Acute Skeletal Muscle Wasting in Critical Illness
Acute Skeletal Muscle Wasting in Critical Illness
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DOI：
10.1001/jama.2013.278481
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发表时间：
2013-10-16
影响因子：
120.7
通讯作者：
Montgomery, Hugh E.
中科院分区：
文献类型：
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作者：
Puthucheary, Zudin A.;Rawal, Jaikitry;Montgomery, Hugh E.
危重疾病的幸存者表现出骨骼肌萎缩与相关的功能损害。目的对骨骼肌萎缩进行全面的前瞻性表征，确定蛋白质合成和分解改变的致病作用。设计、环境和参与者：2009年8月至2011年4月，前瞻性地招募了63名重症患者（59%为男性，平均年龄54.7岁[95% CI， 50.0-59.6岁]），急性生理和慢性健康评估II评分为23.5 (95% CI, 21.9-25.2)，在英国一所大学教学医院和一家社区医院重症监护病房（ICU）入院后24小时内。如果患者年龄大于18岁，预计插管时间超过48小时，重症监护时间超过7天，并且在ICU住院期间存活，则招募患者。在第1、3、7和10天，通过连续超声测量股直肌横截面积（CSA）来确定肌肉损失。在一部分患者中，在第1天和第7天对纤维CSA面积以及蛋白质与DNA的比例进行量化。进行组织病理学分析。此外，肌肉蛋白的合成、分解率和各自的信号通路也被表征。结果：第10天观察到股直肌CSA显著降低（-17.7%[95% CI, -25.9%至8.1%];P < .001）。在第1天和第7天采用所有3种测量方法评估的28例患者中，股直肌CSA下降10.3%(95% CI， 6.1%至14.5%)，纤维CSA下降17.5%(95% CI， 5.8%至29.3%)，蛋白质与DNA的比率下降29.5%（95% CI， 13.4%至45.6%）。与单器官衰竭（-3.0%,95% CI, -5.3%至2.1%）相比，多器官衰竭患者在第7天的股直肌CSA下降幅度更大（-15.7%,95% CI, -27.7%至11.4%），甚至在第3天（分别为-8.7%[95% CI, -59.3%至50.6%]和-1.8%[95% CI, -12.3%至10.5%],P = 0.03）。37例患者中有20例（54.1%）发生肌纤维坏死。与禁食健康对照组（0.039%/小时；95% CI， 0.029%至0.048%/小时）相比，通过肌肉蛋白质合成分数测量的蛋白质合成在第1天降低（0.035%/小时；95% CI， 0.023%至0.047%/小时）（P = 0.57），并在第7天增加（0.076%[95% CI， 0.032%至0.120%/小时]；P = 0.003），与喂养对照组相关（0.065%/小时[95% CI， 0.049%至0.080%/小时]；P = 0.30），与营养负荷无关。腿部蛋白质分解在整个研究过程中保持升高（8.5 [95% CI， 4.7至12.3]至10.6 [95% CI， 6.8至14.4]μ mol苯丙氨酸/分钟/理想体重× 100； P = 0.40）。细胞内信号传导模式支持分解增加（n = 9, r = -0.83, P = 0.005）和合成减少（n = 9, r = -0.69, P = 0.04）。结论和相关性在这些危重患者中，肌肉萎缩在危重患者的第一周发生得早且迅速，并且与单器官衰竭相比，多器官衰竭患者肌肉萎缩更为严重。这些发现可能为危重疾病中的骨骼肌萎缩提供见解。
IMPORTANCE Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment.OBJECTIVE To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown.DESIGN, SETTING, AND PARTICIPANTS Sixty-three critically ill patients (59% male; mean age: 54.7 years [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay.MAIN OUTCOMES AND MEASURES Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized.RESULTS There were significant reductions in the rectus femoris CSA observed at day 10 (-17.7%[95% CI, -25.9% to 8.1%]; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3%(95% CI, 6.1% to 14.5%), the fiber CSA by 17.5%(95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5%(95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (-15.7%; 95% CI, -27.7% to 11.4%) compared with single organ failure (-3.0%; 95% CI, -5.3% to 2.1%) (P < .001), even by day 3 (-8.7%[95% CI, -59.3% to 50.6%] vs -1.8%[95% CI, -12.3% to 10.5%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7 (0.076%[95% CI, 0.032%-0.120%/hour]; P = .03) to rates associated with fed controls (0.065%/hour [95% CI, 0.049% to 0.080%/hour]; P = .30), independent of nutritional load. Leg protein breakdown remained elevated throughout the study (8.5 [95% CI, 4.7 to 12.3] to 10.6 [95% CI, 6.8 to 14.4] mu mol of phenylalanine/min/ideal body weight x 100; P = .40). The pattern of intracellular signaling supported increased breakdown (n = 9, r = -0.83, P = .005) and decreased synthesis (n = 9, r = -0.69, P = .04).CONCLUSIONS AND RELEVANCE Among these critically ill patients, muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure. These findings may provide insights into skeletal muscle wasting in critical illness.