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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

Lin, Pei-Chin MSCP; Chang, Chia-Hsuin MD, ScD; Hsu, Ping-I MD; Tseng, Pi-Lai MS; Huang, Yaw-Bin PhD

doi: 10.1097/CCM.0b013e3181d69ccf
Review Articles

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.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ccmjournal.com).

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.

For information regarding this article, E-mail: yabihu@kmu.edu.tw

© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins