Oral Care Intervention in Mechanically Ventilated Adults

描述（由申请人提供）：呼吸机相关性肺炎（VAP）是一种急性护理并发症，发病率和死亡率较高，住院时间和资源使用成本较高。插管后在重症成人口腔内应用洗必泰（CHX）可降低VAP的风险。在插管过程中，微生物可能被插管从污染的口咽拖到无菌肺，气管内插管（ET）为细菌从口咽直接进入下呼吸道提供了一条通道。然而，插管前口腔消毒的程序并不是常规的，而且关于插管前CHX在危重患者中的作用知之甚少。因此，本提案重点评价了在插管后CHX的已知获益基础上增加插管前CHX剂量以降低VAP风险（通过临床肺部感染评分（CPIS）测量）的获益。为了检查插管前CHX对早期ET定植的影响，我们还建议对参与研究的前24小时内拔管的受试者进行定量微生物检查。此外，我们打算探索选定的生物标志物（降钙素原，细胞因子）作为VAP发展的指标。本研究的主要目的是测试插管前口服CHX对各种机械通气危重成人VAP发展的影响。次要目的是1）测试插管前口服CHX对机械通气成人早期ET定植的影响，2）探索VAP发展和消退的潜在生物标志物。接受气管插管的成人（n = 325）将随机分配至插管前干预组（CHX葡萄糖酸盐0.12%溶液）或对照组。所有受试者将在插管后接受CHX。将使用以初始CPIS作为协变量的两组协方差分析（ANCOVA）模型比较CHX对VAP风险（CPIS评分）的影响。将使用ANCOVA模型以拔管时间作为协变量，类似地检验CHX对插管后前24小时内取出的粪便中对数转换cfu/ml的影响。将使用重复测量回归模型在100例受试者的子集中评价生物标志物，根据CPIS回归生物标志物。该项目将增加有关口腔健康，ET插管和VAP之间关系的知识，并解决了重要的临床结果。插管前口腔消毒可降低VAP的发生率及相关的发病率和死亡率。呼吸机相关性肺炎是机械通气重症患者的严重并发症。本项目中测试的干预措施（在插入气管导管前用氯己定擦拭口腔）可以降低呼吸机相关性肺炎的风险。

DESCRIPTION (provided by applicant): Ventilator-associated pneumonia (VAP) is an acute care complication with high morbidity and mortality, which is costly in length of stay and resources used. Post-intubation application of chlorhexidine (CHX) to the mouths of critically ill adults reduces risk of VAP. During intubation, organisms may be dragged by the tube from the contaminated oropharynx to the sterile lung, and the endotracheal tube (ET) provides a pathway for direct entry of bacteria from the oropharynx to the lower respiratory tract. However, procedures to decontaminate the mouth before intubation are not routine and little is known about the effects of pre-intubation CHX in critically ill patients. Thus, this proposal focuses on evaluating the benefit of adding a pre-intubation CHX dose to the known benefit of post-intubation CHX to reduce the risk of VAP as measured by Clinical Pulmonary Infection Score (CPIS). In order to examine the effect of pre-intubation CHX on early ET colonization, we also propose quantitative microbial examination of ETs of subjects who are extubated in the first 24 hours of study participation. Further, we intend to explore selected biomarkers (procalcitonin, cytokines) as indicators of development of VAP. The primary aim of this study is to test the effect of a pre-intubation oral application of CHX on the development of VAP in a variety of mechanically ventilated, critically ill adults. Secondary aims are 1) to test the effect of a pre-intubation oral application of CHX on early ET colonization in mechanically ventilated adults, and 2) to explore potential biomarkers of VAP development and resolution. Adults undergoing endotracheal intubation (n=325) will be randomized to pre-intubation intervention (CHX gluconate 0.12% solution) or control. All subjects will receive CHX post-intubation. Effect of CHX on risk of VAP (CPIS score) will be compared using a two-group analysis of covariance (ANCOVA) model with initial CPIS as a covariate. Effect of CHX on log-transformed cfu/ml from ETs removed in the first 24 hours after intubation will similarly be tested using an ANCOVA model with time to extubation as a covariate. Biomarkers will be evaluated in a subset of 100 subjects using a repeated measures regression model, regressing biomarkers against CPIS. The project will add to knowledge about the relationships among oral health, ET intubation and VAP, and addresses an important clinical outcome. Pre-intubation oral decontamination could reduce risk of VAP and its associated morbidity and mortality. PUBLIC HEALTH RELEVANCE Ventilator-associated pneumonia is a serious complication in mechanically ventilated critically ill patients. The intervention tested in this project (swabbing the mouth with chlorhexidine before the endotracheal tube is inserted) could reduce the risk of ventilator-associated pneumonia.