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

Abstract

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.