Management of Patients With Ulcer Bleeding

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1–3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy.

[1]  J. Gisbert,et al.  Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. , 2004, Alimentary pharmacology & therapeutics.

[2]  G. Rücker,et al.  Low‐dose aspirin for secondary cardiovascular prevention – cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation – review and meta‐analysis , 2005, Journal of internal medicine.

[3]  W. Murray,et al.  Prediction of rebleeding in peptic ulcers by visual stigmata and endoscopic Doppler ultrasound criteria. , 1990, Endoscopy.

[4]  Jih-Chang Chen,et al.  Risk scoring systems to predict need for clinical intervention for patients with nonvariceal upper gastrointestinal tract bleeding. , 2007, The American journal of emergency medicine.

[5]  A. Chak,et al.  Early endoscopy in upper gastrointestinal hemorrhage: associations with recurrent bleeding, surgery, and length of hospital stay. , 1999, Gastrointestinal endoscopy.

[6]  D. Freitas,et al.  Controlled trial of liquid monopolar electrocoagulation in bleeding peptic ulcers. , 1985, The American journal of gastroenterology.

[7]  Y. Joo,et al.  Optimal injection volume of epinephrine for endoscopic prevention of recurrent peptic ulcer bleeding. , 2004, Gastrointestinal endoscopy.

[8]  K. Tsoi,et al.  Second‐look endoscopy with thermal coagulation or injections for peptic ulcer bleeding: A meta‐analysis , 2010, Journal of gastroenterology and hepatology.

[9]  L. Laine,et al.  Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[10]  Nayoung Kim,et al.  Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea , 2009, Journal of gastroenterology and hepatology.

[11]  P Tugwell,et al.  Prevention of NSAID-induced gastroduodenal ulcers. , 2002, The Cochrane database of systematic reviews.

[12]  G. M. Gulzar,et al.  Comparison of p.o. or i.v. proton pump inhibitors on 72‐h intragastric pH in bleeding peptic ulcer , 2009, Journal of gastroenterology and hepatology.

[13]  M. Chan,et al.  RANDOMIZED TRIAL COMPARING PANTOPRAZOLE INFUSION, BOLUS AND NO TREATMENT ON GASTRIC pH AND RECURRENT BLEEDING IN PEPTIC ULCERS , 2007, ANZ journal of surgery.

[14]  J. Persing,et al.  The national ASGE survey on upper gastrointestinal bleeding. III. Endoscopy in upper gastrointestinal bleeding. , 1981, Gastrointestinal endoscopy.

[15]  O. Blatchford,et al.  A risk score to predict need for treatment for uppergastrointestinal haemorrhage , 2000, The Lancet.

[16]  Charles J. Kahi,et al.  ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use , 2010, The American Journal of Gastroenterology.

[17]  F. Chan,et al.  Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. , 2001, The New England journal of medicine.

[18]  Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. , 2002, The New England journal of medicine.

[19]  T. Kovacs,et al.  Recent advances in the endoscopic diagnosis and therapy of upper gastrointestinal, small intestinal, and colonic bleeding. , 2002, The Medical clinics of North America.

[20]  R. J. Noer Gastrointestinal tract hemorrhage , 1964 .

[21]  S. D. Lee,et al.  Early or delayed endoscopy for patients with peptic ulcer bleeding. A prospective randomized study. , 1996, Journal of clinical gastroenterology.

[22]  H. Tamim,et al.  Effect of erythromycin before endoscopy in patients presenting with variceal bleeding: a prospective, randomized, double-blind, placebo-controlled trial. , 2011, Gastrointestinal endoscopy.

[23]  A. Li,et al.  The evolution of stigmata of hemorrhage in bleeding peptic ulcers: a sequential endoscopic study. , 1998, Endoscopy.

[24]  D. Jensen,et al.  Endoscopic Hemostasis of Ulcer Hemorrhage with Injection, Thermal, and Combination Methods , 2005 .

[25]  P. Romano,et al.  Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial. , 1999, Gastrointestinal endoscopy.

[26]  L. Laine,et al.  Prospective evaluation of immediate versus delayed refeeding and prognostic value of endoscopy in patients with upper gastrointestinal hemorrhage. , 1992, Gastroenterology.

[27]  R. Prescott,et al.  A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer. , 2003, Gastroenterology.

[28]  D. Jensen,et al.  Diagnosis and treatment of severe hematochezia. The role of urgent colonoscopy after purge. , 1988, Gastroenterology.

[29]  R. Greenhalgh,et al.  Effect of early blood transfusion on gastrointestinal haemorrhage , 1986, The British journal of surgery.

[30]  B. Enestvedt,et al.  An evaluation of endoscopic indications and findings related to nonvariceal upper-GI hemorrhage in a large multicenter consortium. , 2008, Gastrointestinal endoscopy.

[31]  C. Bailey Celecoxib Versus Diclofenac and Omeprazole in Reducing the Risk of Recurrent Ulcer Bleeding in Patients With Arthritis , 2003 .

[32]  M. Blaser,et al.  Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection. , 1995, Gastroenterology.

[33]  L. Laine,et al.  Systematic Review of the Predictors of Recurrent Hemorrhage After Endoscopic Hemostatic Therapy for Bleeding Peptic Ulcers , 2008, The American Journal of Gastroenterology.

[34]  V. Wong,et al.  Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding , 2010, Annals of Internal Medicine.

[35]  Thomas R. Riley,et al.  A Randomized Double-blind Placebo-controlled Trial , 2004 .

[36]  G. I. Leontiadis,et al.  Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials. , 2007, Mayo Clinic proceedings.

[37]  L. Spahr,et al.  Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. , 2002, Gastroenterology.

[38]  G. Birnie,et al.  Controlled trial of heater probe treatment in bleeding peptic ulcers , 1989, The British journal of surgery.

[39]  Douglas R. Morgan,et al.  Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management , 1998 .

[40]  R. Collins,et al.  Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. , 2009, Lancet.

[41]  P. Hsu,et al.  Bleeding peptic ulcer--risk factors for rebleeding and sequential changes in endoscopic findings. , 1994, Gut.

[42]  J. Ponsky,et al.  Saline irrigation in gastric hemorrhage: the effect of temperature. , 1980, The Journal of surgical research.

[43]  J. Tsai,et al.  Arterial oxygen desaturation during emergent nonsedated upper gastrointestinal endoscopy in the emergency department. , 1997, The American journal of emergency medicine.

[44]  B. Spiegel,et al.  Minimizing Recurrent Peptic Ulcer Hemorrhage After Endoscopic Hemostasis: The Cost-Effectiveness of Competing Strategies , 2003, American Journal of Gastroenterology.

[45]  B. Spiegel,et al.  Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review. , 2001, Archives of internal medicine.

[46]  R. Marmo,et al.  Combined epinephrine and bipolar probe coagulation vs. bipolar probe coagulation alone for bleeding peptic ulcer: a randomized, controlled trial. , 2004, Gastrointestinal endoscopy.

[47]  L. Laine,et al.  A prospective outcome study of patients with clot in an ulcer and the effect of irrigation. , 1995, Gastrointestinal endoscopy.

[48]  J. Sung,et al.  Endoscopy for upper gastrointestinal bleeding: how urgent is it? , 2009, Nature Reviews Gastroenterology &Hepatology.

[49]  V. Bezlyak,et al.  Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial , 2009, The Lancet.

[50]  L. Laine,et al.  Determination of the optimal technique for bipolar electrocoagulation treatment. An experimental evaluation of the BICAP and Gold probes. , 1991, Gastroenterology.

[51]  D. Lieberman,et al.  Urgent vs. elective endoscopy for acute non-variceal upper-GI bleeding: an effectiveness study. , 2004, Gastrointestinal endoscopy.

[52]  M. Donnino,et al.  Identification and resuscitation of the trauma patient in shock. , 2007, Emergency medicine clinics of North America.

[53]  Á. Lanas,et al.  Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON) , 2011, Heart.

[54]  N. Talley Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding: A Randomized Trial , 2010 .

[55]  V. Wong,et al.  Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. , 2004, Gastroenterology.

[56]  D. Jensen Endoscopic diagnosis and treatment of severe hematochezia , 2001 .

[57]  X. Bobbia,et al.  Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. , 2011, Annals of emergency medicine.

[58]  R. Collins,et al.  Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials , 2009, The Lancet.

[59]  R. Hunt,et al.  International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding , 2010, Annals of Internal Medicine.

[60]  L. Laine,et al.  Randomized Trial of Urgent vs. Elective Colonoscopy in Patients Hospitalized With Lower GI Bleeding , 2010, The American Journal of Gastroenterology.

[61]  F. Burzotta,et al.  A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. , 2006, European heart journal.

[62]  S. Fan,et al.  Bleeding peptic ulcer: A prospective evaluation of risk factors for rebleeding and mortality , 1990, World Journal of Surgery.

[63]  A. Barkun,et al.  Nasogastric aspirate predicts high-risk endoscopic lesions in patients with acute upper-GI bleeding. , 2004, Gastrointestinal endoscopy.

[64]  O. Pascu,et al.  The effect of endoscopic hemostasis with alcohol on the mortality rate of nonvariceal upper gastrointestinal hemorrhage. A randomized prospective study. , 1989, Endoscopy.

[65]  C. Chu,et al.  Different implications of stigmata of recent hemorrhage in gastric and duodenal ulcers , 1988, Digestive Diseases and Sciences.

[66]  James F. Arens,et al.  Practice Guidelines for Sedation and Analgesia by Non-Anesthesiologists , 2002, Anesthesiology.

[67]  W. Chey,et al.  American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection , 2007, The American Journal of Gastroenterology.

[68]  F. Chang,et al.  A prospective, randomized trial of large- versus small-volume endoscopic injection of epinephrine for peptic ulcer bleeding. , 2002, Gastrointestinal endoscopy.

[69]  C. Mowat,et al.  Outpatient management of patients with low-risk upper-gastrointestinal haemorrhage: multicentre validation and prospective evaluation , 2009, The Lancet.

[70]  L. Laine,et al.  Lack of uniformity in evaluation of endoscopic prognostic features of bleeding ulcers. , 1994, Gastrointestinal endoscopy.

[71]  F. Chan,et al.  Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. , 1999, The New England journal of medicine.

[72]  M. Pocard,et al.  Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study. , 2002, Gastrointestinal endoscopy.

[73]  S. D. Lee,et al.  Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation. , 1996, Gastrointestinal endoscopy.

[74]  E. Kuipers,et al.  356: Rebleeding Risk for Oozing Peptic Ulcer Bleeding (PUB) in a Large International Study—A Reassessment Based Upon a Multivariate Analysis , 2010 .

[75]  V. Wong,et al.  High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. , 2009, Gastroenterology.

[76]  E. Kuipers,et al.  Methodology for Randomized Trials of Patients With Nonvariceal Upper Gastrointestinal Bleeding: Recommendations From an International Consensus Conference , 2010, The American Journal of Gastroenterology.

[77]  A. Barkun,et al.  Prokinetics in acute upper GI bleeding: a meta-analysis. , 2010, Gastrointestinal endoscopy.

[78]  Deepak L. Bhatt,et al.  Clopidogrel with or without omeprazole in coronary artery disease. , 2010, The New England journal of medicine.

[79]  D. Kearney,et al.  A Randomized Controlled Trial of Gastric Lavage Prior to Endoscopy for Acute Upper Gastrointestinal Bleeding , 2004, Journal of clinical gastroenterology.

[80]  Pipat Anguravirutt Endoscopy In Upper Gastrointestinal Bleeding. , 2011 .

[81]  F. Chan,et al.  The Effect of Endoscopic Therapy in Patients Receiving Omeprazole for Bleeding Ulcers with Nonbleeding Visible Vessels or Adherent Clots , 2003, Annals of Internal Medicine.

[82]  A. Cutler,et al.  Four-year trends in Helicobacter pylori IgG serology following successful eradication. , 1998, The American journal of medicine.

[83]  G. Guyatt,et al.  GRADE: an emerging consensus on rating quality of evidence and strength of recommendations , 2008, BMJ : British Medical Journal.

[84]  D. Morris,et al.  A comparison of the efficacy and depth of gastric wall injury with 3.2- and 2.3-mm bipolar probes in canine arterial hemorrhage. , 1985, Gastrointestinal endoscopy.

[85]  Welcome Guimera,et al.  Practice Guidelines for Sedation and Analgesia by Non- Anesthesiologists , 2005 .

[86]  J. Geschwind,et al.  Embolization of Acute Nonvariceal Upper Gastrointestinal Hemorrhage Resistant to Endoscopic Treatment: Results and Predictors of Recurrent Bleeding , 2010, CardioVascular and Interventional Radiology.

[87]  K. Palmer,et al.  Comparison of endoscopic injection therapy versus the heater probe in major peptic ulcer haemorrhage. , 1992, Gut.

[88]  J. P. O'sullivan,et al.  Nature of the bleeding vessel in recurrently bleeding gastric ulcers. , 1986, Gastroenterology.

[89]  L. Laine Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. A prospective, randomized trial. , 1990, Gastroenterology.

[90]  L. L. Davis Bleeding peptic ulcer. , 1952, Medical times.

[91]  L. Ger,et al.  When to discharge patients with bleeding peptic ulcers: a prospective study of residual risk of rebleeding. , 1996, Gastrointestinal endoscopy.

[92]  V. Wong,et al.  Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. , 2002, The New England journal of medicine.

[93]  M. Zaballa,et al.  Endoscopic local injection of ethanolamine oleate and thrombin as an effective treatment for bleeding duodenal ulcer: a controlled trial. , 1992, Gut.

[94]  G. Gitnick,et al.  Gastrointestinal and liver disease , 1979 .

[95]  L. Laine,et al.  Effect of Proton-Pump Inhibitor Therapy on Diagnostic Testing for Helicobacter pylori , 1998, Annals of Internal Medicine.

[96]  P. Tugwell,et al.  Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[97]  Loren Laine,et al.  Optimizing bipolar electrocoagulation for endoscopic hemostasis: assessment of factors influencing energy delivery and coagulation. , 2007, Gastrointestinal endoscopy.

[98]  G. Wells,et al.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. , 1999, The New England journal of medicine.

[99]  K. Hirabayashi,et al.  Randomized controlled study of 3 different types of hemoclips for hemostasis of bleeding canine acute gastric ulcers. , 2006, Gastrointestinal endoscopy.

[100]  G. M. Gulzar,et al.  Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: Prospective randomized controlled trial , 2006, Journal of gastroenterology and hepatology.

[101]  S. Köklü,et al.  Intermittent versus Continuous Pantoprazole Infusion in Peptic Ulcer Bleeding: A Prospective Randomized Study , 2008, Digestion.

[102]  F. Chan,et al.  Comparing the Blatchford and pre-endoscopic Rockall score in predicting the need for endoscopic therapy in patients with upper GI hemorrhage. , 2010, Gastrointestinal endoscopy.

[103]  H. Krumholz,et al.  Blood transfusion in elderly patients with acute myocardial infarction. , 2001, The New England journal of medicine.

[104]  V. Wong,et al.  Omeprazole before endoscopy in patients with gastrointestinal bleeding. , 2007, The New England journal of medicine.

[105]  D. Forman,et al.  Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. , 2010, The Cochrane database of systematic reviews.

[106]  C. Hawkey,et al.  Efficacy of Esomeprazole (20 mg Once Daily) for Reducing the Risk of Gastroduodenal Ulcers Associated With Continuous Use of Low-Dose Aspirin , 2008, The American Journal of Gastroenterology.

[107]  P. Boelle,et al.  Erythromycin Infusion Prior to Endoscopy for Acute Upper Gastrointestinal Bleeding: A Randomized, Controlled, Double-Blind Trial , 2006, The American Journal of Gastroenterology.

[108]  K. Palmer,et al.  Endoscopic injection therapy for bleeding peptic ulcer; a comparison of adrenaline alone with adrenaline plus ethanolamine oleate. , 1994, Gut.

[109]  C. Kum,et al.  Combination therapy using adrenaline and heater probe to reduce rebleeding in patients with peptic ulcer haemorrhage: A prospective randomized trial , 1995, The British journal of surgery.

[110]  A. Li,et al.  Endoscopic injection of adrenaline for actively bleeding ulcers: a randomised trial , 1988, British medical journal.

[111]  D. Jaspersen,et al.  Helicobacter pylori eradication reduces the rate of rebleeding in ulcer hemorrhage. , 1995, Gastrointestinal endoscopy.

[112]  D. Jensen,et al.  Hemoclipping of chronic canine ulcers: a randomized, prospective study of initial deployment success, clip retention rates, and ulcer healing. , 2009, Gastrointestinal endoscopy.

[113]  R. Marmo,et al.  Outpatient management for low-risk nonvariceal upper GI bleeding: a randomized controlled trial. , 2002, Gastrointestinal endoscopy.

[114]  P. Wara Endoscopic prediction of major rebleeding--a prospective study of stigmata of hemorrhage in bleeding ulcer. , 1985, Gastroenterology.

[115]  C. Perng,et al.  Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding , 1999, Gut.

[116]  J. Persing,et al.  The national ASGE survey on upper gastrointestinal bleeding. II. Clinical prognostic factors. , 1981, Gastrointestinal endoscopy.

[117]  G. Comer,et al.  Continuous Infusion of Pantoprazole versus Ranitidine for Prevention of Ulcer Rebleeding: A U.S. Multicenter Randomized, Double-Blind Study , 2006, The American Journal of Gastroenterology.

[118]  S C Chung,et al.  Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. , 1999, The New England journal of medicine.

[119]  M. Jensen,et al.  A controlled study of ranitidine for the prevention of recurrent hemorrhage from duodenal ulcer , 1994, The New England journal of medicine.

[120]  J. Sung,et al.  Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. , 1997, Gastrointestinal endoscopy.

[121]  A. Lok,et al.  Effect of omeprazole on duodenal ulcer-associated antral gastritis andHelicobacter pylori , 1991, Digestive Diseases and Sciences.

[122]  V. Wong,et al.  Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial , 2007, The Lancet.

[123]  K. Ho,et al.  Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. , 2011, Endoscopy.

[124]  D. V. van Thiel,et al.  Gastrointestinal tract hemorrhage. The value of a nasogastric aspirate. , 1990, Archives of internal medicine.

[125]  D. Fleischer,et al.  Recurrent bleeding from peptic ulcer associated with adherent clot: a randomized study comparing endoscopic treatment with medical therapy. , 2002, Gastrointestinal endoscopy.

[126]  T. Savides,et al.  Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots. , 2002, Gastroenterology.

[127]  R. Marmo,et al.  Outcome of endoscopic treatment for peptic ulcer bleeding: Is a second look necessary? A meta-analysis. , 2003, Gastrointestinal endoscopy.

[128]  J. Senior,et al.  Misoprostol Reduces Serious Gastrointestinal Complications in Patients with Rheumatoid Arthritis Receiving Nonsteroidal Anti-Inflammatory Drugs , 1995, Annals of Internal Medicine.

[129]  H B Devlin,et al.  Risk assessment after acute upper gastrointestinal haemorrhage. , 1996, Gut.

[130]  E. Kuipers,et al.  Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. , 2009, Annals of internal medicine.

[131]  S. D. Lee,et al.  Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. , 1994, Gut.

[132]  J. Gisbert,et al.  Helicobacter pylori eradication therapy vs. antisecretory non‐eradication therapy for the prevention of recurrent bleeding from peptic ulcer , 2004 .

[133]  A. Chak,et al.  The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis. , 1998, Medical care.

[134]  Horng‐Yuan Wang,et al.  Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleeding. , 2006, World journal of gastroenterology.

[135]  A. Karameris,et al.  Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. , 1995, Gastrointestinal endoscopy.

[136]  M. Swain,et al.  Impaired sympathetic nerve function in the inflamed rat intestine. , 1991, Gastroenterology.