Protein Optimization with Exercise to Improve Muscle Mass and Functional Outcomes (PROXIMUS)

美国儿科重症监护病房(PICU)的死亡率正在改善，导致越来越多的人关注幸存者的生活质量，他们经常有持续性的身体、认知和心理障碍。尤其是机械通风的儿童，会出现制动和营养摄入不足的情况，这会导致在急性疾病期间肌肉丧失。在急性危重病期间，早期活动能力和最佳营养与肌肉质量的保存和缩短机械通气时间有关。这些干预措施可能有可能降低可预防的PICU获得性发病率。然而，在对重症PICU患者的随机研究中，这些干预措施的最佳剂量和长期益处并未显示出来。因此，我们将测试第一个结合高蛋白和个性化运动的儿科专用跨专业干预。这项干预是由营养、早期活动能力、康复运动、肌肉超声(US)和功能结果领域的专家团队开发的。我们提出了一项双中心、试点的可行性随机对照试验(Proximus)，具体目的如下：1)确定在危重儿童急性期比较高蛋白结合个体化运动与标准治疗的随机开放试验的可行性和安全性；2)确定高蛋白和个体化运动对肌肉质量保存的影响；以及3)确定随机后1个月和6个月高蛋白和个体化运动对功能状态的影响。结果：我们将评估一种综合措施的可行性，该措施结合了筛查、登记、分配和依从性/依从性的预定阈值，并在两个手臂之间显著分离蛋白质剂量和运动。安全性将被定义为新的肾损伤和运动相关不良事件的发生率没有差异。在PICU期间，肌肉质量的保存将通过美国测量的股四头肌肌肉厚度(QFMT)的每日变化百分比来评估。我们将使用经过验证的成像协议，具有高可靠性和重复性。我们还将检查两个分支机构在儿童残疾评估量表-计算机适应测试(PEDI-CAT)评估中的标准化标准分数(T-分数)的差异。其他次要结果是美国的功能状态量表、PedsQL和肌肉质量。我们假设，更大规模的试验将是可行和安全的。随机接受联合干预的患者将有较低的QFMT下降和较好的儿科CAT评估分数。Proximus干预有可能深刻改变PICU的医疗保健，并通过改善越来越多的危重疾病儿科幸存者的长期结果，显著影响公共卫生

Mortality in U.S. pediatric intensive care units (PICUs) is improving, resulting in an increased focus on the quality of life of survivors who often have persistent physical, cognitive, and psychological impairments. Mechanically ventilated children in particular experience immobilization and poor nutrient intake, which results in muscle loss during acute illness. Early mobility and optimal nutrition during acute critical illness have been associated with muscle mass preservation and decreased duration of mechanical ventilation. These interventions may have the potential to decrease preventable PICU-acquired morbidities. However, the optimal doses and long-term benefits of these interventions have not been shown in randomized studies of critically ill PICU patients. Thus, we will test the first pediatric-specific, interprofessional intervention that integrates high protein and individualized exercise. This intervention was developed by a team of experts in the fields of nutrition, early mobility, rehabilitative exercise, muscle ultrasound (US), and functional outcomes. We propose a 2-center, pilot feasibility, randomized controlled trial (PROXIMUS) with the following Specific Aims: 1) To determine the feasibility and safety of a randomized open-label trial comparing high protein combined with individualized exercise vs. standard management during the acute phase of critical illness in children; 2) To determine the impact of high protein and individualized exercise on preservation of muscle mass; and 3) To determine the impact of high protein and individualized exercise on functional status at 1 month and 6 months after randomization. Outcomes: We will assess feasibility with a composite measure that combines predetermined thresholds for screening, enrollment, allocation, and compliance/adherence with significant separation in doses of protein and exercise between the two arms. Safety will be defined as absence of difference in rates of new renal injury and exercise-related adverse events. Preservation of muscle mass will be assessed by percent daily change in US-measured quadriceps femoris muscle thickness (QFMT) during the PICU stay. We will use a validated imaging protocol with high reliability and reproducibility. We will also examine the difference in the normative standard scores (T-scores) between the two arms for the Pediatric Evaluation of Disability Inventory – Computer Adaptive Test (PEDI-CAT) assessment. Other secondary outcomes are Functional Status Scale, PedsQL, and muscle quality by US. We hypothesize that a larger trial will be feasible and safe. Patients randomized to the combined intervention will have lower decline in QFMT and better scores on PEDI-CAT assessment. The PROXIMUS intervention has potential to profoundly change medical care in the PICU and substantially impact public health by improving long-term outcomes for the growing number of pediatric survivors of critical illness