Systems and methods for controlling blood oxygenation

Abstract

A system (100, Fig. 1) for controlling blood oxygenation of a patient using an oxygenator 200 having a gas-blood interface 240. The system (100, Fig. 1) includes a controller (150, Fig. 1) configured to receive a measured value of a physiological parameter indicative of oxygenation of a patient's blood and calculate a difference between the measured value and a target value of the physiological parameter. The controller (150, Fig. 1) is further configured to control the gas supply device (300, Fig. 1) to: supply a first oxygenated gas (242a) to a first interface region (240a) of the gas-blood interface (240) and a second oxygenated gas (242b) to a second interface region (240b) of the gas-blood interface (240); in response to the measured value above the target value, reducing the amount of oxygen exposed to the blood by reducing the flow rate of the second oxygenated gas (242b) to reduce the difference; and reducing the oxygen concentration in the first oxygenated gas (242a) and / or its flow rate in response to the flow rate of the second oxygenated gas (242b) reduced to the threshold.

Description

[0001] The present disclosure relates to systems and methods for controlling blood oxygenation in a patient. In particular, the present disclosure relates to systems and methods for improved control of blood oxygenation in patients experiencing low metabolic rates, low blood oxygen saturations, and / or elevated blood carbon dioxide levels.

[0002] Cardiopulmonary perfusion involves extracorporeal oxygenation of a patient's blood, for example, when the patient is unable to oxygenate their own blood through breathing. Extracorporeal oxygenation involves an oxygenator that functions in place of the patient's own lungs (such as during cardiac and / or pulmonary surgery). During extracorporeal oxygenation, the oxygenator is used to control the levels of gases (such as oxygen and carbon dioxide) in the patient's blood, which is a function normally performed by the patient's own lungs. During a surgical procedure involving extracorporeal perfusion, the patient may experience changes in their requirements for the delivery and / or removal of certain gases in their blood.

[0003] For example, the patient may experience a change in their metabolic rate. A change in the patient's metabolic rate results in a change in the consumption of oxygen from the patient's blood. For example, a patient with a healthy or normal metabolic rate will consume more oxygen from their blood than a patient experiencing a low metabolic rate. For example, prior to placing the patient in a state of circulatory arrest (such as for surgery on the patient's heart), the patient's metabolic rate may be intentionally decreased (such as by lowering the patient's body temperature).

[0004] As another example, the patient may experience a change in the oxygen saturation in their blood. For example, the patient may suffer from low oxygen saturation in their blood. A cyanotic patient is a patient suffering from low oxygen saturation in their blood, which typically causes the skin to turn blue. This condition is more common in infants, particularly in infants with congenital heart abnormalities. Such patients are at risk of the harmful effects caused by hyperoxia (i.e., over-oxygenation of the blood).

[0005] As another example, the patient may experience a change in the carbon dioxide level in their blood. For example, during hypothermic circulatory arrest, the patient is cooled to reduce their metabolic rate. At lower temperatures, carbon dioxide is more soluble in the patient's blood, and thus the carbon dioxide level in the patient's blood may increase. After this procedure, the carbon dioxide level must be reduced to avoid the potentially harmful effects of having a significant excess of carbon dioxide in the patient's blood.

[0006] In traditional methods (those involving single-chamber oxygenators), clinicians may regulate the flow rate of the oxygenating gas and / or the oxygen concentration throughout the oxygenator. This can have unintended and undesirable consequences on the overall performance of the oxygenator. For example, if a clinician reduces the flow rate throughout the oxygenator to reduce oxygen delivery, the removal of carbon dioxide and nitrogen will also be reduced. Thus, the clinician may expose the patient to risks associated with poor control of blood gases (e.g., too high or too low levels of oxygen, carbon dioxide, and / or nitrogen). Such poor control can have harmful consequences such as: oxidative stress (in the case of hyperoxemia); increased risk of gas microemboli (in the case of increased nitrogen levels); tissue damage (in the case of hypoxemia); or increased risk of brain swelling (in the case of increased carbon dioxide levels).

[0007] Even in cases where a clinician is able to regulate the gas flow conditions differently for different parts of the oxygenator, incorrect operation of such an oxygenator can also lead to the same harmful consequences. The wide range of permutations available for controlling the oxygenating gas in an oxygenator makes it challenging for a clinician to control each and every gas level in a patient's blood. In particular, certain clinical scenarios require specific regulation of each blood gas component to achieve precise desired physiological effects.

[0008] Accordingly, there is a need to provide systems and methods for controlling blood oxygenation that have improved versatility and are capable of providing precise control of the gases in a patient's blood in specific clinical scenarios.

[0009] It should be noted that, for accuracy and in accordance with the conventions of the medical field, the pressure values given herein are in mmHg ("millimeters of mercury"). However, these values can be easily converted to atm ("atmospheres") since 1 atm is equal to 760 mmHg, or to Pa ("Pascals") since 1 mmHg is approximately equal to 133.3 Pa.

[0010] According to a first aspect, there is provided a system for controlling the blood oxygenation of a patient (as defined in claim 1).

[0011] The system is used to control the blood oxygenation of a patient using an oxygenator having a gas-blood interface. The gas-blood interface is configured to receive blood from the patient and expose the blood to a certain amount of oxygen as the blood passes through the oxygenator to produce oxygenated blood. The gas-blood interface of the oxygenator includes a first interface region and a second interface region, each of which is configured to be independently supplied with a respective oxygenation gas. The system includes a controller. The controller is configured to receive a measured value of a physiological parameter indicating the oxygenation of the patient's blood and calculate the difference between the measured value and a target value of the physiological parameter. The controller is further configured to control a gas supply device to supply a first oxygenation gas to the first interface region and a second oxygenation gas to the second interface region. The controller is also configured to control the gas supply device to reduce the amount of oxygen to which the blood is exposed to reduce the difference in response to a measured value higher than the target value by reducing the flow rate of the second oxygenation gas. The controller is further configured to control the gas supply device to reduce the oxygen concentration and / or its flow rate in the first oxygenation gas in response to the flow rate of the second oxygenation gas being reduced to a threshold.

[0012] Advantageously, supplying oxygenation gas to both the first interface region and the second interface region allows the oxygenation in the patient's blood to be adjusted while exposing the blood to a "high" amount of oxygen in the oxygenator. That is, the entire gas-blood interface is supplied with oxygenation gas. Thus, the blood is exposed to the oxygenation gas in both the first interface region and the second interface region and can therefore exchange gases through the entire gas-blood interface. This is particularly advantageous when the patient requires a "normal" or "healthy" oxygen saturation (e.g., 98.5%).

[0013] The oxygenation gas (e.g., the first oxygenation gas and / or the second oxygenation gas) may include a mixture of oxygen with nitrogen and / or carbon dioxide. For example, the oxygenation gas may include a mixture of nitrogen and oxygen (but no carbon dioxide). The oxygen concentration in the oxygenation gas can be adjusted by adjusting the relative proportions of nitrogen, carbon dioxide, and / or oxygen in the oxygenation gas. The "oxygen concentration in the oxygenation gas" can equivalently be referred to as the "fraction of inspired oxygen" (abbreviated as "FiO2"). The controller can be configured to control one or more valves or actuators that control the gas supply to the oxygenator in order to adjust (i.e., increase or decrease) the concentration of any or all components of the oxygenation gas supplied to each gas-blood interface of the oxygenator. Alternatively or additionally, the controller can be configured to control one or more valves or actuators that control the gas supply to the oxygenator in order to adjust (i.e., increase or decrease) the flow rate of the oxygenation gas supplied to each gas-blood interface of the oxygenator. In this way, the controller can control the composition and / or flow rate of the oxygenation gas supplied to the first gas-blood interface independently of the composition and / or flow rate of the oxygenation gas supplied to the second gas-blood interface.

[0014] Advantageously, the controller is configured to control the gas supply device in a manner that provides physiological benefits during surgery for treating a patient experiencing a low metabolic rate (e.g., a patient experiencing circulatory arrest). A patient experiencing a low metabolic rate has a reduced requirement for oxygenation of the blood because the patient's body will not consume as much oxygen from the blood as part of basic metabolic functions. Thus, during extracorporeal oxygenation, the level of oxygenation in the patient's blood will increase because the patient is not consuming enough of the oxygen supplied to the blood by the oxygenator.

[0015] In such a situation, conventional methods where over-oxygenation is not prevented can result in the patient receiving too much oxygen from the oxygenator, leading to hyperoxia. Alternatively, methods where the flow rate is reduced indiscriminately throughout a single-chamber or multi-chamber oxygenator will result in a complete reduction in oxygenator function, making extracorporeal oxygenation less effective. That is, reducing the flow rate and / or concentration throughout the oxygenator will reduce the delivery of oxygen to the blood and will also reduce the removal of carbon dioxide from the patient's blood. This will in turn lead to the accumulation of these undesired gases in the patient's blood.

[0016] In contrast, the controller disclosed herein is able to avoid hyperoxia while maintaining other oxygenator functions (e.g., carbon dioxide removal, nitrogen removal) in separate chambers. Initially, the controller controls the gas supply device to reduce the flow rate of the second oxygenation gas, thereby reducing the amount of oxygen to which the blood is exposed. During this reduction, an independent supply of oxygenation gas is provided to the first interface region and the second interface region. Thus, while the flow rate of the second oxygenation gas is reduced, the oxygenator is still able to provide gas delivery and / or removal via the first oxygenation gas. In other words, the delivery of oxygen to the blood can be reduced by reducing the flow rate of the second oxygenation gas, but at the same time, sufficient removal of carbon dioxide and nitrogen can be achieved using the first oxygenation gas. In this regard, the first oxygenation gas can be considered a "sweep gas". Similarly, the first interface region can be considered a "sweep chamber" or "sweep region".

[0017] "Independently supplied" means that the composition (e.g., gas concentration) and / or flow conditions (e.g., flow rate) of each respective oxygenation gas can be controlled independently for each interface region. The controller can be configured to change the number of interface regions supplied with oxygenation gas by opening or shutting off one or more of the independent gas supplies. For example, the controller can be configured to open or close one or more valves that allow or prevent gas flow from the independent gas supplies to the respective interface regions.

[0018] Furthermore, after the flow rate of the second oxygenation gas is reduced to a threshold value, the oxygen concentration and / or its flow rate in the first oxygenation gas can then be reduced as needed to further reduce oxygen delivery, thereby allowing a lower oxygen delivery to meet the oxygenation target value for a patient with a low metabolic rate.

[0019] For example, the controller may be configured to control a gas supply device to reduce the oxygen concentration and / or its flow rate in a first oxygenated gas in response to a flow rate of a second oxygenated gas that is reduced to a threshold value and a measured value that remains above a target value.

[0020] The first interface region and the second interface region may be arranged continuously with respect to the direction of blood flow through the oxygenator. That is, when blood flows through the oxygenator, the blood passes through each interface region one after another. For example, the interface regions may be arranged such that the blood first passes through the second interface region and then through the first interface region.

[0021] The first interface region and the second interface region may together constitute the entire gas-blood interface. In other words, the gas-blood interface may be divided only into two interface regions. Thus, it is to be understood that regardless of what proportion of the gas-blood interface forms the first interface region, the remaining proportion of the gas-blood interface will form the second interface region. The first interface region may be smaller than, larger than, or equal to the second interface region in size.

[0022] For example, the gas-blood interface may be split in half such that each of the first interface region and the second interface region accounts for 50% of the gas-blood interface (i.e., a "50 / 50 split"). In another example, the first interface region may account for 40% of the gas-blood interface while the second interface region may account for 60% of the gas-blood interface (i.e., a "40 / 60 split"), and vice versa (i.e., a "60 / 40 split"). Advantageously, when the first interface region supplies oxygenated gas at a standard flow rate typically used during a perfusion process (e.g., the oxygenated gas flow rate is approximately the same as the blood flow rate through the oxygenator, which may be about 4 - 5 liters per minute for example), the first interface region that accounts for 40% of the gas-blood interface provides appropriate regulation (e.g., addition, removal, and / or maintenance) of carbon dioxide. Other possible splits are also contemplated herein, such as: 30 / 70 split, 70 / 30 split, 25 / 75 split, 75 / 25 split, 20 / 80 split, 80 / 20 split, 10 / 90 split, or 90 / 10 split.

[0023] The term "gas-blood interface" refers to a component of an oxygenator that permits gas exchange between the gas supplied to the gas-blood interface and the blood supplied to the gas-blood interface. The gas-blood interface may include one or more groups of hollow fibers. Each group of hollow fibers may include a plurality of hollow fibers. Each group of hollow fibers may be in the form of a bundle of hollow fibers, a mat of hollow fibers, a spiral of hollow fibers, or other hollow fiber configurations known in the art.

[0024] Each hollow fiber within the hollow fiber group may include an opening for receiving oxygenated gas. Each hollow fiber may include a permeable wall that permits gas exchange between the blood and the oxygenated gas. When blood passes through the oxygenator, the hollow fiber group may be arranged to cross (e.g., perpendicularly) the blood flow so as to expose the blood to the oxygenated gas present in the hollow fiber group. The gas-blood interface may include a plurality of hollow fiber groups, each corresponding to a respective one of the interface regions. Alternatively, the gas-blood interface may include a single hollow fiber group, with each interface region corresponding to a portion of the single hollow fiber group.

[0025] The gas supply device may include a gas blender configured to receive one or more supply gases and blend these supply gases to produce one or more oxygenated gases for supply to the oxygenator. For example, the gas blender may be configured to receive an oxygen gas supply, a nitrogen gas supply, and / or a carbon dioxide gas supply. The oxygen gas supply may include a pure oxygen gas supply (i.e., the oxygen gas supply consists of 100% oxygen). The nitrogen gas supply may include a pure nitrogen gas supply (i.e., the nitrogen gas supply consists of 100% nitrogen). Alternatively, the nitrogen gas supply may include a gas mixture containing nitrogen (e.g., the nitrogen gas supply may be air, or may include air). The carbon dioxide gas supply may include a pure carbon dioxide gas supply (i.e., the carbon dioxide gas supply consists of 100% carbon dioxide). Alternatively, the carbon dioxide gas supply may include a gas mixture containing carbon dioxide (e.g., the carbon dioxide gas supply may be air, or may include air). The gas blender may be configured to blend the oxygen gas supply with the nitrogen gas supply and / or the carbon dioxide gas supply to produce one or more oxygenated gases. It should be noted that the blending of the supply gases may produce an oxygenated gas consisting of only one of the supply gases (e.g., the gas blender may supply an oxygenated gas consisting of 100% oxygen).

[0026] It is to be understood that the oxygenated gas may include additional gas components. For example, the oxygenated gas may additionally include one or more anesthetic gases (such as isoflurane, sevoflurane, desflurane, and / or nitrous oxide). The oxygenated gas may additionally or alternatively include other gases common in the art (such as helium and / or argon).

[0027] Alternatively or additionally, the gas supply device may include one or more valves arranged to control the flow rate and / or composition of the first and second oxygenated gases. For example, one or more valves may be present at the gas inlets supplying the oxygenated gases to the first and second interface regions. Controlling these valves can control the flow rates of the first and second oxygenated gases. One or more valves may also be connected to the gas supplies of the component gases that make up the first and second oxygenated gases. For example, one or more valves may control the flow of gases from an oxygen supply, a nitrogen supply, and / or a carbon dioxide supply. Such valves provide control over the gas flow rate and composition. The gas supply device may be integrated with the oxygenator or may be a device provided separately from the oxygenator.

[0028] Advantageously, the controller adjusts the amount of oxygen based on the measured value of a physiological parameter indicative of the oxygenation of the patient's blood to reduce the difference between the target value and the measured value. This control by the controller can be referred to as "closed-loop" control.

[0029] The controller may be configured to continuously perform some or all of these operations. For example, the controller may be configured to continuously receive the measured value, continuously calculate the difference, and / or continuously adjust the amount of oxygen. "Continuously" means that the operation can be performed in a continuous and uninterrupted manner. Alternatively or additionally, the controller may be configured to repeatedly perform some or all of these operations. For example, the controller may be configured to repeatedly receive the measured saturation, repeatedly calculate the difference, and / or repeatedly adjust the amount of oxygen. "Repeatedly" means that the operation can be performed at cyclic discrete intervals (e.g., once every millisecond, once every second, once every minute).

[0030] The physiological parameter can generally include any parameter capable of providing a clinical indication of the oxygenation level of the patient's blood. "Oxygenation level" means the amount indicating how much oxygen is present in the patient's blood. The terms "oxygenation level of the patient's blood" and "oxygenation of the patient's blood" are used interchangeably herein.

[0031] For example, the physiological parameter may include the oxygen saturation in the patient's blood and / or the partial pressure of oxygen in the patient's blood. The physiological parameter may include a function of the oxygen saturation in the patient's blood and / or the partial pressure of oxygen in the patient's blood.

[0032] As used herein, the term "oxygen saturation" refers to the percentage of oxygenated hemoglobin in the patient's blood relative to the total amount of hemoglobin in the patient's blood. The terms "saturation of oxygen" and "oxygen saturation" are used interchangeably herein. The term "adjust" means to increase or decrease a parameter.

[0033] The oxygen saturation may include arterial oxygen saturation, venous oxygen saturation, and / or peripheral oxygen saturation.

[0034] Arterial oxygen saturation (abbreviated as "SaO2") is defined as the oxygen saturation in a patient's arterial blood as directly measured from the blood. In the field of cardiac perfusion, SaO2 is considered the "true" value of the oxygen saturation in a patient's arterial blood. This is in stark contrast to the so-called "peripheral" oxygen saturation in arterial blood (referred to as SpO2). SpO2 is considered an estimate of SaO2 and is measured using pulse oximetry.

[0035] For example, when the measured value is blood oxygen saturation, the target oxygen saturation can be taken as the typical oxygen saturation of a healthy patient, such as an oxygen saturation between 95 - 100%, between 98 - 99%, or approximately 98.5%. Advantageously, an oxygen saturation of 98.5% is roughly the oxygen saturation in the blood of a healthy patient. Additionally, choosing an oxygen saturation below 100% allows for providing "headroom" to further increase the saturation if needed.

[0036] The controller can be configured to receive a target value of a physiological parameter. More specifically, the target value can be received by the controller as an input. For example, the controller can be configured to receive the target value as an input from a user interface. Alternatively or additionally, the controller can be pre-programmed with the target value. Alternatively or additionally, the controller can be configured to retrieve the target value from a look-up table stored locally or on a remote server.

[0037] In some embodiments, the controller is further configured to control a gas supply device to reduce the amount of oxygen to which the blood is exposed by decreasing the oxygen concentration in the second oxygenated gas.

[0038] Advantageously, the controller being configured to control the gas supply device to reduce both the flow rate and the oxygen concentration in the second oxygenated gas provides increased versatility of the system. In particular, both the oxygen concentration and the flow rate of the oxygenated gas affect the delivery of oxygen as well as the removal of nitrogen and carbon dioxide from the blood. Thus, by providing another variable (i.e., oxygen concentration) that can be controlled by the controller, the system is able to more accurately control the delivery of oxygen (by controlling the oxygen concentration) as well as the removal of carbon dioxide and nitrogen (by controlling the flow rate).

[0039] The controller can be configured to control the gas supply device to decrease the oxygen concentration in the second oxygenated gas before, after, and / or simultaneously with decreasing the flow rate of the second oxygenated gas. The controller can be configured to control the gas supply device to decrease the oxygen concentration in the second oxygenated gas before, after, and / or simultaneously with decreasing the oxygen concentration and / or its flow rate in the first oxygenated gas.

[0040] In an alternative embodiment, the controller can be configured to control the gas supply device to reduce the amount of oxygen to which the blood is exposed to reduce the difference by decreasing the oxygen concentration in the second oxygenated gas (rather than decreasing the flow rate of the second oxygenated gas) in response to a measured value that is higher than the target value.

[0041] In some embodiments, the controller is configured to control the gas supply device to reduce the flow rate of the second oxygenated gas while maintaining a constant oxygen concentration and / or a constant flow rate in the first oxygenated gas.

[0042] Advantageously, the gas supply device reduces the flow rate of the second oxygenated gas while maintaining a constant oxygen concentration and a constant flow rate in the first oxygenated gas. This enables the system to reduce oxygen delivery while maintaining the part of the oxygenator that provides the full functionality of the oxygenator. That is, although the flow rate in the second interface region is reduced, the first interface region continues to be supplied with the first oxygenated gas that is maintained in order to continue removing undesired gases from the blood.

[0043] In some embodiments, the constant oxygen concentration in the first oxygenated gas is 100%.

[0044] In other words, the first oxygenated gas can consist of pure oxygen.

[0045] Advantageously, the oxygenated gas consisting only of oxygen does not contain any nitrogen. Nitrogen is a major component of gaseous microemboli (GMEs) or bubbles in the blood passing through the oxygenator. In essence, nitrogen cannot dissolve in the blood and thus causes the formation of GMEs. These GMEs can grow in size by accumulating a layer of substances carried by the blood (such as proteins in the blood) on their outer surfaces. Thus, GMEs act as obstructions in the blood and can lead to serious complications such as tissue or organ damage. When the nitrogen partial pressure in the oxygenated gas is similar or substantially equal to the nitrogen partial pressure in the blood, the nitrogen concentration in the oxygenated gas is too high. Due to the lack of a diffusion gradient between the nitrogen in the blood and the nitrogen in the oxygenated gas, this results in a reduced (or substantially no) removal of nitrogen from the blood when the blood passes through the oxygenator. Correspondingly, due to the high nitrogen content in the blood, there is also a lack of a diffusion gradient between the nitrogen in the GMEs and the nitrogen in the blood itself. Thus, little or no nitrogen diffuses from the GMEs to the blood or from the blood to the oxygenated gas, and thus there is an increased risk that the GMEs will continue to pass through the bloodstream (unchanged by the oxygenator). By providing an oxygenated gas of pure oxygen, a greater diffusion gradient is created between the blood and the oxygenated gas, which in turn leads to a greater diffusion gradient between the GMEs and the surrounding blood. Thus, more nitrogen is transferred from the blood to the oxygenated gas, and more nitrogen is transferred from the GMEs to the blood. Thus, the removal of nitrogen is maximized and thus the risk of GMEs is considerably or completely reduced.

[0046] For similar reasons, carbon dioxide removal is also maximized because the first oxygenated gas does not contain any carbon dioxide. Thus, advantageously, removal of undesired gases (such as carbon dioxide and nitrogen) is maximized even while reducing the flow rate of the second oxygenated gas to reduce the amount of oxygen to which the blood is exposed.

[0047] In some embodiments, the controller is further configured to control the gas supply device to maintain the flow rate of the second oxygenated gas at a threshold. The controller can also be configured to increase the amount of oxygen to which the blood is exposed by increasing the oxygen concentration and / or its flow rate in the first oxygenated gas.

[0048] The controller can be configured to maintain the flow rate of the second oxygenated gas and increase the oxygen concentration and / or its flow rate in the first oxygenated gas after reducing the oxygen concentration and / or its flow rate in the first oxygenated gas. That is, the controller can reduce the oxygen concentration and / or its flow rate in the first oxygenated gas until a target value is reached and then increase these variables. For example, this can be performed in response to a change in the target value (such as an increase) or in response to a change in a measured value (such as due to a physiological change in the patient that causes a change in the metabolic rate).

[0049] The controller can generally be configured to adjust (such as increase and / or decrease) the oxygen concentration and / or its flow rate in the first oxygenated gas while maintaining the flow rate of the second oxygenated gas at a threshold. Generally, the controller can be configured to adjust the oxygen concentration and / or its flow rate in the first oxygenated gas and / or the second oxygenated gas in response to a change in a measured value of a physiological parameter and / or a target value. That is, the controller can be configured to maintain or adjust the oxygen concentration in the patient's blood during a clinical intervention.

[0050] In some embodiments, the threshold is a flow rate of zero.

[0051] That is, the controller initially reduces the flow rate of the second oxygenated gas until the flow rate reaches zero (i.e., there is no longer any flow of the second oxygenated gas in the second interface region). In this case, the controller has reduced the flow rate of the second oxygenated gas until it can no longer be reduced. Thus, at this stage, the amount of oxygen to which the blood is exposed is at the lowest level achievable by only controlling the flow rate of the second oxygenated gas. At this stage, the oxygen concentration in the first oxygenated gas is reduced in order to continue reducing the amount of oxygen to which the blood is exposed. The threshold flow rate does not need to be zero but can instead be some other value suitable for a particular clinical situation.

[0052] Preferably, the controller can be configured to control the gas supply device to: supply a first oxygenated gas to a first interface region and a second oxygenated gas to a second interface region, where the first oxygenated gas consists of pure oxygen; in response to a measured value that is higher than a target value (e.g., due to a decrease in the patient's metabolic rate), reduce the amount of oxygen to which the blood is exposed by reducing the flow rate of the second oxygenated gas to zero in order to reduce the difference; and in response to the flow rate of the second oxygenated gas being reduced to zero and in response to the measured value continuing to be higher than the target value, reduce the oxygen concentration in the first oxygenated gas to reduce the difference.

[0053] In some embodiments, the controller is further configured to control the gas supply device to initially supply only the first oxygenated gas to the first interface region and not supply the second oxygenated gas to the second interface region. The controller can also be configured to control the gas supply device to adjust the amount of oxygen to which the blood is exposed by adjusting the oxygen concentration and / or its flow rate in the first oxygenated gas. The controller can also be configured to control the gas supply device to subsequently initiate the supply of the second oxygenated gas to the second interface region of the gas-blood interface to increase the amount of oxygen to which the blood is exposed.

[0054] It should be understood that the term "initially" in this context refers to the separate supply of the first oxygenated gas before the supply of both the first oxygenated gas and the second oxygenated gas. However, it should also be understood that the controller can be configured to control the gas supply device to stop supplying the second oxygenated gas, and thus the separate supply of the first oxygenated gas can also occur after the supply of both the first oxygenated gas and the second oxygenated gas.

[0055] The controller can be configured to increase and / or reduce the amount of oxygen to which the blood is exposed by increasing and / or reducing the oxygen concentration and / or its flow rate in the first oxygenated gas.

[0056] Advantageously, this functionality allows the blood to be initially exposed to a lower amount of oxygen by supplying only a part of the gas-blood interface (rather than the entire gas-blood interface). Thus, the blood is exposed to the oxygenated gas only in the first interface region and can therefore exchange gases only when in the first interface region of the gas-blood interface. This is particularly advantageous when treating patients who are currently experiencing a decrease in metabolic rate (e.g., patients in circulatory arrest) and / or patients with reduced oxygen saturation (e.g., cyanotic patients). This functionality allows, for example, the patient's current oxygen saturation (or other physiological parameter indicating the oxygenation of the patient's blood) to be selected as the target oxygen saturation (e.g., to initially match the treatment to the patient's current clinical state), even if the patient's oxygen saturation is very low.

[0057] Initially, supplying only the first oxygenated gas to the first interface region may include supplying the first oxygenated gas consisting of pure oxygen. Advantageously, supplying pure oxygen only to the first interface region (e.g., 40% of the gas-blood interface) provides a sufficiently high diffusion gradient for carbon dioxide between the first oxygenated gas and the blood passing through the oxygenator, thus ensuring sufficient removal of carbon dioxide from the blood.

[0058] In particular, this functionality allows the system to expose the blood to a lower amount of oxygen (and thus operate at a lower oxygen saturation) compared to if the entire gas-blood interface were supplied with the oxygenated gas. For example, supplying an oxygenated gas containing 20% oxygen to the entire gas-blood interface would expose the blood to more oxygen compared to if an oxygenated gas containing 20% oxygen were supplied only to 40% of the gas-blood interface.

[0059] Advantageously, this functionality also allows the system to gradually increase the oxygenation of the patient's blood by gradually increasing the oxygen concentration and / or its flow rate in the first oxygenated gas. That is, the controller can be configured to increase the amount of oxygen to which the blood is exposed by adjusting the oxygen concentration and / or its flow rate in the first oxygenated gas. This allows the amount of oxygen to which the blood is exposed to be gradually increased, thereby increasing the oxygenation of the patient's blood.

[0060] At a certain point in time, the system can then start supplying a second oxygenated gas to the second interface region to further increase the amount of oxygen to which the blood is exposed and thus further increase the oxygenation of the patient's blood.

[0061] Generally, the first oxygenated gas can be the same as or different from the second oxygenated gas. For example, the first oxygenated gas can be supplied from a first gas supply independent of the second gas supply that supplies the second oxygenated gas. This allows the flow rates and / or compositions of the first oxygenated gas and the second oxygenated gas to be independently adjusted. Alternatively, the first oxygenated gas and the second oxygenated gas can be supplied from a single gas supply. In this case, the controller can be configured to independently adjust the flow rates of the first oxygenated gas and the second oxygenated gas by controlling which interface regions are supplied by the single gas supply. However, in such an example, it may not be possible to change the composition of the first oxygenated gas independently of the second oxygenated gas.

[0062] In some embodiments, the controller is configured to control the gas supply device to increase the amount of oxygen to which the blood is exposed by increasing the oxygen concentration and / or its flow rate in the first oxygenated gas in response to a measured value below a target value, and to adjust the amount of oxygen to which the blood is exposed.

[0063] In some embodiments, the controller is configured to control the gas supply device to initiate the supply of the second oxygenated gas in response to the oxygen concentration in the first oxygenated gas having increased to a threshold concentration.

[0064] That is, the controller initially increases the oxygen concentration in the first oxygenated gas until the oxygen concentration reaches a threshold concentration, at which point the controller initiates the supply of a second oxygenated gas to the second interface region. For example, the threshold concentration can be 100%. In this case, the controller increases the oxygen concentration in the first oxygenated gas until it can no longer be increased. Thus, at this stage, the amount of oxygen to which the blood is exposed is at its maximum when only supplying gas to the first interface region. At this stage, a second oxygenated gas is supplied to the second interface region in order to continue increasing the amount of oxygen to which the blood is exposed. The threshold concentration need not be 100% and, instead, can be other values suitable for a particular clinical situation.

[0065] Alternatively or additionally, the controller can be configured to control the gas supply device to initiate the supply of the second oxygenated gas in response to the flow rate of the first oxygenated gas having been increased to a threshold flow rate. For example, the threshold flow rate can be the maximum safe flow rate that can be provided by the oxygenator during extracorporeal oxygenation (e.g., 5 liters per minute). The maximum safe flow rate of the oxygenated gas can be determined based on the pressure of the patient's blood in the oxygenator. For example, the maximum safe flow rate of the oxygenated gas can be selected such that the pressure of the oxygenated gas is less than the pressure of the patient's blood in the oxygenator.

[0066] In some embodiments, the controller is further configured to, after initiating the supply of the second oxygenated gas, increase the oxygen concentration and / or its flow rate in the second oxygenated gas to further increase the amount of oxygen to which the blood is exposed.

[0067] In some embodiments, the controller is further configured to receive a second measured value of a second physiological parameter indicative of the carbon dioxide level in the patient's blood. The controller can also be configured to calculate the difference between the second measured value and a second target value of the second physiological parameter.

[0068] Advantageously, the controller is thus configured to monitor the removal of carbon dioxide through the oxygenator. This helps to ensure adequate carbon dioxide removal while the controller adjusts the oxygenated gas in the oxygenator. As described above, adjusting the oxygen concentration and / or its flow rate in the first and second oxygenated gases affects the removal of carbon dioxide. Thus, by monitoring the level of carbon dioxide and comparing it to the target value, the controller can ensure that the level of carbon dioxide is maintained within a safe limit during clinical intervention. For example, the second physiological parameter can be the partial pressure of carbon dioxide (abbreviated as "PaCO2").

[0069] In some embodiments, the controller is further configured to control the gas supply device to increase the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas in response to a second measured value that is higher than the second target value.

[0070] Advantageously, this functionality allows the controller to respond to insufficient removal of carbon dioxide. That is, if the second measured value is higher than the second target value, the level of carbon dioxide is higher than desired, and thus the removal of carbon dioxide is insufficient. The removal of carbon dioxide can be increased by increasing the flow rate of the oxygenated gas flowing through the oxygenator. However, by only increasing the flow rate of the oxygenated gas, the volume of oxygen in the oxygenator will be increased, resulting in an increased delivery of oxygen to the patient's blood and an increased risk of hyperoxia. Therefore, in order to regulate the oxygen delivery while increasing the carbon dioxide removal, the controller is configured to decrease the oxygen concentration in the second oxygenated gas.

[0071] This is particularly advantageous in various clinical scenarios that result in an increase in carbon dioxide in the patient's blood, such as during hypothermic circulatory arrest, during intravascular venous harvesting in coronary artery bypass surgery, or during resuscitation after prolonged perfusion insufficiency (e.g., during cardiopulmonary resuscitation).

[0072] In some embodiments, the controller is configured to control the gas supply device to increase the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas, so as to maintain a constant volume of oxygen in the second interface region.

[0073] Advantageously, the controller thus balances the increase in flow rate by decreasing the oxygen concentration, such that the volume of oxygen gas in the second interface region remains constant. This will result in an increase in carbon dioxide removal (due to the increased flow rate), while not increasing the delivery of oxygen. More specifically, maintaining a constant volume of oxygen means that the diffusion gradient between the second oxygenated gas and the patient's blood remains unchanged, and thus there is little to no change in the transfer of oxygen across the gas-blood interface. Therefore, the removal of carbon dioxide can be increased without affecting the delivery of oxygen.

[0074] It should be understood that these operations can be reversed to achieve the opposite physiological effect. That is, the controller can also be configured to control the gas supply device to decrease the flow rate of the second oxygenated gas while increasing the oxygen concentration in the second oxygenated gas in response to a second measured value that is lower than the second target value. The controller can be configured to decrease the flow rate of the second oxygenated gas while increasing the oxygen concentration in the second oxygenated gas so as to maintain a constant volume of oxygen in the second interface region.

[0075] This is particularly advantageous, for example, in the case of a brain injury. A reduced carbon dioxide level in the blood can reduce the blood flow to the patient's brain, which is particularly advantageous for reducing swelling in the case of a brain injury. In contrast, by reducing the flow rate of the second oxygenated gas, the removal of carbon dioxide can be reduced, thereby increasing the level of carbon dioxide in the patient's blood. If desired, the flow rate of the second oxygenated gas and the oxygen concentration therein can be reduced simultaneously to limit oxygenation as well as carbon dioxide removal, thereby reducing the risk of brain swelling and the risk of brain tissue damage caused by excessive oxygen. Thus, the flow rate of the second oxygenated gas and the oxygen concentration therein can be changed simultaneously to address brain swelling caused by high carbon dioxide levels and to reduce the risk of brain tissue damage associated with excessive oxygen.

[0076] In some embodiments, the controller is configured to control the gas supply device to simultaneously maintain a constant oxygen concentration and a constant flow rate in the first oxygenated gas, while increasing the flow rate of the second oxygenated gas and simultaneously reducing the oxygen concentration in the second oxygenated gas.

[0077] The advantages of maintaining the gas flow conditions (i.e., the oxygen concentration and the flow rate therein) in the first oxygenated gas have been discussed above. As mentioned above, this allows the controller to maintain other oxygenator functions (such as carbon dioxide removal, nitrogen removal) in the first interface region.

[0078] According to a second aspect, there is provided a system for controlling the blood oxygenation of a patient (as defined in claim 15).

[0079] The system is for controlling the blood oxygenation of a patient using an oxygenator having a gas-blood interface configured to receive blood from the patient and to expose the blood to a quantity of oxygen as the blood passes through the oxygenator to produce oxygenated blood. The gas-blood interface of the oxygenator includes a first interface region and a second interface region, each interface region being configured to be independently supplied with a respective oxygenated gas. The system includes a controller. The controller is configured to receive a measured value of a physiological parameter indicative of the carbon dioxide level in the patient's blood and to calculate the difference between the measured value and a target value of the physiological parameter. The controller is further configured to control the gas supply device to supply a first oxygenated gas to the first interface region and a second oxygenated gas to the second interface region. The controller is further configured to control the gas supply device to increase the flow rate of the second oxygenated gas and simultaneously reduce the oxygen concentration in the second oxygenated gas in response to a measured value that is higher than the target value.

[0080] It should be understood that the process of blood oxygenation (comparable to the parameters of oxygenation) involves the addition and / or removal of multiple blood gases (such as oxygen, carbon dioxide, and nitrogen), rather than simply adding oxygen to the blood. In this regard, the system can be regarded as a system for controlling the blood carbon dioxide level of a patient using an oxygenator.

[0081] Advantageously, as discussed above, the controller is thus configured to monitor the removal of carbon dioxide through the oxygenator. Advantageously, as discussed above, this function allows the controller to respond to insufficient removal of carbon dioxide.

[0082] In some embodiments, the controller is configured to control the gas supply device to increase the flow rate of the second oxygenation gas while reducing the oxygen concentration in the second oxygenation gas, so as to maintain a constant volume of oxygen in the second interface region.

[0083] In some embodiments, the controller is configured to control the gas supply device to simultaneously maintain a constant flow rate and / or constant concentration of the first oxygenation gas, while increasing the flow rate of the second oxygenation gas and simultaneously reducing the oxygen concentration in the second oxygenation gas.

[0084] In some embodiments, the system further includes a gas supply device. The gas supply device can be configured to control the flow rate and / or the oxygen concentration therein of the first oxygenation gas and the second oxygenation gas.

[0085] In some embodiments, the system further includes an oxygenator.

[0086] The system can be supplied independently of the oxygenator and / or the gas supply device. For example, the system can include a control module or a control unit, which is configured to be connected to the oxygenator and / or the gas supply device. The system can include an oxygenator and / or a gas supply device that has been connected to the controller and / or integrated with the controller.

[0087] Although the systems described herein generally include a single oxygenator, in some embodiments, the system can include multiple oxygenators. The oxygenators can be arranged in series such that blood received from a patient passes through a first oxygenator and then through a second oxygenator, and so on. Alternatively, the oxygenators can be arranged in parallel and / or in any combination of series and parallel. In such an example, each oxygenator in the system can be connected to a separate, respective gas supply device and / or to a separate, respective independent gas supply. That is, each oxygenator can be configured to expose blood to one or more oxygenating gases that can be controlled independently of one or more oxygenating gases in another oxygenator in the system. Any or all of the oxygenators in the system can include the features and characteristics of the oxygenator described herein. For example, one or more (e.g., all) of the oxygenators in the system can include a gas-blood interface that is divided into a plurality of interface regions. For example, the system can include multiple oxygenators, each including a gas-blood interface that includes a first interface region and a second interface region. Alternatively, a single oxygenator in the system can include multiple interface regions, and any additional oxygenators in the system can include a gas-blood interface having a single interface region (i.e., an undivided gas-blood interface). In this regard, it should be understood that the controller described herein can be configured to control a system that includes multiple oxygenators.

[0088] In some embodiments, the oxygenator includes a gas inlet region for receiving an oxygenating gas into the gas-blood interface. The gas inlet region can include a separator that divides the gas inlet region into a first gas inlet region and a second gas inlet region. The first gas inlet region can be configured to receive a first oxygenating gas. The first gas inlet region can be configured to provide the first oxygenating gas to the first interface region. The second gas inlet region can be configured to receive a second oxygenating gas. The second gas inlet region can be configured to provide the second oxygenating gas to the second interface region.

[0089] The gas-blood interface of the oxygenator can include a plurality of hollow fiber bundles, each hollow fiber bundle corresponding to one of the interface regions and thus corresponding to one of the gas inlet regions. Alternatively, the gas-blood interface can include a single hollow fiber bundle, and each interface region (and thus each gas inlet region) can correspond to a portion of the single hollow fiber bundle.

[0090] One or more separators can divide the gas-blood interface. For example, a separator can extend from the gas inlet region into the gas-blood interface and can extend through the gas-blood interface. In cases where the gas-blood interface includes a plurality of hollow fiber bundles, the hollow fiber bundles can be separated from each other by gaps in which the separators are located.

[0091] At least one of the one or more septa can be movable. For example, the one or more septa can be movable to adjust the relative size of each of the gas inlet regions. The controller can be configured to adjust the position of the one or more septa (e.g., by activating a motor coupled to the one or more septa). For example, the controller can be configured to receive an input representative of a desired physiological parameter value and / or a desired position of the one or more septa. The controller can also be configured to adjust the position of the one or more septa in response to the input. The controller can also be configured to convert the desired physiological parameter value into a position of the one or more septa. For example, by adjusting the one or more septa to increase the size of the interface region supplied by the oxygenated gas, the exposure of the blood to the oxygenated gas increases, which can in turn increase the oxygenation level in the blood.

[0092] In some embodiments, the system further includes a sensor configured to measure a physiological parameter. The controller can be configured to receive the measured value from the sensor.

[0093] The sensor can be configured to measure the physiological parameter (e.g., the oxygen saturation present in oxygenated blood) via spectrophotometry performed on the blood line. Advantageously, spectrophotometry provides a method of measuring a physiological parameter related to blood oxygenation. In addition, spectrophotometry is a non-invasive method that can be performed during surgery without contacting the patient's blood (e.g., to measure pH or body temperature).

[0094] Spectrophotometry for measuring oxygen saturation involves irradiating a white light source onto the blood in the blood line. The white light is at least partially reflected by the blood, and the reflected light is detected by a receiver. The receiver will only detect the wavelengths reflected by the blood and not the wavelengths absorbed by the blood. Some wavelengths in the white light are more strongly absorbed by oxygenated hemoglobin, while other wavelengths are more strongly absorbed by deoxygenated hemoglobin. By measuring the absorption at each wavelength and comparing the relative absorption, the ratio of oxygenated hemoglobin to deoxygenated hemoglobin can be determined, which can in turn be used to determine the oxygen saturation in the blood.

[0095] To assist spectrophotometry, the blood line can be transparent. For example, the blood line can be transparent to each wavelength used in the spectrophotometry.

[0096] In some embodiments, the sensor is located on the blood line. The blood line can be connected to an oxygenator. The blood line can be configured to carry oxygenated blood from the oxygenator to the patient.

[0097] Advantageously, the sensor measures a physiological parameter after oxygenation by the oxygenator. The sensor can be considered to be "downstream of the oxygenator". That is, the blood flows through the sensor after it has passed through the oxygenator. In other words, the sensor is located downstream with respect to the direction of blood flow. In this regard, the physiological parameter measured by the sensor can be considered to constitute an "arterial" measurement. This is in stark contrast to a "venous" measurement, which would be made upstream of the oxygenator (e.g., immediately after the blood leaves the patient, or between the venous reservoir and the oxygenator).

[0098] Venous measurements of physiological parameters are severely affected by patient physiological factors. For example, venous oxygen saturation and venous partial pressure are functions of the patient's metabolic rate, blood flow rate, hemoglobin level, and other physiological parameters. Thus, performing a venous blood oxygenation measurement inherently incorporates uncertainty and a lack of accuracy into the subsequent control of the patient's blood oxygen level based thereon. Clinicians need to know anesthetic factors, the degree of patient paralysis, patient body temperature, the state of the patient's capillary bed, autonomic responses (e.g., immune or inflammatory responses), and various other factors in order to control oxygenation based on venous measurements. Thus, using a sensor to measure physiological parameters after oxygenation provides increased accuracy and safety for a system for controlling blood oxygenation.

[0099] In some embodiments, the system further includes a venous reservoir that receives blood from the patient. The system can also include a pump configured to drive the blood from the venous reservoir through the oxygenator.

[0100] The venous reservoir can be located upstream of the oxygenator. The venous reservoir can be configured to be located between the oxygenator and the patient. That is, the venous reservoir can receive deoxygenated blood from the patient. The pump can be configured to draw deoxygenated blood from the venous reservoir and cause the deoxygenated blood to flow into the oxygenator. The pump can be located upstream of the oxygenator. The pump can be located downstream of the venous reservoir. The pump can be located between the venous reservoir and the oxygenator. The pump can be a centrifugal pump or a roller pump (peristaltic pump).

[0101] It should be understood that any feature, function, characteristic, or advantage described with respect to the first aspect can be applied to the second aspect, and vice versa. Similarly, the features, functions, characteristics, or advantages described with respect to the system can also be applied to the corresponding method, and vice versa.

[0102] Exemplary embodiments will now be described with reference to the accompanying drawings, in which:

[0103] Figure 1 is a schematic diagram of a system for controlling a patient's blood oxygenation;

[0104] Figure 2Schematic diagram of an example of an oxygenator for a system for controlling a patient's blood oxygenation;

[0105] Figure 3A is Figure 2 Schematic diagram of an oxygenator having a first interface region supplied with a first oxygenation gas;

[0106] Figure 3B is Figure 2 Schematic diagram of an oxygenator having a first interface region supplied with a first oxygenation gas and a second interface region supplied with a second oxygenation gas;

[0107] Figure 4 Flowchart of a first example of a method of using an oxygenator to control a patient's blood oxygenation;

[0108] Figure 5 Flowchart of a second example of a method of using an oxygenator to control a patient's blood oxygenation;

[0109] Figure 6 Flowchart of a third example of a method of using an oxygenator to control a patient's blood oxygenation; and

[0110] Figure 7 is a schematic diagram showing Figure 2 the operating state of the oxygenator.

[0111] Figure 1 Depicts a system 100 for controlling a patient's blood oxygenation. The position of the patient relative to the system 100 is shown by an arrow P, which indicates which blood lines (see below) lead to the patient. The system 100 includes an oxygenator 200. The oxygenator 200 includes a gas-blood interface 240 (see Figure 2 ), which is configured to receive blood from the patient and expose the blood to a certain amount of oxygen as the blood passes through the oxygenator 200 to produce oxygenated blood. The structure of the oxygenator 200 will be described in more detail with reference to Figure 2 .

[0112] The system 100 also includes a gas supply device 300. The gas supply device 300 is configured to control the flow rate and / or the oxygen concentration therein of a first oxygenation gas 242a and a second oxygenation gas 242b (as shown in Figure 3A and 3B ). The first oxygenation gas 242a can be supplied to the oxygenator 200 via a first gas inlet 222a. The second oxygenation gas 242b can be supplied to the oxygenator 200 via a second gas inlet 222b.

[0113] The gas supply device 300 is depicted as a single component that receives a first gas supply 302a and a second gas supply 302b. For example, the gas supply device 300 can include a gas blender configured to receive one or more supply gases and blend the supply gases to produce one or more oxygenated gases for supply to the oxygenator 200. However, it should be understood that the gas supply device 300 can include multiple components. For example, in addition to or instead of a gas blender, the gas supply device 300 can include one or more valves that control the flow rate of one or more supply gases to allow the gas supply device 300 to control the flow rate and / or the oxygen concentration therein of one or more supply oxygenated gases supplied to the oxygenator 200. The gas supply device 300 can include valves, actuators, and / or other gas flow control mechanisms that control the gas flow into and / or out of the oxygenator 200.

[0114] The system 100 also includes a sensor 110. The sensor 110 is located downstream of the oxygenator 200. In the depicted example, the sensor 110 is located upstream of the patient on the blood line (in this case the arterial line 132) leaving the oxygenator 200. The sensor 110 can be configured to measure a physiological parameter indicative of the oxygenation of the patient's blood. For example, the sensor 110 is configured to measure the oxygen saturation present in the oxygenated blood (i.e., the blood oxygenated by the oxygenator 200). For example, the sensor 110 can be configured to measure the oxygen saturation present in the oxygenated blood via spectrophotometry performed on the arterial line 132. In this case, the sensor 110 is considered to measure the "arterial oxygen saturation" (SaO2). It should be understood that other techniques for measuring oxygen saturation can also be used with the sensor 110. Additionally, the sensor 110 can be located downstream of the oxygenator 200 and not upstream of the patient. For example, the sensor 110 can include a pulse oximeter attached to the patient. In this case, the sensor 110 would be considered to measure the "peripheral oxygen saturation" (SpO2). SpO2 is understood in the art to represent an estimate of SaO2, and SaO2 is considered the "true" value of the oxygen saturation in the patient's arterial blood.

[0115] Alternatively or additionally, sensor 110 may be configured to measure a physiological parameter indicative of the level of carbon dioxide in a patient's blood. For example, sensor 110 may be configured to measure the partial pressure of carbon dioxide present in oxygenated blood (i.e., blood that has been oxygenated by oxygenator 200). For example, sensor 110 may be configured to measure the partial pressure of carbon dioxide via blood gas analysis such as an arterial blood gas (ABG) test. In such a case, sensor 110 may be an invasive blood gas sensor. It should be understood that other techniques for measuring the partial pressure of carbon dioxide may be used in sensor 110. System 100 may include additional sensors (not shown) to measure the partial pressure of carbon dioxide. That is, the system may include a first sensor 110 for measuring a physiological parameter indicative of the oxygenation of a patient's blood and a second sensor (not shown) for measuring a physiological parameter indicative of the level of carbon dioxide in a patient's blood.

[0116] System 100 further includes a controller 150. Controller 150 is configured to receive measured values from sensor 110 (or any other sensor present in system 100). Controller 150 is also configured to calculate the difference between the measured values and the target values of the physiological parameters. The functions of controller 150 will be described in more detail below with reference to Figures 3A to 5 Controller 150 is communicatively coupled to oxygenator 200, gas supply device 300, and sensor 110, as

[0117] depicted by the dashed lines in Figure 1 . That is, controller 150 may be configured to communicate with oxygenator 200, gas supply device 300, and sensor 110. Such communication may occur via a hardware connection (e.g., a wired connection) or via wireless communication. In this regard, it should be understood that Figure 1 the dashed lines depicted in

[0118] are merely illustrative and do not necessarily represent a physical connection between components. Additionally, it should be understood that controller 150 may be communicatively coupled to more or fewer components in system 100. For example, controller 150 may not necessarily communicate directly with oxygenator 200 and instead may be configured to communicate only with gas supply device 300. Similarly, controller 150 may not necessarily communicate directly with sensor 110 and instead may be configured to communicate with an intermediate transceiver that relays the measured values from sensor 110 to controller 150. Controller 150 may also be configured to communicate with pump 130 and / or other components present in system 100. Those skilled in the art will readily understand other arrangements of the communicative couplings between components.

[0119] The controller 150 may include any suitable type of data processing device, such as a microprocessor, a microcontroller, or an application specific integrated circuit (ASIC). The data processing device may be communicatively coupled to a memory (e.g., volatile memory, non-volatile memory, or both volatile and non-volatile memory) storing processor-executable instructions that cause the controller to perform any of the methods disclosed herein.

[0120] As Figure 1 shown, the system 100 is configured to receive blood from a patient via the venous line 122 and return blood from the patient via the arterial line 132. The connection of the system 100 to the patient is shown by Figure 1 the arrow P in. The system 100 also includes a venous reservoir 120 configured to receive blood from the patient via the venous line 122. The venous reservoir 120 may additionally be configured to receive blood from the patient via one or more salvage lines, one or more flush lines, and / or one or more lines configured to carry a surgical fluid (e.g., priming fluid, volume expander, blood, and / or drug) (such as presented by the line 124 in Figure 1 . The venous reservoir 120 is located upstream of the oxygenator 200, between the patient and the oxygenator 200. It should be understood that in other embodiments, the exact arrangement of the venous reservoir 120 and the pump 130 may vary. Indeed, the system 100 may not necessarily include the venous reservoir 120 and the pump 130. In such cases, the oxygenator 200 may be configured to receive blood directly from the patient.

[0121] Once the blood is collected in the venous reservoir 120, it is driven by the pump 130 through the oxygenator 200. The pump 130 is located downstream of the venous reservoir 120 and upstream of the oxygenator 200. In the depicted embodiment, the pump 130 is a roller pump (or peristaltic pump). However, it should be understood that depending on the circumstances, other types of pumps, such as a centrifugal pump, may be used. The blood exits the pump 130 and is received by the oxygenator 200 via the blood inlet 210. The blood is oxygenated by the oxygenator 200 and then exits the oxygenator via the blood outlet 212, then passes through the sensor 110, and returns to the patient via the arterial line 132. The flow path of the blood through the system 100 is shown by Figure 1 the arrow A in.

[0122] Although the system 100 is depicted as including various components (e.g., the sensor 110, the oxygenator 200, the gas supply device 300, the venous reservoir 120, the pump 130), it should be understood that the system 100 may include only the controller 150. That is, the system 100 does not necessarily include the sensor 110, the oxygenator 200, or Figure 1Any other components depicted. System 100, instead, can be provided as a controller 150, which is configured to communicate with and / or control any of the above components. Figure 1 The additional components in are included within system 100 only for illustrative purposes to show contexts in which controller 150 can operate. However, system 100 can include Figure 1 any or all of the additional components in.

[0123] Figure 2 An exemplary structure of an oxygenator 200 is depicted. As described above, oxygenator 200 includes a blood inlet 210 for receiving blood from a patient and a blood outlet 212 for returning blood to the patient. Oxygenator 200 also includes two gas inlets for receiving two oxygenation gases into oxygenator 200, as depicted by arrow G. Oxygenator 200 includes a first gas inlet 222a and a second gas inlet 222b. The first gas inlet 222a and the second gas inlet 222b are each fluidly connected to a gas inlet zone 230. Oxygenator 200 also includes a gas outlet 226 (which can be referred to as a gas discharge device 226) for releasing exhaust gas from oxygenator 200. The oxygenation gas exits oxygenator 200 from the gas outlet 226 via a gas outlet zone 231.

[0124] The gas inlet zone 230 includes a separator 232, which divides the gas inlet zone 230 into a plurality (in this case, two) of gas inlet regions 234a, 234b. Each gas inlet region 234a, 234b is configured to receive a different oxygenation gas in the respective oxygenation gas. More specifically, the first gas inlet region 234a is configured to receive oxygenation gas from the first gas inlet 222a, while the second gas inlet region 234b is configured to receive oxygenation gas from the second gas inlet 222b.

[0125] Oxygenator 200 also includes a gas-blood interface 240. The gas inlet zone 230 is fluidly connected to the gas-blood interface 240. The gas outlet zone 231 is also fluidly connected to the gas-blood interface 240. That is, the oxygenation gas enters the gas-blood interface 240 from the gas inlet zone 230 and exits the gas-blood interface 240 via the gas outlet zone 231.

[0126] The gas-blood interface 240 can include one or more groups of hollow fibers, and each group of hollow fibers includes a plurality of hollow fibers. Each group of hollow fibers includes an inlet potting fluidly connected to the gas inlet zone 230. Each group of hollow fibers includes an outlet potting fluidly connected to the gas outlet zone 231.

[0127] The gas-blood interface 240 is configured to be supplied with oxygenated gas to expose the blood to a certain amount of oxygen. For example, one or more oxygenated gases can enter the hollow fiber bundle via the inlet encapsulation from the gas inlet region 230. Blood enters the oxygenator 200 via the blood inlet 210. The blood and one or more oxygenated gases pass through the gas-blood interface 240 as they pass through the oxygenator 200. The gas-blood interface 240 is configured to allow gas exchange between the blood and the oxygenated gas supplied to the gas-blood interface 240. This includes the transfer of gases (such as oxygen, carbon dioxide, nitrogen) from the blood into the oxygenated gas, and the transfer of gases (such as oxygen, carbon dioxide) into the blood and out of the oxygenated gas. After gas exchange, the blood (now oxygenated) leaves the oxygenator 200 via the blood outlet 212 and flows to the patient, and the oxygenated gas (now waste gas) leaves the oxygenator 200 via the gas outlet 226.

[0128] As can be seen in Figure 2 the presence of multiple gas inlet regions 234a, 234b effectively allows different proportions of the gas-blood interface 240 to be supplied with the respective oxygenated gases. In this regard, the gas-blood interface 240 includes a plurality (in this case two) of interface regions 240a, 240b each configured to be independently supplied with a respective oxygenated gas.

[0129] As Figure 2 shown, the separator 232 divides the gas inlet region 230 into a first gas inlet region 234a and a second gas inlet region 234b of equal size. That is, the separator 232 divides the gas inlet region 230 (and thus the gas-blood interface 240) in half such that each of the first gas inlet region 234a and the second gas inlet region 234b accounts for 50% of the gas inlet region 230. Further, the separator 232 thus functions to divide the gas-blood interface 240 in half such that each of the first interface region 240a and the second interface region 240b accounts for 50% of the gas-blood interface 240. However, it should be understood that this division is merely an example, and the separator 232 (and / or multiple separators) can be located at different positions to produce different splits of the gas inlet region 230 and the gas-blood interface 240. For example, the separator 232 can be positioned such that the first gas inlet region 234a accounts for 40% of the gas inlet region 230, while the second gas inlet region 234b accounts for 60% of the gas inlet region 230. That is, the gas-blood interface 240 can be divided such that the first interface region 240a accounts for 40% of the gas-blood interface 240, while the second interface region 240b accounts for 60% of the gas-blood interface 240.

[0130] As Figure 2The spacer 232 shown in [Fig.] extends through the gas inlet region 230 but does not extend through the gas-blood interface 240. In such a case, the spacer 232 can be sealed against the inlet of the hollow fiber bundle to prevent gas flow between the interface regions 240a, 240b. Alternatively, the spacer 232 may not be sealed against the inlet, as leakage of gas flow between the gas inlet regions 234a, 234b may be permitted. In other examples, the spacer 232 can extend through the gas inlet region 230 and at least partially through the gas-blood interface 240, thereby physically separating the gas-blood interface 240 into interface regions 240a and 240b.

[0131] It should be noted that, generally, the oxygenated gas supplied to each of the gas inlet regions 234a, 234b (and thus to each of the interface regions 240a, 240b) can be sourced from the same or different gas supplies. The oxygenated gas can have the same composition or different compositions.

[0132] As described above, the gas supply device 300 can include one or more valves arranged to control the flow rate and / or composition of the first and second oxygenated gases. For example, as Figure 2 depicted in [Fig.], the gas supply device can include a first valve 304a configured to control the flow of oxygenated gas into the first gas inlet 222a and a second valve 304b configured to control the flow of oxygenated gas into the second gas inlet 222b. The controller 150 can be configured to control (e.g., open or close) the first valve 304a and the second valve 304b independently of each other to regulate (e.g., increase or decrease) the flow rate through each of the interface regions 240a, 240b. Alternatively or additionally, the gas supply device 300 can include a gas blender (as described above) for controlling gas flow and / or composition. It should be understood that other examples of valves, actuators, blenders, gas flow controllers, or other components for controlling the flow rate and / or composition of gas can be used instead of or in addition to the valves or gas blenders described herein.

[0133] Turning to Figure 3A and 3B , the general function of the oxygenator 200 (and system 100) will be described. As already described, the spacer 232 allows the gas inlet regions 234a, 234b to be independently supplied with respective oxygenated gases. From Figure 3ABeginning, the first gas inlet 222a may be supplied with the first oxygenated gas 242a. The first gas inlet 222a may be supplied with the first oxygenated gas 242a while no oxygenated gas is supplied to the second gas inlet 222b (i.e., only the first gas inlet 222a is supplied with oxygenated gas). This supplies the first oxygenated gas 242a to the first gas inlet region 234a and thus to the first interface region 240a.

[0134] In this case, the blood passing through the oxygenator 200 is exposed to the first oxygenated gas 242a only via a portion (in this case 50%) of the gas-blood interface 240. That is, while the blood passes through the second interface region 240b, the blood is substantially not exposed to the oxygenated gas. The blood is exposed to the first oxygenated gas 242a only when the blood passes through the first interface region 240a. Thus, the amount of oxygen to which the blood in the oxygenator 200 is exposed can be kept low. The concentration and / or flow rate of the first oxygenated gas 242a can be adjusted as described above to further adjust (e.g., increase and / or decrease) the amount of oxygen to which the blood is exposed. It should be understood that a similar effect can also be achieved by supplying oxygen gas only to the second interface region 240b via the second gas inlet 222b, depending on the relative sizes of the first interface region 240a and the second interface region 240b.

[0135] Moving on to Figure 3B , the first oxygenated gas 242a is supplied to the first gas inlet 222a (as Figure 3A such), and the second oxygenated gas 242b is supplied to the second gas inlet 222b. This supplies the second oxygenated gas 242b to the second gas inlet region 234b and thus to the second interface region 240b.

[0136] In this case, the blood passing through the oxygenator 200 is exposed to the second oxygenated gas 242b when the blood passes through the second interface region 240b and is subsequently exposed to the first oxygenated gas 242a when the blood passes through the first interface region 240a. Thus, the amount of oxygen to which the blood is exposed in the oxygenator 200 increases relative to the Figure 3A scenario depicted in. The concentration and / or flow rate of the first oxygenated gas 242a and / or the second oxygenated gas 242b can be adjusted as described above to further adjust (e.g., increase and / or decrease) the amount of oxygen to which the blood is exposed. It should be understood that the flow rate and / or composition of the first oxygenated gas 242a can be adjusted independently of the flow rate and / or composition of the second oxygenated gas 242b.

[0137] In this way, the controller 150 can use the oxygenator 200 and the gas supply device 300 to control the amount of oxygen to which the blood in the oxygenator 200 is exposed.

[0138] The first oxygenated gas 242a and / or the second oxygenated gas 242b may consist of pure oxygen. The first oxygenated gas 242a and / or the second oxygenated gas 242b may include a mixture of oxygen and nitrogen.

[0139] Although a specific example of an oxygenator that may be used with the system 100 has been described, it should be understood that other oxygenators that perform the same or similar functions may be used. For example, the oxygenator may include a plurality of gas inlet zones (each of which is connected to a separate gas inlet). Alternatively, one or more gas inlets may be directly connected to the gas-blood interface, which may be divided into a plurality of interface zones within the oxygenator. It should be understood that there are other configurations of the oxygenator that allow the plurality of interface zones to be independently supplied with the corresponding oxygenated gases. Additionally, although the oxygenator has been shown to have two gas inlet zones and two interface zones, it should be understood that there may be substantially any number of gas inlet zones and interface zones. The more gas inlet zones and interface zones there are, the more independent oxygenated gases can be supplied to the gas-blood interface.

[0140] Reference will now be made to Figures 4 - 7 Describe the overall function of the system 100. It should be understood that the controller 150 may be configured to control the gas supply device 300 to perform any of the methods described herein.

[0141] Figure 4Depicts a first exemplary method 400 of controlling a patient's blood oxygenation as contemplated herein. The controller 150 may be configured to perform any or all of the operations of method 400. Method 400 includes receiving 402 a measured value of a physiological parameter indicative of the oxygenation of the patient's blood. The measured value may be measured, for example, by the sensor 110 and received by the controller 150 from the sensor 110. Method 400 further includes calculating 404 the difference between the measured value and a target value of the physiological parameter. Method 400 further includes supplying 406 a first oxygenation gas 242a to a first interface region 240a of the gas-blood interface 240 and supplying 406 a second oxygenation gas 242b to a second interface region 240b of the gas-blood interface 240. Method 400 further includes, in response to a measured value higher than the target value, reducing 408 the flow rate of the second oxygenation gas 242 to reduce the amount of oxygen to which the blood is exposed to reduce the difference. Method 400 further includes, in response to the flow rate of the second oxygenation gas 242b being reduced to a threshold (and the measured value of the physiological parameter still being higher than the target value), reducing 410 the oxygen concentration and / or its flow rate in the first oxygenation gas 242a. After reducing 408 the flow rate of the second oxygenation gas 242b and / or after reducing 410 the oxygen concentration and / or its flow rate in the first oxygenation gas 242a, the method may include recalculating the difference between the measured value and the target value, as Figure 4 indicated by the return arrow in. It should be understood that the various operations in method 400 and method 400 as a whole may be performed repeatedly and / or continuously. For example, method 400 may include receiving an updated measured value and repeating method 400 in response to the updated measured value.

[0142] It should be understood that the supply of the first and second oxygenation gases may be performed at different time points in method 400. For example, the first and second oxygenation gases may be supplied before receiving the measured value.

[0143] Advantageously, method 400 is particularly beneficial for treating patients with a low metabolic rate. During a surgery involving extracorporeal oxygenation, the patient's metabolic rate may decrease. For example, the patient's metabolic rate may be intentionally decreased by the clinician by reducing the patient's body temperature. After the metabolic rate is reduced, the patient's body will consume less oxygen from the blood, and thus the physiological parameter indicative of the oxygenation of the blood will increase. After this increase, the controller 150 configured to perform method 400 will respond by reducing the flow rate of the second oxygenation gas 242b in the second interface region 240b. While reducing the flow rate of the second oxygenation gas 242b, the constant concentration and / or flow rate of the first oxygenation gas 242a may be maintained.

[0144] Advantageously, the continuous supply of the first oxygenated gas 242a allows the system 100 to continuously provide a "sweeping" function. That is, the first interface region 240a still provides sufficient removal of carbon dioxide and nitrogen, as well as a basal oxygenation level, while reducing the flow rate of the second interface region 240b to reduce the delivery of oxygen. Only when the flow rate of the second oxygenated gas 242b has been reduced to a threshold (e.g., zero), the controller 150 then reduces the oxygen concentration and / or its flow rate in the first oxygenated gas 242a. This allows the amount of oxygen to which the blood is exposed to be further reduced to reach a target value.

[0145] Optionally, the method 400 may further include maintaining the flow rate of the second oxygenated gas 242b at a threshold and increasing the amount of oxygen to which the blood is exposed by increasing 412 the oxygen concentration and / or its flow rate in the first oxygenated gas 242a. For example, the oxygen concentration and / or its flow rate in the first oxygenated gas 242a may be increased back to its original level (i.e., the level before it was reduced in operation 410 in response to the flow rate of the second oxygenated gas 242b being reduced to a threshold). For example, the oxygen concentration in the first oxygenated gas 242a may be increased to 100%.

[0146] As indicated by feature 401, the method 400 may be performed after the method 500 described below with reference to Figure 5 As indicated by feature 414, the method 400 may be performed before the method 600 described below with reference to Figure 6 As described. Alternatively, the method 600 may be performed independently of the method 400.

[0147] Figure 5 Depicts a second example method 500 for controlling a patient's blood oxygen saturation as contemplated herein. The controller 150 may be configured to perform any or all of the operations of the method 500. The method 500 includes initially supplying 502 only the first oxygenated gas 242a to the first interface region 240a of the gas-blood interface 240 and not supplying the second oxygenated gas 242b to the second interface region 240b. The method 500 may further include adjusting 504 the amount of oxygen to which the blood is exposed by adjusting the oxygen concentration and / or its flow rate in the first oxygenated gas 242a. The method 500 further includes subsequently initiating 506 the supply of the second oxygenated gas 242b to the second interface region 240b of the gas-blood interface 240 to increase the amount of oxygen to which the blood is exposed. The supply of the second oxygenated gas 242b may be initiated 506 in response to the oxygen concentration in the first oxygenated gas 242a having increased to a threshold concentration (e.g., 100% oxygen).

[0148] In an exemplary scenario, the oxygenated gas (in the form of the first oxygenated gas 242a) is initially supplied only to the first interface region 240a. At this stage, the first oxygenated gas 242a can include a mixture of nitrogen and oxygen. In this regard, a low oxygen content (and thus a low oxygen saturation in the patient's blood) can be achieved. The oxygen concentration in the first oxygenated gas 242a can be gradually increased to increase the amount of oxygen to which the blood is exposed (and thus increase the oxygen saturation in the blood) until the oxygen saturation (measured by the sensor 110) reaches a first target oxygen saturation (i.e., there is no difference between the first target oxygen saturation and the measured oxygen saturation). At this stage, a second (e.g., higher) target oxygen saturation can be received or retrieved by the controller 150 (or selected by a clinician). To achieve the second target oxygen saturation, the oxygen concentration and / or flow rate of the first oxygenated gas 242a in the first interface region 240a can be increased, and / or the supply of a second oxygenated gas 242b to the second interface region 240b can be initiated. Then, the oxygen concentration and / or its flow rate in the second oxygenated gas 242b can be further adjusted to regulate the amount of oxygen to which the blood is exposed.

[0149] Advantageously, method 500 is particularly beneficial for treating patients experiencing low oxygen saturation. Due to the current low oxygen saturation in the patient's blood, the oxygenator 200 should be operated to expose the blood to a smaller amount of oxygen in order to reduce the risk of oxygen excess. Thus, by initially supplying oxygen only to the first interface region 240a, the oxygenator 200 exposes the blood to a reduced amount of oxygen and thus reduces the risk of over-oxygenating the patient. Then, the oxygenation of the patient can be adjusted by regulating the oxygen concentration and / or its flow rate in the first oxygenated gas 242a. Subsequently, when it is desired to increase the patient's oxygen saturation (e.g., during the end of a clinical intervention, such as after a surgery to repair a congenital heart defect), the supply of the second oxygenated gas 242b can be initiated to increase the amount of oxygen to which the blood is exposed.

[0150] Optionally, method 500 (e.g., regulation 504) can further include, in response to a measured value below a target value, increasing 508 the oxygen concentration and / or its flow rate in the first oxygenated gas 242a to increase the amount of oxygen to which the blood is exposed.

[0151] Optionally, method 500 can further include, after initiating the supply of the first oxygenated gas 242a, increasing 510 the oxygen concentration and / or its flow rate in the second oxygenated gas 242b to further increase the amount of oxygen to which the blood is exposed.

[0152] Figure 6 A third exemplary method 600 for controlling a patient's blood oxygenation as contemplated herein is depicted. The controller 150 can be configured to perform any or all of the operations of method 600. Method 600 can be at Figure 4It is performed after method 400 in [reference], or can be performed independently. That is, the controller 150 can be configured to perform method 400 and / or perform method 600.

[0153] Method 600 includes receiving 602 a measured value of a physiological parameter indicating the carbon dioxide level in a patient's blood. The measured value can be measured, for example, by the sensor 110 and received by the controller 150 from the sensor 110. Method 600 also includes calculating 604 the difference between the measured value and a target value of the physiological parameter. Method 600 also includes supplying 606 a first oxygenated gas 242a to a first interface region 240a of the gas-blood interface 240 and supplying 606 a second oxygenated gas 242b to a second interface region 240b of the gas-blood interface 240. Method 600 also includes, in response to a measured value higher than the target value, increasing 608 the flow rate of the second oxygenated gas 242b while reducing the oxygen concentration in the second oxygenated gas 242b. After increasing 608 the flow rate of the second oxygenated gas 242b, the method can include recalculating the difference between the measured value and the target value, as Figure 6 indicated by the return arrow in [reference]. It should be understood that the various operations in method 600 and method 600 as a whole can be performed repeatedly and / or continuously. For example, method 600 can include receiving an updated measured value and repeating method 600 in response to the updated measured value.

[0154] It should be understood that the supply of the first and second oxygenated gases can be performed at different time points in method 600. For example, the first and second oxygenated gases can be supplied before receiving the measured value.

[0155] Advantageously, method 600 is particularly beneficial for treating patients experiencing an increase in the carbon dioxide level in the blood. For example, during intravascular vein harvesting in coronary artery bypass grafting, during resuscitation after long-term perfusion, or during hypothermic circulatory arrest (where the patient's metabolic rate is reduced), the patient may experience an increase in the carbon dioxide level in the blood. After these increases in carbon dioxide, the controller 150 configured to perform method 600 responds by increasing the flow rate of the second oxygenated gas 242b while reducing the oxygen concentration in the second oxygenated gas 242b. The increase in flow rate results in an increased rate of carbon dioxide removal from the blood, while reducing the oxygen concentration prevents or reduces an increase in oxygen delivery. Thus, oxygen delivery can be maintained while increasing the removal of carbon dioxide from the patient's blood.

[0156] Turning to Figure 7 , an example of the operation of the system as described herein will be described. Figure 7 A schematic diagram showing several "states" that can exist in the operation of the system described herein is shown. In particular, Figure 7Shows a series of states that may occur during the treatment of a patient experiencing a low metabolic rate, insufficient carbon dioxide removal, or low oxygen saturation (e.g., cyanosis).

[0157] Figure 7 Divided into a series of four states (a)-(d), which will be described in sequence below. The transitions between these states are shown by arrows 760, 762, 764, and 766. In each state, the oxygenator 700 is depicted. For clarity, the details of the oxygenator 700 Figure 7 will not be described further and are not labeled. However, it should be understood that the oxygenator 700 may share any or all of the features of the oxygenator 200 described above. Figure 7 The only features labeled in are the first interface region 740a, the second interface region 740b, the first oxygenated gas 742a, and the second oxygenated gas 742b. The following description will start with state (a), but it should be understood that the process is cyclic and thus any state can be considered the "start".

[0158] In state (a), the first interface region 740a is supplied with the first oxygenated gas 742a. The second interface region 740b is not supplied with oxygenated gas. As Figure 7 depicted, the first oxygenated gas 742a is supplied at 100% FiO2. That is, in state (a), the first oxygenated gas 742a consists only of oxygen. The oxygenator 700 can operate in this state to remove carbon dioxide from the patient's blood while also providing oxygen to the blood. In this regard, the first oxygenated gas 742a can be considered a "sweep gas". However, given that the first interface region 740a represents only a certain proportion (e.g., 40%) of the entire gas-blood interface, the supply of the first oxygenated gas 742a may be insufficient to reach the target value of a physiological parameter indicating oxygenation in the patient's blood (e.g., oxygen saturation). For example, a sensor may measure a measured value of the physiological parameter that is below the target value. Then, the system can transition to state (b), as indicated by arrow 760.

[0159] In state (b), the first interface region 740a continues to be supplied with the first oxygenated gas 742a (at 100% FiO2). However, the second interface region 740b now begins to be supplied with the second oxygenated gas 742b. That is, the flow rate of the second oxygenated gas 742b can be increased from zero. The flow rate of the second oxygenated gas 742b can continue to increase until a target value is reached (e.g., until the sensor measures a value equal to the target value). It should be understood that supplying the second oxygenated gas 742b to the second interface region 740b increases the amount of oxygen to which the blood is exposed beyond what might be exposed by supplying only the first interface region 740a. Thus, higher oxygen saturations can be achieved by supplying both interface regions 740a, 740b. The second oxygenated gas 742b can be provided at 100% FiO2 (i.e., pure oxygen). In addition to or instead of adjusting the flow rate of the second oxygenated gas 742b, the oxygen concentration in the second oxygenated gas 742b can also be adjusted. The system can be operated in this state to increase the oxygen saturation in the patient's blood to a healthy level (e.g., 98.5%). However, during the surgical procedure, the patient's metabolic rate may decrease. This in turn means that the blood needs to be exposed to a lower amount of oxygen in the oxygenator to achieve the same oxygen saturation in the patient's blood. This decrease in the metabolic rate can be detected in the form of an increase in the oxygen saturation in the patient's blood caused by continuously supplying the first and second oxygenated gases 742a, 742b at the same oxygen concentration and flow rate (despite the decrease in the metabolic rate). This can be detected by a sensor, for example. In such a case, the system can then transition to state (c), as indicated by arrow 762.

[0160] In embodiments in which the system controls the carbon dioxide level in the patient's blood (in addition to or instead of oxygenating the patient's blood), at state (b), the oxygen concentration in the second oxygenated gas 742b can be decreased while the flow rate of the second oxygenated gas 742b is increased.

[0161] In state (c), the flow rate of the second oxygenated gas 742b is reduced (e.g., reduced to a threshold, such as zero). This reduces the volume of the second oxygenated gas 742b present in the second interface region 740b at a given time. Thereby reducing the amount of oxygen to which the blood is exposed, resulting in a decrease in the oxygenation of the patient's blood. At the lower flow rate of the second oxygenated gas 742b, the measured value can be reduced to a target value. Alternatively, it may be necessary to reduce the flow rate of the second oxygenated gas 742b to zero (such that there is no oxygenated gas in the second interface region 640b) before the target oxygen saturation can be achieved. In some cases, it may be that this reduction to zero is still not sufficient to achieve the target oxygen saturation. Thus, to continue reducing the amount of oxygen to which the blood is exposed (e.g., in response to the flow rate of the second oxygenated gas 742b being reduced to zero), the system can then transition to state (d), as indicated by arrow 764.

[0162] In state (d), there is no supply of oxygenated gas to the second interface region 740b. To further reduce the amount of oxygen to which the blood is exposed, the oxygen concentration and / or its flow rate in the first oxygenated gas 742a can be reduced. This further reduces the oxygen content in the oxygenator 700, and thus allows the physiological parameter indicating the oxygenation in the patient's blood to be further reduced until the measured value reaches the target value. Advantageously, this allows the system to effectively manage the oxygenation level of a patient experiencing a low metabolic rate (e.g., a patient in circulatory arrest). When the patient returns to a higher (e.g., normal) metabolic rate, the FiO2 and / or the flow rate of the first oxygenated gas 742a can be increased again to increase the amount of oxygen present in the oxygenator 700. The FiO2 can be continuously increased until it reaches 100%. The system then transitions back to state (a), as indicated by arrow 766.

[0163] It should be understood that Figure 7 represents a particular example of the operation of the system described herein in a patient who initially has a normal metabolic rate and subsequently has a low metabolic rate. In practice, the metabolic rate of a patient may increase or decrease during a surgical procedure, and thus the system can freely move between Figure 7 all of the states. That is, the system is not limited to the described sequence, and instead can increase and / or decrease the concentration and / or flow rate of the first and / or second oxygenated gas as needed to achieve the target value of the physiological parameter indicating the oxygenation of the patient's blood.

[0164] As already mentioned, depending on the specific clinical scenario, Figure 7 any one of states (a)-(d) in

[0165] For example, in the case of method 400, the system may start in state (c), where two oxygenated gases are supplied, and the flow rate of the second oxygenated gas 642b is reduced to a threshold value (e.g., zero). In this case, in state (d), the oxygen concentration and / or its flow rate in the first oxygenated gas 742a may be reduced and then increased, as discussed above.

[0166] In another example, in the case of method 500, the system may start in state (a), where initially only the first oxygenated gas 242a is supplied, and the oxygen concentration and / or its flow rate in the first oxygenated gas 242a are adjusted.

[0167] In another example, in the case of method 600, the system may start in state (b), where two oxygenated gases are supplied, and the flow rate of the second oxygenated gas 642b is increased. In this case, in state (b), the oxygen concentration in the second oxygenated gas 242b is simultaneously reduced.

[0168] It should be understood that any features, functions, characteristics, or advantages described with respect to the examples of the system mentioned above can be applied to the examples of the methods mentioned above, and vice versa.

[0169] According to the present disclosure, the following aspects are also contemplated.

[0170] Aspect 1. A method of controlling a patient's blood oxygenation using an oxygenator having a gas-blood interface configured to receive blood from a patient and expose the blood to a quantity of oxygen as the blood passes through the oxygenator to produce oxygenated blood, wherein the gas-blood interface includes a first interface region and a second interface region, each of the first interface region and the second interface region being configured to be independently supplied with a respective oxygenated gas, the method comprising:

[0171] Receiving a measured value of a physiological parameter indicative of the oxygenation of the patient's blood;

[0172] Calculating a difference between the measured value and a target value of the physiological parameter;

[0173] Supplying a first oxygenated gas to the first interface region of the gas-blood interface;

[0174] Supplying a second oxygenated gas to the second interface region of the gas-blood interface;

[0175] In response to a measured value above the target value, reducing the quantity of oxygen to which the blood is exposed by reducing the flow rate of the second oxygenated gas to reduce the difference; and

[0176] In response to the flow rate of the second oxygenated gas being reduced to a threshold value, reducing the oxygen concentration and / or its flow rate in the first oxygenated gas.

[0177] Aspect 2. The method according to aspect 1 further includes reducing the amount of oxygen to which the blood is exposed by reducing the oxygen concentration in the second oxygenated gas.

[0178] Aspect 3. The method according to aspect 1 or aspect 2 further includes reducing the flow rate of the second oxygenated gas while maintaining a constant oxygen concentration and / or a constant flow rate in the first oxygenated gas.

[0179] Aspect 4. The method according to aspect 3, wherein the constant oxygen concentration in the first oxygenated gas is 100%.

[0180] Aspect 5. The method according to any one of the foregoing aspects further includes maintaining the flow rate of the second oxygenated gas at a threshold value and increasing the amount of oxygen to which the blood is exposed by increasing the oxygen concentration and / or the flow rate of the first oxygenated gas.

[0181] Aspect 6. The method according to any one of the foregoing aspects, wherein the threshold value is a flow rate of zero.

[0182] Aspect 7. The method according to any one of the foregoing aspects further includes:

[0183] Initially, only the first oxygenated gas is supplied to the first interface region without supplying the second oxygenated gas to the second interface region;

[0184] Adjusting the amount of oxygen to which the blood is exposed by adjusting the oxygen concentration and / or the flow rate of the first oxygenated gas; and

[0185] Subsequently, starting the supply of the second oxygenated gas to the second interface region of the gas-blood interface to increase the amount of oxygen to which the blood is exposed.

[0186] Aspect 8. The method according to aspect 7, wherein adjusting the amount of oxygen to which the blood is exposed includes increasing the amount of oxygen to which the blood is exposed by increasing the oxygen concentration and / or the flow rate of the first oxygenated gas in response to a measured value below a target value.

[0187] Aspect 9. The method according to aspect 7 or aspect 8, wherein the supply of the second oxygenated gas is started in response to the oxygen concentration in the first oxygenated gas having increased to a threshold concentration.

[0188] Aspect 10. The method according to any one of aspects 7 to 9 further includes, after starting the supply of the second oxygenated gas, increasing the oxygen concentration and / or the flow rate of the second oxygenated gas to further increase the amount of oxygen to which the blood is exposed.

[0189] Aspect 11. The method according to any one of the foregoing aspects further includes:

[0190] Receiving a second measured value indicative of a carbon dioxide level in a patient's blood; and

[0191] Calculating a difference between the second measured value and a second target value of the second physiological parameter.

[0192] Aspect 12. The method according to aspect 11, further comprising:

[0193] In response to the second measured value being higher than the second target value, increasing the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas.

[0194] Aspect 13. The method according to aspect 12, wherein increasing the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas maintains a constant volume of oxygen within the second interface region.

[0195] Aspect 14. The method according to aspect 12 or aspect 13, further comprising maintaining a constant oxygen concentration and a constant flow rate of the first oxygenated gas while increasing the flow rate of the second oxygenated gas and simultaneously decreasing the oxygen concentration in the second oxygenated gas.

[0196] Aspect 15. A method of controlling a patient's blood oxygenation using an oxygenator having a gas - blood interface configured to receive blood from a patient and expose the blood to a quantity of oxygen as the blood passes through the oxygenator to produce oxygenated blood, wherein the gas - blood interface includes a first interface region and a second interface region, each of the first interface region and the second interface region being configured to be independently supplied with a respective oxygenated gas, the method comprising:

[0197] Receiving a measured value of a physiological parameter indicative of a carbon dioxide level in a patient's blood;

[0198] Calculating a difference between the measured value and a target value of the physiological parameter;

[0199] Supplying a first oxygenated gas to a first interface region of the gas - blood interface;

[0200] Supplying a second oxygenated gas to a second interface region of the gas - blood interface;

[0201] In response to the measured value being higher than the target value, increasing the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas.

[0202] Aspect 16. The method according to aspect 15, comprising increasing the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas so as to maintain a constant volume of oxygen within the second interface region.

[0203] Aspect 17. The method according to aspect 15 or aspect 16, further comprising maintaining the flow rate and / or concentration of the first oxygenated gas while increasing the flow rate of the second oxygenated gas and simultaneously reducing the oxygen concentration in the second oxygenated gas.

Claims

1. A system for controlling blood oxygenation in a patient using an oxygenator having a gas-blood interface configured to receive blood from the patient and expose the blood to a quantity of oxygen as the blood passes through the oxygenator to produce oxygenated blood, wherein the gas-blood interface includes a first interface region and a second interface region, each of the first interface region and the second interface region being configured to be independently supplied with a respective oxygenation gas, the system including a controller configured to: Receiving a measured value of a physiological parameter indicative of oxygenation of the patient's blood and calculating a difference between the measured value and a target value of the physiological parameter; and control a gas supply device to supply the first oxygenation gas to the first interface region and supply the second oxygenation gas to the second interface region; in response to the measured value being higher than the target value, reduce the quantity of oxygen to which the blood is exposed by reducing the flow rate of the second oxygenation gas to reduce the difference; and in response to the flow rate of the second oxygenation gas decreasing to a threshold, reduce the oxygen concentration in the first oxygenation gas and / or the flow rate of the first oxygenation gas.

2. The system according to claim 1, wherein the controller is further configured to control the gas supply device to reduce the quantity of oxygen to which the blood is exposed by reducing the oxygen concentration in the second oxygenation gas.

3. The system according to claim 1 or claim 2, wherein the controller is further configured to control the gas supply device to reduce the flow rate of the second oxygenation gas while maintaining a constant oxygen concentration in the first oxygenation gas and / or a constant flow rate of the first oxygenation gas.

4. The system according to claim 3, wherein the constant oxygen concentration in the first oxygenation gas is 100%.

5. The system according to any one of the preceding claims, wherein the controller is further configured to control the gas supply device to: maintain the flow rate of the second oxygenation gas at the threshold and increase the quantity of oxygen to which the blood is exposed by increasing the oxygen concentration in the first oxygenation gas and / or the flow rate of the first oxygenation gas.

6. The system according to any one of the preceding claims, wherein the threshold is a flow rate of zero.

7. The system according to any one of the preceding claims, wherein the controller is further configured to control the gas supply device to: initially, supply only the first oxygenation gas to the first interface region and not supply the second oxygenation gas to the second interface region; regulate the quantity of oxygen to which the blood is exposed by adjusting the oxygen concentration in the first oxygenation gas and / or the flow rate of the first oxygenation gas; and subsequently, initiate the supply of the second oxygenation gas to the second interface region of the gas-blood interface to increase the quantity of oxygen to which the blood is exposed.

8. The system according to claim 7, wherein the controller is configured to control the gas supply device to regulate the quantity of oxygen to which the blood is exposed by increasing the oxygen concentration in the first oxygenation gas and / or the flow rate of the first oxygenation gas in response to the measured value being lower than the target value.

9. The system according to claim 7 or 8, wherein the controller is configured to control the gas supply device to initiate the supply of the second oxygenated gas in response to the oxygen concentration in the first oxygenated gas having increased to a threshold concentration.

10. The system according to any one of claims 7 to 9, wherein the controller is further configured to, after initiating the supply of the second oxygenated gas, increase the oxygen concentration in the second oxygenated gas and / or the flow rate of the second oxygenated gas to further increase the amount of oxygen to which the blood is exposed.

11. The system according to any one of the preceding claims, wherein the controller is further configured to: receive a second measured value of a second physiological parameter indicative of the carbon dioxide level in the patient's blood; and calculate the difference between the second measured value and a second target value of the second physiological parameter.

12. The system according to claim 11, wherein the controller is further configured to control the gas supply device to: increase the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas in response to the second measured value being higher than the second target value.

13. The system according to claim 12, wherein the controller is configured to control the gas supply device to increase the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas so as to maintain a constant volume of oxygen in the second interface region.

14. The system according to claim 12 or claim 13, wherein the controller is configured to control the gas supply device to simultaneously maintain a constant oxygen concentration and a constant flow rate of the first oxygenated gas while increasing the flow rate of the second oxygenated gas and while decreasing the oxygen concentration in the second oxygenated gas.

15. A system for controlling blood oxygenation in a patient using an oxygenator having a gas - blood interface configured to receive blood from the patient and expose the blood to a quantity of oxygen as the blood passes through the oxygenator to produce oxygenated blood, wherein the gas - blood interface includes a first interface region and a second interface region, each of the first interface region and the second interface region being configured to be independently supplied with a respective oxygenated gas, the system including a controller configured to: receive a measured value of a physiological parameter indicative of the carbon dioxide level in the patient's blood and calculate the difference between the measured value and a target value of the physiological parameter; and control a gas supply device to supply the first oxygenated gas to the first interface region and supply the second oxygenated gas to the second interface region, increase the flow rate of the second oxygenated gas while decreasing the oxygen concentration in the second oxygenated gas in response to the measured value being higher than the target value.

16. The system according to claim 15, wherein the controller is configured to control the gas supply device to increase the flow rate of the second oxygenated gas while reducing the oxygen concentration in the second oxygenated gas to maintain a constant volume of oxygen in the second interface region.

17. The system according to claim 15 or claim 16, wherein the controller is configured to control the gas supply device to simultaneously maintain a constant flow rate and / or a constant concentration of the first oxygenated gas while increasing the flow rate of the second oxygenated gas and while reducing the oxygen concentration in the second oxygenated gas.

18. The system according to any one of the preceding claims, wherein the system further comprises the gas supply device, the gas supply device being configured to control the flow rate of the first oxygenated gas and the second oxygenated gas and / or the oxygen concentration in the first oxygenated gas and the second oxygenated gas.

19. The system according to any one of the preceding claims, wherein the system further comprises the oxygenator.

20. The system according to claim 19, wherein the oxygenator comprises a gas inlet region for receiving the oxygenated gas into the gas-blood interface, wherein the gas inlet region comprises a separator that divides the gas inlet region into the following regions: A first gas inlet region configured to receive the first oxygenated gas and to supply the first oxygenated gas to the first interface region; and A second gas inlet region configured to receive the second oxygenated gas and to supply the second oxygenated gas to the second interface region.

21. The system according to any one of the preceding claims, wherein the system further comprises a sensor configured to measure the physiological parameter, and wherein the controller is configured to receive the measured value from the sensor.

22. The system according to claim 21, which depends from claim 19 or claim 20, wherein the sensor is located on a blood line that is connected to the oxygenator and is configured to carry the oxygenated blood from the oxygenator to the patient.

23. The system according to any one of claims 19 to 22, wherein the system further comprises: A venous reservoir configured to receive blood from the patient; And A pump configured to drive the blood to flow from the venous reservoir through the oxygenator.

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