Therapeutic Endoscopy and Bleeding Ulcers National Institutes of Health Consensus Development Conference Statement March 6-8, 1989 This statement is more than five years old and is provided solely for historical purposes. Due to the cumulative nature of medical research, new knowledge has inevitably accumulated in this subject area in the time since the statement was initially prepared. Thus some of the material is likely to be out of date, and at worst simply wrong. For reliable, current information on this and other health topics, we recommend consulting the National Institutes of Health's MedlinePlus http://www.nlm.nih.gov/medlineplus/. This statement was originally published as: Therapeutic Endoscopy and Bleeding Ulcers. NIH Consens Statement 1989 Mar 6-8;7(6):1-22. For making bibliographic reference to the statement in the electronic form displayed here, it is recommended that the following format be used: Therapeutic Endoscopy and Bleeding Ulcers. NIH Consens Statement Online 1989 Mar 6-8 [cited year month day];7(6):1-22. Introduction Peptic ulcer disease is a major health problem in the United States that affects more than 4 million people each year. Bleeding is one of the most dread complications of peptic ulcer. Upper gastrointestinal (UGI) bleeding is a common cause of emergency hospitalization in the United States. It has been estimated that more than 100,000 patients with peptic ulcer disease bleed each year. Morbidity and mortality from ulcer bleeding remain significant despite major improvements in the accurate diagnosis of peptic ulcer disease and the use of H2 receptor antagonist drugs and other pharmacological agents. The mortality rate from bleeding ulcers has averaged between 6 and 10 percent over the past 30 years despite advances in diagnosis and treatment. During the past decade there has been a remarkable transition of the application of the endoscope from solely a diagnostic tool to a therapeutic modality. With the advent of this therapeutic role there has been much enthusiasm in utilizing endoscopic techniques in managing high-risk patients. A variety of approaches for endoscopic management of bleeding have evolved, and there has been continuing improvement over the past decade, resulting in considerable interest in evaluating the various treatment options for managing patients with bleeding ulcers. Unfortunately, there have been limited and conflicting clinical studies on the efficacy and safety of the various hemostatic modalities available for treating these ulcers. In an effort to define the role of these methods, the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of Medical Applications of Research of the National Institutes of Health sponsored a Consensus Development Conference on Therapeutic Endoscopy and Bleeding Ulcers. The conference brought together research clinicians and other health professionals and representatives of the public on March 6-8, 1989. Following 2 days of presentations and discussion by the invited experts and the audience, members of a consensus panel drawn from the health care and medical communities weighed the scientific evidence in formulating a statement in response to several questions: Which bleeding ulcer patients are at risk for rebleeding and thus emergency surgery? How effective is endoscopic hemostatic therapy? How safe is endoscopic hemostatic therapy? Which bleeding patients should be treated? What further research is required?   It is important that certain limitations be considered when applying the findings of this conference to a particular bleeding patient. The conference was charged to address specifically the question of therapeutic endoscopy for the treatment of bleeding peptic ulcer. Other causes of UGI bleeding, including gastric and esophageal varices, diffuse erosive gastritis, and Mallory-Weiss tears were necessarily excluded from consideration. It should be noted that the conclusions reached should not be extrapolated to those diseases excluded from consideration. Moreover, a striking finding from the review of available clinical trials of therapeutic endoscopy was the selective inclusion of only a small proportion (10 to 25 percent) of the total population of patients who presented with UGI bleeding. In addition to patients with the above diagnoses, many other patients were also excluded, quite appropriately, due to hemorrhage too massive or too little to justify prudent therapeutic endoscopy. In this conference, the need for emergency surgery was taken as one indicator of inadequately controlled bleeding. Although many patients treated with surgery do well, they are subjected to additional discomfort and cost and to approximately a 10-percent risk of mortality when the surgery must be performed under such emergency conditions. On the other hand, when temporary hemostasis achieved by endoscopic therapy allows resuscitation and hemodynamic control of an unstable patient, considerable benefit may be realized even if surgery must be performed ultimately. For a variety of reasons, a surgeon should be involved from the outset in the team caring for the patient with bleeding peptic ulcer.   Which Bleeding Ulcer Patients Are at Risk for Rebleeding and Thus Emergency Surgery? Clinical Features Magnitude of Bleeding There is consensus that a major predictor of significant persistent or recurrent bleeding is the magnitude of blood loss before initial evaluation. Clear indications of a large and clinically significant volume of blood loss are hemodynamic instability, hematemesis of grossly red material, or red stool. The hazard of hemodynamic instability underlies the importance of careful hemodynamic evaluation in order to detect significant hypovolemia before the appearance of overt shock. Another commonly used indicator of the magnitude of hemorrhage is estimation of the volume of blood lost, often quantitated as the number of units transfused or as a transfusion rate. Although there is general agreement that the volume of blood loss is important, there is substantial uncertainty about the best way to estimate it. Persistent red blood in the nasogastric aspirate correlates with an increased requirement for subsequent transfusion. Although failure of the nasogastric aspirate to clear with irrigation often is taken as an indication of rapid bleeding, this criterion may be misleading Host Factors Patient-related factors also predict persistent or recurrent bleeding. The panel finds that documented coagulopathy and the onset of bleeding in a patient already hospitalized for a related or unrelated condition are predictive of recurrent bleeding. Two other factors, age and the existence of concurrent illnesses, while clearly related to mortality, bear a less clear relationship to prognosis for continued bleeding or rebleeding. Endoscopic Features The first and most important endoscopic predictor of persistent or recurrent bleeding is active bleeding at the time of endoscopy, as evidenced by arterial spurting or oozing. Also of importance is the presence of a discrete protuberance within the ulcer crater, often referred to by endoscopists as a "visible vessel" or "sentinel clot." There is consensus that some pigmented protuberances (red, blue, or purple) imply a high risk of rebleeding, even when not associated with bleeding at the time of endoscopy. There is less agreement on the prognostic significance of a white or black protuberance. A white protuberance may be indicative of an older, more organized process. Although any such lesions often are referred to as "visible vessels," pathologic studies indicate that only some are true vessels. Most frequently, they represent a hemostatic plug (clot) in the underlying vessel or a false aneurysm. The prognostic implications of these distinctions remain unclear. An additional endoscopic predictor of recurrent bleeding is the presence of a clot that adheres to the ulcer base despite gentle washing (adherent clot). Whereas the anatomic location of the ulcer crater often is cited as a prognostic factor, the panel members do not agree that site is clearly predictive. Nevertheless, many endoscopists feel that deep ulcers located high on the lesser curvature of the stomach or in the posterior-inferior wall of the duodenal bulb are at greater risk for severe bleeding due to their proximity to large vessels. Features that clearly appear to be associated with a low frequency of recurrent bleeding include a clean ulcer base or one that contains a flat pigmented spot indicative of old hemorrhage. Value of Combined Clinical and Endoscopic Predictors Whereas the above clinical and endoscopic features are predictive when considered singly, they may become particularly useful as prognostic indicators when considered together.   How Effective Is Endoscopic Hemostatic Therapy? The following consensus statements on the effectiveness of the various endoscopic hemostatic therapies are based on the limited number of studies performed. Results were reported only for the acute hospital stay; only sparse followup data are available. The level of efficacy of individual treatment modalities varies from study to study. Some factors that may account for this variability are small sample sizes, variation in patient characteristics such as age, entry criteria, differing definitions of such terms as "visible vessel" or "rebleed," and timing of endoscopy. Nonetheless, certain conclusions can be drawn from these studies. Most Promising Techniques Multipolar Electrocoagulation (MPEC). MPEC (also known as bipolar) appears to be an effective modality for achieving immediate hemostasis and preventing rebleeding in actively bleeding patients and patients with "visible vessels." The data are less clear that MPEC decreases the need for emergency surgical intervention or decreases mortality. Further advantages of this modality are that it does not require an en face approach to the bleeding point, the endoscopist can control the depth of tissue injury, and the equipment is portable and easy to use. Recommendations are evolving concerning technique in terms of probe size, power setting, pressure applied, and duration and number of pulses delivered. Heater Probe. In comparison with "conventional" medical therapy, the heater probe appears to achieve immediate hemostasis and to reduce rebleeding and the need for emergency surgery. The advantages of heater probe therapy are the same as for MPEC. Early data for MPEC and heater probe suggest no delay in ulcer healing in treated patients. Other Techniques Neodymium-Yttrium-Aluminum-Garnet (ND-YAG) Laser. Nd-YAG laser appears to be effective for achieving immediate hemostasis and preventing rebleeding. Studies have also shown a trend toward reducing need for emergency surgery and lowering mortality. Difficulties in using this instrument include gaining access to the bleeding lesion for an en face approach and training endoscopists in its use. Laser therapy is difficult to master and apply. Furthermore, the Nd-YAG laser is costly to use in relation to other modalities. Although portability has been an obstacle to its use, new portable instrumentation is now available. Injection Therapy. Some agents (e.g., sodium chloride, epinephrine, and ethanol) appear promising for early control of bleeding. Currently there are insufficient data to make specific recommendations concerning the proper role of this approach. However, injection therapies warrant further study because of their technical ease of use, low cost, and promise. Techniques Not Recommended Topical. There is no current evidence for efficacy of the following agents: cyanoacrylate glue, clotting factors, ferromagnetic tamponade, epinephrine lavage, and microcrystalline collagen hemostat. Argon Laser. This technique appears to be effective for immediate hemostasis, but available data do not demonstrate significant reduction in rebleeding, mortality, or need for emergency surgery. This technique has been superseded by other, more effective treatment modalities. Monopolar/Electrohydrothermal Coagulation. This modality appears to be effective for immediate hemostasis. However, monopolar therapy has been replaced by other techniques because of difficulty in its use due to the necessity to meet the bleeding point en face, to control the depth of injury, and the need for multiple cleanings of the probe.   How Safe Is Endoscopic Hemostatic Therapy? Safety may be compromised by: Patient characteristics: Hemodynamic instability and associated illnesses. Ulcer characteristics: Depth and location, especially posterior-inferior duodenal bulb and high lesser curvature of the stomach because of the proximity to large arteries. Method of therapy: Excessive depth of penetration of energy or injectant. The consensus of the panel is that therapeutic endoscopy should be performed only by an endoscopist experienced and qualified in the specific therapeutic techniques. Appropriate professional organizations should develop guidelines for training and for quality assurance. The goal of endoscopic hemostatic treatment is to stop active bleeding and prevent rebleeding while controlling depth of tissue injury and avoiding excessive necrosis, increased bleeding, and perforation. The only indication to remove an adherent clot other than by low-pressure irrigation is in the actively bleeding patient or the patient who has rebled. After clot removal, the endoscopist must be prepared to apply therapy. The risk of precipitating bleeding with therapy is variable but has been as high as 20 percent. While this bleeding can usually be controlled by the same endoscopic hemostatic therapy, occasionally uncontrollable bleeding will require emergency surgical intervention. The risk of perforation has been approximately 1 percent and may require laparotomy should it occur. In the patient population at high risk of rebleeding, the rate of complications of endoscopic hemostatic therapy appears to be acceptably low considering the natural history of the disease. As the technology in this field advances, controlled observations of potential complications are needed to ensure that safety remains within acceptable limits. Which Bleeding Ulcer Patients Should Be Treated? Acute peptic ulcer bleeding will stop spontaneously in approximately 70 to 80 percent of patients. Therefore, there is consensus that a need exists for selectivity in applying endoscopic hemostatic therapy to bleeding ulcers. Such therapy should be directed at selected high-risk patients. A clinical feature of high risk for rebleeding or death is rapid bleeding with substantial blood loss manifested by hemodynamic instability, ongoing transfusion requirement, red hematemesis, or red stool. Other patient characteristics that predict a poor outcome from ulcer bleeding include age greater than 60 years and major associated diseases. Patients whose onset of bleeding occurs in the hospital or who rebleed during hospitalization are also at high risk. Patients with high-risk clinical features are candidates for therapeutic/hemostatic endoscopy. The observations at endoscopy should then determine whether endoscopic hemostatic therapy should be carried out. There is consensus that the findings of pulsatile bleeding ("spurting") or oozing from the ulcer are indications for treatment. In addition, the finding of a pigmented protuberance ("visible vessel" or "sentinel clot") in the ulcer crater is an indication for endoscopic hemostatic therapy. There is agreement that patients with ulcer craters that are clean with or without flat pigmented spots do not require endoscopic hemostatic treatment. In the absence of the clinical risk factors described above, adherent clots (resisting gentle washing) without evident active bleeding should not be removed because of the possible risk of precipitating bleeding. In a deteriorating clinical situation, adherent clots may be removed as long as there is satisfactory endoscopic access and capability for treatment. Surgical backup should be readily available to deal with the possibility of precipitating active bleeding that cannot be controlled endoscopically, and thus the need for early surgical consultation. Patients exsanguinating with torrential bleeding from peptic ulcer represent a special case. The panel agrees that endoscopic localization and treatment should be attempted in concert with the surgeon and without undue delay. It should be recognized that deep ulcers near the left gastric artery high on the lesser curvature of the stomach and those near the gastroduodenal artery in the posterior-inferior duodenal bulb may be at high risk for major bleeding. This emphasizes that surgical support must be available before endoscopic treatment of ulcers in these anatomic locations is undertaken. It is important to resuscitate patients and correct coagulopathy as completely as possible before endoscopic hemostatic therapy. Uncontrollable coagulopathy appears to be a contraindication to endoscopic hemostatic therapy in the patient who is not actively bleeding. However, in the patient who is actively bleeding, endoscopic hemostatic therapy may be attempted despite uncorrectable coagulopathy with the awareness that control of hemorrhage may be temporary. Endoscopic treatment of patients with bleeding peptic ulcers should be carried out only by individuals qualified in therapeutic endoscopy.   What Further Research Is Required? Despite the considerable technical advances that have been made in the past decade in endoscopic hemostatic therapy, firm conclusions regarding clinical applications are limited by a paucity of controlled trials. There is consensus that a number of important issues remain to be resolved and that high priority should be given to continuing scientific evaluation of techniques. There is a strong need to use rigorous scientific methods to resolve the following issues: Standardize use of terminology, particularly descriptive terms such as "visible vessel" (e.g., white, blue, red, black or bare), adherent clot, persistent and recurrent bleeding. Quantitate rebleeding risk associated with endoscopic features such as "visible vessel," adherent clot, size, depth and location of ulcer, and timing of endoscopy. Quantitate rebleeding risk associated with different host factors such as aging, nonsteroidal anti-inflammatory drug use (including aspirin), and associated diseases. Develop a composite system using clinical and endoscopic features to predict risk of persistent or recurrent bleeding. Define optimal treatment regimens for individual and combined treatment modalities to maximize therapeutic effectiveness. Explore improved diagnostic and therapeutic technology through collaboration with bioengineers. Clinical effectiveness and safety of endoscopic hemostatic therapies would be best assessed by multicenter, randomized controlled trials. Ulcer patients at high risk but without active bleeding at endoscopy should be entered into studies comparing endoscopic therapies with medical therapies. There is a lack of consensus regarding the need for a medical therapy control group of patients with active bleeding at endoscopy.   Conclusions and Recommendations In the United States, more than 100,000 patients a year bleed from peptic ulcers. Despite advances in diagnosis and treatment, the mortality rate from bleeding ulcers has remained largely unchanged, averaging between 6 and 10 percent over the past 30 years. Bleeding from peptic ulcers will stop spontaneously in 70 to 80 percent of patients. A surgeon should be involved from the outset in the team caring for the patient with a bleeding peptic ulcer. Patients at high risk for persistent or recurrent bleeding are those with a large initial blood loss and active bleeding or a pigmented protuberance ("visible vessel") at endoscopy. Patients at low risk for subsequent bleeding are those with a clean ulcer base or one that contains a flat pigmented spot at endoscopy. Heater probe and multipolar electrocoagulation (also known as bipolar) are the most promising modalities for endoscopic hemostatic therapy. In the hands of the qualified therapeutic endoscopist, the rate of complications of endoscopic hemostatic therapy is acceptably low considering the natural history of bleeding peptic ulcers. Endoscopic hemostatic therapy should be used only in patients who are at high risk for persistent or recurrent bleeding and death. Clinical efficacy and safety of endoscopic hemostatic therapy should be assessed by multicenter, randomized controlled trials.  Consensus Development Panel Donald O. Castell, M.D. Panel and Conference Chairperson Professor of Medicine Chief of Gastroenterology Bowman Gray School of Medicine Wake Forest University Winston-Salem, North Carolina Ronald G. Blankenbaker, M.D. Vice President for Medical Affairs St. Vincent Hospital and Health Care Center Indianapolis, Indiana Eugene M. Bozymski, M.D. Professor of Medicine Chief of Endoscopy Division of Digestive Diseases and Nutrition University of North Carolina School of Medicine Chapel Hill, North Carolina Gregory B. Bulkley, M.D., F.A.C.S. Mark M. Ravitch Professor of Surgery Director of Surgical Research Johns Hopkins University School of Medicine Baltimore, Maryland Janet D. Elashoff, Ph.D. Professor of Biomathematics University of California at Los Angeles Director Division of Biostatistics Cedars-Sinai Medical Center Los Angeles, California John T. Galambos, M.D. Professor of Medicine Director Division of Digestive Diseases Emory University School of Medicine Atlanta, Georgia John W. Harmon, M.D., F.A.C.S. Chief Surgical Service Professor of Surgery Washington Veterans Administration Medical Center Washington, D.C. C. Michael Knauer, M.D. Chief Division of Gastroenterology Santa Clara Valley Medical Center Clinical Professor of Medicine Stanford University School of Medicine San Jose, California Shoba Krishnamurthy, M.B.B.S. Assistant Professor Department of Medicine University of Washington Staff Gastroenterologist Pacific Medical Center Seattle, Washington Robert H. Moser, M.D. Vice President Medical Affairs The NutraSweet Company Adjunct Professor of Medicine Northwestern University Medical School Deerfield, Illinois David F. Ransohoff, M.D. Associate Professor of Medicine and Epidemiology Yale University School of Medicine New Haven, Connecticut Robert M. Russell, M.D. Professor of Medicine Tufts University Associate Director U.S. Department of Agriculture Human Nutrition Research Center on Aging Boston, Massachusetts Richard E. Sampliner, M.D. Associate Professor of Medicine Chief of Gastroenterology University of Arizona Tucson, Arizona Ida Gatling Scott, R.N., C.G.C. Supervisor Gastrointestinal Procedure Room Washington Hospital Center Washington, D.C. Joseph H. Szurszewski, Ph.D. Conference and Panel Cochairperson Professor and Chairman Department of Physiology and Biophysics Director for Research Mayo Group Practices Mayo Foundation Rochester, Minnesota Speakers Stanley B. Benjamin, M.D. "Therapeutic Endoscopy and Bleeding Ulcers: Methodology" Professor of Medicine Chief Division of Gastroenterology Georgetown University Hospital Washington, D.C. Peter B. Cotton, M.D., F.R.C.P. "Argon Laser/CO2 Treatment of Bleeding Ulcers" Professor of Medicine Duke University Medical Center Durham, North Carolina David A. Gilbert, M.D. "Epidemiology of Upper Gastrointestinal Bleeding" Chief of Gastroenterology Providence Medical Center Clinical Assistant Professor of Medicine University of Washington Seattle, Washington Dennis M. Jensen, M.D. "Heater Probe for Hemostasis of Ulcers" Associate Professor of Medicine Department of Medicine Center for the Health Sciences University of California at Los Angeles School of Medicine Los Angeles, California James H. Johnston, M.D. "Endoscopic Risk Factors" Clinical Associate Professor of Medicine University of Mississippi School of Medicine Jackson, Mississippi Guenter J. Krejs, M.D. "Yag Laser: The Con Approach" Professor and Chairman Department of Medicine Karl-Franzens-Universitat Graz AUSTRIA Loren Laine, M.D. "Bipolar/Multipolar Electrocoagulation" Assistant Professor of Medicine Department of Medicine Section of Gastroenterology University of Southern California School of Medicine Los Angeles, California John P. Papp, M.D., F.A.C.P., F.A.C.G. "Monopolar and Electrohydrothermal Treatment of Upper Gastrointestinal Bleeding" Clinical Professor of Medicine Michigan State University College of Human Medicine Director of the Endoscopy Unit and Swallowing Disorder Center Blodgett Memorial Medical Center Grand Rapids, Michigan Walter L. Peterson, M.D. "Efficacy Criteria--Outcome of Therapy" "Clinical Risk Factors" Chief of Gastroenterology Dallas Veterans Administration Medical Center Associate Professor of Internal Medicine University of Texas Southwestern Medical Center Dallas, Texas David A. Peura, M.D. "Topical Therapy for the Control of Gastrointestinal Bleeding" Chief of Gastroenterology Service Walter Reed Army Medical Center Washington, D.C. J. Loren Pitcher, M.D. "Therapeutic Endoscopy and Bleeding Ulcers: A Historical Overview" Professor of Medicine Associate Dean for Clinical Affairs Chief Medical Officer University of New Mexico Medical Center University of New Mexico School of Medicine Albuquerque, New Mexico Fred E. Silverstein, M.D. "Introduction to Therapeutic Intervention in Peptic Ulcer Bleeding" Professor of Medicine Director Gastrointestinal Endoscopy Service University Hospital Seattle, Washington Choichi Sugawa, M.D. "Injection Therapy" Professor of Surgery Department of Surgery Wayne State University School of Medicine Detroit, Michigan C. Paul Swain, M.D. "Yag Laser: The Pro Approach" "Pathophysiology of the Bleeding" Consultant Gastroenterologist and Senior Lecturer in Medicine The London Hospital London ENGLAND Planning Committee Frank A. Hamilton, M.D., M.P.H. Planning Committee Chairperson Program Director Gastrointestinal Disease Programs Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland Stanley B. Benjamin, M.D. Professor of Medicine Chief Division of Gastroenterology Georgetown University Hospital Washington, D.C. Michael J. Bernstein Director of Communications Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland Linda W. Blankenbaker Program Analyst Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland Benjamin T. Burton, Ph.D., M.S. Associate Director Disease Prevention and Technology Transfer National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland Donald O. Castell, M.D. Panel and Conference Chairperson Professor of Medicine Chief of Gastroenterology Bowman Gray School of Medicine Wake Forest University Winston-Salem, North Carolina James N. Fordham Writer/Editor National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland Willis R. Foster, M.D. Senior Staff Physician Office of Disease Prevention and Technology Transfer National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland V.L. Go, M.D. Professor and Executive Chairman Department of Medicine University of California at Los Angeles Los Angeles, California William S. Hughes, M.D. National Digestive Diseases Advisory Council Washington, D.C. Lawrence F. Johnson, M.D. Professor of Medicine Director Digestive Diseases Division Uniformed Services University of the Health Sciences School of Medicine Bethesda, Maryland Pierre F. Renault, M.D. Deputy Director National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland Fred E. Silverstein, M.D. Professor of Medicine Director Gastrointestinal Endoscopy Service University Hospital University of Washington Seattle, Washington Susan Wallace, M.F.A. Conference Coordinator Prospect Associates Rockville, Maryland Conference Sponsors National Institute of Diabetes and Digestive and Kidney Diseases Phillip Gorden, M.D. Director NIH Office of Medical Applications of Research John H. Ferguson, M.D. Director

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