Biological Response to Time-Controlled Adaptive Ventilation Depends on Acute Respiratory Distress Syndrome Etiology*

Silva, Pedro L.; Cruz, Fernanda Ferreira; Samary, Cynthia dos Santos; Moraes, Lillian; Magalhães, R.F.; Fernandes, Marcos Vinícius de Souza; Bose, Rebeca; Pelegati, Vitor B.; Carvalho, Hernandes F.; Capelozzi, Vera Luíza; Satalin, Joshua; Gatto, Louis A.; Andrews, Penny; Habashi, Nader M.; Nieman, Gary F.; Rocco, Patrícia Rieken Macêdo

doi:10.1097/ccm.0000000000003078

Cited by 31 publications

(35 citation statements)

References 49 publications

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“…Our group has investigated the physiological impact of the TCAV method in both mechanistic and efficacy animal studies (Roy et al, 2012;Emr et al, 2013;Roy S.K. et al, 2013;Kollisch-Singule et al, 2014a,b, 2015aSmith et al, 2015;Silva et al, 2018) and in a meta-analysis of data on SICU patients (Andrews et al, 2013). In addition, the TCAV method is the primary ventilator strategy used at the R Adam Cowley Shock Trauma Center in Baltimore, with well over 1,000,000 h of ventilator time.…”

Section: The Tcav Methods To Open and Stabilize The Acutely Injured Lungmentioning

confidence: 99%

“…Indeed, our work in translational animal models and a meta-analysis of data on surgical intensive care unit (SICU) patients has shown that our time-controlled adaptive ventilation (TCAV) method, using airway pressure release ventilation (APRV) mode, is highly effective at keeping the lung open and stable, significantly reducing morbidity in translational animal models and reducing the ARDS incidence and mortality rates of SICU patients at high risk of developing ARDS (Roy et al, 2012;Andrews et al, 2013;Emr et al, 2013;Roy S.K. et al, 2013;Kollisch-Singule et al, 2014a,b, 2015aNieman et al, Nieman et al, 2015, 2017aSmith et al, 2015;Jain et al, 2016Jain et al, , 2017Satalin et al, 2018;Silva et al, 2018;Mahajan et al, 2019).…”

Section: A Physiologically Informed Strategy To Effectively Open and mentioning

confidence: 99%

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

et al. 2020

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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.

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Section: The Tcav Methods To Open and Stabilize The Acutely Injured Lungmentioning

confidence: 99%

Section: A Physiologically Informed Strategy To Effectively Open and mentioning

confidence: 99%

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

et al. 2020

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“…Three slices (2 × 2 × 2 mm) were cut from three different segments of the left lung and xed (2.5% glutaraldehyde) for electron microscopy. On each lung electron microscopy image (20 elds per animal), degree of interstitial edema, damage to basement membrane, extracellular matrix damage, type II epithelial cell damage, and endothelial cell damage were graded on a ve-point, semiquantitative, severity-based scoring system as follows: 0 = normal lung parenchyma, 1 to 4 = changes in 1 to 25%, 26 to 50%, 51 to 75%, and 76 to 100% of examined tissue, respectively [19].…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome.

Rocha

Samary

Antunes

et al. 2020

Preprint

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Background We evaluated the effects of abrupt versus gradual positive end-expiratory pressure (PEEP) decrease, combined with standard versus high-volume fluid administration, on lung, heart, and kidney damage in an established model of acute respiratory distress syndrome (ARDS). Methods Thirty-five Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer´s lactate [standard (10 mL/kg/h) or high (30 mL/kg/h) fluids]. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease, from 9 to 3 cmH2O. After this period, animals were further ventilated for 10 minutes at PEEP = 3 cmH2O, euthanized, and then lungs and kidney removed for molecular biology analysis. Results At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. The PAT (pulmonary acceleration time)/PET (pulmonary ejection time) ratio was lower in abrupt compared to gradual PEEP decrease, independent of fluid status, suggesting higher pulmonary arterial pressure in rats undergo abrupt PEEP decrease. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (pro-inflammatory marker) and vascular endothelial growth factor (endothelial cell damage marker) compared to the other groups. Standard fluid administration associated with gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Club cell-16 protein expression, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 was higher in high compared to standard fluid administration, independent of PEEP strategy. Conclusion In experimental mild-moderate ARDS, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.

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“…During a pandemic, the number of patients requiring mechanical ventilation may exceed the number of ventilators available, as experienced during previous influenza pandemics, [1] and is expected to occur again given the current trajectory of the COVID-19 pandemic. The recently published guidelines for management of COVID-19 patients [SCCM U.S. ICU Resource Availability for COVID-19 (https://sccm.org/Blog/March-2020/United-States-Resource-Availability-for-COVID- 19)] suggest that the most common reason for COVID-19 patient admission to the intensive care unit (ICU) is severe hypoxic respiratory failure necessitating mechanical ventilation. Acute care hospitals in the U.S.A. own an estimated 62,000 full-featured mechanical ventilators with another ~98,000 older or more basic ventilators (https://sccm.org/Blog/March-2020/United-States-Resource-Availability-for-COVID-19) that could be pressed into service.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have investigated multiple circuit designs on test lungs [4,5,7] using multiple methods of setting the ventilator various ventilator modes including: Controlled Mandatory Ventilation (CMV), [4] Pressure and Volume Control, [5] and Synchronized Intermittent Mandatory Ventilation (SIMV). [6] Previous work from our lab has shown the physiologic [8][9][10][11][12][13][14][15][16][17][18][19] and clinical [20] benefits of the time controlled adaptive ventilation (TCAV) method of setting and adjusting the airway pressure release ventilation (APRV) mode. Briefly, the TCAV method uses the expiratory flow curve to modulate the ventilator settings according to the underlying lung pathology.…”

Section: Introductionmentioning

confidence: 99%

Ventilating Two Subjects with One Ventilator: Achievable but not Advisable

Satalin

Blair

Kollisch-Singule

et al. 2020

Preprint

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Background: The world is in the midst of the COVID-19 viral pandemic and the number of patients requiring mechanical ventilation may exceed the number of ventilators available. New information is being sought on the feasibility of using one ventilator on multiple patients should the need arise. In this study, we hypothesized that two rabbits could be simultaneously mechanically ventilated using a simple, readily available, dual circuit. Methods: Two pairs of New Zealand White rabbits (n=4) were anesthetized and hooked up to a simple dual circuit and ventilated in the Airway Pressure Release Ventilation mode. Arterial and venous lines were placed for arterial blood gases, hemodynamic monitoring and fluid administration. Following one hour of ventilation, a surfactant washout was performed and mechanical ventilation resumed. Animals were euthanized after an additional one hour of ventilation. Results: Both Pairs of rabbits had a similar pre-injury PaO2/FiO2 ratio. Following injury, all rabbits had a decline in PaO2/FiO2 with 2 maintaining a PaO2/FiO2 ratio consistent with moderate ARDS, 1 consistent with mild and 1 return to normal. Both Pairs of rabbits had a similar pre-injury PaCO2. Rabbits in Pair 1 maintained similar arterial carbon dioxide (PaCO2) levels following ARDS. Pair 2 showed an increase in PaCO2 with ARDS due to the much higher PaCO2 in the rabbit with the more severe lung injury.Conclusion: A dual ventilator circuit can be constructed from materials in any respiratory therapy department. Using this dual circuit, two animals with ARDS can be oxygenated and ventilation sufficiently to meet current standards.

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Biological Response to Time-Controlled Adaptive Ventilation Depends on Acute Respiratory Distress Syndrome Etiology*

Abstract: In pulmonary acute respiratory distress syndrome, time-controlled adaptive ventilation led to more pronounced beneficial effects on expression of biomarkers related to overdistension and extracellular matrix homeostasis.

Cited by 31 publications

References 49 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

The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome.

Ventilating Two Subjects with One Ventilator: Achievable but not Advisable

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