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Expert Opin Drug Saf. 2015 Feb;14(2):269-80. doi: 10.1517/14740338.2015.986456. Epub 2014 Nov 25.

Proton pump inhibitors and histamine-2 receptor antagonists in the intensive care setting: focus on therapeutic and adverse events.

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University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy , C238, 12850 East Montview Blvd, Aurora, CO 80045 , USA +1 303 724 2622 ; +1 303 724 0979 ;



Histamine-2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) are frequently used to prevent stress-related mucosal bleeding (SRMB). A paucity of data implicates these agents with pneumonia and Clostridium difficile infection (CDI).


This review comparatively evaluates the effectiveness of H2RAs and PPIs and delineates their associations with these infectious complications. A literature review through 30 September 2014 was performed.


The rate of SRMB is declining, likely due better resuscitation strategies and the early provision of enteral nutrition. Therefore, gastric acid-suppressing therapies arguably reduce SRMB. However, they may contribute to pneumonia and CDI. The risks of these infectious complications depend on the extent of acid suppression and may vary by patient population. PPIs are associated with the greatest hazard for these infections, likely because they provide stronger acid suppression. Intermittent administration of H2RAs has theoretical advantages over continuous H2RA or PPI therapies as this dosing strategy does not fully suppress gastric acid and may limit infection risk. Placebo-controlled studies are warranted because clinical equipoise exists as the detrimental outcomes of these infections may outweigh the benefit of preventing SRMB given the infrequent occurrence of SRMB.


Clostridium difficile; critical care; gastric acid; histamine receptor antagonist; intensive care; pneumonia; proton pump inhibitor; stress ulcer

[Indexed for MEDLINE]

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