Identifying and preventing ventilator induced diaphragm weakness in children

项目摘要 近一半的机械通气（MV）重症成人发生呼吸机诱导的呼吸肌 虚弱（特别是横膈膜），这会影响MV的成功脱机，通常会导致再 插管，并与较高的ICU后死亡率。我们最近发现呼吸肌 虚弱与危重患儿拔管失败有关，但我们仍然缺乏关键信息， 这种弱点的机制和时间，其对呼吸机脱机的重要性，以及其潜在的 通过在MV期间促进患者呼吸努力的更多生理水平来预防。 膈肌无力在暴露于高水平受控通气的患者中最常见。在儿童中， 我们已经表明，通常的护理呼吸机管理通常与最小的患者努力相关， 呼吸了为了提高病人的努力，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）），提供系统性建议，以减少控制通气 在MV的急性期期间，并使用实时措施来调整支持的呼吸机压力， 患者的呼吸努力在呼吸机脱机阶段期间保持在正常范围内。通过第一阶段 在一项临床试验中，我们证明了接受REDvent治疗的患者接受MV治疗的天数少于历史记录， 控制和床边提供者可以很容易地实现REDvent。我们的中心假设是， 将减少呼吸机引起的呼吸肌无力，通过增强 患者有效、无支撑通气的能力以及促进MV撤机。 该申请提出了一项II期对照临床试验，将获得全面的系列评估 呼吸肌强度和结构的变化，以了解呼吸机诱导的呼吸功能的演变。 重症儿童的肌无力，并测试REDvent是否可以保持呼吸肌力量 减少MV的时间。提出了三个综合但独立的具体目标：SA 1将确定 通过检查REDvent是否用于急性期或脱机期呼吸机， 与常规护理相比， 多模式方法，以获得呼吸肌容量，努力，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 确定这种弱点何时出现; SA 3试图确定患者努力的独立影响， 在控制已知或疑似风险后，呼吸肌无力的发展 呼吸肌无力的因素。完成后，这项研究将提供重要信息， 儿童MV期间呼吸肌无力的发病机制和时间，这种无力是否可以 通过使用REDvent在MV期间促进更多的正常患者努力来缓解;为 一项更大规模的III期多中心研究，针对关键临床结局（如28天无呼吸机日）提供动力。

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.