Histamine-2 Receptor Antagonists vs Proton Pump Inhibitors on Gastrointestinal Tract Hemorrhage and Infectious Complications in the Intensive Care Unit

Importance

Histamine-2 receptor antagonists (H₂RAs) and proton pump inhibitors (PPIs) are commonly used to prevent gastrointestinal tract (GI) hemorrhage in critically ill patients. The stronger acid suppression of PPIs may reduce the rate of bleeding but enhance infectious complications, specifically pneumonia andClostridium difficileinfection (CDI).

Objective

To evaluate the occurrence and risk factors for GI hemorrhage, pneumonia, and CDI in critically ill patients.

Design, Setting, and Participants

A pharmacoepidemiological cohort study was conducted of adult patients requiring mechanical ventilation for 24 hours or more and administered either an H₂RA or PPI for 48 hours or more while intubated across 71 hospitals between January 1, 2003, and December 31, 2008. Propensity score–adjusted and propensity-matched multivariate regression models were used to control for confounders.

Main Outcomes and Measures

Primary outcomes were secondary diagnoses ofInternational Classification of Diseases, Ninth Revision (ICD-9)–coded GI hemorrhage, pneumonia, and CDI occurring 48 hours or more after initiating invasive ventilation.

Results

Of 35 312 patients, 13 439 (38.1%) received H₂RAs and 21 873 (61.9%) received PPIs. Gastrointestinal hemorrhage (2.1% vs 5.9%;P < .001), pneumonia (27% vs 38.6%;P < .001), and CDI (2.2% vs 3.8%;P < .001) occurred less frequently in the H₂RA group. After adjusting for propensity score and covariates, odds ratios of GI hemorrhage (2.24; 95% CI, 1.81-2.76), pneumonia (1.2; 95% CI, 1.03-1.41), and CDI (1.29; 95% CI, 1.04-1.64) were greater with PPIs. Similar results were obtained in the propensity-matched models of 8799 patients in each cohort.

Conclusions and Relevance

Proton pump inhibitors are associated with greater risks of GI hemorrhage, pneumonia, and CDI than H₂RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies.