Nutrition and Exercise in Critical Illness (The NEXIS Trial): A Randomized Trial of Combined Cycle Ergometry and Amino Acids in the ICU

项目概要 每年有超过 750,000 名美国人需要机械通气和重症监护病房 (ICU) 幸存者出院后会遭受严重损伤，包括持续性肌肉损伤 虚弱、身体机能受损、生活质量下降以及长期生存率下降。 迫切需要新的策略来改善 ICU 患者的身体恢复。跨越 北美，研究多次表明 ICU 患者营养不良且行动不便 在危重疾病期间长期卧床休息。然而，现有证据表明 在患者入住 ICU 期间尽早实施氨基酸补充和运动可能会 改善结果。其他数据表明，结合起来，这两种干预措施可能 协同作用以改善肌肉质量和身体机能。组合氨基酸 尚未对危重患者进行补充和运动干预的研究。因此，我们 提出一项静脉注射氨基酸创新组合的 II 期随机对照试验 危重患者的补充和早期卧床自行车测力锻炼与常规护理的比较。 我们假设这种新颖的联合干预措施将增强患者当时的身体机能 出院；减少肌肉消耗；改善氨基酸代谢和蛋白质合成； 改善与健康相关的生活质量、身体机能和医疗资源利用率。 我们的初步数据显示了氨基酸和运动干预的可行性和安全性。的 可以对 ICU 患者进行联合干预，即使患者处于镇静状态或昏迷状态，因为在床上 自行车测力运动装置（已上市并获得 FDA 批准用于此目的） 根据患者状态自动在被动或主动模式之间调整。而且，这 在危重疾病期间进行运动干预不会造成心肺风险。我们的 研究团队体现了 ICU 护理的跨学科性质，在所有领域都拥有世界一流的专业知识 这笔补助金的一部分，包括重症监护营养；锻炼/康复； ICU护理、临床护理和 协调；氨基酸代谢测定；和身体成分分析。我们的团队有 在协调多站点 ICU 随机对照试验方面拥有无与伦比的经验，并且之前已取得成功 合作。因此，该团队完全有能力开展这项新颖的随机对照试验，旨在改变 ICU 中的营养和运动范例，并改善越来越多的人的身体状况 ICU 幸存者。

PROJECT SUMMARY More than 750,000 Americans require mechanical ventilation annually, and intensive care unit (ICU) survivors experience substantial impairments after hospital discharge, including persistent muscle weakness, impaired physical functioning, reduced quality of life, and decreased long-term survival. There is an urgent need for new strategies to improve the physical recovery of ICU patients. Across North America, studies repeatedly demonstrate that ICU patients are undernourished and immobilized via prolonged bed rest throughout their critical illness. However, available evidence suggests that both amino acid supplementation and exercise, implemented early during patients' ICU stay, may improve outcomes. Additional data demonstrate that, when combined, these two interventions may behave synergistically to improve muscle mass and physical functioning. A combined amino acid supplementation and exercise intervention has not been investigated in critically ill patients. Thus, we propose a Phase II randomized controlled trial of an innovative combination of intravenous amino acid supplementation and early in-bed cycle ergometry exercise versus usual care in critically ill patients. We hypothesize that this novel combined intervention will increase physical functioning at the time of hospital discharge; reduce muscle wasting; improve amino acid metabolism and protein synthesis; with improved health-related quality of life, physical functioning, and healthcare resource utilization. Our preliminary data show feasibility and safety of both the amino acid and exercise intervention. The combined intervention can be delivered to ICU patients, even if sedated or comatose, since the in-bed cycle ergometry exercise device (already commercially available and FDA-approved for this purpose) automatically adjusts between passive or active mode depending on patient status. Moreover, this exercise intervention does not pose cardiopulmonary risk when delivered during critical illness. Our research team reflects the interdisciplinary nature of ICU care, with world-class expertise in all areas of this grant, including critical care nutrition; exercise/rehabilitation; ICU nursing, clinical care, and coordination; amino acid metabolism measurement; and body composition analysis. Our team has unparalleled experience with coordinating multi-site ICU-based RCTs, and has successful prior collaborations. Hence, the team is well positioned to conduct this novel RCT that aims to change the paradigm for nutrition and exercise in the ICU and improve physical outcomes for the growing number of ICU survivors.