WO2012066280A2

WO2012066280A2 - Blood analysis apparatus and method

Info

Publication number: WO2012066280A2
Application number: PCT/GB2011/001602
Authority: WO
Inventors: Andrew Ian Hart
Original assignee: Spectrum Medical Ltd
Priority date: 2010-11-18
Filing date: 2011-11-15
Publication date: 2012-05-24
Also published as: GB201019488D0; WO2012066280A3; GB2485558B; GB2485558A

Abstract

A blood analysis apparatus is provided for use in a system in which blood from a patient is provided to an oxygenator (40) and in which blood from the oxygenator (40) is provided back to the patient. The apparatus comprises a first group of sensors (6, 7) for directly measuring a corresponding first group of properties of the blood provided to or from the oxygenator (40). The apparatus comprises a second group of sensors (1, 2, 3, 4) for directly measuring a corresponding second group of properties of a gas provided to or from the oxygenator (40). The apparatus comprises a processor (60) for determining a value for the partial pressure of oxygen in the blood and/or a value for the partial pressure of carbon dioxide in the blood in dependence upon the first group of directly measured properties and the second group of directly measured properties.

Description

Blood Analysis Apparatus and Method

The present invention relates to a blood analysis apparatus and method.

Known blood gas analysers typically provide direct measurements of various properties of the blood, such as pH, partial pressure of oxygen (P02), partial pressure of carbon dioxide (PC02), and oxygen saturation. When relating to arterial blood flow (as opposed to venous blood flow), P02 and PC02 are sometimes known respectively as Pa0₂ and PaC0₂, or simply Pa02 and PaC02.

These direct measurements of P02 and PC02 are typically used to evaluate oxygenation of the tissues and pulmonary function. For example, P02 reflects the amount of oxygen gas dissolved in the blood, and is an indicator of the effectiveness of the lungs in transferring oxygen into the blood stream from the air breathed in. Decreased P02 levels may be associated with anaemia, hypoventilation or pulmonary disease. On the other hand, PC02 reflects the exchange of C0₂ through the lungs to the outside air. Increased levels of PC02 may be caused by pulmonary oedema or lung disease, while decreased levels of PC02 may be caused by hyperventilation or hypoxia.

Known techniques for measuring P02 and PC02 are invasive in the sense that contact is required between the sensor being used and the blood being analysed. Even when the measurements are carried out extra-corporeally, such that some degree of invasiveness is anyway required to extract the blood, contact with blood is undesirable for reasons of hygiene and sensor re-use. Such measurements are also direct in the sense that a sensor is provided whose specific purpose is to measure a value of P02 or PC02, as the case may be; the values are not derived from other measured properties, although other measured properties may be taken into account for reasons of accuracy or adjustment.

The present applicant has appreciated the desirability of providing an apparatus and method for the indirect and/or non-invasive determination of P02 and PC02, for example during cardiopulmonary bypass surgery or when membrane oxygenation of patients blood is carried out, for example extra-corporeal membrane oxygenation (ECMO) procedures.

According to a first aspect of the present invention there is provided a blood analysis apparatus for use in a system in which blood from a patient is provided to an oxygenator and in which blood from the oxygenator is provided back to the patient. A first group of sensors is provided for directly measuring a corresponding first group of properties of the blood provided to or from the oxygenator. A second group of sensors is provided for directly measuring a corresponding second group of properties of a gas provided to or from the oxygenator. A processor is provided for determining a value for the partial pressure of oxygen in the blood and/or a value for the partial pressure of carbon dioxide in the blood in dependence upon the first group of directly measured properties and the second group of directly measured properties.

According to a second aspect of the present invention there is provided a blood analysis method. Blood is provided from a patient to an oxygenator. Blood is provided from the oxygenator back to the patient. A first group of properties of the blood provided to or from the oxygenator is directly measured using a corresponding first group of sensors. A second group of properties of a gas provided to or from the oxygenator is directly measured using a corresponding second group of sensors. A value is determined for the partial pressure of oxygen in the blood and/or a value for the partial pressure of carbon dioxide in the blood in dependence upon the first group of directly measured properties and the second group of directly measured properties.

At least one of the first group of sensors may be adapted to measure its corresponding property without coming into contact with the blood. It may be that each of the first group of sensors is adapted to measure its corresponding property without coming into contact with the blood.

The first group of sensors may comprise a blood temperature sensor for measuring a temperature of the blood provided to or from the oxygenator and a blood flow rate sensor for measuring a flow rate of the blood provided to or from the oxygenator. The second group of sensors may comprise a carbon dioxide out sensor for measuring a concentration of carbon dioxide in the gas provided from the oxygenator.

The partial pressure of carbon dioxide in the blood may be determined in dependence upon the measurements of blood temperature, blood flow rate, and concentration of carbon dioxide in the gas provided from the oxygenator.

The second group of sensors may comprise an oxygen in sensor for measuring a concentration of oxygen in the gas provided to the oxygenator. The partial pressure of oxygen in the blood may be determined in dependence upon the measurements of blood temperature, blood flow rate, concentration of carbon dioxide in the gas provided from the oxygenator, and concentration of oxygen in the gas provided to the oxygenator.

The second group of sensors may comprise a carbon dioxide in sensor for measuring a concentration of carbon dioxide in the gas provided to the oxygenator. The partial pressure may be determined in dependence upon the measurement of concentration of carbon dioxide in the gas provided to the oxygenator.

The first group of sensors may comprise one or both of a haemoglobin sensor for measuring a level of haemoglobin in the blood provided to or from the oxygenator and a blood saturation sensor for measuring a level of red blood cell oxygen saturation provided to or from the oxygenator. The partial pressure may be determined in dependence upon the measurement of haemoglobin and/or blood saturation level.

The second group of sensors may comprise one or both of a gas temperature sensor for measuring a temperature of the gas provided to or from the oxygenator and a gas flow rate sensor for measuring a gas flow rate of the gas provided to or from the oxygenator. The partial pressure may be determined in dependence upon the measurement of gas temperature and/or flow rate.

The blood analysis apparatus may comprise a pressure sensor for measuring atmospheric pressure. The blood analysis method may comprise measuring atmospheric pressure. The partial pressure may be determined in dependence upon the measurement of atmospheric pressure.

The pressure sensor may form part of the second group of sensors.

The blood analysis apparatus may comprise a second processor for applying a correction to one or more of the measurements of concentration. The blood analysis method may comprise applying a correction to one or more of the measurements of concentration.

The partial pressure of oxygen in the blood may be determined according to function (11 ) below. The partial pressure of carbon dioxide in the blood may be determined according to function (12) below.

Each of the sensors is adapted to measure its corresponding respective property extracorporeal^. Therefore, a method and apparatus according to an embodiment of the present invention is intended to be used extra-corporeally, and not directly on the human or animal body.

According to a third aspect of the present invention there is provided a program for controlling an apparatus to perform a method according to the second aspect of the present invention or which, when loaded into an apparatus, causes the apparatus to become an apparatus according to the first aspect of the present invention. The program may be carried on a carrier medium. The carrier medium may be a storage medium. The carrier medium may be a transmission medium.

According to an fourth aspect of the present invention there is provided an apparatus programmed by a program according to the third aspect of the present invention.

According to a fifth aspect of the present invention there is provided a storage medium containing a program according to the third aspect of the present invention.

Reference will now be made, by way of example, to the accompanying drawings, in which:

Figure 1 illustrates a system embodying the present invention; and

Figure 2 illustrates a method embodying the present invention.

As mentioned above, the aim of an embodiment of the present invention is to determine the levels of P02 and PC02 within the arterial blood stream, and in particular to achieve this by indirect and/or non-invasive means.

The present applicant has appreciated that, in a situation where cardiopulmonary bypass surgery is being undertaken or when membrane oxygenation of patients blood (e.g. ECMO) is being carried out, there is a possibility of determining P02 and PC02 levels by monitoring the gas conditions being presented to the oxygenator and the gas conditions leaving the oxygenator.

There are several equations that are used in everyday medicine which provide a certain amount of knowledge about the relationship between the gas breathed in and out and the amount of P02 and PC02 that occurs in the blood stream.

A first equation of interest is the following for arterial oxygen content (Ca0₂):

CaQ₂ = Hb(gm/dl)\ 34(0₂ /gm)Hb *Sa0₂ +Pa0₂ * 0.003(m/O₂ ImmHgldl)

However, the present applicant has appreciated that the measurements of Sa02 (arterial oxygen saturation) and Hb (haemoglobin) are needed at a very high precision for this equation to be effective. Furthermore, Pa02 is required, which is what an embodiment of the present invention is seeking to determine.

The well-known alveolar gas equation is also of interest (where PA0₂ is alveolar P0₂ rather than arterial P0₂ or Pa0₂):

PA0₂ = FI0₂ {BP - 47) - 12PaC0₂

In the above equation, FI0₂ is the fraction of inspired oxygen.

The properties that one might therefore consider to be relevant to the above are:

Oxygen % in

Atmospheric pressure

Carbon Dioxide % out

However, the present applicant has appreciated that, although the above equations are physiologically correct, they cannot be used to determine P02 or PC02 when an oxygenator is involved. The oxygenator efficiency and performance has been found to override the equations to make the accuracy unacceptable. However, some of the basic principles can be used in an embodiment of the present invention. The present applicant has therefore appreciated the importance of taking account of and characterising the oxygenator system, and having functions that allow a basic equation to be used and to allow each function to modify the result by correcting for changes in various variables.

The variables (or properties) that have been identified as being useful are, but are not limited to:

Oxygen % in

Carbon Dioxide % in

Blood Temperature

Blood flow rate

Carbon Dioxide % out

Figure 1 illustrates a system embodying the present invention. With a system embodying the present invention, extra-corporeal blood property measurements are made externally of the patient, typically during a procedure in which the patient's blood is routed through a system such as a heart lung machine during a heart bypass operation.

The system comprises a venous blood flow line 20, an arterial blood flow line 30 and an oxygenator 40, for example as part of a heart-lung machine. Thus, in the illustrated example, the venous blood flow line 20 receives de-oxygenated blood from the patient, and the arterial blood flow line 30 provides oxygenated blood to the patient. Blood in the blood flow lines 20 and 30 pass through a sterile channel such as tubing.

Gas is passed to the oxygenator 40 via a gas module 50 comprising sensors 1 to 3, and gas is passed from the oxygenator 40 to a CO2 module comprising a sensor 4. These sensors 1 to 4 are as follows:

Sensor 1 : Percentage of oxygen at inlet to the oxygenator (0₂)

Sensor 2: Percentage of CO2 at inlet to the oxygenator (C0₂in)

Sensor 3: Gas line pressure

Sensor 4: Percentage of C0₂ at exit from the oxygenator (C0₂out) In addition to the above parameters the following are also measured by strategically placed sensors in other locations:

Sensor 5: atmospheric pressure

Sensor 6: blood flow rate

Sensor 7: blood temperature

Sensor 7 is provided on the blood flow line from the oxygenator 40, sensor 6 is provided on the blood flow line to the oxygenator 40, and sensor 5 is provided in a suitable position for measuring atmospheric pressure. The positions of the sensors 6 and 7 with respect to the oxygenator 40 could be different to that as illustrated.

Although an atmospheric pressure sensor 5 and a line pressure sensor 3 are illustrated, in practice it is possible to employ only one of these. As the gas running through the device is vented to atmosphere the line pressure is almost exactly atmospheric pressure, and since the more accurate of the two would generally be line pressure, in practice it would be the line pressure sensor 3 that is used to determine atmospheric pressure. Therefore, in the description that follows, atmospheric pressure readings are indicated as coming from the line pressure sensor 3, so that a separate atmospheric pressure sensor 5 is not required.

Sensors 6 and 7 can be considered as a first group of sensors for directly measuring a corresponding first group of properties of the blood provided to or from the oxygenator 40.

Sensors 1 to 4 can be considered as a second group of sensors for directly measuring a corresponding second group of properties of a gas provided to or from the oxygenator 40.

A more detailed description of each of the sensors 1 to 7 is provided below.

A technique been developed according to an embodiment of the present invention that enables arterial P02 and PC02 to be determined (or inferred or predicted or calculated) using readings from the above sensors. Each of sensors 1 to 7 is preferably non-invasive, in that they are not required to contact the blood in order to operate. For example, a typical non-invasive flow rate sensor 6 measures the flow rate of extra-corporeal blood flow in the tubing by employing ultrasonic energy. In order to achieve the aim of being able to determine arterial P02 and PC02 non-invasively, any sensors which are required solely to enable arterial P02 and PC02 to be determined should be of a non-invasive or non- contact type. However, even if an invasive type sensor is used, an embodiment of the present invention still has the advantage of determining P02 and PC02 levels indirectly; that is, the P02 and PC02 levels are inferred from other measured properties that might anyway be required in the system for other purposes.

It is preferable that levels of arterial P02 and PC02 are corrected for the following interfering variables:

Temperature variations

Pressure variations

Blood flow rate variations

Oxygen inlet percentage variations

Carbon dioxide inlet and outlet variations

To provide the system with these corrections, various sensors can be used as detailed in the above list.

The range required for the oxygen sensor 1 is thought to be quite wide, and hence a sensor that could deal with 0 to 100% would be preferable. Such a sensor is available from a company called FIGARO, in the form for example of an oxygen battery type sensor. This sensor also benefits from being temperature compensated.

The range required for the C0₂ sensors 2 and 4 is thought to be somewhat lower than that for the oxygen sensor 1 , preferably somewhere in the region of 0 to 5% or 0 to 10%. Such a sensor is available from a company called Gas Sensing Solutions, in the form of an IR device that provides both analogue and digital outputs from 0 to 20%. However, an alternative (and perhaps preferred) C0₂ sensor is available from a company called Dynament, in the form of a device having a full scale range of 0 to 10% C0₂ and is temperature compensated: this sensor also uses an infrared measurement technique, with an analogue output, and has proved to be reliable and accurate, with fewer initial reading errors, breakages and zero drift problems compared to other sensors tried.

For the temperature sensor 7, a thermistor arrangement is suitable, for example a 10 K Ohm Negative Temperature Coefficient (NTC) thermistor. Such a sensor is supplied by a company called Epcos which has a range of 0 to 70 degrees C.

A suitable blood flow rate sensor 6 is found in the Spectrum Medical M3 monitor or by Transonic Systems Inc. These provide an accurate measurement of flow over the range of 0 to 10 l/min with a fast response to flow variations.

For pressure sensors 3 and 5 these could be individual devices as this would provide more accuracy but, as mentioned above, it is likely that they would be one device that would read line pressure only. This works on the principle that the line pressure is very close to atmospheric pressure. These pressure sensors will likely be a strain gauge type however other types of sensors would be perfectly acceptable. A typical sensor range for this measurement would be between 600 and 1300 mBar absolute. Such a sensor is supplied by a company called Sensortechnics.

In an embodiment of the present invention, values for P02 and PC02 are derived from measurements from the above-described sensors according to the following functions:

P0₂ = Function of {Tblood , Qblood , 0₂in% , C0₂in% , C0₂out% , Pa} (1 ) PC0₂ = Function of {Tblood , Qblood , C0₂in% , C0₂out% , Pa} (2) where:

Tblood = Blood Temperature (sensor 7; e.g. degrees C)

Qblood = Blood Flow Rate (sensor 6)

0₂in% = 0₂ percentage entering system (various sensors; see below)

C0₂in% = C0₂ percentage entering system (various sensors; see below)

C0₂out% = C0₂ percentage in gas leaving system removed from blood (various

sensors; see below)

Pa = Line or Atmospheric pressure (sensor 3 or 5)

The values for P0₂ and PC0₂ given respectively by functions (1) and (2) are calculated by the first processor (60) illustrated in Figure 1 , in dependence upon readings or a subset of readings from the first group of sensors, the second group of sensors, and any other sensors provided. 11 001602

10

The above-mentioned values for 0₂in%, C0₂in% and C0₂out% are derived from sensor readings which benefit from correction in order to improve performance and accuracy.

In this respect, the 0₂ measurement should ideally be accurate over a range of pressure and temperature conditions. As the chosen sensor is temperature compensated internally further compensation is not required. It has been determined that the following is an appropriate relationship to employ for pressure compensation:

0₂in% = Function of {0₂ , Pa} (3) where:

Pa = Line or Atmospheric pressure (sensor 3 or 5; e.g. mbar)

0₂ = Raw 0₂ sensor reading (sensor 1; e.g. % concentration)

There are two C0₂ measurements of interest, one being the gas entering the system and the other being the difference between the gas entering and the gas leaving. These measurements should also ideally be accurate over a range of a pressure and temperature conditions. As the chosen sensor is temperature compensated internally further compensation is not required. It has been determined that the following is an appropriate relationship to employ for pressure compensation:

C0₂in% = Function of {C0₂in , Pa} (4) C0₂out% = Function of {C0₂out , Pa} - C0₂in% (5) where:

C0₂in = Raw C0₂in sensor reading of gas entering the system (sensor 2; e.g. % concentration)

C0₂out = Raw C0₂out sensor reading of gas leaving the system (sensor 4; e.g. % concentration)

Pa = Atmospheric pressure (sensor 3; e.g. mbar)

As the gas passes through the oxygenator 40, oxygen is absorbed by the blood and carbon dioxide is released. As a result of this, the gas exchange mix that is present as it B2011/001602

11 finishes passing over the blood is not the same as the gas concentration that entered the oxygenator chamber. This final, condition of the gas can be approximated by subtracting the amount of C0₂ exiting from the 0₂ entering. It has been determined that the following is an appropriate relationship to employ for providing this corrected reading:

O₂out% = Function of {0₂in% , C0₂out%} (6)

The corrected values for 0₂in%, 0₂out%, C0₂in% and C0₂out% given respectively by functions (3) to (6) are calculated by the second processor (70) illustrated in Figure 1.

Each of the basic functions set out in (1 ) to (6) above can now be described in more detail, so that the specific interactions of each of the above variables can be shown.

Turning first to function (3), and as mentioned above, in order to ensure that the measured 0₂in% is correct over a range of known use conditions it should ideally be corrected for pressure. In order to do this, the following variables are used to act upon the pressure measurements which are then used to calculate 0₂in%:

0₂Pa_Cai = Line or Atmospheric pressure when 0₂ sensor was calibrated (sensor 3 or 5;

e.g. mbar)

And, based on the above, the function (3) for 0₂in% becomes:

0₂in% = 0₂ ^* (1 - ((Pa - 0₂Pa_Cai)/1000)) (7)

Turning now to functions (4) and (5), and as mentioned above, in order to ensure that the measured C0₂in% and C0₂out% values are correct over a range of known use conditions they should ideally be corrected for pressure. In order to do this, the following variables are used to act upon the pressure measurements which are then used to calculate C0₂in% and C0₂out%:

C0₂Pa_Cai = Line or Atmospheric pressure when C0₂ sensors were calibrated (sensor 3 or 5; e.g. mbar)

And, based on the above, the functions (4) and (5) for C0₂in% and C0₂out% become: C0₂in% = C0₂in ^* (1 - ((Pa - CO₂Pa_Cai)/1000)) (8) C0₂out% = C0₂out ^* (1 - ((Pa - CO₂Pa_Cai)/1000)) - C0₂in% (9)

Turning now to function (6), as mentioned above, in order to provide a corrected reading for 0₂in% which can be used for the final condition of the gas mix within the oxygenator the following variable are used to create 0₂out%:

0₂out% = (0₂in% - C0₂out%) (10)

The system uses a synchronisation point which is where the user provides to the system a set of reading that have been obtained from a Blood Gas Analyser and the system takes a set of predefined readings from sensors. These readings are used by the system to synchronise itself with this point. The readings required from the blood gas analyser are P02 and PC02 measurements, other measurements that are used are taken from the sensors attached to this device. Another way of thinking about this is that synchronisation is a snapshot in time of all sensor readings and results.

Turning now to function (1 ), the P0₂ function uses a number of variables and sensor values to produce a result, including the derived value from function (9) above. For a more accurate result, the following variables are also available for use:

VarQb_P02 = P0₂ blood flow correction constant (see Appendix 3 or 5)

Vartemp₄ = Temperature correction constant at O₂out% of 4 (see Appendix 3 or 5)

Vartemp₆o = Temperature correction constant at 0₂out% of 60 (see Appendix 3 or 5)

Tbloodsync = Blood Temperature at time of synchronisation (sensor 7; e.g. degrees C)

Qbloodsync = Blood flow at time of synchronisation (sensor 6; e.g. l/min)

0₂out%_sync = 0₂out% at time of synchronisation (function 10)

P02_sync = P0₂ value supplied by the user at time of synchronising (e.g. mmHg)

MasterP02_Lut = A table of two columns, first column is 0₂out% and second column is P0₂

Values (see Appendix 1 )

These are used to derive the following:

Qb_P02 = (Qblood - Qblood_sync) ^* VarQb_P02 MasterP02₄ = P02 value from asterP02_Lut at an O₂out% of 4

MasterPO2₆₀ = P02 value from MasterP02_Lut at an 0₂out% of 60

Synctempg_ai_n = ((Vartempeo^* (Tbloodsync- 37) ^* MasterPO2₆₀ + MasterPO2₆₀) - (Vartemp₄

^* (Tblood_sync - 37) + asterP02₄)) / (MasterPO2₆₀ - MasterP02₄)

SynctempP02_Lut= ((Each P02 value in MasterP02_Lut) - MasterP02₄) ^* Synctemp_gai_n +

(Vartemp₄ ^* (Tblood_sync- 37) + MasterP02₄)

SyncP02_Lut= (Each P02 value in SynctempP02_Lut) ^* (P02_sync / (Value from

SynctempP02_Lut when O₂out%_sync is input))

SyncP02₄ = P02 value from SyncP02_Lut at an 0₂out% of 4

SyncPO2₆₀ = P02 value from SyncP02_Lut at an 0₂out% of 60

Workinggain = ((Vartemp₆₀ ^* (Tblood - Tblood_sync) ^* SyncPO2₆₀ + SyncPO2₆₀) - (Vartemp₄

^* (Tblood - Tbiood_sync) ⁺ SyncP02₄)) / (SyncPO2₆₀ - SyncP02₄)

And from this the following can be derived:

= (((Each P02 value in SyncP02_LLrt) - SyncP02₄) ^* Working_gain +

(Vartemp₄ ^* (Tblood - Tblood_sync) + SyncP02₄)) - ((Qblood - Qblood, VarQbpo2)

Value from Working P02_Lut when 0₂out% is input (11)

Turning now to function (2), the PC0₂ function uses a number of variables and sensor values to produce a result, including the derived value from function (8) above, and the P0₂ functions above. For a more accurate result, the following variables are also available for use:

C0₂out% = C0₂out% (function 9) at time of synchronisation

MasterPC02, = A table of three columns, first column is Qblood second column is

X values and third column is C values (see Appendix 2 or 4)

TempPC02, = A table of two columns, first column is blood temperature difference (between blood temperature at time of synchronisation and run time blood temperature) and second column is PC0₂ temperature corrections value (see Appendix 2 or 4)

Note : X and C values referred to above are gain and offsets for the generation of a straight line.(e.g. Y=mX+C) in this case m = Qblood, so for each Qblood entry in the table a bespoke straight line can be generated.

PC02_sync = PC0₂ value supplied by the user at time of synchronising (e.g.

mmHg)

PC02x_syn = X value from MasterPC02_Lut when Qblood_sync is input

PC02c_syn = C value from MasterPC02_Uut when Qblood_sync is input

PC02x = X value' from MasterPC02_Lu, when Qblood is input

PC02c = C value from MasterPC02_Lut when Qblood is input

PC02_temp = Temperature correction value from TempPC02|_Ut when (Tbood - Tbloodsync) is input

MasterPC02 = ((Qblood_sync ^* C0₂out%_sync) ^* PC02x_sync) + PC02c_sync

QbC02 = Qblood ^* C0₂out%

And from this the following can be derived:

PC0₂ = (((QbC02 * PC02x) + (QbC02 * PC02_temp) + PC02c) ^* (MasterPC02 / PC02_sync)

(12)

A blood analysis method according to an embodiment of the present invention is illustrated schematically in the flow chart of Figure 2. Blood is provided from a patient to the oxygenator 40 in step P1 , and blood is provided from the oxygenator 40 back to the patient in step P2, in a continuous loop. The above-mentioned first group of sensors is provided in step S1, while the above-mentioned second group of sensors is provided in step S2. Step S3 comprises directly measuring a first group of properties of the blood provided to or from the oxygenator 40 using corresponding respective ones of the first group of sensors. Step S4 comprises directly measuring a second group of properties of a gas provided to or from the oxygenator 40 using corresponding respective ones of the second group of sensors. Step S5 comprises applying corrections to various ones of the measured 011 001602

15 properties, for example as set out above with reference to functions (6) to (10). In step S6 a value for the partial pressure of oxygen in the blood is determined in dependence upon the first group of directly measured properties (from step S3) and the second group of directly measured properties (from step S4), or a selection thereof. In step S7 a value for the partial pressure of carbon dioxide in the blood is determined in dependence upon the first group of directly measured properties (from step S3) and the second group of directly measured properties (from step S4), or a selection thereof. The properties used in steps S6 and S7 may be different. Processing then loops back to step S3, at least until sufficient determinations of P02 and/or PC02 have been made.

It will be appreciated that, for any sensors illustrated in Figure 1 but not included in any function described above, those sensors may be useful for further enhancements to an embodiment of the present invention, for example in order to provide a more accurate determination of P02 and PC02. It will also be understood that the specific calculations described above with reference to functions (1) to (12) are intended to be illustrative and not limiting; it is perfectly feasible to apply different specific calculations in other embodiments of the present invention.

It will be understood that although the oxygen and carbon dioxide sensors 1 , 2 and 4 are described as measuring a percentage of oxygen or carbon dioxide (as the case may be), those sensors need not measure actual percentages but may instead provide their measurements in any other suitable unit of concentration, with appropriate adjustments to the functions which use those measurements.

It will be appreciated that operation of one or both of the first and second processors 60, 70 could be controlled or provided at least in part by a program operating on the device or apparatus. A single processor or processing unit may be arranged to perform the function of both the first and second processors 60, 70. Such an operating program can be stored on a computer-readable medium, or could, for example, be embodied in a signal such as a downloadable data signal provided from an Internet website. The appended claims are to be interpreted as covering an operating program by itself, or as a record on a carrier, or as a signal, or in any other form.

It will be understood that not all of the variables included in the above-described functions, and in particular in the basic functions (1 ) and (2), are essential. Generally, the more B2011/001602

16 variables that are used in the function, the more accurate the resulting derivation of P02 and PC02, but it is possible to sacrifice a little accuracy by dropping those variables that contribute less to the overall accuracy. This would in turn reduce the overall complexity of the calculations, and also the overall number of sensors required. For example, it might also be possible to drop C0₂in% from function (1 ). Depending on the types of sensors employed, and whether correction for pressure is required, it may also be possible to drop Pa from functions (1) and (2). What variables are included will depend on the particular application, and the accuracy required.

Therefore, the following cut-down version of functions (1) and (2) might be considered:

P0₂ = Function of {Tblood , Qblood , 0₂in% , C0₂out%} (1 ') PC0₂ = Function of {Tblood , Qblood , C0₂out%} (2')

Therefore, at least in respect of function (2') above, the second group of sensors might comprise a single sensor, for measuring a concentration of carbon dioxide in the gas from the oxygenator (40).

A similar situation applies to the correction functions (3) to (6); certain variables could be left out, depending on the accuracy required. For example, C0₂in% could be dropped from function (5). Again, what variables are included will depend on the particular application.

Likewise, it is also possible to include more variables in functions (1 ) and (2), and the associated more detailed functions derived from these basic functions. For example, one might consider including the current value of PC0₂ in function (1). One might also consider adding further sensors to the first and/or second group of sensors to provide further variables for inclusion in the functions. For example, one might include a further sensor in the first group of sensors for measuring hematocrit / haemoglobin concentration, and include a corresponding variable Hct / Hb in one or both of functions (1 ) and (2). One might include a further sensor in the second group of sensors for measuring gas flow rate, and include a corresponding variable Qgas in one or both of functions (1 ) and (2). One might include a further sensor in the second group of sensors for measuring gas temperature, and include a corresponding variable Tgas in one or more of functions (3) to (5). One might include a further sensor in the first group of sensors for measuring blood saturation, and include a corresponding variable Sa02% in one or more of the functions.

It will also be appreciated by the person of skill in the art that various modifications may be made to the above-described embodiments without departing from the scope of the present invention as defined by the appended claims.

During cardiopulmonary bypass surgery the patient body temperature is often lowered during the procedure. The measurements already described above (equations 11 and 12) provide values of p02 and pC02 at a reference temperature of 37 degrees C, which is a typical measurement from a blood gas analyser. However if p02 and pC02 measurements are required at the temperature the sample is taken then additional calculations can be performed to provide these new values:

PC02@Te p = pcO2 *l0^0m9*{m°^{od' 1)} (14)

Appendices

The appendices below provide example values for use in the above embodiments. It is possible to use a different set to cater for different scenarios. For example, Appendices 2 and 3 below are considered to be applicable for a "high flow" scenario (a blood flow rate of say 1 to 7 l/min), while Appendices 4 and 5 below are considered to be applicable for a "low flow" scenario (a blood flow rate of say 0 to 3 l/min). Appendix 1 is considered to be applicable for both of these scenarios. Of course, the invention is not limited to use of these particular sets of values, and different values may be devised according to the particular application. 11 001602

18

Appendix 1

Example of MasterP02_Uut Look Up Table:

0₂out P02

% mmhg

4.000 41.500

6.000 44.400

8.000 48.300

10.000 51.200

12.000 56.000

14.000 60.000

16.000 64.700

18.000 70.500

20.000 76.300

22.000 81.780

24.000 88.800

26.000 96.600

28.000 105.300

30.000 115.900

32.000 126.300

34.000 137.200

36.000 148.800

38.000 161.400

40.000 174.700

42.000 188.500

44.000 203.300

46.000 217.400

48.000 234.800

50.000 252.200

52.000 270.500

54.000 287.900

56.000 302.400

58.000 317.900 60.000 334.300

62.000 347.800

64.000 359.400

66.000 371.000

68.000 382.600

70.000 396.100

72.000 406.800

74.000 419.300

76.000 427.100

78.000 435.700

80.000 443.500

Appendix 2

(A) Example of MasterPC02_Lut Look up Table: for High flow assembly (1 to 7 l/min)

Absolute

Blood

flow

Qblood X C

l/min

0.5 20.4 2

1 18 2

1.5 16 2

2 14.1 2

3 10.89 2

4 8.5 2

5 7.6 2

6 7.3 2

7 7.2 2

(B) Example of TempPC02_lut Look up Table: for High flow assembly (1 to 7 l/min) Blood

Temp Diff PC0₂ temperature correction

Deg C

-22.00 19.00

-17.00 14.00

-12.00 9.50

-7.00 5.00

0.00 0.00

7.00 -3.00

12.00 -6.00

17.00 -8.20

22.00 -11.00 Appendix 3 Examples of Constants used: for High flow assembly (1 to 7 l/min)

VarQbpoz = 12

Vartemp₄ = -3.852

Vartempeo = -0.040

Appendix 4

(A) Example of MasterPC02_Lut Look up Table: for Low flow assembly (0 to 3 l/min)

Absolute

Blood

flow

Qblood X C

l/min

0.5 24.41 2

1 16.54 2

1.5 11.4 2

2 8.6 2

2.5 6.89 2

3 5.76 2

(B) Example of TempPC02|_Ut Look up Table: for Low flow assembly (0 to 3 l/min) Blood

Temp Diff PC0₂ temperature correction

Deg C

-22.00 23.6

-17.00 17.70

-12.00 1 1.80

-7.00 6.70

0.00 0.00

7.00 -3.00

12.00 -6.00

17.00 -8.20

22.00 -1 1.00 Appendix 5

Examples of Constants used: for Low flow assembly (0 to 3 l/min) VarQbp₀₂ = 30

Vartemp₄ = -3.852

Vartempeo = -0.022

Claims

1 . A blood analysis apparatus for use in a system in which blood from a patient is provided to an oxygenator (40) and in which blood from the oxygenator (40) is provided back to the patient, the apparatus comprising a first group of sensors for directly measuring a corresponding first group of properties of the blood provided to or from the oxygenator (40), a second group of sensors for directly measuring a corresponding second group of properties of a gas provided to or from the oxygenator (40), and a processor (60) for determining a value for the partial pressure of oxygen in the blood and/or a value for the partial pressure of carbon dioxide in the blood in dependence upon the first group of directly measured properties and the second group of directly measured properties.

2. A blood analysis method comprising: providing blood from a patient to an oxygenator (40); providing blood from the oxygenator (40) back to the patient; directly measuring a first group of properties of the blood provided to or from the oxygenator (40) using a corresponding first group of sensors; directly measuring a second group of properties of a gas provided to or from the oxygenator (40) using a corresponding second group of sensors; and determining a value for the partial pressure of oxygen in the blood and/or a value for the partial pressure of carbon dioxide in the blood in dependence upon the first group of directly measured properties and the second group of directly measured properties.

3. A blood analysis apparatus or method as claimed in claim 1 or 2, wherein at least one of the first group of sensors is adapted to measure its corresponding property without coming into contact with the blood.

4. A blood analysis apparatus or method as claimed in claim 3, wherein each of the first group of sensors is adapted to measure its corresponding property without coming into contact, with the blood.

5. A b!ood analysis apparatus or method as claimed in any preceding claim, wherein the first group of sensors comprises a blood temperature sensor (7) for measuring a temperature of the blood provided to or from the oxygenator (40) and a blood flow rate sensor (6) for measuring a flow rate of the blood provided to or from the oxygenator (40), and wherein the second group of sensors comprises a carbon dioxide out sensor (4) for measuring a concentration of carbon dioxide in the gas provided from the oxygenator (40).

6. A blood analysis apparatus or method as claimed in claim 5, wherein the partial pressure of carbon dioxide in the blood is determined in dependence upon the measurements of blood temperature, blood flow rate, and concentration of carbon dioxide in the gas provided from the oxygenator.

7. A blood analysis apparatus or method as claimed in claim 5 or 6, wherein the second group of sensors comprises an oxygen in sensor (1 ) for measuring a concentration of oxygen in the gas provided to the oxygenator (40), and wherein the partial pressure of oxygen in the blood is determined in dependence upon the measurements of blood temperature, blood flow rate, concentration of carbon dioxide in the gas provided from the oxygenator (40), and concentration of oxygen in the gas provided to the oxygenator (40).

8. A blood analysis apparatus or method as claimed in claim 5, 6 or 7, wherein the second group of sensors comprises a carbon dioxide in sensor (2) for measuring a concentration of carbon dioxide in the gas provided to the oxygenator (40), and wherein the partial pressure is determined in dependence upon the measurement of concentration of carbon dioxide in the gas provided to the oxygenator (40).

9. A blood analysis apparatus or method as claimed in any one of claims 5 to 8, wherein the first group of sensors comprises one or both of a haemoglobin sensor for measuring a level of haemoglobin in the blood provided to or from the oxygenator (40) and a blood saturation sensor for measuring a level of blood saturation in the blood provided to or from the oxygenator (40), and wherein the partial pressure is determined in dependence upon the measurement of haemoglobin and/or blood saturation level.

10. A blood analysis apparatus or method as claimed in any one of claims 5 to 9, wherein the second group of sensors comprises one or both of a gas temperature sensor for measuring a temperature of the gas provided to or from the oxygenator (40) and a gas flow rate sensor for measuring a gas flow rate of the gas provided to or from the oxygenator (40), and wherein the partial pressure is determined in dependence upon the measurement of gas temperature and/or flow rate.

1 . A blood analysis apparatus or method as claimed in any one of claims 5 to 10, comprising a pressure sensor (3; 5) for measuring atmospheric pressure, and wherein the partial pressure is determined in dependence upon the measurement of atmospheric pressure.

12. A blood analysis apparatus or method as claimed in claim 1 1 , wherein the pressure sensor (3) forms part of the second group of sensors.

13. A blood analysis apparatus or method as claimed in any one of claims 5 to 12, comprising a second processor for applying a correction to one or more of the measurements of concentration.

1 . A blood analysis apparatus or method as claimed in any preceding claim, wherein the partial pressure of oxygen in the blood is determined according to function (11 ) in the appended description.

15. A blood analysis apparatus or method as claimed in any preceding claim, wherein the partial pressure of carbon dioxide in the blood is determined according to function (12) in the appended description.

16. A program for controlling an apparatus to perform a method as claimed in any one of claims 2 to 15, optionally being carried on a carrier medium such as a storage medium or a transmission medium.

17. A storage medium containing a program as claimed in claim 16.