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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，通过增强患者进行有效、无支持通气的能力，并促进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。

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 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.

针对小儿重症监护医学临床研究的常见数据元素的设计和理由。

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

Estimation of inspiratory effort using airway occlusion maneuvers in ventilated children: a secondary analysis of an ongoing randomized trial testing a lung and diaphragm protective ventilation strategy.

DOI：
10.1186/s13054-023-04754-6
发表时间：
2023-11-29
期刊：
Critical care (London, England)
影响因子：
0
作者：
通讯作者：

Direction and Magnitude of Change in Plateau From Peak Pressure During Inspiratory Holds Can Identify the Degree of Spontaneous Effort and Elastic Workload in Ventilated Patients.

DOI：
10.1097/ccm.0000000000004746
发表时间：
2021-03-01
期刊：
Critical care medicine
影响因子：
8.8
作者：
Kyogoku M;Shimatani T;Hotz JC;Newth CJL;Bellani G;Takeuchi M;Khemani RG
通讯作者：
Khemani RG

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