OBJECTIVE To determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients. DESIGN Systematic review and network meta-analysis. DATA SOURCES Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS We included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates. RESULTS Seventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence). CONCLUSIONS For higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019126656.

中文翻译：

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危重患者胃肠道出血预防的功效和安全性：系统评价和网络荟萃分析。

目的确定重症患者中质子泵抑制剂（PPI），组胺2受体拮抗剂（H2RAs），硫糖铝或无胃肠道出血预防（或预防应激性溃疡）对患者重要结局的相对影响。设计系统评价和网络荟萃分析。数据来源截至2019年3月的Medline，PubMed，Embase，Cochrane对照试验中心登记册，试验登记册和灰色文献。选择研究和方法的合格标准我们纳入了随机对照试验，这些试验将预防胃肠道出血与PPI，H2RA或硫糖铝进行了比较与成年危重患者的另一种或安慰剂或无预防措施相比。两名审阅者独立筛选研究是否合格，提取数据并评估偏倚风险。一个平行的指导委员会（BMJ快速推荐）对系统评价进行了严格的监督，包括确定对患者重要的结果。我们进行了成对的随机效应和网络荟萃分析，并使用GRADE评估了每种结果的证据确定性。当偏倚研究的低风险和高风险之间的结果有所不同时，我们将前者用作最佳估计。结果72项试验（包括12 660例患者）被证明是合格的。对于最高出血风险（> 8％）或高出血风险（4-8％）的患者，与安慰剂相比或无预防措施，PPI和H2RA均可减少临床上重要的胃肠道出血（PPI的赔率为0.61（95％置信区间0.42）到0.89），最高风险减少3.3％，高风险患者减少2.3％，具有中等确定性； H2RA的比值比为0.46（0.27至0。79），高风险患者减少4.6％，高风险患者减少3.1％，具有中等确定性）。与没有预防措施相比，两者都可能增加肺炎的风险（PPI的比值1.39（0.98至2.10），高5.0％，确定性低； H2RA的比值比1.26（0.89至1.85），高3.4％，低确定性）。可能都不会影响死亡率（PPI 1.06（0.90至1.28），增加1.3％，中度确定性； H2RAs 0.96（0.79至1.19），减少0.9％，中度确定性）。否则，结果对死亡率，艰难梭菌感染，重症监护病房住院时间，住院时间或机械通气时间的影响没有任何依据（证据的确凿性）。结论对于高危重症患者，与未采取预防措施相比，PPI和H2RA可能会显着减少胃肠道出血。对于低危患者，减少出血可能并不重要。PPI和H2RA均可导致肺炎的严重增加。质量差异的证据表明，干预措施对死亡率或其他医院内发病率结果没有重要影响。系统审查注册PROSPERO CRD42019126656。