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：
9041665
负责人：
GERALD S. SUPINSKI
金额：
$ 56.32万
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/9041665
关键词：
Activities of Daily Living Address Anabolic Agents Attenuated Biological Markers Biopsy Breathing Caring Characteristics Clinical Critical Illness Data Disease Eicosapentaenoic Acid Enhancers Exercise Exercise Tolerance Financial cost Functional disorder Health 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 exercise intolerance improved improved outcome indexing mortality muscle strength patient population pressure prevent 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，机械通气的MICU患者会出现严重的呼吸道和肢体肌肉无力，并且无力与这些患者的临床结局差有关。结果，给药的药物改善骨骼肌肉力量，理论上应减少对机械通气的需求，缩短住院时间，改善死亡率并提高该患者人群的运动耐受性。本提案的目的是解决此问题，并评估合成代谢药物对大型，诊断较大的MICU患者人群中强度和结果的影响。计划了两个实验：AIM 1将检验以下假设：肢体和呼吸道骨骼肌无力可以通过给药羟甲丁酸（HMB）和/或eicosapentaenoic酸（EPA）来减弱重症患者的肢体和呼吸骨骼肌无力。我们将首先测量肌肉强度（磁性刺激的隔膜和股四头肌强度），肌肉大小（diaphragm和股四头肌厚度）以及股四头肌肌肉活检特征（力-PCA关系，生物标志物水平）。我们接下来将机械通风的MICU患者随机接收安慰剂，HMB，EPA或HMB+EPA 10天。然后，我们将在第11天和第21天重复参数测试（肌肉强度，大小和活检特征）。将分析数据，以确定合成代谢处理是否可以改善肌肉强度，增加肌肉大小，改变肌肉生物标志物水平并减少机械通气的持续时间。 AIM 2将检验以下假设：肌肉训练将增加机械通气的MICU患者中对肌肉强度增强子（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，我们将单独将患者随机为安慰剂，肌肉力量增强剂（HMB+EPA），仅针对肌肉训练（呼吸呼吸，腿部循环运动）或增强力量增强剂以及10天的肌肉训练的组合。参数评估将在第11天和第21天重复。我们将确定这些治疗方法是否改善了肌肉强度，肌肉大小，改变生物标志物并减少机械通气的持续时间。我们的试点研究数据表明，EPA和HMB都可以诱导肢体和呼吸肌强度的增加，从而缩短重症患者的机械通气持续时间。这些数据支持我们的假设，并建议拟议的研究可能定义一种新的治疗方法，该治疗方法将对重症患者的护理产生重要影响。