nature reviews gastroenterology - - hepatology9(2)97[1]

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 9 | FEBRUARY 2012 | 97

National Institute for Health and Medical Research (INSERM), CICP 803, Department of Gastroenterology, Centre Hospitalier Universitaire de Dijon, 14 rue Gaffarel, BP77908, 21079Dijon, France (M.Bardou, I. Le Ray). 5301 McKenna, Montral, QC H3T 1T9, Canada (D.Benhaberou-Brun). Gastroenterology Department, McGill University Health Centre, Montral General Hospital site, Room D16157b, 1650Cedar Avenue, Montral, QC H3G 1A4, Canada (A.N.Barkun).

Correspondence to: M. Bardou marc.bardou@ ubourgogne.fr

Diagnosis and management of nonvariceal upper gastrointestinal bleedingMarc Bardou, Dalila Benhaberou-Brun, Isabelle Le Ray and Alan N. Barkun

Abstract | Nonvariceal upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality worldwide. Despite the improvements in the management of this condition in western countries, mortality rates have remained at 510% over the past decade. This article presents the main recommendations for the management of UGIB. Preendoscopic management (including use of scoring scales, nasogastric tube placement and blood pressure stabilization) is crucial for triage and optimal resuscitation of patients, and should include a multidisciplinary approach at an early stage. Unless the patient has specific comorbidities, transfusion should only be considered if their hemoglobin level is 70 g/l. Endoscopic therapy, the cornerstone of therapeutic management of highrisk lesions, should not be delayed for more than 24 h following admission. Several endoscopic techniques, mostly using clips or thermal methods, are available and new approaches are emerging. When endoscopy fails, surgery or arterial embolization should be considered. Although the efficacy of prokinetics and highdose intravenous PPI prior to endoscopy is controversial, the use of an intravenous PPI following endoscopy is strongly recommended. Antiplatelet therapy should be suspended and resumed in 35days. Finally, all patients should be tested for Helicobacter pylori by serology in the acute setting.

Bardou, M. etal. Nat. Rev. Gastroenterol. Hepatol. 9, 97104 (2012); published online 10 January 2012; doi:10.1038/nrgastro.2011.260

IntroductionThe annual incidence of upper gastrointestinal bleeding (UGIB) is 48160 events per 100,000 adults in the US, where it is the cause of around 300,000 hospital admis-sions per year.1,2 In Europe, the annual incidence of UGIB in the general population ranges from 19.43,4 to 57.03,5 events per 100,000 individuals. Why such wide ranges exist is not clear, although the European inci-dences were recorded in countries with different health-care systems and capacities to record cases, namely the UK4 and Estonia.5 Additional factors, such as excess of alcohol intake and Helicobacter pylori prevalence, might also explain this large variation in prevalence. In both North America and Europe, around 8090% of acute UGIB episodes have a nonvariceal etiology; peptic ulcers and gastroduodenal erosions account for the majority of such lesions.6,7

UGIB-related mortality rates have decreased slightly over the past two decades, but are still estimated to be 215%.8,9 Two studies conducted in the UK showed that, despite a notable decrease in mortality in patients with UGIB during 19932007, mortality from peptic ulcer bleeding is still 1013%.7,9 Consequently, a multi-disciplinary group of 34 experts from 15 countries pub-lished international guidelines in 20102 (which were developed from initial guidelines published in 2003)

to help clinicians make informed decisions about the optimal management of patients with nonvariceal UGIB.

This Review discusses the diagnosis of UGIB and describes the optimal management of patients with this condition, in accordance with the current consensus recommendations and contemporary literature. The authors examine endoscopy, bleeding management and pharmaco logical therapy for patients with UGIB.

Pre-endoscopic managementResuscitationResuscitation should be initiated for patients with UGIB prior to any other procedure, and should include stabiliza tion of the blood pressure with continuous infusion of fluids.10,11 The objectives of this treatment are reversal of both hypovolemic shock and blood loss using administra tion of intravenous fluids and blood components. No data suggest that any particular type of colloid solution is safer or more effective than any other in patients who need fluid replacement.12 Although the benefit of red blood cell trans fusions has been questioned (studies in a Cochrane review seemed to exclude a large survival benefit),13 the consensus recommendations indi-cate that patients with hemoglobin levels 70 g/l should receive blood trans fusions to reach a target hemoglobin level of 7090 g/l, provided that the individual has no coronary artery disease, tissue hypoperfusion or acute hemorrhage.2 In patients with acute coronary syndrome, UGIB is associated with a markedly increased mortality,14 and a higher hemoglobin target level, above 10 g/l could be required in patients with cardiorespiratory diseases

Competing interestsA.N. Barkun declares associations with the following companies: AstraZeneca, Takeda Canada. See the article online for full details of the relationships. The other authors declare no competing interests.

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to prevent decompensation.2 Nevertheless, avoidance of unnecessary transfusions is important to reduce the risks related to administration of blood components, such as infectious disease or immuno logical complications, and to promote adherence to appropriate transfusion guidelines, as standard practice is not always followed. For example, the UK audit7 found that 73% of patients had a hemoglobin level >80 g/l, but 43% of these patients had received red blood cell transfusions.15 Randomized trials are needed to determine what the ideal hemo globin threshold level is for transfusion according to patient status, owing to the presence of confounding factors such as comorbidities or selection bias in the current cohort studies.

For patients being treated with anticoagulants, such as warfarin, correction of an increased international normal ized ratio (INR) to 2.5 should be considered.2 An increased INR at initial presentation does not predict rebleeding in patients with UGIB, which suggests that endoscopic therapy does not need to be delayed unless the patients INR (or prothrombin time) is markedly above the normal range (0.81.2). However, an INR 1.5 has been associated with increased patient mortality, which probably reflects the presence of cardio vascular comorbidi ties;16 indeed, the INR seems to be most useful as an indicator of comorbidity at the time of initial assessment in patients with UGIB. The gastrointestinal tract is the site of hemorrhage in 41% of patients with a bleeding episode associated with warfarin therapy.17 Such episodes seem to confer considerable morbidity related to transfusion and hospitalization; approximately 1 in 10 major warfarin-associated bleeds are fatal, and 1 in 12 patients will rebleed after resumption of anti-coagulant treatment, mostly from the original location of the lesion.17

Risk stratification and initial therapyAs major bleeding episodes can be fatal for high-risk patients, the initial assessment must be conducted promptly to predict the need for urgent intervention. Scoring scales have, therefore, been developed to evaluate patients upon their arrival at the emergency department. These scales can be used to identify the need for treat-ments, such as resuscitation, endoscopic management or surgery, as well as to estimate the risk of either rebleed-ing or death.18 The GlasgowBlatchford score (GBS) considers both clinical features and laboratory data (Table1).19 Patients with a score of 0 are considered to be at low risk, and some clinicians recommend that this subgroup of patients could be managed as outpatients,

Key points

Resuscitation should be initiated prior to any diagnostic procedure Gastrointestinal endoscopy allows visualization of the stigmata, accurate

assessment of the level of risk and treatment of the underlying lesion Combination of endoscopic therapies improves control of the gastrointestinal

hemorrhage Intravenous PPI therapy after endoscopy is crucial to decrease the risk of

cardiovascular complications and to prevent recurrence of bleeding Helicobacter pylori testing should be performed in the acute setting

as they do not require early endoscopy.2022 Nevertheless, the classification of patients as low risk might not always be accurate. A retrospective study, in which propensity scores were used to reassess the need for inpatient or out-patient manage ment, found that outpatients had a higher mortal ity rate than inpatients after 30days, suggesting that initial assessment was not conducted properly.23 The GBS is used to determine the need for endoscopy, trans-fusion or surgery and, therefore, enables appropriate resources to be allocated to critically ill patients.20,24 For example, the results of one study suggested that patients with a GBS above the threshold value of 12 are the most likely to benefit from early endoscopy.25

As the GBS enables the identification of patients who might need intervention, this score is considered to be preferable to the pre-endoscopic clinical Rockall score (not to be confused with the complete Rockall score,26 which includes both clinical and endoscopic variables, such as diagnosis of the lesion and stigmata of recent hemorrhage), which can only accurately predict the risk of mortality and is less accurate than the GBS for predict-ing rebleeding or the need for surgery (Table2).27 The risk classification obtained by use of the pre-endoscopic clinical Rockall score has been refined into three levels: low (02), intermediate (34) and high (511).28 The complete Rockall score, if used at the time of endoscopy, can identify low-risk patients and facilitate early dis-charge from hospital.10 Nevertheless, the pre-endoscopic Rockall score is better than the complete Rockall score for prediction of rebleeding and mortality in patients with cirrhosis and variceal bleeding (at least among patients with UGIB).29

Although the use of such scores is strongly encour-aged by professional organizations, such as the British Society of Gastroenterology, whose guidelines advise that all patients with suspected UGIB should undergo

Table 1 | GlasgowBlatchford score assessment criteria

Risk factors at presentation Threshold Score

Blood urea nitrogen (mmol/l) 6.57.98.09.910.024.925.0

2346

Hemoglobin for men (g/l) 120130100119


risk scoring as part of their initial assessment on pre-sentation,30 the benefit of these scores in daily clinical practice has been questioned. Insufficient validation or complexity of use have been cited as problems with these scoring systems.10,28,31 An independent team of researchers who conducted validation studies of both the GBS and Rockall scores (both the pre-endoscopic and complete scores) did not recommend their use in the clinical setting.32

Despite the existence of these predictive scores the clinical endoscopists judgment remains crucial in assessing the patients actual level of risk,33 as endo-scopic predictors of an increased risk of rebleeding and mortality include active bleeding, an ulcer size >2 cm, ulcers located on the lesser curve of the stomach or in the posterior or superior duodenum34 and the presence of high-risk stigmata, factors that are not all included in the complete Rockall score.2 Categories of high-risk lesions include actively spurting (Forrest class Ia), oozing blood (Forrest class Ib), nonbleeding visible vessels (Forrest class IIa) and adherent clot (Forrest class IIb).34 Types of low-risk lesions include flat, pig-mented spots (Forrest class IIc) and clean-based ulcers (Forrest class III).35

The need for accurate risk stratification is widely rec-ognized, but current validated scores are underutilized. Therefore, attempts have been made to define accurate scores that are easier to use than the GBS and Rockall scores. For example, the Progetto Nazional Emorragia Digestiva (PNED) score has been developed to predict the risk of mortality and has been suggested, despite not yet being completely validated, to be superior in

predictive accuracy to the complete Rockall score (Table3).36 This superiority was shown by the areas under the receiver operating characteristic curve (AUC) of 0.81, 95% CI 0.720.90 for the PNED score versus 0.66, 95% CI 0.600.72 for the Rockall score. However, the PNED scoring system still needs to be prospectively validated at the international level. In addition, further data should be collected to establish whether the PNED score is any easier to use than the Rockall score in daily clinical practice.

A retrospective analysis of data on 2,380 patients with UGIB suggested that artificial neuronal networks, using 17 pre-endoscopic input variables, might be useful in triage of patients.37 The performance of the neuronal-network-based model in the prediction of mortality risk was significantly superior to that of the complete Rockall score (AUC 0.95, 95% CI 0.920.98 and 0.67, 95% CI 0.650.69, respectively).37 Again, the validity and applic-ability of this new approach needs to be assessed in a routine clinical setting.

Use of nasogastric tubesPlacement of a nasogastric tube is not routinely necessary and opinion is divided on their usefulness.3840 However, nasogastric tubes might be considered if the presence of blood in the nasogastric aspirate confirms an upper gastrointestinal source of bleeding41 and if any doubt per-sists as to the origin of the gastrointestinal bleed. High-risk patients could especially benefit from nasogastric tube placement, which could facilitate visualiza tion during the endoscopic procedure;34,42 however, opin-ions vary as to whether gastric aspiration and lavage are useful, even in selected, high-risk patients.43,44

Pre-endoscopic pharmacological therapyProkinetic agentsThe use of prokinetic agents (such as erythromycin) before gastrointestinal endoscopy shortens the duration of the procedure,45 and reduces the need for a repeated examination.4648 Administration of an erythromycin infusion also improves endoscopic visualization without

Table 2 | Rockall score assessment criteria

Variables Points

Age (years)

100 bpm 1

Systolic blood pressure


the need for placement of a nasogastric tube or gastric lavage; however, no incremental benefit is obtained from combining erythromycin treatment with naso-gastric lavage.40 In a randomized, placebo-controlled trial that involved patients with bleeding esophageal varices, use of an erythromycin infusion significantly increased the proportion of completely empty stomachs compared with placebo (48.9% with erythromycin versus 23.3% with placebo), reduced the mean endoscopy duration (19.0 min with erythromycin versus 26.0 min with placebo) and shortened the duration of hospital stay, from 5.1days in the placebo cohort to 3.4days for patients treated with erythromycin.49 These results are interesting because the origin of UGIB can only be confi-dently determined at the time of endoscopy, and because a recent audit conducted in the UK showed that the fre-quency of variceal bleeding had more than doubled, from 4.4% in 1993 to 11% in 2007.7 Consequently, even in the absence of data indicating that administration of prokinetic agents can decrease the risk of adverse out-comes (such as mortality and rebleeding) and the need for surgery,4547,50 we suggest that after ruling out contra-indications to these agents (such as hypokalemia or a prolonged QT interval) a 250 mg erythromycin infu-sion should be administered over 2030 min, followed by endoscopy approximately 3045 min after the end of the infusion.2,40

PPI treatment prior to endoscopic diagnosisDespite theoretical pharmacological differences between different PPIs, no data support the use of a particular intravenous PPI in preference to another when treat-ing patients with UGIB. In the following paragraphs, PPI will, therefore, be used as a generic term for all such agents, including omeprazole, pantoprazole and esomeprazole.

The clinical efficacy of starting PPI treatment before endoscopy for UGIB remains a controversial issue. A large, double-blind, randomized, controlled trial51 and a meta-analysis that included 2,223 participants from six other randomized, controlled trials52 both found that pre-endoscopic PPI treatment could reduce the propor-tion of patients identified as having high-risk lesions at early endoscopy and the resultant need for endoscopic therapy. Despite these advantages, clear evidence that pre-endoscopic PPI treatment affects mortality, rebleed-ing or the need for surgery is lacking. Nonetheless, despite the lack of evidence, this approach is widely used.2 No recommendations can be made regarding the optimal dose of PPIs administered pre-endoscopy because the dose response has not yet been assessed in this setting, but a reasonable strategy seems to be to adopt a high-dose regimen of 80 mg PPI (intravenous bolus) followed by an 8 mg/h infusion, as used in two of the largest published randomized, controlled trials.51,53 This approach could be cost-effective if endoscopy will be delayed to >16 h after admission, or if patients have a high likelihood of nonvariceal bleedingespecially in those with high-risk symptoms, such as hematemesis or blood in the nasogastric aspirate.54,55

Endoscopic managementTiming and need for early endoscopyInternational consensus guidelines recommend that endoscopy should be performed within 24 h of presenta-tion2,54 for all patients who present with acute UGIB, because early endoscopy is associated with improved outcomes and a reduced duration of hospitalization for low-risk patients and high-risk patients.2 Despite the strength of this recommendation, highlighted in the 2003 international consensus conference,41 a 2007 UK audit revealed that only 74% of patients admitted with acute UGIB underwent endoscopy during their hospital stay, and only 50% of initial endoscopies took place within 24 h of presentation, even among high-risk patients who had a pre-endoscopy Rockall score 5.7,56 In Spain, almost 40% of initial endoscopies were performed >24 h after admission.57 Further support for the need for 24 h access to endoscopy came from the UK audit, in which it was found that mortality was increased, albeit not significantly, in hospitals that did not have out-of-hours endo scopy facilities (risk-adjusted mortality ratio 1.21, 95% CI 0.961.51).7 Large geographical discrep-ancies were shown by a retrospective Australian study, in which only 1.1% of patients admitted for UGIB did not have an endoscopy performed during their hospital stay.58 Although very urgent endoscopy (within 612 h of presentation) does not convincingly improve out-comes,59 the results of an observational study suggested that for a subgroup of very ill patients (GBS 12), the optimal timing of endoscopy should be within 13 h of presentation.25 In this highly selected population, the inpatient all-cause mortality rate was 0% when endo-scopy was performed within 13 h of presentation, which increased to 44% when endoscopy was performed >13 h after presentation.25

Patients classified as being at a very low risk of rebleed-ing could be discharged from hospital immediately after an early endoscopy (Figure1) if they fulfill specific criteria (Box1).34 Indeed, randomized, controlled trials of highly selected patients at very low risk of rebleeding found that no difference in outcomes resulted from a policy of very early discharge from the emergency room.2,60

Traditional endoscopic therapySeveral endoscopic techniques are effective for manage-ment of acute hemorrhage. Injection of epineph-rine alone improves the clinical outcomes of patients with a high-risk bleeding lesion, but this treatment has increased efficacy (and is considered the optimal approach) when used in combination with another tech-nique, such as clip placement or thermocoagulation,2,11 which are also effective as monotherapies.61,62 Technical difficulties might reduce the effectiveness of some endo-scopic treatments, especially when the bleeding ulcer is located on the lesser curve of the stomach or on the duodenal bulb, or when very active bleeding prevents localization of the lesion.34

A clot in an ulcer bed must be vigorously washed, through the endoscope, to determine whether it remains adherent. Optimal treatment of adherent clots remains

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controversial. Endoscopic approaches should be consid-ered, but intensive intravenous PPI therapy alone might be sufficient.63

Routine second-look endoscopy (that is, after success-ful endoscopic treatment of a bleeding lesion) is not recom mended.2 Two meta-analyses suggested a mar-ginal benefit from this technique in terms of reduced rebleeding rates;64,65 but in one of these analyses, the benefit was restricted to patients who received thermo-coagulation as their second treatment.65 However, these meta-analyses included trials that did not employ todays standards of care. The current recommendation is that the need for second-look endoscopy should be consid-ered on a case-by-case basis,2 for example if the effec-tiveness of endoscopic hemostasis is questionable, or if the patient is at a particularly high risk of rebleeding. Second-look endoscopy might also be considered in the intensive care setting, where assessment of rebleeding might be difficult because of prolonged transit time or cardiovascular treatments.

Emerging endoscopic approachesOne emerging modality is a hemostatic powder com-posed of nanoparticles of inorganic proteins that are sprayed onto the bleeding lesion.66,67 The powder was first tested in a porcine model and was then used in 20 patients with active bleeding lesions (Forrest classIaIb) in a single-arm pilot study.67 Acute hemostasis was achieved in all but one patient, who had a pseudo-aneurysm that required arterial embolization. Bleeding recurred in two patients within 72 h of treatment (as indi-cated by a drop in hemoglobin levels), but neither had active bleeding at scheduled second-look endoscopy.67 As the powder is applied without direct contact with the affected gastric or duodenal tissue, the technique is less demanding than clip placement or thermo coagulation, requires limited expertise and seems to be effective in stopping the bleeding. However, this treatment needs to be tested in patients with acute bleeding.

A method that uses a combination of multiple hemo-static clips and a detachable snare ligation device has been described, but only in a case report, for treating bleeding peptic ulcers.68 This technique has subsequently been used to treat peptic ulcers that were not adequately controlled.69 Clearly, clinical trials to assess this approach are needed, but the technique seems to require a high level of expertise.

Management of continued or recurrent bleedingIf the first attempt at endoscopic hemostasis fails to control peptic ulcer bleeding, surgery is the option most likely to achieve hemostasis. However, repeated endo-scopic therapy carries a lower risk of complications than surgery.70 Nonetheless, early surgical intervention is considered for patients with recurrent massive upper gastrointestinal hemorrhage (necessitating >19 blood transfusions) following initial endoscopic treatment.71 However, patients 80years old and those with serious comorbidities are not suitable candidates for surgery, and arterial embolization can be considered for these

indivi duals.72,73 A meta-analysis concluded that success-ful embolization improves survival, and suggested that this approach might lead to equivalent rates of mortal-ity and clinical success compared with surgery, despite the embolization group being older and having a higher prevalence of comorbidities than the surgical group.74

Pharmacological therapyPPIsOpinions differ about the optimal time to begin intra-venous PPI infusion after endoscopic hemostasis.11,51,75 The goal of PPI therapy is to raise the gastric pH suffi-ciently to promote clot stability and to reduce the effect

Very low-risk patientsDischarge home

All other patientsHospitalization

Low-risk patientsInitiate oral PPI

Assessment and appropriate resuscitationRisk stratication Before endoscopy During early endoscopy

Consider secondary prophylaxis H. pylori testing and treatment COX2 can be considered as an alternative to NSAIDs Platelet-inhibiting agents

High-risk patientsEndoscopic hemostasis

Initiate high-dose intravenous PPI

Figure 1 | Algorithm for optimal management of nonvariceal upper gastrointestinal bleeding. On presentation with UGIB, appropriate resuscitation should be carried out. Patients should be assessed and those at very low risk may be discharged. All other patients should be admitted as inpatients and categorized as lowrisk or highrisk groups to determine treatment options. Oral PPI therapy can be adequate for lowrisk patients but those at high risk should be treated with endoscopy and intravenous, highdose PPI. All patients should be considered for secondary prophylaxis, including Helicobacter pylori testing and treatments, use of COX2 antagonists as an alternative to NSAIDs, and PPI for those taking lowdose aspirin. Abbreviations: COX2, cyclooxygenase2 (also known as prostaglandin G/H synthetase 2); UGIB, upper gastrointestinal bleeding.

Box 1 | Lowrisk nonvariceal UGIB

The following criteria have been proposed to enable the selection of patients with lowrisk nonvariceal UGIB for an abbreviated hospital stay or outpatient treatment. Age


of pepsin and gastric acid.76 In a study that aimed to identify the lowest effective dose of PPI, rather than using a high (or low) dose, continuous infusion was the best way to maintain an intragastric pH >6. Two meta-analyses have confirmed that an intravenous PPI bolus followed by continuous PPI infusion over 72 h reduces the rates of mortal ity, rebleeding and surgery. Mortality was particularly reduced in patients who had previ-ously undergone success ful endoscopic hemostasis.77,78 A placebocontrolled, randomized trial demonstrated that in patients with Forrest class IaIIb bleeding lesions, esomeprazole administered as an 80 mg intravenous bolus over 30 min followed by continuous infusion of 8 mg/h for 71.5 h, which was started after successful endoscopic hemostasis and followed by a 40 mg esomeprazole oral regimen for 27days, significantly reduced rates of rebleeding at 72 h (5.9% in the esomeprazole group com-pared to 10.3% in the placebo cohort). The difference in rebleeding rates remained significant at 7days and 30days after initial presentation.53 However, in this study, the 30-day mortality rate was not significantly reduced by the use of a PPI. As mortality was lower than expected in the placebo group (2.1%), this finding might reflect the exclusion of patients with life-threatening systemic disease (American Society of Anesthesiologists class >3).

High-dose oral PPI treatment after endoscopy was effective in early trials conducted in India and Iran,79,80 but differences in the physiological and pharmaco-dynamic characteristics of the patients, as well as their high H.pylori carriage rate and limited comorbidities make the results of these studies difficult to apply to other populations. The endoscopic treatment adminis-tered was also not the current recommended standard.81 Accordingly, the evidence is currently insuffi cient to support the use of either oral PPIs or low-dose intra-venous PPIs. A study published in 2009 assessed gastric pH in patients receiving a 90 mg oral dose of lansopra-zole followed by 30 mg every 3 h (total dose 300 mg in 24 h), after successful endoscopic treatment for peptic ulcer bleeding. The primary end point was the propor-tion of the 24 h period that the patients had a gastric pH >6 (median 55%). However, large differences in this value were evident between individuals (range 699%).82

Platelet aggregation inhibitorsAntiplatelet therapy should be suspended in patients with high cardiovascular risk who have an acid-related cause of bleeding before performing thera peutic endoscopy, but resumed as soon as the patients risk of cardio vascular events outweighs their risk of rebleedinggenerally within 35days.83 Clinicians should be aware of the possi-bility of an increased risk of cardio vascular events associ-ated with PPI treatment in patients who are also taking clopidogrel, a prodrug that becomes activated after being metabolized by the cytochrome P450 2C19 enzymatic complex that also metabolizes PPIs.84 Nevertheless, the clinical relevance of this increased risk is contro versial85,86 and might not be observed when clopidogrel and low-dose aspirin are used together.87 This possible drug inter-action does not apply to the most recently developed

platelet inhibitors, such as prasugrel or ticagrelor, even though they are also prodrugs, mostly because they share the same metabolic pathways.88,89

H.pylori eradicationAll patients should be tested for infection with H.pylori, which is one of the principal causes of bleeding ulcers. Several testing methods are available.90,91 Urea breath tests are widely used,92 but serology is preferable in acute settings as it has the best diagnostic accuracy in this spe-cific condition.93 A second test should be performed if a negative index result is obtained at the time of acute upper gastrointestinal bleeding.2 Real-time PCR might improve H.pylori detection in patients with peptic ulcer bleeding. Real-time PCR testing for a combination of H.pylori 16S rRNA and ureaseA had a sensitivity of 64% and a specificity of 80% in tissue samples that had pre-viously been considered negative by histological testing alone.94 The low prevalence reported for H.pylori infec-tion in patients with UGIB might be related to the delay in testing, which is usually not performed until 4weeks after the bleeding episode.95

Although a full discussion of secondary prophylaxis of UGIB in patients who bled during antiplatelet treatment or as a result of H.pylori infection is beyond the scope of this Review, guidelines on this topic are provided in a consensus document,2 which urges clinicians to follow a decision-making algorithm that balances the risks and benefits associated with the patients medical condition and the available therapeutic agents.96 After the comple-tion of antibiotic and PPI treatment, a urea breath test might be the most convenient approach to assess the effectiveness of H.pylori eradication treatment (unless repeat endoscopy is indicated, at which point gastric biopsies can be performed).

ConclusionsThe acute management of patients with nonvariceal UGIB (Figure1) has evolved considerably over the past 10years. Application of the existing recommenda-tions should lead to improved outcomes. Clinicians are encouraged to monitor ongoing controversies, such as the optimal PPI dose following endoscopic therapy, emerging endoscopic techniques of hemostasis, and the management of patients with UGIB during treatment with antiplatelet agents.

Review criteria

We conducted a literature search using the OVID, MEDLINE, EMBASE, PubMed and ISI Web of Knowledge 4.0 databases to identify articles published in the English or French languages from January 2008 to September 2011. A search strategy was used to identify randomized controlled trials, cohort and casecontrol studies conducted in adults, using combinations of search terms, including UGIB, epidemiology, motility agents, prokinetics, erythromycin, transfusion, endoscopy and proton pump inhibitors. In addition, recursive searches and crossreferencing were performed and manual searches of the reference lists of articles identified in the initial search were completed.

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Author contributionsAll authors contributed substantially to researching data for the article, discussion of the content, writing the manuscript and editing the text.

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Diagnosis and management of nonvariceal upper gastrointestinal bleedingMarc Bardou, Dalila Benhaberou-Brun, Isabelle Le Ray and Alan N. BarkunIntroductionPre-endoscopic managementKey pointsPre-endoscopic pharmacological therapyEndoscopic managementPharmacological therapyFigure 1 | Algorithm for optimal management of nonvariceal upper gastrointestinal bleeding. On presentation with UGIB, appropriate resuscitation should be carried out. Patients should be assessed and those at very low risk may be discharged. All other patBox 1 | Low-risk nonvariceal UGIBReview criteriaH.pylori eradicationConclusionsAuthor contributions

nature reviews gastroenterology - - hepatology9(2)97[1]

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