized controlled trials indicates that vasoactive drugs, specifically terlipressin and somatostatin, are highly effective in arresting acute bleeding and in preventing early recurrence ofbleeding. 3 The most recent study comparing terlipressin and somatostatin shows a similar rate of success for the 2 drugs (80% and 84%, respectively) in halting the acute bleeding episode. 6 Moreover, the effectiveness of continuous administration of either of these drugs during the 5-day, high-risk period that follows hemostasis in preventing the early recurrence of bleeding is similar to that of emergency sclerotherapy.3.7 These studies indicate that vasoactive drugs are an effective, safe therapy for variceal hemorrhage in cirrhotic patients, that can be used as first-line treatment. Moreover, it is accepted that placebo-controlled studies should not be undertaken 140 GASTROINTESTINAL ENDOSCOPY
when a "proved" method of therapy exists. s Therefore, in the light of current knowledge, use of non-active treatment as a control without administering an accepted backup therapy is probably not acceptable in future studies to evaluate new therapies in acute variceal bleeding. A further aspect that would be worthwhile to emphasize is the incidence of local side effects in the sclerotherapy group. The authors state that injection sclerotherapy can be performed safely, inasmuch as no significant non ulcer complications were seen. However, bleeding caused by sclerosis-induced ulcerations should be considered a major drawback of this procedure, probably the most frequent serious side effect, being present in up to 20% of patients. 9 In the present study, esophageal ulcers were the confirmed source of recurrent bleeding in 6, and probably also in another 3, of the 14 patients that had recurrent bleeding. The authors do not mention the course of these episodes of hemorrhage, which is usually severe. Furthermore, complications of therapeutic endoscopy are closely related to operator expertise, and in the specific setting of acute variceal bleeding it is often difficult to have an experienced endoscopist available on a 24-hour basi~. Thus it is conceivable that the overall rate of comphcatio~s of emergency sclerotherapy may be even higher in general practice than that reported in clinical trials. As pointed out by Dr. Laine, ligation has the potential to reduce the incidence of some of these complications. 5 Vasoactive drugs, such as terlipressin and somatostatin, have the advantages of safety, ease of use in the emergency setting (even before endoscopy), and the possibility of continuing administration for several days with the potential to reduce the chance of early resumption of bleeding. Whether pharmacologic and endoscopic therapy have a synergistic effect in achieving hemostasis of the ruptured varix is the aim of current investigations. Agustin Albillos Jose Luis Calleja Luis Rulz-del-Arbol Madrid. Spain
REFERENCES 1. Hartigan PM, Gebhard RL, Gregory PB. Sclerotherapy for
2.
3.
4.
5.
actively bleeding esophageal varices in male alcoholics with cirrhosis. Gastrointest Endosc 1997;46:1-7. Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis. Ann Intern Med 1995;123:280-7. D'Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995;22:332-54. Burroughs AK, Alexandrino P, Cales P, Fleig W, Grace N, Minoli G, et a1. Sore points. In: Portal hypertension II. Proceedings of the Second Baveno International Workshop. De Franchis R, editor. Oxford: Blackwell Science Ltd; 1996. p. 10-7. Laine L. Management of actively bleeding esophageal varices. Gastrointest Endosc 1997;46:83-4.
VOLUME 49, NO. 1, 1999
Letters to the Editor
6. Feu F, Ruiz del Arbol L, Baftares R, Planas R, Bosch J, et al. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Gastroenterology 1996;111:1291-9. 7. Variceal Bleeding Study Group. Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following variceal hemorrhage in patients with cirrhosis [abstract). Hepatology 1993;18:140. 8. Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med 1994;331:394-8. 9. Shuman BM, Berkman JW, Tedesco FJ, Griffin JW, Assad RT. Complications of endoscopic injection sclerotherapy: a review. Am J Gastroenterol 1987;82:823-9.
Masking of colon vascular ectasias by cold water lavage To the Editor: Vascular ectasias are caprICIOUS structures that respond to a variety of physical and chemical stimuli. Seen in approximately 3% of nonbleeding individuals over the age of 65, 1 these lesions are one of the two most common causes of significant lower intestinal bleeding in the elderly. 2 They may be difficult to find, however, especially in patients with a reduced intravascular volume from a variety of causes including, dehydration, diarrhea due to a vigorous laxative preparation, anemia from a recent bleeding episode, or hypotension. Recently, we observed a prominent vascular ectasia blanch and almost disappear after cleansing the colon wall of stool with a lavage of water at room temperature (Fig. lA-C). The patient is a 65-year-old woman with worsening constipation and a remote history of ulcerative colitis. Colonoscopy revealed extensive diverticulosis of the descending and transverse colon and multiple vascular ectasias of the ascending colon and cecum. Despite a 24hour liquid diet and a full preparation with Nulytely, a veneer of stool coated much of the mucosa, especially the ascending colon. To better visualize the ectasias, the stool was lavaged using a jet of water from the Endo-Irrigator (EI400; Pentax Precision Instruments, Inc., Orangeburg, N.Y.) . Within 10 seconds after the irrigation the lesions within the path of the water stream blanched, only to reappear several minutes later. This observation was repeated several times and photo-documented; no changes occurred in blood pressure, pulse, or oxygen saturation and no additional medications were administered during the observation periods. The observation that relatively cool (room temperature) water used to lavage stool from mucosa can alter the appearance of vascular ectasias adds another physical variable to the factors that can alter the appearance of these vascular lesions. Thus, observation periods should extend several minutes after colon lavage, during which time any previously apparent lesions may reappear.
Figure 1. Vascular ectasia in the ascending colon. Before (A), immediately after (B), and several minutes after (C) irrigation with room temperature water.
Lawrence J. Brandt, MD Deb Mukhopadhyay, MD Montefiore Medical Center Bronx, New York
VOLUME 49, NO.1, 1999
GASTROINTESTINAL ENDOSCOPY
141
Sclerotherapy in acute variceal bleeding To the Editor: We have read with interest the article by Hartigan et aLl regarding the value of emergency injection sclerotherapy in actively bleeding esophageal varices. We agree with the authors that endoscopic sclerotherapy is an effective tool to control overt bleeding from esophageal varices. This assertion is based not only on the results of the present study, but also on those of metaanalysis of randomized trials on the same topic. 2,3 Several issues can be raised from the reading of this sham-controlled study. The study population consists of 49 patients whose varices were actively bleeding at the time of endoscopy and who belong to a group of 253 cirrhotic patients who were dealt with in previous articles by the authors. A more thorough description of the term "active bleeding" would have been advisable. In addition to spurting or oozing of blood from the varix, does this expression encompass the presence of fresh blood within the gastric cavity? Other endpoints of the study are also not clearly defined. The authors do not fix the limits of the time frame to make a distinction between the acute episode of bleeding and early recurrence of bleeding. According to the guidelines set at a consensus meeting held in Baveno in 1994, the acute bleeding episode was represented by an interval of 48 hours from time zero with no evidence of clinically significant bleeding between 24 and 48 hours.4 Recurrent bleeding was defined as any further manifestation of hemorrhage after achieving a 24-hour period ofhemostasis. 4 The distinction is not meaningful because some episodes of recurrent bleeding could in fact represent a lack of control of the index episode. This consideration is particularly important when evaluating a hemostatic method s~ch ~ injection sclerosis, which is considered to be effectIve 10 arresting acute bleeding and in avoiding early recurrence of bleeding. Another point that should be taken into account is the specific design of the study, which compares sclerosis with non-active treatment as the control arm. We agree with Dr. Laine that the study was designed and started a decade ago,5 and since then endoscopic and nonendoscopic treatment of portal hypertension has rapidly evolved. Meta-analysis of randomized controlled trials indicates that vasoactive drugs, specifically terlipressin and somatostatin, are highly effective in arresting acute bleeding and in preventing early recurrence ofbleeding. 3 The most recent study comparing terlipressin and somatostatin shows a similar rate of success for the 2 drugs (80% and 84%, respectively) in halting the acute bleeding episode. 6 Moreover, the effectiveness of continuous administration of either of these drugs during the 5-day, high-risk period that follows hemostasis in preventing the early recurrence of bleeding is similar to that of emergency sclerotherapy.3.7 These studies indicate that vasoactive drugs are an effective, safe therapy for variceal hemorrhage in cirrhotic patients, that can be used as first-line treatment. Moreover, it is accepted that placebo-controlled studies should not be undertaken 140 GASTROINTESTINAL ENDOSCOPY
when a "proved" method of therapy exists. s Therefore, in the light of current knowledge, use of non-active treatment as a control without administering an accepted backup therapy is probably not acceptable in future studies to evaluate new therapies in acute variceal bleeding. A further aspect that would be worthwhile to emphasize is the incidence of local side effects in the sclerotherapy group. The authors state that injection sclerotherapy can be performed safely, inasmuch as no significant non ulcer complications were seen. However, bleeding caused by sclerosis-induced ulcerations should be considered a major drawback of this procedure, probably the most frequent serious side effect, being present in up to 20% of patients. 9 In the present study, esophageal ulcers were the confirmed source of recurrent bleeding in 6, and probably also in another 3, of the 14 patients that had recurrent bleeding. The authors do not mention the course of these episodes of hemorrhage, which is usually severe. Furthermore, complications of therapeutic endoscopy are closely related to operator expertise, and in the specific setting of acute variceal bleeding it is often difficult to have an experienced endoscopist available on a 24-hour basi~. Thus it is conceivable that the overall rate of comphcatio~s of emergency sclerotherapy may be even higher in general practice than that reported in clinical trials. As pointed out by Dr. Laine, ligation has the potential to reduce the incidence of some of these complications. 5 Vasoactive drugs, such as terlipressin and somatostatin, have the advantages of safety, ease of use in the emergency setting (even before endoscopy), and the possibility of continuing administration for several days with the potential to reduce the chance of early resumption of bleeding. Whether pharmacologic and endoscopic therapy have a synergistic effect in achieving hemostasis of the ruptured varix is the aim of current investigations. Agustin Albillos Jose Luis Calleja Luis Rulz-del-Arbol Madrid. Spain
REFERENCES 1. Hartigan PM, Gebhard RL, Gregory PB. Sclerotherapy for
2.
3.
4.
5.
actively bleeding esophageal varices in male alcoholics with cirrhosis. Gastrointest Endosc 1997;46:1-7. Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis. Ann Intern Med 1995;123:280-7. D'Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995;22:332-54. Burroughs AK, Alexandrino P, Cales P, Fleig W, Grace N, Minoli G, et a1. Sore points. In: Portal hypertension II. Proceedings of the Second Baveno International Workshop. De Franchis R, editor. Oxford: Blackwell Science Ltd; 1996. p. 10-7. Laine L. Management of actively bleeding esophageal varices. Gastrointest Endosc 1997;46:83-4.
VOLUME 49, NO. 1, 1999
Letters to the Editor
6. Feu F, Ruiz del Arbol L, Baftares R, Planas R, Bosch J, et al. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Gastroenterology 1996;111:1291-9. 7. Variceal Bleeding Study Group. Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following variceal hemorrhage in patients with cirrhosis [abstract). Hepatology 1993;18:140. 8. Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med 1994;331:394-8. 9. Shuman BM, Berkman JW, Tedesco FJ, Griffin JW, Assad RT. Complications of endoscopic injection sclerotherapy: a review. Am J Gastroenterol 1987;82:823-9.
Masking of colon vascular ectasias by cold water lavage To the Editor: Vascular ectasias are caprICIOUS structures that respond to a variety of physical and chemical stimuli. Seen in approximately 3% of nonbleeding individuals over the age of 65, 1 these lesions are one of the two most common causes of significant lower intestinal bleeding in the elderly. 2 They may be difficult to find, however, especially in patients with a reduced intravascular volume from a variety of causes including, dehydration, diarrhea due to a vigorous laxative preparation, anemia from a recent bleeding episode, or hypotension. Recently, we observed a prominent vascular ectasia blanch and almost disappear after cleansing the colon wall of stool with a lavage of water at room temperature (Fig. lA-C). The patient is a 65-year-old woman with worsening constipation and a remote history of ulcerative colitis. Colonoscopy revealed extensive diverticulosis of the descending and transverse colon and multiple vascular ectasias of the ascending colon and cecum. Despite a 24hour liquid diet and a full preparation with Nulytely, a veneer of stool coated much of the mucosa, especially the ascending colon. To better visualize the ectasias, the stool was lavaged using a jet of water from the Endo-Irrigator (EI400; Pentax Precision Instruments, Inc., Orangeburg, N.Y.) . Within 10 seconds after the irrigation the lesions within the path of the water stream blanched, only to reappear several minutes later. This observation was repeated several times and photo-documented; no changes occurred in blood pressure, pulse, or oxygen saturation and no additional medications were administered during the observation periods. The observation that relatively cool (room temperature) water used to lavage stool from mucosa can alter the appearance of vascular ectasias adds another physical variable to the factors that can alter the appearance of these vascular lesions. Thus, observation periods should extend several minutes after colon lavage, during which time any previously apparent lesions may reappear.
Figure 1. Vascular ectasia in the ascending colon. Before (A), immediately after (B), and several minutes after (C) irrigation with room temperature water.
Lawrence J. Brandt, MD Deb Mukhopadhyay, MD Montefiore Medical Center Bronx, New York
VOLUME 49, NO.1, 1999
GASTROINTESTINAL ENDOSCOPY
141