Background. The mortality from nonvariceal upper gastrointestinal bleeding is still around 5%, despite the increased use of proton-pump inhibitors and the advancement of endoscopic therapeutic modalities. Aim. To review the state-of-the-art management of acute non variceal upper gastrointestinal bleeding from the presentation to the emergency department, risk stratification, endoscopic hemostasis, and postendoscopic consolidation management to reduce the risk of recurrent bleeding from peptic ulcers. Methods. A PubMed search was performed using the following key words acute management, non variceal upper gastrointestinal bleeding, and bleeding peptic ulcers. Results. Risk stratifying patients with acute non variceal upper gastrointestinal bleeding allows the categorization into low risk versus high risk of rebleeding, subsequently safely discharging low risk patients early from the emergency department, while achieving adequate hemostasis in high-risk lesions followed by continuous proton-pump inhibitors for 72 hours. Dual endoscopic therapy still remains the recommended choice in controlling bleeding from peptic ulcers despite the emergence of new endoscopic modalities such as the hemostatic powder. Conclusion. The management of nonvariceal upper gastrointestinal bleeding involves adequate resuscitation, preendoscopic risk assessment, endoscopic hemostasis, and post endoscopic pharmacological and nonpharmacological treatment. 1. Introduction About 10% of the population in the Western world will experience peptic ulcer disease at some point during their lives. Individuals with peptic ulcer disease may present with a variety of gastrointestinal (GI) symptoms including abdominal pain, vomiting, and bleeding. Indeed, peptic ulcer disease is the most common cause of conditions such as upper GI hemorrhage and perforation, which are associated with high mortality and morbidity [1]. Acute upper gastrointestinal bleeding (AUGIB) is one of the commonest causes for hospitalization worldwide. In the United States, there are 250,000 to 300,000 hospital admissions and 15,000 to 30,000 deaths each year resulting from acute upper GI hemorrhage [2]. The mortality from bleeding peptic ulcer disease remains unchanged around 5% [3, 4], despite the use of PPI and advances in endoscopic therapy. The unchanged mortality rate might reflect the increased use of aspirin and NSAID in the elderly population with multiple underlying comorbidities that puts such patients at higher risk of both bleeding and death [5]. The incidence of AUGIB ranges from 48 to 160 cases per 100 000
References
[1]
A. Barkun and G. Leontiadis, “Systematic review of the symptom burden, quality of life impairment and costs associated with peptic ulcer disease,” American Journal of Medicine, vol. 123, no. 4, pp. 358.e2–366.e2, 2010.
[2]
D. A. Gilbert, “Epidemiology of upper gastrointestinal bleeding,” Gastrointestinal Endoscopy, vol. 36, supplement 5, pp. S8–S13, 1990.
[3]
G. F. Longstreth, “Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study,” American Journal of Gastroenterology, vol. 90, no. 2, pp. 206–210, 1995.
[4]
M. E. Van Leerdam, E. M. Vreeburg, E. A. J. Rauws et al., “Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000,” American Journal of Gastroenterology, vol. 98, no. 7, pp. 1494–1499, 2003.
[5]
P. W. Chiu and E. K. Ng, “Predicting poor outcome from acute upper gastrointestinal hemorrhage,” Gastroenterology Clinics of North America, vol. 38, no. 2, pp. 215–230, 2009.
[6]
A. N. Barkun, M. Bardou, E. J. Kuipers et al., “International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding,” Annals of Internal Medicine, vol. 152, no. 2, pp. 101–113, 2010.
[7]
M. A. Almadi, A. Barkun, and J. Brophy, “Antiplatelet and anticoagulant therapy in patients with gastrointestinal bleeding: an 86-year-old woman with peptic ulcer disease,” JAMA, vol. 306, no. 21, pp. 2367–2374, 2011.
[8]
V. Jairath and A. N. Barkun, “The overall approach to the management of upper gastrointestinal bleeding,” Gastrointestinal Endoscopy Clinics of North America, vol. 21, no. 4, pp. 657–670, 2011.
[9]
T. A. Rockall, R. F. A. Logan, H. B. Devlin, and T. C. Northfield, “Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom,” British Medical Journal, vol. 311, no. 6999, pp. 222–226, 1995.
[10]
O. Blatchford, L. A. Davidson, W. R. Murray, M. Blatchford, and J. Pell, “Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study,” British Medical Journal, vol. 315, no. 7107, pp. 510–514, 1997.
[11]
J. P. Wallis, A. W. Wells, and C. E. Chapman, “Changing indications for red cell transfusion from 2000 to 2004 in the North of England,” Transfusion Medicine, vol. 16, no. 6, pp. 411–417, 2006.
[12]
S. A. Hearnshaw, R. F. A. Logan, K. R. Palmer, T. R. Card, S. P. L. Travis, and M. F. Murphy, “Outcomes following early red blood cell transfusion in acute upper gastrointestinal bleeding,” Alimentary Pharmacology and Therapeutics, vol. 32, no. 2, pp. 215–224, 2010.
[13]
C. P. Engelfriet, H. W. Reesink, J. McCullough et al., “Perioperative triggers for red cell transfusions,” Vox Sanguinis, vol. 82, no. 4, pp. 215–226, 2002.
[14]
P. C. Hébert, G. Wells, M. A. Blajchman et al., “A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care,” The New England Journal of Medicine, vol. 340, no. 6, pp. 409–417, 1999.
[15]
A. Shingina, A. N. Barkun, A. Razzaghi, M. Martel, M. Bardou, and I. Gralnek, “Systematic review: the presenting international normalised ratio (INR) as a predictor of outcome in patients with upper nonvariceal gastrointestinal bleeding,” Alimentary Pharmacology and Therapeutics, vol. 33, no. 9, pp. 1010–1018, 2011.
[16]
R. Baradarian, S. Ramdhaney, R. Chapalamadugu et al., “Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality,” American Journal of Gastroenterology, vol. 99, no. 4, pp. 619–622, 2004.
[17]
C. P. Choudari, C. Rajgopal, and K. R. Palmer, “Acute gastrointestinal haemorrhage in anticoagulated patients: diagnoses and response to endoscopic treatment,” Gut, vol. 35, no. 4, pp. 464–466, 1994.
[18]
J. F. Guest, H. G. Watson, and S. Limaye, “Modeling the cost-effectiveness of prothrombin complex concentrate compared with fresh frozen plasma in emergency warfarin reversal in the United kingdom,” Clinical Therapeutics, vol. 32, no. 14, pp. 2478–2493, 2010.
[19]
J. S. Healey, J. Eikelboom, J. Douketis, L. Wallentin, J. Oldgren, S. Yang, et al., “Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial,” Circulation, vol. 126, no. 3, pp. 343–348, 2012.
[20]
A. M. Aljebreen, C. A. Fallone, and A. N. Barkun, “Nasogastric aspirate predicts high-risk endoscopic lesions in patients with acute upper-GI bleeding,” Gastrointestinal Endoscopy, vol. 59, no. 2, pp. 172–178, 2004.
[21]
D. A. Gilbert, F. E. Silverstein, and F. J. Tedesco, “The national ASGE survey on upper gastrointestinal bleeding. III. Endoscopy in upper gastrointestinal bleeding,” Gastrointestinal Endoscopy, vol. 27, no. 2, pp. 94–102, 1981.
[22]
D. A. Corley, A. M. Stefan, M. Wolf, E. F. Cook, and T. H. Lee, “Early indicators of prognosis in upper gastrointestinal hemorrhage,” American Journal of Gastroenterology, vol. 93, no. 3, pp. 336–340, 1998.
[23]
A. Barkun, M. Bardou, and J. K. Marshall, “Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding,” Annals of internal medicine, vol. 139, no. 10, pp. 843–857, 2003.
[24]
P. Almela, A. Benages, S. Peiro, R. Anon, M. M. Perez, A. Pena, et al., “A risk score system for identification of patients with upper-GI bleeding suitable for outpatient management,” Gastrointestinal Endoscopy, vol. 59, no. 7, pp. 772–781, 2004.
[25]
T. F. Imperiale, J. A. Dominitz, D. T. Provenzale et al., “Predicting poor outcome from acute upper gastrointestinal hemorrhage,” Archives of Internal Medicine, vol. 167, no. 12, pp. 1291–1296, 2007.
[26]
T. A. Rockall, R. F. A. Logan, H. B. Devlin, and T. C. Northfield, “Risk assessment after acute upper gastrointestinal haemorrhage,” Gut, vol. 38, no. 3, pp. 316–321, 1996.
[27]
O. Blatchford, W. R. Murray, and M. Blatchford, “A risk score to predict need for treatment for upper-gastrointestinal haemorrhage,” The Lancet, vol. 356, no. 9238, pp. 1318–1321, 2000.
[28]
I. M. Gralnek and G. S. Dulai, “Incremental value of upper endoscopy for triage of patients with acute non-variceal upper-GI hemorrhage,” Gastrointestinal Endoscopy, vol. 60, no. 1, pp. 9–14, 2004.
[29]
S. B. Laursen, J. M. Hansen, and O. B. Schaffalitzky de Muckadell, “The glasgow blatchford score is the most accurate assessment of patients with upper gastrointestinal hemorrhage,” Clinical Gastroenterology and Hepatology, vol. 10, no. 10, pp. 1130.e1–1135.e1, 2012.
[30]
A. J. Stanley, D. Ashley, H. R. Dalton et al., “Outpatient management of patients with low-risk upper-gastrointestinal haemorrhage: multicentre validation and prospective evaluation,” The Lancet, vol. 373, no. 9657, pp. 42–47, 2009.
[31]
S. H. Pang, J. Y. L. Ching, J. Y. W. Lau, J. J. Y. Sung, D. Y. Graham, and F. K. L. Chan, “Comparing the Blatchford and pre-endoscopic Rockall score in predicting the need for endoscopic therapy in patients with upper GI hemorrhage,” Gastrointestinal Endoscopy, vol. 71, no. 7, pp. 1134–1140, 2010.
[32]
J. J. Y. Sung, K. K. F. Tsoi, L. H. Lai, J. C. Y. Wu, and J. Y. W. Lau, “Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis,” Gut, vol. 56, no. 10, pp. 1364–1372, 2007.
[33]
S. El Ouali, A. N. Barkun, J. Wyse, J. Romagnuolo, J. J. Sung, I. M. Gralnek, et al., “Is routine second-look endoscopy effective after endoscopic hemostasis in acute peptic ulcer bleeding? A meta-analysis,” Gastrointestinal Endoscopy, vol. 76, no. 2, pp. 283–292, 2012.
[34]
G. I. Leontiadis, A. Sreedharan, S. Dorward et al., “Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding,” Health Technology Assessment, vol. 11, no. 51, pp. 1–164, 2007.
[35]
A. N. Barkun, “Should every patient with suspected upper GI bleeding receive a proton pump inhibitor while awaiting endoscopy?” Gastrointestinal Endoscopy, vol. 67, no. 7, pp. 1064–1066, 2008.
[36]
A. N. Barkun, M. Martel, Y. Toubouti, E. Rahme, and M. Bardou, “Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses,” Gastrointestinal Endoscopy, vol. 69, no. 4, pp. 786–799, 2009.
[37]
P. Tsibouris, E. Zintzaras, C. Lappas et al., “High-dose pantoprazole continuous infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding,” American Journal of Gastroenterology, vol. 102, no. 6, pp. 1192–1199, 2007.
[38]
M. Vergara, X. Calvet, and J. P. Gisbert, “Epinephrine injection versus epinephrine injection and a second endoscopic method in high risk bleeding ulcers,” Cochrane Database of Systematic Reviews, no. 2, p. CD005584, 2007.
[39]
A. N. Barkun, M. Bardou, M. Martel, I. M. Gralnek, and J. J. Y. Sung, “Prokinetics in acute upper GI bleeding: a meta-analysis,” Gastrointestinal Endoscopy, vol. 72, no. 6, pp. 1138–1145, 2010.
[40]
B. Coffin, M. Pocard, Y. Panis et al., “Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study,” Gastrointestinal Endoscopy, vol. 56, no. 2, pp. 174–179, 2002.
[41]
N. Carbonell, A. Pauwels, L. Serfaty, P. Y. Boelle, L. Becquemont, and R. Poupon, “Erythromycin infusion prior to endoscopy for acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial,” American Journal of Gastroenterology, vol. 101, no. 6, pp. 1211–1215, 2006.
[42]
J. L. Frossard, L. Spahr, P. E. Queneau et al., “Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial,” Gastroenterology, vol. 123, no. 1, pp. 17–23, 2002.
[43]
N. S. Winstead and C. M. Wilcox, “Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost-effectiveness analysis,” Alimentary Pharmacology and Therapeutics, vol. 26, no. 10, pp. 1371–1377, 2007.
[44]
L. Cipolletta, M. A. Bianco, G. Rotondano, R. Marmo, and R. Piscopo, “Outpatient management for low-risk nonvariceal upper GI bleeding: a randomized controlled trial,” Gastrointestinal Endoscopy, vol. 55, no. 1, pp. 1–5, 2002.
[45]
H. J. Lin, K. Wang, C. L. Perng et al., “Early or delayed endoscopy for patients with peptic ulcer bleeding: a prospective randomized study,” Journal of Clinical Gastroenterology, vol. 22, no. 4, pp. 267–271, 1996.
[46]
A. N. Ananthakrishnan, E. L. McGinley, and K. Saeian, “Outcomes of weekend admissions for upper gastrointestinal hemorrhage: a nationwide analysis,” Clinical Gastroenterology and Hepatology, vol. 7, no. 3, pp. 296.e1–302.e1, 2009.
[47]
J. G. Lee, S. Turnipseed, P. S. Romano et al., “Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial,” Gastrointestinal Endoscopy, vol. 50, no. 6, pp. 755–761, 1999.
[48]
J. Chen, Y. C. Yuan, G. I. Leontiadis, and C. W. Howden, “Recent safety concerns with proton pump inhibitors,” Journal of Clinical Gastroenterology, vol. 46, no. 2, pp. 93–114, 2012.
[49]
S. A. Giday, Y. Kim, D. M. Krishnamurty et al., “Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model,” Endoscopy, vol. 43, no. 4, pp. 296–299, 2011.
[50]
R. Marmo, G. Rotondano, R. Piscopo, M. A. Bianco, R. D'Angella, and L. Cipolletta, “Dual therapy versus monotherapy in the endoscopic treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials,” American Journal of Gastroenterology, vol. 102, no. 2, pp. 279–289, 2007.
[51]
L. Laine and K. R. McQuaid, “Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials,” Clinical Gastroenterology and Hepatology, vol. 7, no. 1, pp. 33–47, 2009.
[52]
B. L. Bleau, C. J. Gostout, K. E. Sherman et al., “Recurrent bleeding from peptic ulcer associated with adherent clot: a randomized study comparing endoscopic treatment with medical therapy,” Gastrointestinal Endoscopy, vol. 56, no. 1, pp. 1–6, 2002.
[53]
C. J. Kahi, D. M. Jensen, J. J. Y. Sung et al., “Endoscopic therapy versus medical therapy for bleeding peptic ulcer with adherent clot: a meta-analysis,” Gastroenterology, vol. 129, no. 3, pp. 855–862, 2005.
[54]
J. J. Y. Sung, F. K. L. Chan, J. Y. W. Lau et al., “The effect of endoscopic therapy in patients receiving omeprazole for bleeding ulcers with nonbleeding visible vessels or adherent clots: a randomized comparison,” Annals of Internal Medicine, vol. 139, no. 4, pp. 237–I12, 2003.
[55]
J. Y. W. Lau, S. C. S. Chung, J. W. Leung, K. K. Lo, M. Y. Yung, and A. K. C. Li, “The evolution of stigmata of hemorrhage in bleeding peptic ulcers: a sequential endoscopic study,” Endoscopy, vol. 30, no. 6, pp. 513–518, 1998.
[56]
S. Dorward, A. Sreedharan, G. I. Leontiadis, C. W. Howden, P. Moayyedi, and D. Forman, “Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding,” Cochrane Database of Systematic Reviews, no. 4, p. CD005415, 2006.
[57]
S. A. Giday, “Preliminary data on the nanopowder hemostatic agent TC-325 to control gastrointestinal bleeding.,” Journal of Gastroenterology and Hepatology, vol. 7, no. 9, pp. 620–622, 2011.
[58]
P. I. Hsu, G. H. Lo, C. C. Lo et al., “Intravenous pantoprazole versus ranitidine for prevention of rebleeding after endoscopic hemostasis of bleeding peptic ulcers,” World Journal of Gastroenterology, vol. 10, no. 24, pp. 3666–3669, 2004.
[59]
G. I. Leontiadis and C. W. Howden, “The role of proton pump inhibitors in the management of upper gastrointestinal bleeding,” Gastroenterology Clinics of North America, vol. 38, no. 2, pp. 199–213, 2009.
[60]
G. I. Leontiadis, V. K. Sharma, and C. W. Howden, “Proton pump inhibitor treatment for acute peptic ulcer bleeding,” Cochrane Database of Systematic Reviews, no. 1, p. CD002094, 2006.
[61]
G. Leontiadis and A. Barkun, “Commentary: what is the optimal PPI dosing following endoscopic haemostasis in acute ulcer bleeding?” Alimentary Pharmacology & Therapeutics, vol. 35, no. 11, pp. 1351–1352, 2012.
[62]
K. E. McColl, “Clinical practice. Helicobacter pylori infection,” The New England Journal of Medicine, vol. 362, no. 17, pp. 1597–1604, 2010.
[63]
M. Derogar, G. Sandblom, L. Lundell, N. Orsini, M. Bottai, Y. Lu, et al., “discontinuation of low-dose aspirin therapy after peptic ulcer bleeding increases risk of death and acute cardiovascular events,” Clinical Gastroenterology and Hepatology, 2012. In press.
