Patient Ventilator Asynchrony in Critically Ill Children

项目摘要 机械通气的儿童经常出现患者-呼吸机不同步(PVA)，尽管这是 在文献中没有完全描述，在床边很少被认识到。当通风的时候 患者有自发的努力，呼吸机试图与患者同步，但PVA代表 患者想要的和呼吸机提供的不匹配。PVA在通风系统中很常见 成人呼吸困难，呼吸时间长，感染风险增加，肺损伤，横隔膜 功能障碍和不良的神经认知影响。虽然PVA的类型很多，但它们的种类并不相同 有害的或普遍的。治疗策略应侧重于最有害的PVA形式。尽管我们仍然 不知道哪些PVA亚型是真正最有害的，双循环(DC)呼吸(第二次呼吸在哪里 在第一次呼吸完成之前交付)具有最强的生物学合理性，因为DC 引起肺应激、劳损、呼吸机引起的肺损伤和横隔膜的偏心收缩。 PVA在儿童中的研究不足，尽管它可能更常见，而且很大程度上没有被认识到 即使是训练有素的临床医生。此外，现有的儿科研究未能确定两者之间的明确关系 PVA和更差的临床结果之间的关系，尽管这些研究并没有关注最高风险 患者(如急性呼吸窘迫综合征(ARDS)患者)使用了不同的定义 PVA及其亚型，并已不能充分评价PVA之间的关系 亚型和结果。这项提议将为儿童PVA的治疗策略奠定基础 并将填补关键的知识和实施差距，包括：(1)协调PVA的测量方式和 定义，(2)确定最有害的PVA亚型和处于风险中的患者，以及(3)使用创新和 精准的床边工具，提高对PVA的认识。我们将利用专业知识和初步数据 来自三个顶尖的儿科研究小组，他们拥有使用精确方法捕捉 患者的神经呼吸努力，这是正确识别PVA亚型的关键。这项提案将包括 使用Precision多中心前瞻性收集200名接受呼吸机治疗的儿童的呼吸机波形 捕获神经呼吸努力的技术，以及对现有波形的详细二次分析 以及350多名儿童的临床数据。我们将使用因果推理和调解的方法来评估 PVA亚型与临床和机制预后之间的关系 随机对照试验(REDVent，R01HL124666)，其中PVA比率和亚型可能在 干预组和对照组。这项试验正在开出一种机械通风策略，以促进更多 自主呼吸实现肺和隔膜保护性换气，相较于平时护理。

Project Summary Mechanically ventilated children often have patient-ventilator asynchrony (PVA) although this is incompletely characterized in the literature and infrequently recognized at the bedside. When a ventilated patient has spontaneous effort, the ventilator attempts to synchronize with the patient, but PVA represents a mismatch between what the patient wants and what the ventilator delivers. PVA is common in ventilated adults and is associated with longer duration of ventilation, increased risk of infection, lung injury, diaphragm dysfunction, and adverse neurocognitive effects. While there are many types of PVA, they are not equally harmful or prevalent. Therapeutic strategies should focus on the most harmful forms of PVA. Although we still don’t know which PVA subtypes are truly most harmful, Double Cycled (DC) breaths (where a second breath is delivered before the first breath is complete) have the strongest biological plausibility for harm, because DC induces lung stress, strain, ventilator induced lung injury and eccentric contraction of the diaphragm. PVA is understudied in children, even though it may be more common and goes largely unrecognized even by highly trained clinicians. Moreover, existing pediatric studies have failed to identify a clear relationship between PVA and worse clinical outcomes, although these studies have not focused on the highest risk patients (such as those with Acute Respiratory Distress Syndrome (ARDS)), have used different definitions for PVA and its subtypes, and have been inadequately powered to evaluate the relationship between PVA subtypes and outcome. This proposal will set the stage for therapeutic strategies to manage PVA in children and will fill crucial knowledge and implementation gaps including: (1) harmonizing how PVA is measured and defined, (2) identifying the most harmful PVA subtypes and the patients at risk, and (3) using innovative and accurate bedside tools to improve the recognition of PVA. We will leverage the expertise and preliminary data from three premier pediatric research groups who have the expertise to use precise methods to capture the patient’s neural respiratory effort, which is crucial to correctly identify PVA subtypes. This proposal will include prospective, multi-center collection of ventilator waveforms from 200 ventilated children using precise techniques to capture neural respiratory effort, in addition to detailed secondary analysis of existing waveforms and clinical data from over 350 children. We will use causal inference and mediation approaches to evaluate the relationship between PVA subtypes and clinical and mechanistic outcomes by leveraging data from a randomized controlled trial (REDVent, R01HL124666) where PVA rates and subtypes likely differ between intervention and control groups. This trial is prescribing a mechanical ventilation strategy promoting more spontaneous breathing to achieve lung and diaphragm protective ventilation, compared to usual care.