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. 2022 Jan 7;1(1):CD005415.
doi: 10.1002/14651858.CD005415.pub4.

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding

Takeshi Kanno  1   2   3 , Yuhong Yuan  1   4 , Frances Tse  1   4 , Colin W Howden  5 , Paul Moayyedi  1   4 , Grigorios I Leontiadis  1   4
Affiliations

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding

Takeshi Kanno et al. Cochrane Database Syst Rev. .

Abstract

Background: Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.

Objectives: To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.

Search methods: We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.

Selection criteria: We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.

Data collection and analysis: At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.

Main results: We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.

Authors' conclusions: There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest are declared for the period since April 2015 (i.e. three years prior to the decision to update this review).

T. Kanno: none known

Y. Yuan: none known

F. Tse: none known

C. Howden: has consulted and spoken for RedHill Biopharma, manufacturers of Talicia ‐ a combination product containing omeprazole which is approved in the USA for treatment of H pylori infection; is acting as an expert witness for Takeda, manufacturers of lansoprazole and dexlansoprazole, in litigation.

P. Moayyedi: none known

G. Leontiadis: none known

Figures

1
1
Study flow diagram: review update 03 June 2021
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Trial sequential analysis (TSA) for outcome mortality
5
5
Trial sequential analysis (TSA) for outcome rebleeding
1.1
1.1. Analysis
Comparison 1: Main analysis, Outcome 1: Mortality
1.2
1.2. Analysis
Comparison 1: Main analysis, Outcome 2: Rebleeding
1.3
1.3. Analysis
Comparison 1: Main analysis, Outcome 3: Surgery
1.4
1.4. Analysis
Comparison 1: Main analysis, Outcome 4: Participants requiring blood transfusion
1.5
1.5. Analysis
Comparison 1: Main analysis, Outcome 5: Proportion of participants with stigmata of recent haemorrhage
1.6
1.6. Analysis
Comparison 1: Main analysis, Outcome 6: Proportion of participants with stigmata of recent haemorrhage plus Lau 2007
1.7
1.7. Analysis
Comparison 1: Main analysis, Outcome 7: Proportion of participants with blood in stomach
1.8
1.8. Analysis
Comparison 1: Main analysis, Outcome 8: Proportion of participants with active bleeding
1.9
1.9. Analysis
Comparison 1: Main analysis, Outcome 9: Proportion of participants with active bleeding plus Lau 2007
1.10
1.10. Analysis
Comparison 1: Main analysis, Outcome 10: Endoscopic haemostatic treatment at index endoscopy
2.1
2.1. Analysis
Comparison 2: Subgroup analysis according to risk of bias, Outcome 1: Mortality
2.2
2.2. Analysis
Comparison 2: Subgroup analysis according to risk of bias, Outcome 2: Rebleeding
2.3
2.3. Analysis
Comparison 2: Subgroup analysis according to risk of bias, Outcome 3: Surgery
2.4
2.4. Analysis
Comparison 2: Subgroup analysis according to risk of bias, Outcome 4: Proportion of participants with stigmata of recent haemorrhage
2.5
2.5. Analysis
Comparison 2: Subgroup analysis according to risk of bias, Outcome 5: Endoscopic haemostatic treatment at index endoscopy
3.1
3.1. Analysis
Comparison 3: Subgroup analysis according to geographic location, Outcome 1: Mortality
3.2
3.2. Analysis
Comparison 3: Subgroup analysis according to geographic location, Outcome 2: Rebleeding
3.3
3.3. Analysis
Comparison 3: Subgroup analysis according to geographic location, Outcome 3: Surgery
4.1
4.1. Analysis
Comparison 4: Subgroup analysis according to route of PPI administration, Outcome 1: Mortality
4.2
4.2. Analysis
Comparison 4: Subgroup analysis according to route of PPI administration, Outcome 2: Rebleeding
4.3
4.3. Analysis
Comparison 4: Subgroup analysis according to route of PPI administration, Outcome 3: Surgery
5.1
5.1. Analysis
Comparison 5: Subgroup analysis according to PPI dose (high dose versus non‐high dose), Outcome 1: Mortality
5.2
5.2. Analysis
Comparison 5: Subgroup analysis according to PPI dose (high dose versus non‐high dose), Outcome 2: Rebleeding
5.3
5.3. Analysis
Comparison 5: Subgroup analysis according to PPI dose (high dose versus non‐high dose), Outcome 3: Surgery
6.1
6.1. Analysis
Comparison 6: Subgroup analysis according to control treatment, Outcome 1: Mortality
6.2
6.2. Analysis
Comparison 6: Subgroup analysis according to control treatment, Outcome 2: Rebleeding
6.3
6.3. Analysis
Comparison 6: Subgroup analysis according to control treatment, Outcome 3: Surgery
7.1
7.1. Analysis
Comparison 7: Subgroup analysis according to use of endoscopic haemostatic treatment at index endoscopy, Outcome 1: Mortality
7.2
7.2. Analysis
Comparison 7: Subgroup analysis according to use of endoscopic haemostatic treatment at index endoscopy, Outcome 2: Rebleeding
7.3
7.3. Analysis
Comparison 7: Subgroup analysis according to use of endoscopic haemostatic treatment at index endoscopy, Outcome 3: Surgery
8.1
8.1. Analysis
Comparison 8: Sensitivity analysis restricted to peptic ulcer participants, Outcome 1: Mortality
8.2
8.2. Analysis
Comparison 8: Sensitivity analysis restricted to peptic ulcer participants, Outcome 2: Rebleeding
8.3
8.3. Analysis
Comparison 8: Sensitivity analysis restricted to peptic ulcer participants, Outcome 3: Surgery
See this image and copyright information in PMC

Update of

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References to studies included in this review

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References to other published versions of this review

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