阅读说明：本技术 用于监测不与患者的通气肺相互作用的血流的系统和方法 (System and method for monitoring blood flow that does not interact with a patient's ventilated lung ) 是由 詹姆斯·加里 内森·阿尤比 阿伦·弗雷德里克 汉娜·麦格雷戈 于 2019-08-06 设计创作，主要内容包括：用于监测机械通气或自主呼吸的患者的肺部疾病的进展的方法和系统。通过将特定气体输送至患者并监测各种时间尺度内这些气体的释放,系统监测肺部分流的进展。不需要侵入性的手术,并且该系统能够通过对呼吸气体的单独输送和监测来进行操作。(Methods and systems for monitoring the progression of pulmonary disease in mechanically ventilated or spontaneously breathing patients. By delivering specific gases to the patient and monitoring the release of these gases over various time scales, the system monitors the progress of the pulmonary shunt. No invasive surgery is required and the system can be operated with separate delivery and monitoring of the breathing gas.)

1. A system for monitoring blood flow that does not interact with a ventilated lung of a patient, comprising:

a first source of breathing gas;

a second source comprising a blood-soluble metabolic inert gas;

a gas mixer connected to the first and second sources and adapted to deliver a mixture of the breathing gas and the blood-soluble metabolic inert gas to the airway of the patient;

a gas composition sensor adapted to measure the concentration of the blood-soluble metabolic inert gas present in inhaled and exhaled breath in the patient's airway; and

a control unit operatively connected to the gas mixer and the gas composition sensor, the control unit being adapted to:

a) causing the gas blender to deliver a first number of breaths to the patient, a breath of the first number of breaths comprising the breathing gas and an amount of the blood-soluble metabolic inert gas;

b) determining an end tidal concentration value of the blood soluble metabolic inert gas in exhaled breath of the patient based on measurements from the gas composition sensor during delivery of the first number of breaths to the patient;

c) repeating b) until at least one of: i) at least two consecutive end tidal concentration values of the blood soluble metabolic inert gas in exhaled breath of the patient are substantially equal after a) a predetermined duration has elapsed, or ii);

d) after c), causing the gas blender to deliver a second number of breaths to the patient, the breaths in the second number of breaths not comprising the blood-soluble metabolic inert gas; and

e) determining an end tidal concentration value of the blood soluble metabolic inert gas in exhaled breath of the patient based on measurements from the gas composition sensor during delivery of the second number of breaths to the patient.

2. The system of claim 1, wherein the control unit is further adapted to: estimating a relative composition of blood flow that does not interact with the patient's ventilated lung based on the change in end tidal concentration values in the first number of breaths, or the change in end tidal concentration values in the second number of breaths, or the change in end tidal concentration values in the first and second numbers of breaths.

3. The system of claim 1 or 2, further comprising an airway circuit adapted to be connected to the airway of the patient.

4. The system of any of claims 1-3, wherein the first source of breathing gas is a mechanical ventilator.

5. The system of any one of claims 1 to 4, further comprising a source of oxygen operatively connected to the gas blender, wherein the control unit is further adapted to cause the gas blender to inject oxygen into any information delivered to the patient when a proportion of oxygen in the information delivered to the patient and measured by the gas composition sensor is below a predetermined threshold.

6. The system according to any one of claims 1 to 5, wherein the blood-soluble metabolically inert gas is nitrous oxide.

7. The system according to any one of claims 1 to 6, wherein in a first mode of operation, the control unit sets the first number of breaths such that a combined duration of the first number of breaths is less than an average time of blood recirculation in the patient's lungs.

8. The system according to any one of claims 1 to 7, wherein in a second mode of operation, the control unit sets the first number of breaths such that the duration of the first number of breaths exceeds the mean time for blood recirculation in the patient's lungs.

9. The system of claim 8, wherein the delivery of the first number of breaths continues until measurements from the gas composition sensor indicate a stable end tidal concentration value of the blood-soluble metabolic inert gas in the exhaled breath of the patient.

10. The system of any one of claims 1 to 9, wherein the gas composition sensor comprises:

a first portion comprising a set of optical elements adapted to enable infrared light to illuminate through the patient's airway; and

a second portion comprising an infrared source and an infrared detector, the second portion not intersecting the airway of the patient and connected to the set of optical elements of the first portion by an optical conduit.

11. The system of claim 10, wherein the optical conduit is a flexible optical conduit.

12. The system of any one of claims 1 to 11, wherein the infrared source and the infrared detector are positioned proximate the airway of the patient, the gas composition sensor further comprising a reflective element positioned within a light path defined between the infrared source and the infrared detector.

13. A method for monitoring blood flow that does not interact with a ventilated lung of a patient, comprising:

a) delivering a first number of breaths to the patient, a breath of the first number of breaths comprising a breathing gas and an amount of a blood-soluble metabolic inert gas;

b) determining an end tidal concentration value of the blood soluble metabolic inert gas in exhaled breath of the patient during delivery of the first number of breaths to the patient;

c) repeating b) until at least one of: i) at least two consecutive end tidal concentration values of the blood soluble metabolic inert gas in exhaled breath of the patient are substantially equal after a) a predetermined duration has elapsed, or ii);

d) after c), delivering a second number of breaths to the patient, wherein a breath in the second number of breaths does not include the blood-soluble metabolic inert gas; and

e) determining an end tidal concentration value of the blood soluble metabolic inert gas in exhaled breath of the patient during delivery of the second number of breaths to the patient.

14. The method of claim 13, wherein controlling delivery of a number of breaths to the patient further comprises: controlling the content of the blood-soluble metabolically inert gas in each successive breath delivered to the patient in view of keeping the concentration of the blood-soluble metabolically inert gas constant within the alveolar cavity of the patient.

15. The method of claim 13, wherein controlling delivery of a number of breaths to the patient further comprises: maintaining a constant concentration of the blood-soluble metabolic inert gas in each breath delivered to the patient.

16. The method of any of claims 13 to 15, further comprising: estimating a relative composition of blood flow that does not interact with the patient's ventilated lung based on the change in end tidal concentration values in the first number of breaths, or the change in end tidal concentration values in the second number of breaths, or the change in end tidal concentration values in the first and second numbers of breaths.

Technical Field

The present disclosure relates to the field of respiratory care. More particularly, the present disclosure relates to systems and methods for detecting and monitoring blood flow that does not interact with a patient's ventilated lungs.

Background

Acute Respiratory Distress Syndrome (ARDS) is a rapidly progressing condition in which the lungs exchange gas less efficiently. This perfusion decline is known as "pulmonary shunting," and this injury allows more blood to be "shunted" through the lungs and reduces the absorption of oxygen and other gases in the patient's bloodstream. Due to this shunting, some pulmonary blood flow cannot exchange gas with the ventilation air inhaled by the patient.

Due to pulmonary shunting, no gas exchange may occur between some of the patient's blood flow and some of the ventilated alveoli. The dead space thus created in turn reflects the waste of respiratory effort by spontaneously breathing patients, or the waste of respiratory assistance to patients receiving mechanical ventilation.

Current methods for detecting and monitoring diseases such as ARDS rely on invasive or time consuming methods such as sampling the patient's blood or exposure to chest X-ray imaging. Such an approach is undesirable in various clinical settings. The time and risks associated with such blood sampling and imaging methods are undesirable. Methods that can detect and monitor the progression of the disease in a non-invasive manner are desirable.

Accordingly, there is a need for improved techniques for detecting and monitoring pulmonary blood flow.

Disclosure of Invention

In accordance with the present disclosure, a system for monitoring blood flow that does not interact with a ventilated lung of a patient is provided. The system comprises: a first source of breathing gas; a second source comprising a blood-soluble metabolic inert gas; a gas mixer connected to the first and second sources and adapted to deliver a mixture of breathing gas and blood-soluble metabolic inert gas to the airway of the patient; a gas composition sensor adapted to measure the concentration of blood-soluble metabolic inert gases present in inhaled and exhaled breath in the airways of a patient; and a control unit. The control unit is operatively connected to the gas mixer and the gas composition sensor. The control unit is adapted to: a) causing the gas blender to deliver a first number of breaths to the patient, a breath in the first number of breaths comprising a breathing gas and an amount of a blood-soluble metabolic inert gas; b) determining an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient based on measurements from the gas composition sensor during delivery of the first number of breaths to the patient; c) repeating b) until at least one of: i) at least two consecutive end tidal concentration values of blood soluble metabolic inert gas in the exhaled breath of the patient are substantially equal, or ii) a predetermined duration of time has elapsed after a); d) after c), causing the gas blender to deliver a second number of breaths to the patient, the breaths in the second number of breaths not comprising blood soluble metabolic inert gases; and e) during the second number of breaths delivered to the patient, determining an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient based on the measurements from the gas composition sensor.

In some implementations of the technology, the control unit is further adapted to: estimating a relative composition of blood flow that does not interact with the ventilated lung of the patient based on the change in end tidal concentration values in the first number of breaths, or the change in end tidal concentration values in the second number of breaths, or the change in end tidal concentration values in the first and second numbers of breaths.

In some implementations of the present technology, the system further includes an airway circuit adapted to be connected to an airway of a patient.

In some implementations of the present technology, the first source of breathing gas is a mechanical ventilator.

In some implementations of the present technology, the system further includes a source of oxygen operatively connected to the gas blender, the control unit further adapted to cause the gas blender to inject oxygen into any of the information delivered to the patient when a proportion of oxygen in the information delivered to the patient and measured by the gas composition sensor is below a predetermined threshold.

In some implementations of the technology, the blood-soluble metabolic inert gas is nitrous oxide.

In some implementations of the technology, in the first mode of operation, the control unit sets the first number of breaths such that a combined duration of the first number of breaths is less than an average time of blood recirculation in the lungs of the patient.

In some implementations of the technology, in the second mode of operation, the control unit sets the first number of breaths such that a duration of the first number of breaths exceeds an average time of blood recirculation in the lungs of the patient.

In some implementations of the present technology, the delivery of the first number of breaths continues until the measurements from the gas composition sensor indicate a stable end tidal concentration value of blood soluble metabolic inert gases in the exhaled breath of the patient.

In some implementations of the present technology, a gas composition sensor includes: a first portion comprising a set of optical elements adapted to enable infrared light to illuminate an airway of a patient; and a second portion comprising an infrared source and an infrared detector, the second portion not intersecting the airway of the patient and connected to the set of optical elements of the first portion by an optical conduit.

In some implementations of the present technology, the optical conduit is a flexible optical conduit.

In some implementations of the present technology, the infrared source and the infrared detector are positioned proximate to an airway of the patient, and the gas composition sensor further includes a reflective element positioned within a light path defined between the infrared source and the infrared detector.

In accordance with the present disclosure, a method for monitoring blood flow that does not interact with a ventilated lung of a patient is also provided. The method comprises the following steps: a) causing a first number of breaths to be delivered to the patient, a breath of the first number of breaths comprising a breathing gas and an amount of a blood-soluble metabolic inert gas; b) determining an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient during delivery of the first number of breaths to the patient; c) repeating b) until at least one of: i) at least two consecutive end tidal concentration values of blood soluble metabolic inert gas in the exhaled breath of the patient are substantially equal, or ii) a predetermined duration of time has elapsed after a); d) after c), causing a second number of breaths to be delivered to the patient, the breaths in the second number of breaths not comprising a blood-soluble metabolic inert gas; and e) during the second number of breaths delivered to the patient, determining an end tidal concentration value of blood soluble metabolic inert gas in the exhaled breath of the patient.

In some implementations of the present technology, controlling delivery of a number of breaths to a patient further comprises: the amount of blood-soluble metabolic inert gas delivered to the patient in each successive breath is controlled in view of keeping the concentration of blood-soluble metabolic inert gas constant within the alveolar space of the patient.

In some implementations of the present technology, controlling delivery of a number of breaths to a patient further comprises: the concentration of the blood-soluble metabolic inert gas in each breath delivered to the patient is kept constant.

In some implementations of the technology, the method further includes: estimating a relative composition of blood flow that does not interact with the ventilated lung of the patient based on the change in end tidal concentration values in the first number of breaths, or the change in end tidal concentration values in the second number of breaths, or the change in end tidal concentration values in the first and second numbers of breaths.

The foregoing and other features will become more apparent upon reading of the following non-limiting description of illustrative embodiments thereof, given by way of example only with reference to the accompanying drawings.

Drawings

Embodiments of the present disclosure will now be described, by way of example only, with reference to the accompanying drawings, in which:

FIG. 1 shows an idealized diagram of the human cardiopulmonary system illustrating the effective role of pulmonary bypass;

FIG. 2a is a graph showing the arterial blood content of noble gas as a function of time;

FIG. 2b is a graph showing the end moisture content of the inert gas as a function of time;

FIG. 3 is a schematic diagram of a system implementing a gas control and sensing modality, according to an embodiment;

FIG. 4a shows a cross-sectional view of a gas composition sensor including an airway cell and a sensing cell;

FIG. 4b illustrates the optical path within the gas composition sensor of FIG. 4 a;

FIG. 5a shows an alternative cross-sectional view of a gas composition sensor, illustrating how various components may be located away from or near the gas composition sensor.

FIG. 5b illustrates the optical path within the gas composition sensor of FIG. 5 a;

FIG. 6a shows a cross-sectional side view of a gas composition sensor including an airway cell and a sensing cell according to another embodiment;

FIG. 6b is a cross-sectional elevation view of the gas composition sensor of FIG. 6 a;

FIG. 6c is a transparent perspective view of the gas composition sensor of FIG. 6 a; and

fig. 7 is a sequence diagram illustrating the operation of a method for monitoring blood flow that does not interact with a ventilated lung of a patient.

Detailed Description

Various aspects of the present disclosure generally address one or more problems associated with the detection and monitoring of pulmonary blood flow, particularly where some pulmonary blood flow is not in gas exchange with ventilation air inhaled by a patient.

In general, the present disclosure introduces methods and systems for determining impaired gas exchange in the lungs of a human patient. The disclosed technique enables the determination of the tendency of pulmonary shunts through gas absorption, excretion and recirculation.

In one aspect, the system is designed for mechanically ventilated patients. The system may also be used for spontaneously breathing patients. The system provides information about the efficiency of the lungs as a gas exchange organ and addresses in particular, but not by way of limitation, the progression of diseases such as Acute Respiratory Distress Syndrome (ARDS).

In another aspect, the disclosed system provides a controlled volume of inspired gas to a patient and monitors the concentration of these gases in the patient's inspired and expired breath. Sensitive measurement of these gases creates a mechanism for inferring the perfusion characteristics of the lungs, thereby enabling measurement of how much blood flow is not involved in gas exchange.

Fig. 1 shows an idealized diagram of the human cardiopulmonary system illustrating the effective role of pulmonary bypass. Allowing the patient to inhale component F with gas having a certain solubility₁And tidal volume V_TFunctional Reserve Capacity (FRC) V_FRCAnd (4) ventilating. The alveolar space (alveolarspace) has a volume defined as the sum of tidal volume and functional residual capacity. At the end of expiration, the alveolar space has an average offset F_EWhich is reflected in the end-tidal components of breath. Consider the mass balance of two breaths in which an inhaled gaseous agent is able to exchange gas with the pulmonary blood flow for a duration t that is proportional to the duration of inhalation. Change of end tidal value Δ F of continuous breath under uniform inhalation content_EThere are two sources: variation of gas content composition of FRC, or of effective pulmonary blood flow Q_EPGas exchange of (2). For the blood-soluble gases described in this disclosure, these two terms are in equation [1 ]]The method comprises the following steps:

if mixed intravenous concentrationIs constant or, in the absence of inert (non-metabolic) and non-toxic gases, there are numerous methods which make it possible to use mixtures of inhaled gases with particularly low and particularly high solubility values to obtain an effective pulmonary non-split blood flow Q_EPThe value of (c). Such single-breath, rebreathing and perturbation methods are known in the art and will not be described further.

There is currently no known non-invasive method to reveal the diverted blood flow Q_S. Shunting and efficient pulmonary blood flow Q_EPEqual to cardiac output Q_TCardiac output is the total blood flow that circulates inspired gas around the systemic vasculature and back to the lungs. Thus, the mixed venous blood has a "memory" of the early content of the FRC and acts as a lossy delay line in response to the stimuli caused by respiration.

The present disclosure introduces two stimulation models by which ventilation of a patient may be modified and monitored.

In a first stimulation model, a short series of breaths enriched in gas having significant solubility in blood (e.g., less than five breaths) are provided to the patient. For example, nitrous oxide with an Ostwald (Ostwald) coefficient of 0.47 is a good nominal candidate for the present disclosure. The gas is selected based on its ability to readily diffuse through the alveolar membrane. In most cases, the selected gas is composed of relatively small molecules. The level of available pulmonary blood flow is affected by this stimulus, with V_FRC/V_tThe characteristic time scale of the change in the ratio of (a) to (b) serves as a low pass filter for the ventilation-generated stimulus. The blood entering the systemic circulation is a "split" flow Q without gas exchange_SAnd "split" flow that undergoes gas exchange in the lungs.

The effect of recirculation in this first stimulation model was to alter the mixed venous blood content provided to the lungsIf it is at that momentThe pre-FRC has a static composition, and this change in blood content causes a change in end-tidal gas content. The magnitude of the change in turn reflects the pulmonary shunt component, f_S＝Q_S/Q。

In a second stimulation model, a longer series of breaths enriched in gases with significant solubility in blood are provided to the patient. This gas-rich breath lasts for a period of time longer than the average recirculation time of the patient's systemic vasculature. In this second stimulation model, the end-tidal composition of exhaled breath is recorded. Equation [1 ] in the recirculation of gas-enriched blood]Thereby reducing the affinity of available pulmonary blood for inhaled blood soluble gases. This extent of absorption in turn reflects the pulmonary shunt fraction f_S. Also contemplated is a situation wherein the series of breaths is selected such that its duration is substantially equal to the average recirculation time of the patient's systemic vasculature.

In the present disclosure, it is assumed that the transport of gas-enriched blood through the vasculature and organs of the body can be viewed as a process that changes a negligible amount (if any) within the time scale associated with the stimulation provided to the patient via the patient's breath. Without loss of generality, the end-tidal exhaled breath content may be correlated with an earlier concentration history of soluble gases in the mixed venous blood entering the lungs at the pulmonary arteriesAnd (4) correlating.

The correlation between the previous history of mixed venous blood content and inspired gas content is considered as the transfer function. A plausible function that meets this criterion is a delayed spectral function, such as a low-pass filter, that delays and attenuates the signal present in the arterial component. Equation [2] applies to some function X describing the dispersion in a given patient caused by gas bolus dissolved into the systemic vasculature:

where C is the typical concentration of the hemolyzed physiologically inert gas in the body at time t.

When the blood that shunts "through" the lungs is returned to the lungs, it is not different from the blood provided to the ventilated alveoli of the lungs. The dissolved agent is chosen such that it readily diffuses across the alveolar membrane and, thus, the partial pressure of blood perfusing the ventilated alveoli is in equilibrium with the gas in these alveoli.

The system is operated according to a second stimulation model, and the end tidal exhalation component is used to monitor the relationship that combines capillary end partial pressure with end tidal mass. This relationship is compounded by the assumption in equation [2] that the transfer function f is constant over the duration of the challenge applied and the link between capillary end content and arterial content, where q is unknown, but is expected to change if the patient's ARDS severity changes.

In both cases, the change in end-tidal concentration provides a measure of the degree of pulmonary bypass, whether by absorption into the systemic blood during or elimination from the systemic blood after a series of gas-rich breaths. This causal relationship depends first on the end tidal gas content being an accurate reflection of the alveolar air space (alveolarair airspace). A responsive sensor may be used to detect the portion of exhalation. Another support for this relationship stems from the association between the time series of mixed venous blood and the composition of the alveolar air space.

Fig. 2a is a graph showing the arterial blood content of noble gas as a function of time. Fig. 2b is a graph showing the end moisture content of the inert gas as a function of time. Fig. 2a and 2b are based on a detailed physiological model of adult pigs, which is intended to be used to study these relationships under various stimulation scenarios. The graphs in fig. 2a and 2b show that the arterial blood and the expiration of pigs contain a non-bioinert gas, in this case nitrous oxide (N)₂O) -a model-derived response of multiple breath. The model predicts the effect of increased pulmonary shunt components on arterial and end-tidal composition in patients who are ventilated with multiple breaths using biologically inert but hemolyzed gases.

In the absence of pulmonary bypass (baseline, f)_s0), the gas content in the expired breath decreases during these breaths, indicating that the gas is readily absorbed by the systemic blood. In summary, the graphs in fig. 2a and 2b show a large split component or high f_SHow this occurs results in a change in the amount of gas absorbed into the blood during several breaths of stimulation and also changes the elimination of blood soluble gases after stimulation.

Specifically, fig. 2a and 2b show:

a) elevated shunt composition reduces the reoccurrence of gas in the alveolar space upon the first recirculation of systemic blood flow; and

b) the increased shunt component results in slower elimination of gas from the body due to the reduced end-tidal gas content of the inert gas long after stimulation ceases. When the end-tidal concentration of the inert gas becomes stable, a stable breathing state of the patient is achieved.

Fig. 3 is a schematic diagram of a system implementing a gas control and sensing modality, according to an embodiment. This System is an evolution Of commonly owned international application No. PCT/CA2018/050957, filed on 6.8.2018, entitled "Method And System For Estimating The Efficiency Of The Lung Of application", The entire disclosure Of which is incorporated herein by reference. The mechanical ventilator 20 delivers a life-sustaining flow of gas to the patient through a conventional airway circuit 22. The control unit 24 arranges for multiple breaths to be inhaled with a particular concentration of gas from a gas source, such as a canister 26. These gases are mixed in a gas mixer 28 and the resulting mixed stream passes through a heat and moisture exchange device 30. The control unit 24 is configured to ensure that the oxygen concentration in the inhaled breath is acceptable from a clinical care point of view. The composition of the mixed stream is recorded by a gas composition sensor 32. The method implemented in the control unit 24 performs an analysis, the results of which may be presented to the operator via a display unit 34, which may be comprised in the control unit 24. Alternatively, the display unit 34 may be adjacent to or remote from the control unit 24 in an electronically connected manner or via a wireless connection.

More than one canister 26 is shown in fig. 3, as the addition of non-metabolic gases dilutes the inhaled air and may lead to oxygen starvation. Thus, in one embodiment, one of the tanks 26 may hold oxygen. One of the other gases having the desired solubility in human blood, denoted as "X" in fig. 3, may be selected. These gases are sensed by gas composition sensor 32 so that the concentration profile of these gases throughout the patient's breathing can be measured. One or more of these soluble gases may not be of biological origin in the patient's body and therefore are not functional in the metabolism of the patient, such gases being said to be physiologically inert. The gas composition sensor 32 may use non-dispersive infrared spectroscopy to infer the gas concentration within the breath.

The system of fig. 3 may be used to monitor blood flow that does not interact with the patient's ventilated lungs, for example, in situations where the patient has shunted pulmonary blood flow. In this system, the mechanical ventilator 20 is the first source of breathing gas. One of the tanks 26 is a second source containing a blood-soluble metabolic inert gas. A gas mixer 28 connected to the first and second sources delivers a mixture of breathing gas and blood-soluble metabolic inert gas to the airway of the patient. The gas composition sensor 32 measures the composition of blood-soluble metabolic inert gases present in inhaled and exhaled breath in the patient's airway. The control unit 24 performs the following operations:

a) causing the gas blender 28 to deliver a first number of breaths to the patient, the breaths in the first number of breaths comprising a breathing gas and an amount of blood-soluble metabolic inert gas;

b) determining an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient based on measurements from gas composition sensor 32 during delivery of the first number of breaths to the patient;

c) repeating b) until at least one of: i) at least two consecutive end tidal concentration values of blood soluble metabolic inert gas in the exhaled breath of the patient are substantially equal, or ii) a predetermined duration of time has elapsed after a);

d) after c), causing the gas blender 28 to deliver a second number of breaths to the patient, the breaths in the second number of breaths not comprising blood soluble metabolic inert gases; and

e) during the second number of breaths delivered to the patient, an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient is determined based on the measurements from gas composition sensor 32.

The control unit 24 may also perform many other functions. For example, and without limitation, the control unit 24 may estimate the relative composition of the blood flow that does not interact with the patient's ventilated lungs based on the change in end tidal concentration values in the first number of breaths, or the change in end tidal concentration values in the second number of breaths, or the change in end tidal concentration values in the first number of breaths and the second number of breaths. The control unit 24 may also cause the gas blender 28 to inject oxygen into any information delivered to the patient when the proportion of oxygen in the information delivered to the patient and measured by the gas composition sensor 32 is below a predetermined threshold. The control unit 24 may also set the first number of breaths depending on whether the first or second operation mode is selected such that the combined duration of the first number of breaths is less than or greater than the mean time for blood recirculation in the lungs of the patient. In the second mode of operation, the control unit 24 may also control the delivery of the first number of breaths to continue until the measurements from the gas composition sensor 32 indicate a stable end tidal concentration value of blood soluble metabolic inert gas in the patient's exhaled breath. Various combinations of these features may be implemented in various embodiments of the system.

Fig. 4a shows a cross-sectional view of a gas composition sensor comprising an airway cell and a sensing cell. FIG. 4b shows an optical path within the gas component sensor of FIG. 4 a. Fig. 4a and 4b are not drawn to scale. The dimensions shown in fig. 4b are for illustrative purposes and do not limit the disclosure. In fig. 4b, the direction of the light path is indicated by using arrows. The gas composition sensor 32 of fig. 4a and 4b is one possible embodiment of the gas composition sensor 32 introduced in the description of fig. 3. Referring to fig. 4a, a flow of breathing gas 9 travels through airway shell portion 8 to the patient and from the patient through airway shell portion 8. The sensing portion 3 is assembled on the airway housing portion 8 by using a physical slider and latch 7. The sensing portion 3 is provided with a pair of thin windows 6, the thin windows 6 being substantially transparent to infrared light, for example having a wavelength in the range of about 4.0 to 4.7 microns. Other wavelength ranges may be considered depending on the actual type of hemolyzing inert gas used. The light guide (e.g., optical fiber 1) carries infrared radiation to a set of optics, which may include one or more refractive elements (e.g., lens 4) and at least one reflective element (e.g., mirror 5). The infrared radiation passes through a window 10 fixed to the sensing part 3. After passing through a further window 6 fixed to the airway housing portion 8, the light passes through the flow of breathing gas 9 and the infrared radiation passes through a further pair of windows, further optics and illuminates a second light guide, for example a further optical fibre 1.

Alternative embodiments using the same sensing modality are also contemplated, wherein one or both of the light source and the sensor are mounted in the airway housing portion 8 and electrically connected to the control unit 24 (fig. 3). An alternative cross-sectional view of the gas composition sensor is shown in FIG. 5a, which illustrates an example of this alternative embodiment, showing how various components may be located away from or close to the gas composition sensor, where FIG. 5b shows the optical path within the gas composition sensor of FIG. 5 a. Fig. 5a and 5b are not drawn to scale. In fig. 5a, the infrared detector remains in the control unit 24. The infrared source 11 is located in a gas composition sensor 32 on the flow of breathing gas 9, powered via a flexible cable 12 leading from the control unit 24. The waveform generator 16 and the amplifier 15 are connected to the infrared source 11 via a cable 12. In an embodiment, the infrared sensor 13 is located in the isothermal housing 14 and thus temperature variations, physical shocks and mechanical damages are avoided. The infrared sensor 13 may include a plurality of filters (not shown) that enable sensing of light of a plurality of specific wavelength ranges.

In this alternative embodiment, the infrared detector 13 remains in the control unit 24, where it can be kept in an isothermal and vibration-shielded state. In such an embodiment, the infrared source 11 is present in a portion that fits around the airway portion. Fig. 5b highlights the light paths indicated by using arrows within the embodiment of fig. 5 a.

Fig. 6a shows a cross-sectional side view of a gas composition sensor including an airway cell and a sensing cell according to another embodiment. FIG. 6b is a cross-sectional elevation view of the gas composition sensor of FIG. 6 a. Fig. 6c is a transparent perspective view of the gas component sensor of fig. 6 a. Fig. 6a, 6b and 6c are not drawn to scale. In the embodiment of fig. 6a, 6b, and 6c, gas composition sensor 32 includes a sensor housing 42 that holds active optical components and an airway housing 50 through which a flow of breathing gas 54 flows. The latch arrangement 62 attaches the sensor housing 42 and the airway housing 50. The wires 40 are connected to a collimated infrared source 58 and an infrared sensor 56, both located within the sensor housing 42. Sensor housing 42 also includes a pair of mirrors 46 positioned at an angle in front of infrared light source 58 and infrared sensor 56 for directing light to and from windows 48 and 52. Lens 44 enables light from infrared source 58 to be focused onto first mirror 46. The window 48 and the window 52 enable light to pass between the sensor housing 42 and the airway housing 50.

In fig. 6b and 6c, the direction of the light path is indicated by using arrows. Light emitted by infrared source 58 and deflected by a first one of mirrors 46 passes through window 48 and window 52 and through the entire width of airway housing 50 before reaching mirror 60. The light is then reflected by mirror 60 in substantially opposite directions toward window 52 and window 48 and reaches the second of mirrors 46, deflecting toward infrared sensor 56. The configuration of fig. 6a, 6b and 6c including mirror 60 increases the optical path length between infrared source 58 and infrared sensor 56. The majority of this extended light path actually passes through airway shell 50 twice, and thus light is exposed to respiratory airflow 54 twice. This configuration enables the infrared beam to re-turn on itself, doubling the path length traveled by the light through the airway shell 50, as compared to the embodiments of fig. 4a and 5 a. This longer path length supports a lower minimum detectable concentration of the various gases present in airway housing 50 for a given infrared sensor and infrared source. It is also contemplated that multiple reflective elements may be used at multiple locations within airway shell 50 to enable further increases in path length.

Regardless of the actual configuration of the gas composition sensor 32, having a suitable set of optical windows in the infrared sensor 13 enables rapid measurement of the gas concentration in the breathing air from the patient, these measurements being obtained for a time less than the duration of the patient's inspiratory or expiratory phase. In one particular feature of the ventilation technique, the rate of absorption of the blood-soluble, physiologically inert gas by the patient's blood is influenced by the flow rate of the un-shunted pulmonary blood stream. By monitoring the rate at which such noble gases are drawn into the patient's bloodstream in response to changes in the delivered gas content, a number of cardiopulmonary qualities can be derived, as expressed in the above-mentioned international application No. PCT/CA 2018/050957. In another particular feature of the present ventilation technique, the rate at which such a physiologically inert gas is eliminated from the patient after absorption of the gas is affected by the relative magnitude of the shunted pulmonary blood flow with respect to cardiac output, which in the event of an increase in shunted pulmonary blood flow, is slowed.

Fig. 7 is a sequence diagram illustrating the operation of a method for monitoring blood flow that does not interact with a ventilated lung of a patient. In fig. 7, the sequence 100 includes a plurality of operations, some of which may be performed in a variable order, some of which may be performed concurrently, and some of which may be optional. The sequence 100 begins at operation 110 where a first number of breaths are delivered to a patient at operation 110. The breath of the first number of breaths comprises a breathing gas and an amount of a blood-soluble metabolic inert gas. Operation 110 may optionally include one of sub-operation 112 or sub-operation 114. In sub-operation 112, the content of the blood-soluble metabolic inert gas in each successive breath delivered to the patient is controlled in view of keeping the concentration of the blood-soluble metabolic inert gas constant within the alveolar cavity of the patient. Alternatively, in sub-operation 114, control of the delivery of a number of breaths to the patient is performed by maintaining a constant concentration of the blood-soluble metabolic inert gas in each breath delivered to the patient. Other ways of controlling the content of the blood-soluble metabolic inert gas in each successive breath delivered to the patient are also contemplated, and thus the examples of sub-operations 112 and 114 are not intended to limit the present disclosure.

At operation 120, an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient is determined while the delivery of the first number of breaths to the patient is ongoing. In other words, operation 120 may be performed simultaneously with operation 110. The end tidal concentration value of the blood soluble metabolic inert gas may be determined once at a faster rate or at a slower rate during each expiratory phase of the patient.

Operation 130 verifies whether a predetermined duration has elapsed since operation 110. If the predetermined duration has elapsed, the sequence 100 continues to operation 150. If the predetermined duration has not elapsed, the process 100 continues to operation 140 where a determination is made as to whether at least two consecutive end tidal concentration values of blood soluble metabolic inert gas in the exhaled breath of the patient are substantially equal at operation 140. If at least two consecutive end tidal concentration values are substantially equal, the sequence 100 continues to operation 150. If at least two consecutive end tidal concentration values are not substantially equal, the sequence 100 returns to operation 120. If operation 140 continues with a negative result in successive cycles of sequence 100, operation 130 will eventually determine that the predetermined duration has elapsed. Thus, operation 150 will eventually be reached.

At operation 150, a second number of breaths is delivered to the patient. In this operation, breath of the second number of breaths does not contain blood soluble metabolic inert gases. In the context of the present disclosure, trace amounts of blood-soluble metabolic inert gases may remain in the breath of the second number of breaths, especially if gas mixer 28 does not have perfect insulating properties. The skilled reader will readily recognize that the intent of operation 150 is to not retain clinically significant amounts of blood-soluble metabolic inert gases in these breaths.

At operation 160, an end tidal concentration value of blood soluble metabolic inert gas in exhaled breath of the patient is determined during delivery of the second number of breaths to the patient. Operation 150 and operation 160 may be performed simultaneously.

The end-tidal concentration value changes determined at operation 120 and/or operation 160 may be used to estimate the relative composition of blood flow that does not interact with the ventilated lungs of the patient.

Those of ordinary skill in the art will recognize that the description of the systems and methods for monitoring blood flow that does not interact with the ventilated lungs of a patient is illustrative only and is not intended to be limiting in any way. Other embodiments will readily suggest themselves to such skilled persons having the benefit of this disclosure. Furthermore, the disclosed systems and methods can be customized to provide a valuable solution to existing needs and problems associated with the detection and monitoring of pulmonary blood flow. In the interest of clarity, not all of the routine features of the implementations of the systems and methods are shown and described. In particular, combinations of features are not limited to those presented in the foregoing description, as combinations of elements listed in the appended claims form part of the disclosure. It will, of course, be appreciated that in the development of any such actual implementation of the systems and methods, numerous implementation-specific decisions may be made to achieve the developers' specific goals, such as compliance with application-related, system-related, and business-related constraints, which will vary from one implementation to another and from one developer to another. Moreover, it will be appreciated that a development effort might be complex and time-consuming, but would nevertheless be a routine undertaking of engineering for those of ordinary skill in the respiratory care art having the benefit of this disclosure.

In accordance with the present disclosure, the control unit 24 described herein may be implemented using various types of operating systems, computing platforms, network devices, computer programs, and/or general purpose machines. Further, those of ordinary skill in the art will recognize that less general purpose devices, such as hardwired devices, Field Programmable Gate Arrays (FPGAs), Application Specific Integrated Circuits (ASICs), or the like, may also be used. Where a method comprising a series of operations is implemented by a control unit 24, a processor or a machine operatively connected to a memory, the operations may be stored as a series of instructions readable by the machine, processor or computer, and may be stored on a non-transitory tangible medium.

The disclosure has been described in the foregoing specification by way of non-limiting illustrative embodiments provided by way of example. The illustrative embodiments may be modified arbitrarily. The scope of the claims should not be limited by the embodiments set forth in the examples, but should be given the broadest interpretation consistent with the description as a whole.