Patterns of recruitment and injury in a heterogeneous airway network model

In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air-liquid interfaces, inhibiting gas exchange. This pa- per proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway di- ameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterised by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure (PEEP) reduces the total recruitment time but at the cost of larger stresses exerted on airway walls

Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a devastating complication of numerous underlying conditions, most notably sepsis. Although pathologic vascular leak has been implicated in the pathogenesis of ARDS and sepsis-associated lung injury, the mechanisms promoting leak are incompletely understood. Angiopoietin-2 (Ang-2), a known antagonist of the endothelial Tie-2 receptor, was originally described as a naturally occurring disruptor of normal embryonic vascular development otherwise mediated by the Tie-2 agonist angiopoietin-1 (Ang-1). We hypothesized that Ang-2 contributes to endothelial barrier disruption in sepsis-associated lung injury, a condition involving the mature vasculature. METHODS AND FINDINGS: We describe complementary human, murine, and in vitro investigations that implicate Ang-2 as a mediator of this process. We show that circulating Ang-2 is significantly elevated in humans with sepsis who have impaired oxygenation. We then show that serum from these patients disrupts endothelial architecture. This effect of sepsis serum from humans correlates with measured Ang-2, abates with clinical improvement, and is reversed by Ang-1. Next, we found that endothelial barrier disruption can be provoked by Ang-2 alone. This signal is transduced through myosin light chain phosphorylation. Last, we show that excess systemic Ang-2 provokes pulmonary leak and congestion in otherwise healthy adult mice. CONCLUSIONS: Our results identify a critical role for Ang-2 in disrupting normal pulmonary endothelial function

Computer-aided ventilator resetting is feasible on the basis of a physiological profile.

BACKGROUND: Ventilator resetting is frequently needed to adjust tidal volume, pressure and gas exchange. The system comprising lungs and ventilator is so complex that a trial and error strategy is often applied. Comprehensive characterization of lung physiology is feasible by monitoring. The hypothesis that the effect of ventilator resetting could be predicted by computer simulation based on a physiological profile was tested in healthy pigs. METHODS: Flow, pressure and CO2 signals were recorded in 7 ventilated pigs. Elastic recoil pressure was measured at postinspiratory and post-expiratory pauses. Inspiratory and expiratory resistance as a function of volume and compliance were calculated. CO2 elimination per breath was expressed as a function of tidal volume. Calculating pressure and flow moment by moment simulated the effect of ventilator action, when respiratory rate was varied between 10 and 30 min(-1) and minute volume was changed so as to maintain PaCO2. Predicted values of peak airway pressure, plateau pressure, and CO2 elimination were compared to values measured after resetting. RESULTS: With 95% confidence, predicted pressures and CO2 elimination deviated from measured values with < 1 cm H2O and < 6%, respectively. CONCLUSION: It is feasible to predict effects of ventilator resetting on the basis of a physiological profile at least in health

Population Burden of Long‐Term Survivorship After Severe Sepsis in Older Americans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91328/1/jgs3989.pd

Clinicians’ response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2

Hyperoxia may induce pulmonary injury and may increase oxidative stress. In this retrospective database study we aimed to evaluate the response to hyperoxia by intensivists in a Dutch academic intensive care unit. All arterial blood gas (ABG) data from mechanically ventilated patients from 2005 until 2009 were extracted from an electronic storage database of a mixed 32-bed intensive care unit in a university hospital in Amsterdam. Mechanical ventilation settings at the time of the ABG tests were retrieved. The results of 126,778 ABG tests from 5,498 mechanically ventilated patients were retrieved including corresponding ventilator settings. In 28,222 (22%) of the ABG tests the arterial oxygen tension (PaO2) was > 16 kPa (120 mmHg). In only 25% of the tests with PaO2 > 16 kPa (120 mmHg) was the fraction of inspired oxygen (FiO(2)) decreased. Hyperoxia was accepted without adjustment in ventilator settings if FiO(2) was 0.4 or lower. Hyperoxia is frequently seen but in most cases does not lead to adjustment of ventilator settings if FiO(2) <0.41. Implementation of guidelines concerning oxygen therapy should be improved and further research is needed concerning the effects of frequently encountered hyperoxi

Cost-effectiveness of Implementing Low-Tidal Volume Ventilation in Patients With Acute Lung Injury

Background: Despite widespread guidelines recommending the use of lung-protective ventilation (LPV) in patients with acute lung injury (ALI), many patients do not receive this lifesaving therapy. We sought to estimate the incremental clinical and economic outcomes associated with LPV and determined the maximum cost of a hypothetical intervention to improve adherence with LPV that remained cost-effective. Methods: Adopting a societal perspective, we developed a theoretical decision model to determine the cost-effectiveness of LPV compared to non-LPV care. Model inputs were derived from the literature and a large population-based cohort of patients with ALI. Cost-effectiveness was determined as the cost per life saved and the cost per quality-adjusted life-years (QALYs) gained. Results: Application of LPV resulted in an increase in QALYs gained by 15% (4.21 years for non-LPV vs 4.83 years for LPV), and an increase in lifetime costs of $7,233 per patient with ALI ($99,588 for non-LPV vs $106,821 for LPV). The incremental cost-effectiveness ratios for LPV were$22,566 per life saved at hospital discharge and $11,690 per QALY gained. The maximum, cost-effective, per patient investment in a hypothetical program to improve LPV adherence from 50 to 90$9,482. Results were robust to a wide range of economic and patient parameter assumptions. Conclusions: Even a costly intervention to improve adherence with low-tidal volume ventilation in patients with ALI reduces death and is cost-effective by current societal standards.NIH F32HL090220.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84154/1/Cooke - CEA LPV.pd