质子泵抑制剂预防重症患者应激性溃疡获益与风险的队列研究:附1 972例病例分析

摘要

目的 评价针对重症患者使用质子泵抑制剂(PPI)进行应激性溃疡预防(SUP)的获益与风险.方法 回顾分析2016年1月至2018年12月江苏省苏北人民医院重症加强治疗病房(ICU)收治的成人重症患者的临床资料.根据患者入ICU 48 h内是否接受PPI进行SUP分为两组,接受PPI治疗者为SUP组,未接受者为对照组.采用1∶1倾向性评分匹配模型对两组患者进行配对.记录患者的性别、年龄、基础疾病、ICU主要诊断、入ICU前药物使用情况、入ICU时序贯器官衰竭评分(SOFA)、应激性溃疡(SU)危险因素和PPI用药情况,同时观察患者ICU内消化道出血、医院获得性肺炎、难辨梭状芽孢杆菌感染的发生率及30 d病死率等结局指标.绘制Kaplan-Meier生存曲线,并采用log-rank检验进行生存分析.结果 共入选1 972例重症患者,其中SUP组788例,对照组1 184例;经倾向性评分匹配,最终两组各入选358例患者.倾向性评分匹配前,与对照组比较,SUP组患者年龄更大,基础疾病更多,ICU主要诊断中急性冠脉综合征(ACS)、急性脑血管病、慢性阻塞性肺疾病急性加重(AECOPD)及中毒比例更高,病情更重,SU危险因素更多,提示ICU医师对上述患者更倾向进行SUP.SUP组消化道出血发生率明显低于对照组〔1.8%(14/788)比3.7%(44/1 184),P＜0.05〕,医院获得性肺炎发生率及30 d病死率均明显高于对照组〔6.6%(52/788)比3.5%(42/1 184),17.9%(141/788)比13.1%(155/1 184),均P＜0.01〕;而SUP组与对照组难辨梭状芽孢杆菌感染发生率比较差异无统计学意义〔2.9%(23/788)比1.8%(21/1 184),P＞0.05〕.对两组患者的年龄、基础疾病、病情严重程度和SU危险因素等进行倾向性评分匹配后,SUP组与对照组消化道出血发生率及30 d病死率比较差异均无统计学意义〔2.2%(8/358)比3.4%(12/358),15.9%(57/358)比13.7%(49/358),均P＞0.05〕;而SUP组医院获得性肺炎发生率仍明显高于对照组〔6.7%(24/358)比3.1%(11/358),P＜0.05〕.Kaplan-Meier生存曲线分析显示,倾向性评分匹配前, SUP组30 d累积生存率明显低于对照组(log-rank检验:χ2＝9.224,P＝0.002);倾向性评分匹配后,两组30 d累积生存率比较差异无统计学意义(log-rank检验:χ2＝0.773,P＝0.379).结论 使用PPI进行SUP不能明显降低重症患者消化道出血发生率及病死率,甚至可增加院内获得性肺炎的发生风险.%Objective To investigate the benefits and risks of stress ulcer prevention (SUP) using proton pump inhibitors (PPI) for critical patients. Methods The clinical data of adult critically ill patients admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients who were treated with PPI for SUP within the first 48 hours after ICU admission were enrolled in the SUP group. Those who not received PPI were enrolled in the control group. A one-to-one propensity score matching (PSM) was performed to control for potential biases. The gender, age, underlying diseases, main diagnosis of ICU, drug use before ICU admission, sequential organ failure score (SOFA) at ICU admission, risk factors of stress ulcer (SU) and PPI usage were recorded. The end point was the incidence of gastrointestinal bleeding, hospital acquired pneumonia, Clostridium difficile infection and 30-day mortality. Kaplan-Meier survival curves were plotted, and survival analysis was performed using the log-rank test. Results 1 972 critical patients (788 in the SUP group and 1 184 in the control group) were enrolled, and each group enrolled 358 patients after PSM. Prior to PSM, compared with the control group, the SUP group had older patients, more underlying diseases, higher proportion of acute coronary syndrome (ACS), acute cerebrovascular disease, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and poisoning in main diagnosis of ICU, more serious illness, and more risk factors of SU, indicating that ICU physicians were more likely to prescribe SUP for these patients. The incidence of gastrointestinal bleeding in the SUP group was significantly lower than that in the control group [1.8% (14/788) vs. 3.7% (44/1 184), P < 0.05], while the incidence of hospital acquired pneumonia and 30-day mortality were significantly higher than those in the control group [6.6% (52/788) vs. 3.5% (42/1 184), 17.9% (141/788) vs. 13.1% (155/1 184), both P < 0.01]. There was no significant difference in the incidence of Clostridium difficile infection between the SUP group and the control group [2.9% (23/788) vs. 1.8% (21/1 184), P >0.05]. After the propensity scores for age, underlying diseases, severity of illness and SU risk factors were matched, there was no significant difference in the incidence of gastrointestinal bleeding or 30-day mortality between the SUP group and the control group [2.2% (8/358) vs. 3.4% (12/358), 15.9% (57/358) vs. 13.7% (49/358), both P > 0.05], but the incidence of hospital acquired pneumonia in the SUP group was still significantly higher than that in the control group [6.7% (24/358) vs. 3.1% (11/358), P < 0.05]. Kaplan-Meier survival curve analysis showed that the 30-day cumulative survival rate of the SUP group was significantly lower than that of the control group before the PSM (log-rank test: χ2 = 9.224, P = 0.002). There was no significant difference in the 30-day cumulative survival rate between the two groups after PSM (log-rank test: χ2 = 0.773, P = 0.379). Conclusion For critical patients, the use of PPI for SUP could not significantly reduce the incidence of gastrointestinal bleeding and mortality, but increase the risk of hospital acquired pneumonia.