Pharmacotherapy. 2021 Sep 3. doi: 10.1002/phar.2621. Online ahead of print.
OBJECTIVE: Approximately 1-5% of critically ill patients experience clinically important gastrointestinal bleeding (CIGB). This study assessed the effectiveness and safety of proton-pump inhibitors (PPIs) compared to histamine type 2 receptor antagonists (H2RAs) for prevention of CIGB in mechanically ventilated patients.
DESIGN: Retrospective, single-center, pharmacoepidemiolgic study.
SETTING: Six intensive care units (ICUs).
PATIENTS: Critically ill adults admitted between 9/1/14 and 9/1/19 who received PPIs or H2RAs within 24 hours of intubation and for ≥ 48 hours.
MEASUREMENTS AND MAIN RESULTS: Primary outcomes were CIGB occurring 48 hours after ICU admission and hospital mortality. Secondary outcomes were pneumonia, Clostridioides difficile infection (CDI), acute kidney injury, myocardial infarction / ischemia, thrombocytopenia, and delirium. Outcomes were defined using International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10)-codes with manual cross reference for a hemoglobin drop, transfusion, or hemodynamic compromise to further define CIGB. Of 3,873 patients, 2,061 (53.2%%) received PPIs. CIGB was rare but higher in the PPI group (0.34% vs. 0%, RR=1, 95% CI, 1-1; p=0.013); however substantial group differences existed possibly predisposing the PPI group to CIGB. Hospital mortality was higher in the PPI group (42.1% vs. 29.1%, RR=1.23, 95% CI, 1.17-1.29; p<0.0001). PPIs remained an independent risk factor for mortality after multivariate adjustment (RR=1.61, 95% CI, 1.39-1.88; p<0.0001). Rates of secondary outcomes were similar between groups except thrombocytopenia (4.3% vs. 2.2%, RR=1.02, 95% CI, 1.01-1.03; p=0.0003) and delirium (83.7% vs. 78.1%, RR=1.34, 95% CI, 1.18-1.53; p<0.0001) that were higher in the PPI group.
CONCLUSION: PPIs were associated with CIGB; however, the overall rate of CIGB was low. Compared to H2RAs, PPIs were associated with hospital mortality. Further identification of appropriate selection criteria for ulcer prophylaxis and comparisons of pharmacologic prevention strategies are warranted.