High-dose Intravenous Proton Pump Inhibitors Research Articles

S2451 Acute Esophageal Necrosis: A Rarely Encountered Clinical Entity

Introduction: Acute Esophageal Necrosis (AEN), otherwise known as black esophagus for its remarkable appearance during endoscopy, is a rather rare entity in the gastroenterology field. Case Description/Methods: A 51-year-old male with a past medical history of diabetes complicated by peripheral neuropathy presented to the hospital with left lower extremity swelling and pain after a fall. On admission he underwent lower extremity x-ray with subcutaneous air concerning for necrotizing fasciitis. He was taken emergently to the operating room where he underwent 3 compartment exploration with irrigation and drain placement. On day 7 of hospitalization he developed persistent nausea and vomiting for which we were consulted. The following morning he was taken to the endoscopy suite. He was noted to have circumferential black appearance of the esophagus from 28 to 40 cm with abrupt transition to normal-appearing gastric mucosa at the GE junction. This was endoscopically consistent with acute esophageal necrosis He was placed on high-dose intravenous proton pump inhibitor (PPI) therapy as well as sucralfate suspension. Transfer was facilitated to a tertiary care center where repeat endoscopy confirmed the diagnosis. He had a gastrostomy tube placed and ultimately underwent repeat endoscopy 8 weeks later at the same tertiary care center which revealed severe benign appearing esophageal stricturing with inability to pass adult endoscope. It was recommended to continue on PPI therapy with repeat endoscopic evaluation with possible dilation the following month. Unfortunately, in the meantime the patient expired due to unknown causes (Figure). Discussion: AEN is defined by a circumferential, necrotic appearance that almost always affects the distal esophagus with abrupt cessation of the black contour at the GE junction. Incidence is 0.28%, affects men over 4 times more often than women with a mortality near 32%. AEN is usually multifactorial and affects people with many comorbidities. Presenting symptoms varied greatly, with the most prevalent being hematemesis (34%). Injury is related to esophageal ischemia and topical injury. AEN is almost always diagnosed by endoscopy. Biopsy can rule out other similarly appearing pathologies. Management of AEN typically involves treating the underlying cause. Empirical treatment includes IV fluids, PPI, sucralfate, NPO, and TPN in patients with poor nutritional status after 24 hours.Figure 1.: Multiple images showing diffuse esophageal necrosis with abrupt transition to normal mucosa at the GE junction.

High-Dose Proton Pump Inhibitors Are Superior to Standard-Dose Proton Pump Inhibitors in High-Risk Patients With Bleeding Ulcers and High-Risk Stigmata After Endoscopic Hemostasis.

INTRODUCTION:To define the best cutoff of the Glasgow-Blatchford score (GBS) for identifying high- and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis and compare the efficacy of high-dose and standard-dose intravenous proton pump inhibitors (HD-IVPs and SD-IVPs, respectively) in this patient population.METHODS:We retrospectively reviewed the data of 346 patients with bleeding ulcers and high-risk stigmata who underwent endoscopic hemostasis between March 2014 and September 2018 in our center and were divided into an HD-IVP group and an SD-IVP group. Propensity score–matching analysis was performed to control for selection bias and other potential confounders. Recurrent bleeding rates were calculated according to the GBS.RESULTS:Overall, 346 patients meeting the inclusion criteria were enrolled, with 89 patients in the SD-IVP group and 89 patients in the HD-IVP group after matching with all baseline characteristics balanced (P > 0.05). GBS = 8 was the best cutoff for identifying high-risk rebleeding patients (GBS ≥ 8) with a significant difference (P = 0.015) in recurrence rate between the SD-IVP (17/61, 27.9%) and HD-IVP (7/65, 10.8%) groups and low-risk rebleeding patients (GBS < 8) with no difference (P = 1) in recurrence rate between the SD-IVP (2/28, 7.1%) and HD-IVP (2/24, 8.3%) groups.DISCUSSION:The best cutoff for identifying high-risk and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis was GBS = 8. Although HD-IVP is more effective than SD-IVP in high-risk patients, they are equally effective in low-risk patients.

1809 Gurvits Syndrome: A Rare Cause of Upper Gastrointestinal Bleed

INTRODUCTION: Acute Esophageal Necrosis (AEN), also known as Black Esophagus or Gurvit’s syndrome, is a rare disorder that can present as an acute gastrointestinal (GI) bleed. Given the high risk of perforation and mortality, a GI bleed in the correct clinical context should put AEN on the differential. We discuss clinical, endoscopic and management of AEN. CASE DESCRIPTION/METHODS: 57-year-old female with hypertension and gastroesophageal reflux disease presented after a pre-syncopal event. She was admitted for septic shock secondary to urinary tract infection. She was hypothermic with a blood pressure of 76/48 mm Hg on arrival to the ICU. She was started on broad spectrum antimicrobials, in addition to, norepinephrine and vasopressin to maintain mean atrial pressures above 60 mmHg. On ICU day two, she had multiple episodes of coffee-ground emesis and was intubated for airway protection. Her hemoglobin acutely dropped from 8 g/dl to 6.8 g/dl over 12 hours. EGD revealed circumferential ulceration of the lower esophagus with areas of necrosis. Patient was started on high-dose intravenous proton pump inhibitor and supportive therapy with treatment of septic shock. Three days later an endoscopic nasojejunal tube was placed for enteral feeding which revealed increasing amounts of viable mucosa with a decrease in the area of necrosis. There were no further GI bleed and patient was discharged 30 days later. DISCUSSION: AEN is multifactorial with a combination of an ischemic insult, corrosive injury to the mucosa from gastric contents and impaired reparative mechanism in setting of acute illness. Risk factors include male sex, older age and multiple chronic medical conditions. Men are four times more commonly affected than women. Diagnosis is made via direct visualization with findings of circumferential black discoloration of the distal esophagus that abruptly ends at the gastroesophageal junction. With comparatively less dense vasculature, the distal esophagus is the water-shed area of the esophagus. Treatment of AEN focuses on aggressive treatment of underlying disease, supportive therapy, and acid suppression. Complications of AEN include esophageal perforation, mediastinitis, and abscess formation. Long term complications include stricture formation and stenosis. Insertion of nasogastric tube should be avoided given the high risk of perforation secondary to the friability of the esophageal mucosa. In our patient, endoscopically placed nasojejunal tube was a safer alternative to restoring enteral feeding.

Little Cost Difference Among PPI Therapies for Bleeding Peptic Ulcers

Evidence strongly indicates that high-dose intravenous proton-pump inhibitor (PPI) therapy improves clinical outcomes in patients with bleeding peptic

Timing or Dosing of Intravenous Proton Pump Inhibitors in Acute Upper Gastrointestinal Bleeding Has Low Impact on Costs.

High-dose intravenous proton pump inhibitors (PPIs) post endoscopy are recommended in non-variceal upper gastrointestinal bleeding (UGIB), as they improve outcomes of patients with high-risk lesions. Determine the budget impact of using different PPI regimens in treating non-variceal UGIB, including pre- and post-endoscopic use, continuous infusion (high dose), and intermittent bolus (twice daily) dosing. A budget impact analysis using a decision model informed with data from the literature adopting a US third party payer's perspective with a 30-day time horizon was used to determine the total cost per patient (US$2014) presenting with acute UGIB. The base-case employing high-dose pre- and post-endoscopic IV PPI was compared with using only post-endoscopic PPI. For each, continuous or intermittent dosing regimens were assessed with associated incremental costs. Deterministic and probabilistic sensitivity analyses were performed. The overall cost per patient is $11,399 when high-dose IV PPIs are initiated before endoscopy. The incremental costs are all inferior in alternate-case scenarios: $106 less if only post-endoscopic high-dose IVs are used; with intermittent IV bolus dosing, the savings are $223 if used both pre and post endoscopy and $191 if only administered post endoscopy. Subgroup analysis suggests cost savings in patients with clean-base ulcers who are discharged early after endoscopy. Results are robust to sensitivity analysis. The incremental costs of using different IV PPI regimens are modest compared with total per patient costs.

Endoscopic Suturing for Ulcer Exclusion in Patients With Massively Bleeding Large Gastric Ulcer

Bleeding peptic ulcer is one of the most important causes for hospitalization worldwide. Though endoscopic hemostasis is the current standard of treatment for bleeding peptic ulcers, ulcer rebleeding remained a chief cause of mortality.1Chiu P.W. et al.Clin Gastroenterol Hepatol. 2009; 3: 311-316Abstract Full Text Full Text PDF Scopus (88) Google Scholar One of the important strategies to improve outcomes for bleeding peptic ulcers is to prevent rebleeding. Indeed, endoscopic features for ulcers with high risk of rebleeding include ulcers larger than 2 cm, actively bleeding and those located at posterior duodenal bulb or high lesser curvature.2Johnston J.H. et al.Gastroenterology. 1987; 92: 1101-1108Abstract Full Text PDF PubMed Scopus (111) Google Scholar With the use of high-dose intravenous proton pump inhibitors (PPI), those who developed rebleeding after PPI infusion were patients with significant perioperative risks, high proportion of comorbidities, as well as older age which rendered them high-risk surgical candidates.3Elmunzer B.J. et al.Am J Gastroenterol. 2008; 103: 2625-2632Crossref PubMed Scopus (119) Google Scholar A prototype endoscopic suturing device had been investigated for the safety and efficacy in achieving hemostasis among massively bleeding gastric ulcers.4Chiu P.W. et al.Dig Surg. 2009; 26: 243-248Crossref PubMed Scopus (16) Google Scholar This is an initial report on the clinical application of surgical ulcer exclusion using endoscopic suturing for large bleeding gastric ulcer. The Apollo Overstitch is an endoscopic suturing system which consists of a cap-based suturing system with a curved suture arm extending from one of the dual channels and the anchor exchange system extending from the same channel. The handle to control the suture plication system was mounted onto the shaft of a double-channel endoscope (Olympus 2T100 scope, Olympus Co Ltd, Hong Kong). The Overstitch system attached to the double-channel endoscope was introduced into the stomach through an overtube. The bleeding ulcer was first located with an ordinary single-channel endoscope. Endoscopic suturing begins with the needle first driving through the distal edge of the bleeding ulcer. After closing the curved needle driver, the detachable needle should be grasped by the anchor exchange and detached from the needle driver. After opening the needle driver, the endoscope with Overstitch should be moved away from the distal ulcer edge. The needle should be placed back in the needle driver by the anchor exchange. The needle should then be driven over the proximal edge of the ulcer and the procedure repeated until the 2 edges of the ulcer can be pulled together. The needle anchor should be dropped, while the anchor exchange is replaced by the cinching device which passes along the 2 ‘O’ polypropylene suture. After passage of the cinch to ulcer edge, the polypropylene suture should be tightened against the end of the cinch. The cinch is then closed to cut the stitch and release the plug to tighten the suture, and the ulcer should be excluded from an intragastric high acidity environment to stop current bleeding and prevent rebleeding. Three patients received endoscopic ulcer exclusion for a massively bleeding gastric ulcer. This video shows endoscopic suturing for ulcer exclusion in an actively bleeding gastric ulcer. The patient was a 78-year-old man who presented with passage of tarry stool for 3 days; upper endoscopy showing a 2 cm large gastric ulcer at angular incisura with visible vessel. There was active bleeding from visible vessel (Figure 1). The Overstitch device was introduced through an overtube. The first suture plication was performed over the superior edge of the ulcer. After exchange of the anchor, the second suture plication was performed over the inferior ulcer edge. This process was continued until a figure of eight suture was formed over the ulcer. The anchor was then dropped and the suture was tightened with the cinching device. The ulcer was excluded with adequate hemostasis (Figure 2). The patient had no clinical evidence of rebleeding, and a repeated endoscopy in 72 hours confirmed secure closure of the ulcer.Figure 2Ulcer exclusion achieved after tightening of overstitch.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Surgical exclusion of bleeding ulcer is a conventional treatment for prevention of further bleeding through suture closure of the ulcer and excluding it from intragastric acidity. This is the first technological report on clinical application of endoscopic surgical suturing for ulcer exclusion. The success of endoscopic ulcer exclusion will lead to improvement in primary endoscopic hemostasis, and theoretically excluding the ulcer from acid to prevent further bleeding. The ulcer exclusion shall be a better method to prevent rebleeding compared with adjunctive high-dose proton pump inhibitor infusion or prophylactic angiographic embolization. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0NDRlMDkxM2NmMGRhNGUwNGJiZDFkODUyMjRjMjQxYyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjgxMzYwNDY3fQ.XXJzrp-6yqa5X_Fxu-t93ZJmJ4gGt5KEIICkg-xZWs2P9QUVTwPcWU5BIAoyY161WQqS9Xoq2xlMpMeFIa03TVHD9haMAQ-SBed6va3cMQtozXytNgaNMojGDSQwMA4hN2-dG7kGlLfGkDlU3dV9Oi0epZaZBfhQIxkNVWPYU76Fm68LSNLJ7_1G29qT5DlWZrSOHsW10o5dkts0yBD9W0Bc9PUUOiJX1P41J4-g2lAv77tNCIPyZNrVzhbQnAt1xIYBD1YAb1HHnXEHF1q2P_ISMMsqrfBJmW0OLGH8PblHrNNDwqnDn3pnyRIekdVxovny7vwoogxhrPzxLQT2mw Download .mp4 (43.03 MB) Help with .mp4 files Video 1

Oral vs. Intravenous Esomeprazole in Upper GI Bleeding

High-dose intravenous proton-pump inhibitor (PPI) treatment can reduce rebleeding after endoscopic therapy in patients with high-risk lesions. Some

Sa1139 High-Dose Intravenous Proton Pump Inhibitors for Prevention of Recurrent Peptic Ulcer Bleeding in Chinese and Western Populations: Rebleeding Is Not Influenced by Ethnicity

Sa1139 High-Dose Intravenous Proton Pump Inhibitors for Prevention of Recurrent Peptic Ulcer Bleeding in Chinese and Western Populations: Rebleeding Is Not Influenced by Ethnicity

Effects of intravenous and oral esomeprazole in the prevention of recurrent bleeding from peptic ulcers after endoscopic therapy.

The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis. This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis. A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups. High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.

Predictive Factors for Endoscopic Hemostasis in Patients with Upper Gastrointestinal Bleeding

Predictive Factors for Endoscopic Hemostasis in Patients with Upper Gastrointestinal Bleeding

Non-variceal upper gastrointestinal bleeding: clinical, therapeutic and evolution aspects. Comparison between a tertiary medical center and a municipal hospital.

Upper gastrointestinal bleeding (UGIB) is one of the most common emergencies in gastroenterology practice. In recent years, the introduction of urgent upper gastrointestinal endoscopy (UGIE) and of the treatment with proton pump inhibitors (PPIs) in high doses has resulted in an improvement of the treatment outcome in patients with UGIB, but without a significant improvement in mortality rates. In our study we compared the epidemiological, clinical, therapeutic, and prognostic aspects in patients with non-variceal UGIB admitted over a period of one year in a tertiary center where urgent UGIE is a routine procedure and in a municipal hospital where UGIE with endoscopic hemostasis is not available. Patients admitted to the tertiary medical center had more clinical and endoscopic severity factors compared to those from the municipal hospital: they were older, with more frequent intake of NSAIDs, several comorbidities, some of them severe, and more severe posthemorrhagic anemia. The endoscopic examination revealed that active bleeding and stigmata of recent hemorrhage were more frequent in these patients. Urgent UGIE and, where necessary because of lesions, endoscopic hemostasis were performed in most of these patients. Patients admitted to the municipal hospital were treated more frequently with high-dose intravenous PPIs. Patients undergoing urgent UGIE and endoscopic therapy had a shorter duration of hospitalization. However, there were no differences regarding the need for surgery or mortality rates. The results of our study are consistent with the literature.

Endoscopic Treatment of Upper Gastrointestinal Ulcer Bleeding

Peptic ulcer disease is the most common cause of upper gastrointestinal (GI) bleeding. In most of the cases, bleeding from a peptic ulcer stops spontaneously. Arterial diameters in bleeding ulcers can measure up to 3.45 mm, but in most cases the diameter of the bleeding artery is small (< 2 mm). High-dose intravenous proton pump inhibitors after endoscopic therapy for a bleeding ulcer reduce recurrent bleeding risk and surgery. The endoscopic appearance of an ulcer provides important prognostic information. Clean based ulcers and ulcers with a flat pigmented spot have low rebleeding risks. Major stigmata of hemorrhage (an adherent clot, a visible vessel, or active bleeding) are associated with high rebleeding risks. Endoscopic treatment in patients with high-risk stigmata results in improved outcomes. Common endoscopic techniques and the devices used to treat upper GI ulcer bleeding, including injection therapy, thermal coagulation, endoclip application, and hemostatic powder spray are described in the given video. Different clinical scenarios are presented. This article is part of an expert video encyclopedia.

Obscure bleeding colonic duplication responds to proton pump inhibitor therapy

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation.

High-dose versus low-dose intravenous proton pump inhibitor treatment for bleeding peptic ulcers

Evaluation of: Liu N, Liu L, Zhang H et al. Effect of intravenous proton pump inhibitor regimens and timing of endoscopy on clinical outcomes of peptic ulcer bleeding. J. Gastroenterol. Hepatol. 27(9), 1473–1479 (2012).Peptic ulcer bleeding is a common medical emergency associated with significant mortality and healthcare costs. All recent guidelines agree on the beneficial role of proton pump inhibitor treatment, but there is still controversy regarding the optimal dose and route of administration of proton pump inhibitors. The evaluated article reports on a large, single-center randomized controlled trial that compared the clinical efficacy of a low-dose twice-daily intravenous bolus regimen with a high-dose continuous intravenous infusion regimen in 875 patients with acute bleeding from peptic ulcers. The high-dose regimen was associated with significant reductions in rebleeding, blood transfusion requirements and length of hospital stay. There was no demonstrable difference in mortality or the need for endoscopic hemostatic treatment or surgery. We discuss the strengths and limitations of the evaluated article, as well as the implications for clinical practice.

Risk factors influencing the outcome of peptic ulcer bleeding in end stage renal diseases after initial endoscopic haemostasis

Background and Aims: Patients suffering from peptic ulcer (PU) bleeding who have end-stage renal disease (ESRD) may encounter more adverse outcomes. The primary objective is to investigate the risk factors that influence the outcomes of ESRD and chronic kidney disease (CKD) patients with PU bleeding after successful initial endoscopic haemostasis. Methods: A total of 540 patients with PU bleeding after initial endoscopic haemostasis in a tertiary hospital were investigated retrospectively. They were sorted into three groups after randomised age-matched adjustment: ESRD group (n = 90), CKD group (n = 90) and control group (n = 360). Main outcome measurements were rebleeding, requirement for blood transfusion and surgery, length of hospital stay and mortality. Results: The rebleeding rates were 43% for the ESRD group vs. 21% for the CKD group vs. 12% for the control group (overall p = < 0.001). Multivariate analysis showed the predictors of rebleeding were ESRD, time to endoscope, and non-high-dose proton-pump inhibitors (PPI) users. The risk factors for bleeding-related mortality were presence of moderate degree of CKD and ESRD group, time to endoscope, and Rockall score. All-cause mortality was related to presence of moderate degree of CKD and ESRD group, platelet count, time to endoscope, Rockall score and length of hospital stay. Conclusions: ESRD patients who suffered from PU bleeding were at risk of excessive rebleeding and mortality with frequent occurrence of delayed rebleeding. This study suggests that early endoscopy for initial haemostasis and high-dose intravenous PPI are associated with the reduction of rebleeding risk especially in patients with high Rockall scores.

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.

A summary of recent recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding

Recommendations in managing patients with nonvariceal upper gastrointestinal bleeding were recently updated, addressing resuscitation, risk assessment and pre-endoscopic care, endoscopy, pharmacotherapy, and secondary prophylaxis. Initial adequate resuscitation and risk stratification using validated scales remain critical. Intravenous erythromycin improves visualization when likely to find blood in the stomach. Pre-endoscopic proton pump inhibition (PPI) does not improve outcomes, but downstages high-risk endoscopic lesions and may be considered. In patients on anticoagulants, correction of a coagulopathy is recommended, but should not delay early endoscopy (within 24 h), as it improves clinical outcomes. In patients with high-risk endoscopic stigmata, although better than doing nothing, epinephrine injection alone provides suboptimal efficacy and should be combined with another modality such as clips, thermal or sclerosant injection, which are also efficacious alone. Following an attempt at dislodgment, adherent clots can be treated with high-dose intravenous PPI infusion alone (80 mg bolus and 8 mg/h for 3 days) or following endoscopic hemostasis. The combination is indicated for all other patients with high-risk stigmata as there is currently a lack of high-quality generalizable data supporting other intravenous or oral PPI regimens. A second-look endoscopy is recommended only selectively after endoscopic hemostasis. A negative Helicobacter pylori test requires confirmation in the acute setting. Following appropriate discussions, acetylsalicylic acid (ASA) can soon be restarted acutely after bleeding; long-term PPI co-therapy is imperative in patients having bled on nonsteroidal anti-inflammatory drugs if still needed (preferably with a cyclooxygenase-2, if appropriate) or ASA (not clopidogrel alone). Further work is needed to implement and disseminate these recommendations.

The prognosis of patients having received optimal therapy for nonvariceal upper gastrointestinal bleeding might be worse in daily practice than in randomized clinical trials

Combination of endoscopic haemostatic and high-dose intravenous proton-pump inhibitors is considered to be the standard care for patients with acute peptic ulcer bleeding. This study assessed predictive factors of rebleeding and death in unselected patients presented to our hospital. Consecutive patients with nonmalignant bleeding ulcers and stigmata of recent haemorrhage who received optimal treatment, between 22 August 2003 and 15 October 2007, were studied retrospectively. Among 140 included patients, 45 (32%) rebled and 30 received another haemostatic endoscopy, which was successful in 20 cases. In multivariate analysis, the only significant predictive factor of rebleeding was duodenal site of the ulcer [adjusted odds ratio (OR): 2.75; 95% confidence interval (CI): 1.28-6.19]. In-hospital death occurred in 27 (19%) patients; with five deaths related to uncontrolled or recurrent bleeding. In multivariate analysis, predictors of in-hospital mortality were rebleeding (adjusted OR: 3.28; 95% CI: 1.17-9.16), a Rockall score higher than 6 (adjusted OR: 9.12; 95% CI: 2.57-44.29) and bleeding occurring in the intensive care unit (adjusted OR: 15.68; 95% CI: 4.41-55.82). In unselected patients, rebleeding and mortality rates are substantially higher than those found in prospective randomized clinical trials. Intensive care unit stay is an important predictive factor of hospital mortality and should be considered in further therapeutic trials in ulcer bleeding.

Predicting Mortality in Non-Variceal Upper Gastrointestinal Bleeders: Validation of the Italian PNED Score and Prospective Comparison With the Rockall Score

We sought (i) to validate a new prediction rule of mortality (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to compare the accuracy of the Italian PNED score vs. the Rockall score in predicting the risk of death. We conducted prospective validation of analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008. Outcome measure was 30-day mortality. All the variables used to calculate the Rockall score as well as those identified in the Italian predictive model were considered. Calibration of the model was tested using the chi2 goodness-of-fit and performance characteristics with receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of the two predictive models. Over a 16-month period, data on 1,360 patients were entered in a national database and analyzed. Peptic ulcer bleeding was recorded in 60.7% of cases. One or more comorbidities were present in 66% of patients. Endoscopic treatment was delivered in all high-risk patients followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six patients died (mortality 4.85%; 3.54-5.75). The PNED score showed a high discriminant capability and was significantly superior to the Rockall score in predicting the risk of death (AUC 0.81 (0.72-0.90) vs. 0.66 (0.60-0.72), P<0.000). Positive likelihood ratio for mortality in patients with a PNED risk score >8 was 16.05. The Italian 10-point score for the prediction of death was successfully validated in this independent population of patients with non-variceal gastrointestinal bleeding. The PNED score is accurate and superior to the Rockall score. Further external validation at the international level is needed.

High-dosevslow-dose proton pump inhibitors for upper gastrointestinal bleeding: A meta-analysis

To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.