Alveolar leak develops by a rich-get-richer process in ventilator-induced lung injury

Hamlington, Katharine L.; Bates, Jason H. T.; Roy, Gregory S.; Julianelle, Adele J; Charlebois, Chantel M.; Suki, Bélâ; Smith, Bradford J.

doi:10.1371/journal.pone.0193934

Cited by 33 publications

(47 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…shown that increasing airway pressure in an acutely injured lung will cause a rapid progression of injury in a "rich-get-richer" power-law fashion, supporting the findings in the Guldner study (Hamlington et al, 2018). Combined, these studies suggest that high static stress and strain are associated with volutrauma in acutely injured lung tissue but not in normal lung tissue.…”

Section: Problems With Protecting the Baby Lungsupporting

confidence: 68%

“…Both normal and acutely injured lung tissue are highly susceptible to high alveolar R/D-induced VILI when under high inflation pressure (Jain et al, 2017). These data support the rapid progression of lung injury in a power-law fashion when high static and dynamic strain are combined (Hamlington et al, 2018).…”

Section: Vili Mechanisms: Heterogeneous Alveolar Instability and Collsupporting

confidence: 54%

“…The tears progressed in a rich-get-richer mechanism in which the likelihood of a tear getting larger increased with the size of the initial tear. This mechanism explains why atelectrauma appears to be essential to the initiation of VILI in a normal lung, and why atelectrauma and volutrauma act synergistically once VILI is underway (Hamlington et al, 2018). Permissions obtained from Springer Nature.…”

Section: Ventilating Within the Constraints Of An Acutely Injured Lungmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Problems With Protecting the Baby Lungsupporting

confidence: 68%

Section: Vili Mechanisms: Heterogeneous Alveolar Instability and Collsupporting

confidence: 54%

Section: Ventilating Within the Constraints Of An Acutely Injured Lungmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…We postulate that as the lung opens, the increase in parenchymal tethering of airways [56] and alveolar interdependence [55] reduce lung pathology as a power-law function. Hamlington et al have shown that progressive lung injury advances in power-law fashion where alveolar R/D (atelectrauma) caused the initial holes in the epithelium and that high airway pressure (volutrauma) greatly expands these holes in a power-law or rich-get-richer fashion [60]. Lung protection also arguably follows a power-law function with reestablishment of parenchymal tethering, alveolar interdependence, and surfactant function all working together to accelerate recruitment and stabilization of adjacent tissue.…”

Section: New Concepts Of Ards Pathophysiologymentioning

confidence: 99%

Prevention and treatment of acute lung injury with time-controlled adaptive ventilation: physiologically informed modification of airway pressure release ventilation

Nieman

Gatto

Andrews

et al. 2020

Ann. Intensive Care

View full text Add to dashboard Cite

Mortality in acute respiratory distress syndrome (ARDS) remains unacceptably high at approximately 39%. One of the only treatments is supportive: mechanical ventilation. However, improperly set mechanical ventilation can further increase the risk of death in patients with ARDS. Recent studies suggest that ventilation-induced lung injury (VILI) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/ derecruitment and stress-multiplication. Thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and VILI attenuated. A time-controlled adaptive ventilation (TCAV) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung. The goal of this review is to describe how the TCAV method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury. We present work from our group and others that identifies novel mechanisms of VILI in the alveolar microenvironment and demonstrates that the TCAV method can reduce VILI in translational animal ARDS models and mortality in surgical/trauma patients. Our TCAV method utilizes the airway pressure release ventilation (APRV) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces. Time-controlled adaptive ventilation uses inspiratory and expiratory time to (1) gradually "nudge" alveoli and alveolar ducts open with an extended inspiratory duration and (2) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse. The new paradigm in TCAV is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. This novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. The outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

show abstract

“…Inflammatory response induced by CPB [16] could be exacerbated by accumulation of cytokines. Meanwhile mechanical ventilation itself could worsen ARDS by damaging the alveolocapillary barrier in the lungs [17]. The reduced compliance and a ventilation-perfusion mismatch hinted that the surfactant system was damaged [18,19].…”

Section: Discussionmentioning

confidence: 99%

Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

Zhang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Purpose: To evaluate the effect of low-dose exogenous surfactant therapy on infants suffering acute respiratory distress syndrome (ARDS) after cardiac surgery. Materials and methods: We conducted a retrospective case-control study of the archive data of infants diagnosed with ARDS after cardiac surgery and admitted to pediatric cardiac surgical intensive care unit (PICU). A case was defined as a patient that received surfactant and standard therapy; a control was defined as a patient that underwent standard therapy. Controls were identified by matching patients based on age(±30d), weight(±3kg), risk adjustment congenital heart surgery-1 (RACHS-1), and initial ratio of partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (±10). Outcome variables namely oxygenation indices (OI), ventilation index (VI), mechanical ventilation time and PICU time were compared.Results: Forty-four patients, 22 who received surfactant (surfactant group) and 22 who did not (control group) were analyzed. Surfactant group obtained a significant improvement on OI (13.9 vs 5.62; p=0.000) and VI (42.0 vs 22.4; p=0.000) in 6 hours, while control group got no improvement on OI (13.2 vs 11.5; p=0.065) and VI (40.2 vs 36.4; p=0.100). Compared with control group, surfactant group had shorter ventilation time (133.6h vs 218.4h; p=0.000) and PICU time (10.7d vs 17.5d; p=0.001). Infants in surfactant group under 3 months benefit more from OI and VI than infants over 3 months.Conclusions: In congenital heart disease infants with post-surgery ARDS, low-dose exogenous surfactant treatment could prominently improve oxygenation and reduced mechanical ventilation time and PICU time. And the improvement of oxygenation is more effective for infants under 3 months.

show abstract

Alveolar leak develops by a rich-get-richer process in ventilator-induced lung injury

Cited by 33 publications

References 44 publications

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

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

Prevention and treatment of acute lung injury with time-controlled adaptive ventilation: physiologically informed modification of airway pressure release ventilation

Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

Contact Info

Product

Resources

About