Optimization of identifying insulinaemic pharmacokinetic parameters using artificial neural network.

BACKGROUND AND OBJECTIVE: The identification of insulinaemic pharmacokinetic parameters using the least-squares criterion approach is easily influenced by outlying data due to its sensitivity. Furthermore, the least-squares criterion has a tendency to overfit and produce incorrect results. Hence, this research proposes an alternative approach using the artificial neural network (ANN) with two hidden layers to optimize the identifying of insulinaemic pharmacokinetic parameters. The ANN is selected for its ability to avoid overfitting parameters and its faster speed in processing data. METHODS: 18 voluntarily participants were recruited from the Canterbury and Otago region of New Zealand to take part in a Dynamic Insulin Sensitivity and Secretion Test (DISST) clinical trial. A total of 46 DISST data were collected. However, due to ambiguous and inconsistency, 4 data had to be removed. Analysis was done using MATLAB 2020a. RESULTS AND DISCUSSION: Results show that, with 42 gathered dataset, the ANN generates higher gains, ∅P = 20.73 [12.21, 28.57] mU·L·mmol-1·min-1 and ∅D = 60.42 [26.85, 131.38] mU·L·mmol-1 as compared to the linear least square method, ∅P = 19.67 [11.81, 28.02] mU·L·mmol-1 ·min-1 and ∅D = 46.21 [7.25, 116.71] mU·L·mmol-1. The average value of the insulin sensitivity (SI) of ANN is lower with, SI = 16 × 10-4 L·mU-1 ·min-1 than the linear least square, SI = 17 × 10-4 L·mU-1 ·min-1. CONCLUSION: Although the ANN analysis provided a lower SI value, the results were more dependable than the linear least square model because the ANN approach yielded a better model fitting accuracy than the linear least square method with a lower residual error of less than 5%. With the implementation of this ANN architecture, it shows that ANN able to produce minimal error during optimization process particularly when dealing with outlying data. The findings may provide extra information to clinicians, allowing them to gain a better knowledge of the heterogenous aetiology of diabetes and therapeutic intervention options.

Estimating the incidence of spontaneous breathing effort of mechanically ventilated patients using a non-linear auto regressive (NARX) model.

BACKGROUND AND OBJECTIVE: Mechanical ventilation (MV) provides breathing support for acute respiratory distress syndrome (ARDS) patients in the intensive care unit, but is difficult to optimize. Too much, or too little of pressure or volume support can cause further ventilator-induced lung injury, increasing length of MV, cost and mortality. Patient-specific respiratory mechanics can help optimize MV settings. However, model-based estimation of respiratory mechanics is less accurate when patient exhibit un-modeled spontaneous breathing (SB) efforts on top of ventilator support. This study aims to estimate and quantify SB efforts by reconstructing the unaltered passive mechanics airway pressure using NARX model. METHODS: Non-linear autoregressive (NARX) model is used to reconstruct missing airway pressure due to the presence of spontaneous breathing effort in mv patients. Then, the incidence of SB patients is estimated. The study uses a total of 10,000 breathing cycles collected from 10 ARDS patients from IIUM Hospital in Kuantan, Malaysia. In this study, there are 2 different ratios of training and validating methods. Firstly, the initial ratio used is 60:40 which indicates 600 breath cycles for training and remaining 400 breath cycles used for testing. Then, the ratio is varied using 70:30 ratio for training and testing data. RESULTS AND DISCUSSION: The mean residual error between original airway pressure and reconstructed airway pressure is denoted as the magnitude of effort. The median and interquartile range of mean residual error for both ratio are 0.0557 [0.0230 - 0.0874] and 0.0534 [0.0219 - 0.0870] respectively for all patients. The results also show that Patient 2 has the highest percentage of SB incidence and Patient 10 with the lowest percentage of SB incidence which proved that NARX model is able to perform for both higher incidence of SB effort or when there is a lack of SB effort. CONCLUSION: This model is able to produce the SB incidence rate based on 10% threshold. Hence, the proposed NARX model is potentially useful to estimate and identify patient-specific SB effort, which has the potential to further assist clinical decisions and optimize MV settings.

Protocol conception for safe selection of mechanical ventilation settings for respiratory failure Patients.

BACKGROUND AND OBJECTIVE: Mechanical ventilation is the primary form of care provided to respiratory failure patients. Limited guidelines and conflicting results from major clinical trials means selection of mechanical ventilation settings relies heavily on clinician experience and intuition. Determining optimal mechanical ventilation settings is therefore difficult, where non-optimal mechanical ventilation can be deleterious. To overcome these difficulties, this research proposes a model-based method to manage the wide range of possible mechanical ventilation settings, while also considering patient-specific conditions and responses. METHODS: This study shows the design and development of the "VENT" protocol, which integrates the single compartment linear lung model with clinical recommendations from landmark studies, to aid clinical decision-making in selecting mechanical ventilation settings. Using retrospective breath data from a cohort of 24 patients, 3,566 and 2,447 clinically implemented VC and PC settings were extracted respectively. Using this data, a VENT protocol application case study and clinical comparison is performed, and the prediction accuracy of the VENT protocol is validated against actual measured outcomes of pressure and volume. RESULTS: The study shows the VENT protocols' potential use in narrowing an overwhelming number of possible mechanical ventilation setting combinations by up to 99.9%. The comparison with retrospective clinical data showed that only 33% and 45% of clinician settings were approved by the VENT protocol. The unapproved settings were mainly due to exceeding clinical recommended settings. When utilising the single compartment model in the VENT protocol for forecasting peak pressures and tidal volumes, median [IQR] prediction error values of 0.75 [0.31 - 1.83] cmH2O and 0.55 [0.19 - 1.20] mL/kg were obtained. CONCLUSIONS: Comparing the proposed protocol with retrospective clinically implemented settings shows the protocol can prevent harmful mechanical ventilation setting combinations for which clinicians would be otherwise unaware. The VENT protocol warrants a more detailed clinical study to validate its potential usefulness in a clinical setting.

Assessing the Asynchrony Event Based on the Ventilation Mode for Mechanically Ventilated Patients in ICU.

Respiratory system modelling can assist clinicians in making clinical decisions during mechanical ventilation (MV) management in intensive care. However, there are some cases where the MV patients produce asynchronous breathing (asynchrony events) due to the spontaneous breathing (SB) effort even though they are fully sedated. Currently, most of the developed models are only suitable for fully sedated patients, which means they cannot be implemented for patients who produce asynchrony in their breathing. This leads to an incorrect measurement of the actual underlying mechanics in these patients. As a result, there is a need to develop a model that can detect asynchrony in real-time and at the bedside throughout the ventilated days. This paper demonstrates the asynchronous event detection of MV patients in the ICU of a hospital by applying a developed extended time-varying elastance model. Data from 10 mechanically ventilated respiratory failure patients admitted at the International Islamic University Malaysia (IIUM) Hospital were collected. The results showed that the model-based technique precisely detected asynchrony events (AEs) throughout the ventilation days. The patients showed an increase in AEs during the ventilation period within the same ventilation mode. SIMV mode produced much higher asynchrony compared to SPONT mode (p < 0.05). The link between AEs and the lung elastance (AUC Edrs) was also investigated. It was found that when the AEs increased, the AUC Edrs decreased and vice versa based on the results obtained in this research. The information of AEs and AUC Edrs provides the true underlying lung mechanics of the MV patients. Hence, this model-based method is capable of detecting the AEs in fully sedated MV patients and providing information that can potentially guide clinicians in selecting the optimal ventilation mode of MV, allowing for precise monitoring of respiratory mechanics in MV patients.

Stochastic Modelling of Respiratory System Elastance for Mechanically Ventilated Respiratory Failure Patients.

While lung protective mechanical ventilation (MV) guidelines have been developed to avoid ventilator-induced lung injury (VILI), a one-size-fits-all approach cannot benefit every individual patient. Hence, there is significant need for the ability to provide patient-specific MV settings to ensure safety, and optimise patient care. Model-based approaches enable patient-specific care by identifying time-varying patient-specific parameters, such as respiratory elastance, Ers, to capture inter- and intra-patient variability. However, patient-specific parameters evolve with time, as a function of disease progression and patient condition, making predicting their future values crucial for recommending patient-specific MV settings. This study employs stochastic modelling to predict future Ers values using retrospective patient data to develop and validate a model indicating future intra-patient variability of Ers. Cross validation results show stochastic modelling can predict future elastance ranges with 92.59 and 68.56% of predicted values within the 5-95% and the 25-75% range, respectively. This range can be used to ensure patients receive adequate minute ventilation should elastance rise and minimise the risk of VILI should elastance fall. The results show the potential for model-based protocols using stochastic model prediction of future Ers values to provide safe and patient-specific MV. These results warrant further investigation to validate its clinical utility.

Assessing respiratory mechanics using pressure reconstruction method in mechanically ventilated spontaneous breathing patient.

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.

A patient-specific airway branching model for mechanically ventilated patients.

BACKGROUND: Respiratory mechanics models have the potential to guide mechanical ventilation. Airway branching models (ABMs) were developed from classical fluid mechanics models but do not provide accurate models of in vivo behaviour. Hence, the ABM was improved to include patient-specific parameters and better model observed behaviour (ABMps). METHODS: The airway pressure drop of the ABMps was compared with the well-accepted dynostatic algorithm (DSA) in patients diagnosed with acute respiratory distress syndrome (ARDS). A scaling factor (α) was used to equate the area under the pressure curve (AUC) from the ABMps to the AUC of the DSA and was linked to patient state. RESULTS: The ABMps recorded a median α value of 0.58 (IQR: 0.54-0.63; range: 0.45-0.66) for these ARDS patients. Significantly lower α values were found for individuals with chronic obstructive pulmonary disease (P < 0.001). CONCLUSION: The ABMps model allows the estimation of airway pressure drop at each bronchial generation with patient-specific physiological measurements and can be generated from data measured at the bedside. The distribution of patient-specific α values indicates that the overall ABM can be readily improved to better match observed data and capture patient condition.

Expiratory model-based method to monitor ARDS disease state.

INTRODUCTION: Model-based methods can be used to characterise patient-specific condition and response to mechanical ventilation (MV) during treatment for acute respiratory distress syndrome (ARDS). Conventional metrics of respiratory mechanics are based on inspiration only, neglecting data from the expiration cycle. However, it is hypothesised that expiratory data can be used to determine an alternative metric, offering another means to track patient condition and guide positive end expiratory pressure (PEEP) selection. METHODS: Three fully sedated, oleic acid induced ARDS piglets underwent three experimental phases. Phase 1 was a healthy state recruitment manoeuvre. Phase 2 was a progression from a healthy state to an oleic acid induced ARDS state. Phase 3 was an ARDS state recruitment manoeuvre. The expiratory time-constant model parameter was determined for every breathing cycle for each subject. Trends were compared to estimates of lung elastance determined by means of an end-inspiratory pause method and an integral-based method. All experimental procedures, protocols and the use of data in this study were reviewed and approved by the Ethics Committee of the University of Liege Medical Faculty. RESULTS: The overall median absolute percentage fitting error for the expiratory time-constant model across all three phases was less than 10 %; for each subject, indicating the capability of the model to capture the mechanics of breathing during expiration. Provided the respiratory resistance was constant, the model was able to adequately identify trends and fundamental changes in respiratory mechanics. CONCLUSION: Overall, this is a proof of concept study that shows the potential of continuous monitoring of respiratory mechanics in clinical practice. Respiratory system mechanics vary with disease state development and in response to MV settings. Therefore, titrating PEEP to minimal elastance theoretically results in optimal PEEP selection. Trends matched clinical expectation demonstrating robustness and potential for guiding MV therapy. However, further research is required to confirm the use of such real-time methods in actual ARDS patients, both sedated and spontaneously breathing.