Proton-Pump Inhibitors vs. Histamine-2 Receptor Antagonists to Prevent Stress Gastritis

David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

A surprising finding of increased risk for gastrointestinal bleeding with PPI use is questionable due to study weaknesses.

Critically ill patients are at risk for developing gastrointestinal bleeding (GIB) from stress-related mucosal disease. Prophylactic acid reduction therapy using either proton-pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) is common. However, acid reduction is associated with an increased risk for pneumonia and has been suggested to increase the risk for Clostridium difficile infection (CDI; NEJM JW Gastroenterol Nov 12 2013, NEJM JW Gen Med Jul 31 2012, NEJM JW Gastroenterol Dec 23 2013).

To compare frequencies of GIB, pneumonia, and CDI associated with PPI use versus H2RA use in this setting, investigators retrospectively reviewed patient data from a commercial administrative database. Study patients required mechanical ventilation for at least 24 hours and received either a PPI or an H2RA. Outcomes were defined as secondary diagnoses of GIB, pneumonia, or CDI (based on ICD-9 codes) that occurred ≥48 hours after initiation of ventilation. Other potential covariates were collected.

In 35,312 patients, 62% received PPIs and 38% received H2RAs. All outcomes were more common in the PPI group (GIB, 5.9% vs. 2.1%; pneumonia, 38.6% vs. 27.0%; and CDI, 3.8% vs. 2.2%; P<0.001 for all). Adjustment for covariates, adjustment for a propensity score for acid suppressant choice, and sensitivity analyses did not alter the results.

Citation(s):

MacLaren R et al. Histamine-2 receptor antagonists vs. proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 2014 Feb 17; [e-pub ahead of print].

Kim R and Goss CH.Unintended consequences of therapy in the intensive care unit. JAMA Intern Med 2014 Feb 17; [e-pub ahead of print].