The clinical and economic burden of upper gastrointestinal (GI) bleeding is considerable, with the annual incidence ranging from 48 to 160 cases per 100,000 adults and mortality rates ranging from 10 to 14 percent. In response to new data that may lead to improved patient outcomes, the International Consensus Upper Gastrointestinal Bleeding Conference Group—a multidisciplinary group of 34 experts from 15 countries—developed international guidelines for managing nonvariceal upper GI bleeding. The guidelines include new recommendations, as well as updates to the 2002 guidelines from the British Society of Gastroenterology and the 2003 consensus guidelines from the Nonvariceal Upper GI Bleeding Consensus Conference Group.

The evidence rating system implemented is defined as follows: 1A = strong recommendation, high-quality evidence; 1B = strong recommendation, moderate-quality evidence; 1C = strong recommendation, low- or very low-quality evidence; 2A = weak recommendation, high-quality evidence; 2B = weak recommendation, moderate-quality evidence; 2C = weak recommendation, low- or very low-quality evidence. Grade 1 recommendations should be interpreted as “do it” or “do not do it”; grade 2 recommendations should be interpreted as “probably do it” or “probably do not do it.”

Resuscitation, Risk Assessment, and Pre-endoscopy Management

Revised recommendation: Prognostic scales are recommended for early stratification of patients into low- and high-risk categories for rebleeding and mortality. (Grade: 1C) Early identification of high-risk patients can facilitate appropriate intervention, which minimizes morbidity and mortality. Stratification should be based on clinical, laboratory, and endoscopic criteria. Predictors of increased risk of rebleeding include age older than 65 years; shock; poor overall health; comorbid illnesses; low initial hemoglobin (Hgb) levels; melena; transfusion requirement; fresh red blood on rectal examination, in the emesis, or in the nasogastric aspirate; sepsis; and elevated urea, creatinine, or serum transaminase levels.

New recommendation: Blood transfusions should be administered in patients with an Hgb level of 7 g per dL (70 g per L) or less. (Grade: 1C) Patients should be considered for transfusion based on their underlying condition, hemodynamic status, and markers of tissue hypoxia in acute situations. Red blood cell transfusion is rarely needed in patients with an Hgb level greater than 10 g per dL (100 g per L) and is usually needed when the Hgb level is less than 6 g per dL (60 g per L).

New recommendation: In patients receiving anticoagulants, correction of coagulopathy is recommended, but should not delay endoscopy. (Grade: 2C) Available data suggest that it may not be necessary to delay endoscopy in patients with mild to moderate coagulopathy. One study of patients undergoing endoscopy found no difference in rebleeding, surgery, mortality, or complication rates between patients receiving warfarin (Coumadin) and those not receiving anticoagulants.

New recommendation: Promotility agents should not be used routinely before endoscopy to increase the diagnostic yield. (Grade: 2B) Although promotility agents may be useful in selected patients with suspected blood in the stomach, they are not recommended for routine use in patients with upper GI bleeding.

Revised recommendation: Selected patients with acute ulcer bleeding who are at low risk of rebleeding on the basis of clinical and endoscopic criteria may be discharged promptly after endoscopy. (Grade: 1A) One randomized controlled trial (RCT) assessing the role of early discharge in low-risk patients found no difference in rates of recurrent bleeding. None of the patients who were discharged early experienced serious adverse events, underwent surgery, or died during the 30-day follow-up.

Revised recommendation: Pre-endoscopic proton pump inhibitor (PPI) therapy may be considered to downstage the endoscopic lesion and decrease the need for endoscopic intervention, but should not delay endoscopy. (Grade: 1B) PPI therapy may be useful, especially in patients suspected to have high-risk stigmata. However, it has not been shown to affect rebleeding, surgery, or mortality.

Endoscopic Management

Revised recommendation: Early endoscopy (within 24 hours of presentation) is recommended for most patients with acute upper GI bleeding. (Grade: 1B) Early endoscopy has been shown to be safe and effective in all risk groups, although it may need to be delayed or deferred in certain high-risk patients, such as those with active acute coronary syndrome or suspected perforation.

Revised recommendation: The finding of a clot in an ulcer bed warrants targeted irrigation to attempt dislodgement, with appropriate treatment of the underlying lesion. (Grade: 2B)

Revised recommendation: The role of endoscopic therapy for ulcers with adherent clots is controversial. Intensive PPI therapy alone may be sufficient. (Grade: 2B) Endoscopic therapy for adherent clots involves preinjecting with epinephrine before shaving, followed by applying combination treatment to the remaining stigmata of hemorrhage. A meta-analysis of five RCTs involving patients with adherent clots found no significant benefits for endoscopic therapy compared with no endoscopic therapy.

Revised recommendation: Epinephrine injection alone provides suboptimal effectiveness and should be used in combination with another method. (Grade: 1B)

Revised recommendation: Clips, thermocoagulation, or sclerosant injection should be used in patients with high-risk lesions, alone or in combination with epinephrine injection. (Grade: 1A) Meta-analyses showed that adding a second procedure (e.g., an injection of alcohol, thrombin, or fibrin glue; thermal contact; clips) to epinephrine injection is superior to epinephrine injection alone. Adding a second procedure for high-risk stigmata significantly reduced rebleeding, surgery, and mortality compared with epinephrine monotherapy.

Revised recommendation: Routine second-look endoscopy is not recommended. (Grade: 2B) The most recent data do not show a benefit with second-look endoscopy (i.e., a preplanned systematic endoscopy performed 16 to 24 hours after initial endoscopy). When available, high-dose intravenous PPI therapy is the current standard. Patients with high-risk presentations may benefit from second-look endoscopy, but more research is needed.

Pharmacologic Management

Revised recommendation: An intravenous bolus followed by continuous-infusion PPI therapy should be used to decrease rebleeding and mortality in patients with high-risk stigmata who have undergone successful endoscopic therapy. (Grade: 1A) Strong evidence supports the use of high-dose intravenous PPI therapy following successful endoscopy. No conclusions may be made at this time regarding low-dose intravenous PPI therapy or high-dose oral PPI therapy.

New recommendation: Patients should be discharged with a prescription for a single daily dose oral PPI; the duration should be dictated by the underlying etiology. (Grade: 1C) Once-daily PPI therapy has been shown to be effective in patients with peptic ulcer disease. However, some studies demonstrate relatively low healing rates for complicated or severe esophagitis, and twice-daily doses may be needed.

Nonendoscopic and Nonpharmacologic In-Hospital Management

New recommendation: Most patients who have undergone endoscopic hemostasis for high-risk stigmata should remain hospitalized for at least 72 hours. (Grade: 1C) Studies show that after endoscopic therapy, it takes 72 hours for most high-risk lesions to become low-risk lesions. More research is needed to determine whether selected high-risk patients may be treated in the outpatient setting.

New recommendation: Where available, percutaneous embolization can be considered as an alternative to surgery in patients for whom endoscopic therapy has been unsuccessful. (Grade: 2C) Percutaneous or transcatheter arterial embolization may be considered as an alternative to surgery, especially in patients who are high-risk candidates for surgery. Although uncommon, possible complications include bowel ischemia; secondary duodenal stenosis; and gastric, hepatic, and splenic infarction.

Revised recommendation: Patients with bleeding peptic ulcers should be tested for Helicobacter pylori and receive eradication therapy if it is present, with confirmation of eradication. (Grade: 1A)

New recommendation: Negative H. pylori diagnostic tests obtained in the acute setting should be repeated. (Grade: 1B) Diagnostic tests for H. pylori (e.g., serology, histology, urea breath test, rapid urease test, stool antigen, culture) may show increased false-negative rates in patients with acute bleeding; therefore, repeat testing after an initial negative result is needed.

Postdischarge, Aspirin, and NSAIDs

New recommendation: In patients with previous ulcer bleeding who require a nonsteroidal anti-inflammatory drug (NSAID), treatment with a traditional NSAID plus PPI or a cyclooxygenase-2 (COX-2) inhibitor alone is associated with a clinically important risk of recurrent bleeding. (Grade: 1B)

New recommendation: In patients with previous ulcer bleeding who require an NSAID, the combination of a PPI and a COX-2 inhibitor is recommended to reduce the risk of recurrent bleeding compared with COX-2 inhibitors alone. (Grade: 1B) Adding a PPI to traditional NSAID therapy is recommended to reduce the risk of upper GI complications, although the combination of a COX-2 inhibitor plus a PPI was associated with the greatest reduction in risk. Other studies found a decreased risk of endoscopic ulcers with a COX-2 inhibitor plus a PPI, compared with a COX-2 inhibitor alone.

New recommendation: In patients who take low-dose aspirin and develop acute ulcer bleeding, aspirin therapy should be restarted as soon as the risk of cardiovascular complication is thought to outweigh the risk of bleeding. (Grade: 1B) Discontinuing aspirin therapy for an extended period increases thrombotic risk in patients who require cardio-protective aspirin therapy. One meta-analysis showed that nonadherence or withdrawal of aspirin therapy is associated with a threefold risk of major adverse cardiac events. According to the American Heart Association, the decision to discontinue aspirin therapy in patients with acute ulcer bleeding should be made on an individual basis.

New recommendation: In patients with previous ulcer bleeding who require cardiovascular prophylaxis, clopi-dogrel (Plavix) alone has a higher risk of rebleeding than aspirin combined with a PPI. (Grade: 1B) Two RCTs showed a significant reduction in rebleeding in patients taking aspirin plus a PPI compared with those receiving clopidogrel alone, although there was no significant effect on mortality.