Ventilator-Associated Pneumonia in Patients Using Proton Pump Inhibitors Versus Histamine H2 Receptor Antagonists: A Systematic Review and Meta-Analysis.

Background: The common use of proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RA) in critically ill patients may increase the incidence of pneumonia associated with mechanical ventilation caused by alkalinization of gastric pH and microaspirations. Given the differences in the mechanisms of action of these drugs, we propose to evaluate, through a systematic review and meta-analysis, the incidence of ventilator-associated pneumonia (VAP) in this patient profile. Methods: We systematically searched PubMed, Embase, and Cochrane, and we included articles that evaluated subjects admitted to the ICU using mechanical ventilation for >48 hours, comparing PPI versus H2RA, to evaluate VAP as the primary outcome. Review Manager 5.4.1 was used for statistical analysis, and heterogeneity was examined with the I2 statistic. We use Mantel-Haenszel as a statistical test. Results: A total of 33,471 subjects from 4 randomized controlled trials (RCTs) and 5 nonrandomized cohorts were included. In total, 16,515 (49.34%) subjects received PPI and 16,956 (50.65%) received H2RA. The average age of the population was 56 years. There was no difference in the incidence of VAP when using PPI versus H2RA (5.8% vs 6.1%; odds ratio [OR] 1.04, 95% CI 0.81-1.34, P = .77; I2 = 69%) or all-cause mortality (31.88% vs 20.35%; OR 1.30, 95% CI 0.96-1.76, P = .09; I2 = 93%) between groups. In a subanalysis of RCT-only data (469 subjects), the use of PPI or H2RA was also no different in the incidence of VAP (26.52% vs 20.50%; OR 1.41, 95% CI 0.50-3.98; P = .52; I2 = 76%). Conclusions: The data show that the use of PPI or H2RA was indifferent to the incidence of VAP in subjects receiving mechanical ventilation for more than 48 hours. Furthermore, there was also no difference between the groups in relation to all-cause mortality, hospital stay, ICU stay, or duration of mechanical ventilation.