Estimation of mixed venous oxygen saturation

Abstract

The present disclosure relates to a method for continuously and non-invasively estimating mixed venous blood saturation (SvO2) in a mechanically ventilated subject (3). The method comprises the following steps: measuring the exhaled carbon dioxide (CO2) content of exhaled gas exhaled by the subject; measuring the exhaled flow and volume of the exhaled gas exhaled by the subject; estimating the cardiac output (CO) or effective pulmonary blood flow (EPBF) of the subject based on the measured exhaled CO2 content and the measured exhaled flow or volume using the capnokinetic Fick method; and estimating SvO2 based on the estimated CO or EPBF of the subject.

Description

Technical Field

[0001] The present disclosure relates to methods, computer programs, and systems for continuously and non-invasively estimating mixed venous oxygen saturation (SvO2) in mechanically ventilated subjects. Background Art

[0002] Providing adequate oxygen delivery to ensure satisfactory tissue oxygenation is a central task during mechanical ventilation of critically ill patients. Since cardiac output (CO) is one of the main determinants of oxygen delivery, major efforts have been devoted to developing clinically useful techniques to assess this parameter in mechanically ventilated patients. Many techniques for CO assessment are associated with various limitations, and even if clinicians are able to obtain reliable CO values, it is still not easy to determine whether these values ​​are adequate, insufficient, or excessive. In order to better judge this, CO values ​​need to be interpreted in conjunction with some other factors such as tabulated normal values ​​or plasma lactate levels.

[0003] Instead, a more intuitive way to understand and interpret whole body tissue oxygenation is to monitor mixed venous oxygen saturation (SvO2). SvO2 is the percentage of oxygen in the blood returning to the right side of the heart that is bound to hemoglobin. This reflects the amount of oxygen that remains in the blood after oxygen required by body tissues has been removed. Therefore, changes in SvO2 reflect changes in the balance between oxygen delivery and oxygen demand by tissues.

[0004] Currently, SvO2 is measured invasively by placing a catheter in the patient's pulmonary artery for obtaining a mixed venous blood sample, a practice associated with a questionable risk-benefit relationship, as pulmonary artery catheters (PACs), also known as Swan-Ganz catheters, are associated with significant morbidity and sometimes even mortality. Another disadvantage associated with PACs is that they only allow intermittent analysis of SvO2.

[0005] Central venous oxygen saturation (ScvO2) is sometimes used as a substitute for SvO2. ScvO2 measurements can be obtained through a central venous catheter (CVC) (e.g., an internal jugular or subclavian catheter), which is less invasive than a PAC. Another advantage of using ScvO2 instead of SvO2 is the existence of CVCs equipped with optical fibers that enable continuous monitoring of ScvO2. In clinical practice, it is often assumed that ScvO2 has the same physiological meaning as SvO2, an assumption that is sometimes incorrect because ScvO2 does not always reflect the patient's true mixed venous oxygen saturation, SvO2.

[0006] A non-invasive or at least less invasive method of monitoring true SvO2 would represent a substantial advance in more advanced critical care and hemodynamic monitoring during major surgery in mechanically ventilated patients. Summary of the invention

[0007] It is an object of the present disclosure to provide an improved or at least alternative way of determining mixed venous blood saturation (SvO2) in mechanically ventilated subjects.

[0008] It is another object of the present disclosure to provide a method for determining SvO2 that obviates or at least mitigates one or more of the above-mentioned problems associated with the prior art.

[0009] In particular, it is an object of the present disclosure to provide a method for continuously and non-invasively determining SvO2 which can be easily applied at the bedside of mechanically ventilated subjects.

[0010] According to one aspect, these and other objects are achieved by a method for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject, the method comprising the following steps:

[0011] - measuring the exhaled carbon dioxide (CO2) content in the exhaled breath of the subject;

[0012] - measuring the expiratory flow or volume of exhaled gas exhaled by the subject;

[0013] - using the capnokinetic Fick method to estimate the subject's cardiac output (CO) or effective pulmonary blood flow (EPBF) based on the measured expiratory CO2 content and the measured expiratory flow or volume, and

[0014] - Estimate SvO2 based on the estimated CO or EPBF of the subject.

[0015] By using the non-invasive capnokinetic Fick method to determine the CO or EPBF of a ventilated subject and estimating SvO2 from the CO or EPBF values ​​thus obtained, a "capnokinetic SvO2" derived from mathematical modeling of expired CO2 dynamics can be obtained without the use of an invasive pulmonary artery catheter or central venous catheter. Thus, the method provides a non-invasive or at least minimally invasive way of estimating SvO2.

[0016] Another advantage of the proposed method is that the capnokinetic SvO2 can be estimated continuously (ie, on a breath-by-breath basis) since the capnokinetic Fick method for determining CO or EPBF allows determining CO or EPBF of a ventilated subject on a breath-by-breath basis.

[0017] According to one aspect, the method includes estimating the subject's EPBF based on measured expiratory CO2 content and measured expiratory flow or volume using a capnokinetic Fick method, and estimating SvO2 based on the estimated EPBF.

[0018] Using EPBF instead of CO in the estimation of SvO2 is advantageous because EPBF is related to the end capillary oxygen content (CcO2), which can be estimated from the end capillary oxygen partial pressure (PcO2) of the lung from the known fraction of inspired oxygen (FiO2) and the alveolar gas equation. On the other hand, estimating SvO2 based on CO requires determining the arterial oxygen content (CaO2) of the ventilated subject, which in turn requires estimating the arterial oxygen saturation (SaO2) and the arterial oxygen partial pressure (PaO2).

[0019] The method may also include the steps of estimating the oxygen consumption (VO2) of the ventilated subject based on the volume of CO2 eliminated by the subject through breathing (VCO2) and the respiratory quotient (RQ), and estimating SvO2 based on the estimated VO2 of the subject. VCO2 may be determined based on expiratory CO2 content and expiratory flow or volume measurements. RQ may be an assumed value that may be selected, for example, based on the age, sex, weight, and nutrition of the ventilated subject.

[0020] Introducing RQ into a mathematical model of exhaled CO2 dynamics makes it possible to estimate VO2 from RQ and VCO2, which in turn makes it possible to calculate SvO2 from the Fick equation for oxygen balance in the lungs. VCO2 can be determined, for example, from measured exhaled CO2 content and measured exhaled flow or volume using volumetric capnography. Thus, in some embodiments, the SvO2 of a ventilated subject can be estimated from the estimated CO or EPBF using the calculated VO2 of the subject and the oxygen Fick equation.

[0021] When estimating SvO2 based on an estimated EPBF of the subject, the proposed principles allow calculating SvO2 from an algorithm comprising a quotient between VCO2 and EPBF, which is advantageous because the method becomes relatively robust to errors in the determination of VCO2. This is due to the fact that an error in VCO2 will also introduce an error in the EPBF determination, which will be largely offset when the SvO2 estimation is based on the quotient between VCO2 and EPBF.

[0022] The method may further include the steps of substituting the estimated CO or EPBF and the estimated VO2 of the subject into a Fick equation for deriving oxygen in blood, in which a variable related to the oxygen content per volume unit (CvO2) in mixed venous blood is expressed as the oxygen partial pressure in mixed venous blood (PvO2) and SvO2, and estimating SvO2 by solving the equation for SvO2 thus obtained. These operations allow SvO2 to be estimated from the measured expiratory CO2 content and flow (or volume) in a computationally friendly manner, while bringing the advantages mentioned above.

[0023] For example, SvO2 can be estimated based on the following relationship.

[0024]

[0025] ScO2 is the oxygen saturation of the pulmonary terminal capillaries (fraction), VCO2 is the CO2 elimination (mL min -1 ), C H is the Hüfner constant (mL·g -1 ), Hb is the hemoglobin content in the blood (g·L -1 ), EPBF is effective pulmonary blood flow (L·min -1 ), RQ is the respiratory quotient, α is the solubility constant of O2 in plasma (mL·L -1 kPa -1 ), PcO2 is the terminal pulmonary capillary oxygen partial pressure (kPa), and PvO2 is the mixed venous oxygen partial pressure (kPa).

[0026] To facilitate the use of the capnodynamic Fick method to estimate the CO or EPBF of a ventilated subject, the method may further include the steps of ventilating the subject during the analyzed breathing sequence using a ventilation pattern that includes at least one increase ventilation phase and at least one decrease ventilation phase to introduce a change in the CO2 level exhaled by the subject that can be measured and used to estimate CO or EPBF. As will be described in more detail below. The method may further include the steps of estimating the CO or EPBF of the subject based on the exhaled CO2 content and the exhaled flow or volume measurements obtained during the analyzed breathing sequence using the capnodynamic Fick method, and estimating the subject's SvO2 based on the estimated CO or EPBF of the subject.

[0027] For example, the method may employ the carbon dioxide dynamics Fick method for CO or EPBF estimation, the method comprising the following steps:

[0028] - for a plurality of breaths in the analyzed breathing sequence, determining a fraction (F) of alveolar CO2 corresponding to the subject based on expiratory CO2 content measurements and expiratory flow or volume measurements obtained during the analyzed breathing sequence; A CO2), a first parameter related to the CO2 content of the subject's arterial blood (CaCO2) or the CO2 content of the subject's terminal capillary blood (CcCO2), and a third parameter related to the subject's VCO2, and

[0029] - estimating the CO or EPBF of the subject based on a correlation between the first parameter, the second parameter and the third parameter in the analyzed breathing sequence.

[0030] The above method is typically a computer-implemented method performed by executing a computer program running on a computer system. Therefore, according to another aspect of the present disclosure, a computer program is provided for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject through a system. The system includes a gas analyzer, a flow or volume sensor, and a computer, wherein the gas analyzer is used to measure the exhaled CO2 content in the exhaled gas exhaled by the subject, and the flow or volume sensor is used to measure the exhaled flow or volume of the exhaled gas exhaled by the subject. The computer program includes computer-readable instructions, which, when executed by the computer, cause the system to perform the above method.

[0031] The computer program may include computer readable instructions for estimating SvO2 of a ventilated subject according to any of the principles described above. The computer program may be stored in a non-transitory computer readable storage medium of a computer system, for example, in the above-mentioned computer for running the computer program.

[0032] According to another aspect of the present disclosure, a system configured to perform the above-described method for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject is provided.

[0033] According to one aspect, the system includes a gas analyzer for measuring the exhaled CO2 content in exhaled gas exhaled by the subject, a flow or volume sensor for measuring the exhaled flow or volume of the exhaled gas exhaled by the subject, and a computer. The computer is configured to estimate the subject's CO or EPBF based on the measured exhaled CO2 content and the measured exhaled flow or volume using the carbon dioxide dynamics Fick method, and estimate SvO2 based on the estimated CO or EPBF of the subject.

[0034] The computer may advantageously be configured to estimate the subject's EPBF from the measured expiratory CO2 content and the measured expiratory flow or volume using the capnokinetic Fick method, and to estimate SvO2 based on the estimated EPBF.

[0035] The computer may also be configured to estimate VO2 based on VCO2 and RQ, and to estimate SvO2 based on the estimated VO2.

[0036] The computer may also be configured to estimate SvO2 based on a quotient between VCO2 and EPBF.

[0037] The computer may also be configured to substitute the subject's estimated CO or estimated EPBF and estimated VO2 into a Fick equation for deriving oxygen in the blood, in which variables related to CvO2 are expressed by PvO2 and SvO2, and estimate SvO2 by solving the equation for SvO2 thus obtained.

[0038] In one example, the computer may be configured to estimate SvO2 based on the following relationship.

[0039]

[0040] ScO2 is the oxygen saturation of the pulmonary capillaries (fraction), VCO2 is the CO2 elimination (mL min -1 ), C H (mL·g -1 ) is the Hüfner constant, Hb is the hemoglobin content in the blood (g·L -1 ), EPBF is effective pulmonary blood flow (L·min -1 ), RQ is the respiratory quotient, α is the solubility constant of oxygen in plasma (mL·L -1 kPa -1 ), PcO2 is the partial pressure of oxygen in the terminal pulmonary capillaries (kPa), and PvO2 is the mixed venous partial pressure of oxygen (kPa).

[0041] The gas analyser and the flow or volume sensor of the system may form part of a capnograph, and preferably forms part of a capnograph configured for volumetric capnographing.

[0042] The system may be a monitoring system for monitoring hemodynamic parameters (including SvO2) of a ventilated subject.

[0043] The system may include a display for displaying the subject's hemodynamic parameters (including the estimated SvO2) to a clinician.

[0044] The system may also include a respiratory device, such as a ventilator or anesthesia machine, for providing mechanical ventilation to the subject. The computer may or may not be an internal computer of the respiratory device. Likewise, the display for displaying the subject's hemodynamic parameters (including the estimated SvO2) may or may not be a display of the respiratory device.

[0045] The respiratory apparatus may be configured to ventilate the subject using a ventilation pattern that includes at least one increased ventilation phase and at least one decreased ventilation phase during the analyzed breathing sequence, whereby the computer may be configured to estimate the subject's CO or EPBF based on expiratory CO2 content and expiratory flow or volume measurements obtained during the analyzed breathing sequence using the capnokinetic Fick method. For example, the computer may be configured to estimate the subject's CO or EPBF based on the expiratory CO2 content and expiratory flow or volume measurements obtained during the analyzed breathing sequence. A The subject's CO or EPBF is estimated based on a correlation between a first parameter related to CO2, a second parameter related to the subject's CaCO2 or CcCO2, and a third parameter related to the subject's VCO2, which parameters can be derived from expiratory CO2 content and expiratory flow or volume measurements obtained during the analyzed breathing sequence.

[0046] Further advantageous aspects of the proposed method, computer program and system will be described in the detailed description of embodiments below. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Embodiments of the present disclosure will be more fully understood from the detailed description provided below and the accompanying drawings which are given by way of illustration only. In the different drawings, the same reference numerals correspond to the same elements.

[0048] Figure 1 A system for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject according to an exemplary embodiment of the present disclosure is shown.

[0049] Figure 2 A system for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject according to another exemplary embodiment of the present disclosure is shown.

[0050] Figure 3 is a flow chart illustrating a method for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject according to an exemplary embodiment of the present disclosure.

[0051] Figure 4 is a flow chart illustrating a method for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject according to another exemplary embodiment of the present disclosure. DETAILED DESCRIPTION

[0052] Figure 1 A system 1 for continuously and non-invasively estimating mixed venous oxygen saturation (SvO2) in a mechanically ventilated subject 3 (hereinafter referred to as a patient) according to an exemplary and non-limiting embodiment of the present disclosure is shown.

[0053] The system 1 comprises a breathing apparatus 2, such as a ventilator or anesthesia machine, for providing ventilation therapy in the form of mechanical ventilation to a patient. The breathing apparatus 2 is connected to the patient via an inspiratory line 5 for supplying breathing gases to the patient 3 and an expiratory line 7 for conveying expiratory gases away from the patient 3. The inspiratory line 5 and the expiratory line 7 are connected via a so-called Y-piece 11 to a common line 9, which is connected to the patient 3 via a patient connector 13, such as a mask or an endotracheal tube.

[0054] The system 1 also includes a computer 14 configured to estimate the SvO2 of a ventilated patient based on measured expiratory CO2 content and expiratory flow or volume of expiratory gases exhaled by the patient, as will be described in more detail below.

[0055] In the example shown, the computer 14 is an internal computer of the respiratory device 2, which also constitutes a control unit for controlling the ventilation of the patient based on preset parameters and / or measurements obtained by various sensors of the respiratory device. The computer 14 controls the ventilation of the patient by controlling a pneumatic unit 15 of the respiratory device 2, which is connected on the one hand to one or more gas sources 17, 19 and on the other hand to the inspiration line 5 to regulate the flow and / or pressure of the breathing gas delivered to the patient 3. To this end, the pneumatic unit 15 may include various gas mixing devices and gas regulating devices known in the field of ventilation, such as a gas mixing chamber, a controllable gas mixing valve, one or more controllable inspiration valves and / or exhalation valves, etc.

[0056] The computer 14 includes a processor 21 and a computer-readable data storage medium 23 (e.g., a non-transitory hardware memory device) that stores a computer program for estimating SvO2 of a ventilated patient according to the principles described herein. Unless otherwise specified, the actions and method steps described below are performed or caused by the computer 14 when the processor 21 executes different code segments of the computer program stored in the data storage medium 23.

[0057] The system 1 also includes at least one flow or volume sensor 27 for measuring respiratory flow or volume. The respiratory flow or volume measured by the at least one flow or volume sensor includes at least the expiratory flow or volume of the expiratory gas exhaled by the patient. In some embodiments, the respiratory flow or volume measured by the at least one flow or volume sensor may also include the inspiratory flow or volume of the respiratory gas inhaled by the patient.

[0058] System 1 also includes at least one gas analyzer 29, which includes a carbon dioxide (CO2) sensor for measuring respiratory CO2 content. The CO2 content measured by at least one gas analyzer 29 is typically the CO2 content of the respiratory flow or volume measured by at least one flow or volume sensor 27. The measured respiratory CO2 content includes at least the expiratory CO2 content in the expiratory gas exhaled by the patient. In some embodiments, the measured respiratory CO2 content may also include the inspiratory CO2 content inhaled by the patient during inspiration. Such inspiratory CO2 content may be caused by dead zone rebreathing or rebreathing of the expiratory gas after removing most of the CO2 content in the expiratory gas. The respiratory CO2 content can be measured, for example, as a partial pressure, concentration or volume of CO2.

[0059] At least one flow or volume sensor 27 and at least one gas analyzer 29 are operably coupled to the computer 14 so that the computer estimates the SvO2 of the ventilated patient based on the respiratory flow or volume measurements and the respiratory CO2 content measurements.

[0060] In the illustrated embodiment, the flow or volume sensor 27 and the gas analyzer 29 form part of a capnograph 31, which is configured for volume capnograph measurements. The capnograph 31 is arranged near the patient's airway opening. In this example, the capnograph 31 is arranged in the common line 9 of the breathing circuit, wherein the capnograph 31 is exposed to all gases exhaled and inhaled by the patient 3. The capnograph 31 is connected to the computer 14 via a wired or wireless connection 33, and is configured to transmit the results of the flow or volume measurement and the CO2 measurement to the computer 14 for further processing by the processor 21. The computer 14 can be configured to generate a volume capnograph 35 based on the respiratory flow or volume measurement and the respiratory CO2 content measurement received from the capnograph 31, and optionally display the volume capnograph 35 on a display 37 of the system 1, for example, on a display of the respiratory device 2.

[0061] In other alternative embodiments, the flow or volume sensor 27 and the gas analyzer 29 may be located elsewhere in the breathing circuit, i.e., in other locations of the gas flow path that delivers breathing gases to and from the patient. For example, the flow or volume sensor and / or the gas analyzer 29 may be incorporated into the respiratory device 2 and located in an exhalation module of the respiratory device that is connected to the exhalation line 7 for receiving an exhalation flow of exhalation gas exhaled by the patient.

[0062] Computer 14 is configured to estimate the SvO2 of a ventilated patient based on the patient's estimated cardiac output (CO) or estimated effective (non-shunt) pulmonary blood flow (EPBF).

[0063] The patient's CO or EPBF is estimated non-invasively based on respiratory flow or volume measurements and respiratory CO2 content measurements obtained by flow or volume sensor 27 and gas analyzer 29 using a capnodynamic method based on Fick's principle.

[0064] The capnodynamic Fick method for estimating CO or EPBF typically requires that the level of exhaled CO2 changes by at least 0.2%, preferably about 0.5% or more, during the analyzed breathing sequence. To this end, the computer 14 can be configured to control the respiratory device 2 by changing one or more respiratory device settings to introduce a change in the effective ventilation of the patient that causes the desired change in the level of exhaled CO2 during the analyzed breathing sequence. The computer 14 can then estimate the patient's CO or EPBF based on the respiratory flow or volume measurements and the respiratory CO2 content measurements obtained during the analyzed breathing sequence.

[0065] The breathing sequence analyzed may include any number of breaths, but typically includes 4 to 20 breaths, and preferably 4 to 12 breaths. The breathing sequence analyzed includes at least one increase ventilation phase and at least one decrease ventilation phase, wherein each increase ventilation phase and each decrease ventilation phase includes at least one breath, typically at least two breaths, and preferably two to six breaths. The transition from the increase ventilation phase to the decrease ventilation phase (and vice versa) is achieved by an effective ventilation change of the patient 3. The effective ventilation change can be caused by the computer 14 in any manner known in the art, for example, by changing the duration and / or tidal volume of the breaths delivered to the patient by the respiratory apparatus.

[0066] Preferably, in order to determine CO or EPBF continuously (i.e., on a breath-by-breath basis), the computer 14 is configured to cause the respiratory apparatus 2 to ventilate the patient using a cyclic ventilation pattern that includes alternating periods of reduced ventilation and increased ventilation, wherein each period of reduced ventilation is immediately followed by an increased ventilation period, and vice versa. An increased ventilation breath is a breath that more effectively ventilates the patient's lungs than a reduced ventilation breath, and vice versa. Thus, the purpose of varying the effective ventilation of the patient by providing an alternating sequence of increased ventilation breaths and reduced ventilation breaths is to cause a change in the exhaled CO2 level that can be measured and used for the determination of CO or EPBF. Preferably, but not necessarily, the number of breaths in each cycle of the cyclic ventilation pattern corresponds to the number of breaths in the respiratory sequence being analyzed.

[0067] Computer 14 can be configured to estimate CO or EPBF of a ventilated patient according to any known non-invasive capnodynamic Fick method (e.g., according to any method disclosed in WO 2006 / 119546, US7135001, WO 2013 / 141766, EP2799008, WO 2017 / 105304, WO2017 / 192076, WO 2017 / 192077, or the as-yet-unpublished PCT application PCT / SE2018 / 050606).

[0068] In an illustrative and non-limiting example, computer 14 is configured to estimate the patient's CO or EPBF based on respiratory flow or volume measurements and respiratory CO2 content measurements obtained by flow or volume sensor 27 and gas analyzer 29 using the following capnokinetic equation for a single-chamber lung model, which describes the fraction of alveolar carbon dioxide (F A How CO2 changes with breathing:

[0069]

[0070] Where ELV is the effective lung volume (L) including end-tidal CO2, F A CO2 n is the alveolar CO2 fraction, n is the current breath, n-1 is the previous breath, and EPBF is the effective pulmonary blood flow (L·min -1 ), Δt n is the duration of respiration, CvCO2 is the venous CO2 content (L 气体 ·L 血液 -1 ), CcCO2 n is the CO2 content in the terminal pulmonary capillaries (L 气体 ·L 血液 -1 ), and VTCO2 n is the tidal clearance of CO2.

[0071] F A CO2 n can be measured by the gas analyzer 29, and CcCO2 n and VTCO2 can be obtained from F A CO2 n , tidal volume of breathing n(VT n ) and the known dead volume, as is known in the art, leaving EPBF, CvCO2, and ELV as unknown physiological parameters to be determined.

[0072] Formula 1 is similar to Formula 1 in WO 2013 / 141766, which discloses a non-invasive and continuous method for simultaneously determining ELV, cardiac output and CvCO2. The only difference between the equations is that Formula 1 in WO 2013 / 141766 uses the quantities CaCO2 (arterial CO2 content) and cardiac output (expressed as Q), while Formula 1 above uses the quantities CcCO2 and EPBF.

[0073] For example, the computer 14 may be configured to use the method disclosed in WO 2013 / 141766 based on a directly measurable or derivable parameter ΔF in the analyzed respiratory sequence. A CO2(=F A CO2 n -F A CO2 n-1 ), the correlation between CcCO2 and VTCO2, and determining the parameter triple {ELV, EPBF, CvCO2} from the analyzed respiratory sequence. Similarly, the computer 14 can be configured to use the method disclosed in WO 2013 / 141766 based on the directly measurable or derivable parameter ΔF in the analyzed respiratory sequence. A CO2(=F A CO2 n -F A CO2 n-1 ), the correlation between CaCO2 and VTCO2, and determining the parameter triplet {ELV, cardiac output, CvCO2} from the analyzed respiratory sequence. As is known in the art, and as described in more detail in WO 2013 / 141766, CaCO2 can be obtained from the measured F A The CO2 dissociation curve function of CO2 and the solubility of carbon dioxide in arterial blood is obtained.

[0074] Estimating the EPBF using the method disclosed in WO 2013 / 141766 may involve the following mathematical operations.

[0075] Rearranging Equation 1 so that the unknown parameters are gathered on the left-hand side of the equation:

[0076]

[0077] For breaths n = 1, 2, ..., N in the breath sequence being analyzed, write this equation in matrix form:

[0078]

[0079] When the analyzed respiratory sequence N includes more than three breaths (i.e. when N>3), this becomes an overdetermined system of equations, and the unknown parameter triple {ELV, EPBF·CvCO2, EPBF} and thus the physiological parameters ELV, EPBF and CvCO2 can be determined by finding an approximate solution to the overdetermined system of equations. As is known in the art, the approximate solution to the overdetermined system of equations can be calculated in different ways, for example using the least squares method. The solution to the overdetermined system of equations will depend on the parameter ΔF in the cycle of the analyzed respiratory sequence. A Correlation between CO2, CcCO2 and VTCO2.

[0080] The equation system (Equation 3) can be rewritten as A·x A =a, where

[0081]

[0082] For example, the computer 14 may be configured to calculate the error |A·x A -a|minimization to calculate the approximate solution for the parameter triple {ELV,EPBF·CvCO2,EBBF}. Using the least squares method, the solution can be calculated as:

[0083] x A =(A T A) -1 ·A T ·a (Formula 4)

[0084] Thus, the computer 14 can estimate the EPBF (and ELV and CvCO2) of a ventilated patient based on the flow or volume measurements and CO2 measurements obtained for the analyzed breathing sequence, during which the patient was ventilated using a ventilation mode that causes the level of exhaled CO2 to vary during the analyzed breathing sequence. In a similar manner, the computer 14 can estimate the CO (and ELV and CvCO2) of a ventilated patient as described above and disclosed in more detail in WO 2013 / 141766. For continuous estimation of EPBF or CO, the ventilation mode applied to the patient by the respiratory apparatus 2 should preferably be a cyclic ventilation mode, and the above calculations should be performed by the computer 14 on a breath-by-breath basis.

[0085] The computer 14 then uses the thus estimated EPBF or CO of the ventilated patient to estimate SvO2. This is accomplished by first estimating the patient's oxygen consumption (VO2) from the volume of CO2 eliminated by the patient through breathing (VCO2) and the respiratory quotient (RQ). VO2 can then be estimated as:

[0086]

[0087] Where VO2 is oxygen consumption (mL min -1 ), VCO2 is the volume of CO2 eliminated by breathing (mL min -1 ), RQ is the respiratory quotient.

[0088] VCO2 is determined by computer 14 based on the respiratory flow or volume measurements and the respiratory CO2 content measurements obtained by flow or volume sensor 27 and gas analyzer 29. In the illustrated embodiment utilizing a capnograph 31 for deriving a volumetric capnography, VCO2 may be determined as the area under the curve of the volumetric capnography graph. Typically, an average value of VCO2 is used in the calculation. For example, VCO2 in equation 5 may be an average value of VCO2 over a 20 minute period.

[0089] RQ is a dimensionless number defined as the ratio of the volume of CO2 released to the volume of oxygen absorbed during respiration. RQ is typically in the range of 0.7 to 1.0 and can be set by computer 14 based on input patient parameters related to, for example, the patient's age, sex, and weight.

[0090] Once EPBF or CO and VO2 have been determined by computer 14, SvO2 can be estimated by combining the results with the oxygen Fick equation. It will be shown below how to estimate SvO2 from EPBF using the oxygen Fick equation.

[0091] The oxygen Fick equation for EPBF can be written as:

[0092]

[0093] Where VO2 is oxygen consumption (mL min -1 ), EPBF is the effective (non-shunt) pulmonary blood flow (L·min -1 ), CvO2 is the mixed venous oxygen content (mL·L -1 ), and CcO2 is the oxygen content of the terminal pulmonary capillaries (mL·L -1 ).

[0094] The oxygen content (CcO2) in the pulmonary capillary blood can be expressed as the pulmonary capillary oxygen partial pressure (PcO2) and the pulmonary capillary oxygen saturation (ScO2) as follows:

[0095] CcO2=α·PcO2+C H ·Hb·ScO2 (Formula 7)

[0096] CcO2 is the oxygen content in the blood of the pulmonary terminal capillaries (mL STP ·L 血液 -1); α = 0.224 is the solubility constant of oxygen in plasma (mL STP ·L -1 ·kPa); PcO2 is the partial pressure of oxygen in the terminal pulmonary capillaries (kPa); C H =1.35 is the Hüfner constant (mL STP ·g -1 ); Hb is the hemoglobin content in the blood (g·L -1 ), which can be obtained from blood sampling or any type of hemoglobin screening; and ScO2 is the saturation of end-pulmonary capillaries (fraction). STP is the standard temperature and pressure of 0°C and 1 atm.

[0097] Similarly, the oxygen content in mixed venous blood (CvO2) can be expressed in terms of mixed venous oxygen partial pressure (PvO2) and mixed venous oxygen saturation (SvO2) as:

[0098] CvO2=α·PvO2+C H ·Hb·SvO2 (Formula 8)

[0099] Where CvO2 is the oxygen content in mixed venous blood (mL STP ·L 血液 -1 ); α = 0.224 is the solubility constant of oxygen in plasma (mL STP ·L -1 kPa); PvO2 is the mixed venous oxygen partial pressure (kPa); C H =1.35 is the Hüfner constant (mL STP ·g -1 ); Hb is the hemoglobin content in the blood (g·L -1 ), which can be obtained from blood sampling; and SvO2 is the mixed venous blood oxygen saturation (fraction).

[0100] By combining equations 5 to 8, SvO2 can be estimated by computer 14 as:

[0101]

[0102] ScO2 is the oxygen saturation of the pulmonary capillaries (fraction), VCO2 is the CO2 elimination (mL min -1 ), C H is the Hüfner constant (mL·g -1 ), Hb is the hemoglobin content in blood (g·L -1 ), EPBF is effective pulmonary blood flow (L·min -1 ), RQ is the respiratory quotient, α is the solubility constant of oxygen in plasma (mL·L -1 kPa -1), PcO2 is the terminal pulmonary capillary oxygen partial pressure (kPa), and PvO2 is the mixed venous oxygen partial pressure (kPa).

[0103] PcO2 can be assumed to be related to alveolar oxygen partial pressure (P A O2) balance, and P A O2 can be estimated by computer 14 based on the set fraction of inspired oxygen (FiO2) in the respiratory gas delivered to the patient and the alveolar gas equation (see, for example, Curran-Everett D., A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equation. Adv Physiol Educ. 2006; 30 (2): 58-62).

[0104] ScO2 can be calculated by computer 14 based on PcO2 and the oxygen dissociation curve (see, e.g., Siggaard-Andersen O, Wimberley PD, I, Siggaard-Andersen M., Amathematical model of the hemoglobin-oxygen dissociation curve of human blood and of the oxygen partial pressure as a function of temperature. Clin Chem. 1984; 30(10): 1646-51). Normally, the end capillary blood of the lungs is completely saturated with oxygen, which means that ScO2 is often close to 1.

[0105] Similarly, the computer 14 can use the oxygen dissociation curve to determine the relationship between PvO2 and SvO2, thereby explicitly determining the estimated value of SvO2. The relationship between PvO2 and SvO2 (as indicated by the oxygen dissociation curve) is nonlinear. Therefore, in order to solve Formula 9 about SvO2, the computer 14 can be configured to apply an iterative process to determine the relationship between PvO2 and SvO2. First, the computer can set an assumed initial value of PvO2 (e.g., 5kPa). Together with other quantities on the right hand side of Formula 9, the first value of SvO2 can then be calculated by the computer 14. Based on the SvO2 value calculated in this way, a new PvO2 can be calculated using the inverse relationship of the dissociation curve. The new PvO2 can be used in Formula 9 to calculate a new SvO2 value, and so on. The calculation sequence quickly converges to a unique solution for PvO2 and SvO2, wherein the SvO2 value thus obtained constitutes an estimated SvO2.

[0106] In this way, the computer 14 can non-invasively estimate "capnodynamic SvO2" based on the respiratory CO2 measurements and flow or volume measurements (including at least the expiratory CO2 content measurements and the expiratory flow or volume measurements). In addition to the non-invasive nature of the proposed process, an advantage of the process is that it provides continuous (breath-by-breath) monitoring of SvO2, because the above-mentioned calculations (including the capnodynamic determination of CO or EPBF) can be performed once for each breath.

[0107] Although the estimation of SvO2 described above is based on EPBF, it should be understood that, in view of the teachings disclosed herein, SvO2 can be estimated from CO in a similar manner by replacing EPBF with CO and modifying the above equations accordingly. When doing so, Equation 9, which allows estimation of SvO2 from EPBF, becomes the following equation, which allows estimation of SvO2 from CO:

[0108]

[0109] SaO2 is arterial oxygen saturation (fraction), VCO2 is CO2 elimination (mL min -1 ), C H is the Hüfner constant (mL·g -1 ), Hb is the hemoglobin content in blood (g·L -1 ), CO is cardiac output (L·min -1 ), RQ is the respiratory quotient, α is the solubility constant of oxygen in plasma (mL·L -1 kPa -1 ), PaO2 is the arterial oxygen partial pressure (kPa), and PvO2 is the mixed venous oxygen partial pressure (kPa).

[0110] As is well known in the art, SaO2 can be estimated from peripheral capillary oxygen concentration (SpO2), which in turn can be measured using standard techniques (e.g., pulse oximetry). Once SaO2 is estimated, PaO2 can be estimated by determining the relationship between PaO2 and SaO2 using the oxygen dissociation curve in a process similar to the iterative process described above for determining SvO2 and PvO2 from the oxygen dissociation curve. When SaO2 and PaO2 have been determined, the iterative process can be repeated for SvO2 and PvO2 to find a unique solution for SvO2 and PvO2, wherein the SvO2 value thus obtained constitutes the estimated SvO2.

[0111] Although in the exemplary embodiment shown, the computer 14 is an internal computer of the respiratory apparatus 2, it will be appreciated that the calculations for estimating SvO2 may be performed by any computer configured to receive measurements relating to the CO2 content and flow or volume of exhaled gas exhaled by a mechanically ventilated subject 3. Thus, the computer may, for example, form part of a patient monitoring system for monitoring hemodynamic parameters of a mechanically ventilated patient. Alternatively, the computer may be a separate computer (e.g. a personal computer) configured to receive said measurements from the respiratory apparatus 2 and / or directly from the flow or volume sensor 27 and the gas analyzer 29.

[0112] Figure 2 An alternative embodiment of a system 1 for continuously and non-invasively estimating SvO2 in a mechanically ventilated patient 3 is shown, wherein a computer 14' for estimating SvO2 based on expiratory CO2 content measurements and expiratory flow or volume measurements obtained by a gas analyzer 29 and a flow or volume sensor 27 is located in a patient monitor 39 for monitoring hemodynamic parameters (including SvO2) of the mechanically ventilated patient 3.

[0113] The computer 14' of the patient monitor 39 may include a processor 21' and a computer-readable data storage medium 23' (e.g., a non-transitory hardware memory device) storing the above-described computer program for estimating SvO2 of a ventilated patient according to the principles described herein. The patient monitor 39 also includes a display 37' for displaying hemodynamic parameters (including SvO2) to a clinician.

[0114] In the illustrated embodiment, the patient monitor 39 is configured to receive the exhaled CO2 content measurement and the exhaled flow or volume measurement directly from the gas analyzer 29 and the flow or volume sensor 27. The patient monitor 39 may be connected via a wired or wireless connection (e.g., Figure 2 33' in the figure) is connected to the gas analyzer 29 and the flow or volume sensor 27. Alternatively or in addition, the patient monitor 39 can be connected to the respiratory device 2 and configured to receive the exhaled CO2 content measurement results and the exhaled flow or volume measurement results obtained by the gas analyzer 29 and the flow or volume sensor 27 from the respiratory device 2. Such an optional wired or wireless connection between the patient monitor 39 and the respiratory device 2 (which can exist instead of the wired or wireless connection 33', or in addition to the wired or wireless connection 33') is shown by the dotted line marked as 33".

[0115] Once the capnokinetic SvO2 of the ventilated patient has been estimated, the computer 14, 14' may be configured such that the estimated SvO2 value is displayed to the clinician on either or both of the displays 37, 37'. The displayed SvO2 value may be used as an indicator of adequate oxygen delivery by the respiratory apparatus 2. If the SvO2 value is low, for example, if the SvO2 value drops below a certain threshold, the clinician may take appropriate action (e.g., by performing maneuvers to improve the patient's CO or EPBF) to increase oxygen delivery by the respiratory apparatus and / or improve oxygen uptake by the ventilated patient.

[0116] The system 1 may also be configured to generate an alarm signal when the estimated SvO2 drops below a predetermined threshold to alert a clinician of a potentially critical situation.

[0117] In some embodiments, the system 1 may also be configured to control the respiratory apparatus 2 based on the estimated SvO2, i.e., to use the estimated SvO2 as a control parameter for controlling the respiratory apparatus 2. For example, the computer 14 may be configured to control the respiratory apparatus 2 to increase the oxygen fraction (FiO2) in the respiratory gas delivered to the patient 3 and / or to increase the patient's oxygen uptake when the estimated SvO2 indicates that the patient's oxygenation is low or decreased. For example, the computer 14 may be configured to cause the respiratory apparatus 2 to increase the FiO2 when the estimated SvO2 drops below a certain threshold. Alternatively or additionally, the computer 14 may be configured to cause the respiratory apparatus 2 to perform a maneuver for increasing the CO or EPBF of the patient 3 when the estimated SvO2 drops below a threshold. For example, the maneuver may involve increasing the positive end expiratory pressure (PEEP) to reduce the patient's intrapulmonary shunt, which has the effect of increasing the EPBF / CO ratio.

[0118] In some embodiments, either or both of the computer 14 and the computer 14' may be configured to present a recommendation related to ventilation therapy of the patient provided by the respiratory device 2 based on the estimated SvO2. For example, the computer 14, computer 14' may be configured to present a recommended respiratory device setting or setting adjustment based on the estimated SvO2, such as a recommended FiO2 setting or FiO2 setting adjustment. The computer 14, computer 14' may also be configured to present a recommendation regarding a respiratory device maneuver to be performed or initiated by a respiratory device operator based on the estimated SvO2. For example, the computer 14, computer 14' may be configured to recommend that a respiratory device maneuver to increase PEEP be performed when the estimated SvO2 drops below a threshold.

[0119] Figure 3is a flow chart illustrating a method for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject according to an exemplary embodiment of the present disclosure.

[0120] In a first step S1, a breath CO2 content is measured comprising at least the exhaled CO2 content in exhaled gas exhaled by a subject. The CO2 content is measured by a gas analyzer comprising a CO2 sensor. The gas analyzer may form part of a capnograph configured for volumetric capnographing.

[0121] In a second step S2, a respiratory flow or volume is measured, comprising at least an expiratory flow or volume of expiratory gas exhaled by the subject. The flow or volume is measured by a flow or volume sensor. The flow or volume sensor may form part of a capnograph configured for volume capnographing.

[0122] In a third step S3, the CO or EPBF of the ventilated subject is estimated based on the measured breath CO2 content and the measured respiratory flow or volume using a non-invasive capnokinetic Fick method. The Fick method may be any known non-invasive Fick method for determining CO or EPBF from respiratory flow or volume and CO2 content. CO or EPBF may be estimated by a computer when a processor of the computer executes a computer program.

[0123] In the fourth and final step S4, the SvO2 of the ventilated subject is estimated based on the CO or EPBF estimated in step S3. This step can also be implemented by a computer when a processor of the computer executes a computer program.

[0124] Figure 4 is a flow chart illustrating a method for continuously and non-invasively estimating SvO2 in a mechanically ventilated subject according to another exemplary embodiment of the present disclosure. However, Figure 3 The methods shown in are not limited to any particular method for estimating CO or EPBF. Figure 4 The method shown in utilises the principles of the carbon dioxide kinetic Fick method disclosed in WO 2013 / 141766.

[0125] In this exemplary embodiment, CO or EPBF of a ventilated subject is estimated based on respiratory CO2 content measurements obtained during ventilation of the subject using the following ventilation mode and respiratory flow or volume measurements, which ventilation mode causes a change in the CO2 content of the exhaled gas exhaled by the subject. This is achieved by controlling a respiratory device that provides mechanical ventilation to the subject to introduce a change in the effective ventilation of the subject by ventilating the subject using a ventilation mode that includes at least one increased ventilation phase and at least one reduced ventilation phase. The increased ventilation phase includes one or more breaths of increased ventilation, and the reduced ventilation phase includes one or more breaths of reduced ventilation. Breaths with increased ventilation are breaths that ventilate the patient's lungs more effectively than breaths with reduced ventilation, and vice versa. Therefore, the purpose of changing the effective ventilation of the subject is to obtain a change in the exhaled CO2 level, which can be measured and used to determine CO or EPBF. Therefore, in this context, breaths with reduced ventilation can also be defined as breaths that cause an increase in the exhaled CO2 level compared to breaths with increased ventilation, and vice versa.

[0126] Thus, in a first step (denoted as S30A because the first step can be considered as part of estimating the subject's CO or EPBF that occurs in a subsequent step denoted as S30), the subject is ventilated using a ventilation pattern that includes a plurality of breaths (one or more) of reduced ventilation and a plurality of breaths (one or more) of increased ventilation to introduce a change in the level of CO2 exhaled by the subject.

[0127] In a second step S10, a respiratory CO2 content is measured for the analyzed breathing sequence, during which the subject was ventilated using the ventilation pattern applied to the subject in step S30A. The CO2 content is measured by a gas analyzer comprising a CO2 sensor. The gas analyzer may form part of a capnograph configured for volumetric capnographing.

[0128] In a third step S20, a respiratory flow or volume comprising at least the expiratory flow or volume of expiratory gas exhaled by the subject is measured for the analyzed respiratory sequence. The flow or volume is measured by a flow or volume sensor. The flow or volume sensor may form part of a capnograph configured for volume capnographing.

[0129] In a fourth step S30, the CO or EPBF of the ventilated subject is estimated based on the breath CO content and the breath flow or volume measured during the analyzed breathing sequence using the principles of the capnokinetic Fick method disclosed in WO 2013 / 141766. As described in more detail above, this means that the breath CO content measurements and the breath flow or volume measurements obtained during the analyzed breathing sequence are used to derive an estimate of the subject's F. A A first parameter related to CO2, a second parameter related to either of the subject's CaCO2 (in the determination of CO) or CcCO2 (in the determination of EPBF), and a third parameter related to the subject's VCO2 (sub-step S30B of step S30). Then, the CO or EPBF of the ventilated subject is estimated based on the correlation between the first parameter, the second parameter and the third parameter in the analyzed respiratory sequence, for example using a least squares method (sub-step S30C of step S30). These steps can all be performed by a computer when a processor of the computer executes a computer program.

[0130] In the fifth and final step S40, the SvO2 of the ventilated subject is estimated based on the CO or EPBF estimated in step S30. This step may also be implemented by a computer when a processor of the computer executes a computer program.

[0131] exist Figure 3 and Figure 4 In the embodiment of the present invention, steps S3 and S30 may advantageously comprise estimating the EPBF of the ventilated subject, while steps S4 and S40 advantageously comprise estimating SvO2 from the estimated EPBF using the oxygen Fick equation (Eq. 6) as described in more detail above.

[0132] As from Figure 1 and Figure 2 As understood from the above description, the method may optionally include not Figure 3 or Figure 4 Additional steps as indicated in any of the flowcharts shown. For example, the method may include the additional steps of displaying the estimated SvO2 on a display 37, display 37' of the system 1, presenting a recommendation related to ventilation therapy of the patient provided by the respiratory apparatus 2 (e.g., recommended respiratory apparatus settings or adjustments), and / or controlling the respiratory apparatus 2 based on the estimated SvO2, for example, controlling the respiratory apparatus to increase FiO2 and / or performing an automatic maneuver for increasing the CO or EPBF of the ventilated patient 3.

Claims

1. A computer program product comprising a computer program for continuously and non-invasively estimating the mixed venous blood saturation SvO2 in a mechanically ventilated subject (3) by means of a system (1), the system (1) comprising a gas analyzer (29) for measuring the expiratory CO2 content in expiratory gas exhaled by the subject, a flow or volume sensor (27) for measuring the expiratory flow or volume of expiratory gas exhaled by the subject, and a computer (14), wherein: The computer program includes computer readable instructions which, when executed by the computer, cause the system (1) to perform operations, the operations comprising: - measuring the exhaled CO2 content in exhaled gas exhaled by the subject; - measuring the exhaled flow or volume of exhaled gas exhaled by the subject; - estimating the subject's effective pulmonary blood flow, EPBF, from the measured expiratory CO2 content and the measured expiratory flow or volume using the capnokinetic Fick method, and - estimating SvO2 based on the estimated EPBF of the subject, Therein, SvO2 is estimated based on EPBF rather than cardiac output (CO) so that SvO2 can be estimated without determining the arterial oxygen content (CaO2) of the subject (3).

2. The computer program product according to claim 1, wherein: The operations also include: - estimating the oxygen consumption VO2 of the subject (3) based on the amount of CO2 eliminated by the subject through breathing VCO2 and the respiratory quotient (RQ), and - estimating SvO2 based on the estimated VO2 of the subject, such that SvO2 is estimated based on a quotient between VCO2 and EPBF.

3. The computer program product according to claim 2, wherein: The operations also include: - substituting the subject's estimated EPBF and estimated VO2 into the Fick equation for oxygen in the blood, - variables related to the oxygen content per volume unit (CvO2) in mixed venous blood are expressed in the Fick equation as the oxygen partial pressure in mixed venous blood PvO2 term and SvO2 term, and - Estimate SvO2 by solving the equation thus obtained for SvO2.

4. The computer program product according to any one of claims 1 to 3, wherein: SvO2 is estimated based on the following relationship: ScO2 is the oxygen saturation of the pulmonary capillaries in fractional form, and VCO2 is in mL / min. -1 The amount of CO2 removed per unit, C H mL·g -1 Hüfner constant in g·L -1 The hemoglobin content in the blood is measured in L·min -1 is the effective pulmonary blood flow in units, RQ is the respiratory quotient, and α is in mL·L -1 kPa -1 PcO2 is the solubility constant of O2 in plasma in kPa, PcO2 is the partial pressure of oxygen in the distal pulmonary capillaries in kPa, and PvO2 is the mixed venous partial pressure of oxygen in kPa.

5. The computer program product according to any one of claims 1 to 3, wherein: The operation also includes estimating the EPBF of the subject (3) based on expiratory CO2 content measurements and expiratory flow or volume measurements obtained for the analyzed breathing sequence, during which the subject is ventilated using a ventilation pattern that includes a plurality of breaths with increased ventilation and a plurality of breaths with decreased ventilation.

6. The computer program product according to claim 5, wherein: The operations also include: - determining, for a plurality of breaths in the analyzed breathing sequence, a fraction (F) corresponding to the alveolar CO2 of the subject based on the expiratory CO2 content measurements and the expiratory flow or volume measurements obtained for the analyzed breathing sequence; A CO2), a first parameter related to the CO2 content of the subject's arterial blood (CaCO2) or the CO2 content of the subject's terminal capillary blood (CcCO2), and a third parameter related to the subject's CO2 elimination (VCO2), and - estimating the EPBF of the subject (3) based on the correlation between the first parameter, the second parameter and the third parameter in the analyzed breathing sequence.

7. A system (1) for continuously and non-invasively estimating mixed venous blood saturation SvO2 in a mechanically ventilated subject (3), comprising: - a gas analyzer (29) for measuring the exhaled CO2 content in the exhaled gas exhaled by the subject, - a flow or volume sensor (27) for measuring the exhaled flow or volume of exhaled gas exhaled by the subject, and - Computer (14), Wherein, the computer is configured to: - estimating the subject's effective pulmonary blood flow, EPBF, from the measured expiratory CO2 content and the measured expiratory flow or volume using the capnokinetic Fick method, and - estimating SvO2 based on the estimated EPBF of the subject, Wherein the computer (14) is configured to estimate SvO2 based on EPBF rather than cardiac output (CO) so as to estimate SvO2 without determining the arterial oxygen content (CaO2) of the subject (3).

8. The system (1) according to claim 7, wherein: The computer (14) is configured to: - estimating the oxygen consumption VO2 of the subject (3) based on the amount of CO2 eliminated by the subject through breathing VCO2 and the respiratory quotient (RQ), and - estimating SvO2 based on the estimated VO2 of the subject, such that SvO2 is estimated based on a quotient between VCO2 and EPBF.

9. The system (1) according to claim 8, wherein: The computer (14) is configured to: - substituting the subject's estimated EPBF and estimated VO2 into the Fick equation for oxygen in the blood, - variables related to the oxygen content per volume unit (CvO2) in mixed venous blood are expressed in the Fick equation as the partial pressure of oxygen in mixed venous blood PvO2 term and SvO2 term, and - Estimate SvO2 by solving the equation thus obtained for SvO2.

10. The system (1) according to any one of claims 7 to 9, wherein: The computer (14) is configured to estimate SvO2 based on the following relationship: ScO2 is the oxygen saturation of the pulmonary capillaries in fractional form, and VCO2 is the oxygen saturation in mL / min. -1 The amount of CO2 removed per unit, C H In mL·g -1 Hüfner constant in g·L -1 The hemoglobin content in the blood is measured in units of L·min -1 is the effective pulmonary blood flow in units, RQ is the respiratory quotient, and α is the effective pulmonary blood flow in units of mL·L -1 kPa -1 where PcO2 is the solubility constant of oxygen in plasma in kPa, PcO2 is the partial pressure of oxygen in the distal pulmonary capillaries in kPa, and PvO2 is the mixed venous partial pressure of oxygen in kPa.

11. The system (1) according to any one of claims 7 to 9, further comprising a display (37), wherein: The computer (14) is configured to cause the estimated SvO2 to be displayed to a user on the display.

12. The system (1) according to any one of claims 7 to 9, further comprising a respiratory device (2) for providing mechanical ventilation to the subject (3).

13. The system (1) according to claim 12, wherein: The respiratory apparatus (2) is configured to ventilate the subject (3) using a ventilation pattern including a plurality of breaths with increased ventilation and a plurality of breaths with decreased ventilation, and the computer (14) is configured to estimate the EPBF of the subject (3) based on expiratory CO2 content measurements and expiratory flow or volume measurements obtained for the analyzed respiratory sequence, and the subject is ventilated using the ventilation pattern during the analyzed respiratory sequence.

14. The system (1) according to claim 13, wherein: The computer (14) is configured to determine, for a plurality of breaths in the analyzed breathing sequence, a fraction (F) of alveolar CO2 of the subject based on the expiratory CO2 content measurement and the expiratory flow or volume measurement. A The computer (14) is configured to estimate the EPBF of the subject (3) based on a correlation between the first parameter, the second parameter and the third parameter in the analyzed respiratory sequence.

Images