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

Abstract

IMPORTANCE Histamine-2 receptor antagonists (H 2 RAs) 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 and Clostridium difficile infection (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 H 2 RA 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 of International 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 H 2 RAs 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 H 2 RA 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 H 2 RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies.

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

“…The potential adverse effect of PPI use is the increased incidence of pneumonia and Chlostridium difficilis infection (Maclaren et al, 2014). Given the overall uncertain balance between benefit and arm, some author suggest not to routinely use PPIs (Krag et al, 2016).…”

Stress ulcer prophylaxis in critical illness: a Canadian survey

“…Other recent research shows a growing use of PPIs as the primary SUP agent, ranging from 39-70%. 6,9,10,12 This may reflect perceived superiority of PPIs as indicated in a recent systematic review and meta-analysis. The study at issue showed that PPIs were associated with a 60% relative risk reduction in clinically important stress ulcer-related GI bleeding when compared with H2RAs.…”

“…Their study results showed that 62% of patients received PPIs and 38% received H2RAs. 9 In a recent international survey, PPIs were identified as the most common agent (66%) for SUP. 10 Despite their widespread use, questions are emerging about whether SUP is still indicated.…”

Factors Favouring the Development of Clostridium Difficile Infection in Critically Ill Patients

“…The stronger acid suppression of PPIs enhances the risk of infections. This feature is less expressed in H₂RA activity, and also limits the reperfusion injury in animal models, possibly by reducing oxidative stress after mucosal injury [20]. To see if PPIs administration is a risk factor for infection we use a logistic regression model.…”