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Mechanical ventilation (MV) is a core treatment for patients suffering from respiratory disease and failure. However, MV settings are not standardized due to significant inter- and intra- patient variability in response to care, leading to variability in outcome. There is thus a need to personalize MV settings. This research significantly extends a single compartment lung mechanics model with physiologically relevant basis functions, and uses it to identify patient-specific lung mechanics and predict response to changes in MV settings. Nonlinear evolution of pulmonary elastance over positive end expiratory pressure (PEEP) is modelled by a newly proposed, physiologically relevant and simplified compensatory function to enable prediction of pulmonary response for both volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV), and identified as patientspecific using each patient's data at a baseline PEEP. Predictions at higher PEEP levels test the validity of the proposed models based on errors in predicted peak inspiratory pressure (PIP) in two VCV trials and volume (PIV) in one PCV trial. A total of 210 prediction cases over 36 patients (22 VCV; 14 PCV) yielded absolute predicted PIP errors within 1.0 cmH2O (2.3%) and 3.3 cmH2O (7.3%) for 90% cases in VCV, while predicted PIV errors are within 0.073 L (16.8%) for 85% cases in PCV. In conclusion, a novel deterministic virtual patient model is presented, able to offer accurate prediction of pulmonary response across a wide range of PEEP changes for the two main MV modes used clinically, enabling predictive decision support in real-time to safely personalize and optimize care.

Mechanical ventilation (MV) is used in the intensive care unit (ICU) to treat patients with respiratory failure. However, MV settings are not standardized due to significant inter- and intra- patient variability in response to care, leading to variability in care, outcome, and cost. There is thus a need to personalize MV. This research extends a single compartment lung mechanics model with physiologically relevant basis functions, to identify patient-specific lung mechanics and predict response to changes in MV care. The nonlinear evolution of pulmonary elastance as positive-end-expiratory pressure (PEEP) changes is captured by a physiologically relevant, simplified compensatory equation as a function of PEEP and pressure identification error at the baseline PEEP level. It allows both patient-specific and general prediction of lung elastance of higher PEEP. The prediction outcome is validated with data from two volume-controlled ventilation (VCV) trials and one pressure-controlled ventilation (PCV) trial, where the biggest PEEP prediction interval is a clinically unrealistic 20cmH(2)O, comprising 210 prediction cases over 36 patients (22 VCV; 14 PCV). Predicted absolute peak inspiratory pressure (PIP) errors are within 1.0cmH(2)O and 3.3cmH(2)O for 90% cases in the two VCV trials, while predicted peak inspiratory tidal volume (PIV) errors are within 0.073L for 85% cases in studied PCV trial. The model presented provides a highly accurate, predictive virtual patient model across multiple MV modes and delivery methods, and over clinically unrealistically large changes. Low computational cost, and fast, easy parameterization enable model-based, predictive decision support in real-time to safely personalize and optimize MV care. Copyright (C) 2021 The Authors.

Background: Mechanical ventilation (MV) is a core intensive care unit (ICU) therapy. Significant inter- and intra- patient variability in lung mechanics and condition makes managing MV difficult. Accurate prediction of patient-specific response to changes in MV settings would enable optimised, personalised, and more productive care, improving outcomes and reducing cost. This study develops a generalised digital clone model, or in-silico virtual patient, to accurately predict lung mechanics in response to changes in MV.Methods: An identifiable, nonlinear hysteresis loop model (HLM) captures patient-specific lung dynamics identified from measured ventilator data. Identification and creation of the virtual patient model is fully automated using the hysteresis loop analysis (HLA) method to identify lung elastances from clinical data. Performance is evaluated using clinical data from 18 volume-control (VC) and 14 pressure-control (PC) ventilated patients who underwent step-wise recruitment maneuvers.Results: Patient-specific virtual patient models accurately predict lung response for changes in PEEP up to 12 cmH(2)O for both volume and pressure control cohorts. R-2 values for predicting peak inspiration pressure (PIP) and additional retained lung volume, V-frc in VC, are R-2 =0.86 and R-2 =0.90 for 106 predictions over 18 patients. For 14 PC patients and 84 predictions, predicting peak inspiratory volume (PIV) and V-frc yield R-2 =0.86 and R-2 =0.83. Absolute PIP, PIV and V-frc errors are relatively small.Conclusions: Overall results validate the accuracy and versatility of the virtual patient model for capturing and predicting nonlinear changes in patient-specific lung mechanics. Accurate response prediction enables mechanically and physiologically relevant virtual patients to guide personalised and optimised MV therapy. (C) 2020 Elsevier B.V. All rights reserved.