Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials

Purpose: Stress ulcer prophylaxis (SUP) is commonly prescribed in the intensive care unit. However, data from systematic reviews and conventional meta-analyses are limited by imprecision and restricted to direct comparisons. We conducted a network meta-analysis of randomized clinical trials (RCTs) to examine the safety and efficacy of drugs available for SUP in critically ill patients. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials through April 2017 for randomized controlled trials that examined the efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date or language restrictions were applied. Data on study characteristics, methods, outcomes, and risk of bias were abstracted by two reviewers. Results: Of 96 potentially eligible studies, we included 57 trials enrolling 7293 patients. The results showed that PPIs are probably more effective for preventing clinically important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95% confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13, 0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence). There were no convincing differences among H2RA, sucralfate, and placebo. PPIs probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27; 95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR 1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar across interventions (moderate quality). Estimates of baseline risks of bleeding varied significantly across studies, and only one study reported on Clostridium difficile infection. Definitions of pneumonia varied considerably. Most studies on sucralfate predate pneumonia prevention strategies. Conclusions: Our results provide moderate quality evidence that PPIs are the most effective agents in preventing CIB, but they may increase the risk of pneumonia. The balance of benefits and harms leaves the routine use of SUP open to question.