Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Division of Neonatology, Nagano Children's Hospital, 3100 Toyoshina, Azumino City, Nagano, 399-8288, Japan.
Respir Res. 2019 Dec 23;20(1):293. doi: 10.1186/s12931-019-1265-x.
Ventilator-induced diaphragmatic dysfunction is a serious complication associated with higher ICU mortality, prolonged mechanical ventilation, and unsuccessful withdrawal from mechanical ventilation. Although neurally adjusted ventilatory assist (NAVA) could be associated with lower patient-ventilator asynchrony compared with conventional ventilation, its effects on diaphragmatic dysfunction have not yet been well elucidated.
Twenty Japanese white rabbits were randomly divided into four groups, (1) no ventilation, (2) controlled mechanical ventilation (CMV) with continuous neuromuscular blockade, (3) NAVA, and (4) pressure support ventilation (PSV). Ventilated rabbits had lung injury induced, and mechanical ventilation was continued for 12 h. Respiratory waveforms were continuously recorded, and the asynchronous events measured. Subsequently, the animals were euthanized, and diaphragm and lung tissue were removed, and stained with Hematoxylin-Eosin to evaluate the extent of lung injury. The myofiber cross-sectional area of the diaphragm was evaluated under the adenosine triphosphatase staining, sarcomere disruptions by electron microscopy, apoptotic cell numbers by the TUNEL method, and quantitative analysis of Caspase-3 mRNA expression by real-time polymerase chain reaction.
Physiological index, respiratory parameters, and histologic lung injury were not significantly different among the CMV, NAVA, and PSV. NAVA had lower asynchronous events than PSV (median [interquartile range], NAVA, 1.1 [0-2.2], PSV, 6.8 [3.8-10.0], p = 0.023). No differences were seen in the cross-sectional areas of myofibers between NAVA and PSV, but those of Type 1, 2A, and 2B fibers were lower in CMV compared with NAVA. The area fraction of sarcomere disruptions was lower in NAVA than PSV (NAVA vs PSV; 1.6 [1.5-2.8] vs 3.6 [2.7-4.3], p < 0.001). The proportion of apoptotic cells was lower in NAVA group than in PSV (NAVA vs PSV; 3.5 [2.5-6.4] vs 12.1 [8.9-18.1], p < 0.001). There was a tendency in the decreased expression levels of Caspase-3 mRNA in NAVA groups. Asynchrony Index was a mediator in the relationship between NAVA and sarcomere disruptions.
Preservation of spontaneous breathing using either PSV or NAVA can preserve the cross sectional area of the diaphragm to prevent atrophy. However, NAVA may be superior to PSV in preventing sarcomere injury and apoptosis of myofibrotic cells of the diaphragm, and this effect may be mediated by patient-ventilator asynchrony.
呼吸机诱导的膈肌功能障碍是与 ICU 死亡率较高、机械通气时间延长和机械通气撤机失败相关的严重并发症。虽然神经调节辅助通气（NAVA）与常规通气相比可能与更低的患者-呼吸机不同步相关，但它对膈肌功能障碍的影响尚未得到很好的阐明。
20 只日本白兔随机分为四组，（1）无通气，（2）连续神经肌肉阻滞的控制机械通气（CMV），（3）NAVA，和（4）压力支持通气（PSV）。通气兔发生肺损伤，并继续机械通气 12 小时。连续记录呼吸波，并测量异步事件。随后，处死动物，取出膈肌和肺组织，用苏木精-伊红染色评估肺损伤程度。用三磷酸腺苷染色评估膈肌肌纤维的横截面积，电镜观察肌节破坏，TUNEL 法检测细胞凋亡数，实时聚合酶链反应定量分析 Caspase-3 mRNA 表达。
CMV、NAVA 和 PSV 之间的生理指标、呼吸参数和组织学肺损伤无显著差异。NAVA 的异步事件低于 PSV（中位数[四分位数间距]，NAVA，1.1[0-2.2]，PSV，6.8[3.8-10.0]，p=0.023）。NAVA 和 PSV 之间的肌纤维横截面积无差异，但 CMV 组的 1 型、2A 型和 2B 型纤维横截面积低于 NAVA。NAVA 的肌节破坏面积分数低于 PSV（NAVA 与 PSV；1.6[1.5-2.8]与 3.6[2.7-4.3]，p<0.001）。NAVA 组的细胞凋亡比例低于 PSV（NAVA 与 PSV；3.5[2.5-6.4]与 12.1[8.9-18.1]，p<0.001）。NAVA 组 Caspase-3 mRNA 表达水平呈下降趋势。异步指数是 NAVA 与肌节破坏关系中的中介物。
使用 PSV 或 NAVA 保留自主呼吸可以保持膈肌的横截面积以防止萎缩。然而，与 PSV 相比，NAVA 可能更能预防肌节损伤和膈肌肌成纤维细胞的凋亡，这种作用可能是通过患者-呼吸机不同步介导的。
