Continuous esomeprazole infusion versus bolus administration and second look endoscopy for the prevention of rebleeding in children with a peptic ulcer.

INTRODUCTION: the majority of studies of acute gastrointestinal bleeding in children are retrospective, focusing on therapeutic endoscopy. Previous studies performed in adult patients have demonstrated that both scheduled second look endoscopy and high dose continuous omeprazole infusion are effective in the prevention of peptic ulcer rebleeding. The aim of this study was to compare the efficacy of these two strategies using esomeprazole for the prevention of rebleeding following primary endoscopic hemostasis in children with peptic ulcers. The main outcome was to assess the rebleeding rate within 30 days after the initial hemostasis. METHODS: consecutive pediatric cases who underwent endoscopic treatment for bleeding peptic ulcers were randomized into two treatment groups following hemostasis. The first group received esomeprazole as an intravenous bolus every 12 hours for 72 hours and a routine second look endoscopy within 12-24 hours with endotherapy retreatment in the case of a persistent stigmata of bleeding. The second group received a continuous high dose esomeprazole infusion for 72 hours without endoscopic reassessment unless required due to rebleeding. RESULTS: a total of 63 children were randomized to the second look endoscopy group and 64 to the esomeprazole infusion group. Rebleeding occurred within 30 days in four patients (6.3%) in the first group and in three patients (4.6%) in the second group (p = 0.7). CONCLUSIONS: a pharmaceutical approach using a high dose continuous esomeprazole infusion in children after an initial endoscopic hemostasis has a similar efficacy compared to second look endoscopy and bolus esomeprazole administration for the prevention of peptic ulcer rebleeding. Thus, the discomfort of a second endoscopy in children can be avoided and is only recommended for selected high risk cases.

Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury.

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

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

BACKGROUND AND STUDY AIM: 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. PATIENTS AND METHODS: 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 %. RESULTS: 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). CONCLUSIONS: After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding. TRIAL REGISTRATION: ClinicalTrials.gov (NCT: 00164931).

Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress.

BACKGROUND: The incidence of upper gastrointestinal bleeding from stress ulcers has decreased within the last 30 years. Improvements in intensive care medicine including advanced equipment for artificial ventilation, better sedoanalgesic therapies, and the use of stress ulcer prophylaxis are credited for the decline. OBJECTIVES: To determine the effectiveness of proton pump inhibitors (PPIs) on gastric pH in patients exposed to a defined severe stress situation during a specified time period. METHODS: Prospective open study in a tertiary community hospital. A high dose (80 mg bolus followed by 8 mg/h) of either pantoprazol or omeprazol was infused in 17 patients with opiate dependence who were undergoing ultra-rapid opiate withdrawal by barbiturate anesthesia. MEAN OUTCOME MEASURE: Gastric pH. RESULTS: Gastric pH did not change significantly in the majority of patients (mean pH 1.2 ± 0.9 immediately before, 1.5 ± 1.6 at 60 min after, and 1.3 ± 1.5 at 120 min after PPI infusion began). Gastric pH increased temporarily in two of the nine patients receiving omeprazol. In two of the eight patients, pantoprazol led to a late but sustained increase in gastric pH (pH 3.9 and 6.0 at 120 min post infusion). CONCLUSION: High doses of PPIs are ineffective in elevating gastric pH in patients exposed to severe stress such as ultra-rapid opiate detoxification. Therefore, adequate sedoanalgesia might be the main factor responsible for preventing stress-related bleeding in critically ill patients.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy.

BACKGROUND: High dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy. METHODS: Patients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month. RESULTS: From April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50) in the intravenous group and 4% (2/50) in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01). CONCLUSION: Patients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed. TRIAL REGISTRATION: NCT01123031.

Cost effectiveness of high-dose intravenous esomeprazole for peptic ulcer bleeding.

Peptic ulcer bleeding (PUB) is a serious and sometimes fatal condition. The outcome of PUB strongly depends on the risk of rebleeding. A recent multinational placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT00251979) showed that high-dose intravenous (IV) esomeprazole, when administered after successful endoscopic haemostasis in patients with PUB, is effective in preventing rebleeding. From a policy perspective it is important to assess the cost efficacy of this benefit so as to enable clinicians and payers to make an informed decision regarding the management of PUB. Using a decision-tree model, we compared the cost efficacy of high-dose IV esomeprazole versus an approach of no-IV proton pump inhibitor for prevention of rebleeding in patients with PUB. The model adopted a 30-day time horizon and the perspective of third-party payers in the USA and Europe. The main efficacy variable was the number of averted rebleedings. Healthcare resource utilization costs (physician fees, hospitalizations, surgeries, pharmacotherapies) relevant for the management of PUB were also determined. Data for unit costs (prices) were primarily taken from official governmental sources, and data for other model assumptions were retrieved from the original clinical trial and the literature. After successful endoscopic haemostasis, patients received either high-dose IV esomeprazole (80 mg infusion over 30 min, then 8 mg/hour for 71.5 hours) or no-IV esomeprazole treatment, with both groups receiving oral esomeprazole 40 mg once daily from days 4 to 30. Rebleed rates at 30 days were 7.7% and 13.6%, respectively, for the high-dose IV esomeprazole and no-IV esomeprazole treatment groups (equating to a number needed to treat of 17 in order to prevent one additional patient from rebleeding). In the US setting, the average cost per patient for the high-dose IV esomeprazole strategy was $US14 290 compared with $US14 239 for the no-IV esomeprazole strategy (year 2007 values). For the European setting, Sweden and Spain were used as examples. In the Swedish setting the corresponding respective figures were Swedish kronor (SEK)67 862 ($US9220 at average 2006 interbank exchange rates) and SEK67 807 ($US9212) [year 2006 values]. Incremental cost-effectiveness ratios were $US866 and SEK938 ($US127), respectively, per averted rebleed when using IV esomeprazole. For the Spanish setting, the high-dose IV esomeprazole strategy was dominant (more effective and less costly than the no-IV esomeprazole strategy) [year 2008 values]. All results appeared robust to univariate/threshold sensitivity analysis, with high-dose IV esomeprazole becoming dominant with small variations in assumptions in the US and Swedish settings, while remaining a dominant approach in the Spanish scenario across a broad range of values. Sensitivity variables with prespecified ranges included lengths of stay and per diem assumptions, rebleeding rates and, in some cases, professional fees. In patients with PUB, high-dose IV esomeprazole after successful endoscopic haemostasis appears to improve outcomes at a modest increase in costs relative to a no-IV esomeprazole strategy from the US and Swedish third-party payer perspective. Whereas, in the Spanish setting, the high-dose IV esomeprazole strategy appeared dominant, being more effective and less costly.

Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial.

BACKGROUND: Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups. OBJECTIVE: To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample. DESIGN: Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment. SETTING: 91 hospital emergency departments in 16 countries. PATIENTS: Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata. INTERVENTION: Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days. MEASUREMENTS: The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed. RESULTS: Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively. LIMITATION: Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group. CONCLUSION: High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days. PRIMARY FUNDING SOURCE: AstraZeneca Research and Development.

Protective effect of lysozyme chloride on gastric oxidative stress and hemorrhagic ulcers in severe atherosclerotic rats.

BACKGROUND: Calcium and cholesterol play major roles in the formation of atherosclerosis. Whether severe atherosclerosis induced by co-administration of a mixture containing vitamin D2 (vit D2) and cholesterol can result in gastric hemorrhagic damage is unknown. Gastric oxidative stress and hemorrhagic ulceration in rats with atherosclerosis induced by co-administration of vit D2 and cholesterol and the protective effect of lysozyme chloride on this ulcer model were investigated. MATERIAL/METHODS: Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vit D2 and cholesterol to induce atherosclerosis. Control rats received the same volume of corn oil only. After 24-h fasting followed by gastric surgery, the rat stomachs were irrigated for 3 h with simulated rat gastric juice or normal saline. Various gastric mucosal ulcerogenic factors (acid back-diffusion, lipid peroxides, histamine concentration, and hemorrhagic ulcers) and defensive substances (mucosal glutathione and mucus secretion) were determined. RESULTS: Augmentation of serum calcium concentration, total cholesterol, and low-density lipoprotein was observed in atherosclerotic rats. Greater mucosal ulcerogenic parameters and lower defensive substances were achieved in these rats. High correlation between decreased mucosal glutathione and ulceration as well as between increased mucosal lipid peroxide levels and ulceration was also found in the atherosclerotic rats. Daily intragastric lysozyme chloride dose-dependently protected gastric mucosal hemorrhagic damage in the atherosclerotic rats. CONCLUSIONS: Atherosclerosis induced by co-administration of vit D2 and cholesterol could produce gastric oxidative stress and hemorrhagic ulcer that was ameliorated by lysozyme chloride in rats.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment 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 UGI bleeding significantly reduces the proportion of patients with 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 EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Long-acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia.

BACKGROUND: Octreotide has shown to be effective against rebleeding from gastrointestinal angiodysplasias, but a long-term daily parenteral administration is recommended. Long-acting octreotide (LAR-OCT) could overcome such a limitation, but it has not been studied extensively. AIM: To investigate the usefulness of long-acting octreotide in the control of chronic bleeding from gastrointestinal angiodysplasias. METHODS: Thirteen patients with chronic gastrointestinal bleeding because of angiodysplasias were enrolled. Diagnosis was made by endoscopy and wireless video capsule. Long-acting octreotide was administered intramuscularly at a dosage of 10 mg/monthly for 1 year. Patients were followed up for a minimum period of 1 year, and haemoglobin levels, blood transfusions, iron supplementation and hospitalizations were recorded 1 year before and after starting long-acting octreotide therapy. RESULTS: Follow-up ranged from 12 to 60 months. Nine of 13 patients (69%) did not need blood transfusions and iron supplementation any longer; a partial improvement was observed in one patient; no effect was found in the others. No side effect was recorded in any patient. CONCLUSIONS: Long-acting octreotide for 1 year may be beneficial as a rescue therapy for controlling chronic bleeding from gastrointestinal angiodysplasias in patients not eligible for surgery. Its monthly administration represents an advantage, which makes such a formulation the choice when a long-term treatment is mandatory.

Continuous infusion of high-dose omeprazole is more effective than standard-dose omeprazole in patients with high-risk peptic ulcer bleeding: a retrospective study.

UNLABELLED: High-dose omeprazole reduces the rate of recurrent bleeding after endoscopic treatment of peptic ulcer bleeding. However, the effectiveness of high-dose vs. standard-dose omeprazole in peptic ulcer bleeding has never been shown. AIM: To compare the benefits of high-dose vs. standard-dose omeprazole in peptic ulcer bleeding. METHODS: We reviewed the medical files of patients admitted between 1997 and 2004 for high-risk peptic ulcer bleeding who had undergone successful endoscopic treatment. We distinguished 2 periods: before 2001, standard-dose omeprazole (40 mg/day intravenously until alimentation was possible, then 40 mg/day orally for 1 week); after 2001, high-dose omeprazole (80 mg bolus injection, then 8 mg/h continuous infusion for 72 h, then 40 mg/day orally for 1 week). During both periods, patients subsequently received omeprazole, 20 mg/day, orally for 3 weeks. RESULTS: We enrolled 114 patients (period 1, n = 45, period 2, n = 69). Therapy with high-dose omeprazole significantly decreased the occurrence of poor outcome (27 vs. 12%, P = 0.04), rebleeding (24 vs. 7%, P = 0.01), mortality due to haemorrhagic shock (11 vs. 0%, P < 0.001) and need for surgery (9 vs. 1%, P = 0.05). CONCLUSIONS: In this retrospective study, high-dose omeprazole reduced the occurrence of rebleeding, need for surgery and mortality due to hemorrhagic shock in patients with high-risk peptic ulcer bleeding, as compared with standard-dose omeprazole.

Omeprazole before endoscopy in patients with gastrointestinal bleeding.

BACKGROUND: A neutral gastric pH is critical for the stability of clots over bleeding arteries. We investigated the effect of preemptive infusion of omeprazole before endoscopy on the need for endoscopic therapy. METHODS: Consecutive patients admitted with upper gastrointestinal bleeding underwent stabilization and were then randomly assigned to receive either omeprazole or placebo (each as an 80-mg intravenous bolus followed by an 8-mg infusion per hour) before endoscopy the next morning. RESULTS: Over a 17-month period, 638 patients were enrolled and randomly assigned to omeprazole or placebo (319 in each group). The need for endoscopic treatment was lower in the omeprazole group than in the placebo group (60 of the 314 patients included in the analysis [19.1%] vs. 90 of 317 patients [28.4%], P=0.007). There were no significant differences between the omeprazole group and the placebo group in the mean amount of blood transfused (1.54 and 1.88 units, respectively; P=0.12) or the number of patients who had recurrent bleeding (11 and 8, P=0.49), who underwent emergency surgery (3 and 4, P=1.00), or who died within 30 days (8 and 7, P=0.78). The hospital stay was less than 3 days in 60.5% of patients in the omeprazole group, as compared with 49.2% in the placebo group (P=0.005). On endoscopy, fewer patients in the omeprazole group had actively bleeding ulcers (12 of 187, vs. 28 of 190 in the placebo group; P=0.01) and more omeprazole-treated patients had ulcers with clean bases (120 vs. 90, P=0.001). CONCLUSIONS: Infusion of high-dose omeprazole before endoscopy accelerated the resolution of signs of bleeding in ulcers and reduced the need for endoscopic therapy. (ClinicalTrials.gov number, NCT00164866 [ClinicalTrials.gov] .).

Effect of oral esomeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

BACKGROUND: After endoscopic treatment of bleeding peptic ulcer, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding. The role of oral proton pump inhibitors for these patients is uncertain. The purpose of the present study was to assess whether the use of oral esomeprazole would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. METHODS: Patients with actively bleeding ulcers or ulcers with non-bleeding 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 esomeprazole (40 mg p.o. twice daily for 3 days) or placebo. The outcome measures studied were recurrent bleeding, blood transfusion requirement, surgery and death. RESULTS: A total of 70 patients were enrolled, 35 in each group. Bleeding recurred within 30 days in two patients (5.7%) in the esomeprazole group, as compared with three (8.6%) in the placebo group (P = 0.999). Blood transfusion requirement was 2.8 +/- 1.4 units in the esomeprazole group and 2.7 +/- 1.3 units in the placebo group (P = 0.761). Duration of hospitalization was 4.82 +/- 1.8 days in the esomeprazole group and 4.58 +/- 2.7 days in the placebo group (P = 0.792). No patients needed surgery for control of bleeding and no patients died in both groups. CONCLUSIONS: After successful endoscopic treatment of bleeding peptic ulcer, oral use of esomeprazole might offer no additional benefit on the risk of recurrent bleeding.

Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: a U.S. multicenter randomized, double-blind study.

OBJECTIVES: No North American randomized study has compared ulcer rebleeding rates after endoscopic hemostasis in high-risk patients treated with high-dose intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN) would be lower than with IV ranitidine (RAN). METHODS: This was a multicenter, randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with or without epinephrine injection, then were randomly assigned to IV PAN 80 mg plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding rates up to 30 days were compared in an intention-to-treat analysis. RESULTS: The study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN 77). Demographics, APACHE II scores, ulcer type/location, stigmata, and hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72 patients) with PAN and 14.3% (11 of 77) for RAN (p= 0.19). Rebleeds occurred within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day mortality rate was 4%. Nonbleeding severe adverse events were more common in the RAN than in the PAN group (14 [18.1%]vs 7 [9.7%], p= 0.16). CONCLUSIONS: Because of the small sample size of this study, there was an arithmetic but not significant difference in ulcer rebleeding rates.

Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial.

BACKGROUND AND AIM: Following successful endoscopic therapy in patients with peptic ulcer bleeding, rebleeding occurs in 20% of patients. Rebleeding remains the most important determinant of poor prognosis. We investigated whether or not administration of pantoprazole infusion would improve the outcome in ulcer bleeding following successful endoscopic therapy. METHODS: In this double-blind, placebo-controlled, prospective trial, patients who had gastric or duodenal ulcers with active bleeding or non-bleeding visible vessel received combined endoscopy therapy with injection of epinephrine and heater probe application. Patients who achieved hemostasis were randomly assigned to receive pantoprazole (80 mg intravenous bolus followed by an infusion at a rate of 8 mg per hour) or placebo for 72 h. The primary end-point was the rate of rebleeding. RESULTS: Rebleeding was lower in the pantoprazole group (8 of 102 patients, 7.8%) than in the placebo group (20 of 101 patients, 19.8%; P = 0.01). Patients in the pantoprazole group required significantly fewer transfusions (1 +/- 2.5 vs 2 +/- 3.3; P = 0.003) and days of hospitalization (5.6 +/- 5.3 vs 7.7 +/- 7.3; P = 0.0003). Rescue therapies were needed more frequently in the placebo group (7.8% vs 19.8%; P = 0.01). Three (2.9%) patients in the pantoprazole group and eight (7.9%) in the placebo group required surgery to control their bleeding (P = 0.12). Two patients in the pantoprazole group and four in the placebo group died (P = 0.45). CONCLUSION: In patients with bleeding peptic ulcers, the use of high dose pantoprazole infusion following successful endoscopic therapy is effective in reducing rebleeding, transfusion requirements and hospital stay.

The efficacy of high- and low-dose intravenous omeprazole in preventing rebleeding for patients with bleeding peptic ulcers and comorbid illnesses.

This study sought to determine if high-dose omeprazole infusion could improve the control of rebleeding in patients with comorbid illnesses and bleeding peptic ulcers. After achieving hemostasis by endoscopy, 105 patients were randomized into high-dose (n = 52) and low-dose (n = 53) groups, receiving 200 and 80 mg/day omeprazole, respectively, as a continuous infusion for 3 days. Thereafter, oral omeprazole, 20 mg/day, was given. The cumulative rebleeding rates comparatively rose in both groups (high-dose vs. low-dose group), beginning on day 3 (15.4% vs. 11.3%), day 7 (19.6% vs. 20%), and day 14 (32.7% vs. 28.9%), until day 28 (35.4% vs. 33.3%), and were not significantly different between the two groups (P > 0.50). Multiple logistic regression confirmed that a serum albumin level <3 g/dL was an independent factor associated with rebleeding (P = 0.002). For patients with comorbidities, 3-day omeprazole infusion, despite increasing the daily dose from 80 to 200 mg, was not adequate to control peptic ulcer rebleeding.

Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a prospective and randomized trial.

BACKGROUND: Endoscopic application of hemoclips (HC) was prospectively compared with heat probe (HP) treatment in patients with bleeding ulcers. METHODS: One hundred thirteen patients with major stigmata of ulcer hemorrhage were randomly assigned to receive HP (n = 57) or HC (n = 56). Clinical and endoscopic features were comparable in both groups. Recurrent bleeding was retreated with the modality previously used. Patients in whom treatment or retreatment was unsuccessful underwent emergency surgery. RESULTS: Hemostasis, adequate treatment of visible vessel, 30-day mortality, and emergency surgery rates were similar for both groups. Recurrent bleeding was 21% for HP and 1.8% for HC (p < 0.05). Length of hospital stay and transfusion requirements were significantly lower in the HC group. There was no evidence of clip-induced tissue injury or impaired ulcer healing. Clips dislodged spontaneously in most patients within 8 weeks of treatment. No further hemorrhage occurred on a median follow-up of 11 months (range 1-23). CONCLUSIONS: The hemoclip is safe and effective in the treatment of severe ulcer bleeding and is superior to HP in preventing early recurrent bleeding.