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.
Upper gastrointestinal bleeding (UGIB) is a common Emergency Centre presentation with a high mortality (5–30%). Despite theoretical benefits, tranexamic acid is not widely used for this condition. Tranexamic acid is widely available in the developing world and is on the World Health Organisation’s essential medicines list. This review considers the following three-part question: “In adult patients with upper gastrointestinal bleeding, does tranexamic acid decrease mortality? A systematic review of the literature was performed (1900–2012). Databases searched included: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, National Research Register, NIHR CRN portfolio, and http://ClinicalTrials.gov/. Grey literature databases searched included: Open Grey, Worldcat.org and Google Scholar. The conclusion of this review is that in adult patients with upper gastrointestinal bleeding, the administration of tranexamic acid may lead to a significant decrease in mortality.
A short cut review was carried out to establish whether tranexamic acid should be given to patients having an upper gastrointestinal bleed. Seven studies and two systematic reviews were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that there is insufficient evidence, at the moment, to recommend the use of tranexamic acid in the management of upper gastrointestinal bleeding.
BACKGROUND: Tranexamic acid may reduce upper gastrointestinal bleeding and stabilize patients before endoscopic treatments.
AIM: To review randomized trials on tranexamic acid for upper gastrointestinal bleeding.
METHODS: Manual and electronic searches of The Cochrane Library, MEDLINE, EMBASE and Science Citation Index were combined. Intention-to-treat random effect meta-analyses were performed and results presented as RRs with 95% confidence intervals.
RESULTS: Seven double-blind randomized trials on tranexamic acid vs. placebo were included. Of 1754 patients randomized, 21% were excluded. Only one trial included endoscopic treatments or proton pump inhibitors. Five per cent of patients on tranexamic acid and 8% of controls died (RR: 0.61, 95% CI: 0.42-0.89). No significant differences were found on bleeding, bleeding-related mortality, surgery or transfusion requirements. Adverse events were unclearly reported. Data from three of the included trials suggested that tranexamic acid did not significantly increase the risk of thromboembolic disease.
CONCLUSIONS: The present review suggests that tranexamic acid may reduce all-cause mortality. However, because of limitations in the internal and external validity of included trials, additional evidence is needed before treatment recommendations can be made.
Medical therapy is an attractive adjuvant to endoscopic treatment in upper gastrointestinal (UGI) bleeding. This review aims to assess the treatment effects of proton pump inhibitor (PPI) therapy in acute non-variceal UGI bleeding. Outcome measures evaluated were further bleeding, surgery, all-cause deaths, ulcer deaths and non-ulcer deaths. We searched MEDLINE (1966-2002) and EMBASE (1974-2002) using the terms 'gastrointestinal hemorrhage', 'peptic ulcer hemorrhage', 'proton pump inhibitor', 'omeprazole', 'pantoprazole', 'lansoprazole', 'rabeprazole' and 'esomeprazole'. The search was extended to the Cochrane controlled trials registry database, published abstracts from five international gastroenterology conferences, manufacturers of PPI, known contacts and bibliographies from each full-length published report. We included trials published in English and non-English languages. Eligible studies were randomized controlled trials that compared the treatment effects of PPI therapy with placebo or H2 receptor antagonists in patients with acute non-variceal UGI bleeding. Of the 175 articles screened, 26 controlled trials including 4670 subjects (2317 in treatment arm and 2353 in control arm) were analyzed. The methodology, population, intervention, and outcomes of each selected trial were evaluated using duplicate independent review. Disagreements were resolved by consensus. PPI therapy significantly reduced rates of further bleeding (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40-0.57) and surgery (OR, 0.61; 95% CI, 0.48-0.76). All-cause deaths were unaffected (OR, 1.02; 95% CI, 0.76-1.37). Ulcer deaths showed a significant reduction (OR, 0.58; 95% CI, 0.35-0.96), while non-ulcer deaths showed a significant increase (OR, 1.60; 95% CI, 1.06-2.41) in the PPI therapy group. Sensitivity analysis of 22 trials published in peer-reviewed journals, 10 trials with double-blind design and 19 trials with high quality score and 22 trials using omeprazole in the treatment group showed results similar to those seen in the analysis of all 26 trials, confirming the stability of the conclusions. Subgroup analysis revealed that summary outcome measures were not influenced by control group therapy (placebo vs H2 receptor antagonists) or the use of prior endoscopic treatment to achieve hemostasis (given vs not given). However, the summary treatment effects for further bleeding and need for surgery were significant in only those trials enrolling patients with peptic ulcers having high risk for rebleeding and not in those trials enrolling patients with all causes of UGI bleeding. The summary treatment effects for further bleeding and need for surgery were significant in trials using intravenous as well as oral PPI. However, summary OR for all-cause deaths and non-ulcer deaths in trials using intravenous PPI were higher in the treatment group and not in trials using oral PPI. This raised the possibility of intravenous PPI-therapy-associated non-ulcer deaths in high-risk patients. PPI therapy in acute non-variceal UGI bleeding reduced rates of further bleeding, surgery and deaths caused by ulcer complications. However, non-ulcer deaths were increased. The overall mortality was unaffected. PPI therapy is useful only in a selected group of patients with acute non-variceal UGI bleeding, namely those with peptic ulcers having endoscopic high-risk stigmata for rebleeding.
OBJECTIVE: To see whether fibrinolytic inhibitors are of value when given to patients with upper gastrointestinal haemorrhage.
DESIGN: Meta-analysis of six randomised double blind placebo controlled trials. Two methods used for obtaining an overall estimate of effect, including a random effects model incorporating any heterogeneity of outcome in the estimate of the overall treatment effect.
SETTING: Inpatient care in hospitals in the United Kingdom, Sweden, and Australia.
PATIENTS: 1267 Patients admitted to hospital with primary diagnosis of acute upper gastrointestinal haemorrhage. Five of the six trials included a high proportion of elderly patients. Most patients were bleeding from peptic ulcers in the stomach and duodenum (43-88%) or gastric erosions (4-23%). A variable proportion had a degree of clinical shock at entry.
INTERVENTIONS: Tranexamic acid 3-6 g/day given intravenously for two or three days followed by 3-6 g/day by mouth for a further three to five days (four trials) or 4.5-12 g/day by mouth for two to seven days (two trials).
END POINTS: Frequency of recurrent haemorrhage, need for surgery, and death.
MAIN RESULTS: Treatment with tranexamic acid was associated with a 20-30% reduction in the rate of rebleeding, a 30-40% reduction (95% confidence interval 10% to 60%) in mortality.
CONCLUSIONS: Treatment with tranexamic acid may be of value to patients considered to be at risk of dying after an upper gastrointestinal haemorrhage.
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.
