Abstract

Tidal volume delivered by mechanical ventilation to a sedated patient is distributed in a nonphysiological pattern, causing atelectasis (underinflation) and overdistension (overinflation). Activation of the diaphragm during controlled mechanical ventilation in these sedated patients may provide a method to reduce atelectasis and alveolar inhomogeneity, protecting the lungs from ventilator-induced lung injury while also protecting the diaphragm by preventing ventilator-induced diaphragm dysfunction. We studied the hypothesis that diaphragm contractions elicited by transvenous phrenic nerve stimulation, delivered in synchrony with volume-control ventilation, would reduce atelectasis and lung inhomogeneity in a healthy, normal lung pig model. Twenty-five large pigs were ventilated for 50 h with lung-protective volume-control ventilation combined with synchronous transvenous phrenic-nerve neurostimulation on every breath, or every second breath. This was compared to lung-protective ventilation alone. Lung mechanics and ventilation pressures were measured using esophageal pressure manometry and electrical impedance tomography. Alveolar homogeneity was measured using alveolar chord length of preserved lung tissue. Lung injury was measured using inflammatory cytokine concentration in bronchoalveolar lavage fluid and serum. We found that diaphragm neurostimulation on every breath preserved [Formula: see text]/[Formula: see text] and significantly reduced the loss of end-expiratory lung volume after 50 h of mechanical ventilation. Neurostimulation on every breath reduced plateau and driving pressures, improved both static and dynamic compliance and resulted in less alveolar inhomogeneity. These findings support that temporary transvenous diaphragm neurostimulation during volume-controlled, lung-protective ventilation may offer a potential method to provide both lung- and diaphragm-protective ventilation.NEW & NOTEWORTHY Temporary transvenous diaphragm neurostimulation has been shown to mitigate diaphragm atrophy in a preclinical model. This study contributes to this work by demonstrating that diaphragm neurostimulation can also offer lung protection from ventilator injury, providing a potential solution to the dilemma of lung- versus diaphragm-protective ventilation. Our findings show that neurostimulation on every breath preserved [Formula: see text]/[Formula: see text], end-expiratory lung volume, alveolar homogeneity, and required lower pressures than lung-protective ventilation over 50 h in healthy pigs.

Highlights

  • Delivery of tidal volume by mechanical ventilation to a deeply sedated patient does not follow normal physiological transpulmonary pressure gradients as there are no associated respiratory muscle contractions [1,2,3]

  • Our findings show that neurostimulation on every breath preserved PaO2 /FIO2, end-expiratory lung volume, alveolar homogeneity, and required lower pressures than lung-protective ventilation over 50 h in healthy pigs

  • We aim to show that TTDN can restore some of the benefits of diaphragm contraction to preclinical subjects that are deeply sedated, thereby offering a potential mechanism to prevent the development of all the aspects that contribute to ventilator-induced lung injury (VILI) and VIDD during the acute sedation phase of their intensive care unit (ICU) course in humans

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Summary

Introduction

Delivery of tidal volume by mechanical ventilation to a deeply sedated patient does not follow normal physiological transpulmonary pressure gradients as there are no associated respiratory muscle contractions [1,2,3]. Atelectasis causes injury to lung tissue through the shearing forces created during cycles of alveolar collapse and expansion during mechanical ventilation [5]. Atelectasis is further encouraged by the use of low-volume, lung-protective ventilation strategies, gravitational forces, and increased hydrostatic pressure from abdominal contents due to patient position [6,7,8,9,10,11]. The proportion of tidal volume is increased in open alveoli when atelectasis forms, which increases respiratory system driving pressure, leading to worsening overdistension and injury [5, 13,14,15,16]. Decreased driving pressure is strongly associated with increased survival in patients with acute respiratory distress syndrome (ARDS) [17]

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