Understanding and Improving Dysphagia after Mechanical Ventilation

描述(由申请人提供)：每年有近100万美国人经历急性呼吸衰竭(ARF)，需要在重症监护病房(ICU)进行机械通风。现有证据表明，经口气管插管与吞咽障碍(即吞咽困难)之间存在很强的相关性，导致吸入的因素包括喉部损伤、口咽肌无力、喉部感觉减退和呼吸-吞咽协调失调。了解这些问题对于预防和治疗这类患者的吞咽困难至关重要。拔管后，吞咽困难影响高达83%的患者，使他们患吸入性肺炎的风险比中风患者增加6倍，死亡风险增加3倍。在没有干预的情况下，在ICU的ARF期间会出现相当大的肌肉无力和身体损害，但最近的试验表明，在机械通气期间减少镇静和早期物理康复可以改善这些损害。同样，对气管插管期间的吞咽困难进行早期干预可能会改善患者的预后。这项研究的总体目标是从ARF患者在ICU接受口腔插管的时间起对他们进行评估，以：1)调查吞咽困难的舌无力和其他病理生理学方面；2)在I期临床试验中，评估一种在插管期间进行的新颖的多模式感觉运动干预，以减少拔管后的吞咽困难。这一K23奖项还旨在通过以下方式为首席研究员提供必要的背景知识，以便在以患者为中心的研究中变得独立：1)以临床试验为重点的临床研究方法高级方面的培训；2)为进行这一专注于改善患者结果的I期临床试验提供有指导的研究经验。预计将接受机械通气96小时的患者将在插管后不久连续入选。喉功能、舌力、吞咽病理生理学和呼吸-吞咽协调性将通过有效和可靠的标准化测量进行评估。在口服插管期间，治疗组的患者将接受新颖的早期感觉运动干预，每天60分钟，目标是改善吞咽生理和运动学，以减少吸入和吞咽困难。这些每日会议将持续到拔管后48小时内完成改良的吞钡研究，此后将恢复标准的临床护理。对照组患者将在治疗期间接受标准的临床护理 插管和在他们住院期间。所有受试者都将被跟踪到出院，以确定拟议干预措施的病理生理和临床影响。这项研究的知识将为该小说提供重要的可行性数据和初步疗效数据 为了解ARF患者插管后吞咽困难和误吸的生理机制奠定了重要的基础。

DESCRIPTION (provided by applicant): Annually, nearly 1 million Americans experience acute respiratory failure (ARF) requiring mechanical ventilation in intensive care units (ICU). Existing evidence demonstrates a strong association between oral endotracheal intubation and swallowing impairment (i.e., dysphagia) leading to aspiration, mediated by a combination of factors such as laryngeal injury, oropharyngeal muscle weakness, reduced laryngeal sensation, and breathing-swallowing dyscoordination. Understanding these issues is central to preventing and treating dysphagia in this patient population. After extubation, dysphagia affects up to 83% of patients and predisposes them to a 6-fold increased risk of aspiration pneumonia and a 3-fold increased risk of death compared with stroke patients. Without intervention, considerable muscle weakness and physical impairment occurs during ARF in the ICU, but recent trials demonstrate that less sedation combined with early physical rehabilitation during mechanical ventilation improve these impairments. Similarly, an early intervention for dysphagia during endotracheal intubation may improve patient outcomes. The overall goals of this study are to evaluate ARF patients from the time they are orally intubated in the ICU to: 1) investigate tongue weakness and other pathophysiological aspects of dysphagia, and 2) evaluate, in a Phase I clinical trial, a novel, multimodal, sensorimotor intervention conducted during intubation to reduce dysphagia after extubation. This K23 award also aims to provide the Principal Investigator with the background necessary to become independent in patient-oriented research by: 1) training in advanced aspects of clinical research methods with a focus on clinical trials; and 2) providing a mentored research experience for conducting this Phase I clinical trial focused on improving patient outcomes. Patients who are expected to be intubated with mechanical ventilation for >96 hours will be consecutively enrolled shortly after intubation. Laryngeal function, tongue strength, swallowing pathophysiology, and breathing-swallowing coordination will be evaluated with valid and reliable standardized measures. While orally intubated, patients in the treatment group will receive a novel, early, sensorimotor intervention for 60-minutes daily, targeting improved swallowing physiology and kinematics to reduce aspiration and dysphagia. These daily sessions will continue until the completion of a modified barium swallow study conducted within 48 hours after extubation, and thereafter standard clinical care will resume. Patients in the control group will receive standard clinical care during intubation and throughout their hospital stay. All subjects will be followed to hospital discharge to determine the pathophysiological and clinical impact of the proposed intervention. Knowledge from this study will provide important feasibility data and preliminary efficacy data for the novel intervention and provide a critical foundation for understanding the physiological mechanisms of dysphagia and aspiration after intubation in ARF patients.