Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial
Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial
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DOI：
10.1016/s2213-2600(13)70183-8
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发表时间：
2013-10-01
影响因子：
76.2
通讯作者：
Vanhorebeek, Ilse
中科院分区：
文献类型：
--
作者：
Hermans, Greet;Casaer, Michael P.;Vanhorebeek, Ilse
危重病人可能会出现所谓的重症监护病房获得性虚弱，从而延迟康复。减少肌肉质量，质量，或两者都可能有作用。在成人危重患者中进行的早期肠外营养补充肠内营养（EPaNIC）试验（注册于ClinicalTrials.gov，编号NCT 00512122）显示，与早期PN相比，在重症监护病房中耐受大量营养素缺乏1周（晚期肠外营养[PN]）可加速恢复。弱点的作用尚不清楚。我们的目的是评估是否晚PN和早期PN差异影响肌无力和自噬质量控制myofibrs.Methods在这一前瞻性计划的亚组分析的EPaNIC试验，虚弱（MRC总分）进行了评估，在600清醒，合作的患者。随机分组后8天，从122名患者和20名匹配的健康对照中采集骨骼肌活检，研究自噬和萎缩。我们用Mann-Whitney U检验、中位数检验、Kruskal-Wallis检验或卡方检验来确定差异的显著性。（随机化后中位第9天），而295例接受早期PN的患者中有127例（43%）（绝对差异-9%，95% CI -16至-1; p=0.030）。与早期PN相比，晚期PN的虚弱恢复更快（p=0.021）。与健康对照组相比，重症患者的肌纤维横截面积较小，密度较低，与早期PN和晚期PN相似。与自噬体形成相关的LC 3（微管相关蛋白轻链3）II与LC 3 I的比率在晚期PN患者中高于早期PN（p=0.026），几乎达到健康对照组的两倍（p=0.0016），并且与较少的泛素染色一致（p=0.019）。LC 3 II与LC 3 I比值较高与虚弱程度较轻独立相关（p=0.047）。与对照组相比，患者肌肉活检组织中编码收缩性肌纤维蛋白的mRNA表达较低，E3连接酶表达较高（p
Background Patients who are critically ill can develop so-called intensive-care unit acquired weakness, which delays rehabilitation. Reduced muscle mass, quality, or both might have a role. The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered with ClinicalTrials.gov, number NCT00512122) showed that tolerating macronutrient deficit for 1 week in intensive-care units (late parenteral nutrition [PN]) accelerated recovery compared with early PN. The role of weakness was unclear. Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres.Methods In this prospectively planned subanalysis of the EPaNIC trial, weakness (MRC sum score) was assessed in 600 awake, cooperative patients. Skeletal muscle biopsies, harvested from 122 patients 8 days after randomisation and from 20 matched healthy controls, were studied for autophagy and atrophy. We determined the significance of differences with Mann-Whitney U, Median, Kruskal-Wallis, or chi(2) (exact) tests, as appropriate.Findings With late PN, 105 (34%) of 305 patients had weakness on first assessment (median day 9 post-randomisation) compared with 127 (43%) of 295 patients given early PN (absolute difference -9%, 95% CI -16 to -1; p=0.030). Weakness recovered faster with late PN than with early PN (p=0.021). Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls, similarly with early PN and late PN. The LC3 (microtubule-associated protein light chain 3) II to LC3I ratio, related to autophagosome formation, was higher in patients given late PN than early PN (p=0.026), reaching values almost double those in the healthy control group (p=0.0016), and coinciding with less ubiquitin staining (p=0.019). A higher LC3II to LC3I ratio was independently associated with less weakness (p=0.047). Expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants (p