Endoscopic therapy for upper gastrointestinal bleeding

Upper gastrointestinal bleeding (UGIB) is one of the most common medical emergencies and remains a major cause of morbidity and mortality among patients. Although initially employed diagnostically, endoscopy has steadily replaced surgery as a first-line treatment in all but the haemodynamically unstable patient. A vast selection of techniques and devices are now available to the dedicated therapeutic endoscopist, including injection therapy, electrical or thermal coagulation and mechanical banding or clipping. The use of endoscopic ultrasound for targeting treatment is increasing and the development of new technologies, such as capsule endoscopy, is likely to play an important role in future protocols. However, despite numerous randomized controlled trials and meta-analyses comparing the efficacy of different endoscopic interventions, the implementation of obtained results into treatment regimes has so far failed to impact significantly on overall UGIB mortality, which remains stubbornly at 10-14%. Reducing this continues to be one of the main challenges facing the therapeutic endoscopist.     

The pharmacological therapy of non-variceal upper gastrointestinal bleeding

The modern management of patients with upper gastrointestinal bleeding includes, in selected patients, the performance of timely multimodal endoscopic hemostasis followed by profound acid suppression. This article discusses the available data on the use of antisecretory regimens in the management of patients with bleeding peptic ulcers, which are a major cause of non-variceal upper gastrointestinal bleeding, and briefly addresses other medications used in this acute setting. The most important clinically relevant data are presented, favoring fully published articles.     

Diagnosis and therapy of non-variceal upper gastrointestinal bleeding

Non-variceal upper gastrointestinal bleeding(UGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of oesophageal, gastric or duodenal varices. The clinical presentation varies according to the intensity of bleeding from occult bleeding to melena or haematemesis and haemorrhagic shock. Causes of UGIB are peptic ulcers, Mallory-Weiss lesions,erosive gastritis, reflux oesophagitis, Dieulafoy lesions or angiodysplasia. After admission to the hospital a structured approach to the patient with acute UGIB that includes haemodynamic resuscitation and stabilization as well as pre-endoscopic risk stratification has to be done. Endoscopy offers not only the localisation of the bleeding site but also a variety of therapeutic measures like injection therapy, thermocoagulation or endoclips. Endoscopic therapy is facilitated by acid suppression with proton pump inhibitor(PPI) therapy. These drugs are highly effective but the best route of application(oral vs intravenous) and the adequate dosage are still subjects of discussion. Patients with ulcer disease are tested for Helicobacter pylori and eradication therapy should be given if it is present. Non-steroidal antiinflammatory drugs have to be discontinued if possible. If discontinuation is not possible, cyclooxygenase-2 inhibitors in combination with PPI have the lowest bleeding risk but the incidence of cardiovascular events is increased.     

Non-variceal upper gastrointestinal bleeding

Severe upper gastrointestinal bleeding remains a common medical emergency. In the last two decades endoscopy has become the cornerstone of diagnosis, risk stratification and treatment of peptic ulcer bleeding. Clinical assessment and endoscopic recognition of the stigmata of recent haemorrhage can allow the identification of patients with a high risk of rebleeding. Patients with active bleeding at the time of endoscopy and with non-bleeding visible vessels should receive endoscopic treatment. Studies comparing different treatment modalities are mostly single centre studies with relatively small groups of patients and therefore lack statistical power. Furthermore most of those trials were heterogeneous because of differences in the end points, differences in the risk factors for rebleeding and differences in the levels of experience of the endoscopists in both recognition and treatment of bleeding ulcers. Recently different treatment modalities have been studied. The injection of clot-inducing factors, a combination of injection and thermal therapies, repeat endoscopies and the use of mechanical devices such as clips and ligatures are promising new techniques. However, there are, at present, no convincing data to suggest that any one of these treatment modalities is superior when looking at the overall group of patients with bleeding peptic ulcer. Larger randomized controlled trials must focus on tailoring therapies and using the optimal therapy for different subgroups of patients.     

Nonvariceal upper gastrointestinal bleeding

Nonvariceal UGI bleeding is one of the most common emergencies that gastroenterologists encounter, and continues to be a significant cause of morbidity and mortality. The keys to management are rapid resuscitation and stabilization; appropriate triage based on pre-endoscopic risk factors; early endoscopy to achieve prompt diagnosis and implement hemostatic therapy to high-risk lesions; and aggressive antisecretory therapy (in the case of peptic ulcer bleeding) to reduce the risk of continued or recurrent bleeding.     

内镜治疗在急性非静脉曲张上消化道出血中的应用

急性非静脉曲张上消化道出血是临床常见的急危重症。内镜技术在急性非静脉曲张上消化道出血的治疗中有重要价值。近年此领域有了持续的新进展。本文即就内镜治疗对急性非静脉曲张上消化道出血的适宜治疗患者、治疗时机以及治疗方法和策略等方面给予简述。     

Hyaluronic acid solution injection for upper and lower gastrointestinal bleeding after failed conventional endoscopic therapy

Hyaluronic acid solution injection can be an additional endoscopic modality for controlling bleeding in difficult cases when other techniques have failed. We evaluated 12 cases in which we used hyaluronic acid solution injection for stopping bleeding. Immediately following hyaluronic acid solution injection, bleeding was controlled in 11 out of 12 cases. There was no clinical evidence of renewed bleeding in 11 cases during follow up.Hyaluronic acid solution injection can be a simple and efficient additional method for controlling upper and lower gastrointestinal bleeding after failed endoscopic therapy.     

Management of upper gastrointestinal bleeding

Upper gastrointestinal bleeding secondary to ulcer disease is common and results in substantial patient morbidity and medical expense. After initial resuscitation to stabilize the patient, carefully performed endoscopy provides an accurate diagnosis and identifies high-risk ulcer patients who are likely to rebleed with medical therapy alone and will benefit most from endoscopic hemostasis. For patients with major stigmata of ulcer hemorrhage—active arterial bleeding, nonbleeding visible vessel, and adherent clot—combination therapy with epinephrine injection and either thermal coagulation (multipolar or heater probe) or endoclips is recommended. High-dose intravenous proton pump inhibitors are recommended as concomitant therapy after successful endoscopic hemostasis. Patients with minor stigmata or clean-based ulcers will not benefit from endoscopic treatment and should receive high-dose oral proton pump inhibitor therapy. Effective medical and endoscopic management of ulcer hemorrhage can significantly improve outcomes and decrease the cost of medical care by reducing rebleeding, transfusion requirements, and the need for surgery.     

肝移植术后消化道出血的内镜治疗

目的评价肝移植术后发生食管胃底静脉曲张破裂出血(EVB)患者的内镜治疗效果。方法对2003年5月-2016年4月解放军总医院消化内科收治的8例肝移植术后发生EVB行内镜治疗患者的临床资料,特别是内镜下特点进行回顾性研究,评价其临床效果,包括止血率、治疗后曲张静脉变化、近期复发出血率。结果 8例患者平均55.00(44.75~61.50)岁。肝移植术后出现消化道出血时间平均为71.50(18.75~107.25)个月。原发病包括乙型肝炎肝硬化6例,其中合并肝癌1例,合并酒精性肝硬化1例,急性肝坏死1例,亚急性肝坏死3例;丙型肝炎肝硬化1例;不明原因肝硬化1例。行硬化治疗2例,套扎治疗6例,组织胶治疗6例。内镜下均成功止血,出院时均无再次出血,随访12个月无再发出血,其中1例因静脉曲张复发行择期内镜下治疗。结论肝移植术后消化道出血仍是其严重的并发症,术后除抗病毒等预防外,应密切监测患者有无静脉曲张的出现。     

Drug therapy for non-variceal upper gastrointestinal bleeding. Assessment of options

The efficacy of somatostatin and octreotide have been widely studied in the control of bleeding from oesophageal varices. It has also been suggested that these drugs may be useful for the control of non-variceal upper gastrointestinal (UGI) bleeding, including that from peptic ulcers. In approximately 80% of patients presenting with non-variceal UGI bleeding, haemorrhage ceases spontaneously and does not recur. However, the remaining 20% of patients require active treatment. Results from recent studies have indicated that somatostatin is an effective treatment for the control of non-variceal UGI bleeding in high-risk patients, i.e. those in whom haemorrhage does not cease spontaneously or is likely to recur. In contrast there is no good evidence available at present to support a role for octreotide, histamine (H(2) antagonists) or proton pump inhibitors in this indication. The efficacy of somatostatin in controlling bleeding in patients with non-variceal UGI bleeding at high risk of mortality upon admission, or rebleeding following endoscopy, coupled with an excellent safety and tolerability profile, suggests it may be a valuable therapeutic option in the management of non-variceal bleeding.     

Risk and management of upper gastrointestinal bleeding associated with prolonged dual-antiplatelet therapy after percutaneous coronary intervention

Prolonged dual-antiplatelet therapy with aspirin and clopidogrel is mandatory after drug-eluting stent implantation because of the potential increased risk of late stent thrombosis. The concern regarding prolonged antiplatelet therapy is the increased risk of bleeding. Gastrointestinal bleeding is the most common site of bleeding and presents a serious threat to patients due to the competing risks of gastrointestinal hemorrhage and stent thrombosis. Currently, there are no guidelines and little evidence on how best to manage these patients who are at high risk of morbidity and mortality from both the bleeding itself and the consequences of achieving optimum hemostasis by interruption of antiplatelet therapy. Managing gastrointestinal bleeding in a patient who has undergone recent percutaneous coronary intervention requires balancing the risk of stent thrombosis against further catastrophic bleeding. Close combined management between gastroenterologist and cardiologist is advocated to optimize patient outcomes.     

Proton pump inhibitors therapy vs H2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis

AIM: To compare the therapeutic effects of proton pump inhibitors vs H₂ receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and PubMed for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration’s tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios (OR) and mean difference with 95% confidence interval (CI). RevMan 5.3.3 software and Stata 12.0 software were used for data analyses.RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors (PPI) group and the remaining 605 subjects were in the H₂ receptor antagonists (H₂RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H₂RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate (OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate (OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality (OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference (WMD), -0.70 unit; 95%CI: -1.64 - 0.25] and the time that patients remained hospitalized [WMD, -0.77 d; 95%CI: -1.87 - 0.34]. The Begg’s test (P = 0.283) and Egger’s test (P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H₂RA, PPI may be a more effective therapy.     

Epidemiology of acute upper gastrointestinal bleeding

Acute upper gastrointestinal bleeding is an important emergency situation. Population-based epidemiology data are important to get insight in the actual healthcare problem. There are only few recent epidemiological surveys regarding acute upper gastrointestinal bleeding. Several surveys focusing on peptic ulcer disease showed a significant decrease in admission and mortality of peptic ulcer disease. Several more recent epidemiological surveys show a decrease in incidence of all cause upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding remained stable. Peptic ulcer bleeding is the most common cause of upper gastrointestinal bleeding, responsible for about 50% of all cases, followed by oesophagitis and erosive disease. Variceal bleeding is the cause of bleeding in cirrhotic patients in 50-60%. Rebleeding in upper gastrointestinal bleeding occurs in 7-16%, despite endoscopic therapy. Rebleeding is especially high in variceal bleeding and peptic ulcer bleeding. Mortality ranges between 3 and 14% and did not change in the past 10 years. Mortality is increasing with increasing age and is significantly higher in patients who are already admitted in hospital for co-morbidity. Risk factors for peptic ulcer bleeding are NSAIDs use and H. pylori infection. In patients at risk for gastrointestinal bleeding and using NSAIDs, a protective drug was only used in 10%. COX-2 selective inhibitors do cause less gastroduodenal ulcers compared to non-selective NSAIDs, however, more cardiovascular adverse events are reported. H. pylori infection is found in about 50% of peptic ulcer bleeding patients. H. pylori should be tested for in all ulcer patients and eradication should be given.