Understanding and Improving Dysphagia after Mechanical Ventilation

描述（由申请人提供）：每年有近100万美国人在重症监护室（ICU）经历需要机械通气的急性呼吸衰竭（ARF）。现有证据表明经口气管插管和吞咽障碍之间存在很强的相关性（即，吞咽困难）导致误吸，由诸如喉损伤、口咽肌无力、喉感觉降低和呼吸-吞咽失调等因素的组合介导。了解这些问题是预防和治疗该患者人群吞咽困难的关键。拔管后，吞咽困难影响高达83%的患者，使他们发生吸入性肺炎的风险增加6倍，死亡风险增加3倍。如果不进行干预，ICU中ARF期间会发生相当大的肌无力和身体损伤，但最近的试验表明，在机械通气期间减少镇静并结合早期身体康复可改善这些损伤。同样，气管插管期间吞咽困难的早期干预可能会改善患者的结局。本研究的总体目标是从ARF患者在ICU接受经口插管时开始评价ARF患者，以：1）研究舌无力和吞咽困难的其他病理生理学方面，2）在I期临床试验中评价一种在插管期间进行的新型多模式感觉运动干预，以减少拔管后的吞咽困难。该K23奖项还旨在为主要研究者提供独立进行以患者为导向的研究所需的背景：1）以临床试验为重点的临床研究方法的高级方面的培训;以及2）提供指导研究经验，以进行这项I期临床试验，重点是改善患者的结果。预计机械通气插管>96小时的患者将在插管后不久连续入组。喉功能、舌强度、吞咽病理生理学和呼吸-吞咽协调性将采用有效和可靠的标准化测量进行评价。在口服插管期间，治疗组的患者将接受一种新型的早期感觉运动干预，每天60分钟，旨在改善吞咽生理学和运动学，以减少误吸和吞咽困难。这些每日疗程将持续到拔管后48小时内进行的改良钡剂吞咽研究完成，此后将恢复标准临床护理。对照组患者将在治疗期间接受标准临床护理。 插管和整个住院期间。将对所有受试者进行出院随访，以确定拟定干预的病理生理学和临床影响。这项研究的知识将为新的治疗提供重要的可行性数据和初步的疗效数据。 为了解ARF患者插管后吞咽困难和误吸的生理机制提供了重要的基础。

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.