Comparative Efficacy and Safety of Antiulcer Drugs for Stress Ulcer Prophylaxis (SUP) in Critically Ill Patients: A Systematic Review and Network Meta-Analysis

Abstract

Background: Stress ulcers can affect the prognosis of critically ill patients. However, is stress ulcer prophylaxis (SUP) necessary for critically ill patients? What is the best choice of SUP? There are no specific answers to these two questions. The aim of our study was to conduct a conventional pairwise meta-analysis to assess the effects of SUP versus no prophylaxis and to perform a network meta-analysis to evaluate the efficacy and safety of antiulcer drugs for SUP in adult critically ill patients. Methods: We searched the Cochrane Central Register of Controlled Trials in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and the Web of Science using a combination of MeSH and text words relevant to SUP, critically ill patients, adults, proton pump inhibitors (PPIs), histamine-2-receptor antagonists (H2RAs), sucralfate, and antacids, together with randomized controlled trials from the date of database inception to July 5, 2017. We extracted relevant information using a predefined data extraction form and assessed the risk of bias using the Cochrane risk of bias tool. Our primary outcome was the incidence of gastrointestinal (GI) bleeding. The secondary outcome was all-cause mortality and the risk of pneumonia. Findings: A total of 73 randomized controlled trials, with a total of 10,509 adult critically ill patients, were identified in our study. In the pairwise meta-analysis, we found a statistically significant difference between SUP and no prophylaxis for GI bleeding (RR 0·45, 95% CI 0·38 to 0·53) but no statistically significant differences in mortality (RR 0·96, 95% CI 0·84 to 1·10) or the risk of pneumonia (RR 1·15, 95% CI 0·91 to 1·46). In a 5-node network meta-analysis, pooled effect sizes suggested that, compared to no prophylaxis, all interventions were associated with reduced GI bleeding. Additionally, compared to PPIs (RR 0·60, 95% CI 0·47 to 0·76) and H2RAs (RR 0·77, 95% CI 0·67 to 0·88), sucralfate was associated with a reduction in pneumonia. In an 11-node network meta-analysis, omeprazole was significantly more effective than cimetidine, ranitidine, and sucralfate in preventing GI bleeding, while compared to omeprazole, pantoprazole and ranitidine, sucralfate was associated with a decreased risk of pneumonia. In terms of mortality, the combined results showed no statistically significant differences in any comparisons. Interpretation: SUP is necessary for preventing GI bleeding in adult critically ill patients. We recommend sucralfate as a better choice for SUP in adult critically ill patients. Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81402462, 81571871 and 81770276) and the Yuweihan Fund for Distinguished Young Scholars. Declaration of interests: We declare no competing interests.