This is a grade IIa ulcer (Forrest classification), with a high risk of recurrence. Therefore, endoscopic treatment and hospitalization with intravenous treatment with PPIs (in our setting it is usually omeprazole) for at least 72 hours is clearly indicated. Surgery is indicated in massive bleeding or bleeding refractory to medical treatment.

A 52-year-old man with no concomitant diseases comes to the emergency department for melena of 24 hours evolution without hemodynamic repercussions. He denies taking nonsteroidal anti-inflammatory drugs. The hematocrit is 33% and the rest of the laboratory tests are normal. The upper gastrointestinal endoscopy performed urgently 6 hours after admission shows a normal stomach, without blood or hematic debris and an excavated ulcer of 8 mm in diameter in the anterior face of the duodenal bulb with "visible vessel" at its base and without active bleeding. Which of the following statements is true?

In the initial endoscopy it is indicated to apply an endoscopic therapy and subsequently to establish endovenous treatment with high doses of a proton pump inhibitor. This strategy has been shown to reduce the risk of hemorrhagic recurrence and mortality.

In the initial endoscopy, given the absence of active bleeding, endoscopic therapy is not indicated. Subsequently, to reduce the risk of hemorrhagic recurrence, intravenous treatment with high doses of a proton pump inhibitor should be started.

n initial endoscopy, endoscopic therapy is indicated. Subsequent treatment with high doses of a proton pump inhibitor has not been shown to be of any additional benefit.

Since this is a complicated ulcer (hemorrhage) the best therapeutic option, once the hemorrhagic episode is resolved, is a vagotomy and pyloroplasty.

Treatment of nonvariceal upper gastrointestinal bleeding.

The etiology, pathophysiology, prognostic factors, pharmacologic treatment, and pharmacoeconomic considerations of nonvariceal upper-gastrointestinal-tract bleeding (UGB) are reviewed. UGB is associated with substantial morbidity and mortality. While UGB can be caused by a wide variety of medical conditions, 50% of UGB cases are caused by peptic ulcers. Approximately 80% of all UGB episodes stop bleeding spontaneously. Recurrence of gastrointestinal hemorrhage is associated with an increased mortality rate, a greater need for surgery, blood transfusions, a prolonged length of hospital stay, and increased overall health care costs. All patients with UGB should be evaluated for signs and symptoms of hemodynamic instability and active hemorrhage. Endoscopy within the first 24 hours of a UGB episode is considered the standard of therapy for the management of the initial hemorrhage. However, approximately 20% of patients will experience a rebleeding episode. Acid-suppressive therapy with proton-pump inhibitors (PPIs) in addition to endoscopic hemostasis is effective in reducing the frequency of rebleeding, the need for surgery, transfusion requirements, and the length of hospital stay, but not mortality rates. There are multiple dosing options for administration of PPIs in this setting. More studies are necessary to elucidate the best therapeutic approach to manage UGB. Acid-suppressive therapy is beneficial in the management of UGB. It reduces the frequency of rebleeding, the need for surgery, transfusion requirements, and the length of hospital stay. To date, no pharmacologic intervention has demonstrated a reduction in the mortality rates of patients with UGB. An optimal acid-suppressive regimen has not yet been clearly established.

[Gastrointestinal bleeding].

In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes.

Proton pump inhibitors and recurrent bleeding in peptic ulcer disease.

Peptic ulcer disease (PUD) is one of the main lesions responsible for upper gastrointestinal (GI) bleeding, as well as esophageal varices and Mallory-Weiss tear. Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin are the major responsible causes. In cases of upper GI bleeding, urgent endoscopy is performed after stabilization of vital signs. There are several modalities for controlling bleeding in PUD, such as ethanol injection or hypertonic saline with epinephrine. Recurrent bleeding occurs in 20% of patients after endoscopic therapy. The combination of endoscopic intervention and a proton pump inhibitor (PPI) is necessary to achieve hemostasis of active bleeding. It has been reported that high-dose omeprazole (80 mg bolus injection, then 8 mg/h continuous infusion for 72 h, then 40 mg/day orally for 1 week) can reduce recurrent bleeding, the need for surgery and mortality from hemorrhagic shock in patients with high-risk peptic ulcer bleeding, as compared with standard-dose omeprazole. The metabolism of PPIs is dependent upon P450 2C19 genotypes and the clinical usefulness of genotypic analysis remains to be determined.

Management of patients with ulcer bleeding.

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy.

[Peptic ulcer disease and H. pylori gastritis: key advances in clinical management].

Helicobacter pylori (H. pylori) gastritis and non-steroidal anti-inflammatory drug (NSAID) intake are the most important risk factors for peptic ulcer disease (PUD) and ulcer bleeding. H. pylori infection was shown to increase the risk of ulcer bleeding in patients with PUD who are taking NSAID, aspirin, or another antiplatelet drug. H. pylori-positive patients on combined platelet aggregation inhibition are at the highest risk of bleeding. Evidence-based interdisciplinary treatment recommendations for the safe use of NSAID have been released. For patients with a moderate risk of PUD, the combination of NSAID and a proton pump inhibitor (PPI) or a monotherapy with a selective cyclooxygenase-2 (COX-2) inhibitor is recommended, whereas patients with a high risk of bleeding should receive a combination of a selective COX-2 inhibitor and a PPI. According to a recent randomized trial, hemodynamically stable patients with signs of upper gastrointestinal bleeding and an increased risk of death (Glasgow-Blatchford Score ≥ 12) undergoing endoscopy 6-24 after consultation do not have any disadvantage in terms of 30-day mortality compared to patients receiving endoscopy within 6 hours. After successful endoscopic hemostasis, additional prophylactic angiographic embolization does not reduce the risk of recurrent bleeding. Successful H. pylori eradication reduces the risk of developing gastric cancer (GC) in first-degree relatives of patients with GC by 73 %. In patients with successful endoscopic treatment of early GC, H. pylori testing with subsequent eradication also halves the rate of metachronous GC. Clarithromycin-based triple therapy for H. pylori eradication shows a decreasing effectiveness due to increasing antibiotic resistance, especially against macrolides. Accordingly, bismuth-containing quadruple therapy is widely recommended as the standard empiric first-line therapy.

Effect of scheduled second-look endoscopy on peptic ulcer bleeding: a prospective randomized multicenter trial.

This study aimed to investigate the effectiveness of scheduled second-look endoscopy (EGD) with endoscopic hemostasis on peptic ulcer rebleeding and to identify the risk factors related to the need for second-look EGD. We prospectively randomized patients who had endoscopically confirmed bleeding peptic ulcer with stigmata of active bleeding, visible vessel, or adherent clot into 2 groups between August 2010 and January 2013. Hemoclip application or thermal coagulation and/or epinephrine injection were allowed for initial endoscopic therapy. The same dosage of proton pump inhibitor was injected intravenously. The study group received scheduled second-look EGD 24 to 36 hours after the initial hemostasis, and further therapy was applied if endoscopic stigmata persisted, as above. Those patients who developed rebleeding underwent operation or radiologic intervention despite the additional endoscopic therapy. Outcome measures included rebleeding, amount of transfusion, duration of hospitalization, and mortality. After initial endoscopic hemostasis, 319 eligible patients were randomized into 2 groups. Sixteen (10.1%) and 9 (5.6%) patients developed rebleeding (P = .132), respectively. There was also no difference in surgical intervention (0, 0% vs 1, .6%, P >.999) or radiologic intervention (3, 1.9% vs 2, 1.2%, P = .683), median duration of hospitalization (6.0 vs 5.0 days, P = .151), amount of transfusion (2.4 ± 1.7 vs 2.2 ± 1.6 units, P = .276), and mortality (2, 1.3% vs 2, 1.2%, P > .999) between the 2 groups. Multivariate analysis showed that grades 3 to 4 of endoscopists' estimation to success of initial hemostasis, history of nonsteroidal anti-inflammatory drug (NSAID) use, and larger amounts of blood transfusions (≥4 units of red blood cells) were the independent risk factors of rebleeding. A single EGD with endoscopic hemostasis is not inferior to scheduled second-look endoscopy in terms of reduction in rebleeding rate of peptic ulcer bleeding. Repeat endoscopy would be helpful in the patients with unsatisfactory initial endoscopic hemostasis, use of NSAIDs, and larger amounts of transfused blood. (Clinical trial registration number: KCT0000565; 4-2010-0348.).

Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).

Effect of intravenous proton pump inhibitor regimens and timing of endoscopy on clinical outcomes of peptic ulcer bleeding.

The most effective schedule of proton pump inhibitor (PPI) administration and the optimal timing of endoscopy in acute peptic ulcer bleeding remain uncertain. The aim of this study was to determine the most efficient PPI regimen and optimal timing of endoscopy.   Consecutive patients with suspected bleeding peptic ulcers were enrolled and randomized to receive either a standard regimen or a high-dose intensive intravenous regimen. Only patients with bleeding peptic ulcers diagnosed at initial endoscopy continued the study. High-risk patients received endoscopic hemostasis. The primary outcome measure of recurrent bleeding was compared between the two dosage regimens and between early and late endoscopy. Secondary outcome measures compared included need for endoscopic treatment, blood transfusion, hospital stay, surgery and mortality. A total of 875 patients completed the study. Recurrent bleeding occurred in 11.0% in the standard regimen group, statistically higher than that in the intensive regimen group (6.4%, P=0.02). Mean units of blood transfused and duration of hospital stay were also higher in the standard regimen group (P<0.001 for each compared to intensive regimen group). However, no significant differences were noted between the two groups in the need for endoscopic hemostasis, need for surgery, and mortality. Recurrence of bleeding was similar between the early and late endoscopy groups. Units of blood transfused and length of hospital stay were both significantly reduced with early endoscopy. High-dose PPI infusion is more efficacious in reducing rebleeding rate, blood transfusion requirements and hospital stay. Early endoscopy is safe and more effective than late endoscopy.

Management of acute upper gastrointestinal bleeding.

Upper gastrointestinal bleeding (UGIB) is a common medical emergency, with a reported mortality of 2-10%. Patients identified as being at very low risk of either needing an intervention or death can be managed as outpatients. For all other patients, intravenous fluids as needed for resuscitation and red cell transfusion at a hemoglobin threshold of 70-80 g/L are recommended. After resuscitation is initiated, proton pump inhibitors (PPIs) and the prokinetic agent erythromycin may be administered, with antibiotics and vasoactive drugs recommended in patients who have cirrhosis. Endoscopy should be undertaken within 24 hours, with earlier endoscopy considered after resuscitation in patients at high risk, such as those with hemodynamic instability. Endoscopic treatment is used for variceal bleeding (for example, ligation for esophageal varices and tissue glue for gastric varices) and for high risk non-variceal bleeding (for example, injection, thermal probes, or clips for lesions with active bleeding or non-bleeding visible vessel). Patients who require endoscopic therapy for ulcer bleeding should receive high dose proton pump inhibitors after endoscopy, whereas those who have variceal bleeding should continue taking antibiotics and vasoactive drugs. Recurrent ulcer bleeding is treated with repeat endoscopic therapy, with subsequent bleeding managed by interventional radiology or surgery. Recurrent variceal bleeding is generally treated with transjugular intrahepatic portosystemic shunt. In patients who require antithrombotic agents, outcomes appear to be better when these drugs are reintroduced early.

Peptic ulcer disease

Early endoscopic therapy can help to stop bleeding by using cautery, endoclip, or epinephrine injection. Treatment is indicated if there is active bleeding in the stomach, visible vessels, or an adherent clot. Endoscopy is also helpful in identifying people who are suitable for hospital discharge. Prokinetic agents such as erythromycin and metoclopramide can be given before endoscopy to improve endoscopic view. Either high- or low-dose PPIs are equally effective in reducing bleeding after endoscopy. High-dose intravenous PPI is defined as a bolus dose of 80 mg followed by an infusion of 8 mg per hour for 72 hours—in other words, the continuous infusion of PPI of greater than 192 mg per day. Intravenous PPI can be changed to oral once there is no high risk of rebleeding from peptic ulcer.

Management of bleeding peptic ulcer: current status of intravenous proton pump inhibitors.

Over 80% of ulcer bleeding stops spontaneously, but associated mortality and morbidity remain high. Occurrence of re-bleeding increases mortality 10-fold. Endoscopic findings in those that have bled predict the risk of recurrent bleeding. Patients whose ulcers show a 'flat dot' or clean base (Forrest Class 3) rarely rebleed or need hospitalization. However, actively bleeding ulcers or those with evidence of recent hemorrhage (Forrest Classes 1 and 2) are likely to re-bleed and may need intensive care. Meta-analyses indicate that endoscopic hemostasis has reduced re-bleeding and surgical intervention by over 60% and mortality by 45%. Beyond these reductions, data indicate that (unlike H2-receptor antagonists use, largely devoid of benefits in this area) continuous intravenous infusions of high doses of proton pump inhibitors reduce rebleeding, re-endoscopy, blood transfusion and surgical intervention, but have little effect (beyond endoscopic therapy) on associated mortality, much of it due to conditions other than rebleeding.

Proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding.

Peptic ulcer bleeding is a common and potentially fatal condition. For patients with bleeding peptic ulcers that display major endoscopic stigmata of recent hemorrhage, a combination of endoscopic and pharmacologic therapy is the current standard management. To show our experience with management of peptic ulcer bleeding. Patients who presented with gastrointestinal bleeding caused by peptic ulcer or recent history (< 24 h before presentation) of hematemesis and/or melena admitted to our hospital emergency departments, and patients whose ulcer hemorrhage started after hospitalization for an unrelated medical or surgical condition. Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or endoscopic hemoclips, and randomized to receive intravenous pantoprasole according to the continuous regimen (dose of 5 x 40 mg in continuous infusion of 8 mg/h for 72 h) or the standard regimen (40 mg bolus of PPI twice daily for 3 days). After the infusion, all patients were given 40 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as discovered by the repeated endoscopy. Bleeding recurred in 5 of 34 patients (14.7%) receiving the intensive regimen, and in 8 of 35 (22.8%) patients receiving the standard regimen. Hemoglobin (g/l) rate in standard regimen group was 93.5 +/- 23.8, and in intensive regimen group 106.6 +/- 22.4 (P = 0.042). Mean units of blood transfused for all patients in group were 71.8 +/- 45.8 in the intensive and 45.3 +/- 50.2 in the standard regimen group (P = 0.0257). The duration of hospital stay was 6.4 +/- 2.8 in standard group and 5.8 +/- 2.8 in the intensive group (P = 0.40). In patients with bleeding peptic ulcers with successful endoscopic hemostasis the standard PPI regimen had advantage on transfusion requirements, but no advantage with respect to in-hospital rates of rebleeding rates, need for surgery, length of hospital stay, or death, which corresponds with recent studies.

Gastrointestinal bleeding

The benefits versus risks of placing a nasogastric tube in those with upper GI bleeding are not determined. Endoscopy within 24 hours is recommended, in addition to medical management. A number of endoscopic treatments may be used, including: epinephrine injection, band ligation, sclerotherapy, and fibrin glue depending on what is found. Prokinetic agents such as erythromycin before endoscopy can decrease the amount of blood in the stomach and thus improve the operators view. They also decrease the amount of blood transfusions required. Early endoscopy decreases hospital and the amount of blood transfusions needed. A second endoscopy within a day is routinely recommended by some but by others only in specific situations. Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found. High and low dose PPIs appear equivalent at this point. It is also recommended that people with high risk signs are kept in hospital

High-dose omeprazole infusion compared with scheduled second-look endoscopy for prevention of peptic ulcer rebleeding: a randomized controlled trial.

Previous studies have shown that both scheduled second-look endoscopy and high-dose continuous omeprazole infusion are effective in preventing peptic ulcer rebleeding. The aim of this noninferiority trial was to compare the efficacy of these two strategies for the prevention of rebleeding following primary endoscopic hemostasis. Consecutive patients who received endoscopic treatment for bleeding peptic ulcers (actively bleeding, with nonbleeding visible vessels) were randomized to two treatment groups following hemostasis. One group (second-look endoscopy group) received the proton pump inhibitor (PPI) omeprazole as an intravenous bolus every 12 hours for 72 hours and a second endoscopy within 16 - 24 hours with retreatment for persistent stigmata of bleeding. The other group (PPI infusion group) received continuous high-dose omeprazole infusion for 72 hours. Patients who developed rebleeding underwent surgery if repeat endoscopic therapy failed. The primary outcome was the rebleeding rate within 30 days after initial hemostasis. The margin for noninferiority was set at 5 %. A total of 153 patients were randomized to the PPI infusion group and 152 to the second-look endoscopy group. Rebleeding occurred within 30 days in 10 patients (6.5 %) in the PPI infusion group and in 12 patients (7.9 %) in the second-look endoscopy group (P = 0.646). Surgery was required for rebleeding in six patients from the PPI infusion group and three patients in the second-look endoscopy group (P = 0.32). Intensive care unit stay, transfusion requirements, and mortality were not different between the groups. Patients in the second-look endoscopy group were discharged 1 day earlier than those in the PPI infusion group (P < 0.001). After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding. ClinicalTrials.gov (NCT: 00164931).

[Guidelines of treatment for bleeding peptic ulcer disease].

Peptic ulcer (PU) bleeding is the main cause of non-variceal gastrointestinal bleeding. Negative outcomes include re-bleeding and death, and many of the deaths are associated with decompensation of coexisting medical conditions precipitated by acute bleeding event. Accurate analysis of risk for clinical features can help physician to decide treatment modality. Endoscopy can detect bleeding stigmata and perform therapeutic hemostasis. Proton pump inhibitor (PPI) compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in upper gastrointestinal (UGI) bleeding significantly reduces the proportion of patients with stigmata of recent hemorrhage (SRH) at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with endoscopic hemostasis for those with major SRH, is likely to be the most cost-effective. The treatment of H. pylori infection was found to be more effective than anti-secretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone and eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies to prevent ulcer bleeding among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective treatment. This review focuses specifically on the current treatment of patients with acute bleeding from a peptic ulcer.

Comparison of High Dose and Standard Dose Proton Pump Inhibitor before Endoscopy in Patients with Non-Portal Hypertension Bleeding.

Gastrointestinal bleeding with non-portal hypertension bleeding (non-PHT) is the most common cause of gastrointestinal emergencies with high mortality rate. The majority of non-PHT patient stem from acid related disease. The practice guideline recommends using pre-endoscopic proton pump inhibitors (PPIs). However, the dose and route of PPIs administration were still unclear according to the Association for Gastroenterology. To compare the efficiency of PPIs between high dose and standard dose before endoscopy in patients suffering with gastrointestinal bleeding due to non-PHT. The present study was designed as a prospective, randomized controlled trial. The patients were randomly categorized into two groups, the first group received intravenous pantoprazole 80 mg bolus then continuously drip 8 mg per hour (high dose group) and the other group received intravenous pantoprazole 40 mg twice daily before endoscopy (standard dose group). Baseline characteristics, Blatchford score, endoscopic findings, morbidity, and other complications were recorded. One hundred thirteen patients were recruited. Fifty-eight patients were in the high dose group and 55 patients in the standard dose group. Blatchford scores in the high dose group were slightly higher than the standard dose group but there was no statistically significant difference (12.49+3.29 and 12.38+4.06, respectively, p = 0.876). Twenty-two patients were high-risk for peptic ulcer bleeding from endoscopy. There were significantly less numbers of patient who were high-risk of peptic ulcer bleeding in the high dose group compared to the standard dose group (10 patients [17.24%] and 12 patients [21.82%], respectively, p = 0.025). There was no difference between the two groups in average time of hospital stay (3.03 and 2.89 days, respectively, p>0.05), mean unit of blood transfusion (1.79 and 1.63 units, respectively, p>0.05), and the complications after endoscopy such as recurrent bleeding (0 and 1 patient, respectively, p>0.05), recurrent bleeding and death (0 and 1 patient, respectively, p>0.05). The Blatchford score greater than 10, 11, and 12 showed high sensitivity of 100%, 95%, and 95% respectively with negative predictive values (NPV) of 100%, 97%, and 97% respectively, in predicting high-risk peptic ulcer bleeding. The high dose of PPIs administration before endoscopy reduced the chance of high-risk peptic ulcer bleeding compared to the standard dose. Both high dose and standard dose of PPIs did not affect the time of hospital stay, unit of blood transfusion, the complications after endoscopy, and mortality rate. Standard dose PPIs can be considered using in patients with Blatchford scores lower than 10. High dose PPIs would be beneficial in patients who have Blatchford scores between 10 and 12. For patients who have Blatchford scores greater than 12, high dose PPIs are recommended.

Randomized controlled trial of high dose bolus versus continuous intravenous infusion pantoprazole as an adjunct therapy to therapeutic endoscopy in massive bleeding peptic ulcer.

After therapeutic endoscopy is performed in high-risk patients with peptic ulcer bleeding, rebleeding occurs in about 25 to 30%. High dose intravenous proton pump inhibitors (PPI) have been recommended for the use in high-risk patients to prevent rebleeding following successful therapeutic endoscopy. Compare the efficacy between pantoprazole high dose bolus injections and continuous intravenous infusion to prevent rebleeding in peptic ulcer patients after initial hemostasis is achieved by the therapeutic endoscopy. A clinical block randomized control trial was conducted at Maharaj Nakorn Chiang Mai Hospital in massive peptic ulcer bleeding patients. All patients underwent endoscopic diagnosis and treatment within six hours of admission. Hemostasis was achieved by therapeutic endoscopy in 28 patients who received 80 mg pantoprazole as a loading dose before intervention. They were randomized into two groups. The first group was given a high dose of pantoprazole, 40 mg bolus injections twice daily for seven days (n = 13). The second group was given continuous intravenous infusion of pantoprazole, 8 mg per hour for the first three days, followed with a 40 mg bolus injection twice daily similar to the first group from day 4 until day 7 (n = 15). After the seventh day, both groups were given 20 mg of oral pantoprazole once daily for two months. The data was analyzed by Fisher's exact test to compare the frequency of rebleeding within seven days after therapeutic endoscopy. The frequency of recurrent bleeding between the high dose pantoprazole bolus injection group and the continuous intravenous infusion group was not significantly different, 30.8% and 33.3% respectively (p = 1.0). Three patients in the high dose bolus group and five in the continuous infusion group underwent surgery (p = 0.68). There was no statistically significant difference between the two groups by volume of blood transfusion, length of hospital stay, or mortality. In the present study, both PPI drug administration methods showed an equally effective for massive peptic ulcer bleeding. Further studies with a larger sample size are recommended.

Upper gastrointestinal bleeding

Significant upper gastrointestinal bleeding is considered a medical emergency. Fluid replacement, as well as blood transfusion, may be required. Endoscopy is recommended within 24 hours and bleeding can be stopped by various techniques. Proton pump inhibitors are often used. Tranexamic acid may also be useful. Procedures (such as TIPS for variceal bleeding) may be used. Recurrent or refractory bleeding may lead to need for surgery, although this has become uncommon as a result of improved endoscopic and medical treatment. Upper gastrointestinal bleeding affects around 50 to 150 people per 100,000 a year. It represents over 50% of cases of gastrointestinal bleeding. Depending on its severity, it carries an estimated mortality risk of 11%.

Gastrointestinal bleeding

Peptic ulcers Based on evidence from people with other health problems crystalloid and colloids are believed to be equivalent for peptic ulcer bleeding. Proton pump inhibitors (PPI) may reduce mortality in those with severe disease as well as the risk of re-bleeding and the need for surgery among this group. Oral and intravenous formulations may be equivalent; however, the evidence to support this is suboptimal. In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance. There is tentative evidence of benefit for tranexamic acid which inhibits clot breakdown. Somatostatin and octreotide, while recommended for varicial bleeding, have not been found to be of general use for non variceal bleeds. After treatment of a high risk bleeding ulcer endoscopically giving a PPI once or a day rather than as an infusion appears to work just as well and is less expensive (the method may be either by mouth or intravenously).

Does adding misoprostol to standard intravenous proton pump inhibitor protocol improve the outcome of aspirin/NSAID-induced upper gastrointestinal bleeding?: a randomized prospective study.

Aspirin and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal bleeding is recognized as an important health problem. We performed a single-center randomized clinical trial to compare the effect of high-dose intravenous proton pump inhibitor (omeprazole) alone (group 1) with omeprazole in combination with a low-dose prostaglandin analog (misoprostol; group 2) on clinical outcomes in patients with aspirin/NSAID-induced upper gastrointestinal bleeding. Additionally, we evaluated the contribution of Helicobacter pylori eradication therapy on the late consequences. Patients were recruited to the study if they had upper gastrointestinal bleeding with history of taking aspirin or other NSAIDs within the week before the onset of bleeding. All were evaluated in terms of probable risk factors. After the standard treatment protocol, patients with histologically proven H pylori infection were prescribed a triple eradication therapy for 14 days. The primary end points were recurrent bleeding, surgery requirement, and death rates before discharge and at the end of follow-up period. This study lasted for 2 years. A total of 249 patients with upper gastrointestinal bleeding were admitted, and 49.7% of these patients were users of aspirin/NSAIDs. There were 67 patients in group 1 and 56 in group 2. The distributions for gender, age, comorbidity, H pylori infection, and high-risk ulcer rate were similar in both groups. Among aspirin/NSAID users, endoscopy revealed duodenal ulcer in 47 (38.2%), gastric ulcer in 10 (8.1%), and erosive gastropathy in 33 (26.8%). The overall rebleeding occurred in 12.2%, death in 2.4% of the patients. The in-hospital death (P=.414), rebleeding (P=.925), and surgery (P=.547) rates were similar in both treatment groups. After the follow-up period of 3 months, overall rebleeding occurred in 4.1%, and death in 4.8% of the patients. The overall mortality rate was highest in those >65 years old, who were chronic low-dose aspirin users with comorbidity. One died of transfusion-related graft-versus-host disease. In this pilot study, we indicated that adding misoprostol (600 microg/day) to standardized proton pump inhibitor treatment did not improve or change the rebleeding or mortality rates of patients with upper gastrointestinal bleeding related to aspirin/NSAID use. Other prospective studies on higher doses of misoprostol are needed to establish the coeffect. One should bear in mind that all blood products must be irradiated before transfused to the host.

Management of non-variceal upper gastrointestinal bleeding.

Upper gastrointestinal bleeding (UGIB) is a critical condition that demands a quick and effective medical management. Non-variceal UGIB, especially peptic ulcer bleeding is the most significant cause. Appropriate assessment and treatment have a major influence on the prognosis of patients with UGIB. Initial fluids resuscitation and/or transfusion of red blood cells are necessary in patients with clinical evidence of intravascular volume depletion. Endoscopy is essential for diagnosis and treatment of UGIB, and should be provided within 24 hours after presentation of UGIB. Pre-endoscopic use of intravenous proton pump inhibitor (PPI) can downstage endoscopic signs of hemorrhage. Post-endoscopic use of high-dose intravenous PPI can reduce the risk of rebleeding and further interventions such as repeated endoscopy and surgery. Eradication of Helicobacter pylori and withdrawal of non-steroidal anti-inflammatory drugs are recommended to prevent recurrent bleeding.

Diagnostic and therapeutic options in the management of nonvariceal upper gastrointestinal bleeding.

Upper gastrointestinal bleeding from peptic ulcers is common. Advances in prognostication, therapeutic endoscopy, and medical management have evolved rapidly. Patients most likely to rebleed after therapy can now be identified and monitored more closely, and patients with ulcers of low risk for rebleeding can be managed on an outpatient basis. High-risk patients include those with ulcers containing a visible vessel or who are actively bleeding. Endoscopic therapy is mandatory in high-risk patients and involves at least two hemostatic techniques. Second-look endoscopy and repeated hemostasis should be performed promptly in patients who rebleed. Adjunctive treatment includes intravenous proton pump inhibitor administered in high doses for the first 72 hours after endoscopic therapy. Further studies are needed to determine the optimal combination of hemostatic techniques to better target patients who are at risk for ulcer rebleeding.

Initial factors predicting rebleeding and death in bleeding peptic ulcer disease.

Bleeding peptic ulcer constitutes approximately half of the cases admitted with upper gastrointestinal bleeding. Although the bleeding episode stops spontaneously in most of them, rebleeding occurs in as much as 10-30% of them and has a mortality rate of 5-10%. In this study, we have evaluated the possible significant predictors associated with this adverse outcome. The records of 205 patients admitted to gastrointestinal bleeding unit (GIBU) in Riyadh Central Hospital, during the period May 1996 through to April 1999, with endoscopic confirmed diagnosis of bleeding peptic ulcer disease were reviewed for demography, clinical presentation, hematology, biochemistry, initial blood pressure, nasogastric lavage color, co-morbid disease and endoscopic findings. All the significant factors found initially (P<0.05) were entered into odds ratio and its 95% confidence interval and finally the unconditioned logistic regression model was used to find out the significant independent predictors for both rebleeding and mortality in these patients. The majority of patients (85%) were males and below the age of 60 (73%). Duodenal ulcer was the source of bleeding in 84%. Endoscopy was performed in all patients within 24 hours of admission. Only 15% were actively bleeding at the time of initial endoscopy. Thirty-six patients (17%) rebelled, majority within 72 hours of initial hemostasis. Overall, 11 patients (5%) died, 6 of them were rebleeders. Initial presentation of systolic blood pressure <100 mm Hg, blood in nasogastric tube and visible vessel within the ulcer in endoscopy were independent predictors of rebleeding while initial systolic blood pressure <100 mm Hg and age >60-years were independent predictors of mortality. Improvement of outcome in patients with bleeding peptic ulcer disease can be achieved by early detection of those patients who are at risk of adverse outcome. Patients with the above mentioned independent predictors of rebleeding and mortality are best managed in the intensive care unit with endoscopic hemostasis and proton pump inhibitor (PPI) therapy for a minimum of 5-days of admission.

[Endoscopic treatment of bleeding ulcers: has everything been said and done?].

Endoscopic treatment reduces bleeding recurrence, the need for surgery and mortality in patients with bleeding ulcers. However endoscopic treatment fails in 10-15% of patients, leading to high morbidity and mortality. The therapeutic measures with demonstrated effectiveness in reducing the risk of hemorrhagic recurrence and its complications are combined endoscopic treatment (adrenaline plus a second hemostatic intervention) and proton pump inhibitors. Also useful, although there is less evidence, are immediate resuscitation and <<second look>> endoscopy. Some studies suggest that activated recombinant factor VII infusion or supra-selective arterial embolization can be useful in severe hemorrhage. Further studies are required to determine optimal treatment according to the characteristics of each patient.

Upper gastrointestinal bleeding

The benefits versus risks of placing a nasogastric tube in those with upper gastrointestinal bleeding are not determined. Endoscopy within 24 hours is recommended. Prokinetic agents such as erythromycin before endoscopy can decrease the amount of blood in the stomach and thus improve the operators view. Early endoscopy decreases hospital time and the amount of blood transfusions needed. Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found. It is also recommended that people with high risk signs are kept in hospital for at least 72 hours.

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4<supth</sup-28th day after the first bleeding episode. The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

Gastrointestinal bleeding

Initial treatment focuses on resuscitation which may include intravenous fluids and blood transfusions. Often blood transfusions are not recommended unless the hemoglobin is less than 70 or 80 g/L. Treatment with proton pump inhibitors, octreotide, and antibiotics may be considered in certain cases. If other measures are not effective, an esophageal balloon may be attempted in those with presumed esophageal varices. Endoscopy of the esophagus, stomach, and duodenum or endoscopy of the large bowel are generally recommended within 24 hours and may allow treatment as well as diagnosis. An upper GI bleed is more common than lower GI bleed. An upper GI bleed occurs in 50 to 150 per 100,000 adults per year. A lower GI bleed is estimated to occur in 20 to 30 per 100,000 per year. It results in about 300,000 hospital admissions a year in the United States. Risk of death from a GI bleed is between 5% and 30%. Risk of bleeding is more common in males and increases with age.

Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15 to 20 percent of patients. We assessed whether the use of a high dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus intravenous injection of 80 mg followed by an infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all patients were given 20 mg of omeprazole orally per day for eight weeks. The primary end point was recurrent bleeding within 30 days after endoscopy. We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in 8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5 percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval, 1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three days, which made up the infusion period (5 in the omeprazole group and 24 in the placebo group, P<0.001). Three patients in the omeprazole group and nine in the placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the omeprazole group and 12 (10 percent) in the placebo group died within 30 days after endoscopy (P=0.13). After endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.

Ranitidine

Medical uses Relief of heartburn Short-term and maintenance therapy of gastric and duodenal ulcers With nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the risk of ulceration Proton-pump inhibitors (PPIs) are more effective for the prevention of NSAID-induced ulcers. Pathologic gastrointestinal (GI) hypersecretory conditions such as Zollinger–Ellison syndrome Gastroesophageal reflux disease (GORD or GERD) Erosive esophagitis Part of a multidrug regimen for H. pylori eradication to minimise the risk of duodenal ulcer recurrence Recurrent postoperative ulcer Upper GI bleeding

Endoclip

Endoclips have found a primary application in hemostasis (or the stopping of bleeding) during endoscopy of the upper (through gastroscopy) or lower (through colonoscopy) gastrointestinal tract. Many bleeding lesions have been successfully clipped, including bleeding peptic ulcers, Mallory-Weiss tears of the esophagus, Dieulafoy's lesions, stomach tumours, and bleeding after removal of polyps. Bleeding peptic ulcers require endoscopic treatment if they show evidence of high risk stigmata of re-bleeding, such as evidence of active bleeding or oozing on endoscopy or the presence of a visible blood vessel around the ulcer. The alternatives to endoscopic clipping of peptic ulcers are thermal therapy (such as electrocautery to burn the vessel causing the bleeding), or injection of epinephrine to constrict the blood vessel. Comparative studies between endoclips and thermal therapy make the point that endoclips cause less trauma to the mucosa around the ulcer than electrocautery, but no

Acute upper gastrointestinal bleeding in critically ill patients: causes and treatment modalities.

Upper gastrointestinal bleeding from peptic ulcers or other nonvariceal causes generally stops spontaneously; if it fails to do so, aggressive management is required. Such measures also are necessary for patients at high risk for rebleeding. Endoscopic therapy achieves hemostasis in >90% of bleeding patients and reduces mortality. After successful hemostasis of the initial bleeding episode, the primary concern becomes the prevention of rebleeding, which occurs in up to 20% of patients. Acid suppression with histamine-2-receptor antagonists has been widely used for many years to prevent recurrent bleeding. However, in acutely bleeding patients, these agents have not been shown to reduce the number of episodes of further bleeding or rebleeding or to reduce the need for transfusions or surgery. Omeprazole, an intravenous proton pump inhibitor, significantly reduced the rate of rebleeding in a recent placebo-controlled trial in which only patients with endoscopic confirmation of successful hemostasis were enrolled. Although this drug does not seem to reduce the need for surgical intervention or to decrease mortality, the trial does indicate the promise of intravenous proton pump inhibitors in reducing upper gastrointestinal bleeding. Evidence from additional well-controlled trials is needed to confirm this finding. The use of proton pump inhibitors in this setting also may have a positive economic impact, and a decrease in the percentage of patients who experience rebleeding will eliminate the cost of further management strategies in those cases.

Proton-pump inhibitor

Medical uses These medications are used in the treatment of many conditions, such as: Dyspepsia Peptic ulcer disease including after endoscopic treatment for bleeding As part of Helicobacter pylori eradication therapy Gastroesophageal reflux disease (GERD or GORD) including symptomatic endoscopy-negative reflux disease and associated laryngopharyngeal reflux causing laryngitis and chronic cough Barrett's esophagus Eosinophilic esophagitis Stress gastritis and ulcer prevention in critical care Gastrinomas and other conditions that cause hypersecretion of acid including Zollinger–Ellison syndrome (often 2–3x the regular dose is required)