Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.

Jie Yao, Dominic Wen; Ong, Chengsi; Eales, Nichola Mary; Sultana, Rehena; Ju-Ming Wong, Judith; Lee, Jan Hau

OBJECTIVE To determine the association between stress ulcer prophylaxis on gastrointestinal bleeding, nosocomial pneumonia, mortality, and length of stay in the pediatric intensive care unit (PICU). STUDY DESIGN We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies in the English language assessing effects of proton pump inhibitors and histamine-2 receptor antagonists on PICU patients published before October 2018 from PubMed, EMBASE, CINAHL, and CENTRAL databases. Random-effect Mantel-Haenszel risk difference (MHRD) model was used to pool all the selected studies for meta-analysis. Primary outcomes were incidence of gastrointestinal bleeding and nosocomial pneumonia. Secondary outcomes included mortality and length of PICU stay. RESULTS Seventeen studies (4 randomized controlled trials and 13 observational) comprising 340,763 patients were included. Overall incidence of gastrointestinal bleeding was 15.2%. There was no difference in the risk of gastrointestinal bleeding (MHRD 5.0%; 95%CI -1.0% to 11.0%, I2=62%) between SUP status. There was increased risk of nosocomial pneumonia for patients who received SUP (MHRD 5.3%; 95%CI 3.5% to 7.0%; I2=0%) compared with those who did not. An increased risk of mortality was found in patients receiving SUP (MHRD 2.1%; 95%CI 2.0% to 2.2%; I2=0%), although when one large study was removed in a sensitivity analysis this association was no longer found. No statistical difference was found in length of PICU stay between the groups (standardized mean difference 0.42; 95%CI -0.16 to 1.01 days; I2=89.8%). CONCLUSIONS SUP does not show clear benefit in reducing gastrointestinal bleeding or PICU stay. Observational studies suggest an increased risk of nosocomial pneumonia and mortality with SUP, which needs to be validated in clinical trials.