Review Challenges in the management of acute peptic ulcer bleeding James Y W Lau, Alan Barkun, Dai-ming Fan, Ernst J Kuipers, Yun-sheng Yang, Francis K L Chan Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding Lancet 2013; 381: 2033–43 peptic ulcers. Endoscopic treatment and acid suppression with proton-pump inhibitors are cornerstones in the Institute of Digestive Diseases, management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery The Chinese University of Hong continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and Kong, Hong Kong, China (Prof J Y W Lau MD, recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder Prof F K L Chan MD); Division of has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use Gastroenterology, McGill antiplatelet agents, non-steroidal anti-infl ammatory drugs, and anticoagulants. The management of such patients, University and the McGill especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise University Health Centre, Quebec, Canada the published scientifi c literature about the management of patients with bleeding peptic ulcers, identify directions for (Prof A Barkun MD); Institute of future clinical research, and suggest how mortality can be reduced. Digestive Diseases, Xijing Hospital, Fourth Military Introduction by how participants were sampled, their inclusion Medical University, Xian, China (Prof D Fan MD); Department of Acute upper gastrointestinal bleeding is characterised by criteria, and defi nitions of case ascertainment. Gastroenterology and fresh blood or coff ee ground haematemesis and melaena Emergency surgery for bleeding peptic ulcers has Hepatology, Erasmus MC, (black tarry stool with a characteristic pungent odour). continued to decrease; in the UK, the rate of surgery Rotterdam, Netherlands Anatomically, bleeding arises from a lesion proximal to the dropped from 8% to 2% between 1993 and 2006.1,17 In the (Prof E J Kuipers MD); and Department of ligament of Treitz. In the 2007 UK National Audit, bleeding same period in the USA, admissions to hospital for Gastroenterology and peptic ulcers accounted for 36% of all causes of acute peptic ulcer bleeding fell by 28·2%, the use of endoscopic Hepatology, Chinese PLA upper gastrointestinal bleeding (table 1).1 A systematic treatment increased by 58·9%, and the rate of emergency General Hospital, Beijing, China (Prof Y Yang MD) review reported an incidence of peptic ulcer bleeding that ulcer surgery decreased by 21·9%.20 ranged from 19·4 to 57 per 100 000 population per year in Correspondence to: Prof James Y W Lau, Institute of 2 11 European studies. In China, the prevalence of peptic Initial assessment, resuscitation, and the use of Digestive Diseases, The Chinese ulcer bleeding has not been well studied, although peptic blood products in patients with acute upper University of Hong Kong, ulcer disease is common. In a cross-sectional endoscopic gastrointestinal bleeding Hong Kong, China survey of 3600 volunteers in Shanghai with a mean age of Patients presenting with acute upper gastrointestinal [email protected] 47·7 years, 17·2% of participants had peptic ulcer disease.3 bleeding should be assessed promptly and resuscitated. In two other hospital-based endoscopic surveys under- Volume should be replenished initially with crystalloid taken in Wuhan and Beijing,4,5 the prevalence of peptic solutions. In patients with ongoing blood loss, sympto- ulcer disease was 22·4% and 16·0%, respectively, and the matic anaemia, or those at increased risk of impaired rate of bleeding was estimated to be between 3·9% and tissue oxygenation (eg, patients with chronic heart 5·5%. In a country with a population of 1·33 billion people conditions), blood should be transfused. In haemo- and with a Helicobacter pylori infection rate of 58%, the dynamically stable patients who are not bleeding actively, disease burden is high.6 In this ageing population (the the threshold of transfusion needs to be defi ned. Inter- number of people aged >60 years will double in the next national guidelines recommend a policy of trans fusion to two decades) and with increasing urbanisation, the a haemoglobin concentration of 7 g/dL.21 From the recent prevalence of coronary and cerebro vascular diseases will UK National Audit, patients transfused within 12 h of rise7 and therefore so will the frequency of acute upper their admissions had a twofold increase in rate gastro intestinal bleeding related to use of aspirin and of rebleeding and a 28% increase in mortality.22 The anticoagulants. In a cross-sectional survey of patients with aspirin and nonsteroidal anti-infl ammatory drug- related acute upper gastro intestinal bleeding, investi gators Search strategy and selection criteria 8 reported a low rate of adherence to gastro-protective drugs. We searched PubMed, the Cochrane controlled clinical trial Hospital admissions for peptic ulcer bleeding are registry, and the Chinese language literature through China For more on China National declining ubiquitously because of reduced rates of National Knowledge Infrastructure between January, 1990, Knowledge Infrastructure see 9–16 H pylori infection (fi gure 1). As evident from the two and March, 2012. Search terms were ”ulcer”, ”bleeding peptic http://www.global.cnki.net 1,17 UK National Audits done in 1993 and 2007, the ulcer”, ”gastrointestinal bleeding”, ”gastric ulcer”, ”duodenal mortality rate has improved from 14% to 10% in the ulcer”, ”epidemiology”, ”H. pylori”, ”non-steroidal period between the two audits, despite an unchanged age anti-infl ammatory drugs”, ”aspirin”, and ”proton pump structure (median age 71 and 68 years, respectively). inhibitor”. We selected mostly randomised controlled studies Mortality from bleeding peptic ulcers was 5·8% in 2007. and their meta-analyses, with the intention to address major Multicentre observational studies from the USA, Canada, aspects in the management of acute peptic ulcer bleeding. All and Italy reported similar mortality rates of 2·5, 5·4, and selected studies were published in English or Chinese. 4·9%, respectively.14,18,19 The diff erences can be explained www.thelancet.com Vol 381 June 8, 2013 2033 Review transfusion. In patients who had restrictive transfusion, % (patients, n) rebleeding was less common (10% vs 16%, p=0·01) and Peptic ulcer 36% (1826) survival was higher at 6 weeks (95% vs 91%, hazard ratio Oesophagitis 24% (1177) 0·55, 95% CI 0·33–0·92, p=0·02) than in those in the Gastritis/erosions 22% (1091) liberal transfusion group. The diff erence in survival was No abnormality seen 17% (865) mainly recorded in patients with liver cirrhosis in Child– Duodenitis/erosions 13% (640) Pugh class A and B. In the subgroup of patients with Oesophagogastric varices 11% (544) bleeding peptic ulcers, a trend towards less rebleeding Mallory-Weiss tear 4·3% (213) (9% vs 12%, p=0·09) and a signifi cant reduction in Malignancy 3·7% (187) emergency surgery (2% vs 6%, p=0·04) were noted with Total 5004 restrictive transfusion. Less splanchnic blood fl ow and clotting derangement could explain these signifi cant Data taken from the National United Kingdom Audit on acute upper gastrointestinal bleeding.1 reductions in rebleeding and related deaths. The policy is generally applicable to stable patients with acute upper Table 1: Endoscopic diagnosis for patients presenting with acute upper gastrointestinal bleeding. gastrointestinal bleeding Coagulopathy at presentation is a major adverse prognostic factor. From the UK National Audit,25 coagu- lopathy defi ned by an international normalised ratio 140 Sadic et al,11 2009, Sweden Ohmann et al,10 2005, Germany (INR) above 1·5 was present in 16·4% of patients and Van Leerdam et al,9 2003, Netherlands was associated with a 15% mortality rate (adjusted odds Kang et al,12 2006, Scotland 120 Lanas et al,13 2009, Spain ratio 5·63, 95% CI 3·1–10·3). Coagulopathy is also a Laine et al,14 2012, USA marker for comorbid illnesses, such as chronic liver Wu et al,16 2009, Taiwan (duodenal ulcers) disease. Bleeding in these patients is often more severe, Wu et al,16 2009, Taiwan (gastric ulcers) 100 Loperfido et al,15 2009, Italy and coagulopathy should be corrected in those with active bleeding. The target INR has not been defi ned and 000 population 80 is established by the patient’s indication for anti coagu- lation. A study showed that mild to moderate anti coagu- lation (INR 1·3–2·7) at endoscopy did not increase the 60 risk of recurrent bleeding compared with an INR of less than 1·3.26 One small cohort study with a historical comparison showed that aggressive resusci tation includ- 40 ing correction of coagulation (INR <1·8) led to lower 27 Rate of hospital admission per 100 Rate mortality rates. Published data for the manage ment of 20 coagulopathy are scarce. Risk scores in patients with acute upper 0 gastrointestinal bleeding 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Patients should be risk stratifi ed at presentation. Year Clinical factors that predict a severe bleed and a need for Figure 1: Rate of admission to hospital for peptic ulcer bleeding per 100 000 population in recent time urgent assessment include tachycardia, hypotension, trend series nasogastric aspirate of red blood, and a haemoglobin Data taken from references 9–16. concentration less than 8 g/dL.28 Several scores for risk assessment have been published. The Rockall score is a increased rate of rebleeding was evident in all risk composite score that combines pre-endoscopy clinical categories.