Identifying and preventing ventilator induced diaphragm weakness in children

项目摘要 近一半的机械通气(MV)危重成人会出现呼吸机诱导的呼吸肌 虚弱(尤其是横隔膜)损害了成功的机械通气脱机，常常导致重新脱机。 插管，并与ICU后较高的死亡率有关。我们最近展示了呼吸肌 虚弱与危重儿童拔管失败有关，但我们仍然缺乏关于 这种疲软的机制和时机，它对呼吸机脱机的重要性，以及它的潜力 通过促进更多生理水平的患者在机械通气期间的呼吸努力来预防。 隔肌无力在暴露于高水平受控通风的患者中最为常见。在儿童中， 我们已经证明，常规护理呼吸机管理通常与患者最低限度的 呼吸。为了增强患者的努力，我们开发了一种新的基于计算机的方法(实时努力驱动 呼吸机管理(REDVENT))，提供系统建议以减少受控通风 在MV急性期期间，并使用实时测量来调整支持的呼吸机压力 在呼吸机撤机阶段，患者的呼吸努力保持在正常范围内。通过阶段I 临床试验，我们证明使用REDVENT的患者在MV中花费的天数比历史 控件，床边提供者可以很容易地实现REDvent.我们的中心假设是REDVENT使用 将减少呼吸机引起的呼吸肌无力，通过增强呼吸机的 通过促进机械通气脱机，提高患者的有效无支持呼吸机的能力。 这项申请提出了一项第二阶段对照临床试验，将获得全面的、系列的评估 呼吸肌力量和结构的变化以了解呼吸机诱导呼吸的演变 危重儿童的肌肉无力，并测试REDVENT是否可以保持呼吸肌力量 并减少在MV上的时间。提出了三个既完整又独立的具体目标：SA 1将确定 雷公藤对急性期和脱机两种呼吸机的临床影响 与常规护理相比，管理导致更短的MV脱机时间；SA 2将使用复杂的、 多模式方法，以获得呼吸肌容量、作用力、负荷和 架构，以量化呼吸肌无力对儿童断奶结局的重要性，以及 确定这一弱点何时发展；SA 3寻求确定患者努力的独立效果 呼吸对呼吸肌无力的发展，在控制了已知或怀疑的危险之后 呼吸肌无力的因素。完成后，这项研究将提供关于 儿童MV中呼吸肌无力的发病机制和时机，这种无力是否可以 通过使用REDVENT在MV期间促进更正常的患者努力来缓解；形成以下基础 一项规模更大的第三阶段多中心研究，为关键的临床结果提供动力，如28天无呼吸机日。

Project Summary Nearly half of mechanically ventilated (MV), critically ill adults develop ventilator-induced respiratory muscle weakness (particularly of the diaphragm), which impairs successful weaning from MV, often leads to re- intubation, and is associated with higher post-ICU mortality. We have recently shown that respiratory muscle weakness is associated with extubation failure in critically ill children, but we still lack crucial information on the mechanisms and timing of this weakness, its importance for ventilator weaning, and its potential prevention through promoting more physiologic levels of patient effort of breathing during MV. Diaphragm weakness is most common in patients exposed to high levels of controlled ventilation. In children, we have shown that usual care ventilator management is frequently associated with minimal patient effort of breathing. To enhance patient effort, we developed a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)), which offers systematic recommendations to reduce controlled ventilation during the acute phase of MV, and uses real-time measures to adjust supported ventilator pressures such that patient effort of breathing remains in a normal range during the ventilator weaning phase. Through a Phase I clinical trial, we demonstrated that patients managed with REDvent spent fewer days on MV than historical controls, and bedside providers could easily implement REDvent. Our central hypothesis is that REDvent use will reduce ventilator-induced respiratory muscle weakness, leading to shorter time on MV by enhancing the patient’s capacity for effective, unsupported ventilation and by facilitating MV weaning. This application proposes a Phase II controlled clinical trial that will obtain comprehensive, serial assessments of respiratory muscle strength and architecture to understand the evolution of ventilator-induced respiratory muscle weakness in critically ill children, and test whether REDvent can preserve respiratory muscle strength and reduce time on MV. Three integrated yet independent Specific Aims are proposed: SA 1 will determine the clinical impact of REDvent by examining whether REDvent use for either acute or weaning phase ventilator management results in shorter MV weaning times compared to usual care; SA 2 will use a sophisticated, multi-modal approach to obtain a comprehensive view of respiratory muscle capacity, effort, load, and architecture to quantify the importance of respiratory muscle weakness on weaning outcomes in children, and identify when this weakness develops; SA 3 seeks to determine the independent effect of patient effort of breathing on the development of respiratory muscle weakness, after controlling for known or suspected risk factors for respiratory muscle weakness. Upon completion, this study will provide important information on the pathogenesis and timing of respiratory muscle weakness during MV in children, whether this weakness can be mitigated by promoting more normal patient effort during MV via the use of REDvent; forming the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day Ventilator Free Days.