Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model.

BACKGROUND: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. METHODS: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O2 (FiO2) of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. RESULTS: During tidal ventilation, the expiratory lung collapse increased when I:E <1 [mean (standard deviation) lung collapse=15.7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). CONCLUSIONS: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.

A modification of the Bohr method to determine airways deadspace for non-uniform inspired gas tensions.

BACKGROUND: The Bohr method is a technique to determine airways deadspace using a tracer gas such as carbon dioxide or nitrogen. It is based on the assumption that the inspired concentration of the tracer gas is constant throughout inspiration. However, in some lung function measurement techniques where inspired concentration of the tracer gas may be required to vary, or where rapid injection of the tracer gas is made in real time, uniform inspired concentration is difficult or impossible to achieve, which leads to inaccurate estimation of deadspace using the Bohr equation. One such lung function measurement technique is the inspired sinewave technique. OBJECTIVE: In this paper, we proposed a modification of the Bohr method, relaxing the requirement of absolute uniformity of tracer concentration in the inspired breath. METHOD: The new method used integration of flow and concentration. A computer algorithm sought an appropriate value of deadspace to satisfy the mass balance equation for each breath. A modern gas mixing apparatus with rapid mass flow controllers was used to verify the procedure. RESULT: Experiments on a tidally ventilated bench lung showed that the new method estimated dead space within 10% of the actual values whereas the traditional Bohr deadspace gave more than 50% error. CONCLUSION: The new method improved the accuracy of deadspace estimation when the inspired concentration is not uniform. This improvement would lead to more accurate diagnosis and more accurate estimations of other lung parameters such as functional residual capacity and pulmonary blood flow.

Intra-breath arterial oxygen oscillations detected by a fast oxygen sensor in an animal model of acute respiratory distress syndrome.

BACKGROUND: There is considerable interest in oxygen partial pressure (Po2) monitoring in physiology, and in tracking Po2 changes dynamically when it varies rapidly. For example, arterial Po2 ([Formula: see text]) can vary within the respiratory cycle in cyclical atelectasis (CA), where [Formula: see text] is thought to increase and decrease during inspiration and expiration, respectively. A sensor that detects these [Formula: see text] oscillations could become a useful diagnostic tool of CA during acute respiratory distress syndrome (ARDS). METHODS: We developed a fibreoptic Po2 sensor (<200 µm diameter), suitable for human use, that has a fast response time, and can measure Po2 continuously in blood. By altering the inspired fraction of oxygen ([Formula: see text]) from 21 to 100% in four healthy animal models, we determined the linearity of the sensor's signal over a wide range of [Formula: see text] values in vivo. We also hypothesized that the sensor could measure rapid intra-breath [Formula: see text] oscillations in a large animal model of ARDS. RESULTS: In the healthy animal models, [Formula: see text] responses to changes in [Formula: see text] were in agreement with conventional intermittent blood-gas analysis (n=39) for a wide range of [Formula: see text] values, from 10 to 73 kPa. In the animal lavage model of CA, the sensor detected [Formula: see text] oscillations, also at clinically relevant [Formula: see text] levels close to 9 kPa. CONCLUSIONS: We conclude that these fibreoptic [Formula: see text] sensors have the potential to become a diagnostic tool for CA in ARDS.

A flowing liquid test system for assessing the linearity and time-response of rapid fibre optic oxygen partial pressure sensors.

The development of a methodology for testing the time response, linearity and performance characteristics of ultra fast fibre optic oxygen sensors in the liquid phase is presented. Two standard medical paediatric oxygenators are arranged to provide two independent extracorporeal circuits. Flow from either circuit can be diverted over the sensor under test by means of a system of rapid cross-over solenoid valves exposing the sensor to an abrupt change in oxygen partial pressure, P O2. The system is also capable of testing the oxygen sensor responses to changes in temperature, carbon dioxide partial pressure P CO2 and pH in situ. Results are presented for a miniature fibre optic oxygen sensor constructed in-house with a response time ≈ 50 ms and a commercial fibre optic sensor (Ocean Optics Foxy), when tested in flowing saline and stored blood.

Design of a test system for fast time response fibre optic oxygen sensors.

A test system has been developed that can be used to calibrate and determine the time response, linearity and temperature sensitivity of a fibre optic oxygen sensor. The simple system obviates the need for precision gas standards and the requirement to generate a true square wave step response, which is seldom achievable. The sensor is mounted in a small chamber containing air or a known fraction of oxygen. By means of a computer-controlled switch, the absolute pressure within the chamber can be changed rapidly to a new steady state value. The partial pressure of oxygen changes in direct proportion to the absolute pressure, and so the accuracy and linearity and response time of the PO(2) calibration are limited only by those of the absolute pressure sensor. The temperature sensitivity of a commercial sensor and a means of correction are also described.

Periodic breathing induced by arterial oxygen partial pressure oscillations.

The Grodins model of respiratory control (Grodins et al., 1967) describes cardio-respiratory control for a lung with homogeneous gas concentrations. In this study we modify the Grodins model to take account of the inhomogeneities in gas concentration within the lung that are seen in many subjects with respiratory illnesses. This modification has the effect of lowering arterial oxygen partial pressure significantly. We investigate the effect on cardio-respiratory control of this low arterial oxygen signal and find that the governing equations may be reduced to a single delay-differential equation. This reduced model is found to be a good approximation to the full model and gives predictions that are similar to reported clinical data.

The effect of diffusion in the respiratory tree on the alveolar amplitude response technique (AART).

Theoretical data for the alveolar amplitude response technique (AART) (J. Appl. Physiol. 41 (1976) 419-424) for assessing lung function was simulated using a single path lung model. This model takes account of stratified inhomogeneities in gas concentrations within the respiratory tree. The data was inserted into previously published parameter recovery techniques that may be used to estimate dead-space volume, alveolar volume and cardiac output. These parameter recovery techniques are based on much simpler mathematical models that do not allow stratified inhomogeneities in gas concentrations. It was found that: (i) recovered dead-space volume depended significantly on the ventilation pattern and on the distribution of volume within of the conducting airways; (ii) alveolar volume was recovered to a good degree of accuracy; and (iii) the recovered value of cardiac output was highly dependent on both the choice of inert gas and parameter recovery technique.

A tidal ventilation model for oxygenation in respiratory failure.

We develop tidal-ventilation pulmonary gas-exchange equations that allow pulmonary shunt to have different values during expiration and inspiration, in accordance with lung collapse and recruitment during lung dysfunction (Am. J. Respir. Crit. Care Med. 158 (1998) 1636). Their solutions are tested against published animal data from intravascular oxygen tension and saturation sensors. These equations provide one explanation for (i) observed physiological phenomena, such as within-breath fluctuations in arterial oxygen saturation and blood-gas tension; and (ii) conventional (time averaged) blood-gas sample oxygen tensions. We suggest that tidal-ventilation models are needed to describe within-breath fluctuations in arterial oxygen saturation and blood-gas tension in acute respiratory distress syndrome (ARDS) subjects. Both the amplitude of these oxygen saturation and tension fluctuations, and the mean oxygen blood-gas values, are affected by physiological variables such as inspired oxygen concentration, lung volume, and the inspiratory:expiratory (I:E) ratio, as well as by changes in pulmonary shunt during the respiratory cycle.

Variation of venous admixture, SF6 shunt, PaO2, and the PaO2/FIO2 ratio with FIO2.

BACKGROUND: Measures of impairment of oxygenation can be affected by the inspired oxygen fraction. METHODS: We used a mathematical model of an inhomogenous lung to predict the effect of increasing inspired oxygen concentration (FIO2) on: (1) venous admixture (Qva/Qt); (2) arterial oxygen partial pressure (PaO2); (3) the PaO2/FIO2 index of hypoxaemia; and (4) sulphur hexafluoride (SF6) retention (often taken to be true right-to-left shunt). This model predicts whether or not atelectasis will occur. RESULTS: For lungs with regions of low V/Q, increasing the inspired oxygen concentration can cause these regions to collapse. In the absence of atelectasis, the model predicts that Qva/Qt will decrease and arterial oxygen partial pressure increase as FIO2 is increased. However, when atelectasis occurs, Qva/Qt rises to a constant value, whilst PaO2 falls at first, but then begins to rise again, with increasing FIO2. The SF6 retention increased markedly in some cases at high FIO2. CONCLUSIONS: Venous admixture will estimate true right-to-left shunt at high FIO2, even when oxygen consumption is raised. This model can explain the way that the Pa/Fl ratio changes with increasing inspired oxygen concentration.

The effects of ventilation pattern on carbon dioxide transfer in three computer models of the airways.

We investigate the effects on arterial P(CO(2)) and on arterial-end tidal P(CO(2)) difference of six different ventilation patterns of equal tidal volume, and also of various combinations of tidal volume and respiratory rate that maintain a constant alveolar ventilation. We use predictions from three different mathematical models. Models 1 (distributed) and 2 (compartmental) include combined convection and diffusion effects. Model 3 incorporates a single well-mixed alveolar compartment and an anatomical dead-space in which plug flow occurs. We found that: (i) breathing patterns with longer inspiratory times yield lower arterial P(CO(2)); (ii) varying tidal volume and respiratory rate so that alveolar ventilation is kept constant may change both PA(CO(2)) and the PA(CO(2))-PET(CO(2)) difference; (iii) the distributed model predicts higher end-tidal and arterial P(CO(2)) than the compartmental models under similar conditions; and (iv) P(CO(2)) capnograms predicted by the distributed model exhibit longer phase I and steeper phase II than other models.

Modelling inert gas exchange in tissue and mixed-venous blood return to the lungs.

Inert gas exchange in tissue has been almost exclusively modelled by using an ordinary differential equation. The mathematical model that is used to derive this ordinary differential equation assumes that the partial pressure of an inert gas (which is proportional to the content of that gas) is a function only of time. This mathematical model does not allow for spatial variations in inert gas partial pressure. This model is also dependent only on the ratio of blood flow to tissue volume, and so does not take account of the shape of the body compartment or of the density of the capillaries that supply blood to this tissue. The partial pressure of a given inert gas in mixed-venous blood flowing back to the lungs is calculated from this ordinary differential equation. In this study, we write down the partial differential equations that allow for spatial as well as temporal variations in inert gas partial pressure in tissue. We then solve these partial differential equations and compare them to the solution of the ordinary differential equations described above. It is found that the solution of the ordinary differential equation is very different from the solution of the partial differential equation, and so the ordinary differential equation should not be used if an accurate calculation of inert gas transport to tissue is required. Further, the solution of the PDE is dependent on the shape of the body compartment and on the density of the capillaries that supply blood to this tissue. As a result, techniques that are based on the ordinary differential equation to calculate the mixed-venous blood partial pressure may be in error.

A method of reconstruction of clinical gas-analyzer signals corrupted by positive-pressure ventilation.

The use of sidestream infrared and paramagnetic clinical gas analyzers is widespread in anesthesiology and respiratory medicine. For most clinical applications, these instruments are entirely satisfactory. However, their ability to measure breath-by-breath volumetric gas fluxes, as required for measurement of airway dead space, oxygen uptake, and so on, is usually inferior to that of the mass spectrometer, and this is thought to be due, in part, to their slower response times. We describe how volumetric gas analysis with the Datex Ultima analyzer, although reasonably accurate for spontaneous ventilation, gives very inaccurate results in conditions of positive-pressure ventilation. We show that this problem is a property of the gas sampling system rather than the technique of gas analysis itself. We examine the source of this error and describe how cyclic changes in airway pressure result in variations in the flow rate of the gas within the sampling catheter. This results in the phenomenon of "time distortion," and the resultant gas concentration signal becomes a nonlinear time series. This corrupted signal cannot be aligned or integrated with the measured flow signal. We describe a method to correct for this effect. With the use of this method, measurements required for breath-by-breath gas-exchange models can be made easily and reliably in the clinical setting.

Some factors affecting oxygen uptake by red blood cells in the pulmonary capillaries.

In this study we investigate the equations governing the transport of oxygen in pulmonary capillaries. We use a mathematical model consisting of a red blood cell completely surrounded by plasma within a cylindrical pulmonary capillary. This model takes account of convection and diffusion of oxygen through plasma, diffusion of oxygen through the red blood cell, and the reaction between oxygen and haemoglobin molecules. The velocity field within the plasma is calculated by solving the slow flow equations. We investigate the effect on the solution of the governing equations of: (i) mixed-venous blood oxygen partial pressure (the initial conditions); (ii) alveolar gas oxygen partial pressure (the boundary conditions); (iii) neglecting the convection term; and (iv) assuming an instantaneous reaction between the oxygen and haemoglobin molecules. It is found that: (a) equilibrium is reached much more rapidly for high values of mixed-venous blood and alveolar gas oxygen partial pressure; (b) the convection term has a negligible effect on the time taken to reach a prescribed degree of equilibrium; and (c) an instantaneous reaction may be assumed. Explanations are given for each of these results.

A tidal breathing model of the inert gas sinewave technique for inhomogeneous lungs.

The tidal breathing model conservation of mass equations for the sinewave technique have been described for a homogeneous alveolar compartment by Gavaghan and Hahn, 1996 [Gavaghan, D.J., Hahn, C.E.W., 1996. A tidal breathing model of the forced inspired gas sinewave technique. Respir. Physiol. 106, 209-221]. We develop these equations first to a multi-discrete alveolar compartment lung model and then to a lung model with a continuous distribution of volume, ventilation and perfusion. The effect on the output parameters of a multi-compartment model is discussed, and the results are compared to those derived from the conventional continuous-ventilation model. Using the barely soluble gas argon as the tracer gas, an empirical index of alveolar inhomogeneity is presented which uses the end-expired and mixed-expired partial pressures on each breath. This index distinguishes between a narrow unimodal distribution of ventilation-volume, a wide unimodal distribution of ventilation-volume and a bimodal distribution of ventilation-volume. By using Monte Carlo simulations, this index is shown to be stable to experimental error of realistic magnitude.

Laminated microelectrodes: a simple approach to the construction of inexpensive microelectrodes with a variety of geometries.

Designs for reusable microelectrodes, which are easy to assemble and so do not require special technical skills or services for their construction, are presented. Three types of microelectrodes are fabricated by lamination of metal foil, wire, and wire grids, producing microband, microdisk, and a linear array of microdisk geometries. The electrodes themselves do not need to be polished prior to their use but are observed to be slightly recessed from the surrounding insulating surface. Good agreement is observed between experimental steady-state voltammetric results in nonaqueous solutions and the relevant analytical theory for the voltammetric current.

Within-breath arterial PO2 oscillations in an experimental model of acute respiratory distress syndrome.

Tidal ventilation causes within-breath oscillations in alveolar oxygen concentration, with an amplitude which depends on the prevailing ventilator settings. These alveolar oxygen oscillations are transmitted to arterial oxygen tension, PaO2, but with an amplitude which now depends upon the magnitude of venous admixture or true shunt, QS/QT. We investigated the effect of positive end-expiratory pressure (PEEP) on the amplitude of the PaO2 oscillations, using an atelectasis model of shunt. Blood PaO2 was measured on-line with an intravascular PaO2 sensor, which had a 2-4 s response time (10-90%). The magnitude of the time-varying PaO2 oscillation was titrated against applied PEEP while tidal volume, respiratory rate and inspired oxygen concentration were kept constant. The amplitude of the PaO2 oscillation, delta PaO2, and the mean PaO2 value varied with the level of PEEP applied. At zero PEEP, both the amplitude and the mean were at their lowest values. As PEEP was increased to 1.5 kPa, both delta PaO2 and the mean PaO2 increased to a maximum. Thereafter, the mean PaO2 increased but delta PaO2 decreased. Clear oscillations of PaO2 were seen even at the lowest mean PaO2, 9.5 kPa. Conventional respiratory models of venous admixture predict that these PaO2 oscillations will be reduced by the steep part of the oxyhaemoglobin dissociation curve if a constant pulmonary shunt exists throughout the whole respiratory cycle. The facts that the PaO2 oscillations occurred at all mean PaO2 values and that their amplitude increased with increasing PEEP suggest that QS/QT, in the atelectasis model, varies between end-expiration and end-inspiration, having a much lower value during inspiration than during expiration.

Response-time enhancement of a clinical gas analyzer facilitates measurement of breath-by-breath gas exchange.

Tidal ventilation gas-exchange models in respiratory physiology and medicine not only require solution of mass balance equations breath-by-breath but also may require within-breath measurements, which are instantaneous functions of time. This demands a degree of temporal resolution and fidelity of integration of gas flow and concentration signals that cannot be provided by most clinical gas analyzers because of their slow response times. We have characterized the step responses of the Datex Ultima (Datex Instrumentation, Helsinki, Finland) gas analyzer to oxygen, carbon dioxide, and nitrous oxide in terms of a Gompertz four-parameter sigmoidal function. By inversion of this function, we were able to reduce the rise times for all these gases almost fivefold, and, by its application to real on-line respiratory gas signals, it is possible to achieve a performance comparable to the fastest mass spectrometers. With the use of this technique, measurements required for non-steady-state and tidal gas-exchange models can be made easily and reliably in the clinical setting.

The effect of inspired oxygen concentration on the ventilation-perfusion distribution in inhomogeneous lungs.

The coupled conservation of mass equations for oxygen, carbon dioxide and nitrogen are written down for a lung model consisting of two homogeneous alveolar compartments (with different ventilation-perfusion ratios) and a shunt compartment. As inspired oxygen concentration and oxygen consumption are varied, the flux of oxygen, carbon dioxide and nitrogen across the alveolar membrane in each compartment varies. The result of this is that the expired ventilation-perfusion ratio for each compartment becomes a function of inspired oxygen concentration and oxygen consumption as well as parameters such as inspired ventilation and alveolar perfusion. Another result is that the "inspired ventilation-perfusion ratio and the "expired ventilation-perfusion ratio differ significantly, under some conditions, for poorly ventilated lung compartments. As a consequence, we need to distinguish between the "inspired ventilation-perfusion distribution, which is independent of inspired oxygen concentration and oxygen consumption, and the "expired ventilation-perfusion distribution, which we now show to be strongly dependent on inspired oxygen concentration and less dependent oxygen consumption. Since the multiple inert gas elimination technique (MIGET) estimates the "expired ventilation-perfusion distribution, it follows that the distribution recovered by MIGET may be strongly dependent on inspired oxygen concentration.