Low-flow extracorporeal oxygenation system

Abstract

The present invention relates to a system and method for oxygenating a patient's blood, comprising an extracorporeal blood circulation pathway adapted to be connected to the patient's vascular system, and an apparatus for oxygenating blood entering the extracorporeal blood circulation pathway and recovering CO2 therefrom, wherein the flow rate of blood entering the extracorporeal blood circulation pathway does not exceed 2 / 5 of the patient's blood flow. The extracorporeal blood circulation pathway preferably includes an oxygenator and a cartridge including at least one cannula.

Description

Technical Field

[0001] Field of the Invention The present disclosure relates to systems and methods for treating respiratory failure by an extracorporeal oxygenation system. More specifically, the present disclosure relates to a novel low-flow extracorporeal oxygenation system and method of use for conscious and spontaneously breathing patients.

[0002] Background of the Invention Patients suffering from respiratory failure are often treated by highly invasive mechanical ventilation systems (used in place of spontaneous breathing by forcing air into the patient's failing or non-functional lungs using pressure (positive or negative)). While considered an emergency intervention necessary to treat patients with highly dysfunctional lungs or unconscious patients suffering from respiratory failure, the use of such systems is often seen as a high-risk procedure with a high probability of various complications such as airway damage, pneumothorax, various airway infections, acute respiratory distress syndrome (ARDS), etc. Due to the highly invasive intubation required for mechanical ventilation, such systems are typically used for unconscious patients or patients in a complete state of sedation.

[0003] Procedures that supplement mechanical ventilation are the use of extracorporeal oxygenation systems such as extracorporeal membrane oxygenation (ECMO) systems, which are lung or lung-heart bypass systems that circulate the patient's blood outside the body to remove carbon dioxide (CO2) and increase the oxygenation of the blood. Since such systems typically require a high-speed circulation of the entire volume of the patient's blood, these are also typically considered high-risk procedures that require complete sedation of the patient during treatment.

[0004] Extracorporeal oxygenation machines are used to oxygenate blood outside the patient's body. During the extracorporeal oxygenation process, a cannula is inserted into the patient's vascular system (for example, into the superior vena cava or internal jugular vein). A cannula is a tube that may be inserted into the body to deliver or remove fluids, for example. A cannula may be used to add blood to or remove blood from the patient's vascular system. Before inserting the cannula into the vascular system, it is necessary to prime it by removing all air from it. Priming the cannula and all sterile tubing in the fluid pathway connected to the cannula is necessary because the introduction of air bubbles into the vascular system can cause air embolism (which is dangerous and can even be fatal). Typically, a technician manually primes the cannula by introducing saline solution into it until the cannula is filled with saline. For example, a technician may connect a saline bag to a cannula using two tubes and fill the cannula and tubes through gravity. Cannulas having two lumens are also commercially available. Such a cannula is described in detail in PCT / IL2021 / 051335 of the same inventors and is incorporated herein by reference. In such a scenario, deoxygenated blood leaves the body through the discharge lumen and enters an extracorporeal system, where it is oxygenated using an oxygen supply and returned to the body through the injection lumen. Extracorporeal oxygenation systems known to date currently include two distinct components: a cannula and an oxygenation kit having tubes. Each of these components is primed separately before the start of oxygenation. After intubation of the cannula into the body, the cannula is connected to tubes from the oxygenation kit. The technician cleans the connection point to prevent air from entering the connection area. In some optional embodiments of the present invention, an automated priming system for a cannula and tubes connected through it is provided.

[0005] Preparing an extracorporeal blood oxygenation system for surgery is a complex process requiring skilled technicians, as any error can lead to a life-threatening situation. Furthermore, connecting various tubes to the pump and assembling the system to be ready for use is time-consuming, especially when every second counts with a patient suffering from respiratory failure. Therefore, a simplified, fast, and safe process for assembling the system is needed that minimizes the possibility of human error, increases patient safety, and reduces the time medical teams need to prepare the system for use.

[0006] Non-invasive ventilation (NIV) refers to the delivery of positive pressure ventilation through a non-invasive interface (e.g., BIPAP, CPAP, nasal mask, face mask, oxygen helmet, nasal prongs) rather than through an invasive ventilation approach (endotracheal tube, tracheostomy). The decision to transition from non-invasive to invasive ventilation involves several factors, including the patient's ability to maintain airway patency, their ability to ventilate and oxygenate, and the patient's expected clinical course. Harmful lung-related effects of invasive ventilation include impaired pulmonary barometric pressure, ventilator-associated lung injury, ventilator-associated pneumonia, endogenous positive end-expiratory pressure (auto-PEEP), heterogeneous ventilation, altered ventilator / perfusion mismatch (increased dead space, decreased shunt), diaphragmatic muscle atrophy, respiratory muscle weakness, and impaired mucosal ciliary muscle motility.

[0007] Invasive ventilation will reduce cardiac output and impair hemodynamic stability. Furthermore, it is associated with gastrointestinal stress ulcers, reduced visceral perfusion, decreased gastrointestinal motility, fluid retention, acute renal failure, increased intracranial pressure, fragility, inflammation, and sleep disturbances.

[0008] The present invention is intended to be used to increase blood oxygenation levels and remove CO2, thereby minimizing the effects of interfering with or delaying invasive ventilation and associated harmful lung damage. [Overview of the project]

[0009] Summary of the Invention According to one main aspect of the present invention, a system for extracorporeal oxygenation of blood at low flow rates up to 30 ml / kg per minute is disclosed. The novel extracorporeal oxygenation system provided herein is preferably used for patients with acute respiratory failure treated with non-invasive ventilation who still exhibit spontaneous breathing, and uses a blood circulation volume not exceeding 30 ml / kg per minute. This circulation volume is significantly lower than the circulation volumes used in ECMO, which are in the range of 60-80 ml / kg / min for VV (vein-vein) ECMO and 50-60 ml / kg / min for VA (vein-arterial) ECMO ("Extracorporeal Life Support: The ELSO Red Book", 5th edition, p. 75). Generally, the target flow rates in ECMO are 100-150 ml / kg / min (neonatal), 80-100 ml / kg / min (children), and 60 ml / kg / min (adults). In VV support, blood flow is typically higher than in VA, ranging from 120 ml / kg / min for neonates to 60-80 ml / kg / min for adults. The systems and methods of the present invention may further be used to increase blood oxygenation levels and CO2 removal in mechanically ventilated (MV) patients who are not considered candidates for ECMO based on the severity level determined by the patient's PaO2 / FiO2 ratio.

[0010] The inventors of this invention have reached the remarkable finding that circulating a reduced volume of a patient's blood, and oxygenating only a portion of that blood—neither the entire volume nor most of it—can improve respiration, reduce discomfort, and minimize the risk of complications in conscious patients who are still able to breathe spontaneously. The novel system is designed to support a functioning (but diseased) lung and work in conjunction with a conscious patient who is breathing spontaneously, even with a reduced volume. The novel system provided herein aims to replenish oxygen in the blood that is insufficient due to a impaired lung. This is a key difference in acute respiratory management, because, in contrast to ECMO, which requires the lung to be "shut down" and therefore the replacement of entire lung function, the extracorporeal blood oxygenation system and method of this invention allows the lung to remain in place and be treated by a medical team, instead of placing an excessive load on the lung with mechanical ventilation.

[0011] The novel systems provided herein for extracorporeal blood oxygenation are intended to operate at low flow rates, such as 30 ml / kg / min (but not limited to this), compared to the average blood flow rate of approximately 60–80 ml / kg / min in standard ECMO applications. In some optional embodiments, the novel systems are configured to use a higher pressure drop to induce a higher flow velocity and inhibit coagulation. The systems provided herein may further control the sweep gas flow. As the systems are configured to operate at low blood flow rates and 100% FiO2, carbon dioxide transport can be controlled and maximized by using a higher ratio of gas to blood flow without reducing blood oxygenation, as in ECMO systems. While ECMO systems cannot use high ratios because they reduce blood oxygenation capacity, the novel systems can reduce oxygen transport and increase CO2 removal levels by oxygenating only at low flow rates, such as 1 L / min (but not limited to this), and operating above the blood saturation point.

[0012] Blood oxygenation level (also called oxygen saturation level) indicates the oxygen-saturated hemoglobin within the total hemoglobin in the blood. Normal blood oxygenation levels in humans are approximately 95-100%. Typically, saturation levels below 90% are considered hypoxemia, and patients often need to be connected to a mechanical ventilation system to prevent organ dysfunction and organ failure.

[0013] An extracorporeal blood oxygenation system is typically a system that circulates blood outside the body by connecting to a vein or artery and using a pump to drain blood through the blood vessel (vein or artery), passing it through an external oxygen supply to reduce carbon dioxide (CO2) levels and make the blood oxygen-rich, and then injecting the blood back into the patient's circulatory system. The connection between the extracorporeal blood oxygenation system and the patient is performed by inserting one or more cannulas into one or more of the patient's blood vessels. A cannula is a thin tube inserted into a blood vessel that allows for the extraction of blood from / injection of blood into the blood vessel through it. The cannulas used in the methods according to the present invention are typically selected to be as small as possible so as to allow the blood flow rate required to obtain the desired oxygenation level. In the methods of the present disclosure, the size of the cannula may be selected by considering the required blood flow based on the patient's weight, which indicates each patient's cardiac output.

[0014] As noted, blood extraction and infusion may be performed through the patient's veins or arteries (e.g., the patient's internal jugular vein, femoral vein, subclavian vein, carotid artery, femoral artery, and subclavian artery). In the method of the present disclosure utilizing two separate cannulas (i.e., dual-site intubation), the first vessel may be the patient's femoral vein in some embodiments, and the second vessel may be the patient's internal jugular vein. In the method of the present disclosure utilizing a dual-lumen cannula (i.e., single-site intubation), the vessel may be the patient's internal jugular vein, femoral vein, subclavian vein, carotid artery, femoral artery, or subclavian artery.

[0015] The method of this disclosure is designed for use in conscious patients (i.e., not sedated (or under anesthesia)) who exhibit spontaneous breathing with partial lung function. Therefore, the method of this disclosure provides an oxygenation solution for a population of patients who still exhibit spontaneous breathing, even if not fully effective. The inventors have found that in such patients, partial oxygenation of the blood at low flow rates, combined with spontaneous breathing, significantly increases blood oxygenation and is sufficient to support the treatment of at least partial respiratory failure (and sometimes complete respiratory failure). Efficient external oxygenation of a portion of the blood, along with the contribution of residual gas exchange in the failing lung, allows for sufficient depletion of CO2 and enrichment of oxygen, raising the patient's oxygen saturation level to normal levels during treatment.

[0016] Therefore, the blood circulating volume used in the method of this disclosure is approximately 30 ml / kg per minute at most (i.e., not exceeding 2 / 5 of the patient's average blood flow).

[0017] Therefore, in some embodiments, the method further includes determining at least one of (i) blood circulation volume and (ii) cannula size, the determination being based on the patient's weight or BSA (body surface area) by common practice. After determining the flow rate, the cannula size is selected based on the intubation area and the circulating flow, up to 30 ml / kg per minute. Such determination may be performed in a controller of an extracorporeal blood oxygenation system that receives input in the form of the patient's physical parameters and provides a determination of the appropriate cannula size and blood flow rate to be used. Alternatively, it may be performed manually.

[0018] The method may further involve inputs from and / or monitoring and / or receiving measurements from various sensors associated with an extracorporeal blood oxygenation system that provide measured values ​​and data regarding various patient parameters (e.g., oxygen saturation level, pH, blood pressure, system pressure, blood flow rate, active clotting time, blood temperature, cardiac output, partial pressures of oxygen and CO2, hemoglobin concentration, and others). These monitored parameters are then used by the system controller to modify or adjust the blood circulation volume or other definitive aspects of the system to obtain a desired target oxygenation level.

[0019] As noted above, the method of this disclosure is intended for treating a conscious and spontaneously breathing patient suffering from partial pulmonary failure. However, the method of this disclosure may also be used to treat a patient who is simultaneously treated with mechanical ventilation. In other embodiments, the disclosure provides a method for increasing blood oxygenation levels and CO2 removal in a patient suffering at least partial respiratory failure, the method comprising introducing a first cannula into a first blood vessel to drain blood and introducing a second cannula into a second blood vessel to inject oxygenated blood, the first and second cannulas being connected to an extracorporeal blood oxygenation system through a first and second streamline, respectively, and the method comprising circulating the patient's blood through the extracorporeal blood oxygenation system at a circulation rate not exceeding approximately 30 ml / kg per minute to oxygenate the blood and to remove CO2 from the blood and increase the patient's blood oxygenation level, the patient being simultaneously treated with mechanical ventilation.

[0020] The present invention aims to provide, in one alternative implementation, a system for extracorporeal oxygenation of blood, comprising a reusable base and a disposable cartridge. The reusable base may include a controller and a plurality of pump drive units. The disposable cartridge includes one or more pump heads. Each pump head is controllable by its respective pump drive unit when the cartridge is installed in the base. The disposable cartridge further includes an oxygen supply unit and optionally includes at least one cannula. When the cartridge is installed in the base, the controller is configured to pump blood from the patient's vascular system through a sterile channel (defined by at least one cannula, sterile tubing, a plurality of pump heads and an oxygen supply unit) and to oxygenate the pumped blood.

[0021] The disposable cartridge is preferably a single-unit plug-and-play kit with the minimum number of components that can contribute to the progression of coagulation. Preferably, all components of the cartridge are coated with an anticoagulant material. The system provided herein has a higher flow rate and a higher pressure drop that inhibits coagulation. Additionally, the system is a low-blood-flow system; therefore, it does not require a high level of anticoagulation (very similar to a dialysis system).

[0022] The novel system may have various (non-invasive) sensors and indicators to show blood flow, blood pressure (across and behind the membrane), blood temperature, CO2 level, SVo2 (venous saturation) level, cardiac output, ACT, and other coagulation values.

[0023] Manually priming a cannula requires the technician to possess sufficient skill to perform the priming procedure properly. If the priming is not performed correctly, the patient may be at risk. Furthermore, manual priming is a time-consuming process.

[0024] Therefore, it is an object of this disclosure to provide an automated priming system for cannulas. The automated priming system automatically primes the cannula as soon as the cartridge containing the cannula is connected to the system. Advantageously, the automated priming system eliminates the need for manual priming, saving time and reducing the potential risks arising from human error.

[0025] A further object of this disclosure is to provide an automated priming system as part of an extracorporeal oxygenation system, which may be used as part of an extracorporeal oxygenation system to automatically prime a cannula and to perform extracorporeal oxygenation. Furthermore, a further object of this disclosure is to provide a cartridge that integrates a cannula with an oxygenation system, so that the cannula does not need to be connected to a kit after intubation.

[0026] According to some aspects, a system for automatically priming at least one cannula is disclosed. The system includes a priming cap having an inlet and an outlet sealed from each other, a saline reservoir, a drive unit, a priming pump having a replaceable priming pump head, and a fluid path having sterilized tubing between a first lumen and a second lumen of at least one cannula, the fluid path excluding the priming cap. The priming cap is removably adaptable over the first and second lumens, and when the priming cap is adapted over the first and second lumens, the inlet is in fluid communication with the first lumen of at least one cannula and the outlet is in fluid communication with the second lumen of at least one cannula, and at least one cannula, the priming cap, the saline reservoir, the priming pump head, and the fluid path are configured to form a closed loop for fluid flow. When the priming cap is not adapted over at least one cannula, the at least one cannula is insertable into a patient's vasculature. A controller is configured to operate the priming pump when the priming cap is adapted over at least one cannula, thereby expelling air from the closed loop. Advantageously, the system can prime at least one cannula while the cannula remains within the closed loop and without exposing the cannula to the ambient atmosphere.

[0027] In another implementation of the invention, at least one cannula, the priming cap, the saline reservoir, the priming pump head, and the fluid path are contained within a cartridge. The cartridge is attachable to and removable from a base containing a controller. Advantageously, the cartridge may be disposed of after each use and the controller may be included as part of a reusable base.

[0028] Optionally, the controller is configured to automatically initiate a priming operation upon attachment of the cartridge to the base. Advantageously, the automatic initiation avoids the possibility of errors arising from manual priming.

[0029] Optionally, the system further includes a sterilized patient access kit that includes an introducer, one or more dilators, and a guide wire. Optionally, the controller is configured to operate the priming pump while the sterilized patient access kit remains hermetically sealed. Thus, the priming operation may be completed without the potential of contaminating items in the patient access kit.

[0030] In another implementation according to the present invention, the fluid path includes an oxygenation system. Thus, the automatic priming system may be used to prime the oxygenation system for extracorporeal oxygenation.

[0031] Optionally, the first and second lumens have a drainage lumen and an infusion lumen. When at least one cannula is inserted into the patient's vasculature, the oxygenation system is configured to oxygenate the blood collected via the drainage lumen and return the oxygenated blood via the infusion lumen. Thus, deoxygenated blood and oxygenated blood are transported between the patient's vasculature and the system via separate lumens.

[0032] In another implementation according to the first embodiment, at least one cannula is a double-lumen cannula. Optionally, the double-lumen cannula includes a first lumen and a second lumen arranged side by side, with the width of the first lumen being greater than the corresponding width of the second lumen. Advantageously, this arrangement configuration allows a priming cap to be placed on the double-lumen cannula, with different regions fluidly connected to different lumens. Optionally, the double-lumen cannula further includes a sheath for guiding the double-lumen cannula along a guidewire. The sheath is used to position the double-lumen cannula at a desired location within the patient's vascular system.

[0033] In another implementation of the present invention, the closed loop includes, in order, a first lumen, a fluid path, a second lumen, a priming cap inlet, a saline reservoir, a priming pump head, a priming cap outlet, and again the first lumen.

[0034] In another embodiment, a method for automatically priming at least one cannula is disclosed. The method includes mounting a cartridge to the base of an automatic priming system. The automatic priming system includes a priming cap with a sealed inlet and outlet, a saline reservoir, a priming pump having a drive unit and a replaceable priming pump head, and a fluid path having sterile tubing between a first lumen and a second lumen of at least one cannula, the fluid path not including the priming cap. The priming cap is removably fitted onto at least one cannula, and when the priming cap is fitted onto at least one cannula, the inlet is in fluid communication with the first lumen of at least one cannula and the outlet is in fluid communication with the second lumen of at least one cannula, so that at least one cannula, the priming cap, the saline reservoir, the priming pump head and the fluid path form a closed loop for fluid flow. When the priming cap is not fitted onto at least one cannula, at least one cannula is insertable into the patient's vascular system. The cartridge comprises at least one cannula, a priming cap, a saline reservoir, a priming pump head, and a fluid path. The method further includes activating the priming pump when the priming cap is fitted onto at least one cannula, thereby expelling air from the entire closed loop.

[0035] In another implementation, the method further includes automatically initiating the priming process when the cartridge is mounted to the base. Optionally, the automated priming system further includes a sterile patient penetration kit comprising an introducer, one or more dilators and a guidewire, and the method further includes performing the work steps while the sterile patient penetration kit remains airtight.

[0036] In another implementation of the present invention, at least one cannula is a double-lumen cannula. The method further includes: penetrating the patient's vascular system using an introducer, one or more dilators and a guidewire; extending the guidewire to a target site within the patient's vascular system; dilating a blood vessel in the patient's vascular system using one or more dilators so that the vessel expands to receive a double-lumen cannula therein; removing a priming cap from the double-lumen cannula; guiding the sheath of the double-lumen cannula to a target site along the guidewire; removing the introducer, one or more dilators and the guidewire; and closing the sheath of the double-lumen cannula.

[0037] Optionally, the fluid pathway includes an oxygenation system, and the first and second lumens include a discharge lumen and an injection lumen. The method further includes removing deoxygenated blood from the patient's vascular system via the discharge lumen, oxygenating the deoxygenated blood using the oxygenation system, and returning the oxygenated blood to the patient's vascular system via the injection lumen.

[0038] Optionally, the method further includes performing removal, oxygenation, and return steps while circulating blood through a fluid pathway at a rate not exceeding approximately 30 ml / kg per minute. This rate is suitable for supplemental oxygenation in patients who are able to breathe independently. [Brief explanation of the drawing]

[0039] Examples illustrating embodiments of the present disclosure are described with reference to the attached drawings. The dimensions of components and features shown in the drawings have generally been selected for convenience and clarity of presentation and are not necessarily shown to scale. Many of the drawings presented are in the form of schematics, and as such, certain elements may be greatly simplified or drawn not to scale for the sake of clarity in the drawings. The drawings are not intended to be manufacturing drawings.

[0040] [Figure 1A] Figure 1A is a schematic isometric front view of an extracorporeal oxygenation system having a base and cartridge before connection, according to an embodiment of the present disclosure. [Figure 1B] Figure 1B is a schematic side view of the external system of Figure 1A in a connection configuration according to an embodiment of the present disclosure. [Figure 1C] Figure 1C is a schematic block diagram of an extracorporeal oxygenation machine including an automated priming cartridge according to an embodiment of the present disclosure. [Figure 2] Figure 2 is a schematic block diagram of the components of the automated priming cartridge from the extracorporeal oxygenation machine shown in Figure 1B, according to an embodiment of the present disclosure. [Figure 3] Figure 3 is a schematic block diagram of the automatic priming cartridge of Figure 2 according to an embodiment of the present disclosure, and in particular shows the fluid flow path during the priming operation. [Figure 4] Figure 4 shows a flowchart of 400 steps for one optional method of operating the extracorporeal system shown in Figure 1. [Figure 5A] Figures 5A and 5B are schematic isometric front and rear views, respectively, of a cartridge having an automatic priming system according to an embodiment of the present disclosure. [Figure 5B] Figures 5A and 5B are schematic isometric front and rear views, respectively, of a cartridge having an automatic priming system according to an embodiment of the present disclosure. [Figure 6] Figure 6 illustrates the steps of an automated cannula priming method according to an embodiment of the present disclosure. [Figure 7] Figure 7 illustrates the steps of an external oxygenation method according to an embodiment of the present invention; and, [Modes for carrying out the invention]

[0041] Detailed description of embodiments and examples The following description will describe various aspects of a novel extracorporeal oxygenation system and its method of use. For explanatory purposes, specific configurations and details will be described to provide a complete understanding of the present invention.

[0042] While various features of this disclosure will be described in the context of a single embodiment, such features may also be provided separately or in any suitable combination. Conversely, while this disclosure will be described herein in the context of separate embodiments for clarity, this disclosure may also be implemented in a single embodiment. Furthermore, it should be understood that this disclosure can be performed or implemented in various ways, and that it may be implemented in embodiments other than those exemplary described herein below. The statements, examples, and materials presented in the specification and claims should not be construed as restrictive, but rather as explanatory.

[0043] In one embodiment, the present invention relates to a system for oxygenating a patient's blood, the system having an extracorporeal blood circulation pathway adapted to be connected to the patient's vascular system, and a device for oxygenating the blood flowing into it and recovering CO2 therefrom, wherein the flow rate of blood flowing into the extracorporeal blood circulation pathway does not exceed 2 / 5 of the patient's blood flow. According to embodiments of the present invention, the flow rate is not greater than 30 ml / kg per minute. The system may have a cartridge in the extracorporeal blood circulation pathway that includes an oxygen supply unit and at least one cannula. In such embodiments, the cartridge may have disposable components that come into contact with the patient's blood during extracorporeal blood circulation. The cartridge is configured to be reversibly connected to and operable on a reusable base having at least one controller and one or more pump drive units and motors, the drive units and motors corresponding to a pump head and power source located on the cartridge, respectively. The base may further have at least one fixed sensor and / or user interface. In some embodiments, the cartridge has one or more pump heads, each pump head being controllable by its own pump drive unit and motor located in the base.

[0044] Optionally, the extracorporeal blood circulation pathway may include an automated priming system that is adapted to ensure a safe and embolus-free connection to the patient's vascular system. In such a scenario, the cartridge may further include a saline reservoir connected to the automated priming system.

[0045] The present invention further relates to a cartridge for extracorporeal blood oxygenation, the cartridge having one or more pump heads, each pump head controllable by its own pump drive unit, the cartridge having an oxygen supply unit and at least one cannula. When a single cannula is provided, it is a double cannula. Preferably, all surfaces in contact with blood are coated with an anticoagulant. The disposable cartridge is configured to be inserted into a supplementary base before use, the supplementary base controlling and operating the components of the cartridge.

[0046] In a further aspect of the present invention, a method for supporting a patient having a low blood oxygen saturation level, the method comprising connecting an extracorporeal blood circulation pathway to the patient's vascular system, and a device having a device for oxygenating the blood flowing into it and recovering CO2 therefrom, and adjusting the flow rate of blood flowing into the extracorporeal blood circulation pathway so as not to exceed 30 ml / kg per minute. The patient is able to breathe spontaneously. Alternatively, the patient is mechanically ventilated. Support for the patient may be provided as an auxiliary system to replace ECMO.

[0047] In a further embodiment, the present invention provides a system for the automatic priming of at least one cannula, the system having at least a) a priming cap including an inlet and outlet sealed to each other when mounted on a cannula; b) a saline reservoir; c) a priming pump having a drive unit and a replaceable priming pump head; and d) a fluid path having sterile tubing between a first lumen and a second lumen of at least one cannula, the fluid path not including a priming cap; the priming cap being removablely fitted over the first and second lumens, and when the priming cap is fitted over the first and second lumens, the inlet The system is configured such that the outlet is in fluid communication with the first lumen of at least one cannula, and the outlet is in fluid communication with the second lumen of at least one cannula, and the at least one cannula, priming cap, saline reservoir, priming pump head and fluid path form a closed loop for fluid flow, and the at least one cannula is insertable into the patient's vascular system when the priming cap is not fitted onto the at least one cannula; and e) a controller is provided, which is configured to activate the priming pump when the priming cap is fitted onto the at least one cannula, thereby expelling air from the closed loop. In some optional implementations of the system, the at least one cannula, priming cap, saline reservoir, priming pump head and fluid path are contained within a cartridge, which is mountable to and detachable from a base containing a controller. The controller is configured to automatically initiate priming when the cartridge is mounted to the base. The system may further include a patient intubation kit, which includes an introducer, one or more dilators, and a guidewire, to enable patient intubation.In some embodiments, the controller is configured to activate the priming cap while the sterilized patient penetration kit remains airtight.

[0048] In some other optional embodiments, the fluid path further includes an oxygenation system.

[0049] Optionally, the first and second lumens of the cannula have an discharge lumen and an infusion lumen, and when at least one cannula is inserted into the patient's vascular system, the oxygenation system is configured to oxygenate the blood collected through the discharge lumen and return the oxygenated blood through the infusion lumen. As described above, the system may operate with a single-lumen cannula or with a double-lumen cannula.

[0050] Alternatively, the closed loop has, in order, a first lumen, a fluid path, a second lumen, a priming cap inlet, a saline reservoir, a priming pump head, a priming cap outlet, and again a first lumen.

[0051] In a further aspect of the present invention, a system for extracorporeal oxygenation of blood is provided, the system having a) a reusable base having at least: a controller; one or more pump drive units; and one or more pump motors, and the system having b) a disposable cartridge, the disposable cartridge having: one or more pump heads, each pump head controllable by its respective pump drive unit and motor when the cartridge is installed on the base; an oxygen supply unit; and at least one cannula, the at least one cannula being connected to the patient's vascular system The device includes a discharge lumen for removing deoxygenated blood and an injection lumen for returning oxygenated blood to the patient's vascular system; and has sterile tubing configured to deliver deoxygenated blood from the discharge lumen to an oxygen supply unit and oxygenated blood from the oxygen supply unit to the injection lumen; and when the cartridge is installed on the base, the controller is configured to pump blood from the patient's vascular system through a sterile path defined by at least one cannula, sterile tubing, one or more pump heads and an oxygen supply unit, and to oxygenate the pumped blood.One or more pump drive units of the system may include a priming pump drive unit, further comprising a priming cap with a sealed inlet and outlet, a saline reservoir, and a priming pump head controllable using the priming pump drive unit, all contained within a disposable cartridge; the priming cap is removably fitted onto at least one cannula, and when the priming cap is fitted onto at least one cannula, the inlet is in fluid communication with a first lumen of at least one cannula, and the outlet is in fluid communication with a second lumen of at least one cannula, and at least one cannula, priming cap, saline reservoir, priming pump head, sterile tubing, and oxygen supply unit form a closed loop for fluid flow, and when the priming cap is not fitted onto at least one cannula, at least one cannula is insertable into the patient's vascular system; and the controller is configured to activate the priming pump when the priming cap is fitted onto at least one cannula, thereby expelling air from the closed loop.

[0052] In an additional aspect, the present invention relates to a method for increasing blood oxygenation levels and CO2 removal in a patient capable of spontaneous breathing, the method comprising introducing a first cannula into a first blood vessel to drain blood and introducing a second cannula into a second blood vessel to inject oxygenated blood, the first and second cannulas being connected to an extracorporeal blood oxygenation system through a first streamline and a second streamline, respectively, and the method comprising circulating the patient's blood through the extracorporeal blood oxygenation system at a circulation volume not exceeding approximately 30 ml / kg per minute to oxygenate the blood and to remove CO2 from the blood and increase the patient's blood oxygenation level. Optionally, the method further comprises determining at least one of (i) blood circulation volume and (ii) cannula size, the determination being based on the patient's weight. The determination involves a) determining the blood volume based on the patient's weight and the desired target blood oxygenation level and CO2 removal, and b) determining the appropriate cannula size for the patient based on the desired blood volume.

[0053] The present invention relates to a method for increasing blood oxygenation levels and CO2 removal in a conscious patient capable of spontaneous breathing, the method comprising introducing a double-lumen cannula into the patient's blood vessel, the double-lumen cannula having an evacuation tube for draining deoxygenated blood from the blood vessel and an infusion tube for injecting oxygenated blood into the blood vessel, the evacuation tube and the infusion tube being connected to an extracorporeal blood oxygenation system through a first streamline for evacuation and a second streamline for infusion, and the method comprising circulating the patient's blood through the extracorporeal blood oxygenation system at a circulation rate not exceeding approximately 30 ml / kg per minute to oxygenate the blood and to remove CO2 from the blood and increase the patient's blood oxygenation level. In some optional implementations of the method, a double-lumen cannula is provided having an outer tube surrounding an inner tube. In this optional scenario, one of the outer tube and the inner tube is the evacuation tube and the other is the infusion tube. Alternatively, the discharge and infusion tubes may be arranged side by side in the double-lumen cannula used. Optionally, the method further includes monitoring the patient's blood oxygenation parameters during treatment.

[0054] The following studies were conducted on a 200 lbs / 90 kg Large-White × Landrace pig model. Pigs are considered one of the primary animal species used for translational studies, surgical models, and procedural training due to their predominantly human-like anatomical and physiological characteristics. All pigs used in the following studies underwent individual veterinary examinations, including blood tests (CBC) in the LAHAV CRO laboratory, following facility SOPs. Blood tests, along with general physical examinations performed before the start of the studies, reflected the health status of the pig models and allowed for the determination of each animal's suitability for the study.

[0055] A direct oxygenation device was connected to a pig model via a vein-vein connection to enable extracorporeal oxygenation of pig blood in a closed circulation. The oxygen supply unit of the system contained two compartments connected through a semipermeable membrane partition. Delivering blood through one compartment and oxygen through the other facilitated oxygen exchange into the blood through the semipermeable membrane partition. The blood compartment of the oxygen supply unit was connected to a vein by a 3 / 8'' tube connected to a cannula located in the femoral vein and jugular vein, or alternatively, a double-lumen cannula in the internal jugular vein. The second compartment of the oxygen supply unit was connected to a standard oxygen source. The system pumped blood from the pig's vascular system, oxygenated it, and then returned it to the vascular system, thus increasing the oxygen saturation level and providing respiratory support to the pig model.

[0056] The pig models used in the study were induced into a state of hypoxemia. Oxygen gas concentration was reduced (using nitrogen) to mimic the respiratory failure state of a defective, diseased lung. This was achieved by mixing pure oxygen with medical air and N2O to reduce the oxygen concentration level to ~15%, and therefore reducing the oxygen saturation level of the pig models to ~85% or less, with each pig model responding independently.

[0057] The pigs were anesthetized but their respiration was maintained and they were connected to all relevant equipment in accordance with the facility's SOPs. To control oxygen concentration, an endotracheal tube was connected to a medical oxygen and nitrogen gas mixer. Angiography was used to position a Swan-Ganz catheter (used to monitor blood flow and pressure in and around the heart) and to collect a blood sample from the pulmonary artery as close to the catheter as possible. Monitoring equipment was set up (for continuous recording of vital signs), and arterial blood gas (ABG) was tested and calibrated. The pig models were sedated, and vital signs were continuously monitored.

[0058] For the venotomy, the following access points were established (for blood collection): pulmonary artery, carotid artery, and femoral vein.

[0059] The inlet tube was used to circulate blood drained from the body to an oxygenator, and the outlet tube was used to circulate oxygenated blood back to the body from the oxygenator. The inlet tube was connected to a cannula inserted into the femoral vein, and the outlet tube was connected to a cannula inserted into the jugular vein. In studies performed using a double-lumen cannula inserted into the jugular vein, both the inlet and outlet tubes were connected to the corresponding connectors.

[0060] The system was circulated with physiological saline (~1000 ml) before attachment to the cannula. The cannula tube was connected to the 3 / 8'' diameter inlet and outlet tubes of the system, and the oxygen source was connected to the oxygen inlet of the system's oxygen supply unit using an 8 mm tube, with the oxygen flow rate set to 3 L / min. The gas outlet of the oxygen supply unit remained open throughout the experiment.

[0061] This process was performed and demonstrated by the LAHAV CRO medical team. This was achieved by mixing pure oxygen with medical air and N2O to reduce the oxygen concentration level to ~15%, and thus reducing the oxygen saturation level of the pig models to ~85% or less, with each pig model reacting independently.

[0062] For blood collection, 3 / 8'' × 3 / 8'' T-connectors were used to connect to bidirectional plugs both before and after the oxygen supply unit of the system, enabling the collection of blood samples. Blood was collected from four test points (TPs): TP1 - Femoral vein (femoral vein blood before oxygenation process) TP2 - Outlet of the oxygen supply unit (after oxygenated venous blood, but before mixing with jugular venous blood) TP3 - Pulmonary artery (PA, filled with vena cava blood after extracorporeal oxygenation, after mixing with deoxygenated blood from the jugular vein, and before entering the lungs for the oxygenation process) TP4 - Carotid artery (oxygenated blood after the lungs)

[0063] Study 1-Thigh-Neck Study Part 1 - The objective of this study was to demonstrate that a blood flow of 1 L / min is sufficient to support patients in a hypoxic state, targeting an increase in O2 saturation from <85% to ~95%. This study used 200 lbs / 90 kg pigs and two large, commercially available 18Fr cannulas (Medtronic): the first cannula was inserted into the jugular vein, and the second cannula was connected to the femoral vein. The insertion procedure required surgical insertion using radiographic procedures due to the dimensions and length of the cannula passing through the right atrium of the heart. Blood flow through the extracorporeal oxygenation system was 1–1.5 L / min, oxygen flow rate was 3 L / min, and oxygen ventilation support was low (<20% O2 gas concentration).

[0064] Data were collected and analyzed to assess the minimum blood flow required to increase and stabilize oxygen saturation levels. The results are provided in Table 1.

[0065] [Table 1]

[0066] As can be seen, this method makes it possible to raise oxygen saturation levels from values ​​even below 80% (a condition typically defined as critical illness, where the patient is typically placed on a mechanical ventilation or ECMO system).

[0067] Part 2 - The objective of this study was to evaluate oxygenation at different blood flow rates. Pigs were kept at a stable pO2 level of 100–120 mmHg, and blood flow rates were investigated to assess the minimum flow level that added at least 10 mmHg of oxygen to the blood. All predictive parameters for blood flow levels were the same as those in Part 1 above. The results are provided in Table 2.

[0068] [Table 2]

[0069] The system and methods used successfully enabled an increase in oxygen saturation levels, similar to Part 1 of the study.

[0070] Study 2 - Dual Lumen Cervical Surgery - Cervical Surgery Research The objective of this study was to verify the feasibility of blood oxygenation and CO2 removal using a commercially available double-lumen cannula inserted into the internal jugular vein. A 200 lb / 90 kg pig was used in this study, employing a commercially available 23 Fr double-lumen cannula (Maquet Avalon). The insertion procedure required surgical insertion using radiographic techniques due to the complexity of precise cannula positioning. Blood flow through the extracorporeal oxygenation system was 1–1.5 L / min, oxygen flow rate was 3 L / min, and oxygen ventilation support was low (16% O2 gas concentration).

[0071] The results are provided in Table 3.

[0072] [Table 3]

[0073] By using the extracorporeal oxygenation system of the present invention and the methods described herein, oxygen saturation levels were increased from ~80% to target levels above 95%.

[0074] Study 3 - Small-scale dual-lumen cervical-cervical study The objective of this study was to investigate the feasibility of blood oxygenation and CO2 removal using a small, double-lumen cannula inserted into the internal jugular vein without radiographically guided insertion. The study used 200 lbs / 90 kg pigs and a commercially available 18 Fr small, double-lumen cannula (as disclosed herein). No radiographic imaging (or any other type of imaging) was required for cannula positioning. Blood flow through the extracorporeal oxygenation system was 1–1.5 L / min, oxygen flow was 3 L / min, and oxygen ventilation support was low (14.5% O2 gas concentration).

[0075] A small, double-lumen cannula allowed for simultaneous venous drainage and reinfusion of blood via the internal jugular vein. The extracorporeal oxygenation system included a centrifugal pump driven to pump blood from the pig's right-side internal jugular vein through the cannula's outlet discharge tube. The blood circulated through the system's oxygenator, providing oxygen-rich, CO2-depleted blood. In a closed system, the oxygenated blood circulated back through the cannula's inlet reinfusion tube.

[0076] The pig model was subjected to hypoxemia, achieved by mixing N2O and oxygen in a mixture of different concentrations for ventilation to reach a targeted oxygen saturation level. Oxygen saturation in the pig model was monitored and stabilized at ~85%. Blood samples were collected both before and after the oxygen supply unit of the system at the following points: TP1 - Femoral vein (femoral vein blood before oxygenation process) TP2 - Outlet of the oxygen supply unit (after oxygenated venous blood, but before mixing with jugular venous blood) TP3 - Pulmonary artery (PA, filled with vena cava blood after extracorporeal oxygenation, after mixing with deoxygenated blood from the jugular vein, and before entering the lungs for the oxygenation process) TP4 - Carotid artery (oxygenated blood after the lungs).

[0077] Because the pig was in a state of hypoxemia, the monitor's saturation level showed a degraded blood oxygen saturation level.

[0078] As the system was activated, pig blood was drawn from and returned to the right jugular vein using a small, double-lumen cannula. Oxygen saturation in the pig model was monitored at several intervals, and blood collection was performed from the test point.

[0079] The results are provided in Table 4.

[0080] [Table 4]

[0081] As can be seen in Table 4, low blood flow of 1–1.5 L / min using a small double-lumen cannula resulted in a saturation level of 95–96%. No radiographic guidance was used during the insertion procedure. Furthermore, the increase in the monitored saturation level paralleled the increase in arterial pO2, indicating high oxygenation capacity at low blood flow and low oxygen concentration. The small double-lumen cannula was inserted and removed without complexity, and no signs of thrombosis or fatigue were observed after removal of the cannula from the pig's jugular vein.

[0082] Tables 5-1 and 5-2 show the aggregated results of studies 1-3.

[0083] [Table 5-1]

[0084] [Table 5-2]

[0085] As can be seen from the results, the method of this disclosure provides a safe and consistent level of oxygenation in spontaneously breathing pigs, circulating only a portion (about 1 / 5) of the blood volume at a relatively low blood flow rate. Using a small, dual-lumen cannula, a procedure that is not significantly invasive or complex was achieved without requiring any imaging techniques to guide the cannula into place.

[0086] This disclosure relates in some embodiments to a system for cannulas and sterile tubes connected thereto, and more specifically to an automated priming system integrated into an extracorporeal oxygenation system, but not exclusively to such a system.

[0087] Here, refer to the drawing:

[0088] Figure 1A is a schematic isometric front view of the extracorporeal oxygenation system 100, which has a reusable base 110 and a disposable cartridge 10, the disposable cartridge 10 being a plug-and-play single-unit box containing virtually all, or most, of the disposable components of the system 100 that come into contact with the patient's blood. A detailed description of these components will be provided below with reference to Figures 2-3. These components are assembled and designed to replace the complex multi-step assembly of these disposable instruments and their connection to the extracorporeal oxygenation system with a more user-friendly single-step process, reducing the time and special training required to safely and accurately configure the necessary disposable instruments. In this figure, the cartridge 10 is positioned on top of the base 110, ready to be inserted into it.

[0089] Figure 1B is a schematic side view of the extracorporeal system of Figure 1A according to some optional embodiments of the present disclosure, in which the cartridge 10 and base 110 are connected to each other. The figure shows a cover 11. Before use of the extracorporeal oxygenation system 100, the cover 11 is removed, and the cover of the “window” that allows access to the internal space and components of the cartridge 10 is removed. This allows the operator to pull out a cannula (preferably a primed cannula, but not required) and connect the oxygen supply unit 52 to the oxygen supply source by a dedicated connector 52' ​​(shown in Figure 5A).

[0090] Figure 1C is a schematic block diagram showing the main components of an extracorporeal oxygenation system 100 in several optional implementations of the present invention. As used in this disclosure, an extracorporeal oxygenation system is a system that uses a pump to drain blood through a blood vessel (e.g., a vein or artery), passes the blood through the extracorporeal oxygenation system to reduce carbon dioxide (CO2) levels and make the blood oxygen-rich, and injects the oxygenated blood back into the patient's circulatory system. The extracorporeal oxygenation system may be, for example, an extracorporeal membrane oxygenation (ECMO) system. The extracorporeal oxygenation system may function as the sole source of oxygenation for the patient's blood, or it may be used to complement other sources of oxygen, such as a mechanical ventilator or the patient's independent breathing. In an exemplary embodiment, system 100 is designed for use as a complementary oxygen supply for a patient who is conscious and capable of breathing independently, albeit with reduced efficiency.

[0091] System 100 consists of a reusable base 110, a disposable cartridge 10 that can be connected to the base 100, and a patient penetration kit 130.

[0092] The reusable base 110 includes a user interface 112. The user interface 112 may include a keyboard, a touchscreen, or any other mechanism for receiving user input. The user interface 112 also includes a display for displaying parameters related to the function of the system 100. User input and display parameters may also relate to the function of any of the components of the system 100 (e.g., the flow rate of blood through the system 100, the pressure of blood at different points within the system 100, the temperature of blood, the target oxygenation level of blood flowing through the system 100).

[0093] The base 110 further includes a programmable logic controller 114. The controller 114 may include processing circuitry that executes software including instructions for performing the method according to embodiments of the present disclosure. The processing circuitry may include a computer-readable storage medium having computer-readable program instructions for causing a processor to perform an aspect of the system according to the present disclosure.

[0094] The base 110 further includes a power source 116. The power source 116 may be a power cord connectable to a power grid. Additionally or alternatively, the power source 116 may be a battery (e.g., a rechargeable battery). The power source 116 provides power to the controller and to the pump motor and drive units 120, 122, which are further described herein.

[0095] The base 110 further includes one or more fixed sensors 118. The fixed sensors 118 may include, for example, optical analyzers for measuring parameters such as hematocrit rate, oxygen saturation, hemoglobin, and blood temperature. The fixed sensors 118 may also include flow meters. The fixed sensors 118 may analyze these parameters of blood while the blood is in sterilized tubes.

[0096] Base 110 also includes a blood pump drive unit and motor 120 and a priming pump drive unit and motor 122. The functions of the blood pump and priming pump will be described further herein. Each pump drive unit and motor 120, 122 includes a driver and a motor. The driver is an electronic unit (e.g., a printed circuit board assembly) that receives input signals (e.g., analog signals) for controlling the motor. The motor receives power from a power source 116. The magnets of the magnetic motor control a magnetic impeller, which is part of a disposable pump head in the cartridge 10, through magnetic force. Furthermore, in exemplary embodiments, the priming pump is a peristaltic pump. The pump head is connectable to disposable sterile tubing, which is part of the cartridge 10, to pressurize one or more fluid streamlines in the cartridge 10.

[0097] The base 110 may be installed in a patient room, for example, mounted on a wall. Alternatively, the base 110 may be portable. For example, the base 110 may be located on a rolling cart or inside an ambulance. The patient room, rolling cart, or ambulance may include equipment for use in conjunction with the system 100 (e.g., one or more oxygen canisters, a backup power pack, an uninterruptible power supply (UPS), or a blood heater).

[0098] Referring again to Figure 1C, the system 100 further includes a cartridge 10. The cartridge 10 is a disposable cartridge designed to be removed from and inserted into the base 110. Generally, the cartridge 10 includes components that come into contact with the patient's blood and are therefore replaced between each patient's use. The cartridge 10 includes a cannula 12, a priming cap 22, and a saline reservoir 32, the functions of which will be further described herein. The cartridge 10 also includes a priming pump head 34 and a blood pump head 46, the priming pump head 34 being controlled by a priming pump motor in the base 110, and the blood pump head 46 being controlled by a blood pump motor in the base 110. The cartridge 10 further includes sterile tubing through which fluid flows and which may have sensors 118 fixed around it, and an oxygen supply unit 52 for oxygenating the blood flowing through the cartridge.

[0099] System 100 further includes a patient penetration kit 130. The patient penetration kit 130 includes standard materials used to insert a cannula into the patient's vascular system. These materials include, for example, an introducer 132 which may include a needle or trocar, one or more dilators or inflators 134, and a guidewire 136. The patient penetration kit 130 may be stored separately from the cartridge 10.

[0100] Figures 2 and 3 contain schematic diagrams showing the components and functions of cartridge 10.

[0101] In the configurations shown in Figures 2 and 3, the cartridge 10 is positioned so that the fluid pathway for the cannula 12 is ready to be primed by the injection of saline solution. In this position, the priming cap 22 is fitted over the cannula 12 so that the priming cap 22, the cannula 12, and other components form a closed loop for the injection of saline solution. When the priming cap 22 is removed and the cannula 12 is inserted into the body, the same closed loop is used for the transfer of blood between the patient's vascular system and the oxygenation module 40 contained in the cartridge 10. During the priming process, the cartridge 10 is enclosed in a sterile housing, which may be made of any suitable material. The sterile housing may remain sealed after priming is complete and until the cannula is ready to be inserted into the patient's body.

[0102] Referring to Figure 2, the cartridge 10 includes a cannula 12. In an exemplary embodiment, the cannula 12 is a double-lumen cannula having two lumens arranged side by side. The double-lumen cannula 12 includes a first lumen 14 having an end 15 and a second lumen 16 having an end 17. In an exemplary embodiment, the first lumen 14 is the discharge lumen, with the end 15 being the inlet, and the second lumen 16 is the injection lumen, with the end 17 being the outlet. The discharge lumen 14 is used to collect deoxygenated blood from the patient's vascular system into the cartridge 10, and the injection lumen 16 is used to deliver oxygenated blood from the cartridge 10 into the patient's vascular system. The spread of the injection lumen 16 is greater than the spread of the discharge lumen 14. The non-uniform spread of lumens 14,16 allows different areas of the priming cap 22 to be attached to the ends 15,17 of lumens 14,16, as will be further described herein.

[0103] In some optional embodiments, the double-lumen cannula has an outer tube surrounding an inner tube, where one of the outer and inner tubes is an exhaust tube and the other is an infusion tube. In some such embodiments, the outer tube drains deoxygenated blood from the blood vessel, and the inner tube injects oxygenated, CO2-poor blood into the blood vessel. In other embodiments, the inner tube drains deoxygenated blood from the blood vessel, and the outer tube injects oxygenated blood into the blood vessel. In a side-by-side configuration, one tube is used for draining deoxygenated blood from the blood vessel, and the other tube injects oxygenated, CO2-poor blood into the blood vessel.

[0104] In other embodiments, the discharge pipe and the injection pipe are arranged side by side in the double-lumen cannula.

[0105] In the specific examples described herein, the double-lumen cannula 12 further includes a guidewire sheath 18 having an entrance 19 (not shown). When the cannula 12 is inserted into the patient's body, it is passed through the sheath 18 along the guidewire 136.

[0106] The cannula 12 further includes wings 20. The wings 20 may be attached to the patient's body, for example, with sutures, to ensure that the cannula 12 remains in place during the oxygenation procedure.

[0107] The priming cap 22 is removably fitted onto the ends 15, 17 of the first and second lumens 14, 16. The priming cap 22 includes two regions: a region 23 that is fluid-connected to the outlet 17 of the lumen 16 and leads to the outlet 24 of the priming cap 22; and a region 25 that is fluid-connected to the inlet 15 of the lumen 14 and receives fluid through the inlet 26 of the priming cap 22. Regions 23, 25 are separated by internal seals 28, 30, which may be, for example, O-rings. When fluid enters the priming cap 22 through the inlet 26, the fluid fills the entire region 25 between seals 28 and 30. When fluid enters the priming cap 22 through the outlet of the lumen 16, the fluid fills the entire region 23 between seal 30 and the outlet 24 of the priming cap 22. The positions and orientations of the outlets 24 and inlets 26 within their respective regions 23, 25 are illustrative only, and other positions and orientations are also possible. Furthermore, in the illustrated embodiment, the cannula 12 is a double-lumen cannula, and in an alternative embodiment, the cannula 12 has two separate cannulas, one for discharge and the other for injection. In such an embodiment, there may be a separate priming cap 22 for each cannula, and the priming cap 22 may be divided into two branches (i.e., an inlet branch and an outlet branch).

[0108] The cartridge 10 further includes a saline reservoir 32 connected to the outlet 24 of the priming cap 22 via tubing 31. The saline reservoir 32 is connected to a disposable pump head 34 of a priming pump (whose drive unit is part of the base 10 as described above). In an exemplary embodiment, the priming pump (including the drive unit 122 contained in the base 10) has small dimensions, being up to 10 cm in length and weighing up to 2 kg. In an exemplary embodiment, the priming pump is a peristaltic pump, and the priming pump head 34 is designed to fit around tubing that carries saline from the saline reservoir 32. The peristaltic pump is relatively inexpensive and has a simple interface with disposable, sterilized tubing that carries saline.

[0109] From the priming pump head 34, the fluid path leads to two valves: a pressure gauge valve 36 and a blood pathway valve 38. The pressure gauge valve 36 and the blood pathway valve 38 are controlled separately so that the pressure gauge valve 36 may be open and the blood pathway valve 38 may be closed, or vice versa. The pressure gauge valve 36 is connected to three pressure gauges 44, 48, and 56. This connection is schematically shown in Figure 2 and further shown in Figure 3, with fluid lines connecting the pressure gauge valve 36 to each of the pressure gauges. When the pressure gauge valve 36 is open, fluid (e.g., saline solution) flows between the pump head 34 and the pressure gauges 44, 48, and 56. The pressure gauge valve 36 can be controlled separately to allow the flow of saline solution to any one of the pressure gauges 44, 48, or 56. During the priming process, once the fluid has filled the lines between the pressure gauge valve 36 and the pressure gauges 44, 48, and 56, the pressure gauge valve 36 may be closed. When the blood pathway valve 38 opens, fluid (e.g., saline solution) flows through the tubing 39 between the pump heads 34 to the inlet 26 of the priming cap 22, so that the fluid may continue to prime the area through which blood flows after the cannula 12 is inserted into the patient's vascular system.

[0110] After the fluid enters the inlet 26 of the priming cap 22, the fluid fills the region 25 of the priming cap 22 and enters the discharge lumen 14 of the cannula 12 at the inlet 15. From the discharge lumen 14, the fluid proceeds through the tubing 42, through the pressure gauge 44, or adjacent to the pressure gauge 44.

[0111] The pressure gauge 44 is preferably a membrane pressure sensor having saline solution (from the pressure gauge valve 36) on one side of the membrane and fluid from the blood pathway on the other side of the membrane, but is not necessarily required. The sensor is configured to indicate (for example to the controller) when the pressure difference across the membrane changes. When the cannula 12 is inserted into the patient's vascular system, the pressure gauge 44 is used to confirm that blood is flowing properly from the vein (i.e., that the vein is not collapsed).

[0112] Following the pressure gauge 44, the fluid passes through the blood pump head 46. The blood pump head 46 may include a magnetic impeller which may be controlled by a centrifugal magnetic motor in the blood pump drive unit 120 in the base 110. The blood pump is used to regulate the pressure of the fluid entering the oxygen supply unit 52 so that blood flows through the oxygen supply unit in the desired amount.

[0113] Before entering the oxygen supply unit 52, the fluid passes through or adjacent to the second pressure sensor 48. After leaving the oxygen supply unit 52, the fluid passes through or adjacent to the third pressure sensor 56. Pressure sensors 48 and 56 may be membrane pressure sensors, similar to pressure sensor 44. Pressure sensors 48 and 56 are used to evaluate the efficiency of the oxygen supply unit 52. The oxygen supply unit 52 will become clogged with blood during its use. As a result, the blood will flow more slowly when leaving the oxygen supply unit 52 than when entering it, and a pressure gradient will develop across the oxygen supply unit 52. The pressures at pressure sensors 48 and 56 may be used to detect the presence of such a pressure gradient and thus to determine whether cartridge 10 needs to be replaced.

[0114] Before entering the oxygen supply unit 52, the blood also optionally passes through the analyzer 50. As described above with respect to Figure 1, the analyzer 50 is part of a group of fixed sensors 118 and therefore, technically speaking, part of the base 110. The tubing of the cartridge 10 passes through the analyzer 50, so that the analyzer 50 itself does not come into contact with the fluid. The analyzer 50 may measure oxygen saturation. The analyzer 50 may be, for example, an optical analyzer or an ultrasonic analyzer.

[0115] The blood is then oxygenated by an oxygen supply unit 52. The oxygen supply unit 52 is connected to the oxygen input via a connector 52' ​​and releases carbon dioxide as a byproduct.

[0116] Following oxygenation in the oxygen supply unit 52, the fluid passes through a temperature sensor 54. The temperature sensor 54 may include a metal piece placed inside a sterilized tube. If the temperature sensor 54 indicates that the blood temperature has cooled below a level suitable for reinfusion into the patient, a blood heater (not part of the cartridge 10) may be used to reheat the blood if necessary. The fluid further passes through a flow meter 58 before returning to the infusion lumen 16 of the cannula 12 via a sterilized tube 60. The flow meter 58 may be an ultrasonic meter that is part of the base 10. The flow meter is used to ensure that the output of a blood pump operating on a rotation per minute is converted into a desired flow measured in liters per minute.

[0117] The sterilized tubes 42,60 may be relatively long compared to the other components shown in cartridge 10. In an exemplary embodiment, the sterilized tubes 42,60 include an extended tube 62 schematically shown in Figure 2. The extended tube 62 may be, for example, 1.2 meters in length.

[0118] In light of the above description, it is clear that when the priming cap 22 is fitted over the cannula 12 as shown in Figure 2, the cartridge 10 contains a closed loop for fluid flow. When the priming pump is driven, it draws saline from the saline reservoir 32. When the blood pump valve 38 opens, saline flows through the blood pump valve 38, the priming cap inlet 26, the first lumen 14 (e.g., the discharge lumen), the oxygenation module 40, the second lumen 16 (e.g., the injection lumen), the priming cap outlet 22, and then back to the saline reservoir 32. Throughout this process, air is discharged from the above fluid flow path and deposited into the saline reservoir 32. The discharged air remains in the saline reservoir 32, which is made of a plastic-like material that is sufficiently expandable to accommodate the discharged air.

[0119] In the illustrated embodiment, the closed loop is closed by the oxygenation module 40, but it is further evident that any alternative fluid path between the first lumen 14 and the second lumen 16 may be used. Thus, the cartridge 10 may be used with various systems requiring priming and is not limited to the oxygenation module.

[0120] Furthermore, it is even clearer that the fluid flow through this closed loop may proceed even when the cartridge 10 remains sealed to the ambient atmosphere. Thus, the cannula 12 and the blood flow path may be primed while being maintained in a sterile state.

[0121] In short, the extracorporeal blood oxygenation system of the present invention is used to oxygenate a patient's blood. In one optional embodiment, the cannula 12 is inserted into the patient's jugular vein. Blood exits the jugular vein, enters a drainage lumen, and flows through tubes 42. A blood pump head 46 pumps the blood through an oxygen supply unit 52. The oxygenated blood then returns to the jugular vein through tubes 60 and an infusion lumen 16. The cannula 12 may be inserted at any other suitable point (e.g., the superior vena cava). Furthermore, as described above, the cannula 12 may include two separate cannulas (one for drainage and the other for infusion).

[0122] Optionally, blood oxygenation is performed while circulating blood at a rate no greater than approximately 30 ml / kg per minute for patients who are conscious, able to breathe independently, and for whom oxygenation helps complement the patient's respiration.

[0123] Figure 4 illustrates the steps of flowchart 400 for one optional method of operating the extracorporeal system of Figure 1. Step 401 is an assessment of whether the patient's condition is suitable for treatment with the extracorporeal oxygenation system of the present invention, according to the parameters described above. If the patient is identified as suitable for this treatment, in step 402 the medical team prepares the cannula insertion site for intubation. In step 403 the disposable cartridge is inserted into the base, and in step 404 the system is turned on. In step 405 automatic priming of the disposable circuit is performed, and in step 406 the cover of the opening into the internal space of the cartridge is removed, and the primed cannula is withdrawn from the cartridge. In step 407 an oxygen-rich gas supply is connected to the gas inlet in the cartridge, and the gas flow is turned on. In step 408, the cannula is inserted into the patient's vascular system, and in step 409, the required flow is calculated according to the patient's weight and dimensions within the blood flow range of 10-30 ml / kg / min. In the next step 410, the main pump is activated and treatment begins.

[0124] Figures 5A and 5B are schematic isometric front and rear views, respectively, of a cartridge unit 10 having an automatic priming system and cannula according to several optional embodiments of the present disclosure. In these drawings, the housing is removed for clarity of explanation, and the components contained within the housing are shown. In this particular example, a saline reservoir 32 is connected to a priming cap 22 via tubing 31. The saline reservoir 32 is connected to a disposable pump head 34 of a priming pump, the drive unit of which is part of the base 10 as described above. From the priming pump head 34, the fluid path proceeds to two valves: a pressure gauge valve 36 (not shown in this figure) and a blood path valve 38. The pressure gauge valve 36 is connected to three pressure gauges 44, 48, and 56. When the pressure gauge valve 36 is open, saline flows between the pump head 34 and the pressure gauges 44, 48, and 56. When the blood pathway valve 38 opens, the saline fluid flows through the tubes 39 between the pump heads 34 to the priming cap 22, allowing the fluid to continue priming the area through which blood flows after the insertion of the cannula 12 into the patient's vascular system. After the fluid enters the priming cap 22, it enters the discharge lumen of the cannula 12 and proceeds through the tubes 42 to the pressure gauge 44. Following the pressure gauge 44, the fluid passes through the blood pump head 46. The blood pump is used to regulate the pressure of the fluid entering the oxygen supply unit 52 so that the desired amount of blood flows through the oxygen supply unit. Before entering the oxygen supply unit 52, the fluid passes through a second pressure sensor 48. After leaving the oxygen supply unit 52, the fluid passes through a third pressure sensor 56. Before entering the oxygen supply unit 52, the blood may optionally pass through the analyzer 50. Following oxygenation in the oxygen supply unit 52, the fluid passes through the temperature sensor 54. The oxygen supply unit 52 is connected to the gas supply by a connector 52'.

[0125] Figure 6 shows exemplary steps of flowchart 200 for automatic priming of a closed-loop fluid flow system for cartridge 10. In step 201, the system is started. For example, the user may turn on the power to the controller 114. In step 202, the controller 114 checks whether an available cartridge 10 (abbreviated as "DC") is effectively connected to the base 10. If cartridge 10 is not present, in step 203, the system returns to step 201 and remains ready to operate when cartridge 10 is connected. If cartridge 10 is identified, in step 204, the system turns off the blood pump (abbreviated as "BP"), closes the blood pathway valve 38, and opens the pressure gauge valve 36 (abbreviated as "PM valve"). In step 205, optionally, the user sets the flow rate for the priming pump (abbreviated as "PP") (e.g., 1 liter per minute). Alternatively, the system automatically sets the flow rate or uses a preset flow rate. The flow rate may be set based on criteria including, among other things, the diameter of the tube between the pressure gauge valve 36 and the pressure gauge. In step 206, the user or system sets a time parameter (indicated as “delay”) for the priming pump to operate sufficiently so that the fluid fills all the lines between the pressure gauge valve 36 and the pressure gauges 44, 48, and 56, as shown in Figure 2. The priming cap then operates to fill these lines. In step 207, the system opens the blood pathway valve 38. In step 208, optionally, the user sets the flow rate for the priming pump (e.g., 2 liters per minute). This flow rate may be greater than the flow rate used in step 205 because the tubes in the blood pathway may have a larger diameter. Alternatively, as described above, the system may set the flow rate automatically or use a predetermined flow rate. In step 209, the user or system sets a time parameter (indicated as “delay”) for the priming pump to operate sufficiently so that the air is completely expelled from the closed loop.The priming pump is then activated, and fluid fills all lines between the blood pathway valve 38, the priming cap 22, the cannula 12, and the oxygenation system 40. The order of priming the pressure gauges 44, 48, 56 and the blood pathway is also reversed so that the blood pathway may be primed before the pressure gauges. In steps 210 and 211, priming is complete and the process is finished. In exemplary embodiments, the entire priming process takes approximately 2 minutes. Advantageously, the priming process may be performed entirely autonomously without requiring any manual injection of saline into the cannula or other system components. Alternatively, a bubble sensor(single / plural) may be used to indicate that the priming process is complete.

[0126] Figure 7 shows exemplary steps of the automated priming 300 method as part of the entire process of external oxygenation of a patient according to an embodiment of the present disclosure.

[0127] In step 301, the user installs the cartridge 10 onto the base 110. In step 302, the machine primes the system by activating the priming pump when the priming cap 22 is fitted onto the cannula 12 in the manner described above. Conveniently, this priming operation may be initiated automatically upon detection of the installation of the cartridge 10 onto the base 110.

[0128] In step 303, the user (e.g., a surgeon or nurse) opens the patient puncture kit 130 and inserts the introducer 132, dilator 134, and guidewire 136 into the patient's vascular system. This insertion is performed in any typical manner known to those skilled in the art. For example, a surgeon may puncture the patient's jugular vein or other blood vessel and dilate the vessel using a dilator that increases in diameter. The puncture site is dilated to reach the diameter of the cannula 12.

[0129] In step 304, the user opens the cover of the opening in the cartridge to access the cannula 12 and priming cap 22.

[0130] In step 305, the user removes the priming cap 22 from the cannula 12. At this point, lumens 14 and 16 are removed from the closed loop.

[0131] In step 306, the user inserts the cannula 12 into the patient's vascular system. For example, the surgeon may remove the inflator from the vascular system and leave the guidewire 136 in place. The sheath 18 is passed over the guidewire 136 until the cannula 12 is in place within the patient's body. During the process of inserting the cannula 12 into the patient's vascular system, a small amount of saline may be discharged from the ends 15, 17 of the lumens 14, 16 to ensure that no air is introduced into the cannula 12. Following the placement of the cannula 12, the surgeon sutures the wings 20 of the cannula 12 to the patient's skin to keep the cannula 12 in place. The surgeon then removes the guidewire 136. The sheath 18 is then sealed (e.g., with a cap) or crushed to prevent blood from leaking out of the sheath 18. In step 307, the system 100 oxygenates the blood.

[0132] It should be clear that the descriptions of embodiments and accompanying drawings described herein are for the sole purpose of providing a better understanding of the invention and do not limit its scope. It should also be clear to those skilled in the art that, after reading this specification, adjustments or modifications may be made to the accompanying drawings and the embodiments described above, which would still be covered by the invention.

Claims

1. A system for oxygenating a patient's blood, the system being: An extracorporeal blood circulation pathway adapted to connect to the patient's vascular system; A sensor that provides measurements of patient parameters selected from the group consisting of oxygen saturation level, blood pH, blood pressure, system pressure, blood flow rate, active clotting time, blood temperature, cardiac output, partial pressure to oxygen and CO2, and hemoglobin concentration; A low-flow oxygen supply device that supplies oxygen to the blood flowing into the extracorporeal blood circulation pathway and recovers CO2 from the extracorporeal blood circulation pathway, wherein the flow rate of blood into the extracorporeal blood circulation pathway is limited so as not to exceed 2 / 5 of the patient's normal blood flow rate, thereby enabling the patient's spontaneous breathing; A controller configured to receive patient parameters from the sensor's measurement and to modify or adjust blood flow rate or other decisive aspects of the system based on those parameters to obtain a desired target oxygenation level, The system wherein the flow rate of blood entering the extracorporeal blood circulation pathway is 30 ml / kg per minute or less, and does not exceed 2 / 5 of the patient's blood circulation volume, and the blood circulation volume is determined based on the patient's body weight.

2. The system according to claim 1, further comprising the low-flow oxygen supply device and at least one cartridge including at least one cannula for establishing the extracorporeal blood circulation pathway.

3. The system according to claim 2, wherein at least one component of the cartridge is disposable.

4. The system according to any one of claims 2 to 3, wherein the cartridge is configured to be reversibly connected to a reusable base having at least one controller and one or more pump drive units and motors, and is operable, with each drive unit and motor corresponding to a pump head and power source located on the cartridge, respectively.

5. The system according to claim 4, wherein the base further comprises at least one fixed sensor and / or user interface.

6. The system according to claim 4, wherein the cartridge further comprises one or more pump heads, each pump head being controllable by its respective pump drive unit and motor located in the base.

7. The system according to any one of claims 2, 3, and 5, comprising an automated priming system that ensures the extracorporeal blood circulation pathway is adapted to the patient's vascular system in a safe and embolus-free manner.

8. The system according to claim 7, wherein the cartridge further comprises a saline solution storage unit connected to the automatic priming system.

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