CONTROL OF CARBON DIOXIDE TRANSFER IN OXYGENATOR FOR EXTRACORPOREAL BLOOD GAS EXCHANGE

Abstract

A method for controlling carbon dioxide [CO2] removal in a device for extracorporeal blood gas exchange is disclosed. The device comprises an oxygenator including a membrane acting as a gas-liquid barrier enabling CO2 transfer between a bloodstream and a sweep gas flow through the oxygenator. The method comprises the steps of measuring a pre-oxygenator fraction of CO2 [FCO2.sub.in] in the sweep gas flow upstream of the oxygenator, measuring a pre-oxygenator sweep gas flow rate ({dot over (V)}.sub.in) of the sweep gas flow upstream of the oxygenator, measuring a post-oxygenator fraction of CO2 [FCO2.sub.out] in the sweep gas flow downstream of the oxygenator, measuring a post-oxygenator sweep gas flow rate ({dot over (V)}.sub.out) of the sweep gas flow downstream of the oxygenator, and calculating a net CO2 exchange [{dot over (V)}CO2.sub.net] over the membrane based on measured FCO2.sub.in, {dot over (V)}.sub.in, FCO2.sub.out and {dot over (V)}.sub.out.

Claims

1-20. (canceled)

21. A method for controlling carbon dioxide [CO2] removal in a device for extracorporeal blood gas exchange, wherein the device comprises an oxygenator including a membrane acting as a gas-liquid barrier enabling CO2 transfer between a bloodstream and a sweep gas flow through the oxygenator, comprising the steps of: measuring (S12a) a pre-oxygenator fraction of CO2 [FCO2.sub.in] in the sweep gas flow upstream of the oxygenator; measuring (S12b) a pre-oxygenator sweep gas flow rate ({dot over (V)}.sub.in) of the sweep gas flow upstream of the oxygenator; measuring (S12c) a post-oxygenator fraction of CO2 [FCO2.sub.out] in the sweep gas flow downstream of the oxygenator; measuring (S12d) a post-oxygenator sweep gas flow rate ({dot over (V)}.sub.out) of the sweep gas flow downstream of the oxygenator; and calculating (S12e) a net CO2 exchange [{dot over (V)}CO2.sub.net] over the membrane based on measured FCO2.sub.in, {dot over (V)}.sub.in, FCO2.sub.out and {dot over (V)}.sub.out.

22. The method of claim 21, further comprising the steps of: adding (S11) CO2 to the sweep gas flow upstream of the oxygenator to control a degree of CO2 removal from the bloodstream by the oxygenator; and utilizing (S13) {dot over (V)}CO2.sub.net as a measure of CO2 removal for regulation of the CO2 addition to the sweep gas flow.

23. The method of claim 22, wherein the step of utilizing the measure of CO2 removal for regulation of the addition of CO2 to the sweep gas flow comprises: presenting (S13a) the measure of CO2 removal to an operator of the device as decision support in manual adjustment of the addition of CO2 to the sweep gas flow; and/or presenting (S13b), to the operator, a recommendation for adjustment of the addition of CO2 to the sweep gas flow, based on the measure of CO2 removal and a set target for CO2 removal by the oxygenator; and/or automatically regulating (S13c) the addition of CO2 to the sweep gas flow based on the measure of CO2 removal.

24. The method of claim 21, further comprising the steps of: measuring or estimating a pre-oxygenator fraction of at least one additional gas in the sweep gas flow upstream of the oxygenator, the at least one additional gas being one or more of water vapour (H2O), oxygen [O2], nitrogen gas [N2], and an anaesthetic agent; and/or measuring or estimating a post-oxygenator fraction of the at least one additional gas in the sweep gas flow downstream of the oxygenator; and calculating a compensated pre-oxygenator sweep flow rate [{dot over (V)}.sub.in,comp] based on {dot over (V)}.sub.in, FCO2.sub.in and the pre-oxygenator fraction of the at least one additional gas; and/or calculating a compensated post-oxygenator sweep flow rate [{dot over (V)}.sub.out,comp] based on {dot over (V)}.sub.out, FCO2.sub.out and the post-oxygenator fraction of the at least one additional gas; and calculating {dot over (V)}CO2.sub.net based on at least one of {dot over (V)}.sub.in,comp and {dot over (V)}.sub.out,comp.

25. The method of claim 21, further comprising the steps of: calculating a compensated pre-oxygenator fraction of CO2 [FCO2.sub.in,comp] representing an estimate of a fraction of CO2 at a point of measurement (P1) of {dot over (V)}.sub.in, based on FCO2.sub.in and an estimated addition or removal of water vapour [FH2O.sub.in] to or from the sweep gas between the point of measurement (P1) of {dot over (V)}.sub.in and a point of measurement (P2) of FCO2.sub.in; and/or calculating a compensated post-oxygenator fraction of CO2 [FCO2.sub.out,comp] representing an estimate of a fraction of CO2 at a point of measurement (P3) of {dot over (V)}.sub.out, based on FCO2.sub.out and an estimated addition or removal of water vapour (FH2O.sub.out) to or from the sweep gas between the point of measurement (P3) of {dot over (V)}.sub.out and a point of measurement (P4) of FCO2.sub.out; and calculating {dot over (V)}CO2.sub.net based on at least one of FCO2.sub.in,comp and FCO2.sub.out, comp.

26. The method of claim 24, wherein {dot over (V)}.sub.in,comp is calculated based on FCO2.sub.in,comp and the pre-oxygenator fraction of the at least one additional gas, and/or {dot over (V)}.sub.out,comp is calculated based on FCO2.sub.out, comp and the post-oxygenator fraction of the at least one additional gas.

27. The method of claim 25, wherein {dot over (V)}.sub.in,comp is calculated based on FCO2.sub.in,comp and the pre-oxygenator fraction of the at least one additional gas, and/or {dot over (V)}.sub.out,comp is calculated based on FCO2.sub.out, comp and the post-oxygenator fraction of the at least one additional gas.

28. The method of claim 22, further comprising the steps of: receiving a target value for the measure of CO2 removal, and automatically regulating the addition of CO2 to the sweep gas flow so as to reach and/or maintain the target value for the measure of CO2 removal.

29. The method of claim 28, wherein the device is connected to a patient who is also connected to a mechanical ventilator which is configured to mechanically ventilate the patient through the supply of breathing gas to the lungs of the patient, and wherein the target value is selected to evaluate a ventilatory treatment provided by the mechanical ventilator and/or a lung function of the patient, e.g., by selecting a target value corresponding to zero or near zero CO2 removal.

30. The method of claim 21, wherein the step of measuring (S12d) the post-oxygenator sweep gas flow rate ({dot over (V)}.sub.out) is performed by measuring a flow rate of a whole effluent flow of sweep gas leaving the oxygenator.

31. The method of claim 29, wherein the oxygenator comprises at least two outlets for sweep gas, the method comprising the steps of: preventing the sweep gas to pass through all but one outlet of the oxygenator; and measuring the post-oxygenator sweep gas flow rate ({dot over (V)}.sub.out) as the flow rate of the sweep gas flowing through the one outlet.

32. A computer program for controlling carbon dioxide [CO2] removal in a device for extracorporeal blood gas exchange, wherein the device comprises an oxygenator including a membrane acting as a gas-liquid barrier enabling CO2 transfer between a bloodstream and a sweep gas flow through the oxygenator, the computer program comprising computer-readable instructions which, when executed by a control computer, causes the method of claim 21 to be performed.

33. A computer program product comprising a non-transitory memory hardware device storing a computer program for controlling carbon dioxide [CO2] removal in a device for extracorporeal blood gas exchange, wherein the device comprises an oxygenator including a membrane acting as a gas-liquid barrier enabling CO2 transfer between a bloodstream and a sweep gas flow through the oxygenator, the computer program comprising computer-readable instructions which, when executed by a control computer, causes the method of claim 21 to be performed.

34. A system for controlling carbon dioxide [CO2] removal in a device for extracorporeal blood gas exchange, wherein the device comprises an oxygenator including a membrane acting as a gas-liquid barrier enabling CO2 transfer between a bloodstream and a sweep gas flow through the oxygenator, and at least one control computer configured to: receive a measurement of a pre-oxygenator fraction of CO2 [FCO2.sub.in] in the sweep gas flow upstream of the oxygenator; receive a measurement of a pre-oxygenator sweep gas flow rate ({dot over (V)}.sub.in) of the sweep gas flow upstream of the oxygenator; receive a measurement of a post-oxygenator fraction of CO2 [FCO2.sub.out] in the sweep gas flow downstream of the oxygenator; receive a measurement of a post-oxygenator sweep gas flow rate ({dot over (V)}.sub.out) of the sweep gas flow downstream of the oxygenator; and calculate a net CO2 exchange [{dot over (V)}CO2.sub.net] over the membrane based on measured FCO2.sub.in, {dot over (V)}.sub.in, FCO2.sub.out and {dot over (V)}.sub.out.

35. The system of claim 34, further comprising: a gas regulator adding CO2 to the sweep gas flow upstream of the oxygenator in order to control a degree of CO2 removal from the bloodstream by the oxygenator, wherein the control computer is configured to utilize {dot over (V)}CO2.sub.net as a measure of CO2 removal for regulation of the CO2 addition to the sweep gas flow.

36. The system of claim 35, wherein the control computer is configured to utilize the measure of CO2 removal for regulation of the addition of CO2 to the sweep gas flow by: causing the measure of CO2 removal to be presented to the operator of the device as decision support in manual adjustment of the addition of CO2 to the sweep gas flow, and/or causing a recommendation for adjustment of the addition of CO2 to the sweep gas flow to be presented to the operator of the device, based on the measure of CO2 removal and a set target for CO2 removal by the oxygenator, and/or automatically regulating the addition of CO2 to the sweep gas flow based on the measure of CO2 removal.

37. The system of claim 34, wherein the control computer is configured to: estimate or receive a measurement of a pre-oxygenator fraction of at least one additional gas in the sweep gas flow upstream of the oxygenator, the at least one additional gas being one or more of water vapour (H2O), oxygen [O2], nitrogen gas [N2], and an anaesthetic agent, and/or estimate or receive a measurement of a post-oxygenator fraction of the at least one additional gas in the sweep gas flow downstream of the oxygenator; and calculate a compensated pre-oxygenator sweep flow rate [{dot over (V)}.sub.in,comp] based on {dot over (V)}.sub.in, FCO2.sub.in and the pre-oxygenator fraction of the at least one additional gas; and/or calculate a compensated post-oxygenator sweep flow rate [{dot over (V)}.sub.out,comp] based on {dot over (V)}.sub.out, FCO2.sub.out and the post-oxygenator fraction of the at least one additional gas; and calculate (S2i) {dot over (V)}CO2.sub.net based on at least one of {dot over (V)}.sub.in,comp and {dot over (V)}.sub.out,comp.

38. The system of claim 34, wherein the control computer is configured to: calculate a compensated pre-oxygenator fraction of CO2 [FCO2.sub.in,comp] representing an estimate of a fraction of CO2 at a point of measurement (P1) of {dot over (V)}.sub.in, based on FCO2.sub.in and an estimated addition or removal of water vapour [FH2O.sub.in] to or from the sweep gas between the point of measurement (P1) of {dot over (V)}.sub.in and a point of measurement (P2) of FCO2.sub.in, and/or calculate a compensated post-oxygenator fraction of CO2 [FCO2.sub.out,comp] representing an estimate of a fraction of CO2 at a point of measurement (P3) of {dot over (V)}.sub.out, based on FCO2.sub.out and an estimated addition or removal of water vapour [FH2O.sub.out] to or from the sweep gas between the point of measurement (P3) of {dot over (V)}.sub.out and a point of measurement (P4) of FCO2.sub.out, and calculate {dot over (V)}CO2.sub.net based on at least one of FCO2.sub.in,comp and FCO2.sub.out,comp.

39. The system of claim 37, wherein {dot over (V)}.sub.in,comp is calculated based on FCO2.sub.in,comp and the pre-oxygenator fraction of the at least one additional gas, and/or {dot over (V)}.sub.out,comp is calculated based on FCO2.sub.out and the post-oxygenator fraction of the at least one additional gas.

40. The system of claim 38, wherein {dot over (V)}.sub.in,comp is calculated based on FCO2.sub.in,comp and the pre-oxygenator fraction of the at least one additional gas, and/or {dot over (V)}.sub.out,comp is calculated based on FCO2.sub.out and the post-oxygenator fraction of the at least one additional gas.

41. The system of claim 35, wherein the control computer is configured to: receive a target value for the measure of CO2 removal, and regulate the addition of CO2 to the sweep gas flow so as to reach and/or maintain the target value for the measure of CO2 removal.

42. The system of claim 40, wherein the device is connected to a patient who is also connected to a mechanical ventilator which is configured to mechanically ventilate the patient through the supply of breathing gas to the lungs of the patient, and wherein the target value is selected to evaluate a ventilatory treatment provided by the mechanical ventilator and/or a lung function of the patient, e.g., by selecting a target value corresponding to zero or near zero CO2 removal.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0156] The present invention will become more fully understood from the detailed description provided hereinafter and the accompanying drawings, which are given by way of non-limiting illustration only. In the different drawings, same reference numerals correspond to the same element.

[0157] FIG. 1 illustrates an exemplary non-limiting embodiment of an ECMO-vent system for extracorporeal removal of CO2 from the blood of a patient undergoing mechanical ventilation.

[0158] FIG. 2 illustrates an exemplary non-limiting embodiment of an ECMO device of the ECMO-vent system in FIG. 1.

[0159] FIGS. 3-5 are flow charts illustrating an exemplary non-limiting embodiment of a method for controlling CO2 removal in and by the ECMO device, according to a first aspect of the disclosure.

[0160] FIG. 6 is a flowchart illustrating an exemplary non-limiting embodiment of a method for controlling CO2 removal in and by the ECMO device, according to a second aspect of the disclosure.

DETAILED DESCRIPTION

[0161] The present disclosure relates to the field of extracorporeal blood gas exchange by use of an oxygenator for extracorporeal removal of carbon dioxide (CO2) from the blood of a patient. In particular, the disclosure relates to a method, a computer program and a system for improved control of CO2 removal by the oxygenator through addition of CO2 to a sweep gas flow through the oxygenator.

[0162] The invention will be described in the context of a combined system for extracorporeal blood gas exchange via a membrane oxygenator during lung protective ventilation of the patient using a mechanical ventilator. However, it should be appreciated that the proposed control of the oxygenator is not dependent on the ventilator and that the operation of the oxygenator does not require the presence of a ventilator.

[0163] FIG. 1 illustrates a system 1 for combined mechanical ventilation of the lungs of a patient 3 and extracorporeal removal of CO2 from the blood of the patient 3. The system 1 will hereinafter referred to as an ECMO-vent system. ECMO (extracorporeal membrane oxygenation) is one of several terms used for extracorporeal blood gas exchange where blood is pumped outside the body of a treated patient to a device, sometimes referred to as a heart-lung machine, which removes CO2 and sends oxygen-enriched blood back to the patient. Other terms that are frequently used in the art for the same or similar treatments are ECLA (extracorporeal lung assist), ECCO2R (extracorporeal CO2 removal), ECLS (extracorporeal life support) and ECGE (extracorporeal membrane gas-exchange), all of which are encompassed by the term ECMO as used herein.

[0164] The ECMO-vent system 1 comprises a device 5, hereinafter referred to as an ECMO device, for extracorporeal removal of CO2 from the blood of the patient 3, and a mechanical ventilator 7 for mechanically ventilating the patient 3 through the supply of breathing gas to the lungs of the patient.

[0165] The ventilator 7 comprises or is connected to a source of pressurised breathing gas (not shown), which breathing gas is supplied to the patient 3 via a patient circuit 9. In this example, the patient circuit 9 comprises an inspiratory line 11 for conveying a flow of breathing gas to the patient 3, and an expiratory line 13 for conveying a flow of exhalation gas exhaled by the patient away from the patient. The inspiratory line 11 and the expiratory line 13 are connected to each other via a so called Y-piece 15 which, in turn, is connected to the patient 3 via a common line 17.

[0166] The ECMO device 5 is configured to provide ECMO treatment to the patient 3 by generating an extracorporeal flow of blood from the patient 3, oxygenating the blood through extracorporeal blood gas exchange in which CO2 is removed from, and oxygen (O2) added to, the extracorporeal blood flow, and returning the oxygen-enriched blood to the patient 3.

[0167] To generate the flow of blood to and from the patient 3, the ECMO device 5 may comprise a blood flow generator (not shown), typically in form of one or several roller, turbine and/or centrifugal pumps. The blood flow generator generates a flow of blood through a tubing system forming a blood flow channel 19 of the ECMO device 5, where parts of the channel may be heated to maintain a desired temperature of the blood when returned to the patient 3.

[0168] The blood gas exchange, including blood oxygenation and CO2 removal, takes place in a membrane oxygenator 21 of the ECMO device 5, in which an oxygen-containing sweep gas flow interacts with the blood in the blood flow channel 19 via a membrane 23 of the oxygenator 21. The membrane 23 acts as a gas-liquid barrier enabling transfer of CO2 and O2 content between the bloodstream flowing through the oxygenator 21 on a liquid-side of the membrane 23 and the sweep gas flow flowing through the oxygenator 21 on a gas-side of the membrane 23.

[0169] The sweep gas flow is generated by a sweep gas generator 25 connected to one or more sweep gas sources, typically including one or both of an oxygen source and a source of compressed air. According to the principles of the present disclosure, the sweep gas generator 25 is further connected to a CO2 source in order to control the degree of CO2 removal over the oxygenator 21 through addition of CO2 to the sweep gas flow. The sweep gas generator 23 is configured to deliver a controllable sweep gas composition to the oxygenator 21 at a controllable sweep gas flow rate.

[0170] The composition and, optionally, the flow rate of the sweep gas generated by the sweep gas generator 23 may be automatically controlled by a controller or control computer 27 of the ECMO device 5 based on set target values and sensor data obtained by various sensors 29, 31 of the ECMO device 5. In particular, the control computer 27 of the ECMO device 5 may be configured to automatically control an addition of CO2 to a sweep gas flow comprising any or both of oxygen and air, based on a set target for a measure of CO2 removal by the oxygenator 21.

[0171] Hereinafter, the sweep gas flow upstream of the oxygenator 21 (i.e., before the oxygenator from the sweep gas' point of view) will be referred to as an input sweep gas flow or a pre-oxygenator sweep gas flow, and the sweep gas flow downstream of the oxygenator 21 (i.e., after the oxygenator from the sweep gas' point of view) will be referred to as an output sweep gas flow or a post-oxygenator sweep gas flow. The input sweep gas flow flows from the sweep gas generator 25 to the oxygenator 21 via a sweep gas inlet line 33a of the ECMO device 5, and the output sweep gas flow flows from the oxygenator 21 to atmosphere or an evacuation or recirculation system via a sweep gas outlet line 33b. In most configurations, ECMO systems are open systems, meaning that the post oxygenator sweep gas flow is allowed to escape into the ambient. In some cases, especially when anesthetic agents are added to the sweep gas flow, a closed or semi closed (sweep) gas control system can be envisioned, similar to gas control systems often used in anesthesia machines.

[0172] Likewise, the bloodstream upstream of the oxygenator 21 (i.e., before the oxygenator from the bloodstream's point of view) may hereinafter be referred to as an input bloodstream or pre-oxygenator bloodstream, and the bloodstream downstream of the oxygenator 21 (i.e., after the oxygenator from the bloodstream's point of view) may be referred to as an output bloodstream or post-oxygenator bloodstream. The input bloodstream flows from the patient 3 to the oxygenator 21 via a bloodstream inlet line 19a of the ECMO device 5, and the output bloodstream flows from the oxygenator 21 and back to the patient 3 via a bloodstream outlet line 19b of the ECMO device 5.

[0173] With reference now made to FIG. 2, the sensors 29, 31 of the ECMO device 5 may comprise: [0174] a pre-oxygenator flow rate sensor 29a for measuring a flow rate of the input sweep gas flow, {dot over (V)}.sub.in. The pre-oxygenator flow rate sensor 29a is a mainstream flow sensor, meaning that it is configured to measure the flow rate of the sweep gas flowing in the sweep gas inlet line 33a. The pre-oxygenator flow measurements obtained by the pre-oxygenator flow rate sensor 29a take place at a pre-oxygenator point of flow measurement denoted P1 in the sweep gas inlet line 33a. [0175] a pre-oxygenator gas analyser 29b for measuring a fraction of at least CO2 in the input sweep gas flow, FCO2.sub.in. The pre-oxygenator gas analyser 29b may also be configured to measure a fraction of one or more additional gases selected from the group consisting of oxygen (O2), nitrogen gas (N2), and anaesthetic agents. In this exemplary embodiment, the pre-oxygenator gas analyser 29b is a so called sidestream gas analyser that is configured to withdraw sweep gas samples from the sweep gas inlet line 33a, and measure the fraction of CO2 and, optionally, the fraction of the at least one additional gas in the sweep gas samples at a pre-oxygenator point of CO2 measurement denoted P2. The pre-oxygenator point of CO2 measurement P2 is separated in distance from the point of pre-oxygenator sweep gas flow rate measurements, P1, at least by the length of a pre-oxygenator sample line 34a. In other embodiments, the pre-oxygenator gas analyser 29b may be a so called mainstream gas analyser that is configured to measure the fraction of CO2 and, optionally, the fraction of the at least one additional gas within the sweep gas inlet line 33a. In some embodiments, the pre-oxygenator gas analyser comprises at least a CO2 sensor and an O2 sensor for measuring a fraction of CO2 and O2, respectively, in the sweep gas samples. In some embodiments, the CO2 sensor is a non-dispersive infrared (NDIR) CO2 sensor. In some embodiments, the O2 sensor is a paramagnetic or electrochemical O2 sensor. [0176] a pre-oxygenator temperature sensor 29c for measuring a temperature of the input sweep gas, T.sub.in,gas. [0177] a pressure sensor 29d for measuring a sweep gas circuit pressure, P.sub.gas, substantially corresponding to the sweep gas pressure in the gas inlet line 33a. [0178] a post-oxygenator flow rate sensor 31a for measuring a flow rate of the output sweep gas flow, {dot over (V)}.sub.out. The post-oxygenator flow rate sensor 31a is a mainstream flow sensor, meaning that it is configured to measure the flow rate of the sweep gas flowing in the sweep gas outlet line 33b. The post-oxygenator flow measurements obtained by the post-oxygenator flow rate sensor 31a take place at a post-oxygenator point of flow measurement denoted P3 in the sweep gas outlet line 33b. [0179] a post-oxygenator gas analyser 31b for measuring a fraction of at least CO2 in the output sweep gas flow, FCO2.sub.out. The post-oxygenator gas analyser 31b may also be configured to measure a fraction of one or more additional gases selected from the group consisting of oxygen (O2), nitrogen gas (N2), and anaesthetic agents. In this exemplary embodiment, the post-oxygenator gas analyser 31b is a so called sidestream gas analyser that is configured to withdraw sweep gas samples from the sweep gas outlet line 33b, and measure the fraction of CO2 and, optionally, the fraction of the at least one additional gas in the sweep gas samples at a post-oxygenator point of CO2 measurement denoted P4. The post-oxygenator point of CO2 measurement P4 is separated in distance from the point of post-oxygenator sweep gas flow rate measurements, P3, at least by the length of a post-oxygenator sample line 34b. In other embodiments, the post-oxygenator gas analyser 31b may be a so called mainstream gas analyser that is configured to measure the fraction of CO2 and, optionally, the fraction of the at least one additional gas within the sweep gas outlet line 33b. In some embodiments, the post-oxygenator gas analyser comprises at least a CO2 sensor and an O2 sensor for measuring a fraction of CO2 and O2, respectively, in the sweep gas samples. In some embodiments, the CO2 sensor is an IR spectrometer for IR spectroscopy, such as IR absorption spectroscopy. In some embodiments, the O2 sensor is a paramagnetic O2 sensor. [0180] a post-oxygenator temperature sensor 31c for measuring a temperature of the output sweep gas.

[0181] In some embodiments, the ECMO device 5 may further comprise or be connected to a pre-oxygenator blood gas analyser 32 for measuring a partial pressure of at least CO2 in the input bloodstream, PCO2.sub.in. The pre-oxygenator blood gas analyser 32 may also be configured to measure a partial pressure of O2 in the input bloodstream, PO2.sub.in. The pre-oxygenator blood gas analyser 32 may also be configured to measure a haemoglobin content of the input bloodstream, Hb.sub.in. In some embodiments, the blood gas analyser 32 is not incorporated into the ECMO device 5 but arranged to form part of another medical device that is connected to the ECMO device 5 in order for the ECMO device 5 to receive measurements obtained by the blood gas analyser. For example, the blood gas analyser may form part of a stand-alone blood gas analyser unit, often referred to as a BGA, commonly used for intermittent blood gas analysis during ECMO treatments.

[0182] With simultaneous reference to previous drawings, some functions and features of the ECMO-vent system 1 will now be described with reference to the flowcharts shown in FIGS. 3-6, which flowcharts illustrate methods for controlling CO2 removal in and by the ECMO device 5. Unless stated otherwise, each method is a computer-implemented method that is performed by the ECMO device 5 upon execution of a computer program by at least one processor 37 of the control computer 27. The computer program(s) comprise computer-readable instructions that may be stored in a storage medium of the ECMO-vent system 1, such as a non-transitory hardware memory device 39 of the control computer 27.

[0183] FIG. 3 is a flowchart illustrating a method for controlling CO2 removal in and by the ECMO device according to a first aspect of the present disclosure.

[0184] In a first step, S1, CO2 is added to the sweep gas flow upstream of the oxygenator 25 in order to control a degree of CO2 removal from the bloodstream by the oxygenator 21. CO2 is added to the sweep gas flow via the manually, semi-automatically or automatically controlled sweep gas regulator 25.

[0185] In a second step, S2, a measure of CO2 removal by the oxygenator 21 is determined based on a difference (CCO2.sub.blood) between a measure of a pre-oxygenator content of CO2 (CCO2.sub.in) in the bloodstream upstream of the oxygenator 21 and an estimate of a post-oxygenator content of CO2 (CCO2.sub.out) in the bloodstream downstream of the oxygenator 21. The determination is made by the control computer 27 based on sensor data obtained by the sensors 29a-29d, 31a-31c and 32.

[0186] In a third step, S3, the measure of CO2 removal is utilized for improved regulation of the CO2 addition to the sweep gas flow.

[0187] In some embodiments, the measure of CO2 removal is determined from pre-oxygenator measurements of partial pressures of CO2 (PCO2.sub.in) and 02 (PO2.sub.in) in the input bloodstream, e.g., obtained by the blood gas analyser 32, and post-oxygenator measurements of fractions of CO2 (FCO2.sub.out) and O2 (FO2.sub.out) in the output sweep gas flow, e.g., obtained by the post-oxygenator gas analyser 31b.

[0188] The measure of the pre-oxygenator content of CO2, CCO2.sub.in, in the input bloodstream may be expressed as a function of a pre-oxygenator partial pressure of CO2 (PCO2.sub.in) of the bloodstream, a pre-oxygenator partial pressure of O2 (PO2.sub.in) of the bloodstream, a pre-oxygenator temperature (T.sub.in,blood) of the bloodstream, and a pre-oxygenator haemoglobin concentration (Hb.sub.in) of the bloodstream. Likewise, the estimate of the post-oxygenator content of CO2, CCO2.sub.out, in the output bloodstream may be expressed as a function of a post-oxygenator partial pressure of CO2 (PCO2.sub.out) of the bloodstream, a post-oxygenator partial pressure of O2 (PO2.sub.out) of the bloodstream, a post-oxygenator temperature of the bloodstream (T.sub.out,blood), and a post-oxygenator haemoglobin concentration (Hb.sub.out) of the bloodstream. PCO2.sub.in and PO2.sub.in may be measured by the pre-oxygenator blood gas analyser 32, whereas PCO2.sub.out and PO2.sub.out can be assumed to substantially correspond to measured post-oxygenator fractions of CO2 (FCO2.sub.out) and O2 (FO2.sub.out) in the outlet sweep gas flow. Since the Hb concentration of the bloodstream can be assumed to be constant, Hb.sub.in and Hb.sub.out are cancelled out and the difference between the estimates of CCO2.sub.in and CCO2.sub.out can be calculated from FCO2.sub.in, FO2.sub.in, FCO2.sub.out, FO2.sub.out, T.sub.in,blood and T.sub.out,blood.

[0189] FIG. 4 is a flowchart illustrating a non-limiting example of how the determination of the measure of CO2 removal in step S2 in FIG. 3 can be achieved in more detail.

[0190] As illustrated in FIG. 4, step S2 may comprise the following sub-steps: [0191] S2a) measuring a pre-oxygenator partial pressure of CO2 (PCO2.sub.in) in the bloodstream upstream of the oxygenator 21, e.g., by means of the pre-oxygenator blood gas analyser 32, [0192] S2b) measuring a pre-oxygenator partial pressure of O2 (PO2.sub.in) in the bloodstream upstream of the oxygenator 21, e.g., by means of the pre-oxygenator blood gas analyser 32, [0193] S2c) measuring a post-oxygenator fraction of CO2 (FCO2.sub.out) in the sweep gas flow downstream of the oxygenator 21, e.g., by means of the post-oxygenator gas analyser 31b, [0194] S2d) measuring a post-oxygenator fraction of O2 (FO2.sub.out) in the sweep gas flow downstream of the oxygenator 21, e.g., by means of the post-oxygenator gas analyser 31b, [0195] S2e) estimating a post-oxygenator partial pressure of CO2 (PCO2.sub.out) and a post-oxygenator partial pressure of O2 (PO2.sub.out) in the bloodstream downstream of the oxygenator 21 based on FCO2.sub.out and FO2.sub.out, [0196] S2f) measuring or estimating a pre-oxygenator temperature (T.sub.in,blood) of blood in the bloodstream upstream of the oxygenator 21. T.sub.in,blood may be measured with a pre-oxygenator blood temperature sensor (not shown), or it may be estimated e.g. based on an assumed and/or measured temperature of the patient 3, a temperature of the sweep gas flow, a length of tubing of the blood flow channel 19, and/or an effect of a heater (not shown) for heating blood in the blood flow channel, [0197] S2g) measuring or estimating a post-oxygenator temperature (T.sub.out,blood) of blood in the bloodstream downstream of the oxygenator 21. T.sub.out,blood may be measured with a post-oxygenator blood temperature sensor (not shown), or it may be estimated e.g. based on an assumed and/or measured temperature of the patient 3, a temperature of the sweep gas flow, a length of tubing of the blood flow channel 19, and/or an effect of a heater (not shown) for heating blood in the blood flow channel. [0198] S2h) measuring or estimating a haemoglobin content (Hb) of blood in the bloodstream through of the oxygenator 21, e.g., by means of the pre-oxygenator blood gas analyser 32, and [0199] S2i) determining the difference CCO2.sub.blood between CCO2.sub.in and CCO2.sub.out from the measured and/or estimated quantities. PCO2.sub.in, PO2.sub.in, T.sub.in,blood, PCO2.sub.out, PO2.sub.out, T.sub.out,blood, and Hb.

[0200] As illustrated by dashed lines in FIG. 4, the steps of measuring or estimating T.sub.in,blood, T.sub.out,blood and Hb are optional. Since, for some cases and some oxygenator configurations, T.sub.in,blood can be assumed to substantially correspond to T.sub.out,blood, and since Hb is constant upstream and downstream of the oxygenator 21, the difference CCO2.sub.blood between CCO2.sub.in and CCO2.sub.out can be approximated from PCO2.sub.in, PO2.sub.in, PCO2.sub.out, and PO2.sub.out alone. However, to further improve accuracy in the determination, T.sub.in,blood and T.sub.out,blood may be taken into account. By determining and utilising Hb in the determination of the difference CCO2.sub.blood, the difference can be quantified and an actual net CO2 exchange, {dot over (V)}CO2.sub.net, can be calculated and used as a measure of CO2 exchange over the oxygenator 21.

[0201] FIG. 5 is a flowchart illustrating some non-limiting examples of how the determined measure of CO2 removal can be utilized in step S3 in FIG. 3 in order to improve regulation of the CO2 addition to the sweep gas flow.

[0202] As illustrated in FIG. 5, step S3 may comprise one or more of the following steps: [0203] S3a) presenting the measure of CO2 removal to an operator of the ECMO device 5 as decision support in manual adjustment of the addition of CO2 to the sweep gas flow. The measure of CO2 removal may, for example, be presented on a display comprised in or connected to the ECMO device 5. [0204] S3b) presenting, to the operator of the ECMO device 5, a recommendation for adjustment of the addition of CO2 to the sweep gas flow, based on the measure of CO2 removal and a set target for CO2 removal by the oxygenator. For example, the recommendation may be presented on a display comprised in or connected to the ECMO device 5. The recommendation may, for example, be a recommendation to increase or decrease the addition of CO2 to the sweep gas flow, e.g., by manually increasing or decreasing a set value for the fraction of CO2 (FCO2.sub.in) in the sweep gas flow upstream of the oxygenator 21. [0205] S3c) automatically regulating the addition of CO2 to the sweep gas flow based on the measure of CO2 removal and a set target for CO2 removal. For example, if the set target is zero CO2 removal, the control computer 27 may be configured to control the sweep gas regulator 25 to regulate the fraction of CO2 in the inlet sweep gas flow so as to reach and/or maintain zero CO2 removal.

[0206] FIG. 6 is a flowchart illustrating a method for controlling CO2 removal in and by the ECMO device 5 according to a second aspect of the present disclosure.

[0207] In a first optional step, S11, CO2 is added to the sweep gas flow upstream of the oxygenator 21 to control a degree of CO2 removal from the bloodstream of the patient 3 by the oxygenator 21.

[0208] In a second step, S12, a net CO2 exchange ({dot over (V)}CO2.sub.net) over the membrane 23 of the oxygenator 21 is calculated.

[0209] Step S12 comprises the following sub-steps: [0210] S12a) measuring a pre-oxygenator fraction of CO2 (FCO2.sub.in) in the sweep gas flow upstream of the oxygenator 21, e.g., by means of the pre-oxygenator gas analyser 29b; [0211] S12b) measuring a pre-oxygenator sweep gas flow rate ({dot over (V)}.sub.in) of the sweep gas flow upstream of the oxygenator 21, e.g., by means of the pre-oxygenator flow rate sensor 29a; [0212] S12c) measuring a post-oxygenator fraction of CO2 (FCO2.sub.out) in the sweep gas flow downstream of the oxygenator 21, e.g., by means of the post-oxygenator gas analyser 31b; [0213] S12d) measuring a post-oxygenator sweep gas flow rate ({dot over (V)}.sub.out) of the sweep gas flow downstream of the oxygenator 21, e.g., by means of a post-oxygenator flow rate sensor 31a, and [0214] S12e) calculating {dot over (V)}CO2.sub.net over the membrane 23 based on measured FCO2.sub.in, {dot over (V)}.sub.in, FCO2.sub.out and {dot over (V)}.sub.out.

[0215] In a third optional step, S13, {dot over (V)}CO2.sub.net is utilized as a measure of CO2 removal for improved regulation of the CO2 addition to the sweep gas flow. Step S13 may comprise any of, or any combination of, the steps S3a-S3c illustrated in FIG. 5, using the calculated {dot over (V)}CO2.sub.net as the measure of CO2 removal.

[0216] {dot over (V)}CO2.sub.net may be calculated as the fraction of CO2 (FCO2.sub.in) in the input sweep gas flow times the input sweep gas flow rate ({dot over (V)}.sub.in), minus the fraction of CO2 (FCO2.sub.out) in the output sweep gas flow times the output sweep gas flow rate ({dot over (V)}.sub.out), in accordance with:

[00001]$\begin{array}{cc}\stackrel{.}{V}\mathrm{CO}{2}_{\mathrm{net}}=\left(F\mathrm{CO}{2}_{\mathrm{in}}*{\stackrel{.}{V}}_{\mathrm{in}}\right)-\left(F\mathrm{CO}{2}_{\mathrm{out}}*{\stackrel{.}{V}}_{\mathrm{out}}\right)& \mathrm{eq}.l\end{array}$

[0217] Of course, in order to accurately calculate the flow of CO2 going into and out from the oxygenator 21, the terms FCO2.sub.in and FCO2.sub.out should reflect the true fractions of CO2 at the points of measurements of {dot over (V)}.sub.in and {dot over (V)}.sub.out. Due to the humid environment (often close to 100% RH) downstream the oxygenator, there is often a need for conditioning (e.g., drying) the sweep gas before it enters the gas analyser, e.g., to prevent condensation of water inside the gas analyser. Therefore, with reference again made to FIG. 2, the ECMO device 5 may comprise a water vapour trap or gas sample conditioner (not shown) for conditioning and especially for drying the sweep gas samples withdrawn from the sweep gas outlet line 33b before the sweep gas samples enter the post-oxygenator gas analyser 31b. The gas sample conditioner may, e.g., comprise a piece of Nafion tubing or silica gel. Due to the removal of water by the gas sample conditioner, the composition of the sweep gas samples measured upon is not the same as the composition of the sweep gas flow in the sweep gas outlet line 33b, where {dot over (V)}.sub.out is measured. Therefore, the fraction of CO2, FCO2.sub.out, measured by the sidestream post-oxygenator gas analyser 31b at the point of measurement P4 will not accurately reflect the fraction of CO2 at the point, P3, of output sweep gas flow rate measurements.

[0218] To this end, the method may further comprise the steps of: [0219] calculating a compensated pre-oxygenator fraction of CO2 (FCO2.sub.in,comp) representing an estimate of a fraction of CO2 at the point of measurement, P1, of {dot over (V)}.sub.in, based on FCO2.sub.in and an estimated addition or removal of water vapour, FH2O.sub.in, to or from the sweep gas between the point of measurement, P1, of {dot over (V)}.sub.in and a point of measurement, P2, of FCO2.sub.in, and/or [0220] calculating a compensated post-oxygenator fraction of CO2 (FCO2.sub.out,comp) representing an estimate of a fraction of CO2 at a point of measurement, P3, of {dot over (V)}.sub.out, based on FCO2.sub.out and an estimated addition or removal of water vapour (FH2O.sub.out) to or from the sweep gas between the point of measurement, P3, of {dot over (V)}.sub.out and a point of measurement, P4, of FCO2.sub.out, and [0221] calculating {dot over (V)}CO2.sub.net based on {dot over (V)}.sub.in and {dot over (V)}.sub.out, and at least one of FCO2.sub.in,comp and FCO2.sub.out, comp.

[0222] For example, a compensated post-oxygenator fraction of CO2 (FCO2.sub.out,comp) can be calculated as a function of measured post-oxygenator fraction of CO2 (FCO2.sub.out) and an estimated addition or removal of water vapour (FH2O.sub.out) to or from the sweep gas between the point of measurement, P3, of {dot over (V)}.sub.out and a point of measurement, P4, of FCO2.sub.out, and used in the determination of {dot over (V)}CO2.sub.net according to:

[00002]$\begin{array}{cc}{FC\mathrm{O2}}_{\mathrm{out},\mathrm{comp}}=f\left(F\mathrm{CO}{2}_{\mathrm{out}},FH2O_{\mathrm{out}}\right)& \mathrm{eq}.2\end{array}$$\begin{array}{cc}\stackrel{.}{V}\mathrm{CO}{2}_{\mathrm{net}}=\left(F\mathrm{CO}{2}_{\mathrm{in}}*{\stackrel{.}{V}}_{\mathrm{in}}\right)-\left({F\mathrm{CO2}}_{\mathrm{out},\mathrm{comp}}*{\stackrel{.}{V}}_{\mathrm{out}}\right)& \mathrm{eq}.3\end{array}$

[0223] The estimated addition or removal of water vapour, FH2O.sub.out, may, in some embodiments, be calculated based on: a measured post-oxygenator temperature (T.sub.out,gas), measured by the post-oxygenator temperature sensor 31c; a measured or estimated post-oxygenator relative humidity (RH.sub.out) of the sweep gas flow downstream of the oxygenator; a measured or estimated reference temperature (T.sub.ref) at or close to the point of measurement P4 of FCO2.sub.out, and; a measured or estimated reference relative humidity (RH.sub.ref) at or close to the point of measurement P4 of FCO2.sub.out. In embodiments where the gas sample conditioner comprises a piece of Nafion tubing, the reference relative humidity, RH.sub.ref, can be assumed to correspond to the relative humidity of the air surrounding the Nafion tubing. In embodiments where the gas sample conditioner comprises silica gel, the reference relative humidity, RH.sub.ref, can be assumed to be zero or near zero. The post-oxygenator relative humidity, RH.sub.out can in most situations be assumed to be 100% but may, in some embodiments, be measured by a humidity sensor (not shown) of the ECMO device 5, arranged downstream of the oxygenator 21.

[0224] Another potential source of error in the calculation of {dot over (V)}CO2.sub.net is inaccuracy in sweep gas flow rate measurements. The flow sensors 29a and 31a for measuring {dot over (V)}.sub.in and {dot over (V)}.sub.out are normally calibrated for a specific gas composition and deviations between an assumed composition and an actual composition of the sweep gas measured upon introduces errors in flow rate determinations. Therefore, the method may further comprise the steps of: [0225] measuring or estimating a pre-oxygenator fraction of at least one additional gas in the sweep gas flow upstream of the oxygenator 21, the at least one additional gas being one or more of water vapour (H2O), O2, nitrogen gas (N2), and an anaesthetic agent, and/or [0226] measuring or estimating a post-oxygenator fraction of the at least one additional gas in the sweep gas flow downstream of the oxygenator, and [0227] calculating a compensated pre-oxygenator sweep flow rate ({dot over (V)}.sub.in,comp) based on {dot over (V)}.sub.in, FCO2.sub.in and the pre-oxygenator fraction of the at least one additional gas, and/or [0228] calculating a compensated post-oxygenator sweep flow rate ({dot over (V)}.sub.out,comp) based on {dot over (V)}.sub.out, FCO2.sub.out and the post-oxygenator fraction of the at least one additional gas, and [0229] calculating {dot over (V)}CO2.sub.net based on FCO2.sub.in, FCO2.sub.out and at least one of {dot over (V)}.sub.in,comp and {dot over (V)}.sub.out,comp.

[0230] By taking the composition of the sweep gas into account and compensating the pre-oxygenator and/or the post-oxygenator sweep flow rate measurements {dot over (V)}.sub.in and {dot over (V)}.sub.out based on a measured fraction of at least one additional gas in the sweep gas flow upstream and/or downstream the oxygenator, a more accurate value of {dot over (V)}CO2.sub.net can be obtained.

[0231] For example, a compensated post-oxygenator sweep gas flow rate, {dot over (V)}.sub.out,comp, may be calculated as a function of {dot over (V)}.sub.out, FCO2.sub.out and a post-oxygenator fraction of O2, water vapour and/or N2, according to:

[00003]$\begin{array}{cc}{\stackrel{.}{V}}_{\mathrm{out},\mathrm{comp}}=f\left({\stackrel{.}{V}}_{\mathrm{out}},{F\mathrm{CO2}}_{\mathrm{out}},{F\mathrm{O2}}_{\mathrm{out}},FH2O_{\mathrm{out}},{F\mathrm{N2}}_{\mathrm{out}}\right),& \mathrm{eq}.4\end{array}$

where FCO2.sub.out and FO2.sub.out are the fractions of CO2 and O2 measured by the sidestream post-oxygenator gas analyser 31b, FH2O.sub.out is the fraction of water vapour in the sweep gas flow downstream of the oxygenator, which may be determined from the measured post-oxygenator temperature, T.sub.out,gas, of the sweep gas flow downstream of the oxygenator and the measured or estimated post-oxygenator relative humidity, RH.sub.out, of the sweep gas flow downstream of the oxygenator, and FN2.sub.out is the post-oxygenator fraction of N2 which may be measured by the post-oxygenator gas analyser 31b or be assumed to correspond to the remaining fraction of the post-oxygenator sweep gas flow.

[0232] {dot over (V)}CO2.sub.net may then be calculated as:

[00004]$\begin{array}{cc}\stackrel{.}{V}\mathrm{CO}{2}_{\mathrm{net}}=\left(F\mathrm{CO}{2}_{\mathrm{in}}*{\stackrel{.}{V}}_{\mathrm{in}}\right)-\left(F\mathrm{CO}{2}_{\mathrm{out},\mathrm{comp}}*{\stackrel{.}{V}}_{\mathrm{out},\mathrm{comp}}\right)& \mathrm{eq}.5\end{array}$

[0233] As discussed above, there is often a need for using a gas sample conditioner for drying the gas samples between the sweep gas sampling point in the sweep gas outlet line 33b and the sidestream post-oxygenator gas analyser 31b. The removal or reduction of water vapour content by the gas sample conditioner introduces a deviation between the composition of the sweep gas in the sweep gas outlet line (where {dot over (V)}.sub.out is measured) and the sweep gas samples measured upon by the sidestream gas analyser 31b. Therefore, to further improve accuracy in the determination of the compensated post-oxygenator sweep gas flow rate, {dot over (V)}.sub.out,comp, the compensated post-oxygenator fraction of CO2, FCO2.sub.out,comp, may be advantageously used instead of the measured post-oxygenator fraction of CO2, FCO2.sub.out, in the determination of {dot over (V)}.sub.out,comp, in accordance with:

[00005]$\begin{array}{cc}{\stackrel{.}{V}}_{\mathrm{out},\mathrm{comp}}=f\left({\stackrel{.}{V}}_{\mathrm{out}},{F\mathrm{CO2}}_{\mathrm{out},\mathrm{comp}},{F\mathrm{O2}}_{\mathrm{out}},FH2O_{\mathrm{out}},{F\mathrm{N2}}_{\mathrm{out}}\right)& \mathrm{eq}.6\end{array}$

[0234] Any fractions of additional gases measured by the post-oxygenator sidestream gas analyser 31b, such as measured fractions of O2 (FO2.sub.out) and/or measured fractions of N2 (FN2.sub.out), may also be compensated based on the estimated addition or removal of water vapour, FH2O.sub.out, to or from the sweep gas between the point of measurement, P3, of {dot over (V)}.sub.out and the point of measurement, P4, of the additional gas by the gas analyser. A compensated fraction of the additional gas may be calculated as a function of the measured fraction of the additional gas and the estimated addition or removal of water vapour, FH2O.sub.out, in accordance with:

[00006]$\begin{array}{cc}{F\mathrm{O2}}_{\mathrm{out},\mathrm{comp}}=f\left({F\mathrm{O2}}_{\mathrm{out}},FH2O_{\mathrm{out}}\right)& \mathrm{eq}.7\end{array}$$\begin{array}{cc}{F\mathrm{N2}}_{\mathrm{out},\mathrm{comp}}=f\left(FN{2}_{\mathrm{out}},FH2O_{\mathrm{out}}\right)& \mathrm{eq}.8\end{array}$

[0235] The compensated fractions of the additional gases may then replace the measured fractions of additional gases in eq. 6 to further improve the accuracy in post-oxygenator sweep gas flow rate determination, in accordance with:

[00007]$\begin{array}{cc}{\stackrel{.}{V}}_{\mathrm{out},\mathrm{comp}}=f\left({\stackrel{.}{V}}_{\mathrm{out}},F\mathrm{CO}{2}_{\mathrm{out},\mathrm{comp}},{F\mathrm{O2}}_{\mathrm{out},\mathrm{comp}},FH2O_{\mathrm{out}},{F\mathrm{N2}}_{\mathrm{out},\mathrm{comp}}\right)& \mathrm{eq}.9\end{array}$

[0236] A precise measure of {dot over (V)}CO2.sub.net may then be calculated using eq. 5 with a {dot over (V)}.sub.out,comp value calculated in accordance with eq. 9.

[0237] It should be noted that although described herein as techniques for controlling removal of CO2 from the bloodstream of a patient, the techniques of the first and second aspects of the present disclosure could as well be used to control an addition of CO2 to the bloodstream of the patient via the oxygenator 21. This may sometimes be desired to obtain or maintain a desired pH or partial pressure of CO2 (PCO2) in the blood of the patient 3. Consequently, it should be realised that the disclosed methods for controlling CO2 removal in the ECMO device 5 could be generalised to methods for controlling transfer of CO2 to or from the bloodstream of the patient 3, via the oxygenator 21, in order to control addition or removal of CO2 to or from the blood of the patient. The purpose of controlling CO2 transfer may be any of: 1) ensuring sufficient removal of CO2 from the blood of the patient; 2) keeping CO2 removal constant, e.g., in order to evaluate an ongoing respiratory treatment provided by the mechanical ventilator 7 and/or a lung function of the patient 3, and 3) obtaining or maintaining a set or desired post-oxygenator pH and/or PCO2, in particular during adjustments of the sweep gas flow rate.

[0238] In applications where CO2 transfer over the oxygenator membrane 23 is controlled to obtain or maintain a set or desired post-oxygenator pH and/or PCO2, the control computer 27 of the ECMO device 5 may be configured to automatically control the inlet sweep gas flow rate and/or the addition of CO2 to the inlet sweep gas flow to obtain or maintain pH and/or PCO2.