Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis

• Published in: Intensive care medicine 2019-02, Vol.45 (2), p.143-158
• Main Authors: Barbateskovic, Marija, Marker, Søren, Granholm, Anders, Anthon, Carl Thomas, Krag, Mette, Jakobsen, Janus Christian, Perner, Anders, Wetterslev, Jørn, Møller, Morten Hylander
• Format: Article
• Language: English
• Subjects: Anesthesiology; Bacterial pneumonia; Bleeding; Clinical trials; Complications and side effects; Confidence intervals; Critical Care Medicine; Denmark; Drug therapy; Emergency Medicine; Enteritis; Evidence-based medicine; Histamine; Histamine H2 Antagonists - therapeutic use; Hospital patients; Humans; Inhibitors; Intensive; Intensive care; Intensive Care Units - organization & administration; Ischemia; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Meta-analysis; Mortality; Myocardial ischemia; Pain Medicine; Patients; Pediatrics; Pneumology/Respiratory System; Pneumonia; Pre-Exposure Prophylaxis - methods; Prophylaxis; Proton pump inhibitors; Proton Pump Inhibitors - therapeutic use; Quality of life; Sequential analysis; Stomach Ulcer - drug therapy; Stress; Stress, Psychological - complications; Stress, Psychological - drug therapy; Stress, Psychological - physiopathology; Systematic Review; Ulcers; Upgrading
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-019-05526-z

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.