Identifying and preventing ventilator induced diaphragm weakness in children

识别和预防儿童呼吸机引起的膈肌无力

基本信息

批准号：
10178072
负责人：
Robinder Khemani
金额：
$ 43.29万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10178072
关键词：
Acute Adult Age Algorithms Architecture Atrophic Breathing Child Childhood Clinical Computers Confounding Factors (Epidemiology)Controlled Clinical Trials Critical Illness Critically ill children Data Development Diagnosis Disease Esophagus Evolution Exposure to Failure Histology Impairment Induction of neuromuscular blockade Intubation Knowledge Literature Lung Lung diseases Manometry Measures Mechanical ventilation Mission Multicenter Studies Muscle Weakness National Heart, Lung, and Blood Institute Normal Range Outcome Pathogenesis Patients Phase Phase I Clinical Trials Phase II Clinical Trials Physiological Prevention Protocols documentation Provider Randomized Recommendation Resistance Resolution Respiratory Diaphragm Respiratory Mechanics Respiratory Muscles Risk Factors Sedation procedure Testing Time Ultrasonography Ventilator Ventilator Weaning Weaning acute care airway obstruction base esophagus pressure experience infancy mortality multimodality muscle strength neuromuscular novel phase I trial preservation pressure prevent primary outcome respiratory secondary outcome treatment as usual ventilation

项目摘要

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.

项目摘要近一半的机械通风（MV），危重的成年人会发展出通风器引起的呼吸肌弱点（部分是膜片），这会损害MV成功断奶，通常会导致重新插管，与较高的ICU死亡率有关。我们最近表明呼吸肌弱点与重症儿童的拔管失败有关，但我们仍然缺乏关键信息这种弱点的机制和时机，对呼吸机断奶的重要性及其潜力通过促进MV期间呼吸的患者呼吸努力的更多生理水平通过预防。在暴露于高水平的受控通风的患者中，隔膜无力最常见。在儿童中我们已经表明，通常的护理呼吸机管理经常与患者的努力相关呼吸。为了加强患者的努力，我们开发了一种新型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的急性阶段，并使用实时措施来调整支持的通风压力，以便在通风阶段，患者呼吸的努力仍处于正常范围内。通过第一阶段临床试验，我们证明了治理红色风险的患者在MV上花费的时间比历史少。控件和床头提供商可以轻松实施红色。我们的中心假设是红色的使用将减少通风tor诱导的呼吸道肌肉无力，从而通过增强MV的时间较短患者的有效，无支撑通风的能力并通过支持MV断奶。该申请提出了II期对照临床试验，该试验将获得全面的序列评估呼吸道肌肉力量和结构，以了解通气引起的呼吸道的演变重症儿童的肌肉无力，并测试红色是否可以保持呼吸肌肉力量并减少MV的时间。提出了三个集成但独立的特定目标：SA 1将确定通过检查红色通风机是否用于急性或断奶相呼吸机的临床影响与通常的护理相比，管理层导致MV断奶时间较短； SA 2将使用精致的多模式的方法以获取呼吸肌能力，努力，负载的全面视图和量化呼吸道肌肉无力对儿童断奶结果的重要性，以及确定何时发展； SA 3试图确定患者努力的独立效果控制已知或怀疑的风险后，呼吸呼吸道肌肉无力的发展呼吸道肌肉无力的因素。完成后，本研究将提供有关的重要信息儿童MV期间呼吸道肌肉无力的发病机理和时间，这种弱点是否可以通过使用红色vent在MV期间促进更正常的患者努力来缓解；形成基础一项较大的III期多中心研究，可用于关键的临床结果，例如28天的无呼吸机。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Authors Reply.

DOI：
10.1038/ki.2015.131
发表时间：
2015-07
期刊：
Kidney international
影响因子：
19.6
作者：
Dong Z
通讯作者：
Dong Z

The role of computer-based clinical decision support systems to deliver protective mechanical ventilation.

DOI：
10.1097/mcc.0000000000000688
发表时间：
2020-02
期刊：
Current opinion in critical care
影响因子：
3.3
作者：
Khemani RG;Hotz JC;Sward KA;Newth CJL
通讯作者：
Newth CJL

Design and Rationale for Common Data Elements for Clinical Research in Pediatric Critical Care Medicine.

DOI：
10.1097/pcc.0000000000002455
发表时间：
2020-11
期刊：
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
影响因子：
0
作者：
Ward SL;Flori HR;Bennett TD;Sapru A;Mourani PM;Thomas NJ;Khemani RG
通讯作者：
Khemani RG

Challenges Remain to Assess Post-ICU Morbidity and Identify Attributable Risk in Children With Pediatric Acute Respiratory Distress Syndrome.

DOI：
10.1097/pcc.0000000000002980
发表时间：
2022-07-01
期刊：
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
影响因子：
0
作者：
通讯作者：

Frequency and Risk Factors for Reverse Triggering in Pediatric Acute Respiratory Distress Syndrome during Synchronized Intermittent Mandatory Ventilation.

同步间歇指令通气期间小儿急性呼吸窘迫综合征反向触发的频率和危险因素。

DOI：
10.1513/annalsats.202008-1072oc
发表时间：
2021
期刊：
Annals of the American Thoracic Society
影响因子：
8.3
作者：
Shimatani,Tatsutoshi;Yoon,Benjamin;Kyogoku,Miyako;Kyo,Michihito;Ohshimo,Shinichiro;Newth,ChristopherJL;Hotz,JustinC;Shime,Nobuaki;Khemani,RobinderG
通讯作者：
Khemani,RobinderG