Proton pump inhibitor treatment started before endoscopy in upper gastrointestinal bleeding


Bleeding from the oesophagus (the canal that connects the throat to the stomach), stomach or duodenum (the first part of the small intestine) is a common medical emergency. Research has suggested that reducing the amount of acid in the stomach may help to control the bleeding, but it is unknown if it is beneficial to start such treatment early; that is, before endoscopy (the examination of the oesophagus, stomach and duodenum with a fibreoptic camera).

Review question

We reviewed the evidence about the effect of one type of anti-acid drug (proton pump inhibitors) compared to either no treatment (placebo) or another type of anti-acid drug (histamine-2 receptor antagonists) started before endoscopy in people with upper gastrointestinal bleeding.

Study characteristics

The evidence is current to June 2021. We included six studies involving 2223 participants. All studies were conducted in a hospital setting, and included participants with clinical signs of upper gastrointestinal bleeding.

These studies reported data for the following outcomes: death (5 studies, 2143 participants); recurrence of upper gastrointestinal bleeding (5 studies, 2121 participants); surgery (6 studies, 2223 participants); the proportion of participants with active bleeding or signs of recent serious bleeding at first endoscopy (4 studies, 1332 participants); and the need for endoscopic therapy (such as injecting medicines or cauterising blood vessels) for bleeding (3 studies, 1983 participants). One study reported data for time to discharge, and two studies reported data for blood transfusion requirement.

Key results

It remains uncertain whether treatment with a proton pump inhibitor before endoscopy affected the risk of death, recurrent bleeding, need for surgery, the proportion of participants with findings of active or recent serious bleeding at first endoscopy, time to discharge or blood transfusion requirements. However, treatment with a proton pump inhibitor before endoscopy probably reduced the need for endoscopic treatment of bleeding.

Certainty of the evidence

The certainty (quality) of the evidence was low to moderate, due mainly to limitations in the design and execution of some studies, and the inability to get a precise estimate of the effect (due to inadequate numbers of participants and events in the included studies).

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.

Read the full abstract...

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.


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

Search strategy: 

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.