Mathematical analysis and computer simulation of the respiratorysystem in the newborn infant

A mathematical model of neonatal respiratory control which can be used to simulate the system under different physiological conditions is proposed. The model consists of a continuous plant and a discrete controller. Included in the plant are lungs, body tissue, brain tissue, a cerebrospinal fluid compartment, and central and peripheral receptors. The effect of shunt in the lungs is included in the model, and the lung volume and the dead space are time varying. The controller utilizes outputs from peripheral and central receptors to adjust the depth and rate of breathing, and the effects of prematurity of peripheral receptors are included in the system. Hering-Breuer-type reflexes are embodied in the controller to accomplish respiratory synchronization. The model is examined and its simulation results under test conditions in hypoxia and hypercapnia are presented     

Estimation of chemoreflex loop gain using pseudorandom binary CO2 stimulation

The authors have developed a method for deriving estimates of the chemoreflex control loop gain (LG) from the ventilatory response to inhaled CO₂, modulated between 0% and 5% in the form of a pseudorandom binary sequence. The corresponding changes in alveolar (and thus, arterial) CO₂ result from two components: (1) the direct effect of breath-to-breath changes in inhaled CO₂ and (2) the chemoreflex-mediated changes in ventilation. LG between 0.01 and 0.03 Hz, the frequency range pertinent to periodic breathing, was estimated by computationally delineating the first component from the overall ventilatory response. The method was tested against simulated and experimental data. In both cases, the authors found strong correlations between their predictions and LG magnitude estimates derived by other methods. However, LG phase estimates mere considerably more variable when compared to model predictions based on small-signal analysis. The authors propose that their method, which uses data from a single test procedure lasting <10 min, may be more useful than traditional tests of chemoresponsiveness for the quantitative assessment of respiratory control stability during changes in sleep-wake state     

An adaptive lung ventilation controller

Closed loop control of ventilation is traditionally based on end-tidal or mean expired CO₂. The controlled variables are the respiratory rate RR and the tidal volume V_T. Neither patient size or lung mechanics were considered in previous approaches. Also the modes were not suitable for spontaneously breathing subjects. This report presents a new approach to closed loop controlled ventilation, called adaptive lung ventilation (ALV). ALV is based on a pressure controlled ventilation mode suitable for paralyzed, as well as spontaneously breathing, subjects. The clinician enters a desired gross alveolar ventilation (V_gA' in l/min), and the ALV controller tries to achieve this goal by automatic adjustment of mechanical rate and inspiratory pressure level. The adjustments are based on measurements of the patient's lung mechanics and series dead space. The ALV controller was tested on a physical lung model with adjustable mechanical properties. Three different lung pathologies were simulated on the lung model to test the controller for rise time (T₉₀), overshoot (Y_m), and steady state performance (Δ_max ). The pathologies corresponded to restrictive lung disease (similar to ARDS), a “normal” lung, and obstructive lung disease (such as asthma). Furthermore, feasibility tests were done in 6 patients undergoing surgical procedures in total intravenous anesthesia. In the model studies, the controller responded to step changes between 48 seconds and 81 seconds. It did exhibit an overshoot between 5.5% and 7.9% of the setpoint after the step change. The maximal variation of V _gA' in steady-state was between ±4.4% and ±5.6% of the setpoint value after the step change. In the patient study, the controller maintained the set V_gA' and adapted the breathing pattern to the respiratory mechanics of each individual patient     

A Control System for Long-Term Ventilation of the Lungs

A respirator control system based on a variant process model and optimization of system performance is described. The system attempts to minimize the harmful effects of positive pressure ventilation while meeting the ventilatory requirement of the patient. As alveolar pressure is indicative of respiratory dynamics, it has been used as control parameter. Desired alveolar pressure is derived from a fixed parameter RC lung model while actual alveolar pressure is estimated from the variant lung model which is continuously updated through on-line computation of respiratory mechanical parameters. The controller gain is optimally adjusted so as to minimize error index. The system has been simulated on a digital computer and several representative cases of sudden and gradual parameter variation have been studied. It has been shown that in case of changes in the process, the error quickly damps out to zero.     

A model of the maturation of respiratory control in the newborninfant

A model of automatic neonatal respiratory control has been constructed as an aid in the investigation of a possible maturation in respiratory control loops during the newborn period. The primary objective was to provide a framework for investigating this hypothesis without the need for external stimuli or invasive measurements. Spontaneous sighs provide a physiological disturbance to the respiratory system by transiently altering the levels of the blood gases. The dynamic ventilatory response following such a disturbance was modeled. A change from a highly damped to less damped pattern was found when model parameter values were varied to mimic maturation in the neonatal period. A perturbation model analysis demonstrated the dynamic ventilatory response is most sensitive to factors affecting the gain of the peripheral chemoreflex loop. It is concluded that the model provides valuable insight into the hypothesis that the peripheral chemoreflex matures during the neonatal period and provides a viable method for testing this in the human infant.     

An extended soluble gas exchange model for estimating pulmonaryperfusion. I. Derivation and implementation

A dynamic model for respiratory exchange of blood soluble gas is described. This model includes a general treatment of tidal breathing, an inhomogeneous lung comprising multiple distensible compartments, and nonlinearities due to multiple-gas effects. The motivation for this new model is the continuing interest in estimating pulmonary perfusion from measurements of respiratory soluble gas exchange. Numerical simulation can be employed to investigate the errors that result from simplifications made in the derivations of simpler models used for this purpose. Examples of such simplifications are the assumptions that ventilation is constant and unidirectional, and that multiple soluble gases can be independently modeled. These results can delimit the boundaries within which perfusion estimates can be considered reliable. An example demonstrating the model and its numerical solution is presented.     

The Interaction of FRC and Ventilation on Occlusion Pressure in Conscious Man

Analytical and experimental results relating the interaction of functional residual capacity (FRC) and ventilation (V) on occlusion pressure in conscious man are presented. An analytical model was developed relating the airway pressure measured 100 ms after occlusion (P100) with FRC and V just before occlusion. By relating the change in diaphragmatic force with time during breathing to that during occlusion, it was found that P100 and IFRC could be linearly related. In order to test this model, 16 normal adult subjects with different FRC values (2.0 to 5.6 1) were studied during periods of increasing ventilation. Subjects increased V by rebreathing a mixture of 7% CO2 and 93% 02. Neither AP100/APC02 nor AV/APCO2 could be correlated to FRC since the differences in motoneuron activity in response to hypercapnia were probably greater than the variations in FRC. Linear regression analysis on all 16 subjects demonstrated a significant effect of FRC on the relationships P100 versus V, and AP100/APCO2 versus A V/APCO2. These experimental findings were in close agreement with analytical predictions and suggest that subjects with larger FRC values have a greater ventilation and ventilatory response for the same occlusion pressure and occlusion pressure response, respectively.     

An Optimally Controlled Respirator

An optimally controlled respirator was developed. It has three main features: 1) ventilation is controlled by the patient's metabolic rate from continuously measured C02 output, 2) physiologic dead space approximated as a linear function of tidal volume is used to estimate alveolar ventilation, and 3) respiratory rate is computed to minimize ventilatory work.     

A Theoretical Study of Controlled Ventilation

This paper is a theoretical study of controlled ventilation with a respirator. An electric circuit analog of the respiratory system is used with respiratory parameters of the normal adult. Deleterious effects of positive pressure ventilation are considered and related to the model. The effects considered include peak alveolar pressure and its time of occurrence, work, and average alveolar pressure. Different pressure waveforms are used as the driving source for the respirator model. These waveforms are rectangle, ramp, negative ramp, sine, and exponential.     

Long-term intramuscular electrical activation of the phrenic nerve:efficacy as a ventilatory prosthesis

The efficacy of a system for long-term intramuscular activation of the phrenic nerve as a ventilatory prosthesis was evaluated in seven dogs. Five dogs underwent chronic bilateral intramuscular diaphragm stimulation (IDS) for 61 to 183 days at stimulus parameters selected to evoke at least 120% of the animal's basal ventilation. Two dogs maintained as controls did not undergo chronic stimulation. The ability of IDS to provide long-term ventilation without diaphragm fatigue was evaluated in terms of the ventilatory capacity of IDS, the effects of chronic IDS on diaphragm contractile properties, and the phrenic nerve recruitment properties of chronic IDS electrodes. Hemi-diaphragms with electrodes placed within 2 cm of the phrenic nerve trunk could be completely activated by 25 mA pulses having a 100 μs pulse width. The tidal volume evoked by IDS in this study was 167% (±48 s.d.) of that required for full-time basal ventilation without diaphragm fatigue. Evoked tidal volume increased after 8 to 9 weeks of chronic IDS for stimulus pulse intervals longer than 50 ms. Electrode recruitment properties were stable for both active and passive implanted electrodes. It is concluded from these studies that with properly placed electrodes IDS is capable of providing reliable full-time ventilatory support without fatiguing the diaphragm     

An Adaptive and Predictive Respiratory Motion Model for Image-Guided Interventions: Theory and First Clinical Application

This paper describes a predictive and adaptive single parameter motion model for updating roadmaps to correct for respiratory motion in image-guided interventions. The model can adapt its motion estimates to respond to changes in breathing pattern, such as deep or fast breathing, which normally would result in a decrease in the accuracy of the motion estimates. The adaptation is made possible by interpolating between the motion estimates of multiple submodels, each of which describes the motion of the target organ during cycles of different amplitudes. We describe a predictive technique which can predict the amplitude of a breathing cycle before it has finished. The predicted amplitude is used to interpolate between the motion estimates of the submodels to tune the adaptive model to the current breathing pattern. The proposed technique is validated on affine motion models formed from cardiac magnetic resonance imaging (MRI) datasets acquired from seven volunteers and one patient. The amplitude prediction technique showed errors of 1.9–6.5 mm. The combined predictive and adaptive technique showed 3-D motion prediction errors of 1.0–2.8 mm, which represents an improvement in modelling performance of up to 40% over a standard nonadaptive single parameter motion model. We also applied the combined technique in a clinical setting to test the feasibility of using it for respiratory motion correction of roadmaps in image-guided cardiac catheterisations. In this clinical case we show that 2-D registration errors due to respiratory motion are reduced from 7.7 to 2.8 mm using the proposed technique.      

置换通风条件下室内空气品质研究

通过建立一模型房间,从室内空气温度分布、PPD、悬浮颗粒分布及CO2浓度几方面模拟研究了置换通风条件下室内空气品质。结果显示置换通风条件下的IAQ完全能满足相关规范规定,达到人体对健康的要求。小微粒有很好的跟随性,大微粒在重力作用下下沉到地面,CO2的浓度随高度的增加而增大,呼吸区的空气清新。     

Estimation of Mechanical Parameters in Multicompartment Models Applied to Normal and Obstructed Lungs During Tidal Breathing

A technique is presented which allows quantitative assessment of the use of parallel compartment models for characterizing pulmonary mechanical function during tidal breathing. A model consisting of a conducting airway leading to two parallel parenchymal regions is used. Numerical simulation and sensitivity analysis indicated that a) the compliance of the conducting airway was not significant under the experimental conditions of interest and that b) estimates of the distribution of central and peripheral resistances would not be precise. The techniques were demonstrated using measurements of transpulmonary pressure, flow, and volume changes during tidal breathing obtained from a human subject with normal lungs and a human subject with obstructed lungs. Optimal estimates of the parameters were obtained by minimizing the difference between the model output and experimental data combined from two breathing frequencies. In the estimation procedure, the sum of the peripheral compliances was constrained to equal the independently measured static lung compliance. This constraint was critical for correct evaluation of nonuniform mechanical lung function. From the parameter estimates, the ratio of parenchymal time constants was about five in the subject with normal lungs and 60 in the subject with obstructed lungs. These results suggest that a full study with several normal and obstructed lung subjects is warranted.     

Optimized symbolic dynamics approach for the analysis of the respiratory pattern

Traditional time domain techniques of data analysis are often not sufficient to characterize the complex dynamics of respiration. In this paper, the respiratory pattern variability is analyzed using symbolic dynamics. A group of 20 patients on weaning trials from mechanical ventilation are studied at two different pressure support ventilation levels, in order to obtain respiratory volume signals with different variability. Time series of inspiratory time, expiratory time, breathing duration, fractional inspiratory time, tidal volume and mean inspiratory flow are analyzed. Two different symbol alphabets, with three and four symbols, are considered to characterize the respiratory pattern variability. Assessment of the method is made using the 40 respiratory volume signals classified using clinical criteria into two classes: low variability (LV) or high variability (HV). A discriminant analysis using single indexes from symbolic dynamics has been able to classify the respiratory volume signals with an out-of-sample accuracy of 100%.     

An extended soluble gas exchange model for estimating pulmonaryperfusion. II. Simulation results

The assumptions made in deriving models of soluble gas exchange used for continuous estimation of pulmonary perfusion are critically examined. Comparisons are made between estimation algorithms based on simple and more complex models. The more complex model includes a general treatment of tidal breathing, an inhomogeneous lung comprising multiple distensible compartments, and nonlinearities due to multiple-gas effects. The results show that sensitivity of perfusion estimates to errors inherent in simple linear models. These errors can invalidate the estimates under realistic physiological conditions. Concentration and multiple-gas effects, for example, can cause substantial estimation errors. Large ventilations relative to lung volume can also lead to errors. These simulations can be used to delimit the conditions under which the estimates can be considered reliable. A further set of simulations is used to assess the sensitivity of perfusion estimates to errors in the assumed values of unknown or approximately known model parameters. Inadequate specification of the compartmental structure of the lung (distributions of ventilation/perfusion and ventilation/volume) can cause large estimate errors. Precise estimates of lung tissue volume do not appear to be necessary. These results are important for the practical application of soluble gas methods for pulmonary perfusion determination. In both sets of simulations, it is shown that parameter estimate accuracy must be confirmed independently of goodness-of-fit criteria. Close agreement between predicted and observed end-tidal concentrations does not ensure accurate perfusion estimates.     

新风量和气流组织形式对室内污染物排除效果的影响

提出了一个办公室内的气流场模拟,运用CFD技术对该空间内由于人员呼吸引起的CO2扩散进行数值模拟,考虑了两种不同的通风系统以及不同的新风量,数值模拟的几何形状是三维的,使用k-ε湍流模型进行模拟。结果表明新风量以及空气分布对呼吸区域的空气品质有重要影响。     

Thoracic electrical impedance tomographic measurements during volume controlled ventilation-effects of tidal volume and positive end-expiratory pressure

The aim of the study was to analyze thoracic electrical impedance tomographic (EIT) measurements accomplished under conditions comparable with clinical situations during artificial ventilation. Multiple EIT measurements were performed in pigs in three transverse thoracic planes during the volume controlled mode of mechanical ventilation at various tidal volumes (V(T)) and positive end-expiratory pressures (PEEP). The protocol comprised following ventilatory patterns: 1) V(T)(400, 500, 600, 700 ml) was varied in a random order at various constant PEEP levels and 2) PEEP (2, 5, 8, 11, 14 cm H2O) was randomly modified during ventilation with a constant V(T). The EIT technique was used to generate cross-sectional images of 1) regional lung ventilation and 2) regional shifts in lung volume with PEEP. The quantitative analysis was performed in terms of the tidal amplitude of the impedance change, reflecting the volume of delivered gas at various preset V(T) and the end-expiratory impedance change, revealing the variation of the lung volume at various PEEP levels. The results showed: 1) an increase in the tidal amplitude of the impedance change, proportional to the delivered V(T) at all constant PEEP levels, 2) a rising end-expiratory impedance change, with PEEP reflecting an increase in gas volume, and 3) a PEEP-dependent redistribution of the ventilated gas between the planes. The generated images and the quantitative results indicate the ability of EIT to identify regional changes in V(T) and lung volume during mechanical ventilation.     

Design and control of a demand flow system assuring spontaneous breathing of a patient connected to an HFO ventilator

Lung protective ventilation is intended to minimize the risk of ventilator induced lung injury and currently aimed at preservation of spontaneous breathing during mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is a lung protective ventilation strategy. Commonly used high-frequency oscillatory (HFO) ventilators, SensorMedics 3100, were not designed to tolerate spontaneous breathing. Respiratory efforts in large pediatric and adult patients impose a high workload to the patient and may cause pressure swings that impede ventilator function. A Demand Flow System (DFS) was designed to facilitate spontaneous breathing during HFOV. Using a linear quadratic Gaussian state feedback controller, the DFS alters the inflow of gas into the ventilator circuit, so that it instantaneously compensates for the changes in mean airway pressure (MAP) in the ventilator circuit caused by spontaneous breathing. The undesired swings in MAP are thus eliminated. The DFS significantly reduces the imposed work of breathing and improves ventilator function. In a bench test the performance of the DFS was evaluated using a simulator ASL 5000. With the gas inflow controlled, MAP was returned to its preset value within 115 ms after the beginning of inspiration. The DFS might help to spread the use of HFOV in clinical practice.     

Nonrigid motion modeling of the liver from 3-D undersampled self-gated golden-radial phase encoded MRI

Magnetic resonance imaging (MRI) has been commonly used for guiding and planning image guided interventions since it provides excellent soft tissue visualization of anatomy and allows motion modeling to predict the position of target tissues during the procedure. However, MRI-based motion modeling remains challenging due to the difficulty of acquiring multiple motion-free 3-D respiratory phases with adequate contrast and spatial resolution. Here, we propose a novel retrospective respiratory gating scheme from a 3-D undersampled high-resolution MRI acquisition combined with fast and robust image registrations to model the nonrigid deformation of the liver. The acquisition takes advantage of the recently introduced golden-radial phase encoding (G-RPE) trajectory. G-RPE is self-gated, i.e., the respiratory signal can be derived from the acquired data itself, and allows retrospective reconstructions of multiple respiratory phases at any arbitrary respiratory position. Nonrigid motion modeling is applied to predict the liver deformation of an average breathing cycle. The proposed approach was validated on 10 healthy volunteers. Motion model accuracy was assessed using similarity-, surface-, and landmark-based validation methods, demonstrating precise model predictions with an overall target registration error of TRE = 1.70 ± 0.94 mm which is within the range of the acquired resolution.