Marija Barbateskovic1,2, Søren Marker3,4, Anders Granholm4, Carl Thomas Anthon4, Mette Krag4, Janus Christian Jakobsen5,3,6, Anders Perner3,4, Jørn Wetterslev5,3, Morten Hylander Møller3,4. 1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, 2100, Copenhagen, Denmark. marija.barbateskovic@ctu.dk. 2. Centre for Research in Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. marija.barbateskovic@ctu.dk. 3. Centre for Research in Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4. Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Copenhagen Trial Unit, Centre for Clinical Intervention Research, 2100, Copenhagen, Denmark. 6. Department of Cardiology, Holbaek Hospital, Holbaek, Denmark.
Abstract
PURPOSE: Most intensive care unit (ICU) patients receive stress ulcer prophylaxis. We present updated evidence on the effects of prophylactic proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs) versus placebo/no prophylaxis on patient-important outcomes in adult ICU patients. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials assessing the effects of PPI/H2RA versus placebo/no prophylaxis on mortality, gastrointestinal (GI) bleeding, serious adverse events (SAEs), health-related quality of life (HRQoL), myocardial ischemia, pneumonia, and Clostridium (Cl.) difficile enteritis in ICU patients. RESULTS: We identified 42 trials randomising 6899 ICU patients; 3 had overall low risk of bias. We did not find an effect of stress ulcer prophylaxis on mortality [relative risk 1.03, 95% confidence interval (CI) 0.94-1.14; TSA-adjusted CI 0.94-1.14], but the occurrence of any GI bleeding was reduced as compared with placebo/no prophylaxis (0.60, 95% CI 0.47-0.77; TSA-adjusted CI 0.36-1.00). The conventional meta-analysis indicated that clinically important GI bleeding was reduced (RR 0.63, 95% CI 0.48-0.81), but the TSA-adjusted CI 0.35-1.13 indicated lack of firm evidence. The effects of stress ulcer prophylaxis on SAEs, HRQoL, pneumonia, myocardial ischemia and Cl. difficile enteritis are uncertain. CONCLUSIONS: In this updated systematic review, we were able to refute a relative change of 20% of mortality. The occurrence of GI bleeding was reduced, but we lack firm evidence for a reduction in clinically important GI bleeding. The effects on SAEs, HRQoL, pneumonia, myocardial ischemia and Cl. difficile enteritis remain inconclusive.
PURPOSE: Most intensive care unit (ICU) patients receive stress ulcer prophylaxis. We present updated evidence on the effects of prophylactic proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs) versus placebo/no prophylaxis on patient-important outcomes in adult ICU patients. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials assessing the effects of PPI/H2RA versus placebo/no prophylaxis on mortality, gastrointestinal (GI) bleeding, serious adverse events (SAEs), health-related quality of life (HRQoL), myocardial ischemia, pneumonia, and Clostridium (Cl.) difficileenteritis in ICU patients. RESULTS: We identified 42 trials randomising 6899 ICU patients; 3 had overall low risk of bias. We did not find an effect of stress ulcer prophylaxis on mortality [relative risk 1.03, 95% confidence interval (CI) 0.94-1.14; TSA-adjusted CI 0.94-1.14], but the occurrence of any GI bleeding was reduced as compared with placebo/no prophylaxis (0.60, 95% CI 0.47-0.77; TSA-adjusted CI 0.36-1.00). The conventional meta-analysis indicated that clinically important GI bleeding was reduced (RR 0.63, 95% CI 0.48-0.81), but the TSA-adjusted CI 0.35-1.13 indicated lack of firm evidence. The effects of stress ulcer prophylaxis on SAEs, HRQoL, pneumonia, myocardial ischemia and Cl. difficileenteritis are uncertain. CONCLUSIONS: In this updated systematic review, we were able to refute a relative change of 20% of mortality. The occurrence of GI bleeding was reduced, but we lack firm evidence for a reduction in clinically important GI bleeding. The effects on SAEs, HRQoL, pneumonia, myocardial ischemia and Cl. difficileenteritis remain inconclusive.
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