Treatment of Skeletal Muscle Dysfunction in ICU Patients

ICU 患者骨骼肌功能障碍的治疗

基本信息

批准号：
8707876
负责人：
GERALD S. SUPINSKI
金额：
$ 55.02万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8707876
关键词：
Activities of Daily Living Address Anabolic Agents Attenuated Biological Markers Biopsy Breathing Caring Characteristics Clinical Critical Illness Data Disease Drug Combinations Eicosapentaenoic Acid Enhancers Exercise Exercise Tolerance Financial cost Functional disorder Hospitals Hyperglycemia Intensive Care Units Leg Length of Stay Limb structure Measurement Measures Mechanical ventilation Medical Morbidity - disease rate Muscle Muscle Weakness Muscle function Outcome Patient Care Patients Performance Pharmaceutical Preparations Pharmacotherapy Physicians Pilot Projects Placebos Pneumonia Randomized Reporting Respiratory Diaphragm Respiratory Failure Respiratory Muscles Skeletal Muscle Testing Thick Training Ventilator Work base cytokine design improved indexing mortality muscle strength patient population pressure prevent public health relevance quadriceps muscle research study respiratory response theories treatment effect

项目摘要

DESCRIPTION (provided by applicant): Recent studies indicate that mechanically ventilated MICU patients develop severe respiratory and limb muscle weakness and that weakness is associated with poor clinical outcomes in these patients. As a result, administration of drugs that improve skeletal muscle strength should theoretically reduce the need for mechanical ventilation, shorten hospital stay, improve mortality, and increase exercise tolerance in this patient population. The purpose of the present proposal is to address this issue and evaluate the impact of anabolic agents on strength and outcomes in a large, diagnostically broad based MICU patient population. Two experiments are planned: Aim 1 will test the hypothesis that limb and respiratory skeletal muscle weakness in critically ill patients can be attenuated by administration of hydroxymethylbutyrate (HMB) and/or eicosapentaenoic acid (EPA). We will first measure indices of muscle strength (magnetically stimulated diaphragm and quadriceps strength), muscle size (diaphragm and quadriceps thickness), and quadriceps muscle biopsy characteristics (force-pCa relationships, biomarker levels). We will next randomize mechanically ventilated MICU patients to receive either placebo, HMB, EPA, or both HMB+EPA for 10 days. We will then repeat parameter testing (muscle strength, size and biopsy characteristics) on days 11 and 21. Data will be analyzed to determine if anabolic treatments improve muscle strength, increase muscle size, alter muscle biomarker levels, and reduce the duration of mechanical ventilation. Aim 2 will test the hypothesis that muscle training will augment the response to muscle strength enhancers (HMB+EPA) in mechanically ventilated MICU patients. We will measure muscle strength, size and biomarker levels. We will then randomize patients to either placebo, muscle strength enhancers (HMB+EPA) alone, targeted muscle training alone (loaded breathing, leg cycling exercise), or the combination of strength enhancers plus muscle training for 10 days. Parameter assessment will be repeated at days 11 and 21. We will determine if these treatments improve muscle strength, muscle size, alter biomarkers, and reduce the duration of mechanical ventilation. Our pilot study data suggest that both EPA and HMB can induce increases in both limb and respiratory muscle strength, shortening the duration of mechanical ventilation in critically ill patients. These data support our hypotheses and suggest that the proposed studies are likely to define a new treatment that will have an important impact on the care of critically ill patients.

描述（由申请人提供）：最近的研究表明，机械通气 MICU 患者会出现严重的呼吸和四肢肌肉无力，而这种无力与这些患者的不良临床结果相关。结果，施用药物理论上，提高骨骼肌力量应该减少机械通气的需要，缩短住院时间，提高死亡率，并提高该患者群体的运动耐力。本提案的目的是解决这个问题，并评估合成代谢药物对大量诊断广泛的 MICU 患者群体的力量和结果的影响。计划进行两项实验：目标 1 将检验以下假设：给予羟甲基丁酸 (HMB) 和/或二十碳五烯酸 (EPA) 可以减轻危重患者的四肢和呼吸骨骼肌无力。我们将首先测量肌肉力量指数（磁刺激膈肌和股四头肌力量）、肌肉大小（膈肌和股四头肌厚度）和股四头肌活检特征（力-PCA 关系、生物标志物水平）。接下来，我们将随机分配机械通气 MICU 患者接受安慰剂、HMB、EPA 或 HMB+EPA 治疗，为期 10 天。然后，我们将在第 11 天和第 21 天重复参数测试（肌肉力量、大小和活检特征）。将分析数据以确定合成代谢治疗是否可以改善肌肉力量、增加肌肉大小、改变肌肉生物标志物水平并减少机械通气持续时间。目标 2 将检验以下假设：肌肉训练将增强机械通气 MICU 患者对肌肉力量增强剂 (HMB+EPA) 的反应。我们将测量肌肉力量、大小和生物标志物水平。然后，我们将患者随机分配到安慰剂、单独的肌肉力量增强剂 (HMB+EPA)、单独的针对性肌肉训练（负荷呼吸、腿部循环运动）或力量增强剂加肌肉训练的组合，为期 10 天。将在第 11 天和第 21 天重复参数评估。我们将确定这些治疗是否可以改善肌肉力量、肌肉大小、改变生物标志物并减少机械通气的持续时间。我们的初步研究数据表明，EPA 和 HMB 均可诱导肢体和呼吸肌力量的增加，从而缩短危重患者的机械通气持续时间。这些数据支持我们的假设，并表明拟议的研究可能会定义一种新的治疗方法，对危重患者的护理产生重要影响。