Oral Care Intervention in Mechanically Ventilated Adults

描述（由申请人提供）：呼吸机相关性肺炎（VAP）是一种发病率和死亡率高的急性护理并发症，住院时间和资源使用成本高。危重成人气管插管后应用氯己定（CHX）可降低VAP的风险。在插管过程中，微生物可能被气管管从污染的口咽部拖到无菌的肺部，气管内管（ET）为细菌从口咽部直接进入下呼吸道提供了途径。然而，插管前对口腔进行消毒的程序并不常规，而且对危重患者插管前CHX的效果知之甚少。因此，本提案的重点是评估在已知插管后CHX获益的基础上增加插管前CHX剂量以降低临床肺部感染评分（CPIS）测量的VAP风险的益处。为了研究插管前CHX对早期ET定植的影响，我们还建议在参与研究的前24小时拔管受试者的ET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气管插管前口服CHX对各种机械通气危重成人VAP发展的影响。次要目的是1)测试气管插管前口服CHX对机械通气成人早期ET定植的影响，2)探索VAP发展和解决的潜在生物标志物。接受气管插管的成人（n=325）将随机分为插管前干预组（葡萄糖酸CHX 0.12%溶液）或对照组。所有受试者插管后接受CHX。CHX对VAP风险（CPIS评分）的影响将采用以初始CPIS为协变量的两组协方差分析（ANCOVA）模型进行比较。CHX对插管后24小时内取出ETs的对数转换cfu/ml的影响同样将使用ANCOVA模型进行测试，拔管时间作为协变量。生物标志物将在100名受试者的子集中使用重复测量回归模型进行评估，将生物标志物与CPIS进行回归。该项目将增加对口腔健康、肺脏插管和VAP之间关系的认识，并解决一个重要的临床结果。插管前口腔消毒可降低VAP的风险及其相关的发病率和死亡率。呼吸机相关性肺炎是机械通气危重患者的一种严重并发症。本项目试验的干预措施（在插入气管插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.