Upper Gastrointestinal Bleeding (UGIB)

Back

Practice Essentials

Acute gastrointestinal (GI) bleeding is a potentially life-threatening abdominal emergency that remains a common cause of hospitalization. Upper GI bleeding (UGIB) is defined as bleeding derived from a source proximal to the ligament of Treitz.

The image below depicts an ulcer with active bleeding.



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.

Signs and symptoms

Signs and symptoms of acute UGIB[1] include the following:

See Presentation for more detail.

Diagnosis

Workup may include the following:

Standard CT scanning and ultrasonography may be indicated for the evaluation of the following[2] :

See Workup for more detail.

Management

Treatment may include the following:

Indications for surgery in patients with bleeding peptic ulcers include the following:

See Treatment and Medication for more detail.

Background

Acute gastrointestinal (GI) bleeding is a potentially life-threatening abdominal emergency that remains a common cause of hospitalization.[3, 4]  Upper GI bleeding (UGIB) is defined as bleeding derived from a source proximal to the ligament of Treitz.[5]

The incidence of UGIB is approximately 100 cases per 100,000 population per year.[6] Bleeding from the upper GI tract is approximately 4 times more common than bleeding from the lower GI tract and is a major cause of morbidity and mortality. Mortality rates from UGIB are 6%-10% overall.[6] (See Epidemiology.)

The diagnosis of and therapy for nonvariceal UGIB has evolved since the late 20th century from passive diagnostic esophagogastroduodenoscopy with medical therapy until surgical intervention was needed to active intervention with endoscopic techniques followed by angiographic and surgical approaches if endoscopic therapy fails.[7] (See Workup and Treatment.)

Variceal hemorrhage is not discussed in this article because the underlying mechanisms of bleeding are different and require different therapies.

The underlying mechanisms of nonvariceal bleeding involve either arterial hemorrhage, such as in ulcer disease and mucosal deep tears, or low-pressure venous hemorrhage, as in telangiectasias and angioectasias. In variceal hemorrhage, the underlying pathophysiology is due to elevated portal pressure transmitted to esophageal and gastric varices and resulting in portal gastropathy. A bleeding ulcer is seen below. (See Etiology.)

See Pediatric Gastrointestinal Bleeding for more information on this topic.



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.

In patients with UGIB, comorbid illness, rather than actual bleeding, is the major cause of death. Comorbid illness has been noted in 50.9% of patients, with similar occurrences in males (48.7%) and females (55.4%).

One or more comorbid illnesses have been noted in 98.3% of mortalities in UGIB; in 72.3% of patients, comorbid illnesses have been noted as the primary cause of death.[8, 9] (See Epidemiology and Prognosis.)

Significant comorbidities have become more prevalent as the patient population with UGIB has become progressively older. In a retrospective chart review by Yavorski et al, 73.2% of deaths occurred in patients older than 60 years.[9] (See Epidemiology and Prognosis.)

Rebleeding or continued bleeding is associated with increased mortality; therefore, differentiating the patient with a low probability of rebleeding and little comorbidity from the patient at high risk for rebleeding with serious comorbidities is imperative. (See Presentation and Workup.)

Peptic ulcer disease and UGIB

Peptic ulcer disease (PUD) remains the most common cause of UGIB. In a literature review involving more than 10,000 patients with UGIB, PUD was responsible for 27%-40% of all bleeding episodes.[10] High-risk patient populations at risk for PUD include those with a history of alcohol abuse, chronic renal failure, and/or nonsteroidal anti-inflammatory drug (NSAID) use.[11]

Peptic ulcer disease is strongly associated with Helicobacter pylori infection. The organism causes disruption of the mucous barrier and has a direct inflammatory effect on the gastric and duodenal mucosa, reducing mucosal defenses and increasing the back diffusion of acid by loosening the tight cellular junctions. (Rates of H pylori infection are reportedly lower in patients with complicated ulcer disease than in patients with uncomplicated ulcers. Hosking et al reported a 71% incidence of H pylori infection in patients with bleeding duodenal ulcers; patients with nonbleeding ulcers had an incidence of 93%.) This discrepancy may be due to the decrease in sensitivity of biopsy in patients with ulcer bleeding.[12]

Eradication of H pylori been demonstrated to reduce the risk of recurrent ulcers and, thus, recurrent ulcer hemorrhage after the initial episode. In fact, the proportion of UGIB cases caused by peptic ulcer disease has declined,[13] a phenomenon that is believed to be due to the use of proton pump inhibitors (PPIs) and anti-H pylori therapy.

Duodenal ulcers are more common than gastric ulcers, but the incidence of bleeding is identical for both. In most cases, the bleeding is caused by the erosion of an artery at the base of the ulcer. In approximately 80% of patients, bleeding from a peptic ulcer stops spontaneously.[10]

Initial endoscopic attempts to maintain hemostasis have a high success rate. Bleeding vessels larger than 1.5 mm in diameter are associated with an increased mortality rate due to the difficulty in producing adequate hemostasis with thermal probes.

A minority of patients experience recurrent bleeding after endoscopic therapy, and these cases are usually associated with risk factors for rebleeding. These factors include age older than 60 years, the presence of shock upon admission, coagulopathy, active pulsatile bleeding, and the presence of cardiovascular disease. (The appearance of the ulcer at the time of endoscopy provides important information regarding the risk of rebleeding.) These circumstances are associated with a poorer prognosis and a higher mortality rate.[14]

Despite the dangers associated with a bleeding peptic ulcer, a study by Sung et al of 10,428 cases of such bleeding (in 9,375 patients) found that most deaths were not caused by it.[15] Of the 577 deaths that occurred in the cohort, almost 80% resulted from other causes, including multiorgan failure, pulmonary conditions, and terminal malignancy. The authors concluded that the management of patients with peptic ulcers should focus not only on hemostasis but also on lowering the risk of multiorgan failure and cardiopulmonary death.

Recurrent bleeding risk in peptic ulcers

Forrest et al were the first to classify the stigmata of hemorrhage from peptic ulcers. Based on these classifications, the risk of recurrent bleeding can be predicted. The ulcers at highest risk for rebleeding are those that involve active arterial bleeding or those with a visible, protuberant, nonbleeding vessel at the base of the ulcer. The study not only correlated the incidence of rebleeding with the stigmata of recent bleeding and the endoscopic appearance of an ulcer, but also determined prognostic information regarding the need for surgery. Mortality was also correlated with these factors.[16]

In patients with H pylori infection, the rate of recurrent bleeding is increased. This is why documenting the presence of H pylori and aggressively treating the infection are important.

Patients who are not infected with H pylori may require a subsequent acid-lowering surgical procedure or long-term medical therapy for recurrent ulcer disease and bleeding.

Other causes of UGIB

Other major causes of UGIB are mucosal tears of the esophagus or fundus (Mallory-Weiss tear), erosive gastritis, erosive esophagitis, Dieulafoy lesion, gastric cancer, and ulcerated gastric leiomyoma.

Patients with chronic liver disease and portal hypertension are at an increased risk for variceal hemorrhage and portal gastropathy in addition to ulcer hemorrhage.

Rare causes of UGIB include aortoenteric fistula, gastric antral vascular ectasia, angiectasias, and Osler-Weber-Rendu syndrome.

An aortoenteric fistula results from the erosion of the aortic graft into the bowel lumen, usually at the third or fourth portion of the duodenum. The result is a direct communication between the aortic graft lumen and the bowel lumen. Most aortoenteric fistulas involve the proximal aortic anastomotic suture line.

 Acute stress-related mucosal disease (also known as stress ulcers), a disease process characterized by diffuse superficial mucosal erosions that appear as discrete areas of erythema, can also cause UGIB.[16] The bleeding is usually mild and self-limiting and rarely progresses to life-threatening hemorrhage. Stress ulcers can be detected endoscopically in as many as 75%-100% of critically ill patients, within 24 hours of admission to an intensive care unit (ICU).

In ICU patients, the incidence of clinically significant GI bleeding (eg, hypotension, transfusion) from acute stress ulcer was found to be 1.5%.[17]  Although its incidence has fallen significantly over recent decades, likely due to better overall ICU care, mortality remains high in those with clinically important bleeding.[92] Stress ulcers are historically associated with (1) head injuries, with related elevations in intracranial pressure (Cushing ulcers) and (2) burn injuries (Curling ulcers).

Critically ill patients are at an increased risk of developing stress-related mucosal disease and subsequent stress-ulcer bleeding, most commonly with risk factors of respiratory failure and coagulopathy.[93] Other important factors include acute renal or hepatic failure, sepsis, hypotension, severe head or spinal cord injury, severe burns, acute lung injury, major or prolonged surgery, and a history of GI bleeding.[94]

Angiodysplasia of the upper GI tract accounts for 2%-4% of bleeding lesions.[10] The condition is also a cause of lower GI bleeding in 6% of cases.[16] The lesion is a vascular malformation that represents an abnormal dilation of mucosal and submucosal vessels.

Histologically, angiodysplasias are dilated, thin-walled vascular channels that appear macroscopically as a cluster of cherry spots. When located in the upper GI tract, they most commonly involve the stomach and duodenum. The lesions can be acquired or congenital, as in hereditary hemorrhagic telangiectasia and Osler-Weber-Rendu syndrome.

The acquired angiodysplasias are commonly found in patients with chronic renal failure requiring hemodialysis and with aortic valvular disease (especially aortic stenosis due to Heyde syndrome). Other diseases, such as cirrhosis and von Willebrand disease, are associated with a higher frequency of angiodysplasias. Most lesions are smaller than 1 cm in diameter and can be multiple in 66% of patients.[10]

For patient education information, see the Digestive Disorders Center and the Heartburn and GERD Center, as well as the patient education article Gastrointestinal Bleeding (GI Bleeding).

Etiology

Ulcer-related UGIB

Bleeding peptic ulcers account for the majority of patients presenting with acute upper gastrointestinal (GI) bleeding (UGIB).[3] As previously mentioned, peptic ulcer disease is strongly associated with H pylori infection. The organism causes disruption of the mucous barrier and has a direct inflammatory effect on the gastric and duodenal mucosa.

In cases of ulcer-associated UGIB, as the ulcer burrows deeper into the gastroduodenal mucosa, the process causes weakening and necrosis of the arterial wall, leading to the development of a pseudoaneurysm. The weakened wall ruptures, producing hemorrhage.

The flow through a vessel varies with the fourth power of the radius; thus, small increases in vessel size can mean much larger amounts of blood flow and bleeding, with more severe hypotension and more complications, especially in older patients.

Visible vessels usually range from 0.3-1.8 mm.

Exsanguinating hemorrhage has been reported from larger vessels. The larger vessels are located deeper in the gastric and duodenal submucosa and serosa. Larger branches of the left gastric artery are found high on the lesser curvature, while the pancreatoduodenal artery and its major branches are located posteroinferiorly in the duodenal bulb.

Vomiting-related UGIB

During vomiting, the lower esophagus and upper stomach are forcibly inverted. Vomiting attributable to any cause can lead to a mucosal tear of the lower esophagus or upper stomach. The depth of the tear determines the severity of the bleeding. Rarely, vomiting can result in esophageal rupture (Boerhaave syndrome), leading to bleeding, mediastinal air entry, left pleural effusion (salivary amylase can be present) or left pulmonary infiltrate, and subcutaneous emphysema.

Mallory-Weiss tears in UGIB

Mallory-Weiss tears account for 8%-15% of acute upper GI hemorrhage.[10, 95] Kenneth Mallory and Soma Weiss first described the syndrome in 1929.[18] The occasionally massive UGIB results from a tear in the mucosa of the gastric cardia. Like many upper GI tract lesions, the Mallory-Weiss tear may stop bleeding spontaneously 85%-90% of the time.

This linear mucosal laceration is the result of forceful vomiting, retching, coughing, or straining. These actions create a rapid increase in the gradient between intragastric and intrathoracic pressures, leading to a gastric mucosal tear from the forceful distention of the gastroesophageal junction.[19] In 80%-90% of cases, this is a single, 1.75- to 2.5-cm mucosal tear along the lesser curve of the stomach just distal to the gastroesophageal junction.[18]

See Mallory-Weiss Tear for more information on this topic.

Acute stress-related mucosal disease in UGIB

Acute stress-related mucosal disease (or stress ulcer) results from predisposing clinical conditions that have the potential to alter the local mucosal protective barriers, such as mucus, bicarbonate, blood flow, and prostaglandin synthesis. Any disease process that disrupts the balance of these factors results in diffuse gastric mucosal erosions.

This is most commonly observed in patients who have undergone episodes of shock, multiple trauma, acute respiratory distress syndrome, systemic respiratory distress syndrome, acute renal failure, and sepsis.

The principal mechanisms involved are decreased splanchnic mucosal blood flow and altered gastric luminal acidity.

Dieulafoy lesions in UGIB

The Dieulafoy lesion, first described in 1896, is a vascular malformation of the proximal stomach, usually within 6 cm of the gastroesophageal junction along the lesser curvature of the stomach. However, it can occur anywhere along the GI tract. This lesion accounts for 2%-5% of acute UGIB episodes.[20]

Endoscopically, the lesion appears as a large submucosal vessel that has become ulcerated. Because of the large size of the vessel, bleeding can be massive and brisk. The vessel rupture usually occurs in the setting of chronic gastritis, which may induce necrosis of the vessel wall. Alcohol consumption is reportedly associated with the Dieulafoy lesion.

In a review of 149 cases, the Dieulafoy lesion mostly occurred in men and mostly in those in their third to tenth decade.[21]

NSAIDs in UGIB

NSAIDs cause gastric and duodenal ulcers by inhibiting cyclooxygenase, which causes decreased mucosal prostaglandin synthesis and results in impaired mucosal defenses. Daily NSAID use causes an estimated 40-fold increase in gastric ulcer creation and an 8-fold increase in duodenal ulcer creation.[16]

Long-term NSAID use is associated with a 20% incidence in the development of mucosal ulceration.[22] Medical therapy includes avoiding the ulcerogenic drug and beginning a histamine-2 (H2)–receptor antagonist or a proton pump inhibitor that provides mucosal protection.

Epidemiology

US and international data

The incidence of acute upper gastrointestinal (GI) bleeding (UGIB) is about 100 per 100,000 adults per year. An estimated 15% of patients with UGIB present with hematochezia. In the United Kingdom, UGIB accounts for 70,000 hospital admissions each year, with the majority of cases nonvariceal in origin.[23]  In a nationwide study from Spain, UGIB was six times more common than lower GI bleeding.[24]

UGIB is twice as common in men as in women and increases in prevalence with age (>60 y). However, the death rate is similar in both sexes.[9, 22]

 Despite advances in therapy, in-hospital mortality remains high (13%), and rebleeding is common (15%).[90]

Prognosis

Recurrence of upper gastrointestinal (GI) bleeding (UGIB) is common. In a study to evaluate national 30-day readmissions after upper and lower gastrointestinal (GI) bleeding in US patients, of 82,290 patients admitted for UGIB, the all-cause 30-day readmission rate was 14.6% (vs 14.4% for LGIB).[100] The most common causes of UGIB were GI (33.9%), cardiac (13.3%), infectious (10.4%), and respiratory (7.8%). Significant predictors of 30-day readmission were metastatic disease, discharge against medical advice, and hospital stay for longer than 3 days.[100]

As previously mentioned, age older than 60 years is an independent marker for a poor outcome in UGIB,[25] with the mortality rate ranging from 12% to 25% in this group of patients.

The American Society for Gastrointestinal Endoscopy (ASGE) grouped patients with UGIB according to age and correlated age category to the risk of mortality. The ASGE found a mortality of 3.3% for patients aged 21-31 years, 10.1% for those aged 41-50 years, and 14.4% for those aged 71-80 years.[25]

The following risk factors are associated with an increased mortality, recurrent bleeding, the need for endoscopic hemostasis, or surgery[14, 26] :

Patients who present in hemorrhagic shock have a mortality rate of up to 30%.

History

The history and physical examination of the patient provide crucial information for the initial evaluation of persons presenting with a gastrointestinal (GI) tract hemorrhage.[5, 10] Important information to obtain includes potential comorbid conditions, medication history, and any prior history of GI bleeding, as well as the severity, timing, duration, and volume of the bleeding.[5]

History findings include weakness, dizziness, syncope associated with hematemesis (coffee ground vomitus), and melena (black stools with a rotten odor).

Occasionally, a brisk upper GI bleeding (UGIB) manifests as hematochezia (red or maroon stools); the redder the stool, the more rapid the transit, which suggests a large upper tract hemorrhage. Laine and Shah found that 15% of patients presenting with hematochezia had an upper GI source of bleeding identified at urgent esophagogastroduodenoscopy.[27]

Patients may have a history of dyspepsia (especially nocturnal symptoms), ulcer disease, early satiety, and nonsteroidal anti-inflammatory drug (NSAID), antiplatelet therapy, or aspirin use. A history of recent aspirin ingestion suggests that the patient may have NSAID gastropathy with an enhanced bleeding diathesis from poor platelet adhesiveness.[10]

Many patients with UGIB who are taking NSAIDs present without dyspepsia but with hematemesis or melena as their first symptom, owing to the analgesic effect of the NSAID. Low-dose aspirin (81 mg) has also been associated with UGIB, with or without the addition of NSAID therapy. Using the lowest effective dose for both short-term and long-term users is recommended.[28]

Patients with a history of ulcers are at an especially increased risk for UGIB when taking steroids, aspirin, dual antiplatelet therapy (DAPT) (eg, addition of clopidogrel to aspirin), or NSAID therapy. These high-risk individuals should receive continuous acid suppression with a proton pump inhibitor (PPI). The patient’s ulcer history is also important because recurrence of ulcer disease is common, especially there has not been successful eradication of an H pylori infection.

Patients may present asymptomatically or in a more subacute phase, with a history of dyspepsia and occult intestinal bleeding manifesting as a positive fecal occult blood test result or as iron deficiency anemia.

A history of chronic alcohol use of more than 50 g/d or chronic viral hepatitis (B or C) increases the risk of variceal hemorrhage, gastric antral vascular ectasia (GAVE), or portal gastropathy. Alcohol also interferes with cyclooxygenase (COX)-1 receptor enzymes which reduce the production of cytoprotective prostaglandin and alters gastric mucosal protection.

The finding of subcutaneous emphysema with a history of vomiting is suggestive of Boerhaave syndrome (esophageal perforation) and requires prompt consideration of surgical therapy.

The presence of postural hypotension indicates more rapid and severe blood loss.

A meta-analysis documented the incidence of acute UGIB symptoms as follows (see Physical Examination)[1] :

The importance of the above clinical signs/symptoms in determining the source of GI bleeding is demonstrated in the table below.[1]

Table 1. Probable Source of GI Bleeding Within the Gut



View Table

See Table

Physical Examination

The goal of the patient's physical examination is to evaluate for shock and blood loss.

Patients present with an ulcer that has bled or is actively bleeding (although approximately 80% of ulcers stop bleeding).

Hematemesis and melena are the most common presentations of acute UGIB, and patients may present with both symptoms.

Assessing the patient for hemodynamic instability and clinical signs of poor perfusion is important early in the initial evaluation to properly triage patients with massive hemorrhage to ICU settings.

Worrisome clinical signs and symptoms of hemodynamic compromise include tachycardia of more than 100 beats per minute (bpm), systolic blood pressure of less than 90 mm Hg, cool extremities, syncope, and other obvious signs of shock, ongoing brisk hematemesis, or the occurrence of maroon or bright-red stools, which requires rapid blood transfusion.[29]

Pulse and blood pressure should be checked with the patient in supine and upright positions to note the effect of blood loss. Significant changes in vital signs with postural changes indicate an acute blood loss of approximately 20% or more of the blood volume.

Formal risk scoring systems have been validated and are becoming more widely utilized.

Signs of chronic liver disease should be noted, including spider angiomata, gynecomastia, increased luneals, splenomegaly, ascites, pedal edema, and asterixis.

Signs of tumor are uncommon but portend a poor prognosis. Signs include a nodular liver, an abdominal mass, and enlarged and firm lymph nodes. The finding of telangiectasias may indicate the rare case of Osler-Weber-Rendu syndrome.

Approach Considerations

A complete blood cell (CBC) count with platelet count and differential is necessary to assess the level of blood loss in a patient with upper gastrointestinal (GI) bleeding (UGIB). Where possible, having the patient's previous results as a baseline is useful to gauge this loss. The CBC count should be checked frequently (every 4-6 h initially), depending on the severity of the bleeding, human genetic stability, and apparent rate of blood loss.

Assessing patients' calcium levels is useful in identifying individuals with hyperparathyroidism, but it is especially helpful in monitoring calcium in patients receiving multiple transfusions of citrated blood. Hypercalcemia increases acid secretion.

A gastrin level may identify the rare patient with gastrinoma as the cause of UGIB and multiple ulcers. It is important to recognize that moderately high elevations of gastrin are seen in patients taking proton pump inhibitors (PPIs).

Electrocardiography (ECG) should be considered, especially in those with underlying cardiac disease or risk factors. Close measurement of vital signs, including continuous pulse and blood pressure monitoring, is important and may alert clinicians to important changes in the patient's clinical stability. Careful and ongoing monitoring of volume resuscitation is essential to avoiding end-organ injury, especially acute myocardial infarction due to hypotension.

It is critical to use a multidisciplinary approach in patients with severe UGIB. Intensivists, primary care providers, surgeons, interventional radiologists, and cardiologists may all play an essential role, depending on the presence of patients' comorbidities and their clinical course.

See Upper Gastrointestinal Bleeding Imaging and Esophageal Varices Imaging for more information.

Assessment of hemorrhagic shock

As previously mentioned, patients who present in hemorrhagic shock have a mortality rate of up to 30%. Hemorrhage may be classified based on the amount of blood loss, as noted in the following table.[30]

Table 2. Estimated Fluid and Blood Losses in Shock



View Table

See Table

This classification scheme aids in understanding the clinical manifestations of hemorrhagic shock. In early class 1 shock, the patient may have normal vital signs, even with a 15% loss of total blood volume. As the percentage of blood volume loss increases, pertinent clinical signs, symptoms, and findings become more apparent.

Although early cardiovascular changes occur as blood loss continues, urine output, as a sign of end organ renal perfusion, is only mildly affected until class 3 hemorrhage has occurred.

Bornman et al correlated the presence of shock (defined as a pulse rate >100 bpm or systolic blood pressure [SBP] < 100 mm Hg) with the incidence of rebleeding rates after initial nonsurgical intervention.[30] They found that rebleeding (a marker for increased mortality and need for surgery) occurred in 2% of patients without shock, in 18% with isolated tachycardia, and in 48% with shock.

Schiller et al determined that SBP is a sensitive clinical marker for helping to predict mortality. They correlated mortality rates based on the patient's SBP at the time of bleeding and found mortality rates of 8% for patients with SBP more than 100 mm Hg, rates of 17% for SBP of 80-90 mm Hg, and rates of more than 30% for SBP less than 80 mm Hg.

Unless the patient has evidence of shock, orthostatic testing should be performed to assess and document a hypovolemic state. A positive tilt test finding is defined as an SBP decrease of 10 mm Hg and a pulse rate increase of 20 bpm with standing compared to the supine position. The American Society for Gastrointestinal Endoscopy (ASGE) survey was able to correlate orthostatic changes with the incidence of mortality.[31] The mortality rate when orthostatic changes are present is 13.6%, compared to 8.7% when they are absent.

Knopp et al studied the use of the tilt test in phlebotomized healthy volunteers and found that a positive tilt test result consistently correlated with a blood loss of 1000 mL. This becomes extremely useful when evaluating patients with class 1 hemorrhagic shock.

Hemoglobin Value and Type and Crossmatch Blood

Based on the patient's initial hemoglobin level and clinical assessment of shock, a type and screen or type and crossmatch should be ordered in patients with suspected upper gastrointestinal (GI) bleeding (UGIB). The patient should be crossmatched for 2-6 units, based on the rate of active bleeding. The hemoglobin level should be monitored serially in order to follow the trend. An unstable hemoglobin level may signify ongoing hemorrhage requiring further intervention.

Patients generally require blood transfusions because of hypoperfusion and hypovolemia. Patients with significant comorbid conditions (eg, advanced cardiovascular disease) should receive blood transfusions to maintain myocardial oxygen delivery to avoid myocardial ischemia.[32, 33]

According to the 2008 Scottish Intercollegiate Guidelines Network (SIGN) guideline, patients in shock should receive prompt volume replacement.[35]

However, once the patient has been stabilized, controversy exists regarding strategies for transfusion of red blood cells in GI bleeding, with some studies suggesting improved outcomes with a more judicious use of blood transfusions. In a study that compared the efficacy and safety of a restricted transfusion strategy with those of a liberal transfusion strategy in 921 patients with severe acute UGIB, Villanueva et al concluded that a restrictive strategy (n = 461) significantly improved outcomes in patients with acute UGIB compared with that of a liberal transfusion strategy (n = 460).[32]  In the restrictive strategy, patients were transfused when their hemoglobin level fell below 7 g/dL; in the liberal strategy, patients were transfused when their hemoglobin level fell below 9 g/dL.

One of the criteria used to determine the need for surgical intervention is the number of units of transfused blood required to resuscitate the patient. The more units required, the higher the mortality.[20] Operative intervention may be indicated once the blood transfusion number reaches more than 5 units, as noted in the following table.[20]

Table 3. Effect of Number of Packed Erythrocyte Transfusions on Need for Surgery and Mortality from UGIB



View Table

See Table

BMP, BUN, and Coagulation

The basic metabolic profile (BMP) is useful in evaluating for renal comorbidity in cases of suspected upper gastrointestinal (GI) bleeding (UGIB); however, blood in the upper intestine can elevate the BUN (blood urea nitrogen) level as well. Measurement of coagulation parameters is necessary to assess for continued bleeding. Abnormalities should be corrected rapidly.

The BUN-to-creatinine ratio increases with UGIB. A ratio of greater than 36 in a patient without renal insufficiency is suggestive of UGIB.

Coagulation profile

The patient's prothrombin time (PT), activated partial thromboplastin time (PTT), and international normalized ratio (INR) should be checked to document the presence of coagulopathy. The coagulopathy may be consumptive and associated with a thrombocytopenia.

In a retrospective institutional study, multivariate logistic regression revealed that concomitant antiplatelet therapy, timing of esophagogastroduodenoscopy (EGD) within 12 hours of presentation, and INR level were independent predictors of identification of a source of bleeding.[36] At a threshold of INR 7.5 at presentation, the likelihood of finding an endoscopically significant lesion was less than 20%. The investigators indicated that the relationship between INR elevation and identification of a bleeding source or endoscopic intervention at EGD were antiparallel, but regardless of source identification or endoscopic intervention, important clinical outcomes were unchanged.[36]

A platelet count below 50 × 109 cells/L with active acute hemorrhage may warrant a platelet transfusion and fresh frozen plasma in an attempt to replace lost clotting factors.

The coagulopathy could be a marker of advanced liver disease.

Prolongation of the PT based on an INR of more than 1.5 may indicate moderate liver impairment.

A fibrinogen level of less than 100 mg/dL also indicates advanced liver disease with extremely poor synthetic function.

Risk Scoring

Many tools are used to stratify the severity of bleeding in patients presenting with an acute upper gastrointestinal (GI) bleed (UGIB). Several use the blood urea nitrogen (BUN) or the BUN-to-creatinine ratio as part of the formula when calculating the bleeding risk. The primary goals are to identify those who are at high risk for severe bleeding that requires hospital admission, the necessity of endoscopic intervention, the need for triage to intensive care unit (ICU) admission, the risk for rebleeding, and mortality.[101, 102]

The modified Glasgow-Blatchford bleeding score (GBS) and the Rockall bleeding score are the two systems most commonly used for estimating in-hospital mortality in UGIB. These tools utilize both pre- and post-endoscopy components for scoring. The GBS score helps to identify patients at lower risk for severe bleeding and who might be managed as an outpatient. The Rockall score and the more recent AIMS65 score (Albumin < 3.0 g/dL, International normalized ratio [INR] >1.5, altered Mental status, Systolic blood pressure ≤90 mm Hg, and age >65 y),[189, 187, 188]  reliably predict mortality.[103]

The Progetto Nazionale Emorragia Digestiva (PNED) system, a very complex and relatively new tool, is thought to not only be more selective for classifying a case as severe but also to have a greater predictive capacity for mortality compared with the Rockall score.[104]

Each of these tools is becoming a common component in the risk-stratifying process in current practice for assessing the severity of GI bleeding, triage, and role for endoscopic intervention.[187, 188, 105]

Endoscopy

The development of endoscopy has provided clinicians with the ability for diagnostic and therapeutic approaches to bleeding from the gastrointestinal (GI) tract. Endoscopic examination of the upper GI tract provides useful information regarding the source and site of bleeding.[31, 88, 89]

Endoscopic findings and their incidence rate in patients with upper GI bleeding (UGIB) include the following:

Endoscopy should be performed immediately after endotracheal intubation (if indicated), hemodynamic stabilization, and adequate monitoring in an intensive care unit (ICU) setting have been achieved. Optimize conditions for performing endoscopy, including involvement of multidisciplinary support, obtaining appropriate informed consent, and ensuring the availability of appropriate equipment and personnel. Endoscopy typically takes place within 24 hours. Early studies have shown that emergent endoscopy, within 12 hours or less from presentation, may reveal a higher-risk stigmata of bleeding on endoscopy and require therapeutic intervention, but other clinical endpoints such as the need for surgical intervention, length of stay, and mortality are not significantly impacted.[106, 107, 108]

Although not a widely available or commonly employed modality in the setting of acute UGIB, capsule endoscopy (CE) may identify low-risk lesions in UGIB, potentially allowing a subset of patients to be safely treated as outpatients. In a study of CE in patients with UGIB, of those with duodenal visualization on CE, 23 of 25 (92%) CE findings were concordant with esophagogastroduodenoscopy (EGD) for low-risk lesions that would have been candidates for outpatient management.[38] A cause for bleeding was identified in 62 (75%) patients. CE and EGD findings were concordant in 34 (55%) patients. Among the patients with positive EGD findings, 21 (38%) had negative CE results. Of these, 7 were a result of a lack of duodenal visualization. Of 28 patients with normal EGD results, 7 (25%) had positive CE results.[38]

Chest Radiography

If clinical suspicion is high for aspiration pneumonia, effusion, or esophageal perforation, order chest radiographs to rule our these conditions. Obtain abdominal scout and upright films to exclude a perforated viscus and ileus.

Barium contrast studies are not usually helpful in cases of suspected upper gastrointestinal bleeding and can make endoscopic procedures more difficult (ie, white barium obscuring the view) and dangerous (ie, risk of aspiration).

See Upper Gastrointestinal Bleeding Imaging and Esophageal Varices Imaging for more information on these topics.

Computed Tomography Scanning

Computed tomography (CT) scanning and ultrasonography may be indicated for the evaluation of liver disease for cirrhosis, cholecystitis with hemorrhage, pancreatitis with pseudocyst and hemorrhage, aortoenteric fistula, and other unusual causes of upper gastrointestinal (GI) hemorrhage (UGIB).[2] The 2010 American College of Radiology (ACR) criteria state that CT scanning is particularly useful for localizing obscure UGIB and for evaluating a patient with UGIB and a history of aortic reconstruction or pancreaticobiliary procedure.[37]

CT scanning is useful in the diagnosis of aortoenteric fistula because images may reveal thickened bowel, perigraft fluid collection, extraluminal gas, or inflammatory changes in the area of the duodenum and the aortic graft.

CT angiography (CTA) holds promise as an initial test for acute GI bleeding because of its ubiquity, rapidly performance, and potential to offer diagnostic information for management guidance.[109] CTA has the potential advantage of precisely localizing the source of GI bleeding, and to diagnose underlying pathology that may be the cause of bleeding to direct future management. Moreover, CTA can often identify causes of GI bleeding outside the GI tract (eg, hemobilia). In addition, CTA can not only define the underlying vascular anatomy before patients undergo transcatheter angiography embolization but also identify any anatomic variants that may affect management.[109]

See Upper Gastrointestinal Bleeding Imaging and Esophageal Varices Imaging for complete information on these topics.

Nuclear Medicine Scanning

Nuclear medicine scans may be useful in determining the area of active hemorrhage. Radionuclide imaging for gastrointestinal (GI) bleeding is generally performed with technetium-99m (99mTc)-tagged red blood cells, with an initial injection of radiotracer and subsequent gamma camera imaging. GI bleeding can be identified with visualization of radiotracer activity outside of normal areas of blood pool, which either focally intensifies or moves over time in an antegrade or retrograde manner. In addition, radionuclide studies are highly sensitive: They can detect rates of bleeding as low as 0.05–0.1 mL/minute as well as detect arterial and venous hemorrhages.[109]

However, this imaging modality has a prolonged imaging time and is thereforenot ideal for clinically unstable patients. Radionuclide scans also frequently fail to precisely anatomically localize the site of active bleeding.[109] Nonetheless, radionuclide scanning maintains some appeal as a very noninvasive strategy in evaluating GI bleeding. However, the 2010 American College of Radiology (ACR) criteria state that 99mTc-labeled erythrocyte scans are of limited value in diagnosing upper GI bleeding (UGIB), but continue to be useful in certain cases of obscure UGIB.[37]

Angiography

Angiography may be useful if bleeding persists and endoscopy fails to identify a bleeding site. According to the 2010 American College of Radiology (ACR) guidelines, angiography along with transcatheter arterial embolization (TAE) should be considered for all patients with a known source of arterial upper gastrointestinal (GI) bleeding (UGIB) that does not respond to endoscopic management, or in patients with active bleeding and a negative endoscopy.[37]

In clinically unstable patients, angiography should be considered the preferred diagnostic and therapeutic strategy after failed endoscopy, as it has favorable clinical outcomes compared with emergent surgery for UGIB.[110, 111]

There are highly variable sensitivity and specificity for catheter angiography in the literature, with sensitivity averaging 60%,[110] as well as a 60%-100% technical success rate for UGIB (73%-100% for lower GI bleeding).[98] Angiography not only has a high spatial resolution and can detect rates of bleeding as low as 0.5 mL/min,[115]  but it also has the added major advantage of allowing for treatment of GI bleeding with embolization therapy. However, its primary disadvantage is that it is an invasive and time-consuming procedure with a potentially high radiation dose. In addition, patients may have falsely negative findings in the presence of intermittent GI bleeding and if there is no active bleeding during the angiogram.[109]

In cases of aortoenteric fistula, angiography requires active bleeding (1 mL/min) to be diagnostic.

Multidetector CTA

Multidetector CT angiography (MDCTA) has increasingly been adopted for the diagnosis of acute GI bleeding.[112] Because CT scanning can be acquired rapidly and is nearly universally available in the acute setting, it may be an ideal initial diagnostic test for patients who are unstable with UGIB or lower GI bleeding with failed endoscopy or have a source of bleeding seen on an additional imaging modality.[113]

CTA appears to have a high negative predictive value (NPV) for the identification of obscure GI bleeding that may be useful for excluding patients who are unlikely to benefit from transcatheter mesenteric angiography.[114] In a retrospective study of 20 patients who underwent 20 negative CTA evaluations to assess and treat GI bleeding followed by mesenteric angiography, 18 of the 20 patients also had negative subsequent MA (NPV = 90%).[114] The remaining two cases were false negatives, with UGIB (P < 0.05). The authors concluded CTA may be considered as a first-line diagnostic study for evaluating obscure GI bleeding, and this diagnostic modality could avoid the associated costs, risks, and challenges associated with transcatheter mesenteric angiography.[114]

Nasogastric Lavage

Nasogastric lavage may confirm recent upper gastrointestinal (GI) bleeding (UGIB) (coffee ground appearance), possible active bleeding (red blood in the aspirate that does not clear), or a lack of blood in the stomach (active bleeding less likely but does not exclude an upper GI lesion).

A nasogastric tube is an important diagnostic tool, and tube placement can reduce the patient's need to vomit. Placement for diagnostic purposes is not contraindicated in patients with possible esophageal varices.[39]

The characteristics of the nasogastric lavage fluid (eg, red, coffee grounds, clear) and the stool (eg, red, black, brown) can indicate the severity of the hemorrhage. Red blood with red stool is associated with an increased mortality rate from more active bleeding compared with negative aspirate findings with brown stool.

More recent evidence-based guidelines suggest nasogastric or orogastric lavage is not required in patients with UGIB, but either can be used for diagnosis, prognosis, visualization, or therapeutic effect.[115]

Documentation of an upper GI source

Nasogastric aspirates with blood or coffee-ground material are clear indications of UGIB, and a bloody nasogastric aspirate raises the likelihood of the presence of active bleeding or a nonbleeding visible vessel, as compared to coffee-grounds or a clear nasogastric aspirate. However, a clear or bile-stained nasogastric aspirate may be seen in up to 15%-18% of patients with an upper GI source.[116]  In addition, testing nasogastric aspirates for occult blood has not been proven to be useful.

Prognostic value

Intuitively, a persistently bloody nasogastric aspirate would seem likely to indicate a more severe UGIB episode. A report indicates that a nasogastric aspirate with red blood is associated with more severe bleeding (proportion requiring >5 units of blood and surgery) and raises the likelihood of identifying high-risk stigmata at endoscopy.[116]

Improvement of visualization

The standard small 16-18 gauge nasogastric tube typically used for aspiration is not likely to effectively clear clots from the stomach, despite vigorous lavage. A large-bore orogastric tube is more likely to be successful in clearing the stomach, but the use of a large-bore orogastric tube is difficult and uncomfortable for patients and cannot be recommended routinely.

With regard to therapeutic effect, older surgical literature reported that nasogastric lavage could stop bleeding in a majority of cases and also recommended the use of iced saline. However, UGIB stops spontaneously in most patients without specific therapy, and canine studies with experimentally induced ulcers have indicated that results with lavage are no better, and may even be worse, at temperatures of 0°-4°C (32°-39.2°F)[115] as a result of disruption of the clotting cascade. Patients are invariably uncomfortable with nasogastric tubes in general and often are uncomfortably chilled with cold lavage attempts.

Histologic Findings

In patients with gastric ulcers, the bleeding vessel lies in the deepest layer of the ulcer. Fibrinoid necrosis is observed at the site of perforation of the vessel. Pseudoaneurysmal dilatation of the vessel may be present at the site of perforation. Biopsy samples should be taken from the edge of a gastric ulcer to rule out carcinoma.

The characteristic lesion of H pylori is chronic active gastritis with the organisms observed after routine staining. The lesion of gastric antral vascular ectasia is capillary dilation with fibrin clots and fibromuscular hyperplasia.

However, histologic findings may not offer clinically relevant information in the initial management of upper gastrointestinal (GI) bleeding (UGIB), in part due to the delay in processing of pathologic specimens from the time of the initial esophagogastroduodenoscopy (EGD) and endoscopic biopsies.

Previous reports have noted a decreased sensitivity of biopsies for H pylori during acute GI bleeding, presumed to be due to the buffering effects of blood.[117, 118]  This was primarily for the rapid urease testing. However, histology is not affected by the presence of blood at endoscopy in the diagnosis of H pylori.[119]

Approach Considerations

The goal of medical therapy in upper gastrointestinal (GI) bleeding (UGIB) is to correct shock and coagulation abnormalities and to stabilize the patient so that further evaluation and treatment can proceed. In addition to intravenous (IV) fluids, patients may need transfusion of packed red blood cells. High doses of proton pump inhibitors (PPIs) may reduce the need for endoscopic therapy (see Treatment with proton pump inhibitors).

Various methodologies have been proposed to quantitate rebleeding risk (eg, Rockall score, Baylor score), with several instruments gaining more widespread acceptance.[40] The Blatchford score (range 0-23) in particular can reliably triage patients with presumed UGIB, to hospital discharge for outpatient management with a score of 0, representing a less than 1% chance of requiring intervention,[105] rather than inpatient admission and performance of endoscopy.

The 2008 Scottish Intercollegiate Guidelines Network (SIGN) guideline on the management of acute upper and lower GI bleeding recommends that an initial (pre-endoscopic) Rockall score be calculated for all patients presenting with an acute UGIB. In patients with an initial Rockall score >0, endoscopy is recommended for a full assessment of bleeding risk.[35]

Resuscitation of a hemodynamically unstable patient begins with assessing and addressing the "ABCs" (ie, airway, breathing, circulation) of initial management. (Baradarian et al demonstrated that early, aggressive resuscitation can reduce mortality in acute UGIB.[41] )

Patients presenting with severe blood loss and hemorrhagic shock present with mental status changes and confusion. In such circumstances, patients cannot protect their airway, especially when hematemesis is present. In these cases, patients are at an increased risk for aspiration, which is a potentially avoidable complication that can significantly affect morbidity and mortality. This situation must be recognized early, and patients should be electively intubated in a controlled setting. A multidisciplinary approach, with pulmonologists or intensivists in an intensive care unit (ICU) setting is desirable. Some centers have a dedicated GI bleeding team that utilizes treatment protocols beginning from the emergency department, progressing to the acute-care bed, assuring a controlled setting for endoscopy and delivering optimized in-hospital and postdischarge care.

Intravenous access must be obtained. Bilateral, 16-gauge (minimum), upper extremity, peripheral intravenous lines are adequate for volume resuscitative efforts. Poiseuille’s law states that the rate of flow through a tube is proportional to the fourth power of the radius of the cannula and is inversely related to its length.[22] Thus, short, large-bore, peripheral intravenous lines are adequate for rapid fluid infusion. The 2008 SIGN guideline indicates either colloid or crystalloid solutions may be used to attain volume restoration prior to administering blood products.[35]

There are remarkably few data on optimal fluid resuscitation pathways or algorithms, and very often the approach is based on the patient’s clinical presentation. The choice of fluids, infusion rates, and various in points are largely individual or institutionally driven.

A study published by Kaplan et al indicated that skin temperature on physical examination in combination with serum bicarbonate levels correlated well with the level of systemic perfusion.[42]  Foley catheter placement is helpful to allow a continuous evaluation of the urinary output as a guide to renal perfusion.

Patients with severe coexisting medical illnesses, such as cardiovascular and pulmonary diseases, may require pulmonary artery catheter insertion to closely monitor hemodynamic cardiac performance profiles during the early resuscitative phase.

After the ABCs have been addressed, assess the patient's response to resuscitation, based on evidence of end organ perfusion and oxygen delivery.

Consultation with a surgeon should be considered for all patients with GI hemorrhage. Depending on the patient’s comorbidities, subspecialty consultation is often needed and mirrors the trend in healthcare toward a multidisciplinary team approach.

Once the maneuvers to resuscitate are underway, it is often very helpful to insert a nasogastric tube and perform an aspirate and lavage procedure. This should be the first procedure performed to determine whether the GI bleeding is emanating from above or below the ligament of Treitz. If the stomach contains bile but no blood, UGIB is less likely. If the aspirate reveals clear gastric fluid, a duodenal site of bleeding may still be possible.

In a retrospective review of 1190 patients, Luk et al found that positive nasogastric-tube aspirate findings were 93% predictive of an upper GI source of bleeding.[43]

According to a study performed by the American Society for Gastrointestinal Endoscopy (ASGE), however, a nasogastric-tube aspirate finding can be negative even in the setting of a large duodenal bleeding ulcer. The study compared nasogastric-tube aspirate findings with endoscopic findings of the bleeding source.[26] The investigation revealed that 15.9% of patients with a clear nasogastric-tube aspirate, 29.9% of patients with coffee-ground aspirate, and 48.2% of patients with red blood aspirate had an active upper GI source of bleeding at the time of endoscopy.

A study correlated mortality with the color of the fluid from the nasogastric-tube aspirate and the color of the stool.[2] As shown in the following table, the color of the nasogastric-tube aspirate can be a prognostic indicator.

Table 4. Effect of the Color of the Nasogastric Aspirate and of the Stool on UGIB Mortality Rate



View Table

See Table

See Pediatric Gastrointestinal Bleeding for more information on this topic.

Surgery

Primary surgical intervention should be considered in patients with a perforated viscus (eg, from perforated duodenal ulcer, perforated gastric ulcer, or Boerhaave syndrome). In patients who are poor operative candidates, conservative treatment with nasogastric suction and broad-spectrum antibiotics can be instituted. Endoscopic clipping or sewing techniques have also been used in such patients.

Emergency surgery in UBIG typically entails oversewing the bleeding vessel in the stomach or duodenum (usually preoperatively identified by endoscopy), vagotomy with pyloroplasty, or partial gastrectomy. Angiographic obliteration of the bleeding vessel is often considered a favorable modality in patients who are poor surgical candidates. (See Angiography.)

Treatment-related contraindications and precautions

Contraindications to upper endoscopy include an uncooperative or obtunded patient, severe cardiac decompensation, acute myocardial infarction (unless active, life-threatening hemorrhage is present), and perforated viscus (eg, esophagus, stomach, intestine). Expert subspecialty consultation may be beneficial to optimize the patient and establish a best “window of opportunity” should endoscopy proceed.

Contraindications to emergency surgery include impaired cardiopulmonary status and bleeding diathesis.

Esophagogastroduodenoscopy (EGD) may be more difficult or impossible if the patient has had previous oropharyngeal surgery or radiation therapy to the oropharynx. Altered upper GI tract anatomy from previous surgery (eg, Roux-en-Y gastric bypass) may pose unique challenges to endoscopic management of bleeding.

The presence of a Zenker diverticulum can make intubation of the esophagus more difficult.

Patients with Down syndrome are more sensitive to conscious sedation and, when possible, should be monitored by an anesthesiologist and/or intubated prophylactically prior to the procedure. Monitored anesthesia care has been increasingly used in more challenging and sometimes prolonged cases such as EGD for active UGIB.

Hypotension may be exacerbated by sedation; therefore, patients who are clinically unstable should be carefully sedated. Continuous monitoring in the ICU is warranted and monitored anesthesia care by an anesthesia provider may improve the safety of endoscopy, particularly if there is decompensation or compromise of the airway.

Patients with massive bleeding should be considered for intubation to reduce the increased risk of aspiration. Such patients should be treated in an intensive care setting. As suggested, subspecialty consultation with a pulmonologist or an intensivist may be prudent, and sedation might be best managed with the subspecialists in attendance. Anesthesia assistance should be considered even with intubated patients depending on patients' comorbidities and overall stability.

Ideally, the patient should be stabilized prior to endoscopy and abnormalities in coagulation should be corrected. When this is not possible, the judgment of an experienced endoscopist is vital. The merits of the multidisciplinary team approach in critically ill patients cannot be overemphasized.

Proton-Pump Inhibitors

The relative efficacy of proton-pump inhibitors (PPIs) may be due to their superior ability to maintain a gastric pH at a level above 6.0, thereby protecting an ulcer clot from fibrinolysis.[44]  Current guidelines recommend a regimen of an intravenous (IV) PPI 80-mg bolus, followed by a continuous infusion of 8 mg/hour for 72 hours.[86, 182, 184, 183, 185]

Lau et al demonstrated that high-dose IV omeprazole can accelerate the resolution of the stigmata of recent hemorrhage and reduce the need for endoscopic therapy.[45] Barkun et al showed this therapy to be cost-effective.[46] Laine et al demonstrated that high-dose IV lansoprazole, as well as orally administered high-dose lansoprazole, can maintain the intragastric pH above 6.[47]

A meta-analysis of 24 randomized controlled trials that evaluated PPIs for bleeding ulcers (with or without endoscopic therapy) found a significant reduction in the risk of rebleeding, the need for repeat endoscopic hemostasis, and surgery. An improvement in mortality was also seen in Asian trials and in patients with active bleeding or nonbleeding visible vessels.[48]

A systematic review of six randomized trials comprising 2223 patients to assess the use of a PPI before endoscopic evaluation found that pre-endoscopy PPI therapy did not significantly reduce mortality, rebleeding, or the requirement for surgery.[121] However, there was a significantly lower proportion of peptic ulcers with high-risk stigmata at endoscopy and significantly lower rates of endoscopic treatment.

The 2010 international consensus guidelines on upper gastrointestinal (GI) bleeding (UGIB) recommended the use of IV PPIs in all patients with high-risk lesions post endoscopic therapy; PPI therapy might downgrade the lesion if given pre-endoscopy.[62]

Standard daily-dose oral PPIs may be used in patients who do not have active bleeding or other high-risk stigmata for recurrent bleeding (eg, a visible vessel, adherent clots); in such patients, the risk of recurrent bleeding is low.[115] The goal of treatment in these patients (following resuscitation) should be directed at healing the ulcers and at eliminating precipitating factors (eg, H pylori, nonsteroidal anti-inflammatory drugs [NSAIDs]).

When possible, it is important to take biopsy samples to test for H pylori at the initial endoscopy procedure. Because starting high-dose IV PPI therapy is the mainstay of initial management in UGIB, it is difficult to obtain the initial endoscopic biopsies without the presence of ongoing proton-pump inhibition. It is not well understood whether short-duration proton-pump inhibition alters the sensitivity of biopsies for H pylori. Biopsy specimens should be histologically evaluated when the rapid urease test is negative.[35]

A combined analysis of five studies that evaluated oral dosing with PPI (with or without endoscopic therapy) found a significant reduction in the risk of rebleeding and surgery.[50]

NOTE: Patients with liver cirrhosis may have an increased mortality if treated with PPIs.[124, 190]

PPIs in patients taking antiplatelet or anticoagulant therapy

Standard dose PPI therapy is advised for gastroprotection in all patients on antiplatelet therapy who are at increased risk of GI bleeding (age >65 years or concomitant use of corticosteroids or anticoagulants or history of peptic ulcer). International normalized ratio (INR) monitoring is required when starting or stopping PPI therapy in users of vitamin K antagonists.

No demonstrated interaction exists between PPIs and the novel oral anticoagulants. Based on a documented efficacy, antiplatelet therapy (aspirin < 300 mg/daily, ticlopidine 100 mg/daily, clopidogrel 75 mg/daily) is widely used for both primary and secondary prevention of cardiovascular and cerebrovascular ischemic events.[125, 126] However, antiplatelet drugs may cause adverse GI events (gastroduodenal ulcerations/erosions, overt bleeding, occult bleeding, and rare perforation), with a definite probability of death, particularly in the elderly. Therefore, gastroprotection is advised in those patients at increased GI risk during antiplatelet therapy.

Increased risk factors include age 65 years and older, concurrent use of steroid/anticoagulant therapy, or a history of peptic ulcer disease. The presence of relevant comorbidities (heart failure, renal impairment, stroke, diabetes, ongoing malignancy) and tobacco use are additional risk factors for both GI events and related mortality. Standard PPI dosing is the most effective gastroprotective therapy.

PPI therapy is not effective in preventing bleeding lesions induced by antiplatelet drugs in either the small intestine or the colon.

Anticoagulants, either vitamin K antagonists or novel oral anticoagulants (NOACs) (including dabigatran, rivaroxaban, and apixaban), do not cause gastroduodenal mucosa injury in and of themselves. These agents may, however, facilitate bleeding of preexisting peptic ulcers. Although gastroprotection with a PPI is currently routinely recommended, unless a concomitant antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) therapy is prescribed, data exist that show PPI cotherapy is associated with reduced risk of warfarin-related UGIB.[127]

In patients under acid suppression because of gastroprotection for any acid-related disease, intensified INR monitoring is recommended because PPIs may potentiate vitamin K antagonist-induced anticoagulation, most likely due to facilitated gastric absorption of warfarin.[128]

Therapeutic Endoscopy

For several decades, endoscopy has been the primary method of evaluating and managing upper gastrointestinal (GI) bleeding (UGIB).[129]

Several observational studies, randomized clinical trials, and meta-analyses have demonstrated and supported the idea that early endoscopic hemostatic therapy significantly reduces the rates of recurrent bleeding, the need for emergent surgery, and mortality in patients with acute nonvariceal UGIB. This effect has been more evident in higher-risk patients.[106, 115, 130, 131, 132, 133]

Challenges, such as increasing patient age and comorbidity, the extremely effective antithrombotic or anticoagulant agents, and significant side-effect concerns of the most effective therapeutic agents for ulcer disease, have fortunately been balanced with various endoscopic technological developments and dissemination of evidence-based treatment pathways. Yet the mortality from peptic ulcer bleeding has changed very minimally over this time.[97, 134]

Three significant technological advances have been developed: (1) endoscopic application of Doppler probes to evaluate arteries in the ulcer base, (2) endoscopic application of hemostatic powders, and (3) over-the-scope clips, with enhanced capability over the standard endoclips.

Aside from ulcer hemorrhaging, other causes of GI bleeding, including mucosal tears in the esophagus or upper stomach due to vomiting (Mallory-Weiss tears), venous blebs, and vascular ectasias, can also be treated with endoscopic coagulation.

The bleeding from gastric cancers and ulcers in leiomyomas does not usually respond to endoscopic therapy; surgical or radiologic intervention is needed.

Much debate has focused on the significance of the nonbleeding visible vessel (ie, color, size, diagnostic characteristics, risk of rebleeding) in ulcer hemorrhage. These matters became clarified after the characteristics and significance of the visible vessel in the ulcer crater were defined and the evidence for endoscopic therapy was established, demonstrating that patients requiring therapy to control bleeding or rebleeding could be diagnosed and treated at the time of the upper endoscopy.

The use of Doppler probes to evaluate the arterial flow in the base of ulcers to assess for the rebleeding risk and adequacy of hemostasis may prove to be more accurate than the visual assessment of bleeding stigmata.

Patients should be considered for upper endoscopy if blood loss from the upper GI tract is suspected.

The patient should undergo upper endoscopy prior to any operative intervention in order to diagnose and localize the bleeding site. Most patients (85%-90%) respond to endoscopic therapy.

During the endoscopy, the patient is monitored according to the analgesia and sedation guidelines formulated by the American Society of Anesthesiology. The characteristics of the bleeding lesion are noted, and appropriate therapy is applied when necessary for high-risk lesions or active bleeding.

Urgent endoscopy

Urgent endoscopy is indicated when patients present with hematemesis, melena, or postural changes in blood pressure. Studies have demonstrated a lower rate of rebleeding and shorter length of stay when endoscopy was performed within 24 hours of admission.[43, 51] However, observational studies have not shown a benefit in clinical outcomes when endoscopy was performed within 2 to 12 hours of presentation.[107, 108]

Early endoscopy

Cooper et al studied the effectiveness of performing an early endoscopy within the first 24 hours of an acute UGIB episode and found it to be associated with reductions in the length of hospital stay, rate of recurrent bleeding, and the need for emergent surgical intervention.[51]

According to the 2010 international consensus on nonvariceal UGIB, early endoscopy (within 24 hours of presentation) is appropriate for most patients with UGIB.[52] In a retrospective review involving more than 30,000 cases, Yavorski et al showed that the mortality rates were more than twice as high in patients who did not undergo an early endoscopic procedure than for those who did undergo the procedure early on (11.1% vs 5.2%, respectively).[9] More recent data also suggest endoscopy within 24 hours may have more favorable outcomes.[106, 130]

Studies on the effectiveness of endoscopy on weekends or off-hours have inconsistently shown poorer outcomes.[135, 136]

Endoscopic techniques

There are several currently widely accepted hemostatic treatment options. These include injection of epinephrine and tissue adhesives such as cyanoacrylate, ablative therapy with contact modalities such as thermal coagulation with heater probe and bipolar hemostatic forceps, noncontact modalities such as hemostatic power sprays and argon plasma coagulation, and mechanical hemostasis with band ligation, endoscopic hemoclips, and over-the-scope clips.

The following endoscopic techniques have been developed for achieving hemostasis[10] :

Treatment using a combination of endoscopic therapies has become more common. For example, injection therapy can be applied first to better clarify the bleeding site with at least partial hemostasis, especially in the actively bleeding patient, followed by the application of heater probe or bipolar (gold) probe coagulation with coaptation for definitive hemostatic management. Injection therapy can also be performed prior to endoscopic placement of hemoclips.

According to the 2008 Scottish Intercollegiate Guidelines Network (SIGN) guideline, combinations of endoscopy with an injection of at least 13 mL of 1:10,000 adrenaline, coupled with either a thermal or mechanical treatment, are more effective than single modalities.[35]

The 2010 international consensus guidelines on UGIB recommended the use of endoscopic clips or thermal therapy for high-risk lesions.[52]

Heater probe coagulation

The heater probe consists of a resistor electrode enveloped by a titanium capsule and covered by Teflon (to reduce sticking to the mucosa by the probe). The probe temperature rises to 250°C (482°F).

Bipolar electrocoagulation

The bipolar probe consists of alternating bands of electrodes producing an electrical field that heats the mucosa and the vessel. The electrodes are coated with gold to reduce adhesiveness. The probes are stiff in order to allow adequate pressure to be applied to the vessel to appose the walls and thus produce coaptive coagulation when the electrical-field energy is transmitted. Careful technique is required to heat-seal the perforated vessel.

Injection therapy

Injection therapy involves the use of several different solutions injected into and around the bleeding lesion. Solutions available for injection include epinephrine, sclerosants, and various clot-producing materials, such as fibrin and cyanoacrylate glues.

The epinephrine used for injection is diluted (1:10,000) and injected as 0.5- to 1-mL aliquots. Debate continues over whether the hemostatic effect of epinephrine is due to induced vessel vasoconstriction and subsequent platelet aggregation or to the tamponade effect produced by injecting the volume of drug into the tissue surrounding the bleeding lesion.

Epinephrine injection is often used to reduce the volume of bleeding so that the lesion can be better localized and then treated with a coaptive technique (ie, heater probe, gold probe).

Combining epinephrine injections with human thrombin (600-1000 IU) reduces the risk of bleeding.[6]

Although the epinephrine administered in injection therapy is absorbed into the systemic circulation, this does not appear to have any adverse effects on the hemodynamic status.

Injecting a volume of sterile isotonic sodium chloride solution and providing a tamponade effect also leads to hemostasis, although not as effectively as does epinephrine.[6]

The sclerosant solutions such as ethanol, polidocanol, and sodium tetradecyl sulfate are not frequently administered relative to the use of other available techniques for hemostasis in nonvariceal GI bleeding. Band ligation of esophageal varices is currently used more commonly than sclerosants.

The sclerosants create hemostasis by inducing thrombosis, tissue necrosis, and inflammation at the site of injection. When large volumes are injected, the area of tissue necrosis can produce an increased risk of local complications, such as perforation.[137] Combining the various agents into a single injection has not been shown to be more beneficial than a single-agent therapy alone.[6]

The use of fibrin glue in injection therapy has been shown to be successful, with results similar to those of epinephrine injections.[55]

Cyanoacrylate is effective in achieving hemostasis, with success rates similar to that of hemoclips.[138, 139]

Laser therapy

Laser phototherapy is a noncontact thermal method that uses an Nd:YAG (neodymium-doped yttrium aluminium garnet) laser to create hemostasis by generating heat and direct vessel coagulation. It is not as effective as coaptive coagulation, because it lacks the use of compression to create a tamponade effect.[6] An additional deterrent to its use is expense. Laser therapy has largely been replaced with other endoscopic hemostatic methods.

Hemostatic clips and endoclips

Hemostatic clips are widely available and used in the United States.

With careful placement of the clip, closing the defect in the vessel is possible. Often, depending on the lesion and progress to affect hemostasis, multiple clips are applied. Typically, they become detached and pass from the GI tract within 2 weeks. Hemostatic clips are considered magnetic resonance imaging (MRI)-conditional because they are metallic, and they can serve as radiopaque markers to direct the interventional radiologist during angiography to the relevant area if endoscopy fails to achieve adequate hemostasis. These clips vary in their size and strength. Numerous manufacturers have produced hemostatic clips, with the most significant advancements being the ability to rotate for accurate placement and the ability to reopen and reapply when necessary.

There are substantial data documenting the efficacy of hemoclips, which is similar to that of thermal coagulation methods.[19, 141]

One report, concerning 113 patients with major stigmata of ulcer hemorrhage, found no difference between the use of hemoclips and photocoagulation with regard to hemostasis, 30-day mortality, and the need for emergency surgery.[56] Patients randomized to the endoclip group had significantly lower rebleeding rates (2% vs 21%). However, only 60% of active bleeders were successfully treated with the heater probe, a rate much lower than in previous reports.

A study of 80 patients found a higher rate of control of initial bleeding with the heater probe compared with the Olympus endoclip (100% vs 85%).[57] Rebleeding rates were not significantly different.

No significant differences in procedure duration, initial hemostasis, or rebleeding rates were found in a study of 47 patients comparing combination therapy with epinephrine injection plus monopolar electrocoagulation versus hemoclips.[58]

There are some clinical settings in which endoclips may be preferred over other hemostatic methods. These include the treatment of ulcers in patients who are coagulopathic or who require ongoing anticoagulation; in such patients, electrocoagulation will increase the size, depth, and healing time of treated lesions. Endoclips may also be preferable in the retreatment of lesions that rebleed after initial thermal hemostasis. Finally, some endoscopists, including this author, may choose endoclips as their method of choice for hemostasis to avoid the potential for tissue destruction altogether, thus allowing a potentially safer setting to use any method of choice if repeat endoscopy for hemostasis is required.

Ulcers on the lesser curvature, the posterior duodenum, or the cardia increase the difficulty of clip deployment and clip failure rates.

Larger endoclips, such as the over-the-scope clips, have advantages over smaller hemoclips for the hemostasis of chronic ulcers, fibrotic lesions, and the closure of larger lesions. However, the use of the over-the-scope clips can be cumbersome in upper GI bleeding and, therefore, these clips have been more commonly used in refractory bleeding or as a salvage maneuver, but there are data showing efficacy of these clips as a primary modality.[142, 143]

Argon plasma coagulation

APC is a technique in which a stream of electrons flows along a stream of argon gas. The coagulation is similar to monopolar cautery, with the current flow going from a point of high current density (the point of contact of the gas with the mucosa) to an area of low current density (the conductive pad on the patient's body). The current flows through the body in an erratic path to the pad.

This monopolar cautery technique is similar to the laser technique in that energy is delivered to the vessel for coagulation with apposition of the vessel walls. This technique was found not to be effective for visible vessels larger than 1 mm, owing to the limited depth of burn. Small, superficial vessels such as arteriovenous malformations, telangiectasias, and particularly gastric antral vascular ectasia (GAVE) respond well to treatment by APC.

Hemostatic powder/spray

Hemostatic powders are a novel technique. Thus, data are available data, but no randomized controlled trials evaluating this technique have been conducted yet.[144] These agents have primarily been used as a second-line option when other endoscopic hemostasis techniques have failed. In a literature review of several reported cases, a hemostatic powder spray (Hemospray) was successfully used for hemostasis in 88.5% of 234 cases of UGIB.[145]

The hemosprays have the advantage of excellent initial hemostasis, but they can also obscure the endoscopic views of the underlying lesion. Intuitively, as a purely topical agent, hemosprays would not have the durability of mechanical clips or thermal coactive techniques.

In a retrospective study (2013-2017) that evaluated the effectiveness of a hemospray (Hemospray) for managing diffuse or refractory UGIB in 52 patients treated for peptic ulcer bleeding (n = 18), postinterventional bleeding (n = 13), or other UGIB (n = 21), there was 100% efficacy without adverse effects related to therapy, with immediate hemostasis in 51 patients.[146] Twenty-two patients (43.1%) had recurrent bleeding within 3 days, with a 56.9% overall clinical success, and 25 patients had recurrent bleeding within 7 days (49%), with a 51% overall clinical success. In total, eight patients died (15.4%), two of which were related to bleeding (3.8%). Thus, although these findings indicate a high technical success of the hemospray for treating diffuse or refractory UGIB, the investigators acknowledge there was a high rebleeding risk and further investigation is needed.[146]

Doppler ultrasonographic probes

There is increasing use of Doppler ultrasonographic probe-guided lesion assessment to detect significant arterial flow in the vessel at the ulcer base, thanks to the development of relatively low cost, easy-to-use Doppler units and disposable endoscopic probes.[139, 147] Two studies have shown Doppler probe assessment is more accurate than classic endoscopic scoring of stigmata in the base of ulcers, at predicting rebleeding risk.[148, 149]

Endoscopic treatment decisions

The choice of treatment modality is influenced by the size of the vessel. Animal studies have demonstrated that the heater probe and bipolar probe are effective for vessels as large as 2 mm in diameter.

Other techniques (eg, clips, band ligation) or a combination of techniques are needed for larger vessels or vessels that are not approachable by the heater probe or bipolar probe. (Surgical intervention should be considered when dealing with vessels larger than 2 mm in diameter, discounting an enlargement due to the development of a pseudoaneurysm.) The over-the-scope clips are able to grasp larger areas and apply more mechanical force to larger vessels, making them an option when standard endoclips may not suffice.

It is important to remember when planning endoscopic therapy for a large vessel, that the 7-French heater probe or gold probe catheter can traverse the accessory channel of a standard adult upper endoscope, but a therapeutic endoscope with a larger accessory channel is necessary to pass a 10-French thermal probe.

Ulcers with an overlying clot

In the patient who has an ulcer with an overlying clot, attempting to remove the clot by target washing is critical to allow treatment of the underlying stigmata if appropriate. Endoscopic removal of the clot by washing or cold snare has been demonstrated to be effective in reducing the recurrence of bleeding.[59]

The findings under the clot (eg, bleeding vessel, visible vessel, clean base, examples of which are seen in the images below) help to determine the therapy needed and to improve efficacy by allowing treatment to be applied directly to the vessel. (See also the table below.)



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with a clean base.



View Image

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a clean base.



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with an overlying clot.



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with a visible vessel.



View Image

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a visible vessel.

Table 5. Ulcer Characteristics and Correlations



View Table

See Table

If the clot cannot be removed by washing, then using a cold snare can be effective in dislodging and removing the clot.

Vigorous washing of the clot formed after therapy is useful in determining the adequacy of coagulation. A combination of injection with heater probe or bipolar coaptive coagulation is often used and has been shown to be more effective in patients with active bleeding.

The patient is monitored under the protocol for conscious sedation, also called analgesia and sedation (ie, per the American Society of Anesthesiologists [ASA] and the American Society for Gastrointestinal Endoscopy [ASGE] guidelines). In selected cases, monitored anesthesia care has become the preferred option for sedation and endoscopy.

Active bleeding and rebleeding

Attempting to control active bleeding using the recommended techniques with the appropriate equipment or instituting appropriate therapy for a high-risk lesion is important. The large-channel therapeutic endoscope should be used so that the 10-French thermal probe can be employed for adequate coaptation.

Endoscopists should use the technique with which they have the most familiarity. The endoscopy should not be started unless the endoscopist is equipped for any potential lesions (eg, ulcer, varix, angioectasia, tear, tumor). The patient should be monitored for recurrent bleeding and treated a second time if appropriate. A surgical consultation should be considered for all patients with GI hemorrhage. Subspecialty consultation for multidisciplinary management should be considered, particularly in severe active bleeding.

Rebleeding occurs in 10%-30% of endoscopically treated patients.[35]

Second-look endoscopy

A second attempt at endoscopic control is warranted if the initial endoscopy fails to control the bleeding. Some authorities have concerns about the perils of a second esophagogastroduodenoscopy (EGD), which may result in delayed surgery, perforation, and increased morbidity and mortality. However, this approach has been validated in a large, randomized, controlled trial that showed decreased morbidity and mortality.[62]

Owing to the relatively high rebleeding rate associated with ulcers, some clinicians advocate scheduled second-look endoscopy, with the intent of identifying and proactively managing persistent or recurrent bleeding. This would be a strategy directed at individuals who are very likely to benefit from a second invasive procedure; however, no current guidelines recommend this strategy. A systematic review and meta-analysis of randomized trials assessing otucomes of second-look endoscopy reported a small but significant reduction in rebleeding in patients undergoing the procedure (P< 0.01) but no significant benefit in reducing surgery or death.[150]

In a prospective multicenter study that evaluated the efficacy of scheduled second-look endoscopy (24-36 hours after initial hemostasis) in 319 patients with endoscopically confirmed bleeding peptic ulcer treated unsucessfully with hemoclip application, thermal coagulation, and/or epinephrine injection, investigators found noninferiority of single endoscopy relative to second-look endoscopy for rate of rebleeding (P = 0.132).[151] Independent risk factors for rebleeding included endoscopists’ estimation of poorer success of the initial hemostasis, a patient history of NSAID use, and higher transfusion requirement (4 units of red blood cells). Thus, the researchers concluded that repeat endoscopy may only be beneficial in patients with less-than-satisfactory initial hemostasis at endoscopy, an NSAIDs history, or higher transfusion requirement.[151]

Specific characteristics at endoscopy can predict rebleeding. Rebleeding occurs in 55% of patients who have active bleeding (pulsatile, oozing), in 43% who have a nonbleeding visible vessel, in 22% who have an ulcer with an adherent clot, and in 0-5% who have an ulcer with a clean base.

At endoscopy, the prevalence rate for a clean base is 42%, for a flat spot is 20%, for an adherent clot is 17%, for a visible vessel is 17%, and for active bleeding is 18%. See the images below.



View Image

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a clean base.



View Image

Upper gastrointestinal bleeding (UGIB). Ulcer with a visible vessel.

Freeman et al have described a pale, visible vessel that appears to have a very high risk for rebleeding.[60] This must be differentiated from the presence of a clean ulcer base.

Good visualization is important. The uncleared fundal pool may obscure an ulcer, mucosal tear, gastric varices, portal gastropathy, or tumor (eg, leiomyoma, adenocarcinoma, lymphoma). Endoscopic therapy is recommended for ulcers at increased risk for rebleeding.

Using a combination of techniques is prudent when re-treating the ulcer site because the first therapy may have produced necrosis and weakening of the intestinal wall. Ulcers on the anterior surface of the stomach and duodenum are at an increased risk for perforation. Using injection as the first step increases the thickness of the submucosal layer, thus providing an extra margin of safety.

Even operative techniques can have a significant rebleeding rate with significant mortality, as noted in the study of Poxon et al. In this investigation, the rebleeding rate was 10% (80% mortality for rebleeders) in patients who underwent a conservative surgical technique in which the ulcer base was undersewn.[61] This more conservative approach was compared with the standard surgical technique (ie, vagotomy and pyloroplasty or partial gastrectomy). The comparison of the conservative approach with a standard gastrectomy resulted in similar mortality rates, ie, 26% versus 19%, respectively, with no rebleeding after partial gastrectomy.

Postendoscopic monitoring

Postoperatively, the patient is monitored for recovery from conscious sedation or receives monitored anesthesia care after endoscopy and from general anesthesia after abdominal surgery. Observe and follow the patient's mental status, vital signs, chest, cardiac, and abdominal findings to ascertain that the patient's clinical status has stabilized and that no complications (eg, aspiration, perforation, recurrent bleeding, myocardial infarction due to hypotension) have occurred. Monitor the hemoglobin level.

Bleeding Peptic Ulcer Treatment

Upper gastrointestinal (GI) endoscopy is the most effective diagnostic tool for peptic ulcer disease and has become the method of choice for controlling active ulcer hemorrhage. Failure of endoscopy to maintain hemostasis is one of the indications to initiate surgical intervention, especially in high-risk patients.

In a randomized, prospective trial that included 92 patients with recurrent peptic ulcer bleeding after initial endoscopic therapy for hemostasis, patients who underwent a second endoscopic attempt to control bleeding were found to have decreased transfusion requirements, 30-day mortality rates, and duration of intensive care unit (ICU) stay in comparison with the surgical group.[62]

With the exception of a patient in shock who has a life-threatening recurrent hemorrhage, this study supports attempting another trial of endoscopy to control a bleeding ulcer.

Regardless of the endoscopic therapy, however, 10%-12% of patients with acute ulcerous hemorrhage require an operation as the definitive procedure to control the bleeding ulcer. In most circumstances, the operation is performed emergently, and the associated mortality rate is as high as 15%-25%.

Medical therapy used in conjunction with endoscopy involves proton-pump inhibitor (PPI) administration. PPIs decrease the rebleeding rates in patients with bleeding ulcers associated with an overlying clot or visible, nonbleeding vessel in the base of the ulcer.[63, 64] Consider transcatheter angiographic embolization in patients who are poor surgical candidates. Because of the extensive collateral circulation of the upper GI tract, ischemic complications are rare.

Surgical treatment

If two attempts at endoscopic control of the bleeding vessel are unsuccessful, avoid further attempts (ie, because of increased complication risks and mortality) and pursue surgical intervention. The indications for surgery in patients with bleeding peptic ulcers are as follows:

The operative treatment options for a bleeding duodenal ulcer historically include vagotomy, gastric resection, and drainage procedures. Each specific operative option is associated with its own incidence of ulcer recurrence, postgastrectomy syndrome, and mortality. When making an intraoperative judgment on how to best manage the bleeding ulcer, it is extremely important for the surgeon to be aware of these differences.[16]

The three most common operations performed for a bleeding duodenal ulcer are as follows[10] :

The purpose of the vagotomy is to divide the nerves to the acid-producing body and fundus of the stomach. This inhibits acid production that occurs during the cephalic phase of gastric secretion, thereby decreasing the risk for recurrent ulceration.

In addition to having the same effects as a highly selective vagotomy in the proximal stomach, a truncal vagotomy also has marked effects on distal gastric motor function. It weakens distal gastric peristalsis, thus requiring the creation of a pyloroplasty to decrease the resistance to outflow from the stomach. Proximal vagotomy abolishes gastric receptive relaxation and impairs storage in the proximal stomach. As a result, a more rapid gastric emptying of liquids occurs. A drainage procedure is not required, because the innervation of the antrum and pylorus is still intact. Consequently, the gastric emptying of solid food is not altered. The antropyloric mechanism still functions normally and continues to prevent duodenogastric reflux.

Truncal vagotomy and suture ligation of a bleeding ulcer is a frequently used operation for treating upper GI bleeding in elderly patients with life-threatening hemorrhage and shock. The procedure can be performed rapidly, minimizing the time spent in the operating room under general anesthesia.

Much of what is now known about the operations performed for bleeding duodenal ulcers came from the era before the etiologic role for H pylori and nonsteroid anti-inflammatory drugs (NSAIDs) in the development of peptic ulcers was understood. Reducing gastric acidity has been proven to be beneficial, with lower rebleeding rates when using high-dose omeprazole.[6] Although PPIs seem to have an advantage, they have no effect on mortality.

The diagnosis of H pylori infection is important in the management of patients with a complicated bleeding peptic ulcer. If a patient with a bleeding ulcer requires surgery, then knowledge of the patient's H pylori status becomes pertinent, because it may help guide the decision to choose a particular surgical procedure (eg, simply oversewing the ulcer as opposed to performing an antiulcer operation).

Many studies support the decision to manage the bleeding ulcer in conjunction with eradication of H pylori.

The 2008 Scottish Intercollegiate Guidelines Network (SIGN) guideline recommends testing for H pylori in patients with peptic ulcer bleeding. Eradication therapy should be prescribed for those who test positive for an active infection. In those who take NSAIDs, maintenance antisecretory therapy should consist of daily PPI for prevention of recurrent ulceration after successful healing of the ulcer and H pylori eradication, if the NSAIDs cannot be discontinued.[35, 120, 152]

Bleeding Gastric Ulcer Treatment

The surgical management of bleeding gastric ulcers is slightly different from that of duodenal ulcers, but the concepts are identical. The three most common complications of a gastric ulcer that mandate emergent surgical intervention are hemorrhage, perforation, and obstruction. The goals of surgery are to correct the underlying emergent problem, prevent recurrent bleeding or ulceration, and exclude malignancy.

A bleeding gastric ulcer is most commonly managed by a distal gastrectomy that includes the ulcer, with a gastroduodenostomy or a gastrojejunostomy reconstruction.

The common operations for the management of a bleeding gastric ulcer include (1) truncal vagotomy and pyloroplasty with a wedge resection of the ulcer, (2) antrectomy with wedge excision of the proximal ulcer, (3) distal gastrectomy to include the ulcer, with or without truncal vagotomy, and (4) wedge resection of the ulcer only.

Types of gastric ulcers

The choice of operation for a bleeding gastric ulcer depends on the location of the ulcer and the hemodynamic stability of the patient to withstand an operation. Five types of gastric ulcers occur, based on their location and acid-secretory status.

Type 1 gastric ulcers are located on the lesser curvature of the stomach, at or near the incisura angularis. These ulcers are not associated with a hypersecretory acid state.

Type 2 ulcers represent a combination of 2 ulcers that are associated with a hypersecretory acid state. The ulcer locations occur in the body of the stomach in the region of the incisura. The second ulcer occurs in the duodenum.

Type 3 ulcers are prepyloric ulcers. They are associated with high acid output and are usually within 3 cm of the pylorus.

Type 4 ulcers are located high on the lesser curvature of the stomach and (as with type 1 ulcers) are not associated with high acid output.

Type 5 ulcers are related to the ingestion of NSAIDs or aspirin. These ulcers can occur anywhere in the stomach.

Surgical management according to ulcer type

A vagotomy is added to manage type 2 or type 3 gastric ulcers.

Patients who are hemodynamically stable but have intermittent bleeding requiring blood transfusions should undergo a truncal vagotomy and distal gastric resection to include the ulcer for types 1, 2, and 3 ulcers.

In patients who present with life-threatening hemorrhage and a type 1, 2, or 3 ulcer, biopsy and oversew or excision of the ulcer in combination with a truncal vagotomy and a drainage procedure should be considered.

Patients with type 4 ulcers usually present with hemorrhage. The left gastric artery should be ligated, and a biopsy should be performed on the ulcer. Then, the ulcer should be oversewn through a high gastrotomy.

Rebleeding rates for the procedures that keep the ulcer in situ range from 20% to 40%.[16]

Gastric bleeding in the immediate postoperative period from recurrent peptic ulcer disease is initially best managed by endoscopic or angiographic means. If reoperation is required, gastric resection is usually indicated, because a repeat vagotomy is not reliable and a more definitive solution is warranted.

Stress Ulcer Treatment

Knowledge of the predisposing conditions for stress ulceration allows the clinician to identify patients at risk for developing stress ulceration and gastrointestinal (GI) bleeding—respiratory failure with mechanical ventilation and coagulopathy being very prominent risk factors. Treatment in this group of high-risk patients should focus on prevention. This is best accomplished by treating the underlying causes of ulceration.

Aggressive support of hemodynamic parameters ensures adequate mucosal blood flow. In addition, several strategies have evolved to treat gastric luminal acidity.

Stress-related bleeding usually occurs 7-10 days after the initial insult but may manifest sooner. Initially, endoscopy is the most important diagnostic tool. The acute superficial erosions are multiple, begin in the fundus, and progress toward the antrum. Ninety percent of patients stop bleeding with conservative medical therapy that includes gastric acid–controlling medications to maintain the gastric luminal pH above 5.0.[18]

PPIs are the drugs of choice for acid suppression in stress ulcer prophylaxis (SUP). The risk of bleeding in an intensive care unit (ICU) is reduced by some 60% in patients receiving SUP compared to those treated with placebo or no prophylaxis.[153]  Current evidence does not substantiate routine prophylaxis. Therefore, withhold SUP in the majority of hospitalized patients, unless they have multiple risk factors and are likely to benefit from preventative strategies. Both cost and potential side effects from unnecessary proton-pump inhibitor (PPI) use can be reduced from following these guidelines.[92, 124]

Endoscopic hemostasis is attempted using traditional techniques, including electrocoagulation, argon plasma coagulation (APC), or injection therapy. Selective angiographic catheterization of the left gastric artery may be attempted with selective infusion of vasopressin (48-72 h) or embolization using Gelfoam, coils, or autologous clot to embolize the left gastric artery. Regardless of the angiographic technique used, it is often unsuccessful because of the rich and extensive submucosal plexus and collateral circulation within the stomach.

Surgical treatment

Surgical intervention becomes necessary if nonoperative therapy fails and blood loss continues. The goals of operative treatment are to control bleeding and to reduce recurrent bleeding and mortality. These patients are at extremely high risk, and the most expeditious procedure is the best option.

Simply oversewing an actively bleeding erosion is sometimes effective enough to control the bleeding. In the setting of life-threatening hemorrhage not amenable to endoscopic control, gastric resection with or without vagotomy with reconstruction may be necessary.

The type of gastric resection depends on the location of the gastric erosions, ie, whether they are proximal or distal. The options are antrectomy and subtotal, near total, or total gastrectomy. Operative mortality rates range from 4% to 17%.[65] The choice of the initial operation must be made with an understanding of the patient's condition, the amount and location of gastric disease, and an accurate assessment of one's technical ability to rapidly and safely perform a gastric resection. The trend has been to perform less surgery in general and to minimalize the type of surgical procedure performed.[66]

Managing the underlying insult causing the gastric stress ulcerations is also important. This involves supportive measures to maintain acceptable hemodynamic parameters, to provide adequate nutritional support in the critically ill patient, and to treat sepsis (if present).

Mallory-Weiss Syndrome Treatment

Distinguishing Mallory-Weiss syndrome from Boerhaave syndrome is critical. Although both entities share a common pathogenesis, their management is completely different.

Boerhaave syndrome represents a full-thickness transmural laceration with perforation of the esophagus. A Gastrografin swallow helps to confirm the presence of the perforation in most cases, and prompt surgical intervention is necessary to prevent mediastinitis and sepsis.

However, surgical intervention in Mallory-Weiss syndrome is required to achieve hemostasis in only 10% of cases.[18] The bleeding from a Mallory-Weiss tear spontaneously ceases in over 80% of patients by the time endoscopy is performed.[18, 95]

For patients in whom bleeding is visualized at endoscopy, the endoscopic treatment options are electrocoagulation, heater-probe application, hemoclips, epinephrine injection, or sclerotherapy.

In a series published by Bataller et al, hemostasis was achieved in 100% of patients with Mallory-Weiss tears by using endoscopic sclerotherapy with epinephrine (1:10,000) and 1% polidocanol. Other nonoperative therapies are reserved for cases in which endoscopic attempts at creating hemostasis have failed.

Other available options are angiographic intra-arterial infusion of vasopressin and transcatheter embolization of branches of the left gastric artery using Gelfoam. Avoid the balloon tamponade technique using the Sengstaken-Blakemore tube in this particular circumstance, because this apparatus may extend the mucosal laceration into a transmural laceration with perforation.[18]

Surgical intervention is indicated in patients with continued bleeding after failed attempts at nonoperative therapies.

Bleeding from the gastroesophageal junction is visualized through an anterior gastrotomy. Once the tear is localized, the bleeding is controlled by oversewing the lesion.

The overall mortality rates for patients who require emergent surgery is 15%-25%, in contrast to a mortality of 3% or less for patients whose bleeding stops by the time of the initial endoscopy.[18]

See Mallory-Weiss Tear for more information on this topic.

Dieulafoy Lesion Treatment

The initial endoscopic management of a Dieulafoy lesion can be highly successful. In a report by Norton et al describing their experience with 90 Dieulafoy lesions, endoscopic management achieved primary hemostasis in 96% of cases.[186]  The 30-day mortality was 13%, which is a reflection of the severe comorbid conditions associated with patients who have bleeding from a Dieulafoy lesion.[186]

Contact thermal ablation with a heater probe is a very effective technique, with or without the combined use of epinephrine to slow or stop the bleeding prior to applying the heater probe. Argon plasma coagulation (APC) and endoclips have also been used successfully for hemostasis. No studies have been performed that compare surgical and endoscopic therapy for Dieulafoy lesions.

Although surgical intervention may be required after failed endoscopic therapy, endoscopy is still an important adjunct for management, because a nonbleeding Dieulafoy lesion may be undetectable through a gastrotomy.

Because of this potential problem, a combined endoscopic and surgical approach has been adopted. The vascular malformation can be marked with India ink through the endoscope.

Rebleeding after endoscopic therapy occurs in 11%-15% of cases, with most cases of rebleeding controlled at repeat endoscopy.[21] (Repeat endoscopy in patients who have rebleeding has been validated in controlled studies of endoscopy and surgery.)

Angiodysplasia Treatment

Bleeding from angiodysplasias can range from occult blood loss to life-threatening hemorrhage. Because the lesions are small and superficial, endoscopic therapy is highly successful. Endoscopic treatments and devices used for hemostasis include argon plasma coagulation (APC), contact heat probes, electrocoagulation, and injection therapy.

The contact probe coagulators have been the most common form of endoscopic treatment because of their proven success and ability to target a bleeding lesion tangentially. Similarly, a noncontact option, APC, is very effective with options of a straight firing, side firing, and circumferential firing probes that result in an increased ease of use with targeting these flat and sometimes broad areas of involvement. APC would be the treatment of choice when treating gastric antral vascular ectasia (GAVE), as it allows the endoscopist to apply prompt and effective “painting” of the angiodysplastic lesions in the distal stomach.

Recurrent bleeding can occur from the mucosal injury caused by the coagulation. To overcome the possibility of a delayed hemorrhage, endoscopic band ligation has been applied for hemostasis in nonvariceal gastrointestinal bleeding, including angiodysplasias.[67]

When endoscopic techniques fail, surgical resection becomes necessary. When pangastric involvement is the source of bleeding, a total gastrectomy may be required; however, this is extremely rare. Available nonsurgical options include angiography with catheter-directed vasopressin. Combined hormonal therapy with estrogen and progesterone for patients in whom the diagnosis is unknown and vascular lesions are suggested has not been demonstrated to be effective.

Aortoenteric Fistula

Patients with an aortoenteric fistula most often present with a self-limiting sentinel hemorrhage that is then followed by an exsanguinating, massive gastrointestinal (GI) bleed. For the warning lesser sentinel bleed in a patient with a history of an abdominal aortic aneurysm repair or a known aortic aneurysm, the possibility of a graft-enteric fistula should be considered.

An upper endoscopy is the procedure of choice to help diagnose the fistula. It should be performed to the ligament of Treitz. Upper endoscopy findings also help to exclude other sources of upper GI bleeding (UGIB).

Once the diagnosis of aortoenteric fistula is confirmed or seriously considered, emergency surgical intervention is required. In most instances, the aortic graft is removed after debridement and closure of the duodenum, followed by an extra-anatomic vascular bypass in order to bypass the ligated aorta and revascularize the lower extremities.

Perioperative mortality is 22%-75%,[68] and major complications are common. Published opinions state that graft excision is not necessary as long as no gross contamination and purulence are present at the time of laparotomy.[69] Under these circumstances, antibiotics are administered long-term.

Another option in the surgical literature is the use of endovascular stents to repair the fistula.[70, 71] Endovascular stent management is technically feasible and may be used as a bridge to more definitive treatment after hemodynamic stabilization in high-risk surgical patients. Stent grafting controls hemorrhage immediately; however, because the device is placed in an infected field, adjunctive measures, such as long-term antibiotic use, percutaneous drainage, and bowel diversion, may be required.[72]

Although endovascular stents have been shown to be effective in treating aortoenteric fistulas, case reports have described aortoenteric fistulas in patients with abdominal aortic aneurysm treated initially with stent grafts as well.[73]

Treatment Complications

Complications of endoscopic therapy include aspiration pneumonia and perforation (1% for the first endoscopic therapy, 3% for the second). Bleeding can be caused by drilling into the vessel with contact thermal probes, by perforating the vessel with an injection, or by removing the clot with failure to coagulate the vessel.

Endoscopy is safe and effective in patients who present with upper gastrointestinal (GI) bleeding (UGIB). Careful consideration of the patient’s underlying comorbidities must be used to optimize the performance of endoscopy. As has been stated, mortality in UGIB is most often from the patient’s underlying comorbidities. Therefore, strategies to manage the bleeding episode and in preventing rebleeding need to include the management of the comorbidities. The value of a multidisciplinary team approach in managing these patients is strongly recommended.

The role of therapeutic angiography following failed endoscopic management should be considered as a favorable option to emergency surgery because there are similar success rates with hemostasis but potentially lower morbidity and mortality. (See Angiography)

Complications from emergency abdominal surgery include ileus, sepsis, poor wound healing, and myocardial infarction.

Salvage surgery is associated with a high mortality rate, reflecting the comorbidities of patients who rebleed or continue to bleed.

Posttreatment Monitoring and Care

The 2010 international consensus guidelines on upper gastrointestinal (GI) bleeding (UGIB) state that selected low-risk patients may be discharged immediately following endoscopy, but high-risk patients should remain hospitalized for at least 72 hours.[52]

According to the 2008 Scottish Intercollegiate Guidelines Network (SIGN) guideline, patients with a post-endoscopic Rockall score of less than 3 have a low risk of rebleeding or death and are candidates for early discharge and outpatient follow up.[35]

More recent international validation of the Glasgow-Blatchford bleed score (GBS) has confirmed that a score of 0 or 1 is associated with a very low risk of intervention and that hospital admission and emergency endoscopy are not required.[101]

The goal is to maintain the intragastric pH above 6 to maintain the clot. This is most easily achieved by intravenous proton pump inhibitor (PPI) therapy. After the acute phase, 72 hours, the coagulated vessel should be stable and the patient can be switched to oral therapy. If the patient rebleeds or has ongoing bleeding, repeat endoscopic therapy is suggested. If this is not successful, interventional radiology is performed to clot the bleeding vessel. If this fails, surgery would be considered.

The greatest risk for perforation is usually within the first 48 hours after endoscopic therapy. In the subsequent 48-72 hours after endoscopic therapy, the patient should receive acid-suppressive therapy to maintain a high gastric pH (above 6). A high gastric pH can be achieved by a continuous infusion of high-dose intravenous PPI therapy.

Tachyphylaxis may develop within 24 hours if H2-receptor antagonists are administered.

Patients who do not require endoscopic therapy and do not have other comorbidities should be considered for discharge.

Patients who did not require endoscopic treatment should receive routine, oral dosing of a PPI, ie, daily dosing prior to breakfast. Whether high-dose intravenous proton-pump inhibitor (PPI) therapy is advantageous in this setting remains controversial.

Oral PPI therapy can be used with any of the oral PPI preparations.

Patients should be tested for H pylori either by histology of gastric biopsy specimens taken on initial upper endoscopy or by other tests of active infection. Serologic testing should be avoided as it cannot be used to diagnose an active infection. If H pylori testing is positive, H pylori therapy should be instituted after the patient has been discharged and is in stable condition. Moreover, H pylori eradication should be confirmed 4-6 weeks later in patients with UGIB. This can be done by checking the stool for the H pylori antigen, or an H pylori breath test. The accuracy of eradication testing is much more reliable 2-4 weeks after the therapy has been completed and the patient has had no further antibiotics or antisecretory therapy.[154, 155]

Data on acid suppression via oral PPI therapy in order to produce a reduction in rebleeding are limited. High-dose intravenous PPI therapy appears to reduce rebleeding, but PPIs are not currently approved by the US Food and Drug Administration (FDA) for such treatment. The patient may be fed after recovery from local and intravenous anesthesia.

Some patients may require further endoscopic therapy. If repeat endoscopic therapy is needed, the stomach will usually empty liquids without residue within 2-3 hours. The 2011 American Society of Anesthesiologists (ASA) guidelines recommend a minimum of 2 hours without oral intake before performing endoscopy.[156]

The 2008 SIGN guideline recommends repeat endoscopy and endotherapy within 24 hours when initial endoscopic treatment is deemed suboptimal or in patients in whom rebleeding will likely be life threatening.[35]

If the patient remains stable, the patient can then be started on therapy for ulcer healing.

The patient should continue oral therapy for ulcer disease noted on endoscopy or for ulcers caused by cautery techniques during endoscopic therapy, only for a duration long enough to heal the ulceration.

Long-term acid suppression to prevent ulcer recurrence or its complications may not be required in patients with low-risk endoscopic findings and should be individualized in those with the need for continued nonsteroidal anti-inflammatory drug (NSAID) use, aspirin or other antiplatelet therapies, or anticoagulation.[75, 115]

Aspirin and NSAID therapies should be avoided in view of their adverse effect on platelet aggregation and ulcer healing. However, according to the 2010 international consensus guidelines, resumption of aspirin therapy in patients who require anticlotting prophylaxis should not be delayed as cardiovascular risks outweigh the risk of rebleeding.[52]

The 2008 SIGN guidelines state that patients with healed bleeding ulcers who are negative for H pylori require concomitant PPI therapy at the usual daily dose if NSAIDs, aspirin, or cyclooxygenase (COX)-2 inhibitors are indicated.[35]

If patients must remain on NSAIDs or low-dose aspirin, secondary prophylaxis against NSAID-induced ulcers should be given. According to the 2010 international consensus guidelines on UGIB, postdischarge use of aspirin or NSAIDs requires cotherapy with a PPI.[52]

The patient's hemoglobin value should be monitored to assess the efficacy of iron therapy as an outpatient; further improvement should be noted. Oral or parenteral iron supplementation to treat posthemorrhagic anemia are both effective options. Erythropoietin analogues have been shown to be effective in increasing the rate of hemoglobin production after ulcer hemorrhage, but they may not have a favorable cost-benefit ratio.

Repeat endoscopy should be done at follow-up in patients with gastric ulcers to document ulcer healing and to exclude cancer.[78]

Deterrence and Prevention of UGIB

H pylori eradication therapy should be given if H pylori is present in the setting of any history of ulcer disease. Eradication of H pylori has been demonstrated to reduce the risk of recurrent ulcers and, therefore, recurrent ulcer hemorrhages.

Avoid nonsteroidal anti-inflammatory drugs (NSAIDs). If this is not possible, use the lowest dose and duration.

Proton-pump inhibitors (PPIs) or misoprostol cotherapy should be used along with NSAIDs.

The use of cyclooxygenase (COX)-2 inhibitors has been shown to reduce the risk of ulcer hemorrhage, although only when not combined with aspirin therapy. Concerns have been raised about an increase in myocardial infarction and stroke in patients taking selective COX-2 inhibitors. More recent data suggest this may be a risk with all NSAIDs.[157, 158]

As demonstrated in the study by al-Assi et al, the combination of H pylori infection and NSAID use may increase the risk of ulcer hemorrhage.[1]

Medication Summary

Rebleeding in patients with upper gastrointestinal (GI) hemorrhage (UGIB) is associated with increased morbidity and mortality; therefore, prevention of rebleeding is the major goal of therapy.

There are two approved intravenous (IV) PPIs in use in the United States, pantoprazole (Protonix IV formulation) and esomeprazole magnesium (Nexium IV formulation)

These agents suppress gastric acid secretion by specifically inhibiting the H+/K+/ATPase enzyme system at the secretory surface of gastric parietal cells. Use of the IV preparation has been studied only for short-term therapy (ie, 7-10 d) and may be a useful adjunct via stabilization of the clot by increasing intragastric pH. High-dose IV treatment is the norm; however, high-dose oral therapy may be able to maintain the intragastric pH at about 6 as well.[47]

In severe acute upper GI bleeding (UGIB), IV proton pump inhibition should be initiated once the patient's hemodynamic status has been addressed and appropriate resuscitation measures have been implemented.[120]  Lau and colleagues reported the benefit of a high-dose bolus followed by continuous infusion of omeprazole before patients underwent endoscopy.[123] Endoscopic treatment was required in 19.1% of patients who received omeprazole compared to 28.4% of patients who received placebo (P = 0.007). Similarly, among patients with peptic ulcer disease, in the omeprazole group there were fewer patients with active bleeding in omeprazole group (6.4% vs 14.7%; P = 0.01) and more had clean-based ulcers  (64.2% vs 47.4%; P = 0.001).[123]

A Cochrane systematic review and meta-analysis of six randomized trials (N = 2,223) of pre-endoscopic PPI therapy found no significant differences between the PPI and control groups with respect to mortality (6.1% vs 5.5%), rebleeding (13.9% vs 16.6%), or surgery (9.9% vs 10.2%).[121]  Moreover, PPI therapy significantly reduced the proportion of participants with higher-risk stigmata of hemorrhage (active bleeding, nonbleeding visible vessel, and adherent clot) at index endoscopy (37.2% vs 46.5%) and undergoing endoscopic therapy at index endoscopy (8.6% vs 11.7%).[121]

Another Cochrane meta-analysis of 24 trials comprising 4,373 patients with peptic ulcer bleeding who did not consistently receive endoscopic hemostatic therapy found that PPI therapy was associated with reduced rebleeding and need for surgery surgery, but not mortality except among those at the highest risk.[122] This suggests that if endoscopy will be delayed or cannot be performed, PPI therapy may improve clinical outcomes.

PPI therapy should be discontinued after endoscopy unless the patient has a source for which PPIs may be beneficial (e.g., ulcers and erosions).[115]

The use of H2-receptor antagonists has not been shown to be effective in altering the course of UGIB. A meta-analysis concluded that there was a possible minor benefit with intravenous H2 antagonists in bleeding gastric ulcers but no benefit in duodenal ulcers.[79]

The use of the prokinetics agent to empty the stomach of retained blood or clots to improve endoscopic visualization has been extensively studied. To date, four large randomized controlled trials and three meta-analyses have shown that erythromycin reduces the need for second-look endoscopy but did not significantly reduce clinical outcomes such as blood transfusions, hospital stay, or surgery.[81, 159, 160, 161, 162, 163, 164]

In a meta-analysis by Barkun et al, there were no significant benefits to pre-esophagogastroduodenoscopy metoclopramide therapy, but the findings were limited by the small sample of patients (n = 28), which was represented in abstract form only.[81] Darum and Garretson reported on their experience in a single institution utilizing metoclopramide as a prokinetic in UGIB and found that metoclopramide did not improve visualization during endoscopy when compared with placebo.[166]

The potential side effects of metoclopramide, such as extrapyramidal symptoms or tardive dyskinesia are primarily associated with chronic use; however, due to an FDA black box warning on metoclopramide, the risks have to be balanced against the potential benefit in this setting.[167]

Eradication of H pylori can reduce the risk of rebleeding.[115]  Current anti-H pylori regimens include a variety of drug combinations.

The treatment regimens approved by FDA have 70%-90% H pylori eradication rates.[16]

The common regimens of “triple therapy” with a PPI, clarithromycin, and amoxicillin, or bismuth “quadruple therapy” consisting of a PPI, bismuth, tetracycline, and a nitroimidazole for 10-14 days remain as options for first-line therapy.

Clarithromycin resistance should be taken into consideration, as should previous macrolide exposure and penicillin allergy when considering a H pylori eradication regimen.

The 2017 American College of Gastroenterology (ACG) clinical guideline endorses additional regimens as potential first-line H pylori eradication therapy as follows[154] :

Aspirin and nonsteroidal anti-inflammatory agents (NSAIDs) are very common causes of ulcer bleeding. Antiplatelet drugs are often associated with an increased severity of UGIB and may pose unique challenges in management.[96, 97, 106, 168]

Discontinue NSAIDs when feasible in patients with bleeding from gastric or duodenal ulcers. Selective cyclooxygenase (COX)-2 inhibitors could be substituted, with a reduction in the risk of recurrent ulcer bleeding. Continued concomitant use of PPIs also reduces the risk of recurrent ulcer bleeding.

Take into account concerns for an associated risk of increased cardiovascular and/or cerebrovascular side effects in patients taking selective COX-2 inhibitors and the potential side effects associated with long-term PPI use when managing relative risk reduction.[152]

As noted earlier, al-Assi et al demonstrated that the combination of H pylori infection and NSAID use may increase the risk of ulcer hemorrhage; however, the treatment of H pylori in patients who are taking NSAIDs remains controversial.[1]

In general, aspirin and antithrombotic agents should be withheld until the bleeding is controlled, particularly if serious or life-threatening bleeding is apparent. In patients with significant risk factors or known cardiovascular indications for antithrombotic use, however, these agents should be started back as soon as possible.[168]  A study by Sung et al showed that in patients who had their aspirin held after treatment for a bleeding peptic ulcer, there was a clear increase in 30-day mortality, whereas those who continued taking their aspirin had no increased risk of postprocedure bleeding.[169]

Iron supplementation therapy is commonly used for anemia following UGIB. Oral iron and parenteral iron are both effective when compared with placebo.[170]

GI tolerance, cost, and availability should be considered when determining the best regimen for supplementation, if utilized.

Omeprazole (Prilosec, Prilosec OTC)

Clinical Context:  Omeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump. It usually is given with clarithromycin and amoxicillin (or metronidazole if the patient is allergic to penicillin) when administering proton pump inhibitor–based triple therapy. It might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in long-term NSAID users at high risk.

Lansoprazole (Prevacid, Prevacid 24HR, Prevacid Solu Tab)

Clinical Context:  Lansoprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump. It usually is given with clarithromycin and amoxicillin (or metronidazole if the patient is allergic to penicillin) when administering proton pump inhibitor–based triple therapy. It might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in long-term NSAID users at high risk.

Esomeprazole (Nexium, Nexium 24HR)

Clinical Context:  Esomeprazole is an S-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

Pantoprazole (Protonix)

Clinical Context:  Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Use of the intravenous preparation has only been studied for short-term use (ie, 7-10 d).

Class Summary

PPIs inhibit gastric acid secretion by inhibition of the H+/K+/ATPase enzyme system in the gastric parietal cells. IV therapy may be a useful adjunct via stabilization of the clot by increasing intragastric pH. High-dose intravenous treatment is the norm; however, high-dose oral therapy may be able to maintain the intragastric pH about 6 as well.[47]

Metoclopramide (Metozolv ODT, Reglan)

Clinical Context:  Metoclopramide blocks dopamine receptors (at high dose) and serotonin receptors in chemoreceptor trigger zone of the CNS; and sensitizes tissues to acetylcholine; increases upper GI motility but not secretions; increases lower esophageal sphincter tone.

Erythromycin ethylsuccinate (E.E.S., EryPed)

Clinical Context:  The prokinetic action of the macrolide antibiotic erythromycin is related to its action as a motilin-receptor agonist in the gut and gallblader to the stimulate GI tract.

Class Summary

The use of the prokinetics agent to empty the stomach of retained blood or clots to improve endoscopic visualization has been extensively studied. To date, four large randomized controlled trials and three meta-analyses have shown that erythromycin reduces the need for second-look endoscopy but did not significantly reduce clinical outcomes such as blood transfusions, hospital stay, or surgery.[81, 159, 160, 161, 162, 163, 164]

Bismuth subsalicylate (Kaopectate, Kaopectate Extra Strength, Maalox Total Relief)

Clinical Context:  This agent has a cytoprotective effect on the GI mucosa, probably due to the stimulation of prostaglandin production and modulation of the immune response. In addition, it has been demonstrated that some deposits (probably bismuth salts) appear on both surfaces of the cell wall of H pylori after H pylori from antral epithelium.

Aspirin (Acetylsalicylic acid, ASA, Bayer Advanced Aspirin)

Clinical Context:  Aspirin inhibits the synthesis of prostaglandin by cyclooxygenase; inhibits platelet aggregation; and has antipyretic and analgesic activity. It is metabolized by the liver via microsomal enzyme system.

Ranitidine (Zantac, Zantac 150 Maximum Strength, Zantac 75)

Clinical Context:  Ranitidine Reduces basal and nocturnal gastric acid secretion by competitive inhibition of binding of histamine to receptors (H2 receptor) on the gastric parietal cells. Although not effective as single agents for the eradication of H pylori, appears to increase the systemic absorption of bismuth subsalicylate.

Famotidine (Acid Controller, Act, Dyspep HB)

Clinical Context:  Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Ferrous sulfate (Feosol, Fer-In-Sol, Feratab)

Clinical Context:  Ferrous sulfate is the mainstay treatment for treating patients with iron deficiency anemia. They should be continued for about 2 months after correction of the anemia and its etiologic cause in order to replenish body stores of iron. Ferrous sulfate is the most common and cheapest form of iron utilized. Tablets contain 50-60 mg of iron salt. Other ferrous salts are used and may cause less intestinal discomfort because they contain a smaller dose of iron (25-50 mg). Oral solutions of ferrous iron salts are available for use in pediatric populations.

Carbonyl iron (Feosol (Carbonyl Fe), Icar C, Icar Pediatric)

Clinical Context:  Carbonyl iron is used as a substitute for ferrous sulfate. It has a slower release of iron and is more expensive than ferrous sulfate. The slower release affords the agent greater safety if ingested by children. On a milligram-for-milligram basis, it is 70% as efficacious as ferrous sulfate. Claims are made that there is less gastrointestinal (GI) toxicity, prompting use when ferrous salts are producing intestinal symptoms and in patients with peptic ulcers and gastritis. Tablets are available containing 45 mg and 60 mg of iron.

Ferric carboxymaltose (Injectafer)

Clinical Context:  Ferric carboxymaltose is a nondextran IV colloidal iron hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron. It is indicated for iron deficiency anemia (IDA) in adults who have intolerance or an unsatisfactory response to oral iron.

Ferrous gluconate (Fergon)

Clinical Context:  Ferrous gluconate replaces iron found in hemoglobin, myoglobin, and enzymes; allows the transportation of oxygen via hemoglobin. It is indicated in the prevention and treatment of iron-deficiency anemias.

Ferrous fumarate (Feostat, Ferro-Sequels, Hemocyte)

Clinical Context:  Ferrous fumarate is a replacement of iron stores found in hemoglobin, myoglobin, and enzymes; works to transport oxygen via hemoglobin. It is indicated in the prevention and treatment of iron-deficiency anemias.

Ferumoxytol (Feraheme)

Clinical Context:  Ferumoxytol is iron-carbohydrate complex released within macrophage vesicles; either enters intracellular iron storage (eg, ferritin) or transferred to plasma transferrin for transport to erythroid precursor cells for hemoglobin incorporation. It is indicated for iron deficiency anemia (IDA) in adults who have intolerance to oral iron or have had unsatisfactory response to oral iron.

Ferric maltol (Feraccru)

Clinical Context:  An oral iron replacement that delivers iron for uptake across the intestinal wall and transfer to transferrin and ferritin. It is indicated for iron deficiency in adults.

Class Summary

These agents are used to provide adequate iron for hemoglobin synthesis and to replenish body stores of iron.

Amoxicillin (Amoxil, Moxatag (DSC), Trimox)

Clinical Context:  Amoxicillin inhibits the final stage of bacterial cell wall synthesis by binding to specific PBPs on the inner part of the bacterial wall, leading to bacterial lysis.

Metronidazole (Flagyl, Flagyl ER, Flagyl IV RTU)

Clinical Context:  Metronidazole is reduced to its active form intracellularly only by anaerobic organisms, then disrupts the helical structure of DNA and inhibits bacterial nucleic acid synthesis.

Levofloxacin (Levaquin, Levofloxacin Systemic)

Clinical Context:  Levofloxacin is an L-stereoisomer of its parent compound ofloxacin; the D-isomer form is inactive

This agent inhibits DNA gyrase activity, which in turn promotes breakage of DNA strands.

Levofloxacin is a good monotherapy, with extended coverage against Pseudomonas spp, as well as excellent activity against pneumococcus.

Clarithromycin

Clinical Context:  Clarithromycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl tRNA from ribosomes, causing the arrest of RNA-dependent protein synthesis.

Ciprofloxacin (Cipro, Cipro XR, ProQuin XR)

Clinical Context:  Ciprofloxacin inhibits the relaxation of DNA; inhibits DNA gyrase in susceptible organisms; and promotes breakage of double-stranded DNA.

What are the signs and symptoms of upper gastrointestinal bleeding (UGIB)?How is upper gastrointestinal bleeding (UGIB) defined?Which tests are performed in the workup of upper gastrointestinal bleeding (UGIB)?When is CT scanning and ultrasonography indicated for the workup of upper gastrointestinal bleeding (UGIB)?Which interventions are used in the treatment of upper gastrointestinal bleeding (UGIB)?When is surgery indicated for the treatment of upper gastrointestinal bleeding (UGIB)?What is upper gastrointestinal bleeding (UGIB)?What is the role of peptic ulcer disease in the etiology of upper gastrointestinal bleeding (UGIB)?What is the risk of recurrent upper gastrointestinal bleeding (UGIB) in peptic ulcer disease?What are the major causes of upper gastrointestinal bleeding (UGIB)?What is the pathogenesis of ulcer-related upper gastrointestinal bleeding (UGIB)?How does vomiting cause upper gastrointestinal bleeding (UGIB)?What is the role of Mallory-Weiss tears in the etiology of upper gastrointestinal bleeding (UGIB)?What is the role of cute stress-related mucosal disease (stress ulcers) in the etiology of upper gastrointestinal bleeding (UGIB)?What is the role of Dieulafoy lesions in the etiology of upper gastrointestinal bleeding (UGIB)?What is the role of NSAIDS in the etiology of upper gastrointestinal bleeding (UGIB)?What is the prevalence of upper gastrointestinal bleeding (UGIB)?What are the sexual predilections of upper gastrointestinal bleeding (UGIB)?What is the mortality and morbidity associated with upper gastrointestinal bleeding (UGIB)?What is the prognosis for upper gastrointestinal bleeding (UGIB)?Which clinical history findings are characteristic of upper gastrointestinal bleeding (UGIB)?Which physical findings are characteristic of upper gastrointestinal bleeding (UGIB)?How is upper gastrointestinal bleeding (UGIB) categorized?Which conditions are included in the differential diagnoses of upper gastrointestinal bleeding (UGIB)?What are the differential diagnoses for Upper Gastrointestinal Bleeding (UGIB)?How is upper gastrointestinal bleeding (UGIB) assessed?How is hemorrhagic shock assessed in patients with upper gastrointestinal bleeding (UGIB)?What is the role of transfusion in the initial assessment of upper gastrointestinal bleeding (UGIB)?What is the role of a BMP in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of a coagulation profile in the workup of upper gastrointestinal bleeding (UGIB)?Which to risk-stratifying tools are used in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of endoscopy in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of capsule endoscopy (CE) in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of chest radiography in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of CT scanning in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of CTA in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of nuclear medicine scanning in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of angiography in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of MDCTA in the workup of upper gastrointestinal bleeding (UGIB)?What is the role of nasogastric lavage in the workup of upper GI bleeding (UGIB)?Which nasogastric lavage findings suggest upper GI bleeding (UGIB)?What is the prognostic value of nasogastric lavage findings in upper GI bleeding (UGIB)?How is nasogastric lavage visualization improved for the assessment of upper GI bleeding (UGIB)?Which histologic findings are characteristic of upper GI bleeding (UGIB)?What is the initial treatment for upper GI bleeding (UGIB)?What is the role of surgery in the treatment of upper GI bleeding (UGIB)?What are contraindications to surgery for upper gastrointestinal bleeding (UGIB)?What is the role of proton-pump inhibitors (PPIs) in the treatment of upper gastrointestinal bleeding (UGIB)?What is the efficacy of proton-pump inhibitors (PPIs) in preventing upper gastrointestinal bleeding (UGIB) in patients taking antiplatelet or anticoagulant therapy?What is the role of endoscopy in the treatment of upper gastrointestinal bleeding (UGIB)?When is urgent endoscopy indicated for the treatment of upper gastrointestinal bleeding (UGIB)?What is the efficacy of early endoscopy treatment of upper gastrointestinal bleeding (UGIB)?Which endoscopic techniques are used in the treatment of upper gastrointestinal bleeding (UGIB)?What is heater probe coagulation for upper gastrointestinal bleeding (UGIB)?What is bipolar electrocoagulation for upper gastrointestinal bleeding (UGIB)?What is the role of injection therapy in the treatment of upper gastrointestinal bleeding (UGIB)?What is the role of laser therapy in the treatment of upper gastrointestinal bleeding (UGIB)?What is the role of hemostatic clips in the treatment of upper gastrointestinal bleeding (UGIB)?What is the role of endoclips in the treatment of upper gastrointestinal bleeding (UGIB)?What is the role of argon plasma coagulation (APC) in the treatment of upper gastrointestinal bleeding (UGIB)?What is the role of hemostatic powders in the treatment of upper gastrointestinal bleeding (UGIB)?What is the role of Doppler ultrasonographic probes in the treatment of upper gastrointestinal bleeding (UGIB)?How is a specific endoscopic treatment selected for upper gastrointestinal bleeding (UGIB)?How are ulcers with an overlying blood clot treated?How is active upper gastrointestinal bleeding (UGIB) and rebleeding treated?What is the role of second-look endoscopy in the treatment of upper gastrointestinal bleeding (UGIB)?What is included in post-endoscopic monitoring of upper gastrointestinal bleeding (UGIB)?How is peptic ulcer-related upper gastrointestinal bleeding (UGIB) treated?When is surgery indicated for the treatment of peptic ulcer-related upper gastrointestinal bleeding (UGIB)?How is gastric ulcer-related upper gastrointestinal bleeding (UGIB) treated?How are gastric ulcers classified?What is the role of surgery in the treatment of gastric ulcer-related upper gastrointestinal bleeding (UGIB)?How is stress ulcer-related upper gastrointestinal bleeding (UGIB) treated?What is the role of surgery in the treatment of stress ulcer-related upper gastrointestinal bleeding (UGIB)?How is upper gastrointestinal bleeding (UGIB) caused by Mallory-Weiss syndrome treated?How is upper gastrointestinal bleeding (UGIB) caused by Dieulafoy lesions treated?How is upper gastrointestinal bleeding (UGIB) caused by angiodysplasia treated?How is upper gastrointestinal bleeding (UGIB) caused by aortoenteric fistula treated?What are the possible complications of upper gastrointestinal bleeding (UGIB) treatment?What is included in the long-term monitoring of upper gastrointestinal bleeding (UGIB)?How is upper gastrointestinal bleeding (UGIB) prevented?What is the role of medications in the treatment of upper gastrointestinal bleeding (UGIB)?What is the efficacy of PPIs in the treatment of upper gastrointestinal bleeding (UGIB)?How is H pylori eradicated?What is the role of prokinetics in the treatment of upper gastrointestinal bleeding (UGIB)?How should aspirin, NSAIDS and anti-thrombotics be managed in the presence of upper gastrointestinal bleeding (UGIB)?What is the role of iron supplements in the treatment of upper gastrointestinal bleeding (UGIB)?Which medications in the drug class Antibiotics are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?Which medications in the drug class Iron Products are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?Which medications in the drug class Histamine H2 Antagonists are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?Which medications in the drug class Non-steroidal Anti-inflammatory Drug are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?Which medications in the drug class H pylori Agents are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?Which medications in the drug class Prokinetic Agents are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?Which medications in the drug class Proton Pump Inhibitors are used in the treatment of Upper Gastrointestinal Bleeding (UGIB)?

Author

Bennie Ray Upchurch, III, MD, FACP, AGAF, FACG, FASGE, Staff Physician, Department of Gastroenterology, Licking Memorial Health Systems

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Maurice A Cerulli, MD, FACP, FACG, FASGE, AGAF, Associate Professor of Clinical Medicine, Albert Einstein College of Medicine of Yeshiva University; Associate Professor of Clinical Medicine, Hofstra Medical School

Disclosure: Nothing to disclose.

Shahzad Iqbal, MD, Advanced Endoscopy Fellow, Department of Gastroenterology, Columbia University Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

James de Caestecker, DO Instructor, Department of Surgery, MCP Hahnemann University

James de Caestecker, DO is a member of the following medical societies: American College of Surgeons

Disclosure: Nothing to disclose.

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Alex Jacocks, MD Program Director, Professor, Department of Surgery, University of Oklahoma School of Medicine

Disclosure: Nothing to disclose.

Jason Straus, MD Staff Physician, Department of Surgery, Wright State University School of Medicine

Jason Straus, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, and Society of American Gastrointestinal and Endoscopic Surgeons

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. al-Assi MT, Genta RM, Karttunen TJ, Graham DY. Ulcer site and complications: relation to Helicobacter pylori infection and NSAID use. Endoscopy. 1996 Feb. 28(2):229-33. [View Abstract]
  2. Frattaroli FM, Casciani E, Spoletini D, et al. Prospective study comparing multi-detector row CT and endoscopy in acute gastrointestinal bleeding. World J Surg. 2009 Oct. 33(10):2209-17. [View Abstract]
  3. Lam KL, Wong JC, Lau JY. Pharmacological treatment in upper gastrointestinal bleeding. Curr Treat Options Gastroenterol. 2015 Dec. 13(4):369-76. [View Abstract]
  4. Curdia-Goncalves T, Rosa B, Cotter J. New insights on an old medical emergency: non-portal hypertension related upper gastrointestinal bleeding. Rev Esp Enferm Dig. 2016 Oct. 108(10):648-56. [View Abstract]
  5. Lirio RA. Management of upper gastrointestinal bleeding in children: variceal and nonvariceal. Gastrointest Endosc Clin N Am. 2016 Jan. 26(1):63-73. [View Abstract]
  6. Fallah MA, Prakash C, Edmundowicz S. Acute gastrointestinal bleeding. Med Clin North Am. 2000 Sep. 84(5):1183-208. [View Abstract]
  7. Pongprasobchai S, Nimitvilai S, Chasawat J, Manatsathit S. Upper gastrointestinal bleeding etiology score for predicting variceal and non-variceal bleeding. World J Gastroenterol. 2009 Mar 7. 15(9):1099-104. [View Abstract]
  8. Straube S, Tramer MR, Moore RA, Derry S, McQuay HJ. Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. BMC Gastroenterol. 2009 Jun 5. 9:41. [View Abstract]
  9. Yavorski RT, Wong RK, Maydonovitch C, Battin LS, Furnia A, Amundson DE. Analysis of 3,294 cases of upper gastrointestinal bleeding in military medical facilities. Am J Gastroenterol. 1995 Apr. 90(4):568-73. [View Abstract]
  10. Stabile BE, Stamos MJ. Surgical management of gastrointestinal bleeding. Gastroenterol Clin North Am. 2000 Mar. 29(1):189-222. [View Abstract]
  11. Cheung FK, Lau JY. Management of massive peptic ulcer bleeding. Gastroenterol Clin North Am. 2009 Jun. 38(2):231-43. [View Abstract]
  12. Tiriveedhi K, Simon J, Cerulli MA. Does gastric lavage reduce the detection of Helicobacter pylori in the biopsy specimens?. Gastrointest Endosc. 2007 Apr. 65(5):AB312.
  13. Boonpongmanee S, Fleischer DE, Pezzullo JC, et al. The frequency of peptic ulcer as a cause of upper-GI bleeding is exaggerated. Gastrointest Endosc. 2004 Jun. 59(7):788-94. [View Abstract]
  14. Elmunzer BJ, Young SD, Inadomi JM, Schoenfeld P, Laine L. Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers. Am J Gastroenterol. 2008 Oct. 103(10):2625-32; quiz 2633. [View Abstract]
  15. Sung JJ, Tsoi KK, Ma TK, Yung MY, Lau JY, Chiu PW. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases. Am J Gastroenterol. 2010 Jan. 105(1):84-9. [View Abstract]
  16. Corson JD, Williamson RCN, eds. Surgery. London, UK: Mosby-Year Book; 2001.
  17. Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care. 2005 Mar. 20(1):35-45. [View Abstract]
  18. Cameron JL, ed. Current Surgical Therapy. 5th ed. St. Louis, Mo: Mosby-Year Book; 1995.
  19. Jensen DM, Machicado GA, Hirabayashi K. Randomized controlled study of 3 different types of hemoclips for hemostasis of bleeding canine acute gastric ulcers. Gastrointest Endosc. 2006 Nov. 64 (5):768-73. [View Abstract]
  20. Larson G, Schmidt T, Gott J, Bond S, O'Connor CA, Richardson JD. Upper gastrointestinal bleeding: predictors of outcome. Surgery. 1986 Oct. 100(4):765-73. [View Abstract]
  21. Reilly HF 3rd, al-Kawas FH. Dieulafoy's lesion. Diagnosis and management. Dig Dis Sci. 1991 Dec. 36(12):1702-7. [View Abstract]
  22. Pilotto A, Maggi S, Noale M, Franceschi M, Parisi G, Crepaldi G. Development and validation of a new questionnaire for the evaluation of upper gastrointestinal symptoms in the elderly population: a multicenter study. J Gerontol A Biol Sci Med Sci. 2010 Feb. 65(2):174-8. [View Abstract]
  23. Jairath V, Desborough MJ. Modern-day management of upper gastrointestinal haemorrhage. Transfus Med. 2015 Dec. 25(6):351-7. [View Abstract]
  24. Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol. 2005 Aug. 100(8):1685-93. [View Abstract]
  25. Peter DJ, Dougherty JM. Evaluation of the patient with gastrointestinal bleeding: an evidence based approach. Emerg Med Clin North Am. 1999 Feb. 17(1):239-61, x. [View Abstract]
  26. [Guideline] Adler DG, Leighton JA, Davila RE, et al, for ASGE. ASGE guideline: The role of endoscopy in acute non-variceal upper-GI hemorrhage. Gastrointest Endosc. 2004 Oct. 60(4):497-504. [View Abstract]
  27. Laine L, Shah A. Randomized trial of urgent vs. elective colonoscopy in patients hospitalized with lower GI bleeding. Am J Gastroenterol. 2010 Dec. 105(12):2636-41; quiz 2642. [View Abstract]
  28. Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. 2011 May. 124(5):426-33. [View Abstract]
  29. American College of Surgeons Committee on Trauma. Advanced Trauma Life Support Course Manual. Chicago, Ill: American College of Surgeons; 1997.
  30. Bornman PC, Theodorou NA, Shuttleworth RD, Essel HP, Marks IN. Importance of hypovolaemic shock and endoscopic signs in predicting recurrent haemorrhage from peptic ulceration: a prospective evaluation. Br Med J (Clin Res Ed). 1985 Jul 27. 291(6490):245-7. [View Abstract]
  31. Silverstein FE, Gilbert DA, Tedesco FJ, Buenger NK, Persing J. The national ASGE survey on upper gastrointestinal bleeding. II. Clinical prognostic factors. Gastrointest Endosc. 1981 May. 27(2):80-93. [View Abstract]
  32. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan 3. 368(1):11-21. [View Abstract]
  33. Waknine Y. GI bleeds: withholding transfusions boosts survival. Medscape Medical News. January 4, 2013. Available at http://www.medscape.com/viewarticle/777187. Accessed: January 15, 2013.
  34. [Guideline] Scottish Intercollegiate Guidelines Network (SIGN). Management of acute upper and lower gastrointestinal bleeding. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2008 Sep. (SIGN publication; no. 105):
  35. Peloquin JM, Seraj SM, King LY, Campbell EJ, Ananthakrishnan AN, Richter JM. Diagnostic and therapeutic yield of endoscopy in patients with elevated INR and gastrointestinal bleeding. Am J Med. 2016 Jun. 129 (6):628-34. [View Abstract]
  36. [Guideline] Schenker MP, Majdalany BS, Funaki BS, et al; and Expert Panel on Vascular Imaging and Interventional Radiology. ACR Appropriateness Criteria® upper gastrointestinal bleeding. [online publication]. Reston (VA): American College of Radiology (ACR); 2010.
  37. Chandran S, Testro A, Urquhart P, et al. Risk stratification of upper GI bleeding with an esophageal capsule. Gastrointest Endosc. 2013 Jun. 77(6):891-8. [View Abstract]
  38. Iwasaki H, Shimura T, Yamada T, et al. Novel nasogastric tube-related criteria for urgent endoscopy in nonvariceal upper gastrointestinal bleeding. Dig Dis Sci. 2013 Sep. 58(9):2564-71. [View Abstract]
  39. Monteiro S, Goncalves TC, Magalhaes J, Cotter J. Upper gastrointestinal bleeding risk scores: Who, when and why?. World J Gastrointest Pathophysiol. 2016 Feb 15. 7(1):86-96. [View Abstract]
  40. Baradarian R, Ramdhaney S, Chapalamadugu R, et al. Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol. 2004 Apr. 99(4):619-22. [View Abstract]
  41. Kaplan LJ, McPartland K, Santora TA, Trooskin SZ. Start with a subjective assessment of skin temperature to identify hypoperfusion in intensive care unit patients. J Trauma. 2001 Apr. 50(4):620-7; discussion 627-8. [View Abstract]
  42. Sarin N, Monga N, Adams PC. Time to endoscopy and outcomes in upper gastrointestinal bleeding. Can J Gastroenterol. 2009 Jul. 23(7):489-93. [View Abstract]
  43. Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978 Jan. 74(1):38-43. [View Abstract]
  44. Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med. 2007 Apr 19. 356(16):1631-40. [View Abstract]
  45. Barkun AN, Herba K, Adam V, Kennedy W, Fallone CA, Bardou M. High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis. Aliment Pharmacol Ther. 2004 Mar 1. 19(5):591-600. [View Abstract]
  46. Laine L, Shah A, Bemanian S. Intragastric pH with oral vs intravenous bolus plus infusion proton-pump inhibitor therapy in patients with bleeding ulcers. Gastroenterology. 2008 Jun. 134(7):1836-41. [View Abstract]
  47. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials. Mayo Clin Proc. 2007 Mar. 82(3):286-96. [View Abstract]
  48. Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ. 2005 Mar 12. 330(7491):568. [View Abstract]
  49. Cooper GS, Chak A, Way LE, Hammar PJ, Harper DL, Rosenthal GE. Early endoscopy in upper gastrointestinal hemorrhage: associations with recurrent bleeding, surgery, and length of hospital stay. Gastrointest Endosc. 1999 Feb. 49(2):145-52. [View Abstract]
  50. [Guideline] Barkun AN, Bardou M, Kuipers EJ, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010 Jan 19. 152(2):101-13. [View Abstract]
  51. Matsui S, Kamisako T, Kudo M, Inoue R. Endoscopic band ligation for control of nonvariceal upper GI hemorrhage: comparison with bipolar electrocoagulation. Gastrointest Endosc. 2002 Feb. 55(2):214-8. [View Abstract]
  52. Giday SA, Kim Y, Krishnamurty DM, 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. 2011 Apr. 43(4):296-9. [View Abstract]
  53. Vargas HE, Gerber D, Abu-Elmagd K. Management of portal hypertension-related bleeding. Surg Clin North Am. 1999 Feb. 79(1):1-22. [View Abstract]
  54. Cipolletta L, Bianco MA, Marmo R, et al. Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a prospective and randomized trial. Gastrointest Endosc. 2001 Feb. 53(2):147-51. [View Abstract]
  55. Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD. A prospective, randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic ulcer bleeding. Am J Gastroenterol. 2002 Sep. 97(9):2250-4. [View Abstract]
  56. Saltzman JR, Strate LL, Di Sena V, et al. Prospective trial of endoscopic clips versus combination therapy in upper GI bleeding (PROTECCT--UGI bleeding). Am J Gastroenterol. 2005 Jul. 100(7):1503-8. [View Abstract]
  57. Bini EJ, Cohen J. Endoscopic treatment compared with medical therapy for the prevention of recurrent ulcer hemorrhage in patients with adherent clots. Gastrointest Endosc. 2003 Nov. 58(5):707-14. [View Abstract]
  58. Freeman ML, Cass OW, Peine CJ, Onstad GR. The non-bleeding visible vessel versus the sentinel clot: natural history and risk of rebleeding. Gastrointest Endosc. 1993 May-Jun. 39(3):359-66. [View Abstract]
  59. Poxon VA, Keighley MR, Dykes PW, Heppinstall K, Jaderberg M. Comparison of minimal and conventional surgery in patients with bleeding peptic ulcer: a multicentre trial. Br J Surg. 1991 Nov. 78(11):1344-5. [View Abstract]
  60. Lau JY, Sung JJ, Lam YH, et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. N Engl J Med. 1999 Mar 11. 340(10):751-6. [View Abstract]
  61. Leontiadis GI, Howden CW. The role of proton pump inhibitors in the management of upper gastrointestinal bleeding. Gastroenterol Clin North Am. 2009 Jun. 38(2):199-213. [View Abstract]
  62. Targownik LE, Bolton JM, Metge CJ, Leung S, Sareen J. Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol. 2009 Jun. 104(6):1475-82. [View Abstract]
  63. So JB, Yam A, Cheah WK, Kum CK, Goh PM. Risk factors related to operative mortality and morbidity in patients undergoing emergency gastrectomy. Br J Surg. 2000 Dec. 87(12):1702-7. [View Abstract]
  64. Sadic J, Borgstrom A, Manjer J, Toth E, Lindell G. Bleeding peptic ulcer - time trends in incidence, treatment and mortality in Sweden. Aliment Pharmacol Ther. 2009 Aug 15. 30(4):392-8. [View Abstract]
  65. Jo Y, Matsumoto T, Aoyagi K, Yano Y, Kawasaki A, Fujishima M. Endoscopic band ligation device for bleeding gastric angiodysplasia. Gastrointest Endosc. 1999 Oct. 50(4):599. [View Abstract]
  66. Socrate AM, Rosati L, Locati P. Surgical treatment of aorto-enteric fistulas. Minerva Cardioangiol. 2001 Feb. 49(1):37-45. [View Abstract]
  67. Young RM, Cherry KJ Jr, Davis PM, et al. The results of in situ prosthetic replacement for infected aortic grafts. Am J Surg. 1999 Aug. 178(2):136-40. [View Abstract]
  68. Deshpande A, Lovelock M, Mossop P, Denton M, Vidovich J, Gurry J. Endovascular repair of an aortoenteric fistula in a high-risk patient. J Endovasc Surg. 1999 Nov. 6(4):379-84. [View Abstract]
  69. Lonn L, Dias N, Veith Schroeder T, Resch T. Is EVAR the treatment of choice for aortoenteric fistula?. J Cardiovasc Surg (Torino). 2010 Jun. 51(3):319-27. [View Abstract]
  70. Burks JA Jr, Faries PL, Gravereaux EC, Hollier LH, Marin ML. Endovascular repair of bleeding aortoenteric fistulas: a 5-year experience. J Vasc Surg. 2001 Dec. 34(6):1055-9. [View Abstract]
  71. Abou-Zamzam AM Jr, Bianchi C, Mazraany W, et al. Aortoenteric fistula development following endovascular abdominal aortic aneurysm repair: a case report. Ann Vasc Surg. 2003 Mar. 17(2):119-22. [View Abstract]
  72. Tseng PH, Liou JM, Lee YC, et al. Emergency endoscopy for upper gastrointestinal bleeding in patients with coronary artery disease. Am J Emerg Med. 2009 Sep. 27(7):802-9. [View Abstract]
  73. Penston JG, Wormsley KG. Review article: maintenance treatment with H2-receptor antagonists for peptic ulcer disease. Aliment Pharmacol Ther. 1992 Feb. 6(1):3-29. [View Abstract]
  74. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002 Jun 27. 346(26):2033-8. [View Abstract]
  75. Raskin JB, White RH, Jackson JE, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med. 1995 Sep 1. 123(5):344-50. [View Abstract]
  76. Podolsky I, Storms PR, Richardson CT, Peterson WL, Fordtran JS. Gastric adenocarcinoma masquerading endoscopically as benign gastric ulcer. A five-year experience. Dig Dis Sci. 1988 Sep. 33(9):1057-63. [View Abstract]
  77. Levine JE, Leontiadis GI, Sharma VK, Howden CW. Meta-analysis: the efficacy of intravenous H2-receptor antagonists in bleeding peptic ulcer. Aliment Pharmacol Ther. 2002 Jun. 16(6):1137-42. [View Abstract]
  78. Bai Y, Guo JF, Li ZS. Meta-analysis: erythromycin before endoscopy for acute upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2011 Jul. 34(2):166-71. [View Abstract]
  79. Barkun AN, Bardou M, Martel M, Gralnek IM, Sung JJ. Prokinetics in acute upper GI bleeding: a meta-analysis. Gastrointest Endosc. 2010 Dec. 72(6):1138-45. [View Abstract]
  80. Brooks M. Poorer peptic ulcer outcomes without H. pylori etiology. Reuters Health Information. July 9, 2013.
  81. Brooks M. SSRIs linked to upper GI bleeds. Medscape Medical News. September 24, 2013. Available at http://www.medscape.com/viewarticle/811547. Accessed: September 30, 2012.
  82. Chason RD, Reisch JS, Rockey DC. More favorable outcomes with peptic ulcer bleeding due to Helicobacter pylori. Am J Med. 2013 Sep. 126(9):811-18.e1. [View Abstract]
  83. Wang YP, Chen YT, Tsai CF, et al. Short-term use of serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding. Am J Psychiatry. 2014 Jan. 171(1):54-61. [View Abstract]
  84. [Guideline] Fujishiro M, Iguchi M, Kakushima N, et al. Guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding. Dig Endosc. 2016 May. 28(4):363-78. [View Abstract]
  85. Bonnet N, Paul J, Helleputte T, et al. Novel insights into the assessment of risk of upper gastrointestinal bleeding in decompensated cirrhotic children. Pediatr Transplant. 2019 Jun. 23(4):e13390. [View Abstract]
  86. Aoki T, Nagata N, Yamada A, et al. Next endoscopic approach for acute lower gastrointestinal bleeding without an identified source on colonoscopy: upper or capsule endoscopy?. Endosc Int Open. 2019 Mar. 7(3):E337-E346. [View Abstract]
  87. Micic D, Gaetano JN, Nigam N, et al. Risk factors for small bowel bleeding in an overt gastrointestinal bleeding presentation after negative upper and lower endoscopy. PLoS One. 2019. 14 (2):e0212509. [View Abstract]
  88. D'Souza D, et al. Upper gastrointestinal bleeding. Radiopaedia. Available at https://radiopaedia.org/articles/upper-gastrointestinal-bleeding?lang=us. Accessed: March 24, 2019.
  89. Barletta JF, Bruno JJ, Buckley MS, Cook DJ. Stress ulcer prophylaxis. Crit Care Med. 2016 Jul. 44(7):1395-405. [View Abstract]
  90. Bardou M, Quenot JP, Barkun A. Stress-related mucosal disease in the critically ill patient. Nat Rev Gastroenterol Hepatol. 2015 Feb. 12(2):98-107. [View Abstract]
  91. Quenot JP, Thiery N, Barbar S. When should stress ulcer prophylaxis be used in the ICU?. Curr Opin Crit Care. 2009 Apr. 15(2):139-43. [View Abstract]
  92. Michel L, Serrano A, Malt RA. Mallory-Weiss syndrome. Evolution of diagnostic and therapeutic patterns over two decades. Ann Surg. 1980 Dec. 192(6):716-21. [View Abstract]
  93. Kim BS, Li BT, Engel A, et al. Diagnosis of gastrointestinal bleeding: a practical guide for clinicians. World J Gastrointest Pathophysiol. 2014 Nov 15. 5(4):467-78. [View Abstract]
  94. Peery AF, Crockett SD, Barritt AS, et al. Burden of gastrointestinal, liver, and pancreatic diseases in the United States. Gastroenterology. 2015 Dec. 149(7):1731-1741.e3. [View Abstract]
  95. Schenker MP, Majdalany BS, Funaki BS, et al. ACR appropriateness criteria on upper gastrointestinal bleeding. J Am Coll Radiol. 2010 Nov. 7(11):845-53. [View Abstract]
  96. Norton JA, Foster DS, Ito T, Jensen RT. Gastrinomas: medical or surgical treatment. Endocrinol Metab Clin North Am. 2018 Sep. 47(3):577-601. [View Abstract]
  97. Patel SD, Desai R, Patel U, et al. Thirty-day readmissions after upper and lower gastrointestinal hemorrhage: a national perspective in the United States. J Clin Gastroenterol. 2019 Sep. 53 (8):582-90. [View Abstract]
  98. Stanley AJ, Laine L, Dalton HR, et al, for the International Gastrointestinal Bleeding Consortium. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study. BMJ. 2017 Jan 4. 356:i6432. [View Abstract]
  99. Abougergi MS, Charpentier JP, Bethea E, et al. A prospective, multicenter study of the AIMS65 Score compared with the Glasgow-Blatchford Score in predicting upper gastrointestinal hemorrhage outcomes. J Clin Gastroenterol. 2016 Jul. 50(6):464-9. [View Abstract]
  100. Robertson M, Majumdar A, Boyapati R, et al. Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems. Gastrointest Endosc. 2016 Jun. 83(6):1151-60. [View Abstract]
  101. Contreras-Omana R, Alfaro-Reynoso JA, Cruz-Chavez CE, et al. The Progetto Nazionale Emorragia Digestiva (PNED) system vs. the Rockall score as mortality predictors in patients with nonvariceal upper gastrointestinal bleeding: A multicenter prospective study. Rev Gastroenterol Mex. 2017 Apr - Jun. 82(2):123-8. [View Abstract]
  102. Shahrami A, Ahmadi S, Safari S. Full and modified Glasgow-Blatchford Bleeding Score in predicting the outcome of patients with acute upper gastrointestinal bleeding; a diagnostic accuracy study. Emerg (Tehran). 2018. 6(1):e31. [View Abstract]
  103. Cai JX, Saltzman JR. Initial assessment, risk stratification, and early management of acute nonvariceal upper gastrointestinal hemorrhage. Gastrointest Endosc Clin N Am. 2018 Jul. 28(3):261-75. [View Abstract]
  104. Spiegel BM, Vakil NB, Ofman JJ. Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review. Arch Intern Med. 2001 Jun 11. 161(11):1393-404. [View Abstract]
  105. Tsoi KK, Ma TK, Sung JJ. Endoscopy for upper gastrointestinal bleeding: how urgent is it?. Nat Rev Gastroenterol Hepatol. 2009 Aug. 6(8):463-9. [View Abstract]
  106. Wortman JR, Landman W, Fulwadhva UP, Viscomi SG, Sodickson AD. CT angiography for acute gastrointestinal bleeding: what the radiologist needs to know. Br J Radiol. 2017 Jul. 90(1075):20170076. [View Abstract]
  107. Lee HH, Park JM, Chun HJ, Oh JS, Ahn HJ, Choi MG. Transcatheter arterial embolization for endoscopically unmanageable non-variceal upper gastrointestinal bleeding. Scand J Gastroenterol. 2015 Jul. 50(7):809-15. [View Abstract]
  108. Kyaw M, Tse Y, Ang D, Ang TL, Lau J. Embolization versus surgery for peptic ulcer bleeding after failed endoscopic hemostasis: a meta-analysis. Endosc Int Open. 2014 Mar. 2(1):E6-E14. [View Abstract]
  109. Houist G, Guillaumot MA, Soyer P, Coriat R. [May CT scan replace endoscopy to diagnose upper GI bleeding?] [French]. Presse Med. 2018 Sep. 47(9):831-3. [View Abstract]
  110. Millward SF. ACR appropriateness criteria on treatment of acute nonvariceal gastrointestinal tract bleeding. J Am Coll Radiol. 2008 Apr. 5(4):550-4. [View Abstract]
  111. Shukla PA, Zybulewski A, Kolber MK, Berkowitz E, Silberzweig J, Hayim M. No catheter angiography is needed in patients with an obscure acute gastrointestinal bleed and negative CTA. Clin Imaging. 2017 May - Jun. 43:106-19. [View Abstract]
  112. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012 Mar. 107(3):345-60; quiz 361. [View Abstract]
  113. Aljebreen AM, Fallone CA, Barkun AN. Nasogastric aspirate predicts high-risk endoscopic lesions in patients with acute upper-GI bleeding. Gastrointest Endosc. 2004 Feb. 59(2):172-8. [View Abstract]
  114. Tu TC, Lee CL, Wu CH, et al. Comparison of invasive and noninvasive tests for detecting Helicobacter pylori infection in bleeding peptic ulcers. Gastrointest Endosc. 1999 Mar. 49(3 Pt 1):302-6. [View Abstract]
  115. Liao CC, Lee CL, Lai YC, et al. Accuracy of three diagnostic tests used alone and in combination for detecting Helicobacter pylori infection in patients with bleeding gastric ulcers. Chin Med J (Engl). 2003 Dec. 116(12):1821-6. [View Abstract]
  116. Choi YJ, Kim N, Lim J, et al. Accuracy of diagnostic tests for Helicobacter pylori in patients with peptic ulcer bleeding. Helicobacter. 2012 Apr. 17(2):77-85. [View Abstract]
  117. Ali Khan M, Howden CW. The role of proton pump inhibitors in the management of upper gastrointestinal disorders. Gastroenterol Hepatol (N Y). 2018 Mar. 14(3):169-75. [View Abstract]
  118. Sreedharan A, Martin J, Leontiadis GI, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Jul 7. CD005415. [View Abstract]
  119. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials. Mayo Clin Proc. 2007 Mar. 82(3):286-96. [View Abstract]
  120. Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med. 2007 Apr 19. 356(16):1631-40. [View Abstract]
  121. Buendgens L, Koch A, Tacke F. Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis. World J Crit Care Med. 2016 Feb 4. 5(1):57-64. [View Abstract]
  122. Weisman SM, Graham DY. Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch Intern Med. 2002 Oct 28. 162(19):2197-202. [View Abstract]
  123. [Guideline] US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Mar 17. 150(6):396-404. [View Abstract]
  124. Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016 Dec. 151(6):1105-1112.e10. [View Abstract]
  125. Agewall S, Cattaneo, Collet JP, et al, for the ESC Working Group on Cardiovascular Pharmacology and Drug Therapy and ESC Working Group on Thrombosis. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J. 2013 Jun. 34(23):1708-13, 1713a-1713b. [View Abstract]
  126. [Guideline] Hwang JH, Fisher DA, Ben-Menachem T, et al, for the Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc. 2012 Jun. 75(6):1132-8. [View Abstract]
  127. Jeong N, Kim KS, Jung YS, Kim T, Shin SM. Delayed endoscopy is associated with increased mortality in upper gastrointestinal hemorrhage. Am J Emerg Med. 2019 Feb. 37(2):277-80. [View Abstract]
  128. Lim LG, Ho KY, Chan YH, et al. Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. Endoscopy. 2011 Apr. 43(4):300-6. [View Abstract]
  129. Tai CM, Huang SP, Wang HP, et al. High-risk ED patients with nonvariceal upper gastrointestinal hemorrhage undergoing emergency or urgent endoscopy: a retrospective analysis. Am J Emerg Med. 2007 Mar. 25(3):273-8. [View Abstract]
  130. Schacher GM, Lesbros-Pantoflickova D, Ortner MA, Wasserfallen JB, Blum AL, Dorta G. Is early endoscopy in the emergency room beneficial in patients with bleeding peptic ulcer? A "fortuitously controlled" study. Endoscopy. 2005 Apr. 37(4):324-8. [View Abstract]
  131. [Guideline] 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 Oct. 47(10):a1-46. [View Abstract]
  132. Gupta A, Agarwal R, Ananthakrishnan AN. "Weekend effect" in patients with upper gastrointestinal hemorrhage: A systematic review and meta-analysis. Am J Gastroenterol. 2018 Jan. 113(1):13-21. [View Abstract]
  133. Liu L, Hao D, Liu W, Wang L, Wang X. Does weekend hospital admission affect upper gastrointestinal hemorrhage outcomes?: A systematic review and network meta-analysis. J Clin Gastroenterol. 2018 Aug 16. [View Abstract]
  134. Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol. 2009 Jan. 7(1):33-47; quiz 1-2. [View Abstract]
  135. Jiang Y, Hu J, Li P, Jiang W, Liang W, Wei H. A retrospective analysis of cyanoacrylate injection versus hemoclip placement for bleeding Dieulafoy's lesion in duodenum. Gastroenterol Res Pract. 2018. 2018:3208690. [View Abstract]
  136. Martinez-Alcala A, Monkemuller K. Emerging endoscopic treatments for nonvariceal upper gastrointestinal hemorrhage. Gastrointest Endosc Clin N Am. 2018 Jul. 28(3):307-20. [View Abstract]
  137. Jensen DM, Machicado GA. Hemoclipping of chronic canine ulcers: a randomized, prospective study of initial deployment success, clip retention rates, and ulcer healing. Gastrointest Endosc. 2009 Nov. 70(5):969-75. [View Abstract]
  138. Chan SM, Chiu PW, Teoh AY, Lau JY. Use of the Over-the-Scope Clip for treatment of refractory upper gastrointestinal bleeding: a case series. Endoscopy. 2014 May. 46(5):428-31. [View Abstract]
  139. Manno M, Mangiafico S, Caruso A, et al. First-line endoscopic treatment with OTSC in patients with high-risk non-variceal upper gastrointestinal bleeding: preliminary experience in 40 cases. Surg Endosc. 2016 May. 30(5):2026-9. [View Abstract]
  140. Haddara S, Jacques J, Lecleire S, et al. A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the "GRAPHE" registry). Endoscopy. 2016 Dec. 48(12):1084-95. [View Abstract]
  141. Changela K, Papafragkakis H, Ofori E, et al. Hemostatic powder spray: a new method for managing gastrointestinal bleeding. Therap Adv Gastroenterol. 2015 May. 8(3):125-35. [View Abstract]
  142. Cahyadi O, Bauder M, Meier B, Caca K, Schmidt A. Effectiveness of TC-325 (Hemospray) for treatment of diffuse or refractory upper gastrointestinal bleeding - a single center experience. Endosc Int Open. 2017 Nov. 5(11):E1159-E1164. [View Abstract]
  143. Ghassemi KA, Jensen DM. The cutting edge: Doppler probe in guiding endoscopic hemostasis. Gastrointest Endosc Clin N Am. 2018 Jul. 28(3):321-30. [View Abstract]
  144. Jensen DM, Ohning GV, Kovacs TO, et al. Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding. Gastrointest Endosc. 2016 Jan. 83(1):129-36. [View Abstract]
  145. Jensen DM, Kovacs TOG, Ohning GV, et al. Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes of patients with severe nonvariceal upper gastrointestinal hemorrhage. Gastroenterology. 2017 May. 152(6):1310-1318.e1. [View Abstract]
  146. Marmo R, Rotondano G, Bianco MA, Piscopo R, Prisco A, Cipolletta L. Outcome of endoscopic treatment for peptic ulcer bleeding: Is a second look necessary? A meta-analysis. Gastrointest Endosc. 2003 Jan. 57(1):62-7. [View Abstract]
  147. Park SJ, Park H, Lee YC, et al. Effect of scheduled second-look endoscopy on peptic ulcer bleeding: a prospective randomized multicenter trial. Gastrointest Endosc. 2018 Feb. 87(2):457-65. [View Abstract]
  148. Scarpignato C, Gatta L, Zullo A, Blandizzi C, for the SIF-AIGO-FIMMG Group, on behalf of the Italian Society of Pharmacology, et al. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016 Nov 9. 14(1):179. [View Abstract]
  149. Liu B, Liu S, Yin A, Siddiqi J. Risks and benefits of stress ulcer prophylaxis in adult neurocritical care patients: a systematic review and meta-analysis of randomized controlled trials. Crit Care. 2015 Nov 17. 19:409. [View Abstract]
  150. [Guideline] Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb. 112(2):212-39. [View Abstract]
  151. [Guideline] Malfertheiner P, Megraud F, O'Morain CA, et al, for the European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan. 66(1):6-30. [View Abstract]
  152. [Guideline] Apfelbaum JL, Caplan RA, Connis RT, et al, for the American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: an updated report by the American Society of Anesthesiologists Committee on Standards and Practice Parameters. Anesthesiology. 2011 Mar. 114(3):495-511. [View Abstract]
  153. Pirlamarla P, Bond RM. FDA labeling of NSAIDs: Review of nonsteroidal anti-inflammatory drugs in cardiovascular disease. Trends Cardiovasc Med. 2016 Nov. 26(8):675-80. [View Abstract]
  154. Nissen SE, Yeomans ND, Solomon DH, et al, for the PRECISION Trial Investigators. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016 Dec 29. 375(26):2519-29. [View Abstract]
  155. Carbonell N, Pauwels A, Serfaty L, Boelle PY, Becquemont L, Poupon R. Erythromycin infusion prior to endoscopy for acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Am J Gastroenterol. 2006 Jun. 101(6):1211-5. [View Abstract]
  156. Coffin B, Pocard M, Panis Y, et al, for the Groupe des endoscopistes de garde á l'AP-HP. Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study. Gastrointest Endosc. 2002 Aug. 56(2):174-9. [View Abstract]
  157. Frossard JL, Spahr L, Queneau PE, et al. Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Gastroenterology. 2002 Jul. 123(1):17-23. [View Abstract]
  158. Theivanayagam S, Lim RG, Cobell WJ, et al. Administration of erythromycin before endoscopy in upper gastrointestinal bleeding: a meta-analysis of randomized controlled trials. Saudi J Gastroenterol. 2013 Sep-Oct. 19(5):205-10. [View Abstract]
  159. Szary NM, Gupta R, Choudhary A, et al. Erythromycin prior to endoscopy in acute upper gastrointestinal bleeding: a meta-analysis. Scand J Gastroenterol. 2011 Jul. 46(7-8):920-4. [View Abstract]
  160. Pateron D, Vicaut E, Debuc E, et al, for the HDUPE Collaborative Study Group. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. Ann Emerg Med. 2011 Jun. 57(6):582-9. [View Abstract]
  161. Daram SR, Garretson R. Erythromycin is preferable to metoclopramide as a prokinetic in acute upper GI bleeding. Gastrointest Endosc. 2011 Jul. 74(1):234; author reply 234-5. [View Abstract]
  162. Ehrenpreis ED, Deepak P, Sifuentes H, Devi R, Du H, Leikin JB. The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits. Am J Gastroenterol. 2013 Jun. 108(6):866-72. [View Abstract]
  163. [Guideline] Acosta RD, Abraham NS, Chandrasekhara V, et al, for the ASGE Standards of Practice Committee. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016 Jan. 83(1):3-16. [View Abstract]
  164. Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010 Jan 5. 152(1):1-9. [View Abstract]
  165. Bager P, Dahlerup JF. Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage--a placebo-controlled study. Aliment Pharmacol Ther. 2014 Jan. 39(2):176-87. [View Abstract]
  166. Toews I, George AT, Peter JV, et al. Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units. Cochrane Database Syst Rev. 2018 Jun 4. 6:CD008687. [View Abstract]
  167. Mavrogenis G, Del Natale M. Hemostatic clips and magnetic resonance imaging. Are there any compatibility issues?. Endoscopy. 2013 Nov. 45(11):933. [View Abstract]
  168. Honegger C, Valli PV, Wiegand N, Bauerfeind P, Gubler C. Establishment of Over-The-Scope-Clips (OTSC) in daily endoscopic routine. United European Gastroenterol J. 2017 Mar. 5(2):247-54. [View Abstract]
  169. Kim JW, Jang JY, Lee CK, Shim JJ, Chang YW. Comparison of hemostatic forceps with soft coagulation versus argon plasma coagulation for bleeding peptic ulcer--a randomized trial. Endoscopy. 2015 Aug. 47(8):680-7. [View Abstract]
  170. Lee SD, Kearney DJ. A randomized controlled trial of gastric lavage prior to endoscopy for acute upper gastrointestinal bleeding. J Clin Gastroenterol. 2004 Nov-Dec. 38(10):861-5. [View Abstract]
  171. Ponsky JL, Hoffman M, Swayngim DS. Saline irrigation in gastric hemorrhage: the effect of temperature. J Surg Res. 1980 Mar. 28(3):204-5. [View Abstract]
  172. Jensen DM, Markovic D, Jensen ME, Gornbein J. 784 Red cell transfusions do not increase 30 day mortality rates for unselected patients with severe UGI hemorrhage. Gastroenterology. 2015 Apr. 148(4) Suppl 1:S-154.
  173. Holst LB, Petersen MW, Haase N, Perner A, Wetterslev J. Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. BMJ. 2015 Mar 24. 350:h1354. [View Abstract]
  174. Schultz NH, Tran HTT, Bjornsen S, Henriksson CE, Sandset PM, Holme PA. The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor. Thromb J. 2017. 15:6. [View Abstract]
  175. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015 Aug 6. 373(6):511-20. [View Abstract]
  176. Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015 Aug 15. 386(9994):680-90. [View Abstract]
  177. Yachimski PS, Farrell EA, Hunt DP, Reid AE. Proton pump inhibitors for prophylaxis of nosocomial upper gastrointestinal tract bleeding: effect of standardized guidelines on prescribing practice. Arch Intern Med. 2010 May 10. 170 (9):779-83. [View Abstract]
  178. Worden JC, Hanna KS. Optimizing proton pump inhibitor therapy for treatment of nonvariceal upper gastrointestinal bleeding. Am J Health Syst Pharm. 2017 Feb 1. 74 (3):109-16. [View Abstract]
  179. Laine L. Clinical practice. Upper gastrointestinal bleeding due to a peptic ulcer. N Engl J Med. 2016 Jun 16. 374 (24):2367-76. [View Abstract]
  180. [Guideline] Garcia-Iglesias P, Botargues JM, Feu Caballe F, et al. Management of non variceal upper gastrointestinal bleeding: position statement of the Catalan Society of Gastroenterology. Gastroenterol Hepatol. 2017 May. 40 (5):363-74. [View Abstract]
  181. Norton ID, Petersen BT, Sorbi D, Balm RK, Alexander GL, Gostout CJ. Management and long-term prognosis of Dieulafoy lesion. Gastrointest Endosc. 1999 Dec. 50 (6):762-7. [View Abstract]
  182. Alexandrino G, Carvalho R, Reis J. Comparison of the AIMS65 score with other risk stratification scores in upper variceal and nonvariceal gastrointestinal bleeding. Gut Liver. 2018 Jan 15. 12 (1):111-3. [View Abstract]
  183. Gu L, Xu F, Yuan J. Comparison of AIMS65, Glasgow-Blatchford and Rockall scoring approaches in predicting the risk of in-hospital death among emergency hospitalized patients with upper gastrointestinal bleeding: a retrospective observational study in Nanjing, China. BMC Gastroenterol. 2018 Jun 28. 18 (1):98. [View Abstract]
  184. Saltzman JR, Tabak YP, Hyett BH, Sun X, Travis AC, Johannes RS. A simple risk score accurately predicts in-hospital mortality, length of stay, and cost in acute upper GI bleeding. Gastrointest Endosc. 2011 Dec. 74 (6):1215-24. [View Abstract]
  185. Nardelli S, Gioia S, Ridola L, Farcomeni A, Merli M, Riggio O. Proton pump inhibitors are associated with minimal and overt hepatic encephalopathy and increased mortality in patients with cirrhosis. Hepatology. 2019 Aug. 70 (2):640-9. [View Abstract]

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.

Upper gastrointestinal bleeding (UGIB). Ulcer with a clean base.

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a clean base.

Upper gastrointestinal bleeding (UGIB). Ulcer with an overlying clot.

Upper gastrointestinal bleeding (UGIB). Ulcer with a visible vessel.

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a visible vessel.

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a clean base.

Upper gastrointestinal bleeding (UGIB). Ulcer with a visible vessel.

Upper gastrointestinal bleeding (UGIB). Ulcer with active bleeding.

Upper gastrointestinal bleeding (UGIB). Ulcer with a clean base.

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a clean base.

Upper gastrointestinal bleeding (UGIB). Ulcer with an overlying clot.

Upper gastrointestinal bleeding (UGIB). Ulcer with a visible vessel.

Upper gastrointestinal bleeding (UGIB). Diagram of an ulcer with a visible vessel.

Clinical Indicator Probability of Upper GI Source Probability of Lower GI Source
HematemesisAlmost certainRare
MelenaProbablePossible
HematocheziaPossibleProbable
Blood-streaked stoolRareAlmost certain
Occult blood in stoolPossiblePossible
GI = gastrointestinal.
  Class 1 Class 2 Class 3 Class 4
Blood Loss, mL Up to 750750-15001500-2000>2000
Blood Loss, % blood volume Up to 1515-3030-40>40
Pulse Rate, bpm < 100>100>120>140
Blood Pressure NormalNormalDecreasedDecreased
Respiratory Rate Normal or IncreasedDecreasedDecreasedDecreased
Urine Output, mL/h >3530-4020-3014-20
CNS/Mental Status Slightly



anxious



Mildly



anxious



Anxious,



confused



Confused,



lethargic



Fluid Replacement, 3-for-1 rule CrystalloidCrystalloidCrystalloid and bloodCrystalloid and blood
bpm = beats per minute; CNS = central nervous system
Number of Units TransfusedNeed for Surgery, %Mortality, %
044
1-3614
4-51728
>55743
Nasogastric Aspirate Color Stool Color Mortality, %
ClearBrown or red6
Coffee-groundBrown or black8.2
Red19.1
Red bloodBlack12.3
Brown19.4
Red28.7
UGIB = upper gastrointestinal bleeding.
Ulcer Characteristics Prevalence Rate, % Rebleeding Rate, % Surgery Rate, % Mortality, %
Clean base4250.52
Flat spot201063
Adherent clot1722107
Visible vessel17433411
Active bleeding18553511