The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: A meta-analysis

Objective: To examine the efficacy and safety of proton pump inhibitors in comparison with histamine-2 receptor antagonists for stress-related upper gastrointestinal bleeding prophylaxis among critical care patients. Data Sources: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Study Selection: Randomized, controlled trials that directly compare proton pump inhibitors with histamine-2 receptor antagonists in prevention of stress-related upper gastrointestinal bleeding in intensive care unit patients published before May 30, 2008. Data Extraction: Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. The primary outcome was the incidence of stress-related upper gastrointestinal bleeding, and the secondary outcome measures were the incidence of pneumonia and intensive care unit mortality. Data Synthesis: The random effect model was used to estimate the pooled risk difference between two treatment arms irrespective of drug, dosage, and route of administration. Results: We identified seven randomized, controlled trials with a total of 936 patients for planned comparison. The overall pooled risk difference (95% confidence interval; p value; I-2 statistics) of stress-related upper gastrointestinal bleeding comparing proton pump inhibitors vs. histamine-2 receptor antagonists was -0.04 (95% confidence interval, -0.09-0.01; p = .08; I-2 = 66%). In the sensitivity analysis, removing the Levy study significantly reduced the heterogeneity (from I-2 = 66% to I-2 = 26%) and shifted the overall risk difference closer to the null (pooled risk difference, -0.02; 95% confidence interval, -0.05-0.01; p = .19). There was no difference between proton pump inhibitors and histamine-2 receptor antagonists therapy in the risk of pneumonia and intensive care unit mortality, with pooled risk differences of 0.00 (95% confidence interval, -0.04-0.05; p = .86; I-2 = 0%) and 0.02 (95% confidence interval, -0.04-0.08; p = .50; I-2 = 0%), respectively. Conclusions: This meta-analysis did not find strong evidence that proton pump inhibitors were different from histamine-2 receptor antagonists in terms of stress-related upper gastrointestinal bleeding prophylaxis, pneumonia, and mortality among patients admitted to intensive care units. Because of limited trial data, future well-designed and powerful randomized, clinical trials are warranted. (Crit Care Med 2010; 38: 1197-1205)