Effect of histamine-2-receptor antagonists versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients: a meta-analysis of 10 randomized controlled trials

INTRODUCTION: We conducted a meta-analysis in order to investigate the effect of histamine-2-receptor antagonists (H(2)RA) versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients in the intensive care unit (ICU). METHODS: A systematic literature search of Medline, EMBASE, Cochrane Central Register of Controlled Trials (1966 to January 2010) was conducted using specific search terms. A review of Web of Science and a manual review of references were also performed. Eligible studies were randomized control trials (RCTs) that compared H(2)RA and sucralfate for the prevention of stress ulcer in mechanically ventilated patients. Main outcome measures were rates of overt bleeding, clinically important gastrointestinal (GI) bleeding, ventilator-associated pneumonia, gastric colonization and ICU mortality. RESULTS: Ten RCTs with 2,092 participants on mechanical ventilation were identified. Meta-analysis showed there was a trend toward decreased overt bleeding when H(2)RA was compared with sucralfate (OR = 0.87, 95% CI: 0.49 to 1.53). A total of 12 clinically important GI bleeding events occurred among 667 patients (1.8%) in the H(2)RA group compared with 26 events among 673 patients (3.9%) in the sucralfate groups. Prophylaxis with sucralfate decreased the incidence of gastric colonization (OR = 2.03, 95% CI: 1.29 to 3.19) and ventilator-associated pneumonia (OR = 1.32, 95% CI: 1.07 to 1.64). Subgroup analysis showed H(2)RA was not superior to sucralfate in reducing early-onset pneumonia (OR = 0.62, 95%CI: 0.36 to 1.07) but had a higher late-onset pneumonia rate (OR = 4.36, 95%CI: 2.09 to 9.09) relative to sucralfate. No statistically significant reduction was observed in mortality of ICU between groups (OR = 1.08, 95% CI: 0.86 to 1.34). CONCLUSIONS: In patients with mechanical ventilation, H(2)RA resulted in no differential effectiveness in treating overt bleeding, but had higher rates of gastric colonization and ventilator-associated pneumonia. Additional RCTs of stress ulcer prophylaxis with H(2)RA and sucralfate are needed to establish the net benefit and risks of adverse effect in mechanically ventilated patients.