University of Colorado Skaggs School of Pharmacy, Aurora, Colorado.
Pharmacotherapy. 2019 Mar;39(3):408-420. doi: 10.1002/phar.2172. Epub 2018 Sep 6.
Because recent studies have challenged the efficacy of stress ulcer prophylaxis (SUP) in the critically ill patient, our objective was to evaluate the efficacy of SUP with proton pump inhibitors (PPIs) or histamine -receptor antagonists (H RAs) against placebo, control, no therapy, or enteral nutrition alone in critically ill adults.
Meta-analysis with trial sequential analysis (TSA) of 34 randomized controlled trials.
A total of 3220 critically ill adults who received PPIs or H RAs versus placebo, control, no therapy, or enteral nutrition.
A systematic review was performed using a random effects meta-analysis with TSA according to a predefined protocol. Randomized controlled trials comparing PPIs or H RAs with either placebo, control, no therapy, or enteral nutrition alone were identified through a comprehensive search of the literature. Two blinded reviewers independently assessed studies for inclusion, risk of bias, and extracted data using Cochrane Collaborative methodology. The predefined primary outcomes were clinically important, overt, and any (clinically important plus overt) gastrointestinal bleeding. Secondary outcomes included pneumonia, Clostridium difficile-associated diarrhea (CDAD), and mortality. Subgroup analyses were conducted for the primary outcome by PPI or H RA use, intensive care unit (ICU) subtype, studies published after early goal-directed therapy (EGDT), the presence of risk factors for stress ulceration, and enteral nutrition use. Of the 34 trials included, 33 were judged as high risk of bias and 1 was judged as low risk. Use of SUP significantly reduced clinically important bleeding (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.37-0.76, p<0.001; I = 0%), overt bleeding (RR 0.55, 95% CI 0.39-0.76, p=0.0003; I = 53%), and any bleeding (RR 0.54, 95% CI 0.41-0.71, p<0.00001; I = 58%). TSA confirmed these findings. No significant differences in pneumonia, CDAD, or mortality were noted. Subgroup analyses revealed significant reductions in clinically important bleeding with SUP in neurosurgical patients (RR 0.37, p<0.05) but not in surgery/trauma or medical ICU patients with risk factors. SUP provided no benefit in studies published after EGDT. SUP significantly reduced clinically important bleeding regardless of the use of enteral nutrition (p<0.05).
This meta-analysis demonstrated that SUP use was associated with significant reductions in bleeding but not mortality. SUP should not be abandoned until large randomized trials demonstrate the futility of this intervention.
由于最近的研究对重症患者应激性溃疡预防（SUP）的疗效提出了质疑，我们的目的是评估质子泵抑制剂（PPIs）或组胺-受体拮抗剂（H RAs）与安慰剂、对照、无治疗或单独肠内营养相比，在重症成人中的疗效。
对 34 项随机对照试验进行荟萃分析，结合试验序贯分析（TSA）。
共纳入 3220 例接受 PPI 或 HRA 治疗的重症成人，与安慰剂、对照、无治疗或单独肠内营养相比。
采用随机效应荟萃分析，根据预先制定的方案进行 TSA。通过全面的文献搜索，确定了比较 PPI 或 HRA 与安慰剂、对照、无治疗或单独肠内营养的随机对照试验。两名盲法审查员独立评估研究的纳入、偏倚风险，并使用 Cochrane 协作方法提取数据。预设的主要结局是临床重要的、显性的和任何（临床重要加显性）胃肠道出血。次要结局包括肺炎、艰难梭菌相关性腹泻（CDAD）和死亡率。通过使用 PPI 或 HRA、重症监护病房（ICU）亚型、发表于早期目标导向治疗（EGDT）后的研究、应激性溃疡发生的危险因素和肠内营养使用情况，对主要结局进行了亚组分析。34 项试验中，33 项被评为高偏倚风险，1 项被评为低偏倚风险。使用 SUP 可显著减少临床重要性出血（风险比 [RR] 0.53，95%置信区间 [CI] 0.37-0.76，p<0.001；I ² = 0%）、显性出血（RR 0.55，95% CI 0.39-0.76，p=0.0003；I ² = 53%）和任何出血（RR 0.54，95% CI 0.41-0.71，p<0.00001；I ² = 58%）。TSA 证实了这些发现。在肺炎、CDAD 或死亡率方面无显著差异。亚组分析显示，在神经外科患者中，SUP 可显著减少临床重要性出血（RR 0.37，p<0.05），但在有危险因素的手术/创伤或内科 ICU 患者中无差异。在发表于 EGDT 后的研究中，SUP 无获益。无论是否使用肠内营养，SUP 均可显著减少临床重要性出血（p<0.05）。
本荟萃分析表明，SUP 可显著降低出血风险，但不能降低死亡率。在大规模随机试验证明该干预无效之前，不应放弃 SUP。
