Alan N. Barkun, MD; Majid Almadi, MD; Ernst J. Kuipers, MD; Loren Laine, MD; Joseph Sung, MD; Frances Tse, MD; Grigorios I. Leontiadis, MD; Neena S. Abraham, MD; Xavier Calvet, MD; Francis K.L. Chan, MD; James Douketis, MD; Robert Enns, MD; Ian M. Gralnek, MD; Vipul Jairath, MD; Dennis Jensen, MD; James Lau, MD; Gregory Y.H. Lip, MD; Romaric Loffroy, MD; Fauze Maluf-Filho, MD; Andrew C. Meltzer, MD; Nageshwar Reddy, MD; John R. Saltzman, MD; John K. Marshall, MD; Marc Bardou, MD
Note: This clinical practice guideline (CPG) on UGIB was developed under the direction of Drs. Alan N. Barkun and Marc Bardou, in accordance with the policies and procedures of the CAG and under the direction of CAG Clinical Affairs. It has been reviewed by the CAG Clinical Affairs Committee and the CAG Board of Directors. The CPG was developed after a thorough consideration of the medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian and international panel comprising experts on this topic. The CPG aims to provide a reasonable and practical approach to care for specialists and allied health professionals who are charged with providing optimal care to patients and their families, and it may be subject to change as scientific knowledge and technology advance and as practice patterns evolve.
Disclaimer: The CPG is not intended as a substitute for physicians using their individual judgment in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, the diagnostic and treatment options available, and the available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.
Acknowledgment: The CAG thanks the Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism and Diabetes and the Saudi Gastroenterology Association for their generous support of the guideline process. The consensus group thanks Dr. Waleed Alhazzani (McMaster University) for participation in the development of PICO questions and in preliminary discussions and voting; Paul Sinclair, Cindy Roll, and Lesley Marshall (CAG representatives) for administrative and technical support and logistical assistance; and Pauline Lavigne and Steven Portelance for editorial assistance and medical writing services (supported by funds from the CAG).
Financial Support: By an unrestricted grant to the CAG by the CIHR Institute of Nutrition, Metabolism and Diabetes and the Saudi Gastroenterology Association.
Disclosures: Dr. Barkun reports grants and consulting fees from and advisory board membership at Pendopharm and AtGen, and advisory membership at Olympus and Cook, outside the submitted work. Dr. Chan reports grants from the Research Grant Council of Hong Kong during the conduct of the study and advisory board membership at Pfizer, AstraZeneca, the Rome Foundation, Antibe Therapeutics, and the AGA Council; personal fees and honoraria from Pfizer, AstraZeneca, Eisai, Takeda Pharmaceuticals, EA Pharma, Japan Gastroenterological Endoscopy Society, Takeda (China) Holdings, Ministry of Health of Singapore, Olympus Hong Kong and China, Medical Association of Guangdong Province, and Associacao Dos Medicos Hospitalares Da Funcao Publica De Macau; personal fees and royalties from Wiley; grants from Pfizer, AstraZeneca, Triangle Pharmaceuticals, Given Imaging, Osaka City University, and Olympus Hong Kong and China; and commentary for American College of Physicians Journal Club, Nature Review: Gastroenterology and Hepatology, Evidence-based Medicine and Ministry of Health P.R. China, and Ministry of Health of Singapore, outside the submitted work. Dr. Douketis reports personal fees from Boehringer Ingelheim, Janssen, Pfizer, Bayer, Bristol-Myers Squibb, Sanofi, and Daiichi Sankyo outside the submitted work. Dr. Gralnek reports personal fees from Boston Scientific and Taro Pharmaceuticals outside the submitted work. Dr. Jairath reports personal fees from AbbVie, Takeda, Pfizer, Sandoz, Janssen, Arena Pharma, GSK, Eli Lilly, Ferring, Shire, Robarts Clinical Trials, Genentech, Merck, Topivert, Celltrion, Sublimity Therapeutics, F. Hoffman-La Roche, and Sigmatic Limited outside the submitted work. Dr. Jensen reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases; U.S. Veterans Affairs Clinical Merit Review, and American Society for Gastrointestinal Endoscopy Research Foundation; grants and personal fees from Vascular Technology; and personal fees from Boston Scientific outside the submitted work. Dr. Lip reports consulting and speakers fees from Bayer, Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi Sankyo outside the submitted work. Dr. Meltzer reports an active research grant from Medtronic to study gastrointestinal bleeding and serves on an advisory board for AnX Robotics. Dr. Saltzman reports personal fees from Cook Endoscopy outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1795.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Corresponding Author: Alan N. Barkun, MD, Division of Gastroenterology, McGill University and the McGill University Health Centre, 1650 Cedar Avenue, Room D7.346, Montreal, Quebec H3G 1A4, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Barkun: Division of Gastroenterology, McGill University and the McGill University Health Centre, 1650 Cedar Avenue, Room D7.346, Montreal, Quebec H3G 1A4, Canada.
Dr. Almadi: Division of Gastroenterology, Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University 12372, Riyadh, Saudi Arabia.
Dr. Kuipers: Erasmus MC University Medical Center, P.O. Box 2040, 3000CA Rotterdam, the Netherlands.
Dr. Laine: Section of Digestive Diseases, Yale School of Medicine, P.O. Box 208019, New Haven, CT 06520.
Dr. Sung: Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
Dr. Tse: Division of Gastroenterology, Department of Medicine, McMaster University, Room 2F53, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Dr. Leontiadis: Division of Gastroenterology, Department of Medicine, McMaster University, 1280 Main Street West, Health Sciences Centre, Suite 3V3, Hamilton, Ontario L8S 4K1, Canada.
Dr. Abraham: Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259.
Dr. Calvet: Servei d'Aparell Digestiu, Coproració Sanitária Universitária Parc Taulí, Parc Taulí 1, 08208 Sabadell, Barcelona, Catalunya, Spain.
Dr. Chan: Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR.
Dr. Douketis: Department of Medicine, McMaster University and St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
Dr. Enns: Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia V6Z 2K5, Canada.
Dr. Gralnek: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Dr. Jairath: London Health Sciences Centre, Room A10-228, University Hospital, London, Ontario N6A 4V2, Canada.
Dr. Jensen: Ronald Reagan UCLA Medical Center, Digestive Diseases–Westwood, 200 MP, 200 UCLA Medical Plaza, Suite 365C, Los Angeles, CA 90024.
Dr. Lau: Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.
Dr. Lip: Liverpool Centre for Cardiovascular Science, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, United Kingdom.
Dr. Loffroy: Department of Interventional Radiology, Image-Guided Therapy Centre, Dijon-Bourgogne University Hospital, 14 rue Gaffarel, 21000 Dijon, France.
Dr. Maluf-Filho: Cancer Institute of São Paulo–ICESP–USP, Av. Dr. Arnaldo, 251, CEP 01246-000, São Paulo–SP, Brazil.
Dr. Meltzer: Department of Emergency Medicine, GW Medical Faculty Associates, 2120 L Street Northwest, Washington, DC 20037.
Dr. Reddy: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad–500 082, India.
Dr. Saltzman: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Dr. Marshall: Division of Gastroenterology, McMaster University, 1280 Main Street West, Room 2F59, Hamilton, Ontario L8S 4K1, Canada.
Dr. Bardou: Clinical Investigation Centre INSERM 1432, Hospitalisation Unit and Gastroenterology and Liver Department, CHU Dijon-Bourgogne, Hopital Francois Mitterrand, 14 rue Gaffarel, BP77908, 21079 Dijon Cedex, France.
Author Contributions: Conception and design: A.N. Barkun, M. Almadi, E.J. Kuipers, L. Laine, F. Tse, G.I. Leontiadis, I.M. Gralnek, A.C. Meltzer, J.K. Marshall, M. Bardou.
Analysis and interpretation of the data: A.N. Barkun, M. Almadi, E.J. Kuipers, L. Laine, J. Sung, F. Tse, G.I. Leontiadis, N.S. Abraham, X. Calvet, J. Douketis, R. Enns, I.M. Gralnek, V. Jairath, J. Lau, G.Y.H. Lip, R. Loffroy, F. Maluf-Filho, A.C. Meltzer, J.R. Saltzman, M. Bardou.
Drafting of the article: A.N. Barkun, M. Almadi, J. Sung, F. Tse, G.I. Leontiadis, N.S. Abraham, F.K.L. Chan, R. Enns, I.M. Gralnek, M. Bardou.
Critical revision for important intellectual content: A.N. Barkun, M. Almadi, E.J. Kuipers, L. Laine, J. Sung, F. Tse, G.I. Leontiadis, N.S. Abraham, X. Calvet, F.K.L. Chan, J. Douketis, I.M. Gralnek, V. Jairath, D. Jensen, G.Y.H. Lip, R. Loffroy, F. Maluf-Filho, A.C. Meltzer, N. Reddy, J.R. Saltzman, J.K. Marshall.
Final approval of the article: A.N. Barkun, M. Almadi, E.J. Kuipers, L. Laine, J. Sung, F. Tse, G.I. Leontiadis, N.S. Abraham, X. Calvet, F.K.L. Chan, J. Douketis, R. Enns, I.M. Gralnek, V. Jairath, D. Jensen, J. Lau, G.Y.H. Lip, R. Loffroy, F. Maluf-Filho, A.C. Meltzer, N. Reddy, J.R. Saltzman, J.K. Marshall, M. Bardou.
Statistical expertise: A.N. Barkun, M. Almadi, L. Laine, G.I. Leontiadis.
Obtaining of funding: A.N. Barkun, M. Almadi.
Administrative, technical, or logistic support: A.N. Barkun, G.I. Leontiadis, M. Bardou.
Collection and assembly of data: A.N. Barkun, F. Tse, G.I. Leontiadis, X. Calvet, R. Enns, I.M. Gralnek, F. Maluf-Filho, A.C. Meltzer, J.K. Marshall, M. Bardou.
This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations.
An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional.
Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.
Table 1. Summary of Consensus Recommendations for the Management of UGIB*
Appendix Table 1. Pooled Sensitivity and Specificity of Pre-endoscopic Scoring Systems to Identify Patients at High Risk for Undesirable Clinical Outcomes
Appendix Table 2. Pooled Relative and Absolute Risks for Adverse Outcomes, According to Restrictive or Liberal RBC Transfusion Thresholds in Patients With UGIB
Appendix Table 3. Summary of Adjusted Results From Studies Assessing Timing of Endoscopy in Patients With UGIB at High Risk for Rebleeding or Death
Table 2. Pooled ORs and Absolute Risks of Unfavorable Outcomes, According to PPI Regimen, in Patients with High-Risk Stigmata Who Had Endoscopic Therapy
Appendix Table 4. Areas of Future Research
General Hospital of Heraklion Venizeleio-Pananeio
October 27, 2019
Need for updated recommendations on the use of nasogastric intubation for upper gastrointestinal bleeding?
I read with interest the recently published updated guidelines on the management of patients with nonvariceal upper gastrointestinal bleeding (UGIB) . I would like to comment on the use of nasogastric intubation. Surprisingly, the recommendation to consider nasogastric tube placement for prognostic purposes has remained unchanged since the first guidelines published in 2003  and is not discussed at all in the last update . However, several additional studies, including a recent systematic review, have been published since 2003 . The procedure is very uncomfortable and painful for patients , and in the absence of evidence demonstrating any benefit in terms of patient outcomes the practice of placing a nasogastric tube for UGIB should be limited (if not abandoned).Notable is that guideline recommendations on the use of nasogastric intubation (either for diagnostic or for prognostic purposes) vary substantially and are often conflicting . Use of nasogastric intubation for diagnostic purposes is limited by the insufficient negative predictive value of a non-bloody aspirate, even in cases of severe UGIB . Although a bloody nasogastric aspirate increases the risk for high-risk lesions, a negative nasogastric aspirate cannot rule out an actively bleeding or other high-risk lesion . Most importantly, evidence that nasogastric intubation improves patient-relevant outcomes (mortality, length of hospital stay, need for surgical intervention, rate of rebleeding, or transfusions) is lacking, with most available studies failing to demonstrate any benefit . However, well-designed randomized controlled trials to assess the effect of nasogastric tube placement on patient outcomes are currently lacking .In conclusion, considering the discomfort associated with the placement of a nasogastric tube and the lack of evidence demonstrating any benefit in terms of outcomes, the recommendation for using nasogastric intubation for prognostic purposes should be reevaluated. Several other prognostic tools are available that do not require the placement of a nasogastric tube. References1. Barkun AN, Almadi M, Kuipers EJ, et al. Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019;10.7326/m19-17952. Barkun A, Bardou M, Marshall JK, Group* ftNUGBCC. Consensus Recommendations for Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding. Ann Intern Med. 2003;139(10):843-857.3. Karakonstantis S, Tzagkarakis E, Kalemaki D, Lydakis C, Paspatis G. Nasogastric aspiration/lavage in patients with gastrointestinal bleeding: a review of the evidence. Expert Rev Gastroenterol Hepatol. 2018;12(1):63-72.4. Singer AJ, Richman PB, Kowalska A, Thode HC, Jr. Comparison of patient and practitioner assessments of pain from commonly performed emergency department procedures. Ann Emerg Med. 1999;33(6):652-658.
Alan N Barkun; Loren Laine; Grigorios I. Leontiadis; Marc Bardou
McGill University, Yale School of Medicine, McMaster University, Hospital Francois Mitterrand
November 13, 2019
Authors' Response to Karakonstantis et al
We thank Karakonstantis et al. for their comment concerning the use of the nasogastric tube and acknowledge what the existing evidence for its possible use is. We congratulate them on their recent systematic review that was published after our search criteria limits1. This particular recommendation was not selected for revision as group members did not consider it a priority based on many other numerous emerging, more practice-changing areas of interest that in contrast either required revision from our past guidelines or additions to these. Nonetheless, we concur with the authors that placement of a nasogastric tube provides only modest prognostic information that is based on very low certainty of evidence. It is thus not required in routine clinical practice which is in keeping with other guidelines2,3. 1. Karakonstantis S, Tzagkarakis E, Kalemaki D, Lydakis C, Paspatis G. Nasogastric aspiration/lavage in patients with gastrointestinal bleeding: a review of the evidence. Expert Rev Gastroenterol Hepatol 2018;12:63-72.2. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015;47:a1-46.3. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol 2012;107:345-60; quiz 61.
Saitama Medical University
December 31, 2019
Proton pump inhibitors, anticoagulants and hip fracture risk
In patients with previous ulcer bleeding requiring continued cardiovascular prophylaxis with anticoagulant therapy, the international consensus group suggests using proton pump inhibitor (PPI) therapy versus no PPI therapy (statement E5) (1). Regarding selection of anticoagulants especially in older patients, direct oral anticoagulants (DOACs) rather than vitamin K antagonists such as warfarin might be recommended on the basis of hip fracture risk (2, 3) in addition to the drug interaction with PPIs.I fully agree that the evidence for causal associations between PPI therapy and various reported adverse effects including hip fracture is very weak (1); indeed, most of the adverse effects except intestinal infections appear to be generally associated with poorer health (4). PPI therapy is therefore unlikely to be a modifiable risk factor for hip fracture, whereas many PPI users could potentially have an increased risk of hip fracture indirectly through physical inactivity (2).I have suggested that the adverse effect of vitamin K antagonists on bone material quality in the hip can be compensated by skeletal adaptation to mechanical strain-related stimuli, which is compatible with accumulating clinical data showing no significant relationship between use of vitamin K antagonists and hip fracture risk. Of note, the compensation is limited by physical inactivity that would be essentially linked to osteoporosis as well as sarcopenia (3) and the possibility is supported by a recent finding in DOACs versus warfarin users with atrial fibrillation that relatively lower hip fracture risk was observed in the patients with osteoporosis but not those without osteoporosis (5).References1. Barkun AN, Almadi M, Kuipers EJ, et al. Management of nonvariceal upper gastrointestinal bleeding: guideline recommendations from the international consensus group. Ann Intern Med. 2019;171:805-22.2. Sugiyama T. Proton pump inhibitor therapy and fracture risk: discrepancy of results between observational and interventional studies. Gastroenterology. In press (accepted 30 September 2019).3. Sugiyama T. Anticoagulant therapy and hip fracture risk: a possible involvement of physical activity. J Am Coll Cardiol. In press (accepted 26 November 2019).4. Howden CW, Korvick JA, Harinstein L, et al. Controversies around measuring drug toxicity: US Food and Drug Administration and gastrointestinal perspectives. Gastroenterology. 2020;158:22-7.5. Lutsey PL, Norby FL, Ensrud KE, et al. Association of anticoagulant therapy with risk of fracture among patients with atrial fibrillation. JAMA Intern Med. Epub ahead of print (published online 25 November 2019).
Barkun AN, Almadi M, Kuipers EJ, et al. Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019;171:805–822. [Epub ahead of print 22 October 2019]. doi: https://doi.org/10.7326/M19-1795
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Published: Ann Intern Med. 2019;171(11):805-822.
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