Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding

BACKGROUND: Recent data suggest that profound acid suppression may improve outcomes of patients in peptic ulcer bleeding. AIM: To better characterize the role of different pharmacological therapies in this population. METHODS: MEDLINE was used to identify randomized trials (01/1990-04/2003) that assessed the efficacy of pharmacological treatments for patients with bleeding peptic ulcers exhibiting high-risk stigmata (Forrest Ia-IIb). Three groups of treatment were assessed: proton-pump inhibitors given as high-dose bolus followed by intravenous constant infusion (40-80 mg and at least 6 mg/h), high-dose oral proton-pump inhibitors (at least twice the standard dosage), non-high-dose proton-pump inhibitors (other proton-pump inhibitors dosing schedules). Mixed-effect models were used to determine rate differences between treatment and control groups. RESULTS: Eighteen studies (1855 patients) were included. High-dose intravenous proton-pump inhibitors significantly reduced rebleeding (-14.6%), surgery (-5.4%) and mortality (-2.7%) compared with placebo, and rebleeding (-20.6%) compared with H(2)RA. Compared with placebo, high-dose oral proton-pump inhibitors significantly reduced only rebleeding (-11.8%), while non-high-dose proton-pump inhibitor treatment significantly improved all three outcomes. CONCLUSIONS: High-dose intravenous proton-pump inhibitor significantly decreases ulcer rebleeding, surgery and mortality. Early data on high-dose oral proton-pump inhibitor suggest improved rebleeding. The non-high-dose proton-pump inhibitor regimens, including a broad range of dosing, also improved outcomes, suggesting that doses inferior to those in the high-dose intravenous proton-pump inhibitor may be effective.     

The short-term medical management of non-variceal upper gastrointestinal bleeding

Upper gastrointestinal (UGI) bleeding occurs frequently and results in substantial patient morbidity, mortality and medical expense. After initial resuscitation to stabilize the patient, carefully performed endoscopy provides an accurate diagnosis and can identify high-risk subgroups in ulcer patients who are likely to rebleed with medical therapy alone and would benefit most from endoscopic haemostasis. Several different pharmacological therapies have been used for patients with bleeding ulcers, including intravenous histamine H(2)-receptor antagonists, proton pump inhibitors, somatostatin and octreotide, and tranexamic acid. The results of several studies and meta-analyses favour high-dose, intravenous proton pump inhibitors, such as omeprazole or pantoprazole, after successful endoscopic haemostasis.For patients with ulcer bleeding and low-risk endoscopic stigmata, high-dose oral proton pump inhibitor therapy is suggested. Medical management with proton pump inhibitors is not a substitute for appropriate endoscopic therapy for patients with UGI bleeding and high-risk ulcer stigmata.     

Intravenous esomeprazole: a pharmacoeconomic profile of its use in the prevention of recurrent peptic ulcer bleeding

Intravenous esomeprazole (Nexium?) is approved in Europe for the prevention of rebleeding following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers. In a pivotal clinical trial, patients with peptic ulcer bleeding and high-risk stigmata who received intravenous esomeprazole for 72 hours following endoscopic haemostatic therapy were significantly less likely than those receiving intravenous placebo to experience recurrent peptic ulcer bleeding at days 3, 7 and 30. In addition, the need for repeat endoscopic haemostatic therapy, the total amount of blood transfused and the number of additional hospital days required because of rebleeding were significantly lower in intravenous esomeprazole recipients than in intravenous placebo recipients. All patients received oral esomeprazole for 27 days following intravenous study drug administration. Intravenous esomeprazole was generally well tolerated in the pivotal trial, with infusion-site reactions being among the most commonly reported adverse events. Two pharmacoeconomic analyses conducted from a healthcare payer perspective used decision-tree models with 30-day time horizons to examine the cost effectiveness and cost utility of intravenous esomeprazole in patients with bleeding peptic ulcers who had undergone endoscopic haemostatic therapy. With regard to the incremental cost per bleed averted, intravenous esomeprazole was predicted to be dominant in Spain and cost effective in Sweden and the US compared with no intravenous esomeprazole. Efficacy results and resource utilization data from the pivotal clinical trial were inputted into this model, and the results of the analysis were generally robust to plausible variations in key variables. In the cost-utility analysis, which was conducted in the UK and is available as an abstract and poster, esomeprazole was considered to be the most cost-effective treatment alternative, compared with omeprazole or pantoprazole. For this analysis, clinical outcomes data were obtained from a systematic review and mixed treatment comparison (given the absence of head-to-head trial data), and utility values were proxied from the literature. In conclusion, intravenous esomeprazole prevents peptic ulcer rebleeding in patients who have undergone endoscopic haemostatic therapy. Pharmacoeconomic analyses support the use of intravenous esomeprazole following endoscopic haemostatic therapy in patients with peptic ulcer bleeding and high-risk stigmata.     

Pre-endoscopic proton pump inhibitor therapy reduces recurrent adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding

BACKGROUND: Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce rebleeding rates in patients with high-risk acute non-variceal upper gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy, although its incremental benefit is unproven. AIM: To determine if providing PPIs before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal upper gastrointestinal bleeding patients. METHODS: We performed a retrospective review to identify patients presenting to two tertiary care centres with acute non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects receiving PPI therapy before endoscopy were compared with those not receiving pre-endoscopic PPI therapy. The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality, readmission within 30 days for acute non-variceal upper gastrointestinal bleeding). RESULTS: 385 patients were included in our study [132 (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI]. Patients receiving pre-endoscopic PPI therapy were significantly less likely to develop adverse outcomes compared with those not given pre-endoscopic PPIs (25% vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and length of hospital stay were also significantly lower in patients receiving pre-endoscopic PPI. CONCLUSIONS: The use of PPIs before endoscopy significantly reduces the risk of developing adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding. Future studies are required to better characterize this relationship.     

消化内镜治疗上消化道出血后再出血的危险因素分析

目的 分析消化内镜治疗上消化道出血后再出血的危险因素.方法 选取2018年1月～2019年12月经消化内镜治疗的上消化道出血患者128例,根据术后是否再出血,将患者分为再出血组与未再出血组,各64例.回顾性收集两组患者的临床资料,分析患者发生再出血的危险因素.结果 两组患者性别、性别以及年龄方面比较差异无统计学意义(P...     

Should prophylactic low-dose aspirin therapy be continued in peptic ulcer bleeding?

Patients taking low-dose aspirin for cardiovascular prevention who develop an acute peptic ulcer bleeding event represent a serious challenge in clinical practice. Aspirin discontinuation is associated with increased risk of developing a new cardiovascular event, but there is little evidence on the outcomes and best management strategy in the setting of an acute ulcer bleeding event. In this clinical scenario, it is common clinical practice to interrupt aspirin treatment for various, sometimes long, periods of time. A recent study suggests that patients with bleeding ulcers who keep taking aspirin after successful endoscopic therapy followed by high-dose intravenous pantoprazole, bolus of 80?mg followed by 8?mg/h for 3 days, have a small increase in the risk of rebleeding but a lower overall and cardiovascular 30-day mortality rate than those who stop taking aspirin treatment. Based on current, although limited, data, we propose that these patients should undergo early endoscopic therapy to control bleeding followed by a high-dose intravenous PPI, with early reintroduction of aspirin treatment within a 5-day window after the last dose. However, in patients taking aspirin for the primary prevention of cardiovascular events, it seems reasonable to stop aspirin treatment, re-evaluate the indication and, if needed, reintroduce aspirin after the risk of ulcer rebleeding decreases, usually after hospital discharge. In the presence of an acute ulcer bleeding event soon after the placement of coronary stents, the risk of stent thrombosis with removal of antiplatelet therapy is very high. We believe that early therapeutic endoscopy and a high-dose intravenous PPI is advisable in order to maintain patients on dual antiplatelet therapy. Until more evidence becomes available, clinicians will have to rely on actual data and the use of common sense to select the best option for the patient.     

Intravenous esomeprazole for prevention of peptic ulcer re-bleeding: rationale/design of Peptic Ulcer Bleed study

Background A limited number of trials have investigated the efficacy of proton pump inhibitors for peptic ulcer bleeding, and some study design issues have been identified. Aim To present the design of a large trial evaluating the effects of intravenous esomeprazole on clinical outcomes in high‐risk patients who have undergone endoscopic haemostasis for peptic ulcer bleeding. Methods The Peptic Ulcer Bleed study is an international, randomized, double‐blind, placebo‐controlled trial comparing either esomeprazole 80 mg intravenous bolus infusion for 30 min followed by esomeprazole 8 mg/h intravenously for 71.5 h, or placebo infusion for 72 h, after successful endoscopic haemostasis in patients with peptic ulcer bleeding and associated high‐risk stigmata. All patients will receive once daily oral esomeprazole 40 mg for 27 days after intravenous therapy. The primary end point is the rate of clinically significant re‐bleeding during the first 72 h after endoscopy. Secondary end points include: rate of re‐bleeding during the first 7 and 30 days after treatment; length of hospitalization; mortality; blood transfusion; endoscopic re‐treatment and surgery. Results Expected 2008. Conclusions The carefully designed protocol and quality control measures represent a pragmatic approach to contemporary challenges in peptic ulcer bleeding management and, it is hoped, qualify the Peptic Ulcer Bleed study as a new standard for future interventional studies.     

Prospective evaluation of patients with upper gastrointestinal haemorrhage

A prospective study was conducted to collect data on clinical and endoscopic diagnosis, associated factors and outcome of 112 consecutive patients with acute upper gastrointestinal haemorrhage admitted to the Dunedin public hospitals over an 18 month period. The mean interval between admission and endoscopy was 20.2 hours. There was a poor correlation between the provisional clinical diagnosis and the endoscopic diagnosis. The causes of bleeding were demonstrated at endoscopy in 87.5% of patients. A history of salicylate, non-steroidal anti-inflammatory drug or significant alcohol ingestion was present in about two-thirds of patients with mucosal abnormalities. The incidence of continued or repeated bleeding was 16%; peptic ulcers accounted for half of these patients. The presence of active bleeding or a visible vessel or blood clot on the ulcer surface indicated a 33% chance of rebleeding; none of the peptic ulcer patients without these signs rebled. Surgery was performed in 11.6% of patients, predominantly for peptic ulcer. The overall mortality was 8% (reducing to 5.4% if patients dying in hepatic failure are excluded), most of the deaths occurring in older patients with complicating medical conditions, and not from uncontrolled haemorrhage.     

Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and the beneficial effect of acid suppression

BACKGROUND: The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re-bleeding. The haemostatic mechanisms that may influence the re-bleeding of ulcers are largely unknown. AIM: We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity. METHODS: Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D-Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes. RESULTS: Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24-h ranitidine infusion. CONCLUSIONS: Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.     

肝硬化并发上消化道出血的护理体会

目的：探讨肝硬化伴上消化道出血患者的临床护理体会。方法：对90例肝硬化合并上消化道出血患者进行精心的治疗和护理,观察其效果。结果：90例患者中2例肝性脑病死亡,1例再出血死亡,占3.3%,自动出院5例,占5.6%,82例患者精心地治疗和护理康复出院,占91.1%。结论：良好的临床护理,可降低肝硬化合并上消化道出血患者的死亡率,提高患者的生存质量。     

电话随访对肝硬化合并上消化道出血患者遵医行为及再出血的影响

目的 探讨电话随访对肝硬化合并上消化道出血患者遵医行为及再出血的影响.方法 选择66例肝硬化合并上消化道出血的出院患者,随机分为对照组及随访组各33例,两组患者均给予常规出院健康宣教,随访组在常规宣教的基础上电话随访1年,出院1年时通过问卷调查评价两组患者的遵医行为和上消化道再出血率.结果 随访组患者的遵医行为明显高于对照组(P＜0.01),而上消化道再出血率明显低于对照组(P＜0.01).结论 对肝硬化合并上消化道出血的出院患者实施电话随访,能明显提高患者的遵医行为,降低上消化道再出血率.     

老年上消化道出血312例临床特点分析

目的探讨老年上消化道出血的病因及临床特点。方法对312例老年上消化道出血患者的临床资料进行回顾性分析。结果老年上消化道出血的主要病因依次为消化性溃疡、急性胃黏膜病变、食管静脉曲张、胃癌。其中胃溃疡出血发生率(31.4%,98/312)高于十二指肠溃疡的发生率(21.8%,68/312);临床表现不典型,以无症状、黑便为首发症状多见。伴随病58.0%(181/312)、并发症25.3%(79/312)、再出血率20.5%(64/312)、死亡率达11.2%(35/312)。结论老年上消化道出血仍以消化性溃疡多见,胃溃疡出血发生率增加且伴随病并发症多,再出血率和死亡率高。     

Frequency of inappropriate continuation of acid suppressive therapy after discharge in patients who began therapy in the surgical intensive care unit

STUDY OBJECTIVE: To determine the frequency with which patients who begin to receive stress ulcer prophylaxis in the surgical intensive care unit (SICU) are discharged receiving inappropriate acid suppressive therapy (AST). DESIGN: Prospective, observational evaluation. Setting. Level 1 trauma center and academic tertiary care hospital. PATIENTS: A total of 248 consecutive adult patients admitted to the SICU during a 6-month period who began to receive AST with a proton pump inhibitor or histamine(2)-receptor antagonist. MEASUREMENTS AND MAIN RESULTS: In most patients (237 [95.6%] of 248), initiation of AST was associated with one or more risk factors for gastrointestinal bleeding. Continuation of AST during hospitalization outside the SICU occurred in 215 patients (86.7%). Sixty patients (24.2%) were discharged from the hospital receiving AST: 52 patients (21.0%) went to skilled nursing facilities or rehabilitation centers, and eight (3.2%) were discharged home. Compared with those whose AST was discontinued in the hospital, patients who continued to receive AST after hospital discharge required extended mechanical ventilation (p=0.001), had twice as many risk factors for gastrointestinal bleeding (p<0.001), were frequently discharged with anticoagulant therapy (p<0.001), exhibited longer hospital and SICU stays (p<0.001), and more frequently demonstrated Glasgow Coma Scale scores of 8 or lower and/or had head injury (p<0.001), hepatic failure (p=0.004), and major trauma (p=0.049). Evaluation of continuation of AST during hospitalization revealed that only 7.4% (16/215) of patients at SICU transfer and 5.0% (3/60) of patients at hospital discharge had a compelling risk factor to continue AST as demonstrated by a coagulopathy at discharge; no patients required mechanical ventilation at hospital discharge. CONCLUSION: Most patients inappropriately continued to receive stress ulcer prophylaxis during post-SICU hospitalization. Presence of risk factors for stress ulcer-related gastrointestinal bleeding at SICU admission appears to influence continuation of AST after discharge from the hospital. A low percentage (3.2%) of patients was discharged home receiving inappropriate AST, yet overall, few study patients demonstrated a compelling risk factor for continuation of AST.     

Systematic review and meta-analysis: proton-pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay--results from the Cochrane Collaboration

BACKGROUND: Proton-pump inhibitors reduce re-bleeding and surgical intervention, but not mortality, after ulcer bleeding. AIM: To examine the effects of proton-pump inhibitor treatment on transfusion requirements and length of hospital stay in patients with ulcer bleeding. METHODS: For the Cochrane Collaboration meta-analysis of randomized-controlled trials of proton-pump inhibitor therapy for ulcer bleeding, outcomes of transfusion requirements and hospital stay were summarized, respectively, as mean (+/-s.d.) units transfused and hospital days. We calculated weighted mean difference with 95% confidence interval. We also performed subgroup analyses according to geographical origin of the randomized-controlled trials. RESULTS: There was significant heterogeneity among randomized-controlled trials for either outcome. Overall, proton-pump inhibitor treatment marginally reduced transfusion requirements (WMD = -0.6 units; 95% CI: -1.1 to 0; P = 0.05) and length of hospitalization (WMD = -1.1 days; 95% CI: -1.5 to -0.7; P < 0.0001). Most of the randomized-controlled trials did not state precise criteria for administering blood transfusion and discharging patients, thereby limiting the strength of conclusions on the pooled effects. CONCLUSIONS: Proton-pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization.     

上消化道大出血术后再出血18例分析

目的：探讨上消化道大出血术后再出血的病因及治疗。方法：回顾分析本院1986年5月～2004年8月收治的上消化道大出血术后再出血18例病人的临床资料。结果：18例再出血病人,10例为胃肠吻合口出血,2例为肝硬化胃底食管静脉曲张破裂出血,2例为遗漏高位小弯溃疡出血,2例为胃小弯侧缝合不严出血,2例为应激性溃疡出血。结论：上消化道大出血术后再出血多为手术操作不熟练、不规范,术中探查不全面。首选术式不当。     

Systematic review and meta-analysis: enhanced efficacy of proton-pump inhibitor therapy for peptic ulcer bleeding in Asia--a post hoc analysis from the Cochrane Collaboration

BACKGROUND: Proton-pump inhibitors reduce re-bleeding rates after ulcer bleeding. However, there is significant heterogeneity among different randomized-controlled trials. AIM: To see whether proton-pump inhibitors for ulcer bleeding produced different clinical outcomes in different geographical locations. METHODS: This was a post hoc analysis of our Cochrane Collaboration systematic review and meta-analysis of proton-pump inhibitor therapy for ulcer bleeding. Sixteen randomized-controlled trials conducted in Europe and North America were pooled and re-analysed separately from seven conducted in Asia. We calculated pooled rates for 30-day all-cause mortality, re-bleeding and surgical intervention and derived odds ratios and numbers needed to treat with 95% confidence intervals. RESULTS: There was no significant heterogeneity for any outcome. Reduced all-cause mortality was seen in the Asian randomized-controlled trials (odds ratios = 0.35; 95% confidence interval: 0.16-0.74; number needed to treat = 33), but not in the others (odds ratios = 1.36; 95% confidence interval: 0.94-1.96; number needed to treat--incalculable). There were significant reductions in re-bleeding and surgery in both sets of randomized-controlled trials, but the effects were quantitatively greater in Asia. CONCLUSIONS: Proton-pump inhibitor therapy for ulcer bleeding has been more efficacious in Asia than elsewhere. This may be because of an enhanced pharmacodynamic effect of proton-pump inhibitors in Asian patients.     

Clinical findings, early endoscopy, and multivariate analysis in patients bleeding from the upper gastrointestinal tract.

A simple system has been developed to identify patients with upper gastrointestinal tract haemorrhage who run a high risk of continued bleeding or rebleeding. The system is based on six items of patient data available at or soon after arrival in hospital. It was evaluated in a prospective study of 66 patients with upper gastrointestinal tract haemorrhage. Over half of the patients classified by the system into a high-risk category either continued bleeding or rebled after apparent cessation (as against one out of 33 patients in the low-risk category). The high-rish group also had a higher mortality (21%) than those in the low-risk group (nil). The addition or subtraction of early endoscopic findings made little difference to the accuracy of prognosis.     

质子泵抑制剂治疗上消化道出血的临床效果分析

目的探讨质子泵抑制剂雷贝拉唑治疗上消化道出血的临床效果。方法选取2012年10月～2013年10月本院收治的上消化道出血患者160例，将其按照随机数字表法分为观察组和对照组各80例。观察组采用质子泵抑制剂雷贝拉唑进行治疗，20mg口服，2次／d，对照组采用H2受体拮抗剂西咪替丁进行治疗，400mg静脉滴注。2次／d，两组均治疗3d。比较两组的临床疗效、再出血率及不良反应情况。结果观察组的总有效率为95．00％，显著高于对照组的81．25％（P〈0.05）；观察组的再出血率为5．00％，显著低于对照组的27．50％（P〈0．05）。两组的不良反应发生率差异无统计学意义（P〉0.05）。结论在同等治疗条件下，雷贝拉唑治疗上消化道出血的临床效果优于西咪替丁。可明显抑制再出血的发生，无严重不良反应，值得临床推广应用。     

Bleeding peptic ulcer in the elderly: risk factors and prevention strategies

Peptic ulcer bleeding is a frequent and dramatic event with both a high mortality rate and a substantial cost for healthcare systems worldwide. It has been found that age is an independent predisposing factor for gastrointestinal bleeding, with the risk increasing significantly in individuals aged>65 years and increasing further in those aged>75 years. Indeed, bleeding incidence and mortality are distinctly higher in elderly patients, especially in those with co-morbidities. NSAID therapy and Helicobacter pylori infection are the most prevalent aetiopathogenetic factors involved in peptic ulcer bleeding. The risk of bleeding seems to be higher for NSAID- than for H. pylori-related ulcers, most likely because the antiplatelet action of NSAIDs impairs the clotting process. NSAID users may be classified as low or high risk, according to the absence or presence of one or more of the following factors associated with an increased risk of bleeding: co-morbidities; corticosteroid or anticoagulant co-therapy; previous dyspepsia, peptic ulcer or ulcer bleeding; and alcohol consumption. Different types of NSAIDs have been associated with different bleeding risk, but no anti-inflammatory drug, including selective cyclo-oxygenase (COX)-2 inhibitors, is completely safe for the stomach. Furthermore, even low-dose aspirin (acetylsalicylic acid) [<325 mg/day] and a standard dose of non-aspirin antiplatelet treatment (clopidogrel or ticlopidine) have been found to cause bleeding and mortality. No clear risk factor favouring H. pylori-related ulcer bleeding has been identified. Peptic ulcer bleeding prevention remains a challenge for the physician, but data are now available on use of a safer and cheaper strategy for both low- and high-risk patients. Unfortunately, despite the fact that several society and national guidelines have been formulated, these are poorly followed in clinical practice. Proton pump inhibitor (PPI) or misoprostol therapy and H. pylori eradication in NSAID-naive patients are the most commonly proposed strategies. Selective COX-2 inhibitor therapy in high-risk patients has also been suggested, but concerns over the possible cardiovascular adverse effects of some of these agents should be taken into account. Moreover, switching to selective COX-2 inhibitors in patients with previous bleeding is not completely risk free, and concomitant PPI therapy is also needed. H. pylori eradication is mandatory in all patients with peptic ulcer, and such an approach has been found to be significantly superior to PPI maintenance therapy. H. pylori eradication is frequently achieved with sequential therapy in elderly patients with peptic ulcer. In conclusion, upper gastrointestinal bleeding is a dramatic event with a high mortality rate, particularly in the elderly. Some effective preventative strategies are now available that should be implemented in clinical practice.     

Review of immediate-release omeprazole for the treatment of gastric acid-related disorders

Immediate-release omeprazole (Zegerid®, Santarus) is the first immediate-release oral proton pump inhibitor to reach the market. As a powder formulation for oral suspension, it is indicated for the treatment of gastroesophageal reflux disease, erosive oesophagitis, duodenal ulcer and gastric ulcer, and is the only proton pump inhibitor approved for the reduction of risk of upper gastrointestinal bleeding in critically ill patients. Administration of immediate-release omeprazole at bedtime results in a rapid and sustained elevation of gastric pH, and seems to provide better night time control of gastric acidity than that observed with conventional morning dosing of delayed-release proton pump inhibitors. The immediate-release formulation may provide a good treatment option for patients who require flexible dosing, quick onset of action and nocturnal gastric acid control.