From the Department of Anesthesiology (T.B., C.B., R.R., J.G., H.D., C.S.B.), the Department of Intensive and Intermediate Care (T.B., G.M., C.S.B.), and the Institute of Neuropathology (J.W.), Rheinisch-Westfalian Technical University Aachen, Aachen, Germany; and the Laboratory of Pneumology, Catholic University of Leuven, Leuven, Belgium (A.D., G.G.-R.).
Anesthesiology. 2018 Apr;128(4):784-795. doi: 10.1097/ALN.0000000000002081.
Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients' mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction.
Twenty-four rats were separated into three groups (n = 8/group). Two groups were mechanically ventilated during either dexmedetomidine or pentobarbital exposure for 24 h, referred to as interventional groups. A third group of directly euthanized rats served as control. Force generation, fiber dimensions, proteolysis markers, protein oxidation and lipid peroxidation, calcium homeostasis markers, and glucose transporter-4 (Glut-4) translocation were measured in the diaphragm.
Diaphragm force, corrected for cross-sectional area, was significantly decreased in both interventional groups compared to controls and was significantly lower with dexmedetomidine compared to pentobarbital (e.g., 100 Hz: -18%, P < 0.0001). In contrast to pentobarbital, dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001) and impaired Glut-4 translocation (-73%, P < 0.0005). It activated autophagy, the calcium-dependent proteases, and caused lipid peroxidation similarly to pentobarbital.
Twenty-four hours of mechanical ventilation during dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm dysfunction, possibly through impaired Glut-4 translocation. Although dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit oxidative stress and activation of the proteolytic pathways.
麻醉剂对机械通气患者至关重要，因为任何影响膈肌功能的因素都可能对撤机进程产生负面影响，进而影响患者的死亡率。右美托咪定可能具有抗氧化和抗蛋白水解特性，但它也会减少肌肉对葡萄糖的摄取，从而可能损害膈肌的力量产生。本研究检验了右美托咪定可以抑制呼吸机相关性膈肌功能障碍的假设。
将 24 只大鼠分为三组（每组 8 只）。两组大鼠在右美托咪定或戊巴比妥暴露 24 小时期间进行机械通气，称为干预组。第三组直接安乐死的大鼠作为对照组。测量膈肌的力生成、纤维尺寸、蛋白水解标志物、蛋白氧化和脂质过氧化、钙稳态标志物和葡萄糖转运蛋白-4（Glut-4）易位。
与对照组相比，两组干预组的膈肌力（校正横截面积）均显著降低，且右美托咪定组明显低于戊巴比妥组（例如 100 Hz：-18%，P < 0.0001）。与戊巴比妥不同，右美托咪定不会导致膈肌萎缩，但会引起更多的蛋白氧化（200%对戊巴比妥的 73%，P = 0.0015），诱导更少的肌肉萎缩 F 盒上调（149%对戊巴比妥的 374%，P < 0.001），并损害 Glut-4 易位（-73%，P < 0.0005）。它激活自噬和钙依赖性蛋白酶，并引起脂质过氧化，与戊巴比妥相似。
在右美托咪定镇静下进行 24 小时机械通气导致通气相关性膈肌功能障碍恶化，可能是通过损害 Glut-4 易位。尽管右美托咪定可预防膈肌纤维萎缩，但它不能抑制氧化应激和蛋白水解途径的激活。
