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Proton Pump Inhibitors vs. Histamine 2 Receptor Antagonists for Stress-Related Mucosal Bleeding Prophylaxis in Critically Ill Patients: A Meta-Analysis

Barkun, Alan N MD, MSc1, 2; Bardou, Marc MD, PhD3, 4; Pham, C Q D PharmD5, 6; Martel, Myriam BSc1

American Journal of Gastroenterology: April 2012 - Volume 107 - Issue 4 - p 507–520
doi: 10.1038/ajg.2011.474

OBJECTIVES: H2-receptor antagonists (H2RA) have been shown to reduce stress-related mucosal bleeding (SRMB), yet randomized controlled trials assessing proton pump inhibitors (PPIs) have yielded conflicting results. The objective of this study was to evaluate the efficacy of PPIs vs. H2RAs in the prophylaxis of SRMB in critically ill adults with risk factors for bleeding.

METHODS: Tailored literature searches of the past four decades were conducted. Outcomes measured were the decreases in rates of clinically significant bleeding (B, primary outcome of the meta-analysis), nosocomial pneumonia (P), and mortality (M) (secondary outcomes). Study heterogeneity was sought and quantified. Results are reported as odd ratios (ORs) with 95% confidence intervals (CIs).

RESULTS: Eight fully published randomized controlled trials and five abstracts met the inclusion criteria. Prophylactic PPI administration significantly decreased the incidence of bleeding (N=1,587 patients, OR=0.30; 95% CI: 0.17–0.54), number needed to treat=39; 95% CI: 21–303 with no observed statistical heterogeneity among the relevant comparisons (P=0.93,I2=0.0%). No statistical differences were noted for the development of nosocomial pneumonia (n=7,N=1,017 patients, OR=1.05; 95% CI: 0.69–1.62) or mortality (n=8,N=1,260 patients, OR=1.19; 95% CI: 0.84–1.68) or (and no heterogeneity was found for either:P=0.85,I2=0.0%, andP=0.96,I2=0%, respectively).

CONCLUSIONS: In critically ill patients at risk for the development of SRMB, PPI prophylaxis significantly decreased rates of clinically significant bleeding compared with H2RA, without affecting the development of nosocomial pneumonia or mortality rates. The magnitude of the beneficial effect, and its clinical relevance, now requires further characterization using cost-effectiveness analysis considering the incidence of stress-related mucosal disease-related bleeding.

1 Division of Gastroenterology, McGill University Health Center, McGill University, Montreal, Québec, Canada

2 Division of Clinical Epidemiology, McGill University Health Center, McGill University, Montreal, Québec, Canada

3 INSERM CIC-P 803, CHU de Dijon, Dijon, France

4 Université de Bourgogne, Dijon, France

5 Faculty of Pharmacy, University of Montreal, Montréal, Québec, Canada

6 Health Canada, Government of Canada, Ottawa, Ontario, Canada

Correspondence: Alan N. Barkun, MD, MSc, Division of Gastroenterology, McGill University Health Center, Montreal General Hospital Site, Room D7-346, 1650 Cedar Avenue, Montréal, Québec, Canada H3G 1A4. E-mail:

Received 5 July 2011; accepted 2 December 2011

published online 31 January 2012

© The American College of Gastroenterology 2012. All Rights Reserved.
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