Validation of at-the-bedside formulae for estimating ventilator driving pressure during airway pressure release ventilation using computer simulation.

BACKGROUND: Airway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation. METHODS: We used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV. RESULTS: Levels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text]. CONCLUSIONS: Levels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.

Pre-hospital continuous positive airway pressure after blast lung injury and hypovolaemic shock: a modelling study.

BACKGROUND: In non-traumatic respiratory failure, pre-hospital application of CPAP reduces the need for intubation. Primary blast lung injury (PBLI) accompanied by haemorrhagic shock is common after mass casualty incidents. We hypothesised that pre-hospital CPAP is also beneficial after PBLI accompanied by haemorrhagic shock. METHODS: We performed a computer-based simulation of the cardiopulmonary response to PBLI followed by haemorrhage, calibrated from published controlled porcine experiments exploring blast injury and haemorrhagic shock. The effect of different CPAP levels was simulated in three in silico patients who had sustained mild, moderate, or severe PBLI (10%, 25%, 50% contusion of the total lung) plus haemorrhagic shock. The primary outcome was arterial partial pressure of oxygen (Pao2) at the end of each simulation. RESULTS: In mild blast lung injury, 5 cm H2O ambient-air CPAP increased Pao2 from 10.6 to 12.6 kPa. Higher CPAP did not further improve Pao2. In moderate blast lung injury, 10 cm H2O CPAP produced a larger increase in Pao2 (from 8.5 to 11.1 kPa), but 15 cm H2O CPAP produced no further benefit. In severe blast lung injury, 5 cm H2O CPAP inceased Pao2 from 4.06 to 8.39 kPa. Further increasing CPAP to 10-15 cm H2O reduced Pao2 (7.99 and 7.90 kPa, respectively) as a result of haemodynamic impairment resulting from increased intrathoracic pressures. CONCLUSIONS: Our modelling study suggests that ambient air 5 cm H2O CPAP may benefit casualties suffering from blast lung injury, even with severe haemorrhagic shock. However, higher CPAP levels beyond 10 cm H2O after severe lung injury reduced oxygen delivery as a result of haemodynamic impairment.

Modeling Mechanical Ventilation In Silico-Potential and Pitfalls.

Computer simulation offers a fresh approach to traditional medical research that is particularly well suited to investigating issues related to mechanical ventilation. Patients receiving mechanical ventilation are routinely monitored in great detail, providing extensive high-quality data-streams for model design and configuration. Models based on such data can incorporate very complex system dynamics that can be validated against patient responses for use as investigational surrogates. Crucially, simulation offers the potential to "look inside" the patient, allowing unimpeded access to all variables of interest. In contrast to trials on both animal models and human patients, in silico models are completely configurable and reproducible; for example, different ventilator settings can be applied to an identical virtual patient, or the same settings applied to different patients, to understand their mode of action and quantitatively compare their effectiveness. Here, we review progress on the mathematical modeling and computer simulation of human anatomy, physiology, and pathophysiology in the context of mechanical ventilation, with an emphasis on the clinical applications of this approach in various disease states. We present new results highlighting the link between model complexity and predictive capability, using data on the responses of individual patients with acute respiratory distress syndrome to changes in multiple ventilator settings. The current limitations and potential of in silico modeling are discussed from a clinical perspective, and future challenges and research directions highlighted.

An in-silico porcine model of phosgene-induced lung injury predicts clinically relevant benefits from application of continuous positive airway pressure up to 8 h post exposure.

We present the first computational model of the pathophysiological consequences of phosgene-induced lung injury in porcine subjects. Data from experiments previously performed in several cohorts of large healthy juvenile female pigs (111 data points from 37 subjects), including individual arterial blood gas readings, respiratory rate and heart rate, were used to develop the computational model. Close matches are observed between model outputs (PaO2 and PaCO2) and the experimental data, for both terminally anaesthetised and conscious subjects. The model was applied to investigate the effectiveness of continuous positive airway pressure (CPAP) as a pre-hospital treatment method when treatment is initiated at different time points post exposure. The model predicts that clinically relevant benefits are obtained when 10 cmH2O CPAP is initiated within approximately 8 h after exposure. Supplying low-flow oxygen (40%) rather than medical air produced larger clinical benefits than applying higher CPAP pressure levels. This new model can be used as a tool for conducting investigations into ventilation strategies and pharmaceutical treatments for chemical lung injury of diverse aetiology, and for helping to refine and reduce the use of animals in future experimental studies.

A computational cardiopulmonary physiology simulator accurately predicts individual patient responses to changes in mechanical ventilator settings.

We present new results validating the capability of a high-fidelity computational simulator to accurately predict the responses of individual patients with acute respiratory distress syndrome to changes in mechanical ventilator settings. 26 pairs of data-points comprising arterial blood gasses collected before and after changes in inspiratory pressure, PEEP, FiO2, and I:E ratio from six mechanically ventilated patients were used for this study. Parallelized global optimization algorithms running on a high-performance computing cluster were used to match the simulator to each initial data point. Mean absolute percentage errors between the simulator predicted values of PaO2 and PaCO2 and the patient data after changing ventilator parameters were 10.3% and 12.6%, respectively. Decreasing the complexity of the simulator by reducing the number of independent alveolar compartments reduced the accuracy of its predictions. Clinical Relevance- These results provide further evidence that our computational simulator can accurately reproduce patient responses to mechanical ventilation, highlighting its usefulness as a clinical research tool.

First-principles many-body study of the electronic and optical properties of CsK2Sb, a semiconducting material for ultra-bright electron sources.

We present a comprehensive first-principles investigation of the electronic and optical properties of CsK2Sb, a semiconducting material for ultra-bright electron sources for particle accelerators. Our study, based on density-functional theory and many-body perturbation theory, provides all the ingredients to model the emission of this material as a photocathode, including band gap, band dispersion, and optical absorption. An accurate description of these properties beyond the mean-field picture is relevant to take into account many-body effects. We discuss our results in the context of state-of-the-art electron sources for particle accelerators to set the stage towards improved modeling of quantum efficiency, intrinsic emittance, and other relevant quantities determining the macroscopic characteristics of photocathodes for ultra-bright beams.

Electronic structure and core electron fingerprints of caesium-based multi-alkali antimonides for ultra-bright electron sources.

The development of novel photocathode materials for ultra-bright electron sources demands efficient and cost-effective strategies that provide insight and understanding of the intrinsic material properties given the constraints of growth and operational conditions. To address this question, we propose a viable way to establish correlations between calculated and measured data on core electronic states of Cs-K-Sb materials. To do so, we combine first-principles calculations based on all-electron density-functional theory on the three alkali antimonides Cs3Sb, Cs2KSb, and CsK2Sb with x-ray photoemission spectroscopy (XPS) on Cs-K-Sb photocathode samples. Within the GW approximation of many-body perturbation theory, we obtain quantitative predictions of the band gaps of these materials, which range from 0.57 eV in Cs2KSb to 1.62 eV in CsK2Sb and manifest direct or indirect character depending on the relative potassium content. Our theoretical electronic-structure analysis also reveals that the core states of these systems have binding energies that depend only on the atomic species and their crystallographic sites, with largest shifts of the order of 2 eV and 0.5 eV associated to K 2p and Sb 3d states, respectively. This information can be correlated to the maxima in the XPS survey spectra, where such peaks are clearly visible. In this way, core-level shifts can be used as fingerprints to identify specific compositions of Cs-K-Sb materials and their relation with the measured values of quantum efficiency. Our results represent the first step towards establishing a robust connection between the experimental preparation and characterization of photocathodes, the ab initio prediction of their electronic structure, and the modeling of emission and beam formation processes.

Learning ideals: Critical reflections on a near-peer initiative at Leeds.

This article was migrated. The article was marked as recommended. Previous definitions of peer-assisted learning portray the peer-teacher as a non-expert in teaching content and delivery. In this paper, we reflect on a near-peer initiative at our medical school which seems to depart from this definition. This initiative involves intercalating medical education students in the delivery of foundational sessions on professionalism for first year students for a full year, with individual supervision and support from an experienced teacher and extended medical education study. Reflections from a range of people involved are brought together to begin to understand the supportive features and challenges of near-peer teaching in our context and to identify areas for future research. These reflections highlight the potential for differences and contradictions in the ways that teachers and learners are understood within peer-assisted learning initiatives, and emphasize the need to consider the teaching context in peer-assisted learning scholarship.

Lung epithelial permeability and inhaled furosemide: added dimensions in asthmatics.

OBJECTIVE: Lung clearance rates of inhaled (99m)Tc-DTPA aerosols constitute a sensitive index to evaluate the permeability changes characteristic of airway epithelial damage. It was thought that edema of the airway wall which is reported in asthma could be relieved with a diuretic like furosemide, helping to relieve the symptoms. We intended to study the effect of inhaled furosemide on lung epithelial permeability in asthmatics and smokers with the help of (99m)Tc-DTPA lung clearance test (LCT). METHODS: The study included three groups (n = 15), viz. normal healthy controls, asymptomatic chronic smokers, and chronic persistent asthmatics. Each subject underwent the LCT twice, baseline and post-furosemide (Lasix) study, within a week's interval. The post-furosemide study was carried out 15 min after inhalation of 10 mg of lasix. Lung epithelial permeability was determined in terms of clearance half-life (T (1/2)). RESULTS: The baseline mean T (1/2) values for controls, smokers, and asthmatics were 50.95 +/- 16.58, 20.81 +/- 5.47, 24.06 +/- 6.19 min, respectively. Post-lasix T (1/2) values were 50.83 +/- 15.84, 20.70 +/- 5.65, 41.27 +/- 15.07 min, respectively. There was a significant difference (P < 0.001) in baseline and post-lasix clearance values in asthmatics only. CONCLUSION: Baseline lung epithelial permeability was altered in smokers and asthmatics compared to the controls. Furosemide was effective only in asthmatics in reverting the permeability almost back to the normal range. Inhaled furosemide was effective even in moderate and severe asthmatics. Furosemide has multiple mechanisms of action. It possibly acts at bronchial level in view of the pathology in asthmatics lying in the airways.