Prevention of GI bleeding in critically ill patients is a common practice in the ICU. The two most common classes that are used for such indication are histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs).1,2 Several systematic reviews have shown that PPIs further lower bleeding rates by having a profound acid suppression effect.3-5 This effect has been shown in some epidemiologic studies outside the ICU to be associated with pneumonia or Clostridium difficile infection (CDI).6,7 Therefore, to study this association in critically ill adult patients, the authors sought to evaluate whether the use of PPIs was associated with pneumonia and CDI in adults critically ill patients. Their hypothesis is that the stronger acid-suppressing effects of PPIs may decrease the occurrence of GI bleeding but may increase the risk of both pneumonia or Clostridium difficile infection (CDI) in mechanically ventilated adults.
The study is a retrospective analysis involving adult patients admitted to the ICU between January 2003- December 2008 and requiring mechanical ventilation for ≥ 24 hours. Patients were either receiving a histamine-2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) for ≥ 48 hours.8 Exclusion criteria include: a diagnosis of variceal hemorrhage; GI hemorrhage or a coded bleeding event within 24 hours of requiring invasive ventilation; administration of PPIs exceeding twice daily dosing (including infusion), octreotide, somatostatin during the first 24 hours of invasive ventilation; or administration of both an H2RA and PPI while in the ICU. Multiple covariates were assessed including but not limited to the duration of acid-suppressing therapy, length of mechanical ventilation, length of ICU stay, kidney injury, septic shock, thrombocytopenia, corticosteroid use, etc. 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.
In total, 35,312 patients from 71 hospitals were included (13,439 in H2RA group and 21,873 in the PPI group). Famotidine was the most common H2RA prescribed (12.7% of patients receiving H2RAs received high-dose administration). Pantoprazole was the most common PPI prescribed (47% of patients receiving PPIs received high dose administration, 98.9% of high dose was twice daily dosing). Following adjustments, odds ratio of developing secondary 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 in the PPI group. Following propensity matching the rates of GI hemorrhage, pneumonia and CDI remained higher in the PPI group.
Limitations mentioned by authors include the fact that data was only available through December 2008, so any practice changes that occurred between then and the present have not been captured. The authors gave ventilator-associated pneumonia as an example where the ICD-9 code was made available in 2009.
In conclusion, PPIs were more likely to be associated with GI hemorrhage compared to H2RAs which contradicts what the authors hypothesized in that stronger acid suppression reduces GI bleeding. In addition, the results also ...