The increased risk of pneumonia from proton pump inhibitors (PPI) has been addressed in recent studies. This study aimed to investigate the risk of hospital-acquired pneumonia (HAP) in critically ill patients receiving PPI or sucralfate. This retrospective observational cohort study analyzed patients who were prescribed with PPIs or sucralfate for stress ulcer prophylaxis in intensive care units (ICU). A propensity score and other risk factors were used to calculate the adjusted odds ratio (OR) for the two groups. The final cohort comprised 388 patients with 302 patients on PPI and 86 patients on sucralfate therapies. HAP developed in 63 patients (20.86%) on PPI, and 8 patients (9.30%) on sucralfate (adjusted OR 3.37, 95% CI 1.35-8.45, p-value 0.009). The enrolled patients on PPI therapy with an APACHE II score > 13 (adjusted OR 3.70, 95% CI 1.04-13.10, p-value 0.043), or those on PPI therapy with an ICU stay of more than 8 days (adjusted OR 9.04, 95% CI 1.94-42.06, p-value 0.005) had the highest risk of developing HAP. Patients in medical ICU treated with PPIs had a higher risk of developing HAP than those treated with sucralfate. For the ICU patients requiring stress ulcer prophylaxis, sucralfate can be considered as a priority treatment. The risk and benefit of PPI treatment should be evaluated for patients who may have a longer ICU stay or have a high APACHE II score.

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