title: pre-endoscopic intravenous proton pump inhibitors for … · pre-endoscopic intravenous ppis...
Post on 29-Jan-2020
1 Views
Preview:
TRANSCRIPT
-
Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in
Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic review s. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts w ithin the time allow ed. Rapid responses should be considered along w ith other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a
recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for w hich little information can be found, but w hich may in future prove to be effective. While CADTH has taken care in the preparation
of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in w hich a third party ow ns copyright. This
report may be used for the purposes of research or private study only . It may not be copied, posted on a w eb site, redistributed by email or stored on an electronic system w ithout the prior w ritten permission of CADTH or applicable copyright ow ner.
Links: This report may contain links to other information available on the w ebsites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners’ own terms and conditions .
TITLE: Pre-Endoscopic Intravenous Proton Pump Inhibitors for Emergency Department Patients with Upper Gastrointestinal Bleeds: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines
DATE: 05 February 2016
CONTEXT AND POLICY ISSUES
Upper gastrointestinal bleeding (UGIB) is a frequent cause of hospital admission.1 It is associated with substantial clinical and economic burden.2 UGIB is associated with morbidity and mortality. Mortality related to UGIB has been estimated to be 2% to 15%.3 The incidence of UGIB in the United States of America (USA) has been estimated as 48 to 160 events per 100,000 adults per year.3 UGIB results from various conditions and can be life-threatening.4 The causes for UGIB include peptic ulcer, arteriovenous malformation, Mallory-Weiss tear, aortoenteric fistula, esophageal varices, and malignancy.4,5 Peptic ulcer is the most common cause of UGIB in patients without known cirrhosis.4 Peptic ulcer is associated with risk factors such as advanced age; Helicobacter pylori infection; and use of nonsteroidal anti-inflammatory drugs and aspirin.4 It is estimated that 80% to 90% of all UGIB are non-variceal.6,7 Patients with UGIB typically present with symptoms of hematemesis (vomiting of blood or coffee-ground-like material) and/or, melena (dark, tarry stools).1,8 The initial management of patients with UGIB involves assessment of hemodynamic stability and the need for resuscitation.9 This information is used to assist in making decisions regarding triage, resuscitation, empiric medical therapy, and diagnostic procedures.8 Endoscopy is used with the aim of both diagnosis and when possible treatment.8 Drugs used for medical therapy include proton pump inhibitors (PPIs) and histamine receptor antagonist. PPIs include drugs such as esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. Proton pump inhibitors (PPIs) block the gastric enzyme, H2K-ATPase, and suppress gastric acid secretion.10 Inhibition of gastric acid secretion enhances healing of acid-related diseases such as peptic ulcer disease.10 It has been suggested that UGIB may be controlled by decreasing the amount of acid in the stomach.11 There is controversy regarding the usefulness of initial treatment with intravenous PPIs prior to endoscopy for managing patients with UGIB. It was apparent from a previous CADTH Rapid
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 2
Response report12 on pantoprazole and a review13 on the management of patients with UGIB, that there were inconsistencies in the recommendations for the use of PPI prior to endoscopy. A Cochrane systematic review by Sreedharan et al.11 published in 2010, included six randomized controlled trials, and concluded that PPI administration prior to endoscopy in patients with UGIB significantly reduced the proportion of patients with stigmata of recent hemorrhage (SRH; active bleeding, adherent clot, or non-bleeding visible vessel). Though this pre-endoscopic PPI treatment reduces the requirement for endoscopic therapy during the index endoscopy there was no evidence that this early PPI treatment affects clinically important outcomes such as mortality, re-bleeding, and need for surgery.11 There remains a lack of definitive data to recommend the correct route of administration, best-practice dosing, as well as suggested timing of initiation of PPI treatment in UGIB.3,14 The purpose of this report is to review the clinical efficacy of pre-endoscopic intravenous proton pump inhibitors (PPI) for patients with UGIB and to review the evidence-based guidelines regarding the use of proton pump inhibitors before endoscopy in patients with UGIB. RESEARCH QUESTIONS
1. What is the clinical effectiveness of intravenous proton pump inhibitors initiated before
endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department?
2. What is the comparative clinical effectiveness of continuous versus intermittent dosing of
intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department?
3. What is the cost-effectiveness of intravenous proton pump inhibitors initiated before
endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department?
4. What are the evidence-based guidelines regarding the use of proton pump inhibitors
before endoscopy in patients with upper gastrointestinal bleeds? KEY FINDINGS
One observational study on patients with upper gastrointestinal bleeding who received either proton pump inhibitor infusion or saline infusion before endoscopy showed that overall there were no statistically significant differences between the two modalities with respect to endoscopic signs of bleeding, recurrent bleeding, emergency surgery, or mortality. No relevant studies, on the comparative clinical effectiveness of continuous versus intermittent dosing of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department, were identified. No relevant studies, on the cost-effectiveness of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department, were identified. Recommendations regarding the use of proton pump inhibitors before endoscopy in patients with upper gastrointestinal bleeding were inconsistent. Two guidelines recommended pre-
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 3
endoscopic PPI, one guideline recommended pre-endoscopic PPI in case of delayed endoscopy and one guideline did not recommend pre-endoscopic PPI. METHODS
Literature Search Methods
A limited literature search was conducted on key resources including Ovid Medline, Ovid Embase, PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit retrieval by publication type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2011 and January 4, 2016. Rapid Response reports are organized so that the evidence for each research question is presented separately. Selection Criteria and Methods
One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.
Table 1: Selection Criteria Population Q1 to 3: Adult patients with an upper gastrointestinal bleed (e.g.,
peptic ulcer bleed) presenting to the emergency department, excluding patients with variceal bleeds
Q4: Same as above without restriction to emergency department setting
Intervention Q1, 3, and 4: Intravenous (IV) proton pump inhibitors (PPIs) (e.g., pantoprazole, omeprazole, rabeprazole, lansoprazole, esomeprazole) administered prior to endoscopy
Q2: Continuous IV PPI therapy (initial bolus + continuous infusion) Comparator Q1 and 3: Oral PPIs, H2RA, placebo, or no treatment pre-endoscopy;
Any of the above therapies provided post-endoscopy
Q2: Intermittent IV PPI therapy
Q4: No comparator required
Outcomes Q1 and 2: Clinical effectiveness and harms (e.g., rate of re-bleeding, need for transfusion, need for admission, length of hospital/ICU/emergency department stay, requirement for surgery, need for intervention, proportion of patients receiving endoscopy)
Q3: Cost-effectiveness outcomes
Q4: Evidence-based guidelines regarding the provision of pre-endoscopic intravenous proton pump inhibitors
Study Designs Health technology assessments (HTA), systematic reviews (SR), meta-analyses (MA), randomized controlled trials (RCT), observational studies, economic studies and evidence-based guidelines
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 4
Exclusion Criteria
Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published prior to 2011. Guidelines which did not appear to be evidence based or had unclear methodology were excluded. Critical Appraisal of Individual Studies The included observational study was critically appraised using the Downs and Black checklist,15 and guidelines were assessed with the AGREE II instrument.16 Summary scores were not calculated for the included studies; rather, a review of the strengths and limitations of each included study were described narratively. SUMMARY OF EVIDENCE Quantity of Research Available
A total of 194 citations were identified in the literature search. Following screening of titles and abstracts, 170 citations were excluded and 24 potentially relevant reports from the electronic search were retrieved for full-text review. One potentially relevant publication was retrieved from the grey literature search. Of these 25 potentially relevant articles, 20 publications were excluded for various reasons, while five publications met the inclusion criteria and were included in this report. These were comprised of one observational study17 and four evidence-based guidelines.18-21 Appendix 1 describes the PRISMA flowchart of the study selection. Additional references of potential interest are provided in Appendix 7. Summary of Study Characteristics
Observational study Characteristics of the included observational study are summarized below and details are available in Appendix 2, Table A1. One relevant observational study17 was identified. It was published from Hungary in 2012. It was a retrospective study using data from medical records of patients with UGIB, who were admitted to the Emergency Department of a teaching hospital in Hungary. Of the 1369 patients admitted during April 2007 and July 2011, 1036 patients were excluded for various reasons and 333 patients, who were admitted during duty hours, were included in the analysis. PPI (pantoprazole) was compared with saline infusion. The age (mean or median not specified) of the patients was 63 years in the PPI group and 66 years in the saline group. The proportion of males was 72.9% in the PPI group and 63.4% in the saline group. Pantoprazole was administered as 80 mg bolus followed by 8 mg per hour continuous infusion. Outcomes reported were endoscopic signs of bleeding, urgent endoscopy, recurrent bleeding, emergency surgery and mortality. Guidelines A description of the included guidelines is summarized below and details are available in Appendix 2, Table A2 and Appendix 3, Table A3.
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 5
Four relevant guidelines18-21 were identified. One guideline18 was published from Europe in 2015 by the European Society of Gastrointestinal Endoscopy (ESGE). One guideline19 was published from United States of America (USA) in 2012. One guideline21 was published from the United Kingdom (UK) in 2012, by the National Institute of Health and Care Excellence (NICE). One guideline was a consensus statement20 published from Asia in 2011. All the guidelines were on the management of patients with UGIB and included a section on the use of PPI prior to endoscopy. Three guidelines19-21 provided explanations for the levels of evidence and one guideline18 did not. One guideline19 provided explanations for the strengths of recommendation and the other three guidelines18,20,21 did not. Details on the grading of evidence and strength of recommendation are provided in Appendix 3, Table A3. Summary of Critical Appraisal
Observational Study Critical appraisal of the included observational study is summarized below and details are available in Appendix 4, Tables A4. The included observational study17 specified the objective, and the inclusion and exclusion criteria and described the patient characteristics, intervention and outcomes. It was a retrospective study and potential for selection bias or performance bias cannot be ruled out. However, the characteristics of the patients in the PPI and saline groups appeared to be similar. The patients included in the analyses were those who had been admitted during duty hours; a large number of the patients were admitted during non-duty hours and were excluded from the analyses. No details regarding admissions during duty hours or non-duty hours were reported and the impact of this exclusion on the findings is unclear. Also, some patients were excluded from the analyses because of essential data missing in the records and the impact of these patients being excluded is unclear. A number of subgroup analyses were conducted but characteristics of the patients in these subgroups were not reported, hence comparability of the subgroups was unclear. It was also unclear if the subgroup analyses had been pre-planned or conducted after reviewing the data which could potentially introduce bias. In the light of these issues, the subgroup findings need to be viewed with caution. Sample size and power calculations were not mentioned. Disclosures of conflicts of interest were not mentioned. Generalizability is limited as the study was conducted at a single center and the patient population from different regions may be different and as policies and procedures across different hospitals may vary. Guidelines Critical appraisal of the guidelines are summarized below and details are available in Appendix 4, Table A5 The objectives were clearly stated in all the guidelines.18-21 The intended users of the guidelines were specified in three guidelines18,20,21 and not specified in one guideline.19 For three guidelines18,20,21 the guideline development group was comprised of individuals from relevant areas (such as gastroenterologists). One guideline19 was authored by two individuals and their areas of expertise were not specified. In two guidelines18,21 the methodology appeared to be rigorous; multiple databases were searched and a systematic review was conducted. In one guideline20 multiple databases were searched, in one guideline19 a single database was searched and in both guidelines details of methodology were sparse. In all guidelines the
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 6
evidence was graded. The strength of the recommendation was specified in two guidelines18,19 and not specified in two guidelines.20,21 In two guidelines18,20 it was mentioned that there were no competing interests. In one guideline,21 the guideline development group members was required to disclose their conflicts of interest and appropriate measures were taken in case of conflicts. In one guideline,19 the authors had associations with industry. One guideline20 was funded by industry. Summary of Findings
What is the clinical effectiveness of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department? Findings are summarized below and details are provided in Appendix 5, Tables A6. No relevant HTA, systematic review or RCT was identified. One relevant observational study17 based on data from medical records was identified. This included retrospective study17 compared outcomes in patients who were administered PPI prior to endoscopy with outcomes in patients who were administered saline prior to endoscopy. The study showed that the 30-day mortality rate was 6.3% in the PPI group and 4.3% in the saline group; the difference was not statistically significant (P = 0.49). The actively bleeding ulcers detected at endoscopic examination was in 19.2% patients in the PPI group compared to 24.7% patients in the saline group; the difference was not statistically significant (P = 0.29). The proportion of patients with clots detected at endoscopic examination was 21.7% in the PPI group and 12.9% in the saline group; the difference was not statistically significant (P = 0.50) No statistically significant differences were found between the two groups with respect to emergency surgery, urgent endoscopy, or recurrent bleeding. The authors also analyzed various subgroups. The different durations of PPI infusion did not appear to have significant differential effects on the outcomes. Mortality rates were 5.6%, 7.1% and 6.1% for the subgroups with PPI infusion of 0 to 4 hours, >4 hours and >6 hours, respectively; however the proportions were not statistically significantly different compared with the saline group (4.3%), (P values between 0.39 and 0.65). The proportions of patients with actively bleeding ulcers detected at endoscopic examination were 22.5%, 14.3% and 14.6% for the three subgroups with PPI infusion of 0 to 4 hours, >4 hours and >6 hours, respectively; however the proportions were not statistically significantly different compared with the saline group (24.7%), (P values between 0.07 and 0.69). The proportions of patients with clots detected at endoscopic examination were 25.3%, 16.3% and 27.1% for the three subgroups with PPI infusion of 0 to 4 hours, >4 hours and >6 hours, respectively; however the difference compared to the saline group (12.9%) was statistically significant for the 0 to 4 hour PPI group (P = 0.02) and not statistically significantly different for the > 4 hours PPI group or the > 6 hours PPI group; P = 0.50 and 0.44 respectively. In the subgroup of patients with duodenal ulcer bleeds there was no statistically significant difference in outcomes between the PPI group and the saline group (P values between 0.28 and 0.98). In the subgroup of patients with gastric ulcer bleeds there was no statistically significant difference in most outcomes between the PPI group and the saline group (P values between 0.11 and 0.82) except for clots. In the subgroup of patients with gastric ulcer bleeds, the proportion of patients with clots were 25.0% for the PPI group and 10.9% for the saline group (P = 0.04).
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 7
What is the comparative clinical effectiveness of continuous versus intermittent dosing of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department? No relevant studies on the comparative clinical effectiveness of continuous versus intermittent dosing of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department were identified What is the cost-effectiveness of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department? No relevant studies on the cost-effectiveness of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department were identified What are the evidence-based guidelines regarding the use of proton pump inhibitors before endoscopy in patients with upper gastrointestinal bleeds? The included guidelines are summarized below and details are available in Appendix 6, Table A7 Three guidelines18-20 used the clinical evidence from a Cochrane systematic review published by Sreedharan et al. in 2010. This Cochrane review mentioned that PPI administration prior to endoscopy in patients with UGIB, significantly reduced the proportion of patients with stigmata of recent hemorrhage (active bleeding, adherent clot, or non-bleeding visible vessel) .The Cochrane review also mentioned that though this pre-endoscopic PPI treatment reduces the requirement for endoscopic therapy during the index endoscopy there is no evidence that this early PPI treatment affects clinically important outcomes such as mortality, re-bleeding and need for surgery. Two guidelines18,20 also considered findings of one cost-effectiveness study which suggested that high dose PPI prior to endoscopy may be an effective and cost saving way to treat patients with UGIB. One guideline21 reviewed the findings from RCTs and concluded that with use of PPI prior to endoscopy there were no improvements in mortality, re-bleeding, or need for surgery and the quality of evidence was described as very low to low (Appendix 6, Table A7). In the light of conclusions from the clinical review, the guideline development group for this guideline did not think it was necessary to explore cost-effectiveness. The recommendations from the individual guidelines are presented in Table 2.
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 8
Table 2: Summary of Recommendationns
Guideline Author or Group, Year, Country
Recommendation
ESGE,18
2015, Europe
“ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80mg then 8mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence).” Page: a1
Laine,19 2012, USA
“Pre-endoscopic intravenous proton pump inhibitor (PPI) (e.g., 80 mg bolus followed by 8 mg / h infusion) may be considered to decrease the proportion of patients who have higher risk stigmata of hemorrhage at endoscopy and who receive endoscopic therapy. However, PPIs do not improve clinical outcomes such as further bleeding, surgery, or death (Conditional recommendation, high-quality evidence). If endoscopy will be delayed or cannot be performed, intravenous PPI is recommended to reduce further bleeding (Conditional recommendation, moderate-quality evidence).” Page: 348
NICE,21 2012, UK “Do not offer acid-suppression drugs (proton pump inhibitors or H2-receptor antagonists) before endoscopy to patients with suspected non-variceal upper gastrointestinal bleeding.” Page: 160
Sung,20 2011, Asia “Pre-endoscopy proton pump inhibitor is recommended where early endoscopy or endoscopic expertise is not available within 24 h (agreement: 86.7%, level of evidence: low)” Page: 1172
ESGE = European Society of Gastrointestinal Endoscopy, H2-RA = histamine receptor antagonist, NICE = National Institute of Health and Care Excellence, UGIH = upper gastrointestinal hemorrhage, PPI = proton pump inhibitor, UK = United Kingdom, USA = United States of America
Limitations Clinical evidence was limited. No HTA, systematic review or RCT was identified; only one retrospective observational study was identified. Retrospective studies are prone to selection bias. Generalizability of the findings is limited as they pertain to an emergency department in one particular hospital. No relevant cost-effectiveness studies were identified. Neither the included study nor the guidelines were from Canada. Hence applicability in the Canadian setting is unclear. The recommendations in the guidelines did not specifically mention if they were for patients in the emergency department. Considering the variability in the recommendations from the different guidelines, a definitive conclusion is difficult.
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 9
CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING
One relevant observational study and four relevant guidelines were identified. No relevant HTAs, systematic reviews, RCTs or economic studies were identified. One observational study, on patients with upper gastrointestinal bleeding who received either proton pump inhibitor infusion or saline infusion before endoscopy, showed no statistically significant differences between the two modalities with respect to endoscopic signs of bleeding, recurrent bleeding, emergency surgery or mortality. Recommendations regarding the use of proton pump inhibitors before endoscopy in patients with upper gastrointestinal bleeding were inconsistent. Two guidelines18,20 recommended pre-endoscopic PPI, one guideline19 recommended pre-endoscopic PPI in case of delayed endoscopy and one guideline21 did not recommend pre-endoscopic PPI. The variations in the recommendations appear to arise from the extent of importance given to certain outcomes. The three guidelines18-20 that were in favor of use of pre-endoscopic PPI considered the findings from the Cochrane review published in 2010. This Cochrane review mentioned that PPI administration prior to endoscopy in patients with UGIB, significantly reduced the proportion of patients with stigmata of recent hemorrhage, which reduced the need for endoscopic therapy, however this did not translate to reduction in re-bleeding, need for surgery, or mortality. The guideline21 that was not in favor of use of pre-endoscopic PPI, considered findings from a systematic review conducted by the guideline authors. This systematic review included four of the six RCTs included in the Cochrane review and also found no differences with respect to re-bleeding, need for surgery, or mortality for pre-endoscopic use of PPI compared to pre-endoscopic use of placebo or histamine 2 receptor antagonists. The authors did not assess the proportion of patients with stigmata of recent hemorrhage, likely because it was not considered an important outcome. There is controversy around the clinical significance of reduction in the proportion of patients with stigmata of recent hemorrhage as it does not translate to reduction in re-bleeding, need for surgery, or mortality.22,23 No relevant studies, on the comparative clinical effectiveness of continuous versus intermittent dosing of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department, were identified. No relevant studies, on the cost-effectiveness of intravenous proton pump inhibitors initiated before endoscopy in patients with upper gastrointestinal bleeds presenting to the emergency department, were identified. PREPARED BY:
Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca
http://www.cadth.ca/
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 10
REFERENCES
1. Hegade VS, Sood R, Mohammed N, Moreea S. Modern management of acute non-
variceal upper gastrointestinal bleeding. Postgrad Med J. 2013 Oct;89(1056):591-8.
2. Bethea ED, Travis AC, Saltzman JR. Initial assessment and management of patients with nonvariceal upper gastrointestinal bleeding. J Clin Gastroenterol. 2014 Nov;48(10):823-9.
3. Bardou M, Benhaberou-Brun D, Le Ray I, Barkun AN. Diagnosis and management of nonvariceal upper gastrointestinal bleeding. Nat Rev Gastroenterol Hepatol. 2012 Feb;9(2):97-104.
4. DeLaney M, Greene CJ, Hess J, Sachs C. Emergency department evaluation and management of patients with upper gastrointestinal bleeding. Emerg Med Pract. 2015 Apr;17(4):1-20.
5. Holster IL, Kuipers EJ. Management of acute nonvariceal upper gastrointestinal bleeding: current policies and future perspectives. World J Gastroenterol [Internet]. 2012 Mar 21 [cited 2016 Jan 8];18(11):1202-7. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309909
6. Wee E. Management of nonvariceal upper gastrointestinal bleeding. J Postgrad Med. 2011 Apr;57(2):161-7.
7. Khamaysi I, Gralnek IM. Acute upper gastrointestinal bleeding (UGIB) - initial evaluation and management. Baillieres Best Pract Res Clin Gastroenterol. 2013 Oct;27(5):633-8.
8. Saltzman JR. Approach to acute upper gastrointestinal bleeding in adults. 2015 Nov 12 [cited 2016 Jan 15]. In: UpToDate [Internet]. Waltham (MA): UpToDate; c2005 - . Available from: www.uptodate.com Subscription required.
9. Saltzman JR. Overview of the treatment of bleeding peptic ulcers. 2015 Sep 1 [cited 2016 Jan 15]. In: UpToDate [Internet]. Waltham (MA): UpToDate; c2005 - . Available from: www.uptodate.com Subscription required.
10. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep [Internet]. 2008 Dec [cited 2016 Jan 15];10(6):528-34. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855237
11. Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;(7):CD005415.
12. Continuous versus intermittent intravenous pantoprazole for acute gastrointestinal bleeding: a review of the clinical effectiveness and guidelines [Internet]. Ottawa: CADTH; 2015 May 1. [cited 2015 Jan 21]. (Rapid response report: summary with critical appraisal). Available from: https://www.cadth.ca/sites/default/files/pdf/htis/may-2015/RC0653%20Pantoprazole%20for%20GI%20bleeds%20Final.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309909http://www.uptodate.com/http://www.uptodate.com/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855237https://www.cadth.ca/sites/default/files/pdf/htis/may-2015/RC0653%20Pantoprazole%20for%20GI%20bleeds%20Final.pdfhttps://www.cadth.ca/sites/default/files/pdf/htis/may-2015/RC0653%20Pantoprazole%20for%20GI%20bleeds%20Final.pdf
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 11
13. Taylor AA, Redfern OC, Pericleous M. The management of acute upper gastrointestinal bleeding: a comparison of current clinical guidelines and best practice. EMJ Gastroenterol [Internet]. 2014 [cited 2016 Jan 15];3:73-82. Available from: http://emjreviews.com/wp-content/uploads/The-Management-of-Acute-Upper-Gastrointestinal-Bleeding-A-Comparison-of-Current-Clinical-Guidelines-and-Best-Practice.pdf
14. Lu Y, Barkun AN. Endoscopic management of acute non variceal upper gastrointestinal bleeding. J Gastroenerol Hepatol Res [Internet]. 2015 [cited 2016 Feb 4];4(3):1515-23. Available from: http://www.ghrnet.org/index.php/joghr/article/view/1122/1220
15. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health [Internet]. 1998 Jun [cited 2016 Feb 2];52(6):377-84. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1756728/pdf/v052p00377.pdf
16. Brouwers M, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in healthcare. CMAJ [Internet]. 2010 Dec [cited 2106 Feb 2];182(18):E839-E842. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001530/pdf/182e839.pdf
17. Rácz I, Szalai M, Dancs N, Kárász T, Szabó A, Csöndes M, et al. Pantoprazole before endoscopy in patients with gastroduodenal ulcer bleeding: does the duration of infusion and ulcer location influence the effects? Gastroenterol Res Pract [Internet]. 2012 [cited 2016 Jan 8];2012:561207. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483715
18. Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy [Internet]. 2015 Oct [cited 2016 Jan 8];47(10):a1-46. Available from: https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0034-1393172.pdf
19. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012 Mar;107(3):345-60.
20. Sung JJ, Chan FK, Chen M, Ching JY, Ho KY, Kachintorn U, et al. Asia-Pacific Working Group consensus on non-variceal upper gastrointestinal bleeding. Gut [Internet]. 2011 Sep [cited 2016 Jan 8];60(9):1170-7. Available from: http://gut.bmj.com/content/60/9/1170.full.pdf+html
21. Acute upper gastrointestinal bleeding in over 16s: management [Internet]. London: National Institute for Health and Clinical Excellence; 2012 Jun 13. [cited 2016 Jan 15]. (NICE Clinical guideline 141). Available from: http://www.nice.org.uk/guidance/cg141
22. Cabot JC, Shah K. Are proton-pump inhibitors effective treatment for acute undifferentiated upper gastrointestinal bleeding? Ann Emerg Med. 2014 Jun;63(6):759-60.
http://emjreviews.com/wp-content/uploads/The-Management-of-Acute-Upper-Gastrointestinal-Bleeding-A-Comparison-of-Current-Clinical-Guidelines-and-Best-Practice.pdfhttp://emjreviews.com/wp-content/uploads/The-Management-of-Acute-Upper-Gastrointestinal-Bleeding-A-Comparison-of-Current-Clinical-Guidelines-and-Best-Practice.pdfhttp://emjreviews.com/wp-content/uploads/The-Management-of-Acute-Upper-Gastrointestinal-Bleeding-A-Comparison-of-Current-Clinical-Guidelines-and-Best-Practice.pdfhttp://www.ghrnet.org/index.php/joghr/article/view/1122/1220http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1756728/pdf/v052p00377.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001530/pdf/182e839.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483715https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0034-1393172.pdfhttps://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0034-1393172.pdfhttp://gut.bmj.com/content/60/9/1170.full.pdf+htmlhttp://www.nice.org.uk/guidance/cg141
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 12
23. Yachimski P. Proton pump inhibitors given before endoscopy for upper gastrointestinal bleeding do not improve survival, rebleeding or need for surgery. Evid Based Med. 2011 Feb;16(1):13-4.
24. Tsoi KK, Lau JY, Sung JJ. Cost-effectiveness analysis of high-dose omeprazole infusion before endoscopy for patients with upper-GI bleeding. Gastrointest Endosc. 2008 Jun;67(7):1056-63.
25. Al-Sabah S, Barkun AN, Herba K, Adam V, Fallone C, Mayrand S, et al. Cost-effectiveness of proton-pump inhibition before endoscopy in upper gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2008 Apr;6(4):418-25.
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 13
ABBREVIATIONS
ESGE European Society of Gastrointestinal Endoscopy FU follow-up GRADE Grading of Recommendations Assessment, Development, and Evaluation H2-RA histamine receptor antagonist PPI proton pump inhibitor mg milligram NICE National Institute of Health and Care Excellence SD standard deviation SRH stigmata of recent hemorrhage UGIB upper gastrointestinal bleeding UK United Kingdom USA United States of America
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 14
APPENDIX 1: Selection of Included Studies
170 citations excluded
24 potentially relevant articles retrieved for scrutiny (full text, if
available)
1 potentially relevant report retrieved from other sources (grey
literature, hand search)
25 potentially relevant reports
20 reports excluded: - irrelevant population (1) - irrelevant interventions (5) - survey (1) - non-English publication (1) - guidelines with unclear methods (4) - other (review articles) (8)
5 reports included in review
194 citations identified from electronic literature search and
screened
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 15
APPENDIX 2: Characteristics of Included Publications
Table A1: Characteristics of Included Clinical Studies
First
Author, Publication
Year,
Country
Study Design Patient
Characteristics
Intervention(s) Comparator(s) Clinical
Outcomes
Observational study Rácz,
17
2012,
Hungary
Retrospective (medical
records), single center (Gastroenterol
ogy Emergency Department of
teaching hospital in Győr) study.
Medical records of
UGIB patients admitted between April
2007 and July 2011. (In January
2009, preemptive PPI use was
included in the protocol for managing
UGIB patients arriving to the hospital during
the evening or night. Before that saline
infusion was used during the pre-
endoscopy period.)
Patients with UGIB
N = 333 (240 with bolus plus
infusion PPI [P], 93 with saline [S])
Age (years): 63.4 ± 15.2 in P,
66.0 ± 13.4 in S. % Male;
72.9% in P, 63.4% in S.
Hemoglobin (g/dL): 95.3 ± 30.2 in P,
96.8 ± 30.4 in S
PPI (pantaprazol, 80
mg bolus followed by continuous
infusion of 8 mg/hour) prior to endoscopy.
Duration of infusion before
endoscopy (hours) (mean ± SD): 6.9 ± 13.2
Saline prior to endoscopy.
Duration of infusion before
endoscopy (hours) (mean ± SD): 5.5 ± 12.9
Endoscopic signs of
bleeding, urgent endoscopy,
recurrent bleeding, emergency
surgery, mortality
N = total number of patients, P = PPI, PPI = proton pump inhibitor, S = saline, SD = standard deviation, UGIB = upper gastrointestinal bleeding
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 16
Table A2: Characteristics of Included Guidelines
Objectives Methodology
Gralnek (ESGE),18
2015, Europe
This guideline is on the diagnosis and management of
non-variceal upper gastrointestinal hemorrhage. It is to assist endoscopists in
providing care to patients.
Multiple databases (such as Medline, Embase, the Cochrane library, HEED) searched and systematic review conducted.
Evidence graded using GRADE Guideline was externally reviewed. Mechanism in place for updating guideline.
Laine,19
2012, USA
This guideline is on the management of patients with overt UGIB.
Medline database was searched. No additional details on methodology. Evidence graded using GRADE Guideline was externally reviewed.
No mention regarding updating of guidelines
NICE,21
2012, UK
This guideline is on the management of acute UGIB in adults and in young persons
(≥ 16 years). It is to assist healthcare professional in their practice.
Multiple databases (such as Medline, Embase, Cinahl, the Cochrane library, HEED) searched and systematic review conducted. Evidence graded using GRADE
Guideline was externally reviewed. Mechanism in place for updating guideline.
Sung,20
2011, Asia-Pacific
This is a consensus statement
on the management of non-variceal UGIB.
Multiple databases (such as Medline, Embase, Cochrane Register of
Controlled Trials) searched. Few details on methodology Evidence graded using GRADE Guideline was externally reviewed.
Mechanism for updating was unclear. It was mentioned that it was hoped that the consensus strategies would be updated regularly and adopted by health authorities.
ESGE = European Society of Gastrointestinal Endoscopy, GRADE = Grading of Recommendations assessment, development and Evaluation, NICE = National Institute of Health and Care Excellence, UK = United Kingdom, USA = United States of America
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 17
APPENDIX 3: Grading of Recommendations and Levels of Evidence
Table A3: Grading of Recommendations and Levels of Evidence Guideline Society
and/or Author, Year, Country,
Topic
Recommendation grade and Level of Evidence
Gralnek (ESGE),18 2015, Europe
Strength of Recommendations
Details not reported Levels of Evidence
GRADE used Details not reported
Laine,19 2012, USA
Strength of Recommendations
Strength Explanation
Strong Desirable effects of intervention clearly outweigh the undesirable effects
Conditional Uncertainty exists regarding trade-offs
Levels of Evidence using GRADE:
Level Explanation
High “Further research is very unlikely to change our confidence in the estimate of effect “ Page: 345
Moderate “Further research is likely to have an important impact on
our confidence in the estimate of effect and may change the estimate” Page: 345
Low “Further research is very likely to have an important impact on our confidence in the estimate of effect and is
likely to change the estimate” Page: 345
Very Low “Any estimate of effect is very uncertain” Page: 345
NICE,21
2012, UK Levels of Evidence using GRADE: Level Explanation
High “Further research is very unlikely to change our confidence in the estimate of effect” Page: 30
Moderate “Further research is likely to have an important impact on
our confidence in the estimate of effect and may change the estimate” Page: 30
Low “Further research is very likely to have an important impact on our confidence in the estimate of effect and is
likely to change the estimate” Page: 30
Very Low “Any estimate of effect is very uncertain” Page: 30
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 18
Table A3: Grading of Recommendations and Levels of Evidence
Guideline Society and/or Author, Year, Country,
Topic
Recommendation grade and Level of Evidence
Sung,20 2011, Asia-Pacific
Strength of Recommendations Details not reported
Levels of Evidence
Level Explanation
High “Further research is very unlikely to change our confidence in the estimate of effect” Page: 1171
Moderate “Further research is likely to have an important impact on
our confidence in the estimate of effect and may change the estimate” Page: 1171
Low “Further research is very likely to have an important impact on our confidence in the estimate of effect and is
likely to change the estimate” Page: 1171
Very Low “Any estimate of effect is uncertain” Page: 1171
ESGE = European Society of Gastrointestinal Endoscopy, GRADE = Grading of Recommendations assessment, development and
Evaluation, NICE = National Institute of Health and Care Excellence, UK = United Kingdom, USA = United States of America
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 19
APPENDIX 4: Critical Appraisal of Included Publications
Table A4: Strengths and Limitations of Observational Study using Downs and Black Checklist15
Strengths Limitations
Observational study Rácz,
17 2012, Hungary
Objectives were clearly stated.
Inclusion and exclusion criteria were stated
Patient characteristic, interventions and
outcomes were described.
P-values were provided
Not randomized; a retrospective study using medical records
Sample size calculation was not provided
Disclosure of conflicts of interest not provided
Generalizability limited to the study population (patients at one center in Hungary)
Table A5: Strengths and Limitations of Guidelines using AGREE II16 l
Strengths Limitations
Gralnek (ESGE),18 2015, Europe
The scope and purpose were clearly stated.
The guideline development group comprised of individuals from relevant areas (such as gastroenterologist, gastrointestinal
endoscopist, interventional radiologist, surgeon)
The methods used for the development of the
guidelines appear to be rigorous (multiple database searched, and systematic review conducted)
Grading of evidence was done using the GRADE tool.
Strength of recommendation was stated
Cost implications were considered
It was mentioned that there were no competing interests
Unclear if patient input was sought
Unclear if organizational barriers were considered.
Laine,19 2012, USA
The scope was clearly stated.
Grading of evidence was done using the GRADE tool.
Strength of recommendation was stated
The intended users of the guidelines was not specified
The guideline was developed by two
individuals but their areas of expertise were not specified.
A single database was searched. Details of methodology were sparse.
Unclear if patient input was sought, however it was mentioned that patient preferences were considered.
Unclear if organizational barriers were considered.
Conflicts of interest were declared. Both authors were associated with industry
http://www.agreetrust.org/wp-content/uploads/2013/06/AGREE_II_Users_Manual_and_23-item_Instrument_ENGLISH.pdf
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 20
Table A5: Strengths and Limitations of Guidelines using AGREE II16 l
Strengths Limitations
NICE,21 2012, UK
The scope and purpose were clearly stated.
The guideline development group comprised of individuals from relevant areas (such as gastroenterologist, hepatologist, surgeon,
interventional radiologist, nurse practitioner, economist, researcher and patient representative)
The methods used for the development of the guidelines appear to be rigorous (multiple database searched, and systematic review
conducted)
Patient input was sought
Cost implications were considered where appropriate. In the light of conclusions from the
clinical review regarding administration of PPI prior to endoscopy, the GDG did not think it was necessary to explore cost-effectiveness.
Grading of evidence was done using the GRADE tool
Guideline development group members were
required to disclose their conflicts of interest. Members were either required to withdraw completely or for the part of the discussion, if
their declared interest made it appropriate.
Unclear if organizational barriers were considered.
Strength of recommendations were not stated, however the evidence was graded
Sung,20 2011, Asia-Pacific The scope and purpose were clearly stated.
The guideline (consensus statement ) development group comprised of experts from 12 Asian countries in areas of acute UGIB, and
evidence-based medicine.
Multiple databases (such as Medline, Embase, Cochrane Register of Controlled Trials)
Grading of evidence was done using the
GRADE tool.
A modified Delphi process was used to make recommendations. The extent of agreement
was provided.
Cost implications were considered
It was mentioned that there were no competing interests
Details of methodology were sparse
Unclear if patient input was sought
Unclear if organizational barriers were considered.
Strength of the recommendation was not
stated.
Funded by pharmaceutical industry
ESGE = European Society of Gastrointestinal Endoscopy, GRADE = Grading of Recommendations Assessment, Development and Evaluation UK = United Kingdom, USA = United States of America
http://www.agreetrust.org/wp-content/uploads/2013/06/AGREE_II_Users_Manual_and_23-item_Instrument_ENGLISH.pdf
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 21
APPENDIX 5: Main Study Findings and Author’s Conclusions
Table A6: Summary of Findings of Included Clinical Studies
Main Study Findings and Author’s Conclusions
Observational study Rácz,
17 2012, Hungary
Main Findings: Outcomes with PPI (pantoprazole) infusion compared to saline infusion prior to endoscopy in UGIB patients
Outcome Number (%) of patients with outcome P value
Pantoprazole,
N = 240
Saline,
N = 93
Endoscopic signs of bleeding
Active bleeding 46 (19.2) 23 (24.7%) 0.26
Non bleeding visible vessel 49 (20.4%) 18 (19.3%) 0.83
Clot 52 (21.7%) 12 (12.9%) 0.50
Pigmented spot and clean base 93 (38.8%) 40 (43.0%) 0.48
Urgent endoscopy 19 (7.9%) 8 (8.6%) 0.89
Recurrent bleeding 40 (16.7%) 13 (13.9%) 0.55
Emergency surgery 21 (8.8%) 10 (10.7%) 0.57
Mortality 15 (6.3%) 4 (4.3%) 0.49 N = total number of patients in the group
Outcomes with PPI (pantoprazole) infusion of different durations compared to saline infusion prior to endoscopy in UGIB patients
Outcome Number (%) of patients with outcome
P value
Pantoprazole
subgroups (different infusion times)
Saline,
N = 93
Pantoprazol, 0 to 4 hours, N = 142
Endoscopic signs of bleeding - Active bleeding 32 (22.5%) 23 (24.7%) 0.69
Endoscopic signs of bleeding - Clot 36 (25.3%) 12 (12.9%) 0.02
Mortality 8 (5.6%) 4 (4.3%) 0.65
Pantoprazol, > 4 hours, N = 98
Endoscopic signs of bleeding - Active bleeding 14 (14.3%) 23 (24.7%) 0.07
Endoscopic signs of bleeding - Clot 16 (16.3%) 12 (12.9%) 0.50
Mortality 7 (7.1) 4 (4.3%) 0.39
Pantoprazol, > 6 hours, N =82
Endoscopic signs of bleeding - Active bleeding 12 (14.6%) 23 (24.7%) 0.09
Endoscopic signs of bleeding - Clot 14 (27.1%) 12 (12.9%) 0.44
Mortality 5 (6.1%) 4 (4.3%) 0.59 N = total number of patients in the group, , PPI = proton pump inhibitor, UGIB = upper gastrointestinal bleeding
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 22
Table A6: Summary of Findings of Included Clinical Studies
Main Study Findings and Author’s Conclusions
Outcomes with PPI (pantoprazole) infusion compared to saline infusion prior to endoscopy in UGIB patients (with duodenal ulcers)
Outcome Number (%) of patients with outcome P value
Pantoprazole,
N = 128
Saline,
N = 47
Endoscopic signs of bleeding
Active bleeding 31 (24.2%) 14 (29.8%) 0.46
Non bleeding visible vessel 27 (21.1%) 7 (14.8%) 0.36
Clot 24 (18.7%) 7 (14.8%) 0.55
Pigmented spot and clean base 46 (35.9%) 19 (40.4%) 0.59
Urgent endoscopy 11 (8.5%) 5 (10.6%) 0.64
Recurrent bleeding 22 (17.2%) 9 (19.1%) 0.76
Emergency surgery 15 (12.3%) 8 (17.0%) 0.36
Mortality 7 (5.7%) 3 (6.3%) 0.76 N = total number of patients in the group, , PPI = proton pump inhibitor, UGIB = upper gastrointestinal bleeding
Outcomes with PPI (pantoprazole) infusion compared to saline infusion prior to endoscopy in UGIB patients (with gastric ulcers)
Outcome Number (%) of patients with outcome P value
Pantoprazole,
N = 112
Saline,
N = 46
Endoscopic signs of bleeding
Active bleeding 15 (13.4%) 9 (19.5%) 0.32
Non bleeding visible vessel 22 (19.6%) 11 (23.9%) 0.55
Clot 28 (25.0%) 5 (10.9%) 0.04
Pigmented spot and clean base 47 (41.9%) 21 (45.6%) 0.67
Urgent endoscopy 8 (7.1%) 3 (6.5%) 0.82
Recurrent bleeding 18 (16.1%) 4 (8.7%) 0.22
Emergency surgery 6 (5.3%) 2 (4.3%) 0.79
Mortality 8 (7.1%) (2.2%) 0.22 N = total number of patients in the group, PPI = proton pump inhibitor, UGIB = upper gastrointestinal bleeding
Authors’ Conclusions: “In conclusion, according to our retrospective analysis profound acid suppression in gastroduodenal ulcer bleeding patients awaiting endoscopy did not decrease significantly the ratio of active bleeding and the
need for endoscopic therapy; however a trend of less active bleeding was seen with longer pantoprazole treatment. Preemptive administration of high-dose pantoprazole for longer than 4 hours decreased the severity of bleeding at first endoscopy in gastric ulcer patients but not in duodenal ulcer patients.”
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 23
APPENDIX 6: Guidelines and Recommendations
Table A7: Summary of Guidelines and Recommendations
Gralnek, European Society of Gastrointestinal Endoscopy (ESGE)18 2015, Europe Findings:
Clinical evidence from a Cochrane review by Sreedharan et al. published in 2010 was used for the
guideline report. This Cochrane review included six RCTs with 2223 patients with UGIB. PPI (oral or intravenous) was compared with H2-RA or placebo. This Cochrane review concluded that PPI administration prior to endoscopy in patients with UGIB, significantly reduced the proportion of patients
with SRH. Though this pre-endoscopic PPI treatment reduces the requirement for endoscopic therapy during the index endoscopy there is no evidence that this early PPI treatment affects clinically important outcomes such as mortality, re-bleeding and need for surgery.
Two cost-effectiveness studies (Tsoi et al.
24 and Al-Sabah et al.
25 both published in 2008) using
decision analytic models were included in the guideline report. The study by Tsoi concluded that use of
high dose PPI prior to endoscopy appeared to be an effective and cost -savings way to treat patients with UGIB. The study by Al-Sabah concluded that intravenous PPIs given prior to endoscopy were slightly more effective than no administration.
Recommendation: “ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80mg then 8mg/hour), in patients presenting with acute UGIH awaiting
upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence).” Page: a1
(H2-RA = histamine receptor antagonist, SRH = stigmata of recent hemorrhage , UGIH = upper gastrointestinal hemorrhage, PPI = proton pump inhibitor)
Laine,19 2012, USA Findings:
Clinical evidence from a Cochrane review by Sreedharan et al. published in 2010 was used for the guideline report. This Cochrane review included six RCTs with 2223 patients with UGIB. PPI (oral or intravenous) was compared with H2-RA or placebo. This Cochrane review concluded that PPI
administration prior to endoscopy in patients with UGIB, significantly reduced the proportion of patients with SRH. Though this pre-endoscopic PPI treatment reduces the requirement for endoscopic therapy during the index endoscopy there is no evidence that this early PPI treatment affects clinically
important outcomes such as mortality, re-bleeding and need for surgery.
Recommendation: “Pre-endoscopic intravenous proton pump inhibitor (PPI) (e.g., 80 mg bolus followed by 8 mg / h
infusion) may be considered to decrease the proportion of patients who have higher risk stigmata of hemorrhage at endoscopy and who receive endoscopic therapy. However, PPIs do not improve clinical outcomes such as further bleeding, surgery, or death (Conditional recommendation, high-quality
evidence). If endoscopy will be delayed or cannot be performed, intravenous PPI is recommended to reduce
further bleeding (Conditional recommendation, moderate-quality evidence).” Page: 348
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 24
Table A7: Summary of Guidelines and Recommendations
NICE,21 2012, UK Findings:
Clinical studies: Outcomes with PPI treatment compared to placebo treatment in UGIB patients prior to endoscopy
Outcome No. of RCTs
No. of patients
Findings Quality of evidence
Mortality (≤30 days) 3 1983 No statistical or clinical difference in mortality rate
low
Re-bleeding (≤30
days)
3 1983 No statistical or clinical
improvement in re-bleeding rate
low
Surgery for continued or recurrent bleeding
(≤30 days)
3 1983 No statistical or clinical improvement in re-bleeding
rate
low
Blood transfusion requirement
1 631 No statistical or clinical improvement in the average unit of blood transfusions
moderate
Patients needing blood
transfusion
2 1352 No significant differences moderate
Length of hospital stay 1 631 No statistical or clinical improvement in the average length of hospital stay
moderate
FU = follow -up, PPI = proton pump inhibitor , RCTs = randomized controlled trials, UGIB = upper gastrointestinal bleeding
Outcomes with PPI treatment compared to H2-RA treatment in UGIB patients prior to endoscopy
Outcome No. of
RCTs No. of patients
Findings Quality of evidence
Mortality (≤30 days FU)
1 102 No statistical or clinical difference in mortality rate
Very low
Surgery for continued
or recurrent bleeding (≤30 days FU)
1 102 No statistical or clinical
difference in re-bleeding rate
Very low
Patients needing blood transfusion
1 102 No statistical or clinical difference in the rate of
patients needing blood transfusion
Very low
FU = follow -up, H2-RA = histamine 2 receptor antagonist , PPI = proton pump inhibitor , RCTs = randomized controlled trials, UGIB = upper gastrointestinal bleeding
Economic studies: “The GDG did not consider it necessary to explore the cost-effectiveness of PPIs versus H₂-RAs or placebo pre-endoscopy, as it had concluded from the clinical review that there was no benefit from these agents when given routinely pre-endoscopy.” Page: 154 (GDG = Guideline Development Group, H2-RA = histamine 2 receptor antogonist , PPI = proton pump inhibitor)
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 25
Table A7: Summary of Guidelines and Recommendations
Recommendation:
“Do not offer acid-suppression drugs (proton pump inhibitors or H2-receptor antagonists) before endoscopy to patients with suspected non-variceal upper gastrointestinal bleeding.” Page: 160
Sung,20 2011, Asia Findings:
Clinical evidence from a Cochrane review by Sreedharan et al. published in 2010 was used for the guideline report. This Cochrane review included six RCTs with 2223 patients with UGIB. PPI (oral or
intravenous) was compared with H2-RA or placebo. This Cochrane review concluded that PPI administration prior to endoscopy in patients with UGIB, significantly reduced the proportion of patients with SRH. Though this pre-endoscopic PPI treatment reduces the requirement for endoscopic therapy
during the index endoscopy there is no evidence that this early PPI treatment affects clinically important outcomes such as mortality, re-bleeding and need for surgery.
One cost-effectiveness study by Tsoi et al.24
published in 2008 was considered. This study used a decision analysis based on the Hong Kong model. According to this study, the use of high dose PPI prior to endoscopy increases the upfront cost but reduces subsequent procedures and hence
decreases the duration of hospital stay, and thus is still cost-effective.
Recommendation:
“Pre-endoscopy proton pump inhibitor is recommended where early endoscopy or endoscopic expertise is not available within 24 h (agreement: 86.7%, level of evidence: low)” Page: 1172
-
Pre-Endoscopic Intravenous PPIs for Patients with Upper Gastrointestinal Bleeds 26
APPENDIX 7: Additional References of Potential Interest
Guidelines (Unclear Methodology) Laursen SB, Jorgensen HS, Schaffalitzky de Muckadell OB. Management of bleeding gastroduodenal ulcers. Dan Med J [Internet]. 2012;59(7):C4473. Available from: http://www.danmedj.dk/portal/pls/portal/!PORTAL.wwpob_page.show?_docname=9102913.PDF Colle I, Wilmer A, Le Moine O, Debruyne R, Delwaide J, Dhondt E, et al. Upper gastrointestinal tract bleeding management: Belgian guidelines for adults and children. Acta Gastroenterol Belg. 2011;74(1):45-66. Economic Studies (Prior to Literature Search Period) Al-Sabah S, Barkun AN, Herba K, Adam V, Fallone C, Mayrand S, et al. Cost-effectiveness of proton-pump inhibition before endoscopy in upper gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2008 Apr;6(4):418-25. Tsoi KK, Lau JY, Sung JJ. Cost-effectiveness analysis of high-dose omeprazole infusion before endoscopy for patients with upper-GI bleeding. Gastrointest Endosc. 2008 Jun;67(7):1056-63
http://www.danmedj.dk/portal/pls/portal/!PORTAL.wwpob_page.show?_docname=9102913.PDFhttp://www.danmedj.dk/portal/pls/portal/!PORTAL.wwpob_page.show?_docname=9102913.PDF
Context and policy issuesResearch questionSkey FindingsMethodsLiterature Search MethodsSelection Criteria and MethodsExclusion CriteriaCritical Appraisal of Individual Studies
Summary of EVIDENCEQuantity of Research AvailableSummary of Study CharacteristicsSummary of Critical AppraisalSummary of FindingsLimitations
Conclusions and implications for decision or policy makingReferencesABBREVIATIONS
top related