A Physiologically Informed Strategy to Effectively Open, Stabilize, and Protect the Acutely Injured Lung

Abstract

Acute respiratory distress syndrome (ARDS) causes a heterogeneous lung injury and remains a serious medical problem, with one of the only treatments being supportive care in the form of mechanical ventilation. It is very difficult, however, to mechanically ventilate the heterogeneously damaged lung without causing secondary ventilatorinduced lung injury (VILI). The acutely injured lung becomes time and pressure dependent, meaning that it takes more time and pressure to open the lung, and it recollapses more quickly and at higher pressure. Current protective ventilation strategies, ARDSnet low tidal volume (LVt) and the open lung approach (OLA), have been unsuccessful at further reducing ARDS mortality. We postulate that this is because the LVt strategy is constrained to ventilating a lung with a heterogeneous mix of normal and focalized injured tissue, and the OLA, although designed to fully open and stabilize the lung, is often unsuccessful at doing so. In this review we analyzed the pathophysiology of ARDS that renders the lung susceptible to VILI. We also analyzed the alterations in alveolar and alveolar duct mechanics that occur in the acutely injured lung and discussed how these alterations are a key mechanism driving VILI. Our analysis suggests that the time component of each mechanical breath, at both inspiration and expiration, is critical to normalize alveolar mechanics and protect the lung from VILI. Animal studies and a meta-analysis have suggested that the time-controlled adaptive ventilation (TCAV) method, using the airway pressure release ventilation mode, eliminates the constraints of ventilating a lung with heterogeneous injury, since it is highly effective at opening and stabilizing the time-and pressure-dependent lung. In animal studies it has been shown that by "casting open" the acutely injured lung with TCAV we can (1) reestablish normal expiratory lung volume as assessed by direct observation of subpleural alveoli; (2) return normal parenchymal microanatomical structural support, known as alveolar interdependence and parenchymal tethering, as assessed by morphometric analysis of lung histology; (3) facilitate regeneration of normal surfactant function measured as increases in surfactant proteins A and B; and (4) significantly increase lung compliance, which reduces the pathologic impact of driving pressure and mechanical power at any given tidal volume.

Functional pathophysiology of SARS-CoV-2-induced acute lung injury and clinical implications

“…Because the TCAV method has been applied successfully for rescue of refractory hypoxemia (130)(131)(132), it could also be used on patients with phenotype-H SARS-CoV-2 (Fig. 1B), since it a highly effective method to open and stabilize the acutely injured lung (133). However, the preferred strategy would be to use TCAV early, as soon as the standard protocol criteria for intubation are met.…”

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

“…In an excellent report published in Frontiers of Physiology, Nieman et al (2020), described ARDS as a pathologic tetrad with four central components: (1) Endothelial Leakage characterized by increased pulmonary capillary permeability; (2) Surfactant Deactivation resulting into high alveolar surface tension; (3) Alveolar Edema involving flooding alveoli with edema fluid; and finally (4) alveolar recruitment/derecruitment with each breath (Figure 1). It is worth noting that surfactant deactivation occurs quite early in ARDS and the surfactant loss is further exacerbated by the proteins in the edema fluid and by improper ventilation.…”

“…Thus, the pathologic tetrad sets up a vicious cycle of high microvascular permeability → edema → surfactant deactivation → high alveolar surface tension → more edema → alveolar R/D → further increase in microvascular permeability → severe ARDS. (B) The co-atomized surfactant-ambroxol combination will thus impede the above cycle with reduced inflammation and lowered microvascular permeability → reduced edema → surfactant replenishment and activation → lowered alveolar surface tension → less edema → recovered lung function (Reproduced under Creative Commons Attribution License (CC BY) from Nieman et al (2020).…”

Implementation and feasibility of inverse-ratio Airway Pressure Release Ventilation (APRV): Switching from Conventional Ventilation to APRV in Two French ICUs.

“…TCAV is aimed at limiting Ventilator-Induced Lung Injury and has been proposed since 2005 [6][7][8] . In TCAV, expiration is interrupted before the expiratory ow reaches zero, at 75% of the slope of the expiratory ow curve, voluntarily creating an intrinsic PEEP and preventing cyclic alveolar opening and re-collapse [9][10][11] . The bene cial impact of TCAV was suggested by experimental and animal studies, by limiting atelectrauma and stabilizing the alveoli, thus reducing Ventilator-Induced Lung Injury 12,13 . In the ICU, the use of APRV/TCAV remains limited as reported by a recent meta-analysis of 5 studies including 330 patient 14 .…”