title: Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.
abstract: BACKGROUND
  There is conflicting evidence regarding the clinical efficacy of proton pump inhibitors (PPI) initiated before endoscopy for upper gastrointestinal bleeding.
  
  
  OBJECTIVE
  To systematically review evidence from randomised controlled trials (RCTs) of PPI treatment initiated before endoscopy for upper gastrointestinal bleeding.
  
  
  METHODS
  We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE and CINAHL databases and major conference proceedings to September 2005, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model. Searches were re-run in February 2006 and October 2008.
  
  
  METHODS
  We selected randomised controlled trials (RCTs), of hospitalised participants with unselected upper gastrointestinal bleeding, undergoing active treatment with a proton pump inhibitor PPI (oral or intravenous) and control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment prior to endoscopy. Outcomes were assessed at 30 days and included mortality, rebleeding and surgery. Also assessed were stigmata of recent haemorrhage (SRH; active bleeding, non bleeding visible vessel or adherent clot) at index endoscopy, length of hospital stay, blood transfusion requirements and requirement for endoscopic therapy at index endoscopy.
  
  
  METHODS
  At least two review authors assessed eligibility criteria and extracted data regarding outcomes and factors affecting methodological quality.
  
  
  RESULTS
  Six RCTs comprising 2223 participants were included. There was no statistical heterogeneity among trials for dichotomous outcomes. There were no statistically significant differences in mortality, rebleeding or surgery between PPI and control treatment. Unweighted pooled mortality rates were 6.1% and 5.5% respectively (odds ratio (OR)1.12; 95% CI 0.72 to 1.73). Unweighted pooled rebleeding rates were 13.9% and 16.6% respectively (OR 0.81; 95%CI 0.61 to 1.09). Pooled rates for surgery were 9.9% and 10.2% respectively (OR 0.96 95% CI 0.68 to 1.35). PPI treatment compared to control significantly reduced the proportion of participants with SRH at index endoscopy; unweighted pooled rates were 37.2% and 46.5% respectively (OR 0.67; 95% CI 0.54 to 0.84). However, this result was not robust to sensitivity analysis. PPI treatment compared to control significantly reduced endoscopic therapy at index endoscopy; unweighted pooled rates were 8.6% and 11.7% respectively (OR 0.68; 95% CI 0.50 to 0.93). For continuous outcomes (length of hospital stay and blood transfusion requirements), quantitative analysis could not be performed.
  
  
  CONCLUSIONS
  PPI treatment initiated before endoscopy for upper gastrointestinal bleeding might reduce the proportion of participants with SRH at index endoscopy and significantly reduces requirement for endoscopic therapy during index endoscopy. However, there is no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding or need for surgery.
authors.affiliation: Department of Gastroenterology, United Lincolnshire Hospitals NHS Trust, Lincoln County Hospital, Greetwell Road, Lincoln, Lincolnshire, UK, LN2 2YE.
authors.forename: Aravamuthan
authors.initials: A
authors.lastname: Sreedharan
authors.forename: Janet
authors.initials: J
authors.lastname: Martin
authors.forename: Grigorios I
authors.initials: GI
authors.lastname: Leontiadis
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dorward
authors.forename: Colin W
authors.initials: CW
authors.lastname: Howden
authors.forename: David
authors.initials: D
authors.lastname: Forman
authors.forename: Paul
authors.initials: P
authors.lastname: Moayyedi
mesh_terms: D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D016099:Endoscopy, Gastrointestinal; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy* / Q000401:mortality; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D054328:Proton Pump Inhibitors; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors