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; I2 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; I2 = 66%). In the sensitivity analysis, removing the Levy study significantly reduced the heterogeneity (from I2 = 66% to I2 = 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; I2 = 0%) and 0.02 (95% confidence interval, −0.04-0.08; p = .50; I2 = 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.
From the Department of Pharmacy (P-CL, P-LT), Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; School of Pharmacy (P-CL), College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine (C-HC), National Taiwan University Hospital, Taipei, Taiwan; Institute of Preventive Medicine (C-HC), College of Public Health, National Taiwan University, Taipei, Taiwan; Division of Gastroenterology (P-IH), Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Pharmacy (Y-BH), College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
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We thank Dr. Wen-Yi Shau, Dr. Chien-Hung Lee, and Dr. Yiqing Song for conducting, reviewing, and commenting on the analysis.
The authors have not disclosed any potential conflicts of interest.
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