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Efficacy and Safety of Stress Ulcer Prophylaxis in Critically Ill Patients: A Network Meta-Analysis of Randomized Trials
Alhazzani W, Alshamsi F, Belley-Cote E, et al. Intensive Care Med. 2018; 44: 1-11.
Study Question: What is the effect of stress ulcer prophylaxis (SUP) with proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), or sucralfate versus no prophylaxis on clinically important GI bleeding (CIB), pneumonia (PNA), Clostridium difficile infection, and death?
Study Description: This meta-analysis included randomized controlled trials assessing PPIs, H2RAs, sucralfate, and/or placebo and reporting on CIB, pneumonia, mortality, or C. difficile infection. Five random effects network meta-analyses (one for each outcome) were performed. The surface under the cumulative ranking curve (SUCRA) statistic was calculated as a parameter to rank treatment.
Results: Fifty-seven trials with 7293 patients were included. Although variable SUP regimens were administered in the trials, there were no concerns for intransivity or incoherence. The network meta-analysis provided moderate-quality evidence for reduction in CIB with PPI vs. H2RA (OR 0.38, 95% CI 0.20-0.73), PPI vs. placebo (OR 0.24, 95% CI 0.1-0.6), and PPI vs sucralfate (OR 0.3, 95% CI 0.13-0.69). The SUCRA statistic estimated PPIs ranked first in decreasing CIB, followed by H2RA, sucralfate, then placebo. The network meta-analysis showed an increased risk of PNA for H2RA vs. sucralfate (OR 1.3, 95% CI 1.08-1.58) and PPI vs. sucralfate (OR 1.65, 95% CI 1.2-2.27). C. difficile infection was only reported in one trial and therefore excluded from analysis. There was no difference between groups for all-cause mortality. PPI impact on CIB was estimated to have an absolute risk reduction of 1.6% relative to placebo, but with an absolute increase of 3.1% in the risk of PNA.
Conclusion(s): PPIs are most effective for stress ulcer prophylaxis; however, the relative risk of PNA and rates C. difficile infection should be considered when deciding on PPI use.
Perspective: Results from this meta-analysis are consistent with prior observational studies and meta-analyses suggesting that PPIs are more effective in decreasing occurrence of CIB but may increase risk of PNA. However, these statistics serve only as information to guide treatment rather than dictate treatment strategy. Two multicenter clinical trials are ongoing (SUP-ICU and REVISE) and should provide more information specifically regarding the use of PPIs for SUP in critically-ill patients.