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Neurally adjusted ventilatory assist mitigates ventilator-induced diaphragm injury in rabbits

島谷 竜俊 広島大学

2020.03.23

概要

Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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. ...

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