Prophylactic Proton Pump Inhibitors in Critically Ill Patients Undergoing Invasive Ventilation: A Systematic Review and Meta‐Analysis of Randomized Trials

Objective To assess the safety and efficacy of prophylactic proton pump inhibitors (PPIs) among critically ill adults undergoing invasive ventilation. Methods We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published up to September 19, 2024. Eligible trials compared prophylactic PPIs with placebo or no prophylaxis for upper gastrointestinal bleeding (UGIB) prevention in adults receiving invasive ventilation. Nine RCTs encompassing 8388 patients were included. Data were pooled using Review Manager 5.4, with a random‐effects model applied to all outcomes. Results All‐cause mortality rates were comparable between the PPI and control groups (odds ratio OR: 0.98; 95% confidence interval CI: 0.89−1.07; I 2 = 0%; p = 0.61). PPI prophylaxis significantly reduced the incidence of UGIB (OR: 0.42; 95% CI: 0.23−0.75; I 2 = 33%; p = 0.003) and clinically important UGIB (OR: 0.36; 95% CI: 0.19−0.69; I 2 = 10%; p = 0.002). The analysis revealed no significant increase in the risk of ventilator‐associated pneumonia (OR, 0.99; 95% CI, 0.87 to 1.12; I 2 = 0%; p = 0.86) or Clostridioides difficile infection (OR, 1.63; 95% CI, 0.97 to 2.73; I 2 = 0%; p = 0.07) with PPI use. Durations of intensive care unit stay and invasive ventilation did not differ significantly between groups. Conclusion Among mechanically ventilated patients, prophylactic PPI therapy significantly decreased UGIB and clinically important UGIB risk compared to placebo, without affecting all‐cause mortality.