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  1. Wong JW, Chiew YS, Desaive T, Chase JG
    Biomed Eng Online, 2022 Feb 09;21(1):11.
    PMID: 35139858 DOI: 10.1186/s12938-022-00983-y
    BACKGROUND: Surges of COVID-19 infections have led to insufficient supply of mechanical ventilators (MV), resulting in rationing of MV care. In-parallel, co-mechanical ventilation (Co-MV) of multiple patients is a potential solution. However, due to lack of testing, there is currently no means to match ventilation requirements or patients, with no guidelines to date. In this research, we have developed a model-based method for patient matching for pressure control mode MV.

    METHODS: The model-based method uses a single-compartment lung model (SCM) to simulate the resultant tidal volume of patient pairs at a set ventilation setting. If both patients meet specified safe ventilation criteria under similar ventilation settings, the actual mechanical ventilator settings for Co-MV are determined via simulation using a double-compartment lung model (DCM). This method allows clinicians to analyse Co-MV in silico, before clinical implementation.

    RESULTS: The proposed method demonstrates successful patient matching and MV setting in a model-based simulation as well as good discrimination to avoid mismatched patient pairs. The pairing process is based on model-based, patient-specific respiratory mechanics identified from measured data to provide useful information for guiding care. Specifically, the matching is performed via estimation of MV delivered tidal volume (mL/kg) based on patient-specific respiratory mechanics. This information can provide insights for the clinicians to evaluate the subsequent effects of Co-MV. In addition, it was also found that Co-MV patients with highly restrictive respiratory mechanics and obese patients must be performed with extra care.

    CONCLUSION: This approach allows clinicians to analyse patient matching in a virtual environment without patient risk. The approach is tested in simulation, but the results justify the necessary clinical validation in human trials.

  2. Wong JW, Chiew YS, Desaive T, Chase JG
    IFAC Pap OnLine, 2021;54(15):121-126.
    PMID: 38620762 DOI: 10.1016/j.ifacol.2021.10.242
    Surges of COVID-19 infections could lead to insufficient supply of mechanical ventilators, and rationing of needed care. Multiplexing mechanical ventilators (co-MV) to serve multiple patients is a potential temporary solution. However, if patients are ventilated in parallel ventilation, there is currently no means to match ventilation requirements or patients, with no guidelines to date for co-MV. This research uses patient-specific clinically validated respiratory mechanics models to propose a method for patient matching and mechanical ventilator settings for two-patient co-MV under pressure control mode. The proposed method can simulate and estimate the resultant tidal volume of different combinations of co-ventilated patients. With both patients fulfilling the specified constraint under similar ventilation settings, the actual mechanical ventilator settings for co-MV are determined. This method allows clinicians to analyze in silico co-MV before clinical implementation.
  3. Chase JG, Chiew YS, Lambermont B, Morimont P, Shaw GM, Desaive T
    Crit Care, 2020 05 14;24(1):222.
    PMID: 32410701 DOI: 10.1186/s13054-020-02945-z
  4. Chase JG, Chiew YS, Lambermont B, Morimont P, Shaw GM, Desaive T
    Crit Care, 2020 07 10;24(1):415.
    PMID: 32650807 DOI: 10.1186/s13054-020-03152-6
  5. Chiew YS, Pretty CG, Shaw GM, Chiew YW, Lambermont B, Desaive T, et al.
    PMID: 28435689 DOI: 10.1186/s40814-015-0006-2
    BACKGROUND: Selecting positive end-expiratory pressure (PEEP) during mechanical ventilation is important, as it can influence disease progression and outcome of acute respiratory distress syndrome (ARDS) patients. However, there are no well-established methods for optimizing PEEP selection due to the heterogeneity of ARDS. This research investigates the viability of titrating PEEP to minimum elastance for mechanically ventilated ARDS patients.

    METHODS: Ten mechanically ventilated ARDS patients from the Christchurch Hospital Intensive Care Unit were included in this study. Each patient underwent a stepwise PEEP recruitment manoeuvre. Airway pressure and flow data were recorded using a pneumotachometer. Patient-specific respiratory elastance (Ers ) and dynamic functional residual capacity (dFRC) at each PEEP level were calculated and compared. Optimal PEEP for each patient was identified by finding the minima of the PEEP-Ers profile.

    RESULTS: Median Ers and dFRC over all patients and PEEP values were 32.2 cmH2O/l [interquartile range (IQR) 25.0-45.9] and 0.42 l [IQR 0.11-0.87]. These wide ranges reflect patient heterogeneity and variable response to PEEP. The level of PEEP associated with minimum Ers corresponds to a high change of functional residual capacity, representing the balance between recruitment and minimizing the risk of overdistension.

    CONCLUSIONS: Monitoring patient-specific Ers can provide clinical insight to patient-specific condition and response to PEEP settings. The level of PEEP associated with minimum-Ers can be identified for each patient using a stepwise PEEP recruitment manoeuvre. This 'minimum elastance PEEP' may represent a patient-specific optimal setting during mechanical ventilation.

    TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12611001179921.

  6. Chiew YS, Tan CP, Chase JG, Chiew YW, Desaive T, Ralib AM, et al.
    Comput Methods Programs Biomed, 2018 Apr;157:217-224.
    PMID: 29477430 DOI: 10.1016/j.cmpb.2018.02.007
    BACKGROUND AND OBJECTIVE: Respiratory mechanics estimation can be used to guide mechanical ventilation (MV) but is severely compromised when asynchronous breathing occurs. In addition, asynchrony during MV is often not monitored and little is known about the impact or magnitude of asynchronous breathing towards recovery. Thus, it is important to monitor and quantify asynchronous breathing over every breath in an automated fashion, enabling the ability to overcome the limitations of model-based respiratory mechanics estimation during asynchronous breathing ventilation.

    METHODS: An iterative airway pressure reconstruction (IPR) method is used to reconstruct asynchronous airway pressure waveforms to better match passive breathing airway waveforms using a single compartment model. The reconstructed pressure enables estimation of respiratory mechanics of airway pressure waveform essentially free from asynchrony. Reconstruction enables real-time breath-to-breath monitoring and quantification of the magnitude of the asynchrony (MAsyn).

    RESULTS AND DISCUSSION: Over 100,000 breathing cycles from MV patients with known asynchronous breathing were analyzed. The IPR was able to reconstruct different types of asynchronous breathing. The resulting respiratory mechanics estimated using pressure reconstruction were more consistent with smaller interquartile range (IQR) compared to respiratory mechanics estimated using asynchronous pressure. Comparing reconstructed pressure with asynchronous pressure waveforms quantifies the magnitude of asynchronous breathing, which has a median value MAsyn for the entire dataset of 3.8%.

    CONCLUSION: The iterative pressure reconstruction method is capable of identifying asynchronous breaths and improving respiratory mechanics estimation consistency compared to conventional model-based methods. It provides an opportunity to automate real-time quantification of asynchronous breathing frequency and magnitude that was previously limited to invasively method only.

  7. Lee JWW, Chiew YS, Wang X, Mat Nor MB, Chase JG, Desaive T
    Biomed Eng Online, 2022 Feb 11;21(1):13.
    PMID: 35148759 DOI: 10.1186/s12938-022-00981-0
    BACKGROUND AND OBJECTIVE: Mechanical ventilation (MV) is the primary form of care for respiratory failure patients. MV settings are based on general clinical guidelines, intuition, and experience. This approach is not patient-specific and patients may thus experience suboptimal, potentially harmful MV care. This study presents the Stochastic integrated VENT (SiVENT) protocol which combines model-based approaches of the VENT protocol from previous works, with stochastic modelling to take the variation of patient respiratory elastance over time into consideration.

    METHODS: A stochastic model of Ers is integrated into the VENT protocol from previous works to develop the SiVENT protocol, to account for both intra- and inter-patient variability. A cohort of 20 virtual MV patients based on retrospective patient data are used to validate the performance of this method for volume-controlled (VC) ventilation. A performance evaluation was conducted where the SiVENT and VENT protocols were implemented in 1080 instances each to compare the two protocols and evaluate the difference in reduction of possible MV settings achieved by each.

    RESULTS: From an initial number of 189,000 possible MV setting combinations, the VENT protocol reduced this number to a median of 10,612, achieving a reduction of 94.4% across the cohort. With the integration of the stochastic model component, the SiVENT protocol reduced this number from 189,000 to a median of 9329, achieving a reduction of 95.1% across the cohort. The SiVENT protocol reduces the number of possible combinations provided to the user by more than 1000 combinations as compared to the VENT protocol.

    CONCLUSIONS: Adding a stochastic model component into a model-based approach to selecting MV settings improves the ability of a decision support system to recommend patient-specific MV settings. It specifically considers inter- and intra-patient variability in respiratory elastance and eliminates potentially harmful settings based on clinically recommended pressure thresholds. Clinical input and local protocols can further reduce the number of safe setting combinations. The results for the SiVENT protocol justify further investigation of its prediction accuracy and clinical validation trials.

  8. Damanhuri NS, Chiew YS, Othman NA, Docherty PD, Pretty CG, Shaw GM, et al.
    Comput Methods Programs Biomed, 2016 Jul;130:175-85.
    PMID: 27208532 DOI: 10.1016/j.cmpb.2016.03.025
    BACKGROUND: Respiratory system modelling can aid clinical decision making during mechanical ventilation (MV) in intensive care. However, spontaneous breathing (SB) efforts can produce entrained "M-wave" airway pressure waveforms that inhibit identification of accurate values for respiratory system elastance and airway resistance. A pressure wave reconstruction method is proposed to accurately identify respiratory mechanics, assess the level of SB effort, and quantify the incidence of SB effort without uncommon measuring devices or interruption to care.

    METHODS: Data from 275 breaths aggregated from all mechanically ventilated patients at Christchurch Hospital were used in this study. The breath specific respiratory elastance is calculated using a time-varying elastance model. A pressure reconstruction method is proposed to reconstruct pressure waves identified as being affected by SB effort. The area under the curve of the time-varying respiratory elastance (AUC Edrs) are calculated and compared, where unreconstructed waves yield lower AUC Edrs. The difference between the reconstructed and unreconstructed pressure is denoted as a surrogate measure of SB effort.

    RESULTS: The pressure reconstruction method yielded a median AUC Edrs of 19.21 [IQR: 16.30-22.47]cmH2Os/l. In contrast, the median AUC Edrs for unreconstructed M-wave data was 20.41 [IQR: 16.68-22.81]cmH2Os/l. The pressure reconstruction method had the least variability in AUC Edrs assessed by the robust coefficient of variation (RCV)=0.04 versus 0.05 for unreconstructed data. Each patient exhibited different levels of SB effort, independent from MV setting, indicating the need for non-invasive, real time assessment of SB effort.

    CONCLUSION: A simple reconstruction method enables more consistent real-time estimation of the true, underlying respiratory system mechanics of a SB patient and provides the surrogate of SB effort, which may be clinically useful for clinicians in determining optimal ventilator settings to improve patient care.

  9. Kim KT, Morton S, Howe S, Chiew YS, Knopp JL, Docherty P, et al.
    Trials, 2020 Feb 01;21(1):130.
    PMID: 32007099 DOI: 10.1186/s13063-019-4035-7
    BACKGROUND: Positive end-expiratory pressure (PEEP) at minimum respiratory elastance during mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) may improve patient care and outcome. The Clinical utilisation of respiratory elastance (CURE) trial is a two-arm, randomised controlled trial (RCT) investigating the performance of PEEP selected at an objective, model-based minimal respiratory system elastance in patients with ARDS.

    METHODS AND DESIGN: The CURE RCT compares two groups of patients requiring invasive MV with a partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio ≤ 200; one criterion of the Berlin consensus definition of moderate (≤ 200) or severe (≤ 100) ARDS. All patients are ventilated using pressure controlled (bi-level) ventilation with tidal volume = 6-8 ml/kg. Patients randomised to the control group will have PEEP selected per standard practice (SPV). Patients randomised to the intervention will have PEEP selected based on a minimal elastance using a model-based computerised method. The CURE RCT is a single-centre trial in the intensive care unit (ICU) of Christchurch hospital, New Zealand, with a target sample size of 320 patients over a maximum of 3 years. The primary outcome is the area under the curve (AUC) ratio of arterial blood oxygenation to the fraction of inspired oxygen over time. Secondary outcomes include length of time of MV, ventilator-free days (VFD) up to 28 days, ICU and hospital length of stay, AUC of oxygen saturation (SpO2)/FiO2 during MV, number of desaturation events (SpO2 

  10. Chase JG, Preiser JC, Dickson JL, Pironet A, Chiew YS, Pretty CG, et al.
    Biomed Eng Online, 2018 Feb 20;17(1):24.
    PMID: 29463246 DOI: 10.1186/s12938-018-0455-y
    Critical care, like many healthcare areas, is under a dual assault from significantly increasing demographic and economic pressures. Intensive care unit (ICU) patients are highly variable in response to treatment, and increasingly aging populations mean ICUs are under increasing demand and their cohorts are increasingly ill. Equally, patient expectations are growing, while the economic ability to deliver care to all is declining. Better, more productive care is thus the big challenge. One means to that end is personalised care designed to manage the significant inter- and intra-patient variability that makes the ICU patient difficult. Thus, moving from current "one size fits all" protocolised care to adaptive, model-based "one method fits all" personalised care could deliver the required step change in the quality, and simultaneously the productivity and cost, of care. Computer models of human physiology are a unique tool to personalise care, as they can couple clinical data with mathematical methods to create subject-specific models and virtual patients to design new, personalised and more optimal protocols, as well as to guide care in real-time. They rely on identifying time varying patient-specific parameters in the model that capture inter- and intra-patient variability, the difference between patients and the evolution of patient condition. Properly validated, virtual patients represent the real patients, and can be used in silico to test different protocols or interventions, or in real-time to guide care. Hence, the underlying models and methods create the foundation for next generation care, as well as a tool for safely and rapidly developing personalised treatment protocols over large virtual cohorts using virtual trials. This review examines the models and methods used to create virtual patients. Specifically, it presents the models types and structures used and the data required. It then covers how to validate the resulting virtual patients and trials, and how these virtual trials can help design and optimise clinical trial. Links between these models and higher order, more complex physiome models are also discussed. In each section, it explores the progress reported up to date, especially on core ICU therapies in glycemic, circulatory and mechanical ventilation management, where high cost and frequency of occurrence provide a significant opportunity for model-based methods to have measurable clinical and economic impact. The outcomes are readily generalised to other areas of medical care.
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