OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

Armauer Hansen Research Institute Addis Ababa Ethiopia

Center of Evidence Based Education and Arts Therapies A JBI Affiliated Group Palacky University Olomouc Faculty of Education Olomouc Olomoucký Czech Republic

Centro Universitário Arthur Sá Earp Neto UNIFASE Petropolis Brasil

Cochrane Czech Republic Czech Republic a JBI Centre of Excellence Czech GRADE Network Institute of Health Information and Statistics of the Czech Republic Prague Czech Republic

Cochrane Germany Cochrane Germany Foundation Freiburg Germany

Czech National Centre for Evidence Based Healthcare and Knowledge Translation Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

Department of Anesthesia McMaster University Hamilton Ontario Canada

Department of General Visceral Thorax and Vascular Surgery University Hospital Bonn Bonn Germany

Department of Health Research Methods Evidence and Impact McMaster University Hamilton Ontario Canada

Ethiopian Evidence Based Health Care Center Institute of Health A Joanna Briggs Institute's Center of Excellence Faculty of Public Health Institute of Health Jimma University Jimma Ethiopia

Institute for Evidence in Medicine Medical Center Faculty of Medicine University of Freiburg Freiburg im Breisgau Germany

Medical Intensive Care Unit Christian Medical College and Hospital Vellore India

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