• Pei-Chin Lin, Chia-Hsuin Chang, Ping-I Hsu, Pi-Lai Tseng, and Yaw-Bin Huang.
• Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
• Crit. Care Med. 2010 Apr 1;38(4):1197-205.

ObjectiveTo 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 SourcesPubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov.Study SelectionRandomized, 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 ExtractionTwo 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 SynthesisThe random effect model was used to estimate the pooled risk difference between two treatment arms irrespective of drug, dosage, and route of administration.ResultsWe 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 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 = 66%). In the sensitivity analysis, removing the Levy study significantly reduced the heterogeneity (from I = 66% to I = 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 = 0%) and 0.02 (95% confidence interval, -0.04-0.08; p = .50; I = 0%), respectively.ConclusionsThis 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.

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