In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications

Das, Anup; Saffaran, Sina; Chikhani, Marc; Scott, Timothy; Laviola, Marianna; Yehya, Nadir; Laffey, John G.; Hardman, Jonathan G.; Bates, Declan G.

doi:10.1097/cce.0000000000000202

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…Subjects in the present study had poor response to high PEEP (dramatic increase in Pplat, driving pressure, mechanical power with reduction in MAP). These poor responses to high PEEP suggest poor lung recruitability in these subjects, which is consistent with our previous study in which lung recruitability was directly measured (19) and other studies (31)(32)(33)(34)(35). However, subjects in our study also presented with low baseline compliance, which were not the proposed "type H phenotype" patients and differ from other studies.…”

Section: Discussionsupporting

confidence: 90%

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome

et al. 2021

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Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics.Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP–fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2.Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP–FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8).Conclusions: In our cohort with COVID-19–induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04359251.

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Section: Discussionsupporting

confidence: 90%

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome

et al. 2021

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“…(29-34), the model provides a heterogeneous disease profile distributed across 100 gas-exchanging compartments implementing (a) vasodilation leading to hyperperfusion of collapsed lung regions, (b) disruption of hypoxic pulmonary vasoconstriction, with hypoperfusion of normally aerated lung regions (c) disruption of alveolar gas-exchange due to the effects of pneumonitis, and (d) heightened vascular resistance due to the presence of microthrombi, while maintaining relatively well preserved lung compliance and gas volumes. It replicates closely the levels of ventilation-perfusion mismatch and hypoxemia (34, 35), as well as the lack of responsiveness to PEEP (36-38), that has been documented in some patients with COVID-19; see (28) and the supplementary file for full details.…”

Section: Methodssupporting

confidence: 75%

“…The core model used in this study is a multi-compartmental computational simulator that has been previously used to simulate mechanically ventilated patients with various pulmonary disease states (20)(21)(22)(23)(24)(25)(26)(27), including COVID-19 ARDS (28). The simulator offers several advantages, including the capability to define a large number of alveolar compartments (each with its own individual mechanical characteristics), with configurable alveolar collapse, alveolar stiffening, disruption of alveolar gas-exchange, pulmonary vasoconstriction and vasodilation, and airway obstruction.…”

Section: Methodsmentioning

confidence: 99%

High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study

Weaver

Das

Saffaran

et al. 2021

Preprint

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There is ongoing controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a recently developed computational simulator that replicates distinctive features of COVID-19 pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator was calibrated to represent a spontaneously breathing COVID-19 patient with severe hypoxaemia (SaO2 80.6%) and relatively well-preserved lung mechanics (lung compliance of 47.5 ml/cmH2O), being treated with supplemental oxygen (FiO2 = 100%). Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 15/14, 7/20, 15/20, 10/30, 12/30, 10/35, 12/35, 10/40, 12/40 ml/kg / breaths/min. Lung compliance was unaffected by increased VT but decreased significantly at higher RR. While oxygenation improved, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 10.1 cmH2O at baseline to 30 cmH2O at VT/RR of 15 ml/kg / 20 breaths/min and to 54.6 cmH2O at 12 ml/kg / 40 breaths/min. Dynamic strain increased from 0.3 to 0.49 at VT/RR of 12 ml/kg / 30 breaths/min, and to 0.6 at 15 ml/kg / 20 breaths/min. Mechanical power increased from 7.83 J/min to 17.7 J/min at VT/RR of 7 ml/kg / 20 breaths/min, and to 240.5 7 J/min at 12 ml/kg / 40 breaths/min. Our results suggest that the forces generated during increased inspiratory effort in severe COVID-19 are compatible with the development of P-SILI. If conventional oxygen therapy or non-invasive ventilation is ineffective in reducing respiratory effort, control of driving and transpulmonary pressures with invasive ventilation may reduce the risk of P-SILI and allow time for the resolution of the underlying condition.

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“…Thus, impaired hypoxic pulmonary vasoconstriction (HPV) as a cause for severe hypoxia in early COVID-19 patients should not be the sole mechanism. Studies based on in-silico [15] and mathematical [16] modelling also reinforce that even complete loss of HPV could not recreate severe hypoxia observed in COVID-19 pneumonia.…”

Section: Statement Of Hypothesismentioning

confidence: 89%

Epithelial-endothelial cross-talk hypothesis explains the early pathobiology of COVID-19 pneumonia

Jain¹

2021

Preprint

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Since the outbreak of the novel coronavirus disease 2019 , researchers around the globe are constantly puzzled by a well reported clinical finding of pronounced arterial hypoxemia, yet without proportional signs of respiratory distress (i.e. silent hypoxemia or happy hypoxemia) in this disease. Based upon the findings of increased intrapulmonary shunt in COVID-19, many proceed to propose the concept of pulmonary vasoplegia, and not just the loss of hypoxic pulmonary vasoconstriction, as mechanism behind this phenomenon of silent hypoxemia. Further, assumptions were made in proposing inflammatory vasodilators such as prostaglandins and bradykinins to be the pathological mediators. However, a closer look in to the physiology of renin-angiotensin system may suggest the predominant role of angiotensin-converting enzyme and angiotensin II-mediated pulmonary vasoconstriction to be an early mechanism for silent hypoxia. This theory not only supports other clinical symptomatology of COVID-19, including lack of nasal symptoms and absence of asthma as a risk-factor, but also corelates with the histopathological data and the radiological findings of COVID-19 disease.

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In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications

Abstract: Supplemental Digital Content is available in the text.

Cited by 15 publications

References 29 publications

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome

High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study

Epithelial-endothelial cross-talk hypothesis explains the early pathobiology of COVID-19 pneumonia

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