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

Abstract

Introduction: 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).

Areas covered: 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.

Expert opinion: 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.

Keywords:

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

Declaration of interest

R MacLaren is a voting member of the Society of Critical Care Medicine’s Taskforce on Stress Ulcer Prophylaxis Guidelines. He is a research consultant for GlaxoSmithKline, previous recipient of investigator-initiated research grants from Hospira and medico-legal consultant for Gordon and Rees, LLC, Denver, CO and for Rutherford Mullin Moore, LLC, Denver, CO. LE Kassel is an expert consultant for Northwest Iowa Compounding and Mansmith Pharmacies, Emmetsburg, IA. TH Kiser is an educational consultant for Janssen Pharmaceuticals, recipient of an investigator-initiated research grant from Pfizer and medico-legal consultant for McConnell Fleischner Houghtaling, LLC, Denver, CO. DN Fish is an expert consultant for Bayer and recipient of an investigator-initiated research grant from Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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