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18 November 2003 | Volume 139 Issue 10 | Pages 843-857
Background: The management of patients with acute nonvariceal upper gastrointestinal bleeding has evolved substantially over the past 10 years amid a paucity of published consensus guidelines.
Purpose: To provide evidence-based management recommendations that address clinically relevant issues.
Review and Consensus Processes: A multidisciplinary consensus group of 25 voting participants representing 11 national societies used a 7-step approach to develop recommendation statements according to accepted standards. Sources of data included narrative and systematic reviews as well as published and new meta-analyses. The quality of the evidence, the strength of the recommendation, and the level of consensus were graded according to recognized classifications.
Main Findings: Recommendations emphasize appropriate initial resuscitation of the patient and a multidisciplinary approach to clinical risk stratification that determines the need for early endoscopy. Early endoscopy allows safe and prompt discharge of selected patients classified as low risk. Endoscopic hemostasis is reserved for patients with high-risk endoscopic lesions. Although monotherapy with injection or thermal coagulation is effective, the combination is superior to either treatment alone. The placement of endoscopic clips for endoscopic hemostasis appears promising. High-dose intravenous proton-pump inhibition is recommended in patients who have undergone successful endoscopic therapy. Routine second-look endoscopy is not recommended. Patients with upper gastrointestinal bleeding should be tested for Helicobacter pylori infection and receive eradication therapy if infection is present.
Future Directions: The efficacy of newer endoscopic therapeutic technologies, the optimal regimen of proton-pump inhibition, and the roles of other pharmacologic agents require further research.
*For a list of the voting participants in the Nonvariceal Upper GI Bleeding Consensus Conference Group, see the Appendix.
In this context, it is surprising that, except for the recent British Society of Gastroenterology guidelines (9), the last widely disseminated consensus conference and publication of practice guidelines occurred more than 10 years ago (11, 12). Since publication of the British Society of Gastroenterology guidelines, new data have become available and are strengthened by a series of evidence-based systematic reviews and meta-analyses performed for this consensus (13, 14). The current guidelines are a consensus paper with multisociety representation. CLINICAL GUIDELINES
Consensus Recommendations for Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding
Upper gastrointestinal (GI) bleeding represents a substantial clinical and economic burden. It has a prevalence of approximately 170 cases per 100 000 adults per year (1), at an estimated total cost of $750 million in U.S. dollars (2). Peptic ulcer disease accounts for 50% to 70% of cases of acute nonvariceal upper GI bleeding (3, 4). Despite recent advances in therapy, mortality rates have remained essentially unchanged at 6% to 8% (1, 2, 5). This could be explained by the fact that patients are older and have more concurrent illnesses; it may also be due to underuse of endoscopic hemostatic techniques. The Canadian Registry in Upper Gastrointestinal Bleeding and Endoscopy (RUGBE) initiative and international data have demonstrated wide variations in the utilization and timing of different diagnostic and therapeutic technologies, as well as disparate management approaches (4-10).
Methods
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Methods
Author & Article Info
References
The recommendation statements were developed according to generally accepted standards (15, 16). A 7-step approach addressing most of 37 pertinent criteria of validity was followed (16-20). The process of guideline development is described in the Figure.
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The need for clinical practice guidelines on the management of patients with nonvariceal upper GI bleeding was identified by an initial review of the existing literature, current recommendations, and the timing of previously published guidelines. Recommendations are directed primarily to the management of nonvariceal bleeding largely due to peptic ulcers.
Membership of the Consensus Group
An organizing committee selected a multidisciplinary group of 25 voting participants for their expertise in the management of patients with acute nonvariceal upper GI bleeding, evidence-based medicine, and continuing medical education. The group included Canadian and international gastroenterologists, endoscopists, surgeons, family physicians, emergency medicine physicians, pharmacologists, epidemiologists (with methodologic and health economic expertise), and a hospital pharmacist. The attendees represented 11 national societies (Appendix). A representative from the Canadian Association of General Surgeons reviewed the consensus guidelines a posteriori. Nonvoting observers included representatives from government (Health Canada), the pharmaceutical industry, and distributors and manufacturers of endoscopic equipment (Appendix).
Determination of Clinically Relevant Issues
The issues were determined according to perceived clinical importance, likelihood of being resolved with the existing knowledge base, applicability to current practice, and perceived need for change (16). The RUGBE data were critical to this process (4). The conference organizer and a small working group generated a list of topics and circulated it electronically in advance (21, 22). For each topic, a statement was proposed to the consensus conference participants for discussion, revision, and voting.
Nature and Extent of Background Preparation
Literature review methods for relevant articles included MEDLINE searches and manual searches of bibliographies of key articles published in English between 1966 and June 2002. Search terms included upper GI bleeding, non-variceal, guidelines, meta-analysis, naso-gastric tube, risk stratification, re-bleeding, mortality, surgery, endoscopy, second-look, clot, stigmata, injection, thermal coaptive, laser, hemostatic clips, proton pump inhibitor, histamine-receptor antagonist, somatostatin, and octreotide. We referred to past reviews, meta-analyses, and published consensus conferences to summarize data up to 1992. New systematic reviews were conducted on data from the past 10 years on the prevalence and natural history of nonvariceal GI bleeding, risk stratification, and various management strategies. Economic considerations were recognized, but the country-specific nature of most cost data limited the review. Data were formally reviewed, including previous consensus opinions (for recommendations 1, 2, 3, and 18), narrative reviews (for recommendations 4, 11, 12, 13, 14, and 19), systematic reviews (for recommendations 5.1, 5.2, 6, and 20), and meta-analyses (for recommendations 7, 8, 9, 10, 15, 16, and 17).
Data available only in abstract form were not considered, with the exception of results from 2 meta-analyses by Bardou and colleagues from McGill University (13, 14) and the RUGBE initiative (4), which had been submitted for publication at the time of writing of this manuscript. In addition, for recommendations 7 and 10, data from pivotal abstracts were discussed in detail and were published within 3 months following the conference (23, 24). Consequently, a postconference Delphi process was carried out and results from this final vote were included.
More than 875 articles were initially reviewed, and the Delphi process identified 20 issues for discussion. A series of original meta-analyses, including 71 articles and nearly 9000 patients, were performed (13, 14). The key results of specific meta-analyses follow individual statements when appropriate, and full methods and results are available in separate publications (13, 14).
Delphi Consensus Process
Each statement was graded to indicate the level of evidence available and the strength of the recommendation by using the classification system of the Canadian Task Force on the Periodic Health Examination (Table 1) (25). This scheme was developed to assess therapeutic literature, not literature addressing prognosis (25).
General Organization
A 2-day consensus conference was held in June 2002 under the auspices of the Canadian Association of Gastroenterology. The conference was conducted according to generally accepted standards for the development of clinical practice guidelines (15, 16). At the consensus conference, data were presented and the statements and the grades attributed to evidence were discussed, modified if necessary, and voted on by each participant according to the recognized criteria shown in Table 1 (26).
The Canadian Association of Gastroenterology, which administered all aspects of the meeting, secured multipartner funding from industry sponsors. Additional funds were obtained through a peer-review grant received by the Canadian Institutes of Health Research and an internal award from the Research Institute of the McGill University Health Centre. Statements of conflicts of interest were obtained from all voting participants, and additional ethical information was collected (27).
Preparation Process and Format of the Report
A working group drafted the manuscript, which was then reviewed by all voting conference participants and the nonvoting chair, who approved the final draft. A brief narrative summary regarding the pediatric patient was prepared and can be accessed at http://www.cag-acg.org/cag_at_glance/positions.htm. An algorithm specifically designed for use in Canada is also under development.
Role of the Funding Sources
The funding sources had no role in the design, conduct, and reporting of the study or in the decision to submit the results for publication.
Recommendation Statements
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Initial Management
Recommendation 1: Hospitals should develop institution-specific protocols for multidisciplinary management, which should include access to an endoscopist with training in endoscopic hemostasis. Recommendation: C (vote: a, 100%); Evidence: III
Previous consensus groups have recommended a multidisciplinary approach with early involvement of a gastroenterologist and surgeon (9, 11, 12, 28). Hospitals with endoscopy services should have a multidisciplinary team in place with a prespecified chain of notification. Not all institutions have immediate access to these specialists, and not all patients require urgent endoscopy; thus, institution-specific protocols should be developed and updated. Endoscopy privileges should be reserved for practitioners who are properly trained according to established credentialing recommendations (29, 30).
Recommendation 2: Support staff trained to assist in endoscopy should be available for urgent endoscopy. Recommendation: C (vote: a, 92%; b, 8%); Evidence: III
Support staff, including appropriately trained endoscopy assistants, should be available to assist with urgent endoscopies. Any patient identified as high risk for rebleeding ideally should be admitted to a monitored setting for at least the first 24 hours (9). If intensive care beds are unavailable, wards with more intensive monitoring than standard units can be considered.
Recommendation 3: Immediate evaluation and appropriate resuscitation are critical to proper management. Recommendation: C (vote: a, 96%; b, 4%); Evidence: III
Patients with acute bleeding should be evaluated immediately on presentation. Resuscitation, including stabilization of blood pressure and restoration of intravascular volume (9, 11, 12, 28), should precede further diagnostic and therapeutic measures.
Recommendation 4: In selected patients, the placement of a nasogastric tube can be considered because the findings may have prognostic value. Recommendation: B (vote: a, 40%; b, 36%; c, 24%); Evidence: II-3
The presence of blood in nasogastric aspirate confirms an upper GI source. Although some data do not support the placement of a nasogastric tube (31), the detection of red blood with an in-and-out nasogastric tube has been shown to predict poor outcome and the need for emergency endoscopy (4, 5, 32-37). In RUGBE, the presence of bright blood in the aspirate was an independent predictor of rebleeding (Appendix Table 1) (4). Although the consensus panel felt that diagnostic nasogastric aspiration is redundant, if very early endoscopy is to be performed orogastric or nasogastric lavage may be helpful to clear the stomach of blood and clots before endoscopy.
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Risk Stratification
Recommendation 5.1: Clinical (nonendoscopic) stratification of patients into low- and high-risk categories for rebleeding and mortality is important for proper management. Available prognostic scales may be used to assist in decision making. Recommendation: B (vote: a, 76%; b, 24%); Evidence: II-2
Approximately 80% of patients will stop bleeding spontaneously without recurrence (10). Most morbidity and mortality occur among the remaining 20% who have continued or recurrent bleeding (10). Thus, the main goal of management is to identify patients at high risk for an adverse outcome on the basis of clinical (4, 11, 38-40), laboratory (4, 32), and endoscopic variables (4, 10, 39, 41).
Many risk stratification schemes use both clinical and endoscopic criteria. However, patients must often be triaged before endoscopy (4, 42), and reports disagree on the additional prognostic power provided by endoscopic findings (32, 43, 44). There is a large body of evidence on risk stratification using clinical criteria, with variations in patient samples, standards of care, and analytic approaches. Older studies predated modern resuscitation and endoscopy, many included univariate but not multivariate analyses, and few provided prospective validation (45).
We reviewed studies from the past 10 years that used multivariate analyses (1, 4, 32-34, 37, 41, 44, 46-59). The evidence on which such stratification is based stems principally from cohort studies and not cohort-type analyses of actual trials. Clinical predictors of increased risk for rebleeding included age older than 65 years; shock; poor overall health status; comorbid illnesses; low initial hemoglobin level; melena; transfusion requirement; and fresh red blood on rectal examination, in the emesis, or in the nasogastric aspirate (Appendix Table 1) (4, 37, 41, 46-48, 51-59). An increased risk for death was associated with age older than 60 years; shock; poor overall health status; comorbid illnesses; continued bleeding or rebleeding; fresh red blood on rectal examination, in the emesis, or in the nasogastric aspirate; onset of bleeding while hospitalized for another reason; sepsis; or elevated urea, creatinine, or serum aminotransferase levels (Appendix Table 2) (1, 4, 32-34, 49, 56, 58). The setting in which care is provided and the specialty of the attending physician may also influence patient outcomes (60-62).
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The nonendoscopic-based risk score determined by Blatchford and colleagues (63) is calculated from patients' admission hemoglobin level, blood urea level, pulse, systolic blood pressure, presence of syncope or melena, and evidence of hepatic disease or cardiac failure. Cameron and associates (64) have also identified a preendoscopic stratification scheme (64). Concerns about generalizability and validation in different patient populations remain.
Recommendation 5.2: Early stratification of patients into low- and high-risk categories for rebleeding and mortality, based on clinical and endoscopic criteria, is important for proper management. Available prognostic scales may be used to assist in decision making. Recommendation: A (vote: a, 96%; b, 4%); Evidence: I
Previous consensus guidelines and several cohort studies have demonstrated that the risk for rebleeding or continued bleeding is strongly associated with the hemorrhagic stigmata seen at endoscopy (10, 11, 41, 44, 53, 56). In an analysis of data from 37 prospective trials in which patients did not receive endoscopic therapy, Laine and Peterson (10) found that the rate of further bleeding was less than 5% in patients with a clean ulcer base and increased to 10% in patients with a flat spot, 22% in those with an adherent clot, 43% in those with a nonbleeding visible vessel, and 55% in those with active bleeding (oozing and spurting). More recent studies that included multivariate analyses confirmed the increased risk for rebleeding associated with active bleeding and high-risk endoscopic stigmata (Appendix Table 2) (4, 41, 44, 46, 56, 57). Other such endoscopic features included ulcer size (>1 or 2 cm) (52-54, 57, 58) and the site of bleeding (the posterior lesser gastric curvature and posterior duodenal wall) (53, 57).
Several validated scoring systems based on combinations of clinical and endoscopic characteristics can accurately predict the risk for rebleeding or death and permit early discharge and outpatient management of patients at low risk without an increased rate of negative sequelae (see recommendation 6) (37, 48, 49, 51, 63, 65-68). Here, too, the evidence stems principally from cohort studies and not cohort-type analyses of comparative trials. Widely referenced systems include the Rockall risk score, which includes age, presence of shock, comorbid conditions, diagnosis, and endoscopic stigmata of recent hemorrhage (69), and the Baylor bleeding score, generated only from patients who underwent therapeutic endoscopy (51). The Rockall risk score has been validated in most but not all studies for predicting rebleeding; death; and, consequently, health care resource utilization (70-72).
Endoscopic Therapy
Recommendation 6: Early endoscopy (within the first 24 hours) with risk classification by clinical and endoscopic criteria allows for safe and prompt discharge of patients classified as low risk (Recommendation: A [vote: a, 92%; b, 8%]; Evidence: I); improves patient outcomes for patients classified as high risk (Recommendation: C [vote: a, 64%; b, 36%]; Evidence: II-2); and reduces resource utilization for patients classified as either low or high risk (Recommendation: A [vote: a, 88%; b, 12%]; Evidence: I).
The definition of early endoscopy varies widely among studies, from 2 to 24 hours after presentation to the emergency department (41, 73-77). In the RUGBE cohort, first endoscopy in "real life" was performed within 24 hours of presentation in 76% of patients (mean [±SD], 23 ± 38 hours) (4). This was similar to the rate of 78% reported in a survey in the Amsterdam area (42). The consensus panel agreed to define early as within the first 24 hours.
Several observational studies (65, 67, 76, 78-80) and a systematic review (81) support the use of early endoscopic stratification for all risk groups. Studies in low-risk patients have shown no major complications in those triaged to outpatient care with early endoscopy (65, 67, 73, 75, 78, 79, 82, 83). A retrospective cohort trial found reductions in both length of hospital stay and need for surgery with early endoscopy in unselected patients (76).
In a randomized, controlled trial, early endoscopy and endoscopic therapy reduced transfusion requirements and length of hospital stay in patients with bloody nasogastric tube aspirate but not in those with clear or "coffee-grounds" aspirate (74). Studies in patients at low risk (66, 73, 75), patients at high risk (74), and unselected patients (69, 76, 82) have demonstrated statistically significant reductions in length of hospital stay. In patients at low risk, 2 randomized, controlled trials have demonstrated cost reductions of 43% to 91% with the use of early endoscopy (73, 75).
Recommendation 7: A finding of low-risk endoscopic stigmata (a clean-based ulcer or a nonprotuberant pigmented dot in an ulcer bed) is not an indication for endoscopic hemostatic therapy (Recommendation: A [vote: a, 100%]; Evidence: I). A finding of a clot in an ulcer bed warrants targeted irrigation in an attempt at dislodgment, with appropriate treatment of the underlying lesion (Recommendation: A [vote: a, 72%; b, 28%]; Evidence: I). A finding of high-risk endoscopic stigmata (active bleeding or a visible vessel in an ulcer bed) is an indication for immediate endoscopic hemostatic therapy (Recommendation: A [vote: a, 100%]; Evidence: I).
On the basis of the favorable natural history discussed in recommendation 5, the 1989 National Institutes of Health Consensus Conference did not recommend any endoscopic treatment for patients with low-risk endoscopic stigmata (a clean-based ulcer or a nonprotuberant pigmented spot in an ulcer bed) (11). Furthermore, the 2 meta-analyses that have demonstrated the benefits of endoscopic therapy mainly examined patients with high-risk rather than low-risk stigmata, with resultant statistically significant decreases in rates of further bleeding, surgery, and mortality (84, 85). Modern endoscopic hemostasis techniques were reviewed more recently in meta-analyses of 56 studies. Bardou and colleagues (13, 14) showed that, compared with drug or placebo treatment, endoscopic treatment was associated with statistically significant absolute decreases in rates of rebleeding, surgery, and mortality.
The optimal management of adherent clots has long been controversial, since this finding obscures underlying stigmata that may be at high or low risk for rebleeding. The risk for rebleeding with clots that remained adherent after washing has been reported as only 8% in 1 study (86) but as high as 25% to 29% in others (47, 87). Two recent studies found that endoscopic therapy for adherent clots statistically significantly reduced the rate of rebleeding compared with medical therapy alone (23, 24).
Recommendation 8: No single solution for endoscopic injection therapy is superior to another for hemostasis. Recommendation: A (vote: a, 92%; b, 8%); Evidence: I
The meta-analyses by Bardou and colleagues (13, 14), which included 38 relevant studies (52, 88-124), demonstrated no statistically significant benefits of 1 solution over another for endoscopic injection. In individual trials, no statistically significant differences were seen for epinephrine alone versus distilled water (52), cyanoacrylate (107), epinephrine in combination with ethanolamine or polidocanol (94, 123), thrombin (89, 104), sodium tetradecyl sulfate (96), or ethanol (97, 109). Ethanol injection was superior to sprayed epinephrine plus thrombin (103) and epinephrine plus polidocanol (121). In 1 study, no statistically significant differences were seen in treatment with normal saline, hypertonic saline (3% NaCl), 50% glucose–water solution, or pure alcohol (108). Some data suggested that injection of fibrin glue was the same as or better than polidocanol (90, 120).
Recommendation 9: No single method of endoscopic thermal coaptive therapy is superior to another. Recommendation: A (vote: a, 100%); Evidence: I
The McGill University meta-analyses by Bardou and colleagues (13, 14) included 20 studies relevant to this question (93, 95, 100, 105, 106, 110-112, 116, 122, 124-133) and demonstrated no statistically significant benefit of one coaptive endoscopic technique over another. Most individual randomized studies have shown no differences in rates of rebleeding, surgery, and mortality among coaptive therapy with heater probe thermocoagulation, multipolar electrocoagulation, or neodymium yttrium–aluminium–garnet laser when compared with injection therapy, although some studies have shown differences in rates of hemostasis (93, 95, 110, 112, 116, 122, 132). Laser therapy is no longer commonly used for acute management of high-risk patients because of high costs and poor portability of the equipment (134).
Argon plasma coagulation is a noncoaptive method of electrocoagulation in which current is applied to tissues by means of ionized argon gas (plasma) (135). Early uncontrolled experience found it was safe, effective, and easy to perform, with advantages over standard electrocoagulation (135). In a prospective study comparing argon plasma coagulation with heater probe in 41 patients with bleeding peptic ulcers, rates of hemostasis, recurrent bleeding, mortality, and surgery were comparable in both groups, with argon plasma coagulation providing faster hemostasis (126). However, the statistical power of the study was insufficient to conclude equivalence. A larger study, published since the consensus conference was held, suggested no difference between injection plus heater probe and injection plus argon plasma coagulation in 185 patients with high-risk lesions (136).
Recommendation 10: Monotherapy, with injection or thermal coagulation, is an effective endoscopic hemostatic technique for high-risk stigmata; however, the combination is superior to either treatment alone. Recommendation: B (vote: a, 48%; b, 48%; c, 4%); Evidence: I
Previous meta-analyses of injection or thermal endoscopic hemostatic therapies reported statistically significant relative decreases in rebleeding rates (odds ratio, 0.27 to 0.31) and mortality (odds ratio, 0.55 to 0.7) compared with standard therapy (84, 85). The more recent McGill University meta-analyses by Bardou and colleagues found statistically significant reductions in the absolute rates of rebleeding and mortality with endoscopic treatment compared with placebo or pharmacotherapy (see previously discussed recommendations) (13, 14). Combination therapy with both injection and coaptive therapy has shown superiority over medical therapy (23, 24, 137). How combination therapy compares with endoscopic monotherapy and whether combination therapy should be the initial approach remains controversial. Bardou and colleagues (13, 14) investigated combinations of 2 endoscopic methods in 8 studies: epinephrine injection plus thermal treatment in 5 studies (23, 24, 98, 111, 137), epinephrine injection plus laser treatment in 2 studies (102, 113), and epinephrine injection plus clips in 1 study (99). Combination treatment was associated with statistically significant reductions in absolute rates of rebleeding compared with injection alone, thermal treatment alone, or pharmacotherapy. Similar reductions in rebleeding were not observed when the combination was compared with hemoclip therapy alone, despite statistically significant reductions in surgery rates. In an analysis of the 5 studies combining thermal methods with injection (23, 24, 98, 111, 137), combination treatment was associated with statistically significant reductions in absolute rates of rebleeding compared with pharmacologic, injection, or thermal treatment alone. The absolute mortality rates were statistically significantly lower with combination therapy than with pharmacologic or injection therapy. Stratification by endoscopic stigmata yielded insufficient data to compare the combination of injection plus nonlaser thermal therapy with single treatment methods for lesions other than actively spurting lesions (98) and adherent clots (23, 24). Combined injection and laser therapy has shown no substantial advantage over use of injection alone (102, 113).
Recommendation 11: The placement of clips is a promising endoscopic hemostatic therapy for high-risk stigmata. Recommendation: B (vote: a, 44%; b, 52%; c, 4%); Evidence: I
Several randomized, controlled trials have investigated the use of endoscopic clips, alone (99, 127, 138) or in combination (99, 138, 139), for endoscopic hemostasis. Endoscopic clips have shown superiority over heater probe (127) or injection therapy (99) in 2 trials but higher failure rates compared with injection therapy (138) in another. Studies of the combination of injection plus endoscopic clips have demonstrated no statistically significant benefit over injection alone (138, 139) or clips alone (99). The finding of increased rebleeding with the combination of injection and clips compared with clips alone (99, 138) requires further study.
The variable success of endoscopic clips may reflect difficulty with their placement. Some studies report outcomes only of patients in whom clips were successfully placed, rather than performing an intention-to-treat analysis. It is likely that further improvement in the clips and their ease of placement will lead to more widespread use. It was suggested that as the choice of endoscopic therapeutic method evolves, it may, in the future, be tailored to the nature of the underlying high-risk lesion.
Recommendation 12: Routine second-look endoscopy is not recommended. Recommendation: E (vote: a, 92%; b, 8%); Evidence: I
Four randomized, controlled trials have specifically examined the utility of scheduled (programmed) repeated endoscopy after endoscopic hemostatic therapy. Messmann and coworkers (140) found that scheduled repeated endoscopies after initial successful treatment did not improve outcomes compared with second endoscopy performed only at recurrent hemorrhage. In a study of patients with high-risk stigmata, Villanueva and colleagues (141) noted a statistically nonsignificant trend toward better outcomes in the group that received routine second-look endoscopy within 24 hours. A study by Saeed and associates (142) in highly selected patients who had undergone initial endoscopic therapy for persistent high-risk lesions showed benefits for those randomly assigned to repeated hemostatic treatment compared with no retreatment. Rutgeerts and coworkers (120) did not find superiority of repeated sessions versus a single session of fibrin glue injection in patients with high-risk stigmata but did find that the former was superior to polidocanol injection. The variability in patient samples and interventions limits any attempt to pool these data quantitatively. Second-look endoscopy may therefore be of statistical benefit in select high-risk patients, but data are conflicting regarding its routine use. A second endoscopy is ultimately needed in patients whose initial endoscopic examination is incomplete because of technical reasons (such as excessive blood).
Recommendation 13: In cases of rebleeding, a second attempt at endoscopic therapy is generally recommended. Recommendation: A (vote: a, 100%); Evidence: I
In the only randomized comparison, immediate endoscopic retreatment in patients with rebleeding after endoscopic hemostasis reduced the need for surgery without increasing the risk for death and was associated with fewer complications than surgery (143). However, these surgical procedures performed in Hong Kong were somewhat more complex and had greater attendant morbidity than those usually performed in North America. This limits the generalizability of the results. Endoscopic therapy should be tailored according to available expertise.
Recommendation 14: Surgical consultation should be sought for patients who have failed endoscopic therapy. Recommendation: B (vote: a, 100%); Evidence: II-2
In the RUGBE cohort, continued bleeding or rebleeding was noted in 14.1% of patients, and 6.5% required surgery (4). Similar proportions, after differing patient population characteristics are taken into account, have been reported in other large cohorts (34, 42, 49, 56, 81, 144-147). In the study by Lau and colleagues of patients at high risk (143), 27% of those with rebleeding after endoscopic treatment required salvage surgery. Thus, early surgical consultation may be particularly beneficial in patients at high risk for failed endoscopic retreatment.
Pharmacotherapy
Recommendation 15: H 2 -receptor antagonists are not recommended in the management of patients with acute upper GI bleeding. Recommendation: D (vote: a, 92%; b, 8%); Evidence: I
An initial 1985 meta-analysis by Collins and Langman (148), which included 27 randomized trials with more than 2500 patients, suggested that H2-receptor antagonist treatment might reduce the rates of rebleeding, surgery, and death by approximately 10%, 20%, and 30%, respectively, compared with placebo or usual care. However, these results were statistically significant only for surgery and death, and it appeared that the benefit was confined to patients with bleeding gastric ulcers (Appendix Table 3) (148). A 2000 meta-analysis by Selby and associates (149), which included 21 studies and 3566 patients treated with H2-receptor antagonists or proton-pump inhibitors, demonstrated statistically significant reductions in rates of rebleeding and surgery but not mortality compared with placebo. Another recent meta-analysis by Levine and coworkers (150) concluded that intravenous H2-receptor antagonists provided no additional benefit in bleeding duodenal ulcers but provided small but statistically significant absolute risk reductions in rebleeding (7.2%), surgery (6.7%), and death (3.2%) in patients with bleeding gastric ulcer compared with placebo.
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In the McGill University meta-analyses by Bardou and colleagues (13, 14), which included 16 relevant studies assessing H2-receptor antagonist therapy (100, 114, 119, 125, 129, 132, 137, 151-159), no statistically significant improvement in outcomes was noted compared with other pharmacotherapy or endoscopic therapy. However, the results were not stratified according to H2-receptor antagonist dosing regimens or ulcer location.
Recent meta-analyses have found proton-pump inhibitors to be more effective than H2-receptor antagonists (160) and H2-receptor antagonists or placebo (161) in preventing persistent or recurrent bleeding (160, 161) and surgery (161) in selected patients. Given the proven benefit of proton-pump inhibitors (see recommendation 17) and the inconsistent and at best marginal benefits of H2-receptor antagonists, the latter are not recommended for the management of acute upper GI bleeding.
Recommendation 16: Somatostatin and octreotide are not recommended in the routine management of patients with acute nonvariceal upper GI bleeding. Recommendation: C (vote: a, 96%; b, 4%); Evidence: I
A meta-analysis of 14 trials, including 1829 patients treated with somatostatin or octreotide compared with H2-receptor antagonists or placebo, found a reduced risk for rebleeding (Appendix Table 3) (162). The overall results suggested a decreased need for surgery in the somatostatin group, but this was not statistically significant in a subgroup analysis of investigator-blinded trials (162), and no adjustment for confounding or stratification by stigmata was made.
In the McGill University meta-analyses by Bardou and colleagues (13, 14), neither somatostatin nor octreotide improved outcomes compared with other pharmacotherapy or endoscopic therapy (132, 153, 157, 158, 163). Several studies have shown octreotide to be similar to or better than ranitidine in terms of rebleeding but statistically significantly less effective than endoscopic hemostatic therapy (132, 153, 157). In other studies, somatostatin was no more effective than ranitidine (158) but was superior to secretin (163).
The panel felt there was little evidence to support somatostatin or octreotide in the routine management of acute upper GI bleeding. However, this therapy might be useful for patients who are bleeding uncontrollably while awaiting endoscopy or for patients with nonvariceal bleeding who are awaiting surgery or for whom surgery is contraindicated. Although not part of the formal recommendation, this suggestion was made in light of the favorable safety profile of these medications in the acute setting.
Recommendation 17: An intravenous bolus followed by continuous-infusion proton-pump inhibitor is effective in decreasing rebleeding in patients who have undergone successful endoscopic therapy. Recommendation: A (vote: a, 100%); Evidence: I
Four randomized trials specifically assessing high-dose bolus and continuous-infusion proton-pump inhibitors, largely in patients with high-risk stigmata following endoscopic therapy, have shown decreased rebleeding and, in some cases, reduced need for surgery compared with H2-receptor antagonists or placebo (151, 164-166). Two recent meta-analyses demonstrated that intravenous proton-pump inhibitors were more effective than H2-receptor antagonists in preventing persistent or recurrent bleeding (160, 161). Only 1 showed a decrease in surgery rates (161), and neither demonstrated a decrease in mortality rates (Appendix Table 3) (160, 161). The McGill University meta-analyses (13, 14) found that high-dose proton-pump inhibitor therapy after successful endoscopic therapy led to a statistically significant reduction in the absolute rate of rebleeding compared with H2-receptor antagonists alone, H2-receptor antagonists in combination with somatostatin, or placebo. Intravenous proton-pump inhibitors also statistically significantly reduced absolute mortality rates compared with placebo and surgery rates compared with placebo or a combination of H2-receptor antagonists and somatostatin (13, 14). The only study of continuous proton-pump inhibitor infusion that did not show benefit over a regular intravenous omeprazole dosage of 20 mg/d (167) was not included in the meta-analysis; more than 25% of patients had low-risk endoscopic lesions, and the published data did not allow results in the high-risk group to be adequately analyzed separately. Among 156 patients with nonbleeding visible vessels and adherent clots, a recent randomized trial by Sung and colleagues (168) demonstrated the superiority of a combination of intravenous high-dose omeprazole infusion and endoscopic hemostasis over intravenous high-dose treatment alone.
Of interest, the RUGBE registry appeared to confirm that proton-pump inhibitor therapy reduces rates of rebleeding and mortality in high-risk patients and even suggested a trend toward decreased rebleeding in patients with low-risk stigmata after adjustment for confounders (4). These data require prospective confirmation from properly designed comparative trials.
Both the rationale for the use of proton-pump inhibition and the existing data suggest that this is a class effect and that the improvement in rebleeding can be achieved by using either intravenous omeprazole or pantoprazole, 80-mg bolus followed by 8 mg/h for 72 hours after endoscopic therapy. It is unclear what the threshold, or lowest effective dose, would be and whether it would differ among proton-pump inhibitors.
Recommendation 18: In patients awaiting endoscopy, empirical therapy with a high-dose proton pump inhibitor should be considered. Recommendation: C (vote: a, 40%; b, 32%; c, 16%; d, 12%); Evidence: III
This recommendation is based primarily on consensus formed by consideration of biological plausibility of physiologic effect and best available evidence. One study of the use of intravenous proton-pump inhibitors before endoscopic therapy in unselected patients with upper GI bleeding found no difference compared with placebo, despite an improvement in endoscopic stigmata. However, doses of proton-pump inhibitors (omeprazole, 80-mg bolus plus 40 mg intravenously every 8 hours for 1 day, followed by 40 mg orally every 12 hours for 4 days) may have been suboptimal (169). Two studies in Asia compared oral omeprazole, 40 mg every 12 hours for 5 days, with either placebo (without endoscopic therapy) (170) or endoscopic injection of alcohol for high-risk lesions (171). A third study compared the same omeprazole dosage after endoscopic injection therapy with placebo (172). All showed decreased rebleeding with or without decreased rates of surgery. A study from Iran using oral omeprazole, 20 mg every 6 hours for 5 days, which was published after the consensus conference, also suggested decreased rebleeding compared with placebo after injection hemostasis (173). Western trials assessing high-dose oral proton-pump inhibition have included few patients or have adopted an unblinded assessment of outcomes (153, 155), have yielded disparate results, and do not allow definitive conclusions. Indeed, the applicability of the Asian results to a western population has been questioned because of possible differences in physiologic characteristics and proton-pump inhibitor metabolism (174-177). The RUGBE data have suggested some efficacy in patients with both low- and high-risk endoscopic lesions (4). Recent analyses suggest that preendoscopy administration of proton-pump inhibitors may be cost-effective in certain situations (178, 179).
This recommendation recognizes the excellent safety profile of proton-pump inhibitors. The panel did not explicitly endorse an optimal route of administration, although some advocated an intravenous route for patients at high risk and an oral route for those at low risk. Proton-pump inhibitor infusion is not a replacement for urgent endoscopy and hemostasis, where appropriate.
Recommendation 19: Patients considered at low risk for rebleeding after endoscopy can be fed within 24 hours. Recommendation: A (vote: a, 88%; b, 12%); Evidence: I
A randomized trial has shown that the time of refeeding does not influence the hospital course of patients at low risk (180). Patients with major hemorrhage and endoscopic findings of a Mallory–Weiss tear or an ulcer with a clean base, flat spot, or clot may be fed and discharged home immediately after stabilization. The decision is otherwise made on a case-by-case basis depending on the patient's clinical status and the likelihood of repeated endoscopy or surgery.
Recommendation 20: Patients with upper GI bleeding should be tested forHelicobacter pyloriand receive eradication therapy if infection is present. Recommendation: A (vote: a, 96%; b, 4%); Evidence: I
Post-treatment H. pylori infection status has been shown to be an independent predictor of rebleeding (181). Eradication of H. pylori has been demonstrated, in a meta-analysis of selected patients with duodenal ulcers not associated with nonsteroidal anti-inflammatory medication intake (182) and in many randomized, controlled trials (183-187), to reduce the rate of ulcer recurrence and rebleeding in complicated ulcer disease.
Most tests of active infection may exhibit increased false-negative rates in the context of acute bleeding (188-192). Although the optimal diagnostic approach remains unclear, it may include acute testing for H. pylori infection, followed, if results are negative, by a confirmatory test outside the acute context of bleeding. There is no rationale for urgent intravenous eradication therapy; oral therapy can be initiated either immediately or during follow-up in patients found to have H. pylori infection.
Ulcers Associated with Nonsteroidal Anti-Inflammatory Drugs
All of the preceding recommendations also apply to patients who have ulcers associated with nonsteroidal anti-inflammatory drugs. The roles of cyclooxygenase-2 selective inhibitors, coprescription, or H. pylori eradication in patients with bleeding ulcers associated with nonsteroidal anti-inflammatory drugs were beyond the scope of the consensus conference, which focused principally on acute management.
Future Directions
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The conference did not address a formal blueprint for the application of these guidelines as planned. However, we hope that dissemination of the guidelines will result in their implementation and will ultimately improve patient care. Setting quality indicator benchmarks for main outcomes (for example, rebleeding and surgical and mortality rates, as well as duration of hospitalization) may assist the measurement of delivered care. Finally, it is anticipated that these guidelines will need to be updated as data become available for emerging diagnostic and therapeutic technologies.
Appendix: List of Attendees
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Canada: John K. Marshall (Non-Voting Chair), David Armstrong, Marc Bardou, Alan Barkun, J. Decker Butzner, Naoki Chiba, Alan Cockeram, Brian Craig, Robert Enns, Carlo A. Fallone, Marty Fishman, Nigel Flook, Jamie Gregor, Jonathan Love, Norm Marcon, Janet Martin, Joseph Romagnuolo, Alaa Rostom, Sandrine Sabbah, Anthony Taylor, Alan Thomson, and Sander Veldhuyzen van Zanten.
International: Livio Cipolletta, Martin Freeman, James Lau, and Joseph Sung.
Robin McLeod reviewed the manuscript as representative for the Canadian Association of General Surgeons.
Represented Societies
Canadian Association of Gastroenterology (CAG), CAG Practice Affairs Committee, CAG Endoscopy Committee, Canadian Association of General Surgeons, Canadian Association of Emergency Physicians, Canadian Society of Hospital Pharmacists, College of Family Physicians of Canada, Canadian Society of Primary Care Gastroenterology, CAG Pediatrics Committee, American Society for Gastrointestinal Endoscopy, and Health Canada.
Nonvoting Observers
Abdullah M. Hassen (Health Canada); Paul Sinclair (CAG); and representatives of the pharmaceutical industry from Abbott Laboratories Ltd., Altana Canada Inc., AstraZeneca Canada, Carsen Group Inc., Janssen-Ortho Inc., and Pentax Precision Instrument Corp.
Author and Article Information
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TopMethodsAuthor & Article InfoReferences |
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Acknowledgments: The authors thank Pauline Lavigne for the preparation of the manuscript. They also acknowledge the contributions of Dalila Benhaberou-Brun, Mary Muccino, Debbie Ross, and Shelley Natovitch, as well as Paul Sinclair and Sandra Daniels, in assisting in the organization of the Consensus Conference. The Canadian Association of Gastroenterology thanks the sponsors of the Banff Consensus Conference: Abbott Laboratories Ltd., Altana Canada Inc., AstraZeneca Canada, and Janssen-Ortho Inc. It also thanks the conference's supporters: Carsen Group Inc. and Pentax Precision Instrument Corp.
Grant Support: In part by "arms-length" grants to the Canadian Association of Gastroenterology from Abbott Laboratories Ltd., Altana Pharma Canada Inc., AstraZeneca Canada, Carsen Group Inc. (distributors for Olympus in Canada), Janssen-Ortho Inc., and Pentax Precision Instrument Corp.; a peer-reviewed grant from the Canadian Institutes for Health Research; and an institutional award from the McGill University Health Centre Research Institute. The RUGBE initiative referred to in the consensus document was a collaborative effort supported by the Canadian Association of Gastroenterology and an unrestricted grant from Altana Pharma Canada (formerly Byk Canada Inc.).
Potential Financial Conflicts of Interest:Consultancies: A. Barkun (Altana Pharma Canada Inc.); Honoraria: A. Barkun (Altana Pharma Canada Inc.); Grants received: A. Barkun (Altana Pharma Canada Inc.).
Requests for Single Reprints: Alan Barkun, MD, MSc, Division of Gastroenterology, Montreal General Hospital Site, McGill University Health Centre, 1650 Cedar Avenue, Room D7.148, Montreal, Quebec H3G 1A4, Canada.
This consensus conference was endorsed and organized by the Canadian Association of Gastroenterology and was held in Banff, Alberta, Canada, on 8–9 June 2002.
Current Author Addresses: Dr. Barkun: Division of Gastroenterology, Montreal General Hospital Site, McGill University Health Centre, 1650 Cedar Avenue, Room D7.148, Montreal, Quebec H3G 1A4, Canada.
Dr. Bardou: Faculté de Médecine de Dijon, 7, boulevard Jeanne d'Arc, BP 87900, 21079 Dijon Cedex, France.
Dr. Marshall: Division of Gastroenterology, Room 4W8, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
References
|
|---|
|
TopMethodsAuthor & Article InfoReferences |
|---|
1. Blatchford O, Davidson LA, Murray WR, Blatchford M, Pell J. Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study BMJ. 1997;315:510-4. [PMID: 9329304].
2. Jiranek GC, Kozarek RA. A cost-effective approach to the patient with peptic ulcer bleeding Surg Clin North Am. 1996;76:83-103. [PMID: 8629205].[Medline]
3. Marshall JK, Collins SM, Gafni A. Prediction of resource utilization and case cost for acute nonvariceal upper gastrointestinal hemorrhage at a Canadian community hospital Am J Gastroenterol. 1999;94:1841-6. [PMID: 10406245].[Medline]
4. Barkun AN, Chiba N, Enns R, Marshall J, Armstrong D, Sabbah S, et al. Use of a national endoscopic database to determine the adoption of emerging pharmacological and endoscopic technologies in the everyday care of patients with upper GI bleeding: the RUGBE initiative [Abstract] Am J Gastroenterol. 2001;96:261.[Medline]
5. Silverstein FE, Gilbert DA, Tedesco FJ, Buenger NK, Persing J. The national ASGE survey on upper gastrointestinal bleeding. II. Clinical prognostic factors Gastrointest Endosc. 1981;27:80-93. [PMID: 6971776].[Medline]
6. Mondardini A, Barletti C, Rocca G, Garripoli A, Sambataro A, Perotto C, et al. Non-variceal upper gastrointestinal bleeding and Forrest's classification: diagnostic agreement between endoscopists from the same area Endoscopy. 1998;30:508-12. [PMID: 9746157].[Medline]
7. Lau JY, Sung JJ, Chan AC, Lai GW, Lau JT, Ng EK, et al. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts Gastrointest Endosc. 1997;46:33-6. [PMID: 9260702].[Medline]
8. Bair D, Zhou P, Chan R, Armstrong D. Intravenous acid suppression-appropriateness of use in a tertiary care setting [Abstract] Can J Gastroenterol. 2001;15(Suppl A):21-A.[Medline]
9. Non-variceal upper gastrointestinal haemorrhage: guidelines Gut. 2002;51(Suppl 4):iv1-6. [PMID: 12208839].
10. Laine L, Peterson WL. Bleeding peptic ulcer N Engl J Med. 1994;331:717-27. [PMID: 8058080].
11. Therapeutic endoscopy and bleeding ulcers. Natl Inst Health Consens Dev Conf Consens Statement. 1989; 7:1-7. [PMID: 2677688].
12. Guidelines for good practice in and audit of the management of upper gastrointestinal haemorrhage. Report of a joint working group of the British Society of Gastroenterology, the Research Unit of the Royal College of Physicians of London and the Audit Unit of the Royal College of Surgeons of England. J R Coll Physicians Lond. 1992; 26:281-9. [PMID: 1404024].[Medline]
13. Bardou M, Youssef M, Toubouti Y, Benhaberou-Brun D, Rahme E, Barkun A. Newer endoscopic therapies decrease both re-bleeding and mortality in high risk patients with acute peptic ulcer bleeding: a series of meta-analyses [Abstract] Gastroenterology. 2003;123:239.
14. Bardou M, Toubouti Y, Benhaberou-Brun D, Rahme E, Barkun A. High dose proton pump inhibition decrease both re-bleeding and mortality in high-risk patients with acute peptic ulcer bleeding. A series of meta-analyses [Abstract] Gastroenterology. 2003;123:625.
15. Hayward RS, Wilson MC, Tunis SR, Bass EB, Rubin HR, Haynes RB. More informative abstracts of articles describing clinical practice guidelines Ann Intern Med. 1993;118:731-7. [PMID: 8460861].
16. Lomas J. Words without action? The production, dissemination, and impact of consensus recommendations Annu Rev Public Health. 1991;12:41-65. [PMID: 2049143].[Medline]
17. Field MJ, Lohr KN, eds. Clinical Practice Guidelines: Directions for a New Program. Washington, DC: National Academy Pr; 1990.
18. Field MJ, Lohr KN, eds. Clinical Practice Guidelines: From Development to Use. Washington, DC: National Academy Pr; 1992.
19. Cluzeau FA, Littlejohns P, Grimshaw JM, Feder G, Moran SE. Development and application of a generic methodology to assess the quality of clinical guidelines Int J Qual Health Care. 1999;11:21-8. [PMID: 10411286].
20. Eccles M, Clapp Z, Grimshaw J, Adams PC, Higgins B, Purves I, et al. North of England evidence based guidelines development project: methods of guideline development BMJ. 1996;312:760-2. [PMID: 8605466].
21. Cook DJ, Greengold NL, Ellrodt AG, Weingarten SR. The relation between systematic reviews and practice guidelines Ann Intern Med. 1997;127:210-6. [PMID: 9245227].
22. Dalkey N. An experimental study of group opinion: the Delphi Method. Futures. 1969:408-26.
23. Bleau BL, Gostout CJ, Sherman KE, Shaw MJ, Harford WV, Keate RF, et al. Recurrent bleeding from peptic ulcer associated with adherent clot: a randomized study comparing endoscopic treatment with medical therapy Gastrointest Endosc. 2002;56:1-6. [PMID: 12085028].[Medline]
24. Jensen DM, Kovacs TO, Jutabha R, Machicado GA, Gralnek IM, Savides TJ, et al. Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots Gastroenterology. 2002;123:407-13. [PMID: 12145792].[Medline]
25. Goldbloom R, Battista RN. The periodic health examination: 1. Introduction CMAJ. 1986;134:721-3. [PMID: 3948088].[Medline]
26. An evidence-based appraisal of reflux disease management—the Genval Workshop Report. Gut. 1999;44 Suppl 2:S1-16. [PMID: 10741335].
27. Giacomini MK, Cook DJ, Streiner DL, Anand SS. Using practice guidelines to allocate medical technologies. An ethics framework Int J Technol Assess Health Care. 2000;16:987-1002. [PMID: 11155847].[Medline]
28. Clinical pathways for general surgeons: acute upper GI bleeding—peptic ulcer Am Surg. 1999;65:295-7. [PMID: 10075313].[Medline]
29. Eisen GM, Baron TH, Dominitz JA, Faigel DO, Goldstein JL, Johanson JF, et al. Methods of granting hospital privileges to perform gastrointestinal endoscopy Gastrointest Endosc. 2002;55:780-3. [PMID: 12024127].[Medline]
30. MacSween HM. Canadian Association of Gastroenterology Practice Guideline for granting of privileges to perform gastrointestinal endoscopy Can J Gastroenterol. 1997;11:429-32. [PMID: 9286478].[Medline]
31. Cuellar RE, Gavaler JS, Alexander JA, Brouillette DE, Chien MC, Yoo YK, et al. Gastrointestinal tract hemorrhage. The value of a nasogastric aspirate Arch Intern Med. 1990;150:1381-4. [PMID: 2196022].
32. Zimmerman J, Siguencia J, Tsvang E, Beeri R, Arnon R. Predictors of mortality in patients admitted to hospital for acute upper gastrointestinal hemorrhage Scand J Gastroenterol. 1995;30:327-31. [PMID: 7610347].[Medline]
33. Zimmerman J, Meroz Y, Arnon R, Tsvang E, Siguencia J. Predictors of mortality in hospitalized patients with secondary upper gastrointestinal haemorrhage J Intern Med. 1995;237:331-7. [PMID: 7891055].[Medline]
34. Perng CL, Lin HJ, Chen CJ, Lee FY, Lee SD, Lee CH. Characteristics of patients with bleeding peptic ulcer requiring emergency endoscopy and aggressive treatment Am J Gastroenterol. 1994;89:1811-4. [PMID: 7942673].[Medline]
35. Bordley DR, Mushlin AI, Dolan JG, Richardson WS, Barry M, Polio J, et al. Early clinical signs identify low-risk patients with acute upper gastrointestinal hemorrhage JAMA. 1985;253:3282-5. [PMID: 3873550].
36. Consensus development summaries. Endoscopy in upper GI bleeding. Sponsored by the National Institute of Arthritis, Metabolism, and Digestive Diseases, NIH. Conn Med. 1981; 45:445-8. [PMID: 6972854].
37. Corley DA, Stefan AM, Wolf M, Cook EF, Lee TH. Early indicators of prognosis in upper gastrointestinal hemorrhage Am J Gastroenterol. 1998;93:336-40. [PMID: 9517635].[Medline]
38. Schiller KF, Truelove SC, Williams DG. Haematemesis and melaena, with special reference to factors influencing the outcome Br Med J. 1970;2:7-14. [PMID: 5440587].
39. Branicki FJ, Coleman SY, Fok PJ, Pritchett CJ, Fan ST, Lai EC, et al. Bleeding peptic ulcer: a prospective evaluation of risk factors for rebleeding and mortality. World J Surg World J Surg. 1990;14:262-9. [PMID: 2327100].[Medline]
40. Peterson WL. Therapeutic endoscopy and bleeding ulcers. Clinical risk factors Gastrointest Endosc. 1990;36:S14-5. [PMID: 2242801].
41. Hsu PI, Lin XZ, Chan SH, Lin CY, Chang TT, Shin JS, et al. Bleeding peptic ulcer—risk factors for rebleeding and sequential changes in endoscopic findings Gut. 1994;35:746-9. [PMID: 8020797].
42. Vreeburg EM, Snel P, de Bruijne JW, Bartelsman JF, Rauws EA, Tytgat GN. Acute upper gastrointestinal bleeding in the Amsterdam area: incidence, diagnosis, and clinical outcome Am J Gastroenterol. 1997;92:236-43. [PMID: 9040198].[Medline]
43. Farrell RJ, Alsahli M, LaMont JT. Is successful triage of patients with upper-gastrointestinal bleeding possible without endoscopy? Lancet. 2000;356:1289-90. [PMID: 11073012].[Medline]
44. Chung IK, Kim EJ, Lee MS, Kim HS, Park SH, Lee MH, et al. Endoscopic factors predisposing to rebleeding following endoscopic hemostasis in bleeding peptic ulcers Endoscopy. 2001;33:969-75. [PMID: 11668406].[Medline]
45. Hussain H, Lapin S, Cappell MS. Clinical scoring systems for determining the prognosis of gastrointestinal bleeding Gastroenterol Clin North Am. 2000;29:445-64. [PMID: 10836189].[Medline]
46. Jaramillo JL, Galvez C, Carmona C, Montero JL, Mino G. Prediction of further hemorrhage in bleeding peptic ulcer Am J Gastroenterol. 1994;89:2135-8. [PMID: 7977228].[Medline]
47. Lin HJ, Wang K, Perng CL, Lee FY, Lee CH, Lee SD. Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation Gastrointest Endosc. 1996;43:470-3. [PMID: 8726760].[Medline]
48. Kollef MH, O'Brien JD, Zuckerman GR, Shannon W. BLEED: a classification tool to predict outcomes in patients with acute upper and lower gastrointestinal hemorrhage Crit Care Med. 1997;25:1125-32. [PMID: 9233736].[Medline]
49. Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage Gut. 1996;38:316-21. [PMID: 8675081].
50. Kubba AK, Choudari C, Rajgopal C, Ghosh S, Palmer KR. Reduced long-term survival following major peptic ulcer haemorrhage Br J Surg. 1997;84:265-8. [PMID: 9052452].[Medline]
51. Saeed ZA, Winchester CB, Michaletz PA, Woods KL, Graham DY. A scoring system to predict rebleeding after endoscopic therapy of nonvariceal upper gastrointestinal hemorrhage, with a comparison of heat probe and ethanol injection Am J Gastroenterol. 1993;88:1842-9. [PMID: 8237930].[Medline]
52. Lai KH, Peng SN, Guo WS, Lee FY, Chang FY, Malik U, et al. Endoscopic injection for the treatment of bleeding ulcers: local tamponade or drug effect? Endoscopy. 1994;26:338-41. [PMID: 8076564].[Medline]
53. Villanueva C, Balanzo J, Espinos JC, Domenech JM, Sainz S, Call J, et al. Prediction of therapeutic failure in patients with bleeding peptic ulcer treated with endoscopic injection Dig Dis Sci. 1993;38:2062-70. [PMID: 8223082].[Medline]
54. Lin HJ, Perng CL, Lee FY, Lee CH, Lee SD. Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study Gut. 1994;35:1389-93. [PMID: 7959193].
55. Terdiman JP, Ostroff JW. Risk of persistent or recurrent and intractable upper gastrointestinal bleeding in the era of therapeutic endoscopy Am J Gastroenterol. 1997;92:1805-11. [PMID: 9382041].[Medline]
56. Katschinski B, Logan R, Davies J, Faulkner G, Pearson J, Langman M. Prognostic factors in upper gastrointestinal bleeding Dig Dis Sci. 1994;39:706-12. [PMID: 7908623].[Medline]
57. Brullet E, Campo R, Calvet X, Coroleu D, Rivero E, Simo Deu J. Factors related to the failure of endoscopic injection therapy for bleeding gastric ulcer Gut. 1996;39:155-8. [PMID: 8977333].
58. Brullet E, Calvet X, Campo R, Rue M, Catot L, Donoso L. Factors predicting failure of endoscopic injection therapy in bleeding duodenal ulcer Gastrointest Endosc. 1996;43:111-6. [PMID: 8635702].[Medline]
59. Mahadeva S, Linch M, Hull MA. Variable use of endoscopic haemostasis in the management of bleeding peptic ulcers Postgrad Med J. 2002;78:347-51. [PMID: 12151690].
60. Cooper GS, Chak A, Harper DL, Pine M, Rosenthal GE. Care of patients with upper gastrointestinal hemorrhage in academic medical centers: a community-based comparison Gastroenterology. 1996;111:385-90. [PMID: 8690203].[Medline]
61. Cooper GS, Chak A, Way LE, Hammar PJ, Harper DL, Rosenthal GE. Endoscopic practice for upper gastrointestinal hemorrhage: differences between major teaching and community-based hospitals Gastrointest Endosc. 1998;48:348-53. [PMID: 9786105].[Medline]
62. Quirk DM, Barry MJ, Aserkoff B, Podolsky DK. Physician specialty and variations in the cost of treating patients with acute upper gastrointestinal bleeding Gastroenterology. 1997;113:1443-8. [PMID: 9352845].[Medline]
63. Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage Lancet. 2000;356:1318-21. [PMID: 11073021].[Medline]
64. Cameron EA, Pratap JN, Sims TJ, Inman S, Boyd D, Ward M, et al. Three-year prospective validation of a pre-endoscopic risk stratification in patients with acute upper-gastrointestinal haemorrhage Eur J Gastroenterol Hepatol. 2002;14:497-501. [PMID: 11984147].[Medline]
65. Longstreth GF, Feitelberg SP. Outpatient care of selected patients with acute non-variceal upper gastrointestinal haemorrhage Lancet. 1995;345:108-11. [PMID: 7815854].[Medline]
66. Hay JA, Maldonado L, Weingarten SR, Ellrodt AG. Prospective evaluation of a clinical guideline recommending hospital length of stay in upper gastrointestinal tract hemorrhage JAMA. 1997;278:2151-6. [PMID: 9417008].
67. Lai KC, Hui WM, Wong BC, Ching CK, Lam SK. A retrospective and prospective study on the safety of discharging selected patients with duodenal ulcer bleeding on the same day as endoscopy Gastrointest Endosc. 1997;45:26-30. [PMID: 9013166].[Medline]
68. Park KG, Steele RJ, Mollison J, Crofts TJ. Prediction of recurrent bleeding after endoscopic haemostasis in non-variceal upper gastrointestinal haemorrhage Br J Surg. 1994;81:1465-8. [PMID: 7820473].[Medline]
69. Rockall TA, Logan RF, Devlin HB, Northfield TC. Selection of patients for early discharge or outpatient care after acute upper gastrointestinal haemorrhage. National Audit of Acute Upper Gastrointestinal Haemorrhage Lancet. 1996;347:1138-40. [PMID: 8609747].[Medline]
70. Vreeburg EM, Terwee CB, Snel P, Rauws EA, Bartelsman JF, Meulen JH, et al. Validation of the Rockall risk scoring system in upper gastrointestinal bleeding Gut. 1999;44:331-5. [PMID: 10026316].
71. Sanders DS, Carter MJ, Goodchap RJ, Cross SS, Gleeson DC, Lobo AJ. Prospective validation of the Rockall risk scoring system for upper GI hemorrhage in subgroups of patients with varices and peptic ulcers Am J Gastroenterol. 2002;97:630-5. [PMID: 11922558].[Medline]
72. Dulai GS, Gralnek IM, Oei TT, Chang D, Alofaituli G, Gornbein J, et al. Utilization of health care resources for low-risk patients with acute, nonvariceal upper GI hemorrhage: an historical cohort study Gastrointest Endosc. 2002;55:321-7. [PMID: 11868003].[Medline]
73. Cipolletta L, Bianco MA, Rotondano G, Marmo R, Piscopo R. Outpatient management for low-risk nonvariceal upper GI bleeding: a randomized controlled trial Gastrointest Endosc. 2002;55:1-5. [PMID: 11756905].[Medline]
74. Lin HJ, Wang K, Perng CL, Chua RT, Lee FY, Lee CH, et al. Early or delayed endoscopy for patients with peptic ulcer bleeding. A prospective randomized study J Clin Gastroenterol. 1996;22:267-71. [PMID: 8771420].[Medline]
75. Lee JG, Turnipseed S, Romano PS, Vigil H, Azari R, Melnikoff N, et al. Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial Gastrointest Endosc. 1999;50:755-61. [PMID: 10570332].[Medline]
76. Cooper GS, Chak A, Connors AF Jr, Harper DL, Rosenthal GE. The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis Med Care. 1998;36:462-74. [PMID: 9544587].[Medline]
77. Chak A, Cooper GS, Lloyd LE, Kolz CS, Barnhart BA, Wong RC. Effectiveness of endoscopy in patients admitted to the intensive care unit with upper GI hemorrhage Gastrointest Endosc. 2001;53:6-13. [PMID: 11154481].[Medline]
78. Cebollero-Santamaria F, Smith J, Gioe S, Van Frank T, Mc Call R, Airhart J, et al. Selective outpatient management of upper gastrointestinal bleeding in the elderly Am J Gastroenterol. 1999;94:1242-7. [PMID: 10235201].[Medline]
79. Longstreth GF, Feitelberg SP. Successful outpatient management of acute upper gastrointestinal hemorrhage: use of practice guidelines in a large patient series Gastrointest Endosc. 1998;47:219-22. [PMID: 9540873].[Medline]
80. Almela P, Benages A, Peiro S, Minguez M, Pena A, Pascual I, et al. Outpatient management of upper digestive hemorrhage not associated with portal hypertension: a large prospective cohort Am J Gastroenterol. 2001;96:2341-8. [PMID: 11513172].[Medline]
81. Cooper GS, Chak A, Way LE, Hammar PJ, Harper DL, Rosenthal GE. Early endoscopy in upper gastrointestinal hemorrhage: associations with recurrent bleeding, surgery, and length of hospital stay Gastrointest Endosc. 1999;49:145-52. [PMID: 9925690].[Medline]
82. Spiegel BM, Vakil NB, Ofman JJ. Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review Arch Intern Med. 2001;161:1393-404. [PMID: 11386888].
83. Almela P, Benages A, Peiro S, Grau F, Minguez M, Pena A, et al. [Outpatient care of upper gastrointestinal hemorrhage not related to portal hypertension] Med Clin (Barc). 2000;114(Suppl 2):68-73. [PMID: 10916810].
84. Sacks HS, Chalmers TC, Blum AL, Berrier J, Pagano D. Endoscopic hemostasis. An effective therapy for bleeding peptic ulcers JAMA. 1990;264:494-9. [PMID: 2142225].
85. Cook DJ, Guyatt GH, Salena BJ, Laine LA. Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis Gastroenterology. 1992;102:139-48. [PMID: 1530782].[Medline]
86. Laine L, Stein C, Sharma V. A prospective outcome study of patients with clot in an ulcer and the effect of irrigation Gastrointest Endosc. 1996;43:107-10. [PMID: 8635701].[Medline]
87. Lau JY, Chung SC, Leung JW, Lo KK, Yung MY, Li AK. The evolution of stigmata of hemorrhage in bleeding peptic ulcers: a sequential endoscopic study Endoscopy. 1998;30:513-8. [PMID: 9746158].[Medline]
88. Acalovschi I, Pascu O, Draghici A. Nonsurgical control of upper gastrointestinal hemorrhage in old age patients: intragastric norepinephrine and endoscopic alcoholization of lesions Intensive Care Med. 1990;16:180-3. [PMID: 2191020].[Medline]
89. Balanzo J, Villanueva C, Sainz S, Espinos JC, Mendez C, Guarner C, et al. Injection therapy of bleeding peptic ulcer. A prospective, randomized trial using epinephrine and thrombin Endoscopy. 1990;22:157-9. [PMID: 2209496].[Medline]
90. Berg PL, Barina W, Born P. Endoscopic injection of fibrin glue versus polidocanol in peptic ulcer hemorrhage: a pilot study Endoscopy. 1994;26:528-30. [PMID: 7828565].[Medline]
91. Bour B, Pariente EA, Hamelin B, Garcia E. Orally administered omeprazole versus injection therapy in the prevention of rebleeding from peptic ulcer with visible vessel. A multicenter randomized study Gastroenterol Clin Biol. 1993;17:329-33. [PMID: 8349066].[Medline]
92. Carter R, Anderson JR. Randomized trial of adrenaline injection and laser photocoagulation in the control of haemorrhage from peptic ulcer Br J Surg. 1994;81:869-71. [PMID: 8044606].[Medline]
93. Choudari CP, Rajgopal C, Palmer KR. Comparison of endoscopic injection therapy versus the heater probe in major peptic ulcer haemorrhage Gut. 1992;33:1159-61. [PMID: 1427365].
94. Choudari CP, Palmer KR. Endoscopic injection therapy for bleeding peptic ulcer; a comparison of adrenaline alone with adrenaline plus ethanolamine oleate Gut. 1994;35:608-10. [PMID: 8200551].
95. Chung SC, Leung JW, Sung JY, Lo KK, Li AK. Injection or heat probe for bleeding ulcer Gastroenterology. 1991;100:33-7. [PMID: 1983848].[Medline]
96. Chung SC, Leung JW, Leong HT, Lo KK, Li AK. Adding a sclerosant to endoscopic epinephrine injection in actively bleeding ulcers: a randomized trial Gastrointest Endosc. 1993;39:611-5. [PMID: 8224679].[Medline]
97. Chung SC, Leong HT, Chan AC, Lau JY, Yung MY, Leung JW, et al. Epinephrine or epinephrine plus alcohol for injection of bleeding ulcers: a prospective randomized trial Gastrointest Endosc. 1996;43:591-5. [PMID: 8781939].[Medline]
98. Chung SS, Lau JY, Sung JJ, Chan AC, Lai CW, Ng EK, et al. Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers BMJ. 1997;314:1307-11. [PMID: 9158465].
99. Chung IK, Ham JS, Kim HS, Park SH, Lee MH, Kim SJ. Comparison of the hemostatic efficacy of the endoscopic hemoclip method with hypertonic saline-epinephrine injection and a combination of the two for the management of bleeding peptic ulcers Gastrointest Endosc. 1999;49:13-8. [PMID: 9869717].[Medline]
100. Gralnek IM, Jensen DM, Gornbein J, Kovacs TO, Jutabha R, Freeman ML, et al. Clinical and economic outcomes of individuals with severe peptic ulcer hemorrhage and nonbleeding visible vessel: an analysis of two prospective clinical trials Am J Gastroenterol. 1998;93:2047-56. [PMID: 9820371].[Medline]
101. Grosso C, Rossi A, Gambitta P, Bini M, Zanasi G, Pirone Z, et al. Non-bleeding visible vessel treatment: perendoscopic injection therapy versus omeprazole infusion Scand J Gastroenterol. 1995;30:872-5. [PMID: 8578185].[Medline]
102. Heldwein W, Avenhaus W, Schonekas H, Kaess H, Muller-Lissner S, Hasford B, et al. Injection of fibrin tissue adhesive versus laser photocoagulation in the treatment of high-risk bleeding peptic ulcers: a controlled randomized study Endoscopy. 1996;28:756-60. [PMID: 9007429].[Medline]
103. Koyama T, Fujimoto K, Iwakiri R, Sakata H, Sakata Y, Yamaoka K, et al. Prevention of recurrent bleeding from gastric ulcer with a nonbleeding visible vessel by endoscopic injection of absolute ethanol: a prospective, controlled trial Gastrointest Endosc. 1995;42:128-31. [PMID: 7590047].[Medline]
104. Kubba AK, Murphy W, Palmer KR. Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin Gastroenterology. 1996;111:623-8. [PMID: 8780566].[Medline]
105. Laine L. Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. A prospective, randomized trial Gastroenterology. 1990;99:1303-6. [PMID: 2210238].[Medline]
106. Laine L, Estrada R. Randomized trial of normal saline solution injection versus bipolar electrocoagulation for treatment of patients with high-risk bleeding ulcers: is local tamponade enough? Gastrointest Endosc. 2002;55:6-10. [PMID: 11756906].[Medline]
107. Lee KJ, Kim JH, Hahm KB, Cho SW, Park YS. Randomized trial of N-butyl-2-cyanoacrylate compared with injection of hypertonic saline-epinephrine in the endoscopic treatment of bleeding peptic ulcers Endoscopy. 2000;32:505-11. [PMID: 10917181].[Medline]
108. Lin HJ, Perng CL, Lee FY, Chan CY, Huang ZC, Lee SD, et al. Endoscopic injection for the arrest of peptic ulcer hemorrhage: final results of a prospective, randomized comparative trial Gastrointest Endosc. 1993;39:15-9. [PMID: 8454139].[Medline]
109. Lin HJ, Perng CL, Lee SD. Is sclerosant injection mandatory after an epinephrine injection for arrest of peptic ulcer haemorrhage? A prospective, randomised, comparative study Gut. 1993;34:1182-5. [PMID: 8406150].
110. Lin HJ, Lee FY, Kang WM, Tsai YT, Lee SD, Lee CH. Heat probe thermocoagulation and pure alcohol injection in massive peptic ulcer haemorrhage: a prospective, randomised controlled trial Gut. 1990;31:753-7. [PMID: 2196207].
111. Lin HJ, Tseng GY, Perng CL, Lee FY, Chang FY, Lee SD. Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding Gut. 1999;44:715-9. [PMID: 10205211].
112. Llach J, Bordas JM, Salmeron JM, Panes J, Garcia-Pagan JC, Feu F, et al. A prospective randomized trial of heater probe thermocoagulation versus injection therapy in peptic ulcer hemorrhage Gastrointest Endosc. 1996;43:117-20. [PMID: 8635703].[Medline]
113. Loizou LA, Bown SG. Endoscopic treatment for bleeding peptic ulcers: randomised comparison of adrenaline injection and adrenaline injection + Nd:YAG laser photocoagulation Gut. 1991;32:1100-3. [PMID: 1955161].
114. Moreto M, Zaballa M, Suarez MJ, Ibanez S, Ojembarrena E, Castillo JM. Endoscopic local injection of ethanolamine oleate and thrombin as an effective treatment for bleeding duodenal ulcer: a controlled trial Gut. 1992;33:456-9. [PMID: 1582586].
115. Oxner RB, Simmonds NJ, Gertner DJ, Nightingale JM, Burnham WR. Controlled trial of endoscopic injection treatment for bleeding from peptic ulcers with visible vessels Lancet. 1992;339:966-8. [PMID: 1348805].[Medline]
116. Panes J, Viver J, Forne M. Randomized comparison of endoscopic microwave coagulation and endoscopic sclerosis in the treatment of bleeding peptic ulcers Gastrointest Endosc. 1991;37:611-6. [PMID: 1756919].[Medline]
117. Pescatore P, Jornod P, Borovicka J, Pantoflickova D, Suter W, Meyenberger C, et al. Epinephrine versus epinephrine plus fibrin glue injection in peptic ulcer bleeding: a prospective randomized trial Gastrointest Endosc. 2002;55:348-53. [PMID: 11868007].[Medline]
118. Pulanic R, Vucelic B, Rosandic M, Opacic M, Rustemovic N, Krznaric Z, et al. Comparison of injection sclerotherapy and laser photocoagulation for bleeding peptic ulcers Endoscopy. 1995;27:291-7. [PMID: 7555933].[Medline]
119. Rajgopal C, Palmer KR. Endoscopic injection sclerosis: effective treatment for bleeding peptic ulcer Gut. 1991;32:727-9. [PMID: 1855676].
120. Rutgeerts P, Rauws E, Wara P, Swain P, Hoos A, Solleder E, et al. Randomised trial of single and repeated fibrin glue compared with injection of polidocanol in treatment of bleeding peptic ulcer Lancet. 1997;350:692-6. [PMID: 9291903].[Medline]
121. Rutgeerts P, Gevers AM, Hiele M, Broeckaert L, Vantrappen G. Endoscopic injection therapy to prevent rebleeding from peptic ulcers with a protruding vessel: a controlled comparative trial Gut. 1993;34:348-50. [PMID: 8472981].
122. Sofia C, Portela F, Gregorio C, Rosa A, Camacho E, Tome L, et al. Endoscopic injection therapy vs. multipolar electrocoagulation vs. laser vs. injection + octreotide vs. injection + omeprazole in the treatment of bleeding peptic ulcers. A prospective randomized study Hepatogastroenterology. 2000;47:1332-6. [PMID: 11100345].[Medline]
123. Villanueva C, Balanzo J, Espinos JC, Fabrega E, Sainz S, Gonzalez D, et al. Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol J Clin Gastroenterol. 1993;17:195-200. [PMID: 8228078].[Medline]
124. Waring JP, Sanowski RA, Sawyer RL, Woods CA, Foutch PG. A randomized comparison of multipolar electrocoagulation and injection sclerosis for the treatment of bleeding peptic ulcer Gastrointest Endosc. 1991;37:295-8. [PMID: 2070977].[Medline]
125. Chua RT, Lin HJ, Wang K, Perng CL, Lo WC, Lee CH, et al. Intravenous omeprazole prevents rebleeding in peptic ulcer patients with a non-bleeding visible vessel: a preliminary report of a randomized controlled study Zhonghua Yi Xue Za Zhi (Taipei). 1996;57:139-45. [PMID: 8634929].
126. Cipolletta L, Bianco MA, Rotondano G, Piscopo R, Prisco A, Garofano ML. Prospective comparison of argon plasma coagulator and heater probe in the endoscopic treatment of major peptic ulcer bleeding Gastrointest Endosc. 1998;48:191-5. [PMID: 9717787].[Medline]
127. Cipolletta L, Bianco MA, Marmo R, Rotondano G, Piscopo R, Vingiani AM, et al. Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a prospective and randomized trial Gastrointest Endosc. 2001;53:147-51. [PMID: 11174282].[Medline]
128. Hui WM, Ng MM, Lok AS, Lai CL, Lau YN, Lam SK. A randomized comparative study of laser photocoagulation, heater probe, and bipolar electrocoagulation in the treatment of actively bleeding ulcers Gastrointest Endosc. 1991;37:299-304. [PMID: 2070978].[Medline]
129. Jaramillo JL, Carmona C, Galvez C, de la Mata M, Mino G. Efficacy of the heater probe in peptic ulcer with a non-bleeding visible vessel. A controlled, randomised study Gut. 1993;34:1502-6. [PMID: 8244132].
130. Lin HJ, Lee FY, Kang WM, Tsai YT, Lee SD, Lee CH. A controlled study of therapeutic endoscopy for peptic ulcer with non-bleeding visible vessel Gastrointest Endosc. 1990;36:241-6. [PMID: 2194899].[Medline]
131. Lin HJ, Wang K, Perng CL, Lee CH, Lee SD. Heater probe thermocoagulation and multipolar electrocoagulation for arrest of peptic ulcer bleeding. A prospective, randomized comparative trial J Clin Gastroenterol. 1995;21:99-102. [PMID: 8583095].[Medline]
132. Lin HJ, Wang K, Perng CL, Chua RT, Lee CH, Lee SD. Octreotide and heater probe thermocoagulation for arrest of peptic ulcer hemorrhage. A prospective, randomized, controlled trial J Clin Gastroenterol. 1995;21:95-8. [PMID: 8583094].[Medline]
133. Matthewson K, Swain CP, Bland M, Kirkham JS, Bown SG, Northfield TC. Randomized comparison of Nd YAG laser, heater probe, and no endoscopic therapy for bleeding peptic ulcers Gastroenterology. 1990;98:1239-44. [PMID: 2182370].[Medline]
134. Myszor MF, Rich AJ, Bottrill P, Record CO. The impact of an endoscopic laser service on gastroenterological practice Q J Med. 1989;70:73-9. [PMID: 2594950].
135. Ginsberg GG, Barkun AN, Bosco JJ, Burdick JS, Isenberg GA, Nakao NL, et al. The argon plasma coagulator: February 2002 Gastrointest Endosc. 2002;55:807-10. [PMID: 12024132].[Medline]
136. Chau CH, Siu WT, Law BK, Tang CN, Kwok SY, Luk YW, et al. Randomized controlled trial comparing epinephrine injection plus heat probe coagulation versus epinephrine injection plus argon plasma coagulation for bleeding peptic ulcers Gastrointest Endosc. 2003;57:455-61. [PMID: 12665753].[Medline]
137. Tekant Y, Goh P, Alexander DJ, Isaac JR, Kum CK, Ngoi SS. Combination therapy using adrenaline and heater probe to reduce rebleeding in patients with peptic ulcer haemorrhage: a prospective randomized trial Br J Surg. 1995;82:223-6. [PMID: 7749698].[Medline]
138. Gevers AM, De Goede E, Simoens M, Hiele M, Rutgeerts P. A randomized trial comparing injection therapy with hemoclip and with injection combined with hemoclip for bleeding ulcers Gastrointest Endosc. 2002;55:466-9. [PMID: 11923755].[Medline]
139. Buffoli F, Graffeo M, Nicosia F, Gentile C, Cesari P, Rolfi F, et al. Peptic ulcer bleeding: comparison of two hemostatic procedures Am J Gastroenterol. 2001;96:89-94. [PMID: 11197294].[Medline]
140. Messmann H, Schaller P, Andus T, Lock G, Vogt W, Gross V, et al. Effect of programmed endoscopic follow-up examinations on the rebleeding rate of gastric or duodenal peptic ulcers treated by injection therapy: a prospective, randomized controlled trial Endoscopy. 1998;30:583-9. [PMID: 9826134].[Medline]
141. Villanueva C, Balanzo J, Torras X, Soriano G, Sainz S, Vilardell F. Value of second-look endoscopy after injection therapy for bleeding peptic ulcer: a prospective and randomized trial Gastrointest Endosc. 1994;40:34-9. [PMID: 8163132].[Medline]
142. Saeed ZA, Cole RA, Ramirez FC, Schneider FE, Hepps KS, Graham DY. Endoscopic retreatment after successful initial hemostasis prevents ulcer rebleeding: a prospective randomized trial Endoscopy. 1996;28:288-94. [PMID: 8781792].[Medline]
143. Lau JY, Sung JJ, Lam YH, Chan AC, Ng EK, Lee DW, et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers N Engl J Med. 1999;340:751-6. [PMID: 10072409].
144. Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study Am J Gastroenterol. 1995;90:206-10. [PMID: 7847286].[Medline]
145. Guglielmi A, Ruzzenente A, Sandri M, Kind R, Lombardo F, Rodella L, et al. Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer Endoscopy. 2002;34:778-86. [PMID: 12244498].[Medline]
146. Yavorski RT, Wong RK, Maydonovitch C, Battin LS, Furnia A, Amundson DE. Analysis of 3,294 cases of upper gastrointestinal bleeding in military medical facilities Am J Gastroenterol. 1995;90:568-73. [PMID: 7717312].[Medline]
147. Peura DA, Lanza FL, Gostout CJ, Foutch PG. The American College of Gastroenterology Bleeding Registry: preliminary findings Am J Gastroenterol. 1997;92:924-8. [PMID: 9177503].[Medline]
148. Collins R, Langman M. Treatment with histamine H2 antagonists in acute upper gastrointestinal hemorrhage. Implications of randomized trials N Engl J Med. 1985;313:660-6. [PMID: 2862581].[Abstract]
149. Selby NM, Kubba AK, Hawkey CJ. Acid suppression in peptic ulcer haemorrhage: a "meta-analysis" Aliment Pharmacol Ther. 2000;14:1119-26. [PMID: 10971227].[Medline]
150. Levine JE, Leontiadis GI, Sharma VK, Howden CW. Meta-analysis: the efficacy of intravenous H2-receptor antagonists in bleeding peptic ulcer Aliment Pharmacol Ther. 2002;16:1137-42. [PMID: 12030956].[Medline]
151. Lin HJ, Lo WC, Lee FY, Perng CL, Tseng GY. A prospective randomized comparative trial showing that omeprazole prevents rebleeding in patients with bleeding peptic ulcer after successful endoscopic therapy Arch Intern Med. 1998;158:54-8. [PMID: 9437379].
152. Cardi M, Muttillo IA, Amadori L, Barillari P, Sammartino P, Arnone F, et al. [Intravenous omeprazole versus ranitidine in the treatment of hemorrhagic duodenal ulcer: a prospective randomized study] Ann Chir. 1997;51:136-9. [PMID: 9297869].[Medline]
153. Coraggio F, Rotondano G, Marmo R, Balzanelli MG, Catalano A, Clemente F, et al. Somatostatin in the prevention of recurrent bleeding after endoscopic haemostasis of peptic ulcer haemorrhage: a preliminary report Eur J Gastroenterol Hepatol. 1998;10:673-6. [PMID: 9744696].[Medline]
154. Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer J Clin Gastroenterol. 1995;21:103-6. [PMID: 8583073].[Medline]
155. Michel P, Duhamel C, Bazin B, Raoul JL, Person B, Bigard MA, et al. [Lansoprazole versus ranitidine in the prevention of early recurrences of digestive hemorrhages from gastroduodenal ulcers. Randomized double-blind multicenter study] Gastroenterol Clin Biol. 1994;18:1102-5. [PMID: 7750682].[Medline]
156. Villanueva C, Balanzo J, Torras X, Sainz S, Soriano G, Gonzalez D, et al. Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study Endoscopy. 1995;27:308-12. [PMID: 7555936].[Medline]
157. Lin HJ, Perng CL, Wang K, Lee CH, Lee SD. Octreotide for arrest of peptic ulcer hemorrhage—a prospective, randomized controlled trial Hepatogastroenterology. 1995;42:856-60. [PMID: 8847035].[Medline]
158. Okan A, Simsek I, Akpinar H, Ellidokuz E, Sanul AR, Aksoz K. Somatostatin and ranitidine in the treatment of non-variceal upper gastrointestinal bleeding: a prospective, randomized, double-blind, controlled study Hepatogastroenterology. 2000;47:1325-7. [PMID: 11100343].[Medline]
159. Walt RP, Cottrell J, Mann SG, Freemantle NP, Langman MJ. Continuous intravenous famotidine for haemorrhage from peptic ulcer Lancet. 1992;340:1058-62. [PMID: 1357453].[Medline]
160. Gisbert JP, Gonzalez L, Calvet X, Roque M, Gabriel R, Pajares JM. Proton pump inhibitors versus H2-antagonists: a meta-analysis of their efficacy in treating bleeding peptic ulcer Aliment Pharmacol Ther. 2001;15:917-26. [PMID: 11421865].[Medline]
161. Zed PJ, Loewen PS, Slavik RS, Marra CA. Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers Ann Pharmacother. 2001;35:1528-34. [PMID: 11793613].[Abstract]
162. Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis Ann Intern Med. 1997;127:1062-71. [PMID: 9412308].
163. Tulassay Z, Bodnar A, Farkas I, Papp J, Gupta R. Somatostatin versus secretin in the treatment of actively bleeding gastric erosions Digestion. 1992;51:211-6. [PMID: 1356864].[Medline]
164. Goletti O, Sidoti F, Lippolis PV, De Negri F, Cavina E. Omeprazole versus ranitidine plus somatostatin in the treatment of severe gastroduodenal bleeding: a prospective, randomized, controlled trial Ital J Gastroenterol. 1994;26:72-4. [PMID: 7913348].[Medline]
165. Hasselgren G, Lind T, Lundell L, Aadland E, Efskind P, Falk A, et al. Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding. Results of a placebo-controlled multicenter study Scand J Gastroenterol. 1997;32:328-33. [PMID: 9140154].[Medline]
166. Lau JY, Sung JJ, Lee KK, Yung MY, Wong SK, Wu JC, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers N Engl J Med. 2000;343:310-6. [PMID: 10922420].
167. Udd M, Miettinen P, Palmu A, Heikkinen M, Janatuinen E, Pasanen P, et al. Regular-dose versus high-dose omeprazole in peptic ulcer bleeding: a prospective randomized double-blind study Scand J Gastroenterol. 2001;36:1332-8. [PMID: 11761026].[Medline]
168. Sung JJ, Chan FK, Lau JY, Yung MY, Leung WK, Wu JC, et al. The effect of endoscopic therapy in patients receiving omeprazole for bleeding ulcers with nonbleeding visible vessels or adherent clots: a randomized comparison Ann Intern Med. 2003;139:237-43. [PMID: 12965978].
169. Daneshmend TK, Hawkey CJ, Langman MJ, Logan RF, Long RG, Walt RP. Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial BMJ. 1992;304:143-7. [PMID: 1737157].
170. Khuroo MS, Yattoo GN, Javid G, Khan BA, Shah AA, Gulzar GM, et al. A comparison of omeprazole and placebo for bleeding peptic ulcer N Engl J Med. 1997;336:1054-8. [PMID: 9091801].
171. Jung HK, Son HY, Jung SA, Yi SY, Yoo K, Kim DY, et al. Comparison of oral omeprazole and endoscopic ethanol injection therapy for prevention of recurrent bleeding from peptic ulcers with nonbleeding visible vessels or fresh adherent clots Am J Gastroenterol. 2002;97:1736-40. [PMID: 12135028].[Medline]
172. Javid G, Masoodi I, Zargar SA, Khan BA, Yatoo GN, Shah AH, et al. Omeprazole as adjuvant therapy to endoscopic combination injection sclerotherapy for treating bleeding peptic ulcer Am J Med. 2001;111:280-4. [PMID: 11566458].[Medline]
173. Kaviani MJ, Hashemi MR, Kazemifar AR, Roozitalab S, Mostaghni AA, Merat S, et al. Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: a prospective, double-blind, randomized, clinical trial Aliment Pharmacol Ther. 2003;17:211-6. [PMID: 12534405].[Medline]
174. Khuroo MS, Verma SL. Gastric secretory pattern in normal subjects and duodenal ulcer patients in Kashmir J Indian Med Assoc. 1974;63:185-7. [PMID: 4448925].[Medline]
175. Ahmed SZ, Khuroo MS, Ismail SM. Minimal dose of histamine acid phosphate (H.A.P.) for maximal gastric acid secretion in subjects from Kashmir J Assoc Physicians India. 1975;23:321-5. [PMID: 1184555].[Medline]
176. Li Y, Sha W, Nie Y, Wu H, She Q, Dai S, et al. Effect of intragastric pH on control of peptic ulcer bleeding J Gastroenterol Hepatol. 2000;15:148-54. [PMID: 10735538].[Medline]
177. Goldstein JA. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily Br J Clin Pharmacol. 2001;52:349-55. [PMID: 11678778].[Medline]
178. Barkun A, Kennedy W, Herba K, Fallone C. The cost effectiveness of proton pump inhibitor continuous infusion (IV PPI) administered prior to endoscopy in the treatment of patients with non-variceal upper GI bleeding [Abstract]. The RUGBE Investigators Gastroenterology. 2002;122:67.
179. Enns RA, Gagnon YM, Rioux KP, Levy AR. Cost-effectiveness in Canada of intravenous proton pump inhibitors for all patients presenting with acute upper gastrointestinal bleeding Aliment Pharmacol Ther. 2003;17:225-33. [PMID: 12534407].[Medline]
180. Laine L, Cohen H, Brodhead J, Cantor D, Garcia F, Mosquera M. Prospective evaluation of immediate versus delayed refeeding and prognostic value of endoscopy in patients with upper gastrointestinal hemorrhage Gastroenterology. 1992;102:314-6. [PMID: 1727765].[Medline]
181. Lai KC, Hui WM, Wong WM, Wong BC, Hu WH, Ching CK, et al. Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage—a long-term randomized, controlled study Am J Gastroenterol. 2000;95:2225-32. [PMID: 11007222].[Medline]
182. Sharma VK, Sahai AV, Corder FA, Howden CW. Helicobacter pylori eradication is superior to ulcer healing with or without maintenance therapy to prevent further ulcer haemorrhage Aliment Pharmacol Ther. 2001;15:1939-47. [PMID: 11736725].[Medline]
183. Graham DY, Hepps KS, Ramirez FC, Lew GM, Saeed ZA. Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease Scand J Gastroenterol. 1993;28:939-42. [PMID: 8284627].[Medline]
184. Rokkas T, Karameris A, Mavrogeorgis A, Rallis E, Giannikos N. Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease Gastrointest Endosc. 1995;41:1-4. [PMID: 7698617].[Medline]
185. Jaspersen D, Koerner T, Schorr W, Brennenstuhl M, Raschka C, Hammar CH. Helicobacter pylori eradication reduces the rate of rebleeding in ulcer hemorrhage Gastrointest Endosc. 1995;41:5-7. [PMID: 7698624].[Medline]
186. Riemann JF, Schilling D, Schauwecker P, Wehlen G, Dorlars D, Kohler B, et al. Cure with omeprazole plus amoxicillin versus long-term ranitidine therapy in Helicobacter pylori-associated peptic ulcer bleeding Gastrointest Endosc. 1997;46:299-304. [PMID: 9351030].[Medline]
187. Sung JJ, Leung WK, Suen R, Leung VK, Chan FK, Ling TK, et al. One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding Dig Dis Sci. 1997;42:2524-8. [PMID: 9440631].[Medline]
188. Grino P, Pascual S, Such J, Casellas JA, Niveiro M, Andreu M, et al. Comparison of diagnostic methods for Helicobacter pylori infection in patients with upper gastrointestinal bleeding Scand J Gastroenterol. 2001;36:1254-8. [PMID: 11761013].[Medline]
189. Lee JM, Breslin NP, Fallon C, O'Morain CA. Rapid urease tests lack sensitivity in Helicobacter pylori diagnosis when peptic ulcer disease presents with bleeding Am J Gastroenterol. 2000;95:1166-70. [PMID: 10811322].[Medline]
190. Archimandritis A, Tzivras M, Sougioultzis S, Papaparaskevas I, Apostolopoulos P, Avlami A, et al. Rapid urease test is less sensitive than histology in diagnosing Helicobacter pylori infection in patients with non-variceal upper gastrointestinal bleeding J Gastroenterol Hepatol. 2000;15:369-73. [PMID: 10824879].[Medline]
191. Colin R, Czernichow P, Baty V, Touze I, Brazier F, Bretagne JF, et al. Low sensitivity of invasive tests for the detection of Helicobacter pylori infection in patients with bleeding ulcer Gastroenterol Clin Biol. 2000;24:31-5. [PMID: 10679585].[Medline]
192. Houghton J, Ramamoorthy R, Pandya H, Dhirmalani R, Kim KH. Human plasma is directly bacteriocidal against Helicobacter pylori in vitro, potentially explaining the decreased detection of Helicobacter pylori during acute upper GI bleeding Gastrointest Endosc. 2002;55:11-6. [PMID: 11756907].[Medline]
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 J. Romagnuolo, A. N. Barkun, R. Enns, D. Armstrong, J. Gregor, and for the Registry for Upper GI Bleeding and Endosco Simple Clinical Predictors May Obviate Urgent Endoscopy in Selected Patients With Nonvariceal Upper Gastrointestinal Tract Bleeding Arch Intern Med, February 12, 2007; 167(3): 265 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rahme, M. Bardou, K. Dasgupta, Y. Toubouti, J. Ghosn, and A. N. Barkun Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study Rheumatology, February 1, 2007; 46(2): 265 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Thomsen, A. Riis, S. Christensen, M. Norgaard, and H. T. Sorensen Diabetes and 30-Day Mortality From Peptic Ulcer Bleeding and Perforation: A Danish population-based cohort study Diabetes Care, April 1, 2006; 29(4): 805 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cohen and J. A. Rebuck Proton-pump inhibitors for upper-gastrointestinal bleeding Am. J. Health Syst. Pharm., February 1, 2006; 63(3): 214 - 216. [Full Text] [PDF]
|
|
|
|
 |
|
 J. W Devlin, L. S Welage, and K. M Olsen Proton Pump Inhibitor Formulary Considerations in the Acutely Ill Part 2: Clinical Efficacy, Safety, and Economics Ann. Pharmacother., November 1, 2005; 39(11): 1844 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
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|
J. W Devlin, L. S Welage, and K. M Olsen Proton Pump Inhibitor Formulary Considerations in the Acutely Ill Part 1: Pharmacology, Pharmacodynamics, and Available Formulations Ann. Pharmacother., October 1, 2005; 39(10): 1667 - 1677. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
K. Rivkin and A. Lyakhovetskiy Treatment of nonvariceal upper gastrointestinal bleeding Am. J. Health Syst. Pharm., June 1, 2005; 62(11): 1159 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Olsen Use of acid-suppression therapy for treatment of non-variceal upper gastrointestinal bleeding Am. J. Health Syst. Pharm., May 15, 2005; 62(10_Supplement_2): S18 - S23. [Abstract] [Full Text] [PDF]
|
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|
|
|
J. W. Devlin Proton pump inhibitors for acid suppression in the intensive care unit: Formulary considerations Am. J. Health Syst. Pharm., May 15, 2005; 62(10_Supplement_2): S24 - S30. [Abstract] [Full Text] [PDF]
|
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|
 |
|
 R P Arasaradnam and M T Donnelly Acute endoscopic intervention in non-variceal upper gastrointestinal bleeding Postgrad. Med. J., February 1, 2005; 81(952): 92 - 98. [Abstract] [Full Text] [PDF]
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 A. Andriulli, V. Annese, and G. Leandro Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding Ann Intern Med, July 6, 2004; 141(1): 78 - 79. [Full Text] [PDF]
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|
|
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K. M. Kessler Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding Ann Intern Med, July 6, 2004; 141(1): 79 - 79. [Full Text] [PDF]
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M. S. Khuroo and M. S. Khuroo Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding Ann Intern Med, July 6, 2004; 141(1): 79 - 80. [Full Text] [PDF]
|
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|
 |
|
 Practice Guideline: Management of Nonvariceal Upper GI Bleeding Journal Watch (General), December 26, 2003; 2003(1226): 1 - 1. [Full Text]
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