Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, CO.
PGY2 Emergency Medicine Pharmacy Resident, Froedtert and the Medical College of Wisconsin, Wauwatosa, WI.
J Clin Gastroenterol. 2023 Jul 1;57(6):586-594. doi: 10.1097/MCG.0000000000001723.
The aim was to systematically evaluate risks and benefits of proton pump inhibitor (PPI) use for stress ulcer prophylaxis in the critically ill patient.
Whether PPIs increase mortality in the critically ill patient remains controversial.
Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies with trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis.
A total of 31 studies in 78,009 critically ill adults receiving PPIs versus any comparator were included. PPI use was associated with an increased mortality risk in all studies [19.6% PPI vs. 17.5% comparator; RR: 1.10; 95% confidence interval (CI): 1.02-1.20; P =0.01], in the subgroup of RCTs (19.4% vs. 18.7%; RR: 1.05; 95% CI: 1.0-1.09, P =0.04), but not cohort studies (19.9% vs. 16.7%; RR: 1.12; 95% CI: 0.98-1.28, P =0.09). Results were maintained with a Bayesian sensitivity analysis (RR: 1.13; 95% credible interval: 1.035-1.227) and a fragility index analysis, but not sequential analysis ( P =0.16). RCTs with a higher baseline severity of illness revealed the greatest mortality risk with PPI use (32.1% PPI vs. 29.4% comparator; RR: 1.09; 95% CI: 1.04-1.14; P <0.001). PPI use reduced clinically important bleeding in RCTs (1.4% PPI vs. 2.1% comparator; RR: 0.67; 95% CI: 0.5-0.9; P =0.009) but increased bleeding in cohort studies (2.7% PPI vs. 1.2% comparator; RR: 2.05; 95% CI: 1.2-3.52; P =0.009). PPI use was not associated with a lower incidence of clinically important bleeding when compared with histamine-2 receptor antagonists (1.3% vs. 1.9%; RR: 0.59; 95% CI: 0.28-1.25, P =0.09).
This meta-analysis demonstrated an association between PPI use and an increased risk of mortality.
系统评估质子泵抑制剂（PPI）用于预防危重病患者应激性溃疡的风险和益处。
PPI 是否会增加危重病患者的死亡率仍存在争议。
对随机对照试验（RCT）和队列研究进行系统评价和荟萃分析，并进行试验序贯分析、贝叶斯敏感性分析和脆弱性指数分析。
共纳入 31 项研究，涉及 78009 例接受 PPI 与任何对照比较的危重病成年人。在所有研究中，PPI 组的死亡率高于对照组[19.6%PPI 与 17.5%对照组；RR：1.10；95%置信区间（CI）：1.02-1.20；P=0.01]，在 RCT 亚组中（19.4%与 18.7%；RR：1.05；95%CI：1.0-1.09，P=0.04），但在队列研究中没有（19.9%与 16.7%；RR：1.12；95%CI：0.98-1.28，P=0.09）。贝叶斯敏感性分析（RR：1.13；95%可信区间：1.035-1.227）和脆弱性指数分析结果保持一致，但试验序贯分析结果不一致（P=0.16）。具有更高基线疾病严重程度的 RCT 显示，PPI 治疗的死亡率风险最高（32.1%PPI 与 29.4%对照组；RR：1.09；95%CI：1.04-1.14；P<0.001）。PPI 在 RCT 中降低了临床重要性出血的发生率（1.4%PPI 与 2.1%对照组；RR：0.67；95%CI：0.5-0.9；P=0.009），但在队列研究中增加了出血的发生率（2.7%PPI 与 1.2%对照组；RR：2.05；95%CI：1.2-3.52；P=0.009）。与组胺 2 受体拮抗剂相比，PPI 治疗与较低的临床重要性出血发生率无关（1.3%与 1.9%；RR：0.59；95%CI：0.28-1.25，P=0.09）。
本荟萃分析表明，PPI 使用与死亡率增加之间存在关联。
