近日，首都医科大学北京朝阳医院刘丽宏教授及其团队对危重病人胃肠出血预防的有效性和安全性进行了系统回顾和荟萃分析。这一研究成果于2020年1月6日发表在国际顶尖学术期刊《英国医学杂志》上。

为了评估重症患者使用质子泵抑制剂（PPIs），组胺-2受体拮抗剂（H2RAs），硫糖铝或无胃肠道出血预防（或应激性溃疡预防）对重要结局的影响，研究组对截至2019年3月Medline、PubMed、Embase等大型数据库中相应的随机对照试验进行了系统回顾和荟萃分析。由两位评审员独立筛选、提取数据、评估偏倚风险。

研究组共确定了72项试验，包括12660名患者。对于极高出血风险（>8%）和高出血风险（4-8%）的患者，PPIs和H2RAs与安慰剂或不采取预防措施相比，临床上均可显著减少消化道出血。其中PPIs分别减少了3.3%的极高出血风险和2.3%的高出血风险，而H2RAs则分别减少了4.6%和3.1%。

但PPIs和H2RAs与不采取预防措施相比，均增加了肺炎的风险。但两者可能均对死亡率无影响。由于证据不足，研究结果无法确定PPIs和H2RAs对死亡率、艰难梭菌感染、重症监护时间、住院时间或机械通气时间的影响。

总之，对于高危的危重患者，PPIs和H2RAs与不采取预防措施相比，可显著减少胃肠道出血，但对于低出血风险的患者，减少出血并不显著。PPIs和H2RAs可导致肺炎患病率显著增加。可变质量证据表明，干预措施对死亡率或院内其他发病率的结果并无显著影响。

附：英文原文

Title: Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: systematic review and network meta-analysis

Author: Ying Wang, Zhikang Ye, Long Ge, Reed A C Siemieniuk, Xin Wang, Yingkai Wang, Liangying Hou, Zhuo Ma, Thomas Agoritsas, Per Olav Vandvik, Anders Perner, Morten H Mller, Gordon H Guyatt, Lihong Liu

Issue&Volume: 2020/01/06

Abstract: 

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.

DOI: 10.1136/bmj.l6744

Source: https://www.bmj.com/content/368/bmj.l6744